Rosen's Emergency Medicine: Concepts and Clinical Practice [9 ed.] 9780323354790, 9996111695, 9996111636, 2016055133, 9789996111693, 9789996111631

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Rosen's Emergency Medicine: Concepts and Clinical Practice [9 ed.]
 9780323354790, 9996111695, 9996111636, 2016055133, 9789996111693, 9789996111631

Table of contents :
Front Matter
Copyright Page
Acknowledgments
Contributors
Preface to the Ninth Edition
How This Medical Textbook Should Be Viewed by the Practicing Clinician and Judicial System
Part I: Fundamental Clinical Concepts
Section One: Critical Management Principles
Chapter 1: Airway
Principles
Background
Anatomy, Physiology, and Pathophysiology
Failure to Maintain or Protect the Airway
Failure of Ventilation or Oxygenation
Anticipated Clinical Course
Identification of the Difficult Airway
Difficult Direct Laryngoscopy: LEMON
L—Look Externally.
E—Evaluate 3-3-2.
M—Mallampati Scale.
O—Obstruction or Obesity.
N—Neck Mobility.
Difficult Bag-Mask Ventilation: MOANS
Difficult Extraglottic Device Placement: RODS
Difficult Cricothyrotomy: SMART
Measurement and Incidence of Intubation Difficulty
Confirmation of Endotracheal Tube Placement
Management
Decision Making
Difficult Airway
Failed Airway
Methods of Intubation
Rapid Sequence Intubation
Preparation.
Preoxygenation.
Pretreatment.
Paralysis With Induction.
Positioning.
Placement of Tube.
Postintubation Management.
Delayed Sequence Intubation
Blind Nasotracheal Intubation
Awake Oral Intubation
Oral Intubation Without Pharmacologic Agents
Pharmacologic Agents
Neuromuscular Blocking Agents
Succinylcholine.
Uses and Dosing.
Cardiovascular Effects.
Fasciculations.
Hyperkalemia.
Masseter Spasm.
Malignant Hyperthermia.
Competitive Agents.
Rocuronium.
Paralysis After Intubation.
Induction Agents
Etomidate.
Ketamine.
Propofol.
Other Induction Agents.
Special Clinical Circumstances
Status Asthmaticus
Hemodynamic Consequences of Intubation
Elevated Intracranial Pressure
Hypotension and Shock
Potential Cervical Spine Injury
Airway Devices and Techniques
Direct Versus Video Laryngoscopy
Videolaryngoscopes
Fiberoptic and Video Intubating Stylets
Flexible Intubating Scopes
Extraglottic Devices
Laryngeal Mask Airways.
Other Extraglottic Devices.
Surgical Airway Management
Needle Cricothyrotomy With Transtracheal Jet Ventilation
Cricothyrotomy
Outcomes
References
Chapter 1: Questions & Answers
Chapter 2: Mechanical Ventilation and Noninvasive Ventilatory Support
Perspective
Principles of Mechanical Ventilation
Physiology of Positive-Pressure Breathing
Invasive Mechanical Ventilation: Control Variable and Ventilator Mode
Positive End-Expiratory Pressure
Noninvasive Techniques
Management
Decision Making: Noninvasive Versus Invasive Ventilation
Approach to Initial Ventilator Settings
Noninvasive Ventilation
Mechanical Ventilation of the Intubated Patient
Ongoing Management
Sedation and Analgesia of the Ventilated Patient
Complications
Troubleshooting the Ventilator
Special Clinical Circumstances
Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Status Asthmaticus
Acute Respiratory Distress Syndrome
Outcomes
References
Chapter 2: Questions & Answers
Chapter 3: Pain Management
Principles
Background and Importance
Anatomy, Physiology, and Pathophysiology
Pain Conduction Pathways
Pain Detection
Information Transmission
Peripheral Nerve Fibers.
Pain Transmission
Dorsal Horn.
Visceral Pain.
Ascending Tracts Associated With Pain.
Pain Modulation
Central Sensitization
Pain Expression
Reflex Responses to Pain
Endorphin System
Acute Versus Chronic Pain
Management
Decision Making
Pain Assessment
Oligoanalgesia
Pain Measurement
Treatment Groups
Chronic Pain.
Recurrent Pain.
Chronic Pain of Malignancy.
Neuropathic Pain.
Acute Pain.
Pharmacologic Therapy
Opioid Analgesic Agents
Mechanism of Action and Toxic Effects.
Drug-Seeking Behavior.
Administration of Pain Control.
Specific Agents
Morphine.
Meperidine.
Hydromorphone.
Fentanyl.
Oxycodone.
Hydrocodone.
Codeine.
Methadone.
Naloxone.
Tramadol.
Tapentadol.
Opioid Agonist-Antagonist Analgesic Agents.
Opioid Use for Acute Abdominal Pain.
Nonopioid Analgesic Agents
Acetaminophen.
Nonsteroidal Antiinflammatory Drugs
Drug Interactions With Nonsteroidal Antiinflammatory Drugs
Aspirin.
Oral Anticoagulants.
Angiotensin-Converting Enzyme Inhibitors.
Diuretics.
Glucocorticoids.
Lithium.
Nonselective Cyclooxygenase Inhibitor Selection.
Ketorolac Tromethamine.
Ibuprofen.
Skeletal Muscle Relaxants.
Nitrous Oxide–Oxygen Mixtures.
Ketamine.
Local Anesthesia
Mechanism of Action.
Classes of Local Anesthetic Agents.
Allergic Reactions.
Local and Systemic Toxicity
Local Toxicity.
Systemic Toxicity.
Reducing the Pain of Local Anesthetic Injection.
Topical Anesthesia
Topical Anesthetics Applied to Intact Skin
Eutectic Mixture of Local Anesthetics.
Ethyl Chloride and Fluoromethane Sprays.
Agents Applied to Mucosal Surfaces
Cocaine.
Lidocaine.
Tetracaine.
Benzocaine.
Agents Applied to Open Skin: Lidocaine, Epinephrine and Tetracaine.
Nonpharmacologic Interventions
Transcutaneous Electrical Nerve Stimulation
Hypnosis
Out-of-Hospital Analgesia
Outcomes: Treatment Endpoints
References
Chapter 3: Questions & Answers
Chapter 4: Procedural Sedation and Analgesia
Principles
Background
Terminology
Management
Decision Making
Patient Assessment.
Preprocedural Fasting.
Personnel.
Supplies and Equipment.
Monitoring Devices and Techniques.
Recovery.
Postprocedure Recovery and Discharge.
Pharmacologic Therapy
Routes of Administration.
Opioids.
Fentanyl.
Morphine.
Benzodiazepines.
Midazolam.
Barbiturates.
Ketamine.
Sedative-Hypnotics
Etomidate.
Propofol.
Ketamine Plus Propofol.
Ultra—Fast-Acting Agents.
Reversal and Rescue Agents.
Naloxone.
Flumazenil.
Drug Selection and Administration
References
Chapter 4: Questions & Answers
Chapter 5: Monitoring the Emergency Patient
Blood Pressure Measurement
Principles
Decision Making
Devices and Techniques
Pulse Oximetry
Principles
Decision Making
Devices and Techniques
End-Tidal Carbon Dioxide Monitoring
Principles
Anatomy and Pathophysiology
Management
Capnography in Spontaneously Breathing Patients
Rapid Assessment of Critically Ill Patients.
Assessment and Measurement of Response to Treatment in Patients With Acute Respiratory Distress.
During Procedural Sedation and Analgesia.
Rapid Assessment of Obtunded or Unconscious Patients.
Rapid Assessment of Patients With Severe Illness.
Cerebral Function Monitoring
Principles
Fetal Monitoring
Principles
Monitor Alarms and Limits
References
Chapter 5: Questions & Answers
Chapter 6: Shock
Principles
Background and Importance
Anatomy, Physiology, and Pathophysiology
Specific Causes
Hemorrhagic Shock
Septic Shock
Cardiogenic Shock
Neurogenic Shock
Management
Decision Making
Monitoring Perfusion Status
Quantitative Resuscitation
Pharmacology
Volume Replacement
Crystalloids.
Colloids and Hypertonic Saline.
Blood Products.
Vasopressors
Inotropes
Antimicrobial Therapy
Corticosteroids
Special Cases
Devices and Procedures
Ventilation
Source Control
Intraaortic Balloon Pumps and Percutaneous Coronary Intervention
Pericardiocentesis and Thrombectomy
Outcomes
References
Chapter 6: Questions & Answers
Chapter 7: Brain Resuscitation
Principles
Background
Anatomy, Physiology, and Pathophysiology
Elevated Intracranial Pressure
Management
Decision Making
Pharmacology, Devices, and Techniques
Cardiopulmonary Resuscitation
Reperfusion
Optimizing Perfusion and Oxygenation.
Elevated Intracranial Pressure
Medical Treatment.
Surgical Treatment.
Maintenance of Body Temperature
Resuscitative Mild Hypothermia
Avoidance of Hyperglycemia
Seizure Management
Outcomes
Summary
References
Chapter 7: Questions and Answers
Chapter 8: Adult Resuscitation
Principles
Background
Anatomy, Physiology, and Pathophysiology
Management
Decision Making
History and Physical Examination
Monitoring
Arterial Blood Pressure and Coronary Perfusion Pressure
End-Tidal Carbon Dioxide
Central Venous Oxygen Saturation
Pharmacologic Therapy
Devices and Techniques
Echocardiography
Laboratory Testing
Resuscitation
Defibrillation
Pulseless Electrical Activity
Asystole
Extracorporeal Cardiopulmonary Resuscitation
Outcomes
Post–Cardiac Arrest Care
Hypothermic Targeted Temperature Management
Coronary Angiography and Primary Percutaneous Coronary Intervention
References
Chapter 8: Questions & Answers
Section Two: Signs, Symptoms, and Presentations
Chapter 9: Fever in the Adult Patient
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach and Algorithm
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
Disposition
References
Chapter 9: Questions and Answers
Chapter 10: Weakness
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach and Algorithm
Differential Considerations
Diagnostic Algorithm
Critical Diagnoses
Unilateral Weakness
Combination of Arm, Hand, or Leg With Ipsilateral Facial Involvement.
Combination of Arm, Hand, or Leg With Contralateral Facial Involvement.
Combination of Arm, Hand, or Leg Without Facial Involvement.
One Limb Only (Monomelic Weakness, Monoparesis, or Monoplegia).
Bilateral Weakness
Lower Extremities Only (Paraparesis or Paraplegia).
Upper Extremities Only.
All Four Extremities Without Facial Involvement (Quadriparesis or Quadriplegia).
Proximal Portions of Extremities Only.
Distal Portions of Extremities Only.
Facial Weakness Without Extremity Involvement
Unilateral Facial Droop.
Facial Weakness Not Limited to Cranial Nerve VII and Muscle of Expression.
Pivotal Findings
Management
Disposition
Reference
Chapter 10: Questions and Answers
Chapter 11: Cyanosis
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Pivotal Findings
Symptoms
Signs
Laboratory and Ancillary Testing
Other Diagnostic Modalities
Imaging
Electrocardiography and Echocardiography
Differential Algorithms
Critical Diagnoses
Emergent Diagnoses
Empirical Management
Specific Strategies
Methemoglobinemia and Sulfhemoglobinemia
Other Causes of Cyanosis
Patient Disposition
Admission
Discharge
References
Chapter 11: Questions and Answers
Chapter 12: Syncope
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Studies
Diagnostic Algorithm
Empirical Management
References
Chapter 12: Questions and Answers
Chapter 13: Depressed Consciousness and Coma
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
References
Chapter 13: Questions & Answers
Chapter 14: Confusion
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
References
Chapter 14: Questions & Answers
Chapter 15: Seizures
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Laboratory Testing
Imaging Studies
Electroencephalography
Diagnostic Algorithm
Empirical Management
Prehospital Management
Emergency Department Management
Disposition
References
Chapter 15: Questions & Answers
Chapter 16: Dizziness and Vertigo
Perspective
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Physical Examination
Vital Signs.
Head and Neck.
Neurologic Examination.
Positional Testing.
HINTS.
Ancillary Testing
Radiologic Imaging.
Diagnostic Algorithm
Empirical Management
Disposition
References
Chapter 16: Questions & Answers
Chapter 17: Headache
Perspective
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
Disposition
References
Chapter 17: Questions & Answers
Chapter 18: Diplopia
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Monocular Cause.
Mechanical Orbitopathy.
Isolated Oculomotor Nerve Palsy.
Neuroaxial Process Involving the Brainstem and Related Cranial Nerves.
Neuromuscular Disorder.
Signs
Monocular Cause.
Mechanical Orbitopathy.
Isolated Oculomotor Nerve Palsy.
Neuroaxial Process Involving the Brainstem and Related Cranial Nerves.
Neuromuscular Disorder.
Ancillary Testing
Diagnostic Algorithm
Empirical Management
Management Algorithm
References
Chapter 18: Questions & Answers
Chapter 19: Red and Painful Eye
Perspective
Epidemiology and Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Signs
Visual Acuity
Visual Field Testing
External Examination
Extraocular Muscle Function
Pupillary Evaluation
Ancillary Testing
Swinging Flashlight Test
Pressure Determination
Slit-Lamp Examination
Direct Funduscopic Examination
Topical Anesthetics
Imaging
Laboratory Testing
Diagnostic Algorithm
Critical Diagnoses
Emergent Diagnoses
Urgent Diagnoses
Empirical Management
References
Chapter 19: Questions & Answers
Chapter 20: Sore Throat
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms and Signs
Ancillary Testing
Imaging
Diagnostic Algorithm
Critical and Emergent Diagnoses
Empirical Management
References
Chapter 20: Questions & Answers
Chapter 21: Hemoptysis
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Critical Diagnoses
Bronchoscopy
Empirical Management
References
Chapter 21: Questions & Answers
Chapter 22: Dyspnea
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Duration of Dyspnea.
Onset of Dyspnea.
Positional Changes.
Signs
Ancillary Testing
Diagnostic Algorithm
Critical Diagnoses
Emergent Diagnoses
Empirical Management
References
Chapter 22: Questions & Answers
Chapter 23: Chest Pain
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Rapid Stabilization and Assessment
Pivotal Findings
History
Physical Examination
Ancillary Studies
Diagnostic Table
Empirical Management
References
Chapter 23: Questions & Answers
Chapter 24: Abdominal Pain
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Rapid Assessment and Stabilization
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Critical Diagnoses
Emergent Diagnoses
Empirical Management
Disposition
Bibliography
Chapter 24: Questions & Answers
Chapter 25: Jaundice
Perspective
Epidemiology
Pathophysiology
Normal Bilirubin Metabolism
Abnormalities in Bilirubin Metabolism
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Signs
Laboratory Tests
Imaging
Diagnostic Algorithm
Empirical Management
References
Chapter 25: Questions & Answers
Chapter 26: Nausea and Vomiting
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Studies
Diagnostic Algorithm
Empirical Management
Special Situations
Opioid-Induced Vomiting
Headache
Pregnancy
Chemotherapy
Cyclical Vomiting
Vertigo
Disposition
References
Chapter 26: Questions & Answers
Chapter 27: Gastrointestinal Bleeding
Perspective
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Relevant Medical History
Signs
Ancillary Testing
Occult Blood and Guaiac Bedside Testing
Laboratory Studies
Electrocardiography
Imaging
Diagnostic Algorithm
Management
Empirical Treatment
Resuscitation
Blood Product Transfusion
Nasogastric Aspiration and Lavage
Sengstaken-Blakemore Tube
Pharmacologic Agents
Definitive Management
Consultation
Endoscopy
Colonoscopy
Disposition
References
Chapter 27: Questions & Answers
Chapter 28: Diarrhea
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Signs and Symptoms
Ancillary Testing
Blood Tests.
Lactate.
Hemoccult and Fecal Cell Count.
Assays for Fecal Calprotectin and Fecal Lactoferrin.
Clostridium difficile Toxin Assay.
Escherichia coli O157:H7 Toxin Assay.
Stool Culture for Bacteria.
Stool Examination for Ova and Parasites.
Giardia Antigen Assay and Serologic Testing for Amebiasis.
Radiographic Studies.
Gastrointestinal Referral.
Diagnostic Algorithm
Critical Diagnoses
Emergent Diagnoses
Empirical Management
References
Chapter 28: Questions & Answers
Chapter 29: Constipation
Principles
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Diagnosis Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
References
Chapter 29: Questions & Answers
Chapter 30: Acute Pelvic Pain
Perspective
Epidemiology
Pathophysiology
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
References
Chapter 30: Questions & Answers
Chapter 31: Vaginal Bleeding
Perspective
Epidemiology
Pathophysiology
Nonpregnant Patients
Pregnant Patients
Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Diagnostic Algorithm
Empirical Management
Disposition
References
Chapter 31: Questions & Answers
Chapter 32: Back Pain
Perspective
Epidemiology
Pathophysiology
II. Diagnostic Approach
Differential Considerations
Pivotal Findings
Symptoms
Signs
Ancillary Testing
Laboratory Tests
Imaging
Diagnostic Algorithm
Critical Diagnoses
Empirical Management
Acknowledgments
References
Chapter 32: Questions & Answers
Part II: Trauma
Section One: General Concepts and System Injuries
Chapter 33: Multiple Trauma
Principles
Epidemiology
Anatomy and Physiology
Pathophysiology
Clinical Features
Primary Survey
Secondary Survey
Differential Diagnoses
Diagnostic Testing
Laboratory Evaluation
Radiographic Evaluation
Management
Out-of-Hospital Management
Emergency Department
Disposition
References
Chapter 33: Questions & Answers
Chapter 34: Head Trauma
Principles of Disease
Background and Importance
Anatomy and Pathophysiology
Scalp and Cranium
Brain and Cerebrospinal Fluid
Cerebral Hemodynamics and Increased Intracranial Pressure
Increased Intracranial Pressure
Cushing’s Reflex
Definitions and Patterns of Injury
Traumatic Brain Injuries: Severe, Moderate, and Mild
Direct and Indirect Injuries
Direct Injury.
Indirect Injury.
Neurochemical Cascade
Penetrating Head Trauma
Scalp Wounds
Skull Fractures
Linear Fractures
Depressed Fractures
Basilar Fractures
Extra-Axial and Intra-Axial Intracranial Injuries
Extra-Axial Injury
Epidural Hematoma.
Subdural Hematoma.
Traumatic Subarachnoid Hemorrhage.
Subdural Hygroma.
Intra-Axial Injury
Diffuse Axonal Injury and Traumatic Axonal Injury.
Cerebral Contusions.
Intracerebral Hematoma.
Intracerebellar Hematoma.
Primary and Secondary Brain Injuries
Primary Brain Injury
Secondary Systemic Insults
Hypotension.
Hypoxia.
Hypocarbia and Hypercarbia.
Anemia.
Hyperpyrexia.
Altered Levels of Consciousness
Cerebral Herniation Syndromes
Uncal Herniation
Central Transtentorial Herniation
Cerebellotonsillar Herniation
Upward Transtentorial Herniation
Moderate and Severe Traumatic Brain Injury
Clinical Features and History
Common Presentations of Specific Lesions
Epidural Hematoma
Subdural Hematoma
Traumatic Subarachnoid Hemorrhage
Subdural Hygroma
Traumatic Axonal Injury
Cerebral Contusion
Intracerebral Hematoma
Traumatic Intracerebellar Hematoma
Physical Examination
Acute Neurologic Examination
General.
Glasgow Coma Scale.
Pupillary Examination.
Motor Examination.
Brainstem Function.
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Neuroimaging
Skull Radiography.
Computed Tomography.
Pneumocephalus.
Epidural Hematoma.
Subdural Hematoma.
Traumatic Subarachnoid Hemorrhage.
Subdural Hygroma.
Diffuse Axonal Injury/ Traumatic Axonal Injury.
Cerebral Contusions.
Intracerebral Hematoma.
Traumatic Intracerebellar Hematoma.
Cerebral Edema.
Rotterdam Computed Tomography Score.
Management
Out-of-Hospital Care
Airway.
Hypotension.
Agitation.
Emergency Department Management
General.
Airway.
Hypotension.
Brain-Directed Hyperosmolar Therapy.
Hyperventilation.
Cranial Decompression.
Hemostatic Agents.
Induced Hypothermia.
Seizure Prophylaxis.
Antibiotic Prophylaxis.
Other Therapies
Corticosteroids.
Barbiturates.
Monitoring of Intracranial Pressure and Cerebral Spinal Fluid Drainage.
Glucose Control and Nutrition.
Erythropoietin.
Progesterone.
Hyperbaric Oxygen Therapy.
Management of Specific Injuries
Scalp Wounds.
Skull Fractures.
Linear Fractures.
Depressed Fractures.
Basilar Skull Fractures.
Extra-Axial Lesions
Epidural Hematoma.
Subdural Hematoma.
Traumatic Subarachnoid Hemorrhage.
Subdural Hygroma.
Intra-Axial Lesions
Cerebral Contusion.
Intracerebral Hematoma.
Intracerebellar Hematoma.
Complications and Outcome
Seizures
Central Nervous System Infections
Meningitis After Basilar Fractures.
Brain Abscess.
Cranial Osteomyelitis.
Medical Complications
Disseminated Intravascular Coagulation.
Neurogenic Pulmonary Edema.
Cardiac Dysfunction.
Disposition
Mild Traumatic Brain Injury
Clinical Features and History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Neuroimaging in the Emergency Department With Computed Tomography
Other Neuroimaging Modalities
Structural MRI.
Susceptibility-Weighted Imaging.
Diffusion Tensor Imaging.
Computed Tomography Angiography and Magnetic Resonance Angiography.
Ancillary Studies
Laboratory Testing.
Neuropsychological Testing.
Disposition
Complications
Postconcussive Syndrome
Seizures
Posttraumatic Transient Cortical Blindness
Special Populations With Mild Traumatic Brain Injury
Mild Traumatic Brain Injury and Concussion in Sports
Military Personnel and Blast Injury
Anticoagulated Patients
Patients on Anticoagulant Medications.
Patients With Inherent Bleeding Disorders.
Head Trauma in Older Adults
References
Chapter 34: Questions & Answers
Chapter 35: Facial Trauma
Principles
Background and Importance
Anatomy of the Face
Bones
Nerve Supply
Ears
Eyes
Nose
Mouth
Temporomandibular Joint
Soft Tissue, Vasculature, and Specialized Glands
Pathophysiology
Clinical Features
History
Physical Examination
Eyes and Orbits.
Oropharynx.
Ears.
Nose.
Neurologic Examination
Differential Diagnosis Based on Anatomic Site
Soft Tissue Injuries and Lacerations
Mouth
Perioral Burns
Cheeks
Nose
Ears
Eyes
Fractures and Dislocations
Forehead
Orbit
Midface
Zygoma
Mandible
Dental and Alveolar Trauma
Temporomandibular Joint
Diagnostic Testing
Imaging
Management
Out-of-Hospital Care
Emergency Department Treatment
General Measures
Disposition
References
Chapter 35: Questions & Answers
Chapter 36: Spinal Injuries
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Classification of Spinal Column Injuries
Flexion.
Shear Injury.
Flexion-Rotation.
Extension.
Vertical Compression.
Classification of Spinal Cord Injuries
Primary Spinal Cord Injury.
Secondary Spinal Cord Injury.
Classification of Cervical Soft Tissue Injuries
Clinical Features
Neurologic Evaluation
Spinal Cord Lesions
Complete Spinal Cord Lesions
Incomplete Spinal Cord Lesions
Differential Diagnosis
Diagnostic Testing
Radiographic Evaluation
Indications
Cervical Plain Radiographs
Cross-Table Lateral View.
Odontoid View.
Anteroposterior View.
Flexion and Extension Views.
Advanced Imaging: Computed Tomography and Magnetic Resonance
Management
Spinal Column Stabilization
Out-of-Hospital Care
Emergency Department
Airway Management
Spinal Shock
Pharmacologic Treatment for Incomplete Cord Injury
Associated Injuries
Cardiopulmonary
Gastrointestinal and Genitourinary
Skin
Definitive Treatment and Prognosis
Disposition
Cervical Soft Tissue Injuries
Minor Fractures
References
Chapter 36: Questions & Answers
Chapter 37: Neck
Principles
Background
Anatomy
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Airway
Breathing
Circulation
Cervical Spine
Thoracotomy
Venous/Arterial Air Embolism
Nasogastric Tubes
Pharyngoesophageal Trauma
Principles
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Laryngotracheal Trauma
Principles
Clinical Features
Diagnostic Testing
Management
Vascular Trauma
Principles
Penetrating Injury
Blunt Injury
Clinical Features
Penetrating Injury
Blunt Trauma
Diagnostic Testing
Penetrating Trauma
Blunt Trauma
Other Radiographic Options
Management
Penetrating Injury
Blunt Injury
Nervous System, Glandular, and Retropharyngeal Injuries
Near Hanging and Strangulation
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
References
Chapter 37: Questions & Answers
Chapter 38: Thoracic Trauma
Chest Wall Injury
Rib Fracture
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Sternal Fracture
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Nonpenetrating Ballistic Injury
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Disposition
Pulmonary Injuries
Pulmonary Contusion and Laceration
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Laboratory
Radiology
Management
Pneumothorax
Principles
Background and Importance
Pathophysiology
Simple Pneumothorax.
Communicating Pneumothorax.
Tension Pneumothorax.
Clinical Features
Diagnostic Testing
Occult Pneumothorax
Management
Simple Pneumothorax
Communicating Pneumothorax
Tension Pneumothorax
Hemothorax
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Tracheobronchial Injury
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Diaphragmatic Injury
Principles
Background and Importance
Pathophysiology
Diagnostic Testing
Management
Cardiovascular Trauma
Blunt Cardiac Trauma
Myocardial Concussion
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Laboratory Tests and Electrocardiogram
Management
Disposition
Myocardial Contusion
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Laboratory Tests and Electrocardiogram
Electrocardiogram.
Cardiac Biomarkers.
Imaging
Management
Disposition
Myocardial Rupture
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Penetrating Cardiac Trauma
Acute Pericardial Tamponade
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Radiology
Ultrasound.
Radiography.
Electrocardiography
Management
Emergency Department Thoracotomy
Indications for Emergency Department Thoracotomy.
Blunt Aortic Injury
Principles
Background and Importance
Pathophysiology
Clinical Features
Diagnostic Testing
Chest Radiography
Chest Computed Tomography Scan
Management
Stabilization and Empirical Therapy
Definitive Management
Endovascular Repair.
Esophageal Perforation
Principles
Background and Importance
Pathophysiology
Clinical Features
Iatrogenic
Foreign Bodies
Caustic Burns
Penetrating and Blunt Trauma
Spontaneous Rupture
Diagnostic Testing
Radiology
Endoscopy
Management
References
Chapter 38: Questions & Answers
Chapter 39: Abdominal Trauma
Principles
Background
Penetrating Abdominal Trauma
Blunt Abdominal Trauma
Anatomy and Physiology
Pathophysiology
Penetrating Abdominal Trauma
Stab Wounds.
Gunshot Wounds: Ballistics.
High-Velocity Missiles.
Shotgun Wounds.
Blunt Abdominal Trauma
Seatbelt Injuries.
Iatrogenic Injuries.
Clinical Features
Penetrating Abdominal Trauma
Stab Wounds.
Gunshot Wounds.
Blunt Abdominal Trauma
Physical Examination
Penetrating Abdominal Trauma
Stab Wounds.
Gunshot Wounds.
Blunt Abdominal Trauma
Differential Diagnoses
Trauma Versus Medical Condition
Single Versus Multisystem Trauma
Single Versus Multiple Intraperitoneal Organ Injury
Intraperitoneal Injury Versus Necessary Laparotomy
Diagnostic Testing
Ultrasonography
Laboratory
Hematocrit
White Blood Cell Count
Chemistry
Radiology
Plain Radiographs
Computed Tomography
Magnetic Resonance Imaging
Management
Penetrating Abdominal Trauma: Stab Wounds
Anterior Abdomen
Step I: Clinical Indications for Emergent Laparotomy.
Step II: Peritoneal Violation.
Step III: Injury Requiring Laparotomy.
Thoracoabdominal Penetration
Flank and Back
Penetrating Abdominal Trauma: Gunshot Wounds
Step I: Clinical Indications for Laparotomy
Step II: Peritoneal Violation
Thoracoabdominal
Flank and Back
Shotgun Wounds
Blunt Abdominal Trauma
Operative Versus Nonoperative Management
Pelvic Fracture
Multiple System Injury
Bedside Procedures
Diagnostic Peritoneal Lavage
Local Wound Exploration
Therapeutic Angioembolization
Disposition
Consultation
Transfer
References
Chapter 39: Questions & Answers
Chapter 40: Genitourinary System
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Renal Trauma
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Ureteral Trauma
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Bladder Trauma
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Urethral Trauma
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Genital Trauma
Clinical Features
Differential Diagnoses
Diagnostic Testing
Imaging
Management
References
Chapter 40: Questions & Answers
Chapter 41: Peripheral Vascular Injury
Principles
Background and Importance
Anatomy and Physiology
Upper Extremity
Lower Extremity
Pathophysiology
Penetrating Trauma
Blunt Trauma
Complete Occlusive Injury
Transection.
Thrombosis.
Reversible Arterial Spasm.
Nonocclusive Injuries
Intimal Flap.
Pseudoaneurysm.
Arteriovenous Fistula.
Compartment Syndrome.
Clinical Features
Hard Findings of Vascular Injury
Soft Findings of Vascular Injury
Asymptomatic High-Risk Wounds
History
Physical Examination
Differential Diagnoses
Diagnostic Testing
Plain Radiography
Pulse Oximetry and Near-Infrared Spectroscopy
Handheld Doppler
Arterial Pressure Index and Ankle-Brachial Index
Ultrasound
Computed Tomography and Magnetic Resonance Imaging
Arteriography
Diagnosis of Specific Vascular Injuries
Management
Major Vascular Injuries
Upper Extremity Arterial Injuries
Lower Extremity Arterial Injuries
Late Complications of Arterial Injury
Venous Injuries
Minor Vascular Injuries
Arterial Spasm
Antibiotics
Disposition
References
Chapter 41: Questions & Answers
Section Two: Orthopedic Lesions
Chapter 42: General Principles of Orthopedic Injuries
Management Principles
Fractures
Fracture Nomenclature
General Descriptors
Descriptive Modifiers
Fracture Eponyms
Fracture Healing
Diagnostic Modalities for Fractures
Plain Radiography
Special Imaging Techniques
Computed Tomography.
Magnetic Resonance Imaging.
Ultrasound Imaging.
Complications of Fractures
Infection (Osteomyelitis)
Hemorrhage
Vascular Injuries
Nerve Injuries
Compartment Syndrome
Pathophysiology.
Anatomic Considerations and Risk Factors.
Clinical Presentation.
Diagnostic Tests.
Treatment, Complications, and Disposition.
Avascular Necrosis
Fat Embolism Syndrome
Fracture Blisters
Complications of Immobilization
Damage Control Orthopedic Surgery
Subluxation and Dislocations
Nomenclature
Assessment
Treatment
Soft Tissue Injuries
Sprains
Nomenclature
Assessment
Treatment and Disposition
Strains
Nomenclature
Assessment
Treatment and Disposition
Tendinitis and Tendinosis
Bursitis
Treatment Modalities
Splinting and Bandaging
Field Care
Emergency Department Care
Upper Extremity
Sling-and-Swathe and Velpeau Bandages.
Clavicle Fractures.
Plaster and Fiberglass Splints.
Forearm and Wrist Splints.
Lower Extremity
Ankle.
Casts
Thermal Therapy
References
Chapter 42: Questions & Answers
Chapter 43: Hand
Principles
Anatomy
Muscles and Tendons
Intrinsic Musculature.
Extrinsic Musculature.
Extensor Tendons.
Flexor Tendons.
Synovial Spaces.
Blood Supply
Arterial System.
Venous and Lymphatic Systems.
Nerve Supply
Motor Innervation.
Sensory Distribution.
Fingertip
Nail
Clinical Features
Diagnostic Testing
Management of Specific Injuries
Traumatic Injuries
Fingertip Injuries
Acute Nail Bed Injuries
Subungual Hematoma.
Nail Bed Lacerations.
Foreign Bodies in the Hand
Hand Fractures
Principles
Clinical Features
Distal Phalanx Fractures.
Management.
Complications.
Middle and Proximal Phalangeal Fractures.
Management.
Complications.
Metacarpal Fractures.
Metacarpal Fractures of the Index, Middle, Ring, and Little Fingers.
Management.
Complications.
Metacarpal Fractures of the Thumb.
Soft Tissue Injuries
Dislocations and Ligamentous Injuries
Principles
Interphalangeal Joint Injuries
Distal Interphalangeal Joint
Proximal Interphalangeal Joint
Management.
Injury to the Interphalangeal Joint of the Thumb
Metacarpophalangeal Joint Injury
Management.
Injury to the Metacarpophalangeal Joint of the Thumb
Management.
Carpometacarpal Joint Injury
Management.
Injuries to the Carpometacarpal Joint of the Thumb.
Ulnar Collateral Ligament Injuries
Management.
Radial Collateral Ligament Injuries.
Tendon Injuries
Extensor Tendon Injuries
Principles.
Clinical Features and Management
Zone I Extensor Injuries.
Zone II Extensor Injuries.
Zone III Extensor Injuries.
Zone IV Extensor Injuries.
Zone V Extensor Injuries.
Zone VI Extensor Injuries.
Zone VII and VIII Extensor Injuries.
Flexor Tendon Injuries
Principles.
Zone I.
Zone II.
Zone III.
Zones IV and V.
Clinical Features.
Management.
Complications.
Vascular Injuries
Management
Nerve Injuries
Management
Complications
Amputations
Principles
Management
Complications
Fingertip Amputations
Principles.
Classification.
Management.
Complications.
Ring Avulsion Injuries.
Mutilating Injuries.
High-Pressure Injection Injuries
Principles
Clinical Features
Management
Compartment Syndrome in the Hand
Principles
Clinical Features
Management
Infections of the Hand
Paronychia
Principles.
Management.
Felon
Principles.
Management.
Complications.
Herpetic Whitlow
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Complications.
Tenosynovitis
Principles.
Clinical Features.
Management.
Deep Space Infections
Principles.
Clinical Features.
Management.
Septic Arthritis
Principles.
Clinical Features.
Management.
Osteomyelitis
Clinical Features.
Management.
Nontraumatic Disorders of the Hand
Stenosing Tenosynovitis
Ganglion
References
Chapter 43: Questions & Answers
Chapter 44: Wrist and Forearm
Wrist
Principles
Anatomy and Physiology
Clinical Features
Diagnostic Testing: Radiology
Management and Disposition
Carpal Injuries
Scaphoid Fractures
Lunate Fractures
Triquetral Fractures
Pisiform Fractures
Hamate Fractures
Trapezium Fractures
Capitate Fractures
Trapezoid Fractures
Carpal Instability
Radiocarpal Instability and Dislocation
Distal Radius and Ulna Injuries
Colles’ Fracture
Smith’s Fracture
Barton’s Fracture
Hutchinson’s Fracture
Distal Radioulnar Joint Disruption
Soft Tissue Injuries of the Wrist
Carpal Tunnel and Acute Carpal Tunnel Syndrome
de Quervain’s Disease and Intersection Syndrome
Forearm
Principles
Anatomy
Clinical Features
Diagnostic Testing: Radiology
Management and Disposition
Forearm Injuries
Shaft Fractures of Radius and Ulna
Ulna Shaft Fractures
Monteggia’s Fracture
Galeazzi’s Fracture
Essex-Lopresti Lesion
Acknowledgment
References
Chapter 44: Questions & Answers
Chapter 45: Humerus and Elbow
Principles
Clinical Features
Differential Diagnosis
Fractures
Shaft of the Humerus
Clinical Features.
Diagnostic Testing.
Management.
Disposition.
Distal Humerus
Suprarcondylar Fractures.
Extension Type Supracondylar Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Flexion Type Supracondylar Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Transcondylar Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Intercondylar Fractures
Clincial Features.
Diagnostic Testing.
Management and Disposition.
Condylar Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Capitellum and Trochlea Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Epicondylar Fractures
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Olecranon
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Radial Head and Neck
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Dislocations/Subluxations
Elbow
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Radial Head Subluxation
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Soft Tissue Disorders
Epicondylitis
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Olecranon Bursitis
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Biceps Tendon Rupture
Clinical Features.
Diagnostic Testing.
Management and Disposition.
References
Chapter 45: Questions & Answers
Chapter 46: Shoulder
Principles
Anatomy
Clinical Features
History
Physical Examination
Diagnostic Testing
Radiology
Specific Injuries
Fractures
Clavicle
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Disposition.
Complications.
Scapula
Principles.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Complications.
Proximal Humerus
Principles.
Clinical Features.
Management.
Complications.
Proximal Humeral Epiphysis
Principles.
Clinical Features.
Management.
Complications.
Dislocations
Sternoclavicular
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Complications.
Acromioclavicular Joint
Principles.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Complications.
Glenohumeral Dislocations
Principles.
Anterior Dislocations
Pathophysiology.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Complications.
Anterior Subluxation
Posterior Dislocation
Pathophysiology.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Complications.
Inferior Glenohumeral Dislocation (Luxatio Erecta)
Pathophysiology.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Complications.
Scapulothoracic Dissociation
Soft Tissue Conditions
Impingement Syndromes
Principles.
Clinical Features.
Management.
Rotator Cuff Tears
Principles.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Lesions of the Biceps Muscle
Bicipital Tendinitis
Pathophysiology.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Ruptures of the Biceps Tendon
Principles.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Subluxations and Dislocations of the Biceps Tendon
Calcific Tendinitis
Pathophysiology.
Clinical Features.
Diagnostic Testing
Radiology.
Management.
Adhesive Capsulitis
Principles.
Clinical Features.
Management.
Injection Therapy
References
Chapter 46: Questions & Answers
Chapter 47: Musculoskeletal Back Pain
Principles
Background
Epidemiology
Anatomy and Physiology
Pathophysiology
Uncomplicated Back Pain
Nerve Root Syndromes
Skeletal Causes
Clinical Features
History
Physical Examination
Differential Diagnoses
Diagnostic Testing
Laboratory Testing
Imaging Studies
Plain Radiographs
Computed Tomography
Magnetic Resonance Imaging
Computed Tomography Myelogram
Management
Uncomplicated Back Pain
Disk Herniation
Nerve Root Pain
Epidural Abscess and Spinal Osteomyelitis
Epidural Hematoma
Cauda Equina Syndrome
Malignancy
Fracture
Disposition
References
Chapter 47: Questions & Answers
Chapter 48: Pelvic Trauma
Perspective
Background
Epidemiology
Anatomy
Bony and Ligamentous Anatomy
Vascular Anatomy
Neurologic Anatomy
Pathophysiology and Key Patterns of Pelvic Fracture
Stable Injuries (Tile Type A)
Undisplaced or Minimally Displaced Fractures of the Pelvic Ring.
Transverse Fractures of the Sacrum.
Avulsion Fractures.
Stress Fractures.
Pathologic and Insufficiency Fractures.
Partially Stable and Unstable Injuries (Tile Types B and C)
Anteroposterior Compression.
Lateral Compression.
Vertical Shear.
Vertical Sacral Fractures.
Open Pelvic Fractures
Penetrating Pelvic Trauma
Associated Pelvic Injuries
Urologic Injury
Neurologic Injury
Gynecologic Injury
Associated Non-Pelvic Injuries
Acetabular Fractures
Coccyx Fractures
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Radiology
Plain Radiography
Computed Tomography
Evaluation of Hemorrhage
Diagnostic Peritoneal Lavage
Ultrasound
Computed Tomography
Management
Resuscitation
Control of Hemorrhage
Stabilizing the Pelvis
Noninvasive Techniques.
Formal External Fixation.
Angiography and Embolization
Hemodynamically Unstable Patients With Pelvic and Intra-Abdominal Hemorrhage
Disposition
Acknowledgments
References
Chapter 48: Questions & Answers
Chapter 49: Femur and Hip
Principles
Anatomy of the Hip and Femur
Skeletal Anatomy
Musculature
Arterial Supply
Venous System
Nerves
Pathophysiology
Osteoporosis of the Femur
Fractures and Trauma of the Femur and Hip
Osteoarthritis of the Hip.
Avascular Necrosis
Myositis Ossificans
Calcific Bursitis and Calcifying Peritendinitis
Neoplastic Disease in the Hip
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Radiographic Evaluation
Occult Hip Fracture
Management
Traction and Immobilization
Open Fracture Care
Compartment Syndrome
Pain Management
Systemic Analgesia
Pharmacologic Approaches
Femoral Nerve Block
Hip Arthroplasty
Fractures of the Hip and Femur
Avulsion Fractures
Proximal Femoral Fractures
Femoral Neck Fractures
Classification.
Intertrochanteric Fractures
Isolated Fractures of the Greater or Lesser Trochanter
Subtrochanteric Fractures
Femoral Shaft Fractures
Stress Fractures
Pathophysiology.
Dislocations and Fracture-Dislocations of the Hip and Femur
Hip Dislocations
Fracture-Dislocation of the Femoral Head
Dislocation of Hip Prosthetics
Soft Tissue Injuries
Muscular Injuries
The Hamstrings.
The Quadriceps.
Iliopsoas Strain.
Hip Adductor Strain.
Gluteus Muscle Strain.
Tendon Injuries
Osteitis Pubis
Vascular Injuries
Neurologic Injuries
Acknowledgments
References
Chapter 49: Questions & Answers
Chapter 50: Knee and Lower Leg
Knee
Principles
Background and Importance
Anatomy and Physiology
Clinical Features
Physical Examination
Tests for Specific Injuries and Disturbances
Anterior Drawer Test.
Posterior Drawer Test.
Posterior Sag Sign Test.
Collateral Ligament Stress Test.
Assessing for Meniscal Tears.
Mcmurray’s Test.
Apley’s Test.
Diagnostic Testing
Radiologic Evaluation
Angiography
Duplex Ultrasonography
Radionuclide Bone Scan
Arthroscopy
Joint Injection
Arthrocentesis
Knee Injuries
Dislocation
Anatomy and Pathophysiology
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management
Distal Femur Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Tibial Plateau Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Fractures of the Intercondylar Eminence (Tibial Spine)
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Osteochondritis Dissecans
Extensor Mechanism Injuries
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management
Patellar Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management
Patellar Dislocation
Anatomy and Pathophysiology
Clinical Features
Diagnostic Strategies
Management and Disposition
Cruciate and Collateral Ligament Injuries
Clinical Features
Cruciate Ligament Injuries.
Collateral Ligament Injuries.
Diagnostic Testing
Management and Disposition
Meniscal Injuries
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Overuse Syndromes
Patellofemoral Pain Syndrome
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management
Iliotibial Band Syndrome
Clinical Features
Management and Disposition
Peripatellar Tendinitis
Plica Syndrome
Popliteus Tendinitis
Bursitis
Septic Arthritis
Baker’s Cyst
Leg
Principles
Anatomy and Pathophysiology
Clinical Features
Proximal Extraarticular Tibial Fractures
Subcondylar Tibial Fractures
Tibial Tubercle Fractures
Anatomy and Pathophysiology.
Clinical Features.
Diagnostic Testing.
Management.
Tibial Shaft Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Proximal Fibula Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Proximal Tibiofibular Joint Dislocations
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management
Stress Fractures
Anatomy and Pathophysiology
Clinical Features
Diagnostic Testing
Management
Compartment Syndrome
Soft Tissue Injuries Involving the Lower Leg
Strains
Gastrocnemius Strain.
Plantaris Strain and Rupture.
Shin Splints
Foreign Bodies
References
Chapter 50: Questions & Answers
Chapter 51: Ankle and Foot
Ankle
Principles
Anatomy
Pathophysiology
Clinical Features
Physical Examination
Diagnostic Testing
Radiology
Other Imaging Techniques
Specific Pathologic Conditions
Ankle Fractures: General Considerations
Pathophysiology
Management
Disposition
Unimalleolar Fractures
Lateral Malleolar Fractures
Medial Malleolar Fractures
Posterior Malleolar Fractures
Bimalleolar Fractures
Trimalleolar Fractures
Open Fractures
Management
Complications
Pilon Fractures
Pathophysiology
Management
Complications
Soft Tissue Injuries
Ligament Injuries
Pathophysiology.
Clinical Features.
Diagnostic Tests and Differential Diagnosis.
Management.
Disposition.
Tendon Injuries
Achilles Tendon Rupture.
Peroneal Tendon Dislocation or Rupture.
Tibialis Posterior Tendon Rupture.
Other Tendon Injuries.
Ankle Dislocations
Foot
Principles of Disease
Anatomy
Clinical Features
Diagnostic Testing: Radiology
Specific Pathologic Conditions
Hindfoot Injuries
Talar Fractures
Principles of Disease: Anatomy.
Pathophysiology.
Minor Talar Fractures.
Major Talar Fractures.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Osteochondral Lesions
Subtalar Dislocations
Principles of Disease: Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Total Talar Dislocation
Calcaneal Fractures
Principles of Disease: Anatomy.
Pathophysiology.
Intraarticular Calcaneal Fractures.
Extraarticular Calcaneal Fractures.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Midtarsal Joint Injuries
Midfoot Injuries
Navicular Fractures
Principles of Disease: Anatomy.
Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Cuboid Fractures
Cuneiform Fractures
Dislocations of the Navicular, Cuboid, and Cuneiforms
Lisfranc (Tarsometatarsal) Fractures and Dislocations
Principles of Disease: Anatomy.
Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Forefoot Injuries
Metatarsal Fractures
Metatarsal Shaft Fractures
Principles: Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Metatarsal Head and Neck Fractures.
Metatarsal Base Fractures
Pathophysiology.
Fifth Metatarsal.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Phalangeal Fractures
Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Sesamoid Fractures
Metatarsophalangeal Dislocations
Pathophysiology.
Clinical Features.
Diagnostic Testing: Radiology.
Management.
Disposition.
Interphalangeal Joint Dislocations
Foot Pain
Perspective.
Hindfoot Pain.
Midfoot Pain.
Forefoot Pain.
Special Considerations
Complex Regional Pain Syndrome
Stress Fractures
Pathophysiology
Clinical Features
Diagnostic Testing: Radiology
Management
Disposition
Tendon Injuries
Crush Injuries, Amputations, and Major Vascular Injuries
Compartment Syndrome
Principles of Disease: Pathophysiology
Clinical Features
Diagnostic Testing: Special Procedures
Management
Disposition
Acknowledgment
References
Chapter 51: Questions & Answers
Section Three: Soft Tissue Injuries
Chapter 52: Wound Management Principles
Principles
Anatomy of Skin and Fascia
Wound Biology
Biomechanical Properties of Skin
Clinical Features
History
Risk Factors
Physical Examination
Diagnostic Testing
Management
Anesthesia
Anesthetic Agents
Allergy
Skin Preparation
Wound Preparation
Débridement
Wound Cleansing
Irrigation
Wound Closure
Decision-Making
Wound Tension
Suture Technique
Basic and Advanced Techniques
Simple Sutures.
Procedure.
Intradermal (Buried) Sutures.
Procedure.
Scalp Laceration Repair.
Procedure.
Skin Tears.
Vertical Mattress Sutures.
Procedure.
Horizontal Mattress Sutures.
Procedure.
Dog-Ear Deformity Repair.
Procedure.
Corner Stitch (Half-Buried Horizontal Mattress Sutures).
Procedure.
V-Y Wound Closure.
Procedure.
Materials
Suture.
Needles.
Tape.
Staples.
Tissue Adhesives.
Antibiotic Prophylaxis
Contamination, Crush, and Host Factors
Open Fractures, Joint Wounds, and Gunshot Wounds
Bites and Puncture Wounds
Cat Bites.
Dog Bites.
Hand Bites.
Intraoral Lacerations.
Puncture Wounds of the Foot.
Drains, Dressings, and Immobilization
Drains
Dressings
Immobilization
Disposition
Wound Care Instructions
Tetanus Immunization
References
Chapter 52: Questions & Answers
Chapter 53: Foreign Bodies
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Eye
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Ear
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Nose
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Airway
Principles
Background and Importance
Anatomy and Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Gastrointestinal Tract
Principles
Pharynx and Esophagus
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Stomach and Bowel
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Rectum
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Genitourinary Tract
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Soft Tissues
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 53: Questions & Answers
Chapter 54: Mammalian Bites
Principles
Background
Dog Bites
Principles
Clinical Features
Capnocytophaga Canimorsus
Differential Diagnoses
Diagnostic Testing
Management
Prophylactic Antibiotics
Disposition
Cat Bites
Principles
Clinical Features
Bacteriology
Pasteurella Multocida.
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Other Mammals
Monkeys
Principles
Clinical Features
Differential Diagnoses
Management
Disposition
Rodents
Principles
Clinical Features
Differential Diagnoses
Management
Disposition
Ferrets
Domestic Herbivores
Sheep, Cattle, and Pigs
Horses
Camels
Wild Animals
Bears
Wild Cats
Coyotes and Wolves
Management
Other Prophylaxis
Disposition
Human Bites
Principles
Clinical Features
Fight Bites (Clenched Fist Injury)
Other Human Bites
Bacteriology.
Differential Diagnoses
Diagnostic Testing
Management
Prophylactic Antibiotics
Disposition
References
Chapter 54: Questions & Answers
Chapter 55: Venomous Animal Injuries
Principles
Epidemiology
Venom Delivery
Venomous Reptiles
Snakes
Epidemiology
Classification and Characteristics
Identification
Other Reptiles
Toxins
Venom Delivery
Clinical Features
Pit Vipers
Coral Snakes
Gila Monster
Infection
Differential Diagnoses
Diagnostic Testing
Management
Out-of-Hospital Care
Emergency Department Care
Patient History.
Patient Examination.
Initial Medical Care.
Antivenom.
Administration of Antivenom.
Dosage and Precautions.
Coral and Exotic Snakes.
Wound Care.
Serum Sickness.
Other Envenomation.
Disposition
Venomous Arthropods
Hymenoptera
Clinical Features
“Killer Bees.”
Fire Ants.
Differential Diagnoses
Diagnostic Testing
Management
Prehospital Care.
Emergency Department Care.
Disposition
Spiders and Scorpions
Black Widow Spider
Clinical Features.
Differential Diagnoses.
Diagnostic Testing.
Management.
Latrodectus Antivenom.
Disposition
Brown Recluse Spider
Clinical Features.
Differential Diagnoses.
Diagnostic Testing.
Management.
Disposition.
Other Spiders
Scorpions
Clinical Features.
Differential Diagnoses.
Diagnostic Testing.
Management.
Disposition
Other Arthropods
Venomous Marine Animals
Principles
Venom Delivery
Bites
Nematocysts
Toxicity.
Clinical Features
Stings
Sea Urchins.
Cone Shells.
Stingray.
Bony Fishes.
Management
Nematocysts
Fish
Disposition
References
Chapter 55: Questions & Answers
Chapter 56: Thermal Burns
Principles
Background
Epidemiology
Anatomy and Physiology
Pathophysiology of Burns
Clinical Features
Classification and Diagnosis of Burns
Differential Diagnoses
Diagnostic Testing
Management
Initial First Aid
Airway Management
Breathing Management: Recognition and Management of Inhalation Injury
Circulation Management and Fluid Resuscitation
Escharotomy
Local Wound Therapies
Pain Management
Disposition
References
Chapter 56: Questions & Answers
Chapter 57: Chemical Injuries
Principles
Community Preparedness and HazMat Response
Contingency Plan
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Ocular Injuries
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Specific Toxins
Hydrofluoric Acid
Principles
Clinical Features
Inhalational Exposure
Gastrointestinal Exposure
Ocular Exposure
Dermal Exposure
Differential Diagnoses
Diagnostic Testing
Management
Infiltration Therapy
Subcutaneous.
Intravenous and Intra-Arterial.
Ocular Exposures
Systemic Toxicity
Disposition
Formic Acid
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Anhydrous Ammonia
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Cement
Phenol and Derivatives
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Polyethylene Glycol Therapy
Treatment of Systemic Toxicity
Disposition
Phosphorus
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Nitrates and Nitrites
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Hydrocarbons
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Tar
Principles
Clinical Features
Management
Disposition
Elemental Metals
Chromium
Miscellaneous Gases
Chlorine
Phosgene
Nitrogen Oxides
Chemical Terrorism
Principles
Response
Chemical Agents
Nerve Agents
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Vesicants
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Cyanide
Principles
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 57: Questions & Answers
Section Four: Violence and Abuse
Chapter 58: Sexual Assault
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Sexually Transmitted Infections
Alcohol- or Drug-Facilitated Rape
Evaluating the Victim of Attempted Strangulation
Management
Medical Forensic Examination
General Principles of Evidence Collection
Special Techniques
Colposcopy.
Toluidine Blue Dye.
Alternate Light Source.
Special Populations
Older Adult Sexual Assault
Male Sexual Assault
Further Considerations
Definitive Treatment to Prevent Sexually Transmitted Infections and Pregnancy
Disposition
Testifying in Court
References
Chapter 58: Questions & Answers
Chapter 59: Intimate Partner Violence and Abuse
Principles
Background and Importance
Causes and Natural History of Intimate Partner Violence
Clinical Features
Injury Presentations
Gynecologic-Related Presentations
Mental Health Presentations
Alcohol and Drug Use and Intimate Partner Violence
Chronic Medical Conditions
Pain Syndromes
Diagnostic Considerations
Differential Diagnosis
Human Trafficking
Diagnostic Testing
Screening
Management
Intervention
Danger Assessment
Mental Health Screening
Privacy and Confidentiality Considerations
Documentation
Intimate Partner Violence Coding and Diagnosis
Disposition
References
Chapter 59: Questions & Answers
Part III: Medicine and Surgery
Section One: Head and Neck Disorders
Chapter 60: Oral Medicine
Introduction
Disorders of the Tooth
Principles
Anatomy
Pathophysiology
Clinical Features
Physical Examination
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Disorders of the Gingiva and Periodontium
Principles
Anatomy
Pathophysiology
Gingivitis and Periodontitis.
Pericoronitis.
Gingival Hyperplasia.
Clinical Features
Historical Features
Physical Examination
Differential Diagnosis
Diagnostic Testing
Management
Gingivitis and Periodontitis
Pericoronitis
Disposition
Disorders Involving Dental Procedures
Principles
Anatomy
Pathophysiology
Clinical Features
Historical Features
Physical Examination
Diagnostic Testing
Management
Disposition
Odontogenic and Deep Neck Infections
Principles
Anatomy
Pathophysiology
Clinical Features
Historical Features
Physical Examination
Diagnostic Testing
Management
Disposition
Dentoalveolar Trauma
Principles
Anatomy
Pathophysiology
Dental Fractures.
Concussion, Subluxation, Luxation, and Avulsion.
Clinical Features
Historical Features
Physical Examination
Diagnostic Testing
Management
Dental Fractures
Tooth Avulsion
Luxation and Alveolar Fractures
Soft Tissue Injuries
Disposition
Temporomandibular Joint Disorder and Dislocation
Principles
Anatomy
Pathophysiology
Temporomandibular Joint Disorder.
Temporomandibular Joint Dislocation.
Clinical Features
Historical Features
Temporomandibular Joint Disorder.
Temporomandibular Joint Dislocation.
Physical Examination
Temporomandibular Joint Disorder.
Temporomandibular Joint Dislocation.
Differential Diagnoses
Diagnostic Testing
Management
Temporomandibular Joint Disorder
Temporomandibular Joint Dislocation
Disposition
References
Chapter 60: Questions & Answers
Chapter 61: Ophthalmology
Traumatic Conditions
Principles
Periorbital Contusions and Eyelid Lacerations
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Conjunctival and Scleral Injuries: Subconjunctival Hemorrhage, Conjunctival Laceration, and Scleral Laceration
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Corneal Injuries: Corneal Abrasions, Foreign Bodies, and Lacerations
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Corneal Abrasions.
Corneal Foreign Bodies.
Corneal Lacerations.
Anterior Segment Injuries: Traumatic Hyphema, Iritis, Cyclodialysis, and Lens Dislocation
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Traumatic Iritis, Hyphema, and Cyclodialysis.
Lens Subluxation and Dislocation.
Posterior Segment/Ocular Injuries: Commotio Retinae, Retinal Detachment, Intraocular Foreign Body, and Perforated Globe
Clinical Features and Differential Diagnosis
Diagnostic Evaluation
Management and Disposition
Retinal Injuries.
Intraocular Foreign Bodies and Globe Rupture.
Retrobulbar and Peribulbar Injuries: Orbital Wall Fracture, Retrobulbar Hemorrhage, and Optic Nerve Injury
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Orbital Wall Fractures.
Retrobulbar Hemorrhage.
Optic Nerve Injury.
Chemical Exposures and Glues
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Inflammatory Conditions
Principles
The Conjunctiva and Cornea: Keratitis, Pterygium and Pinguecula
Clinical Features and Differential Diagnosis
Diagnostic Evaluation
Management and Disposition
Superficial Punctate Keratitis and Radiation Keratitis.
Pterygium and Pinguecula.
The Globe: Uveitis, Scleritis, and Episcleritis
Clinical Features and Differential Diagnosis
Diagnostic Evaluation
Management and Disposition
The Orbit: Orbital Pseudotumor, Orbital Apex Syndrome, and Thyroid Orbitopathy
Clinical Features, Differential Diagnosis, and Diagnostic Evaluation
Management and Disposition
Infectious Conditions
Principles
The Conjunctiva: Allergic, Viral and Bacterial Conjunctivitis, and Ophthalmia Neonatorum
Clinical Features, Differential Diagnosis, and Diagnostic Testing
Management and Disposition
Allergic and Viral Conjunctivitis.
Bacterial Conjunctivitis.
Ophthalmia Neonatorum.
The Cornea: Corneal Ulcers, Herpes Simplex Keratitis, and Herpes Zoster Keratitis
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Corneal Ulcers and Infiltrates.
Herpes Simplex Keratitis.
Herpes Zoster Keratitis.
The Eyelids and Periorbital Area: Hordeolum, Chalazion, Dacryocystitis, Blepharitis, and Cellulitis
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Hordeolum and Chalazion.
Dacryocystitis.
Blepharitis.
Periorbital Cellulitis.
The Globe: Endophthalmitis
Clinical Features, Differential Diagnosis, and Diagnostic Testing
Management and Disposition
Acute Angle-Closure Glaucoma
Principles
Clinical Features, Differential Diagnosis, and Diagnostic Testing
Management and Disposition
Primary Disorders of Vision
Principles
Blurred Vision: Optic Neuritis, Toxic and Metabolic Disturbances, and Papilledema
Clinical Features and Differential Diagnosis
Diagnostic Testing, Management, and Disposition
Optic Neuritis.
Toxic and Metabolic Visual Disturbances.
Papilledema.
Visual Field Disturbances: Floaters, Flashes, and Field Deficits
Clinical Features and Differential Diagnosis
Diagnostic Testing, Management, and Disposition
Vitreous Hemorrhage and Detachment.
Retinal Detachment.
Chiasmal and Cortical Disturbances.
Sudden Vision Loss: Retinal Artery and Vein Occlusion, and Ischemic Optic Neuropathy
Clinical Features and Differential Diagnosis
Diagnostic Testing, Management, and Disposition
Central Retinal Artery Occlusion.
Central Retinal Vein Occlusion.
Ischemic Optic Neuropathy.
Functional Vision Loss
Clinical Features, Differential Diagnosis, Diagnostic Testing, Management, and Disposition
Diplopia
Anisocoria
Principles
Clinical Features and Differential Diagnosis
Adie’s and Argyll Robertson Pupils
Pharmacologic Mydriasis and Miosis
Third-Nerve Palsy
Horner’s Syndrome
Physiologic and Headache-Associated Anisocoria
Diagnostic Testing, Management, and Disposition
Nystagmus
Principles
Clinical Features, Differential Diagnosis, Diagnostic Evaluation, Management, and Disposition
Peripheral Nystagmus and Central Nystagmus
Toxic and Metabolic Nystagmus
References
Chapter 61: Questions & Answers
Chapter 62: Otolaryngology
Otitis Media
Principles
Anatomy and Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Otitis Externa
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Necrotizing (Malignant) External Otitis
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Mastoiditis
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Sudden Hearing Loss
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Epistaxis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Sialolithiasis
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Neck Masses
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management and Disposition
References
Chapter 62: Questions & Answers
Section Two: Pulmonary System
Chapter 63: Asthma
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Symptoms
Differential Diagnoses
Diagnostic Testing
Pulmonary Function Studies
Blood Gas Analysis
Other Blood Testing
Future Monitoring Strategies
Management
Oxygen Administration
Adrenergic Medication
Nebulizer Versus Metered-Dose Inhaler and Valved Holding Chamber.
Intravenous Adrenergic Agonists.
Subcutaneous Adrenergic Agents.
Long-Acting Beta-2 Agonists.
Corticosteroids
Systemic Corticosteroids.
Inhaled Corticosteroids.
Corticosteroids and Discharged Patients.
Corticosteroid-Resistant Asthma.
Methylxanthines
Leukotriene Modifiers
Other and Future Therapies
Special Situations
Pregnancy
Aspirin-Exacerbated Respiratory Disease
Exercise-Induced Asthma
Perimenstrual Asthma
Critical Asthma Syndromes
Clinical Approach to the Critically Ill Asthmatic
Disposition
References
Chapter 63: Questions & Answers
Chapter 64: Chronic Obstructive Pulmonary Disease
Principles
Background
Pathophysiology
Clinical Features
Symptoms and Natural History
Severity of Airflow Limitation
Physical Examination
Differential Diagnoses
Diagnostic Testing
Pulse Oximetry, Blood Gas Analysis, and Capnography
Chest Radiography
Spirometry
Sputum Examination
Electrocardiogram and Cardiac Monitoring
Blood Tests
Management
Oxygenation and Ventilation
General Drug Therapy
Bronchodilators
Corticosteroids
Antibiotics
Other Therapeutic Agents
Mucokinetic Medications and Mucus Clearance Strategies.
Heliox.
Respiratory Stimulants.
Prevention of Chronic Obstructive Pulmonary Disease Exacerbations via Anti-Inflammatory Therapy.
Future Therapies for Chronic Obstructive Pulmonary Disease Exacerbations.
Disposition
References
Chapter 64: Questions & Answers
Chapter 65: Upper Respiratory Tract Infections
Pharyngitis (Tonsillopharyngitis)
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Lingual Tonsillitis
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Laryngitis
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnoses
Management
Disposition
Adult Epiglottis
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Peritonsillitis (Peritonsillar Cellulitis and Peritonsillar Abscess)
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Ludwig’s Angina
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Retropharyngeal Abscess
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Parapharyngeal Abscess
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Strategies
Management
Disposition
Rhinosinusitis
Principles
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 65: Questions & Answers
Chapter 66: Pneumonia
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 66: Questions & Answers
Chapter 67: Pleural Disease
Spontaneous Pneumothorax
Principles
Background and Importance
Anatomy and Physiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Pleural Inflammation and Effusion
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 67: Questions & Answers
Section Three: Cardiac System
Chapter 68: Acute Coronary Syndrome
Principles
Epidemiology
Spectrum of Illness: Coronary Artery Disease and Acute Coronary Syndrome
Stable Angina
Unstable Angina
Acute Myocardial Infarction
Pathophysiology
Clinical Features
Prehospital Evaluation
Emergency Department Evaluation
History
Classic History.
Nontraditional (or Atypical) History.
Outcomes in Nontraditional Presentations
Physical Examination
Missed Diagnosis of Acute Coronary Syndrome
Early Complications of Acute Myocardial Infarction
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Electrocardiography
Electrocardiographic Abnormalities in Acute Coronary Syndromes.
Anatomic Location of Acute Myocardial Infarction.
Electrocardiographic Differential Diagnosis of ST Segment Elevation.
Non–ST Segment Elevation Myocardial Infarction.
Electrocardiographic Adjuncts in the Diagnosis of Acute Coronary Syndrome.
Limitations of Electrocardiography in Acute Coronary Syndrome.
Chest Radiography
Serum Markers
Troponins.
Other Serum Markers.
Multiple Marker Strategies.
Exercise Testing
Echocardiography
Myocardial Scintigraphy (Nuclear Imaging)
Coronary Computed Tomography Angiography
Observation Unit Evaluation
Management
Time-Sensitive Nature of Acute Coronary Syndrome Therapy
Pharmacologic Intervention
Oxygen
Nitroglycerin
Morphine and Other Opioid Analgesic Agents
β-Adrenergic Blockers
Angiotensin-Converting Enzyme Inhibitors
HMG–Coenzyme A Reductase Inhibitors (Statins)
Calcium Channel Blockade
Antiplatelet Therapy
Aspirin.
Glycoprotein IIb/IIIa Receptor Inhibitors.
PSY12 Receptor Inhibitor Agents.
Antithrombins
Heparins.
Other Antithrombins: Bivalirudin, Fondaparinux, and Hirudin.
Reperfusion Therapies
Fibrinolytic Therapy
Fibrinolytic Agent Selection.
Eligibility Criteria for Fibrinolytic Agent Therapy.
12-Lead Electrocardiogram.
Patient Age.
Time From Symptom Onset.
Blood Pressure Extremes.
Retinopathy.
Cardiac Arrest Requiring Cardiopulmonary Resuscitation.
Previous Stroke or Transient Ischemic Attack.
Previous Myocardial Infarction or Coronary Artery Bypass Graft.
Recent Surgery or Trauma.
Menstruation.
Percutaneous Coronary Intervention.
Rescue Percutaneous Coronary Intervention.
Facilitated Percutaneous Coronary Intervention.
Choice of Reperfusion Therapy.
Reperfusion Therapy in Cardiogenic Shock.
Resuscitated Cardiac Arrest With Suspected Acute Coronary Syndrome
Management Summary: Potential Pharmacologic Management Approach
Disposition
Transfer of a Patient With Acute Coronary Syndrome
References
Chapter 68: Questions & Answers
Chapter 69: Dysrhythmias
Principles
Cardiac Cellular Electrophysiology
Anatomy and Conduction
Mechanisms of Dysrhythmia Formation
Classification of Antidysrhythmic Drugs
Class IA Agents
Procainamide
Class IB Agents
Lidocaine
Class IC Agents
Flecainide
Propafenone
Class II Agents
Esmolol
Metoprolol
Class III Agents
Bretylium
Amiodarone
Ibutilide
Sotalol
Dofetilide
Dronedarone
Class IV Agents
Diltiazem
Verapamil
Miscellaneous Agents
Digoxin
Magnesium
Adenosine
Approach to Dysrhythmia: Recognition and Management
Clinical Features
Initial Assessment of Stable Patients
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Management
Sinus Bradycardia and Sinoatrial and Atrioventricular Block
Sinus Bradycardia
Sinus Dysrhythmia
Sinus Arrest and Sinoatrial Exit Block
Sick Sinus Syndrome
Atrioventricular Block
First-Degree Atrioventricular Block
Second-Degree Atrioventricular Block
Type I Second-Degree Atrioventricular Block.
Type II Second-Degree Atrioventricular Block.
Third-Degree Atrioventricular Block
Extrasystoles
Premature Atrial Contractions
Premature Ventricular Contractions
Narrow-Complex Tachycardia
Sinus Tachycardia
Atrial Tachycardia
Atrial Fibrillation
Atrial Flutter
Atrioventricular Nodal Reentrant Tachycardia
Junctional Tachycardia
Preexcitation and Accessory Pathway Syndromes
Wide-Complex Tachycardia
Ventricular Tachycardia
Torsades de Pointes
Brugada’s Syndrome
Disposition
References
Chapter 69: Questions & Answers
Chapter 70: Implantable Cardiac Devices
Principles
Clinical Features
Pacemaker Terminology
Pacemaker Components
History
Physical Examination
Differential Diagnosis
Complications of Implantation
Infection
Thrombophlebitis
The “Pacemaker Syndrome”
Pacemaker Malfunction
Failure to Capture
Inappropriate Sensing
Undersensing
Oversensing
Inappropriate Pacemaker Rate
Diagnostic Testing
Chest Radiograph
12-Lead Electrocardiogram
Management
Advanced Cardiac Life Support Interventions
Disposition
Implantable Cardioverter- Defibrillators
Principles
Clinical Features
Terminology and Components
Differential Diagnosis
Complications of Implantation
Malfunction
Diagnostic Testing
Management
Advanced Cardiac Life Support Interventions
Disposition
Biventricular Pacing
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Cardiac Assist Devices
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 70: Questions & Answers
Chapter 71: Heart Failure
Principles
Background
Epidemiology
Anatomy and Physiology
Cellular Mechanisms
Cardiac Physiology
Physiologic Mechanisms
Increase in Stroke Volume
Increased Systemic Vascular Resistance
Development of Cardiac Hypertrophy
Neurohormonal Modulation
Cardiac Neurohormonal Response
Central and Autonomic Nervous System Neurohormonal Response
Renal Neurohormonal Response
Vascular Endothelial Neurohormonal Response
Pathophysiology
Maladaptive Changes in Heart Failure
Primary Disease Processes Resulting in Heart Failure
Coronary Artery Disease.
Cardiomyopathy and Myocarditis.
Valvular Heart Disease.
Pericardial Diseases.
Pulmonary Disease.
Classification of Heart Failure
Acute Versus Chronic Heart Failure.
Systolic Versus Diastolic Dysfunction.
Right-Sided Versus Left-Sided Heart Failure.
High-Output Versus Low-Output Failure.
Precipitating Causes of Heart Failure and Exacerbating Factors
Sodium and Volume Excesses
Systemic Hypertension
Myocardial Infarction and Ischemia
Systemic Infection
Dysrhythmias
Acute Hypoxia and Respiratory Problems
Anemia
Pregnancy
Thyroid Disorders
Acute Myocarditis
Acute Valvular Dysfunction
Pulmonary Embolus
Sympathomimetic or Alcohol Excess
Excessive Exertion or Trauma
Pharmacologic Complications
Clinical Features
History
Physical Examination
Differential Diagnoses
Diagnostic Testing
Management
Acute Heart Failure
Acute Heart Failure With Adequate Perfusion
Oxygen and Ventilation
Vasodilator Agents
Nitrates
Morphine Sulfate
Loop Diuretics
Other Therapies
Treatment of Acute Heart Failure in Hypotensive Patients
Inotropic or Vasopressor Therapy
Rate and Rhythm Controllers
Chronic Heart Failure
Common Therapeutic Agents in Chronic Heart Failure
Renin Angiotensin System Blocking Drugs.
Beta-Blocker and Combined Alpha- and Beta-Blocker Therapy.
Diuretics.
Nitrates.
Cardiac Glycosides.
Other Considerations in Chronic Heart Failure
Electrical Therapy.
Antidysrhythmic Therapy.
Calcium Channel Blockers.
Ultrafiltration and Renal Dialysis.
Coronary Artery Bypass Grafting and Angioplasty.
Phosphodiesterase Inhibitors.
Statins and Polyunsaturated Fatty Acids.
Anemia.
Sleep Apnea-Related Respiratory Support.
Exercise Programs.
Advanced Surgical Therapies.
Psychosocial Factors.
Disposition
Admission Criteria, Observation Units, and Predictors of Readmission
References
Chapter 71: Questions & Answers
Chapter 72: Pericardial and Myocardial Disease
Pericardial Disease (Pericarditis)
Principles
Pericardial Anatomy Physiology and Pathophysiology
Specific Disorders: Idiopathic Pericarditis
Principles and Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Complications
Uremic Pericardial Disease
Principles
Clinical Features and Diagnostic Testing
Management and Disposition
Post–Myocardial Infarction Pericarditis
Postinjury Pericarditis
Principles
Clinical Features, Diagnostic Testing, Management, and Disposition
Neoplastic Pericardial Disease
Principles
Clinical Features and Diagnostic Strategies
Management and Disposition
Radiation-Induced Pericarditis
Pericardial Disease Related to Connective Tissue Disorders
Miscellaneous Infectious Causes of Pericarditis
Tuberculous Pericarditis
Other Causes of Pericarditis
Pericardial Effusion
Principles and Clinical Features
Diagnostic Testing
Management and Disposition
Cardiac Tamponade
Principles
Clinical Features and Diagnostic Testing
Management and Disposition
Purulent Pericarditis
Principles
Pathophysiology
Clinical Features and Diagnostic Testing
Management and Disposition
Pneumopericardium
Principles
Clinical Features and Diagnostic Testing
Management and Disposition
Constrictive Pericarditis
Principles and Pathophysiology
Clinical Features
Diagnostic Testing and Management
Myocardial Diseases
Myocarditis
Principles
Pathophysiology
Clinical Features
Diagnostic Testing
Differential Diagnosis
Management
Disposition
Chagas’ Disease
Principles and Clinical Features
Diagnostic Testing
Management
Trichinosis
Diphtheria
Lyme Disease
Epidemiology and Clinical Features
Other Causes of Myocarditis
Cocaine Cardiotoxicity
Cardiomyopathies and Specific Heart Muscle Disease
Principles
Pathophysiology
Dilated Cardiomyopathy
Principles
Pathophysiology
Clinical Features
Diagnostic Testing
Management and Disposition
Outcome
Hypertrophic Cardiomyopathy
Principles
Pathophysiology
Clinical Features
Diagnostic Testing
Differential Diagnosis
Management
Disposition
Restrictive Cardiomyopathy
Principles
Pathophysiology
Clinical Features and Diagnostic Testing
Management and Disposition
Arrhythmogenic Right Ventricular Cardiomyopathy
Peripartum Cardiomyopathy
Principles
Clinical Features and Diagnostic Testing
Management and Disposition
Takotsubo Cardiomyopathy
Principles
Clinical Features and Diagnostic Testing
Management and Disposition
Ion Channelopathies
Principles
Sudden Death
References
Chapter 72: Questions & Answers
Chapter 73: Infective Endocarditis, Rheumatic Fever, and Valvular Heart Disease
Infective Endocarditis
Principles
Background and Importance
Pathophysiology
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management
Disposition
Prophylaxis
Rheumatic Fever
Principles
Background and Importance
Pathophysiology
Clinical Features and Differential Diagnosis
Diagnostic Testing
Management and Disposition
Valvular Heart Disease
Principles
Anatomy and Physiology
Mitral Stenosis
Pathophysiology
Clinical Features
Management
Mitral Regurgitation
Pathophysiology
Clinical Features
Management
Aortic Stenosis
Pathophysiology
Clinical Features
Management
Aortic Insufficiency
Pathophysiology
Clinical Features
Management
Mitral Valve Prolapse
Pathophysiology
Clinical Features
Management
Complications of Prosthetic Valves
Disposition
References
Chapter 73: Questions & Answers
Section Four: Vascular System
Chapter 74: Hypertension
Principles
Background
Importance
Definition of Hypertension and Relevant Terminology
Physiology of Hypertension
Neurohormonal Dysregulation
Vascular Modulation
Sodium Intake
Psychosocial Stress
Obesity
Pathophysiology of Target-Organ Damage
Clinical Features
Hypertensive Emergency
Hypertensive Encephalopathy
Other Hypertension-Related Emergencies
Blood Pressure Elevation
Acute Target Organ Damage in the Context of Systemic Illness
Absence of Target Organ Dysfunction
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Management
Acute Blood Pressure Control
Antihypertensive Therapy
Blood Pressure Goals
Acute Coronary Syndrome and Acute Heart Failure
Aortic Dissection
Acute Ischemic Stroke
Spontaneous Intracranial Hemorrhage
Hypertensive Encephalopathy
Acute Kidney Injury
Preeclampsia and Eclampsia
Sympathetic Crises
Chronic Antihypertensive Therapy
Disposition
References
Chapter 74: Questions & Answers
Chapter 75: Aortic Dissection
Principles
Epidemiology
Anatomy and Physiology
Pathophysiology
Classification
Clinical Features
History
Physical Examination
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Electrocardiography
Chest Radiography
Echocardiography
Computed Tomography
Magnetic Resonance Imaging
Choice of Diagnostic Test
Management
Emergency Department
Recommended Therapy
Alternative Agents
Operative and Interventional Repair
Disposition
References
Chapter 75: Questions & Answers
Chapter 76: Abdominal Aortic Aneurysm
Principles
Epidemiology
Pathophysiology
Natural History
Clinical Features
Unruptured Aneurysms
Ruptured Aneurysms
Pain-Hypotension-Mass Triad
Aortoenteric Fistula
Arteriovenous (Aortocaval) Fistula
Differential Diagnoses
Diagnostic Testing
Abdominal Radiography
Ultrasonography
Computed Tomography
Other Diagnostic Modalities
Management
Ruptured Aneurysms
Fluid Resuscitation
Diagnostic Confirmation
Surgery and Mortality
Intact, Asymptomatic Aneurysms
Traditional Repair
Endovascular Repair
Survival
Late Complications of Repair
Graft Infection
Aortoenteric Fistula
Pseudoaneurysm (Anastomotic Aneurysm)
Complications of Endovascular Aneurysm Repair
Disposition
References
Chapter 76: Questions & Answers
Chapter 77: Peripheral Arteriovascular Disease
Principles
Principles of Disease
Arterial Anatomy
Pathophysiology
Atherosclerosis
Aneurysms
Arterial Embolism
Thromboembolism.
Atheroembolism.
Arterial Thrombosis
Inflammation
Trauma
Vasospasm
Arteriovenous Fistulae
Clinical Features
History
Acute Arterial Occlusion
Chronic Arterial Insufficiency
Physical Examination
Arterial Embolism
Arterial Thrombosis
Inflammation
Vasospasm
Arteriovenous Fistulae
Differential Diagnosis
Diagnostic Testing
Noninvasive Assessment
Contrast Arteriography
Computed Tomography and Magnetic Resonance Imaging
Management
Noninvasive Therapy
Acute Anticoagulation With Heparin
Fibrinolytic Therapy
Invasive Therapy
Fogarty Catheter Thrombectomy
Peripheral Percutaneous Transluminal Angioplasty
Grafting
Sympathectomy
Hyperbaric Therapy
Disposition
Specific Arteriovascular Diseases
Diseases of Chronic Arterial Insufficiency
Arteriosclerosis Obliterans
Clinical Features and Differential Diagnosis
Management
Buerger’s Disease (Thromboangiitis Obliterans)
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Diseases of Acute Arterial Occlusion
Arterial Embolism
Differential Diagnosis
Management
Atheroembolism (Blue Toe Syndrome)
Clinical Features
Differential Diagnosis
Management
Arterial Thrombosis
Management
Peripheral Arterial Aneurysms
Lower Extremity
Upper Extremity
Viscera
Splenic Artery Aneurysms
Hepatic Artery Aneurysms
Superior Mesenteric Artery Aneurysms
Infected Aneurysms
Mycotic Aneurysms
Atherosclerotic Arteries
Preexisting Aneurysms
Post-Traumatic Pseudoaneurysms
Traumatic Aneurysms
Vasospastic Disorders
Thoracic Outlet Syndrome
Principles
Clinical Features
Physical Examination
Ancillary Evaluation
Differential Diagnosis
Management
Disposition
Peripheral Arteriovenous Fistulae
Differential Diagnosis
Management
Vascular Abnormality Caused by Drug Abuse
Principles
Clinical Features
Management
References
Chapter 77: Questions & Answers
Chapter 78: Pulmonary Embolism and Deep Vein Thrombosis
Principles
Anatomy and Pathophysiology of Thrombosis
Clinical Features
Diagnosis
Differential Diagnosis
Diagnostic Testing
Laboratory Evaluation
Radiographic Evaluation
Management
Superficial Leg Thrombophlebitis
Isolated Calf Vein Thrombosis
Phlegmasia Cerulea Dolens (Painful Blue Leg)
Upper Extremity Venous Thromboses
Complications
Disposition
Pulmonary Embolism
Principles
Pathophysiology of Pulmonary Vascular Occlusion
Clinical Features
Differential Diagnosis
Diagnostic Testing
Pregnant Women
Management
Standard Anticoagulation
Fibrinolytic (Thrombolytic) Therapy
Surgical Embolectomy
Disposition
References
Chapter 78: Questions & Answers
Section Five: Gastrointestinal System
Chapter 79: Esophagus, Stomach, and Duodenum
Dysphagia
Principles
Background
Oropharyngeal Dysphagia.
Esophageal Dysphagia.
Pathophysiology
Clinical Features
Oropharyngeal Dysphagia
Esophageal Dysphagia
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Foreign Bodies
Principles
Background
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Upper Esophagus
Lower Esophagus
Stomach
Disposition
Esophageal Perforation
Principles
Background
Anatomy and Physiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Esophagitis
Principles
Gastroesophageal Reflux Disease
Eosinophilic Esophagitis
Infectious Esophagitis
Pill Esophagitis
Radiation-Induced Esophagitis
Clinical Features
Gastroesophageal Reflux Disease
Eosinophilic Esophagitis
Infectious Esophagitis
Pill Esophagitis
Differential Diagnosis
Diagnostic Testing
Management
Gastric Reflux
Eosinophilic Esophagitis
Infectious Esophagitis
Pill Esophagitis
Disposition
Gastritis and Peptic Ulcer Disease
Principles
Background
Pathophysiology
Clinical Features
Complications
Differential Diagnosis
Diagnostic Testing
Management
Antacids
Histamine Blockers
Proton Pump Inhibitors
Prostaglandins
Other Agents
Disposition
Gastric Volvulus
Principles
Clinical Features
Complications
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 79: Questions & Answers
Chapter 80: Disorders of the Liver and Biliary Tract
Hepatic Disorders
Hepatitis
Viral Hepatitis
Principles
Hepatitis A.
Hepatitis B.
Hepatitis C and E.
Hepatitis D.
Hepatitis E and G.
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Prevention and Postexposure Management.
Disposition
Alcoholic Hepatitis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Cirrhosis
Principles
Clinical Features
Diagnostic Testing
Management
Ascites
Gastrointestinal Bleeding
Hepatorenal Syndrome
Hepatic Encephalopathy
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Spontaneous Bacterial Peritonitis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Hepatic Abscesses
Pyogenic Abscess
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Amebic Abscess
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Miscellaneous Disorders and Conditions of the Liver
Liver Disease in Pregnancy
Benign Cholestasis
Acute Fatty Liver
Budd-Chiari Syndrome
Liver Transplantation
Biliary Tract Disorders
Cholelithiasis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Special Considerations
Disposition
Cholecystitis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Special Considerations
Acalculous Cholecystitis.
Emphysematous Cholecystitis.
Disposition
Cholangitis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Sclerosing Cholangitis
AIDS Cholangiopathy
References
Chapter 80: Questions & Answers
Chapter 81: Pancreas
Acute Pancreatitis
Background
Causes
Anatomy and Physiology
Pathophysiology
Disease Classification
Clinical Features
Differential Diagnoses
Diagnostic Testing
Laboratory Results
Imaging
Predicting Disease Severity
Management
Disposition
Chronic Pancreatitis
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Pancreatic Cancer
Clinical Features
Diagnostic Testing
Management
References
Chapter 81: Questions & Answers
Chapter 82: Disorders of the Small Intestine*
Small Bowel Obstruction
Background
Anatomy and Physiology
Pathophysiology
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Laboratory
Imaging
Management
Disposition
Acute Mesenteric Ischemia
Background
Anatomy and Physiology
Pathophysiology
Mesenteric Arterial Embolism
Mesenteric Arterial Thrombosis
Nonocclusive Mesenteric Ischemia
Mesenteric Venous Thrombosis
Unusual Causes of Mesenteric Ischemia
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Imaging
Management
Disposition
References
Chapter 82: Questions & Answers
Chapter 83: Acute Appendicitis
Principles
Background
Anatomy and Physiology
Pathophysiology
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Laboratory Data
White Blood Cell Count
C-Reactive Protein
Combined Inflammatory Markers
Urinalysis
Other Laboratory Tests
Imaging Tests
General Principles
Radiography
Graded-Compression Ultrasound
Computed Tomography
Magnetic Resonance Imaging
Combined Imaging Pathways
Summary of Imaging Methods
Management
Supportive Care
Antibiotic Therapy
Definitive Treatment
Disposition
References
Chapter 83: Questions & Answers
Chapter 84: Gastroenteritis
Overview
Background
Pathophysiology
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Bacterial Gastroenteritis
Invasive Bacteria
Campylobacter Enteritis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Salmonellosis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Shigellosis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Yersinia enterocolitica Gastroenteritis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Vibrio parahaemolyticus Gastroenteritis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Enterohemorrhagic (Shiga Toxin–Producing) Escherichia coli
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Noninvasive Toxin-Forming Bacteria
Staphylococcus spp.
Epidemiology
Pathophysiology
Clinical Features
Management
Clostridium perfringens
Epidemiology
Pathophysiology
Clinical Features
Management
Bacillus cereus
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Cholera and Noncholera Vibrio Species
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Enterotoxigenic Escherichia coli
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Clostridium difficile Colitis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Viral Gastroenteritis
Norovirus
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Rotavirus
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Parasites
Giardia
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Amebiasis
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Food Poisoning
Principles
Clinical Features
Diagnostic Testing
Management
Scombroid Fish Poisoning
Epidemiology
Pathophysiology
Clinical Features
Management
Ciguatera Fish Poisoning
Epidemiology
Pathophysiology
Clinical Features
Management
Specific Groups with Gastroenteritis
Traveler’s Diarrhea
Epidemiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Gastroenteritis in the Immunocompromised Host With HIV/AIDS
Clinical Features
Diagnostic Testing
Management
References
Chapter 84: Questions & Answers
Chapter 85: Disorders of the Large Intestine
Irritable Bowel Syndrome
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Diverticular Disease
Principles
Clinical Features
Diverticulosis
Diverticulitis
Differential Diagnosis
Diagnostic Testing
Uncomplicated Diverticulitis
Complicated Diverticulitis
Abdominal Computed Tomography.
Barium Enema.
Water-Soluble Contrast Enema.
Ultrasonography.
Colonoscopy.
Plain Radiography Without Contrast.
Management
Diverticulosis
Uncomplicated Diverticulitis
Complicated Diverticulitis
Definitive Management
Disposition
Large Bowel Obstruction
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Imaging Studies
Plain Radiography.
Computed Tomography.
Colonoscopy and Water-Soluble Contrast Enema.
Management
Disposition
Volvulus
Principles
Sigmoid Volvulus
Cecal Volvulus
Clinical Features
Sigmoid Volvulus
Cecal Volvulus
Differential Diagnosis
Diagnostic Testing
Sigmoid Volvulus
Cecal Volvulus
Management
Sigmoid Volvulus
Cecal Volvulus
Disposition
Intussusception
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Ultrasound Examination
Plain Radiography
Computed Tomography
Barium Enema
Colonoscopy
Management
Disposition
Inflammatory Bowel Disease
Principles
Ulcerative Colitis
Crohn’s Disease
Clinical Features
Toxic Megacolon
Extraintestinal Manifestations
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Colonic Ischemia
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Imaging Studies
Plain Radiography.
Computed Tomography.
Barium Enema.
Colonoscopy.
Angiography.
Management
Disposition
Radiation Proctocolitis
Principles
Acute Radiation Proctocolitis
Chronic Radiation Proctocolitis
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Acute Radiation Proctocolitis
Chronic Radiation Proctocolitis
Disposition
References
Chapter 85: Questions & Answers
Chapter 86: Disorders of the Anorectum
Principles
Clinical Features
Specific Anorectal Problems
Hemorrhoids
Principles
Clinical Features
Management
Anal Fissures
Principles
Clinical Features
Management
Abscesses and Fistulae
Principles
Management
Perirectal and Perianal Abscesses.
Ischiorectal Abscess.
Intersphincteric Abscess.
Supralevator Abscess.
Postanal Abscess.
Horseshoe Abscess.
Necrotizing Infection.
Fistulae.
Pilonidal Disease
Principles
Management
Hidradenitis Suppurativa
Principles
Clinical Findings
Differential Diagnosis
Management
Proctalgia
Levator Ani Syndrome
Proctalgia Fugax
Fecal Incontinence
Principles
Clinical Features
Management
Pruritis Ani
Principles
Diagnostic Testing
Management
Sexually Transmitted Disease and Proctitis
Principles
Gonorrhea.
Chlamydial Infection and Lymphogranuloma Venereum.
Herpes Simplex Virus Infection.
Syphilis.
Chancroid.
Condyloma Acuminatum.
Ulcerative Lesions in HIV-Infected Patients.
Management
Radiation Proctitis
Rectal Prolapse
Rectal Foreign Bodies
Principles
Clinical Features
Diagnostic Testing
Management
References
Chapter 86: Questions & Answers
Section Six: Genitourinary and Gynecologic Systems
Chapter 87: Renal Failure
Acute Kidney Injury
Clinical Features
Differential Diagnosis
Prerenal Azotemia
Postrenal (Obstructive) Acute Kidney Injury
Intrinsic Acute Kidney Injury
Acute Glomerulonephritis.
Acute Interstitial Nephritis.
Intrarenal Vascular Disease of the Kidney.
Acute Tubular Necrosis.
Diagnostic Testing
Urine Volume
Urinalysis
Heme.
Protein.
Serum and Urine Chemical Analysis
Creatinine and Blood Urea Nitrogen.
Urine Sodium and Fractional Excretion of Sodium.
Renal Imaging
Computed Tomography.
Ultrasonography.
Analysis of Information
Management
Hyperkalemia and Other Metabolic Derangements
Hyperkalemia.
Hypocalcemia.
Hyperphosphatemia.
Hypermagnesemia.
Disturbances of Volume Regulation.
Disposition
Chronic Kidney Disease
Causes
Pathophysiology
Clinical Features
Cardiovascular System
Pulmonary Effects
Neurologic Features
Gastrointestinal System
Dermatologic Features
Musculoskeletal System
Immunologic Considerations
Hematologic Effects
Differential Diagnosis
Diagnostic Testing
Management
Hyperkalemia
Pulmonary Edema
Infection
Dialysis
Major Dialysis Modalities.
Hemodialysis.
Peritoneal Dialysis.
Indications for Dialysis.
Complications of Dialysis
Hemodialysis
Vascular Access–Related Complications
Non–Vascular Access–Related Complications
Hypotension.
Shortness of Breath.
Chest Pain.
Neurologic Dysfunction.
Peritoneal Dialysis
References
Chapter 87: Questions & Answers
Chapter 88: Sexually Transmitted Diseases
Principles
Disorders Characterized by Genital Ulcers
Herpes
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Syphilis
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Chancroid
Principles
Clinical Features
Diagnostic Testing
Management
Disorders Characterized by Genital Discharge
Gonorrhea
Principles
Clinical Features
Diagnostic Testing
Treatment
Disposition
Chlamydia
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Nongonococcal Urethritis
Trichomoniasis
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Pelvic Inflammatory Disease
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Bacterial Vaginosis
Principles
Clinical Features and Diagnostic Testing
Management
Vulvovaginal Candidiasis
Principles
Clinical Features and Diagnostic Testing
Management
Epithelial Cell Infections
Condyloma Acuminata (Genital Warts)
Principles
Clinical Findings
Diagnostic Testing
Management
Molluscum Contagiosum
Ectoparasites
Pediculosis Pubis
Scabies
References
Chapter 88: Questions & Answers
Chapter 89: Selected Urologic Disorders
Urinary Tract Infection in Adults
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Urinalysis and Urine Culture
Imaging
Management
Simple Urinary Tract Infection
Complex Urinary Tract Infection
Disposition.
Complicated Urinary Tract Infection in High-Risk Populations
Pregnancy.
Indwelling and Temporary Urinary Catheters.
Prostatitis
Clinical Features
Diagnostic Testing
Management
Renal Calculi
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Urinalysis and Culture
Other Laboratory Tests
Imaging
Radiography of the Kidney, Ureter, and Bladder.
Intravenous Pyelography.
Computed Tomography.
Ultrasonography.
Management
Disposition
Indications for Admission
Outpatient Management
Bladder (Vesical) Calculus
Clinical Features
Diagnostic Testing
Management
Acute Scrotal Pain
Specific Disorders
Testicular Torsion
Clinical Features.
Differential Diagnosis.
Diagnostic Testing
Urinalysis.
Imaging.
Management.
Disposition.
Torsion of Appendages of the Testis
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Epididymitis
Clinical Features.
Diagnostic Testing.
Management.
Disposition.
Orchitis
Clinical Features.
Diagnostic Testing.
Management.
Testicular Tumors
Principles.
Clinical Features.
Diagnostic Testing.
Management and Disposition.
Testicular Trauma
Inguinal Hernia, Acute Hydrocele, Varicocele, and Spermatocele
Acute Urinary Retention
Epidemiology
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Hematuria
Clinical Features
Diagnostic Testing
Management and Disposition
References
Chapter 89: Questions & Answers
Chapter 90: Selected Gynecologic Disorders
Ovarian Torsion
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Imaging
Ultrasonography.
Computed Tomography.
Magnetic Resonance Imaging.
Laparoscopy.
Management and Disposition
Ovarian Cysts and Masses
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Imaging
Ultrasonography.
Computed Tomography.
Magnetic Resonance Imaging.
Management and Disposition
Abnormal Uterine Bleeding in the Nonpregnant Patient
Principles
Clinical Features
History
Physical Examination
Differential Diagnosis
Diagnostic Strategies
Laboratory Studies
Imaging
Management
Disposition
Emergency Contraception
References
Chapter 90: Questions & Answers
Section Seven: Neurology
Chapter 91: Stroke
Principles
Background
Epidemiology
Ischemic Stroke
Transient Ischemic Attack
Hemorrhagic Stroke
Pathophysiology
Anatomy and Physiology
Clinical Features
Ischemic Stroke
Hemorrhagic Stroke
Differential Diagnosis
Ischemic Stroke
Hemorrhagic Stroke
Diagnostic Testing
Ischemic Stroke
Transient Ischemic Attack
Hemorrhagic Stroke
Management
Ischemic Stroke
Blood Pressure Management
Thrombolytic Therapy
Endovascular Rescue Therapy
Anticoagulation
Intracerebral Hemorrhage
Disposition
Ischemic Stroke and Transient Ischemic Attacks
References
Chapter 91: Questions & Answers
Chapter 92: Seizures
Principles
Background and Classification
Epidemiology
Pathophysiology
Clinical Features
Clinical History
Physical Examination
Differential Diagnosis
Convulsive Syncope
Nonepileptic Attacks
Diagnostic Testing
Laboratory Studies
Electrocardiogram
Neuroimaging
Lumbar Puncture
Electroencephalogram
Management
Initiation of Antiepileptic Drugs
First-Time Seizures
Patients With a History of Seizures
Special Cases
Alcohol-Related Seizures
Toxins
Post-Traumatic Seizures
Pregnancy
Disposition
References
Chapter 92: Questions & Answers
Chapter 93: Headache Disorders
Primary Headache Disorders
Migraine Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Cluster Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Tension-Type Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Secondary Headache Disorders
Subarachnoid Hemorrhage
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Intracranial Neoplasm
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Giant Cell Arteritis
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Carotid and Vertebral Artery Dissection
Principles
Clinical Features
Carotid Artery Dissection.
Vertebral Artery Dissection.
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Cerebral Venous Thrombosis
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Idiopathic Intracranial Hypertension
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Post–Dural Puncture Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Post-Traumatic Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Hypertensive Headache
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Reversible Cranial Vasoconstriction Syndrome
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 93: Questions & Answers
Chapter 94: Delirium and Dementia
Overview
Delirium
Principles
Background
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Studies
Management
Disposition
Dementia
Principles
Background
Pathophysiology
Clinical Features
Differential Diagnosis
Senescent Forgetfulness
Delirium
Depression
Diagnostic Strategies
Cognitive Evaluation
Laboratory Tests and Imaging Studies
Summary
Management
Disposition
References
Chapter 94: Questions & Answers
Chapter 95: Brain and Cranial Nerve Disorders
Trigeminal Neuralgia (Cranial Nerve V)
Principles
Clinical Features
Differential Diagnosis
Diagnostic Strategies
Management
Disposition
Facial Nerve Paralysis (Cranial Nerve VII)
Principles
Clinical Features
Bell’s Palsy
Ramsey Hunt Syndrome
Lyme Disease
Bacterial Ear Infections
Differential Diagnosis
Diagnostic Strategies
Management
Bell’s Palsy
Ramsay Hunt Syndrome
Lyme Disease
Bacterial Infections
Disposition
Vestibular Schwannoma (Cranial Nerve VIII)
Principles
Clinical Features
Differential Diagnosis
Diagnostic Strategies
Management
Disposition
Diabetic Cranial Mononeuropathy
Principles
Clinical Features
Differential Diagnosis
Diagnostic Studies
Management
Cerebral Venous Thrombosis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Strategies
Management
Disposition
Multiple Sclerosis
Principles
Clinical Features
Differential Diagnosis
Diagnostic Strategies
Management
Treatment of Disease Progression
Treatment of Acute Exacerbations
Treatment of Complications
Disposition
References
Chapter 95: Questions & Answers
Chapter 96: Spinal Cord Disorders
Principles
Anatomy
Classification of Spinal Cord Syndromes
Complete (Transverse) Spinal Cord Syndrome
Incomplete Spinal Cord Lesions
Central Cord Syndrome.
Brown-Séquard Syndrome.
Anterior Cord Syndrome.
Conus Medullaris and Cauda Equina Syndromes
Clinical Features
History
Physical Examination
Motor Function
Sensory Function
Reflexes
Differential Diagnosis
Diagnostic Testing
Management
Specific Disease Processes
Intrinsic Cord Lesions
Multiple Sclerosis
Transverse Myelitis
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Strategies.
Management.
Spinal Subarachnoid Hemorrhage
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
Syringomyelia
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
Human Immunodeficiency Virus Myelopathy
Spinal Cord Infarction
Extrinsic Cord Lesions
Spinal Epidural Hematoma
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
Spinal Epidural Abscess
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
Diskitis
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
Neoplasm
Principles.
Clinical Features.
Differential Diagnosis.
Diagnostic Testing.
Management.
References
Chapter 96: Questions & Answers
Chapter 97: Peripheral Nerve Disorders
Overview
Principles
Differential Diagnosis
Diagnostic Testing
Specific Types of Neuropathies
Type 1: Demyelinating Polyneuropathy (Guillian-Barré Syndrome)
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Type 2: Distal Symmetrical Polyneuropathy
Principles
Clinical Findings
Differential Diagnosis
Diagnostic Testing
Management
Type 3: Asymmetric Proximal and Distal Peripheral Neuropathies (Radiculopathies and Plexopathies)
Type 4: Isolated Mononeuropathies
Radial Mononeuropathy
Principles.
Clinical Findings.
Diagnostic Testing.
Management.
Ulnar Mononeuropathy
Principles and Clinical Findings.
Diagnostic Testing.
Management.
Median Mononeuropathy
Principles.
Clinical Findings.
Diagnostic Testing.
Management.
Sciatic Mononeuropathy
Principles.
Clinical Findings.
Diagnostic Testing.
Management.
Lateral Femoral Cutaneous Mononeuropathy
Principles.
Clinical Findings.
Diagnostic Testing.
Management.
Common Peroneal Mononeuropathy
Principles.
Clinical Findings.
Diagnostic Testing.
Management.
Type 5: Mononeuropathy Multiplex
Principles
Clinical Findings
Lyme Disease.
Diagnostic Testing
Management
Type 6: Amyotrophic Lateral Sclerosis
Principles
Clinical Findings
Diagnostic Testing
Management
Type 7: Sensory Neuronopathy (Ganglionopathy)
Principles
Clinical Findings
Diagnostic Testing
Management
References
Chapter 97: Questions & Answers
Chapter 98: Neuromuscular Disorders
Principles
Clinical Features
History
Physical Examination
Differential Diagnosis
Myelopathies
Motor Neuron Disease
Neuropathies
Diseases of the Neuromuscular Junction
Myopathies
Diagnostic Testing
Laboratory Studies
Special Studies
Disorders of the Neuromuscular Junction
Myasthenia Gravis
Principles
Myasthenic Crisis.
Lambert-Eaton Syndrome.
Clinical Features
Diagnostic Testing
Management
Cholinesterase Inhibitors.
Immunosuppressant Drugs.
Thymectomy.
Immunomodulatory Therapy.
Disposition
Botulism
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Tick Paralysis
Principles
Clinical Features
Management
Disposition
Disorders of the Muscles
Inflammatory Disorders
Principles
Clinical Features
Diagnostic Testing
Management
Disposition
Metabolic Disorders
Periodic Paralysis
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Disposition.
References
Chapter 98: Questions & Answers
Chapter 99: Central Nervous System Infections
Principles
Overview
Bacterial Meningitis
Tuberculous Meningitis
Viral Meningitis and Encephalitis
Fungal Meningitis
Central Nervous System Abscess
Clinical Features
Meningitis
Viral Encephalitis
Central Nervous System Abscess
Differential Diagnosis
Diagnostic Testing
Laboratory Testing
Neuroimaging
Cerebrospinal Spinal Fluid Analysis
Opening Pressure
Cerebrospinal Spinal Fluid Collection
Cerebrospinal Spinal Fluid Cell Count
Gram’s Stain
Xanthochromia
Glucose
Protein
India Ink Preparation
Lactic Acid and Other Markers
Antigen Detection
Bacteriologic Cultures
Additional Investigations
Management
Bacterial Meningitis
Tuberculous Meningitis
Fungal Meningitis
Viral Meningitis
Viral Encephalitis
Central Nervous System Abscess
Chemoprophylaxis
Immunoprophylaxis
Disposition
References
Chapter 99: Questions & Answers
Section Eight: Psychiatric and Behavioral Disorders
Chapter 100: Thought Disorders
Principles
Clinical Features
Differential Diagnosis
Medical Disorders
Psychiatric Disorders
Diagnostic Testing
Management
Disposition
References
Chapter 100: Questions & Answers
Chapter 101: Mood Disorders
Principles
Epidemiology
Pathophysiology
Neurophysiology
Neuroanatomy
Endocrine System
Genetics
Psychosocial Factors
Clinical Features
Major Depressive Disorder
Mood Disturbances
Disturbances in Psychomotor Activity
Vegetative Disturbances
Thought Process and Content
Masked Depression
Special Considerations
Children and Adolescents.
Disruptive Mood Dysregulation Disorder.
Geriatric Patients.
Other Depressive Disorders
Postpartum Depression
Persistent Depressive Disorder
Premenstrual Dysphoric Disorder
Seasonal Affective Disorder
Bipolar Disorders
Manic Episode
Cyclothymic Disorder
Mood Disorders Caused by a General Medical Condition
Mood Disorders Caused by Medications or Other Substances
Differential Diagnosis
Medical Disorders, Medications, and Substance Abuse or Withdrawal
Grief and Bereavement
Adjustment Disorders
Borderline Personality Disorder
Dementia
Diagnostic Testing
Management
Disposition
References
Chapter 101: Questions & Answers
Chapter 102: Anxiety Disorders
Principles
Background
Epidemiology
Pathophysiology
Clinical Features
Panic Disorder
Generalized Anxiety Disorder
Post-Traumatic Stress Disorder
Specific Phobias
Obsessive-Compulsive Disorder
Somatic Symptoms and Related Disorders
Differential Diagnosis
Cardiac Diseases
Endocrine Diseases
Respiratory Diseases
Neurologic Disorders
Drug Intoxication and Withdrawal States
Diagnostic Testing
Management
Pharmacologic Treatment
Nonpharmacologic Therapy
Disposition
References
Chapter 102: Questions & Answers
Chapter 103: Somatoform Disorders
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 103: Questions & Answers
Chapter 104: Factitious Disorders and Malingering
Principles
Clinical Features
Factitious Disorders
Factitious Disorders Imposed on Self
Psychological Symptoms.
Physical Symptoms.
Approach to Diagnosis.
Munchausen Syndrome.
Factitious Disorder Imposed on Another
Perpetrator Characteristics.
Victim Characteristics.
Approach to Diagnosis.
Malingering
Differential Diagnosis
Management
Factitious Disorders
Malingering
Disposition
References
Chapter 104: Questions & Answers
Chapter 105: Suicide
Principles
Background
Epidemiology
Risk Factors
Self-Harm
Mental Illness
Alcohol and Substance Abuse
Adolescence
Older Age
Chronic Illness
Other Risk Factors
Methods of Suicide
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Suicide Precautions
Use of Restraints
Pharmacologic Treatments
Risk Assessment
Documentation
Disposition
Psychiatric Hospitalization
Discharge
References
Chapter 105: Questions & Answers
Section Nine: Immunologic and Inflammatory
Chapter 106: Arthritis
Principles
Background
Pathophysiology
Clinical Features
History
Physical Examination
General Examination
Joints
Spine
Upper Extremities
Lower Extremities
Diagnostic Testing
Laboratory Tests
Radiologic Tests
Plain Radiography
Computed Tomography, Magnetic Resonance Imaging, and Sonography
Arthrocentesis
Indications and Contraindications.
Complications.
Technique.
Synovial Fluid Examination.
General Appearance.
Synovial Fluid Studies.
White Blood Cell Count.
Crystal Analysis.
Differential Diagnosis and Management
Acute Monoarticular Arthritis
Nongonococcal Bacterial Septic Arthritis
Principles
Epidemiology.
Pathophysiology.
Microbiology.
Clinical Features.
Diagnostic Testing.
Management.
Gonococcal Arthritis
Principles.
Clinical Features.
Management.
Gouty Arthritis
Principles
Epidemiology.
Pathophysiology.
Clinical Features.
Diagnostic Testing.
Laboratory Tests.
Radiologic Tests.
Management.
Nonsteroidal Antiinflammatory Drugs.
Colchicine.
Steroids.
Adrenocorticotropic Hormone (Corticotropin).
Other Agents.
Summary.
Calcium Pyrophosphate Dihydrate Deposition Disease (Pseudogout)
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Basic Calcium Phosphate Hydroxyapatite Crystal Disease
Acute Calcific Periarthritis
Trauma and Hemarthrosis
Chronic Monoarticular Arthritis
Osteoarthritis (Degenerative Joint Disease)
Principles.
Clinical Features.
Management
Nonpharmacologic Therapy.
Pharmacologic Therapy.
Summary.
Acute Polyarticular Arthritis
Lyme Disease
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Acute Rheumatic Fever
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Chronic Polyarthritis
Rheumatoid Arthritis
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Adult-Onset Still’s Disease
Relapsing Polychondritis
Seronegative Spondyloarthropathies
Ankylosing Spondylitis
Clinical Features.
Management.
Reactive Arthritis (Formerly Reiter’s Syndrome)
Clinical Features.
Management.
Enteropathic Arthritis.
Psoriatic Arthritis.
Fibromyalgia
Clinical Features.
Management.
Polymyalgia Rheumatica
Scleroderma (Systemic Sclerosis)
Disposition
References
Chapter 106: Questions & Answers
Chapter 107: Tendinopathy and Bursitis
Tendinopathy
Principles
Background
Pathophysiology
Clinical Features
General Tendinopathy
Specific Tendinopathies
Shoulder.
Impingement Syndrome and Rotator Cuff Tendinopathies.
Bicipital Tendinopathy.
Calcific Tendinopathy.
Elbow.
Lateral Epicondylitis.
Medial Epicondylitis.
Wrist
de Quervain’s Tenosynovitis.
Knee
Patellar Tendinopathy.
Ankle
Achilles Tendinopathy.
Achilles Tendon Rupture.
Differential Diagnosis
Diagnostic Testing
Management
General Tendinopathy
Specific Tendinopathies
Impingement Syndrome and Rotator Cuff Tendinopathies.
Calcific Tendinopathy.
Lateral and Medial Epicondylitis.
de Quervain’s Tenosynovitis.
Achilles Tendinopathy and Rupture.
Disposition
Bursitis
Principles
Clinical Features
Olecranon and Prepatellar Bursitis
Subacromial Bursitis
Trochanteric Bursitis
Ischiogluteal Bursitis
Iliopsoas Bursitis
Pes Anserine Bursitis
Diagnostic Testing
Differential Diagnosis
Management
Septic Bursitis
Nonseptic Bursitis
Disposition
References
Chapter 107: Questions & Answers
Chapter 108: Systemic Lupus Erythematosus and the Vasculitides
Systemic Lupus Erythematosus
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
The Patient With Undiagnosed or Suspected Systemic Lupus Erythematosus
Acute Presentations in the Patient With Known Systemic Lupus Erythematosus
Systemic Lupus Erythematosus Exacerbation
Specific Symptoms and Presentations of Systemic Lupus Erythematosus
Fever.
Neuropsychiatric Presentations.
Headache.
Seizure.
Focal Neurologic Findings.
Psychiatric Symptoms.
Cardiorespiratory Presentations and Diseases.
Coronary Artery Disease.
Pericardial Disease.
Pulmonary Embolism.
Pleuritis.
Pneumonia.
Undifferentiated Dyspnea.
Musculoskeletal Presentations.
Gastrointestinal Presentations.
Dermatologic Presentations.
Renal Disease.
Complications Due to Medications
Diagnostic Testing
Laboratory Tests
Imaging Studies
Radiography.
Computed Tomography.
Echocardiography and Ultrasound.
Nuclear Imaging.
Differential Diagnosis
Management
Special Considerations
Antiphospholipid Syndrome
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Drug-Induced Lupus
Disposition
Vasculitides
Principles
Clinical Features
Vasculitis Presenting With Large-Vessel Occlusive Symptoms
Giant Cell Arteritis
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Takayasu’s Arteritis
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Vasculitis Typified by Pulmonary-Renal Manifestations
Wegener’s Granulomatosis
Principles.
Clinical Features and Diagnostic Testing.
Management.
Goodpasture’s Syndrome
Principles.
Clinical Features and Diagnostic Testing.
Management.
Microscopic Polyangiitis
Principles.
Clinical Features and Diagnostic Testing.
Management.
Churg-Strauss Syndrome
Principles.
Clinical Features and Diagnostic Testing.
Management.
Vasculitis With Characteristic Cutaneous Manifestations
Erythema Nodosum
Principles.
Clinical Features.
Management.
Henoch-Schönlein Purpura
Principles.
Clinical Features and Diagnostic Testing.
Management.
Polyarteritis Nodosa
Principles.
Clinical Features.
Management.
Behçet’s Disease
Principles.
Clinical Features and Diagnostic Testing.
Management.
Vasculitis Associated With Environmental or Foreign Antigen Exposure
Vasculitis Caused by Cocaine Adulterated With Levamisole.
Cryoglobulinemic Vasculitis.
References
Chapter 108: Questions & Answers
Chapter 109: Allergy, Hypersensitivity, and Anaphylaxis
Allergy
Principles
Background and Terminology
Pathophysiology
Development of the Immune System and Mechanism of Immune-Mediated Injury.
T-Cell Development.
B-Cell Development and Immunoglobulins.
Classification of Reactions
Anaphylaxis
Principles
Epidemiology and Risk Factors
Common Triggers for Anaphylaxis
Foods.
Insect Stings.
Drugs.
Natural Rubber Latex.
Radiocontrast Media.
Exercise Induced Anaphylaxis.
Idiopathic Anaphylaxis.
Mediators of Anaphylaxis
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Overview
Positioning
Epinephrine
Airway
Volume Expansion
Antihistamines
Glucocorticoids
Patients Receiving Beta-Blockade
Disposition
Urticaria and Angioedema
Principles and Clinical Features
Diagnostic Strategies
Management
Angioedema With Urticaria
Angioedema Without Urticaria
Disposition
References
Chapter 109: Questions & Answers
Chapter 110: Dermatologic Presentations
Overview
Principles
Background
Anatomy and Physiology
Clinical Features
Diagnostic Testing
Management
Disposition
Infectious Disorders
Bacterial Infections
Impetigo
Folliculitis
Cellulitis
Abscess
Carbuncle
Methicillin-Resistant Staphylococcus Aureus
Erythema Migrans
Necrotizing Fasciitis
Meningococcal Infection
Scarlet Fever
Syphilis
Gonococcal Dermatitis
Staphylococcal Scalded Skin Syndrome
Toxic Shock Syndrome
Rocky Mountain Spotted Fever
Viral Infections
Herpes Simplex Virus
Varicella-Zoster Virus
Varicella.
Herpes Zoster.
Viral Exanthems
Roseola Infantum.
Measles.
Rubella.
Erythema Infectiosum.
Fungal Infections
Tinea Corporis
Tinea Capitis
Kerion
Tinea Pedis
Tinea Versicolor
Tinea Unguium (Onychomycosis)
Candidiasis
Oral Candidiasis.
Cutaneous Candidiasis.
Vulvovaginal Candidiasis.
Infestations
Scabies
Pediculosis
Bed Bugs
Allergic Reactions
Contact Dermatitis
Urticaria
Poison Ivy
Drug Reactions
Inflammatory Conditions
Atopic Dermatitis
Pityriasis Rosea
Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
Erythema Multiforme
Toxic Epidermal Necrolysis
Erythema Nodosum
Lichen Planus
Autoimmune Disorders
Bullous Pemphigoid
Pemphigus Vulgaris
Cutaneous Malignancies
Skin Conditions Associated With Systemic Disease
Management
Disposition
References
Chapter 110: Questions & Answers
Section Ten: Hematology and Oncology
Chapter 111: Blood and Blood Components
Principles
Background and Importance
Anatomy, Physiology, and Pathophysiology
Blood Banking
Blood Typing
Type and Screen.
Type and Crossmatch.
Management
Decision Making
Pharmacology
Devices and Techniques
Whole Blood
Packed Red Blood Cells
Fresh-Frozen Plasma
Outcomes
Safety and Effectiveness
Complications
Adverse Effects of Massive Transfusions
Adverse Effects of Nonmassive RBC Transfusion
References
Chapter 111: Questions & Answers
Chapter 112: Anemia and Polycythemia
Anemia
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Anemias Due to Decreased Red Blood Cell Production
Principles
Background and Importance
Iron Deficiency Anemia
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Thalassemia
Principles.
Pathophysiology.
Clinical Features.
Diagnostic Testing.
Management.
Sideroblastic Anemia
Principles.
Clinical Features.
Differential Diagnosis.
Management.
Anemia of Chronic Disease
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Macrocytic and Megaloblastic Anemias
Principles.
Clinical Features.
Differential Diagnoses.
Diagnostic Testing.
Management.
Normochromic and Normocytic Anemias
Principles.
Differential Diagnoses.
Aplastic Anemia
Principles.
Clinical Features.
Diagnostic Testing.
Management.
Increased Red Blood Cell Destruction
Principles
Pathophysiology
Clinical Features
Differential Diagnoses
Intrinsic Enzyme Defects.
Intrinsic Membrane Abnormality.
Intrinsic Hemoglobin Abnormality.
Extrinsic Alloantibodies.
Extrinsic Autoantibodies.
Extrinsic Mechanical Causes.
Environmental Causes.
Abnormal Sequestration.
Diagnostic Testing
Management
Sickle Cell Disease
Principles.
Clinical Features.
Differential Diagnoses
Sickle Cell–β-Thalassemia.
Diagnostic Testing
Management
Disposition
Polycythemia
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 112: Questions & Answers
Chapter 113: White Blood Cell Disorders
White Blood Cell Disorders
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Chronic Myeloid Leukemia
Principles
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Lymphocytic Leukocytosis
Principles
Anatomy and Physiology
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Leukopenia
Principles
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Disposition
References
Chapter 113: Questions & Answers
Chapter 114: Disorders of Hemostasis
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
History and Physical Examination
Thrombocytopenia
Immune Thrombocytopenia.
Idiopathic Thrombocytopenic Purpura.
Nonimmune Thrombocytopenia.
Thrombotic Thrombocytopenic Purpura.
Dilutional Thrombocytopenia.
Thrombocytopathy
Adhesion Defects.
Release Defects.
Aggregation Defects.
Thrombocytosis
Disorders of the Coagulation Pathway
Abnormal Prothrombin Time and Other Test Results Normal
Abnormal Partial Thromboplastin Time and Other Test Results Normal
Hemophilia A.
von Willebrand’s Disease.
Hemophilia B (Christmas Disease).
Miscellaneous Coagulation Disorders
Disseminated Intravascular Coagulation.
Differential Diagnosis
Diagnostic Testing
Complete Blood Count and Blood Smear
Platelet Count
Bleeding Time and Platelet Function Assay
Prothrombin Time
Partial Thromboplastin Time
Anti-Xa Assay
Fibrinogen
Thrombin Time
Clot Solubility
Factor Level Assays
Management
Out-of-Hospital Treatment
Platelet Disorders
Platelet Transfusions.
Medication-Induced Thrombocytopenia
Post-Transfusion Thrombocytopenia
Heparin-Induced Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura
Hemophilia A
Management of Hemophilia A
Preparation.
Replacement Therapy.
Prophylaxis.
Hemophilia B
von Willebrand’s Disease
Medication-Induced Bleeding
Disseminated Intravascular Coagulation
Disposition
References
Chapter 114: Questions & Answers
Chapter 115: Selected Oncologic Emergencies
Introduction
Febrile Neutropenia
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Metastatic Spinal Cord Compression
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Malignant Pericardial Disease
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Hypercalcemia
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Tumor Lysis Syndrome
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Leukostasis
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Superior Vena Cava Syndrome
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Conclusion
References
Chapter 115: Questions & Answers
Section Eleven: Metabolism and Endocrinology
Chapter 116: Acid-Base Disorders
Principles
Specific Acid-Base Disorders
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Acidosis
Elevated Anion Gap Metabolic Acidosis
Lactic Acidosis.
Diabetic Ketoacidosis.
Alcoholic Ketoacidosis.
Methanol and Ethylene Glycol.
Renal Failure.
Isoniazid Toxicity.
Salicylate Toxicity.
Iron Ingestion.
Normal Anion Gap Metabolic Acidosis
Physiologic Compensation for Metabolic Acidosis
Metabolic Alkalosis
Diagnostic Testing and Mixed Disorders
Management
Acidosis
Alkalosis
References
Chapter 116: Questions & Answers
Chapter 117: Electrolyte Disorders
Hyperkalemia
Principles
Clinical Features
Diagnostic Strategies
Management
Hypokalemia
Principles
Clinical Features
Diagnostic Testing
Management
Hypernatremia
Principles
Clinical Features
Diagnostic Testing
Management
Hyponatremia
Principles
Pseudohyponatremia
Hypovolemic Hyponatremia
Hypervolemic Hyponatremia
Euvolemic Hyponatremia
Diagnostic Testing
Clinical Features
Management
Hypovolemic Hyponatremia
Hypervolemic Hyponatremia
Euvolemic Hyponatremia
Hypercalcemia
Principles
Clinical Features
Diagnostic Testing
Management
Hypocalcemia
Principles
Clinical Features
Diagnostic Strategies
Management
Hypermagnesemia
Principles
Clinical Features
Diagnostic Testing
Management
Hypomagnesemia
Principles
Patients Maintained on Diuretics
Malnourished and Alcoholic Patients
Patients With Hypokalemia
Patients With Acute Coronary Artery Disease and Ventricular Arrhythmias
Patients Receiving Specific Medications
Clinical Features
Diagnostic Testing
Management
Hyperphosphatemia
Principles
Clinical Features
Management
Hypophosphatemia
Principles
Clinical Features
Management
References
Chapter 117: Questions & Answers
Chapter 118: Diabetes Mellitus and Disorders of Glucose Homeostasis
Diabetes Mellitus
Principles
Background
Normal Physiology
Insulin.
Glucose Regulatory Mechanisms.
Pathophysiology
Types of Diabetes
Type 1 Diabetes Mellitus.
Type 2 Diabetes Mellitus.
Gestational Diabetes.
Diabetes of Other Causes.
Prediabetes.
Epidemiology
Clinical Features
Type 1
Type 2
Diagnostic Testing
Serum Glucose Level
Glycosylated Hemoglobin
Urine Glucose Level
Urine Ketone Level
Dipstick Blood Glucose Level
Management
Approach to New-Onset Hyperglycemia in the Emergency Department
Management of Diabetes
Oral Hypoglycemic Agents.
Biguanides.
Sulfonylureas.
Thiazolidinediones.
α-Glucosidase Inhibitors.
Meglinitides.
Glucagon-Like Peptide Analogues and Agonists.
Dipeptidyl Peptidase-4 Inhibitors.
Amylin Analogue.
Sodium-Glucose Cotransporter 2 Inhibitors.
Insulin.
Pancreas Transplantation.
New Trends in Diabetes Management.
Diabetic Ketoacidosis
Principles
Pathophysiology
Causes
Clinical Features
Diagnostic Testing
Differential Diagnoses
Management
Insulin
Intravenous Fluids
Potassium
Magnesium
Acidosis
Complications
Disposition
Hyperglycemic Hyperosmolar State
Principles
Pathophysiology
Causes
Clinical Features
Diagnostic Testing
Differential Diagnoses
Management
Intravenous Fluids
Electrolytes
Insulin
Other Considerations
Acute Complications
Disposition
Late Complications of Diabetes
Vascular Complications
Diabetic Nephropathy
Retinopathy
Neuropathy
The Diabetic Foot
Infections
Cutaneous Manifestations
Skin Conditions.
Acanthosis Nigricans.
Necrobiosis Lipoidica Diabeticorum.
Xanthoma Diabeticorum.
Bullosis Diabeticorum.
Diabetic Dermopathy.
Impetigo or Intertrigo.
Diabetes in Pregnancy
Hypoglycemia
Principles
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 118: Questions & Answers
Chapter 119: Rhabdomyolysis
Principles
Background
Physiology
Pathophysiology
Clinical Features
Complications
Early Complications
Compartment Syndrome.
Electrolyte Disorders and Acidosis.
Hypovolemia.
Hepatic Dysfunction.
Late Complications
Myoglobin-Induced Acute Kidney Injury.
Disseminated Intravascular Coagulation.
Diagnostic Testing
Serum Creatine Kinase
Serum and Urine Myoglobin
Urine Dipstick and Urinalysis
Other Laboratory Findings
Prognostic Tests in Rhabdomyolysis
Management
Fluid Replacement and Urine Alkalinization
Diuretics
Mannitol
Furosemide
Acetazolamide
Experimental Therapies
Renal Replacement Therapy
Disposition
Prognosis
References
Chapter 119: Questions & Answers
Chapter 120: Thyroid and Adrenal Disorders
Hyperthyroidism
Principles
Background
Anatomy and Physiology
Pathophysiology
Graves’ Disease.
Toxic Multinodular Goiter.
Toxic Adenoma.
Thyroiditis.
Silent Thyroiditis.
Postpartum Thyroiditis.
Subacute Thyroiditis.
Suppurative Thyroiditis.
Drug-Induced Thyroiditis.
Factitious Thyroiditis.
Subclinical Hyperthyroid.
Clinical Features
History and Physical Examination
Thyroid Storm
Diagnostic Testing
Differential Diagnosis
Management
Supportive Treatment
Symptomatic Treatment
Thyroid-Directed Treatment
Reducing Thyroid Hormone Production.
Inhibiting Thyroid Hormone Release.
Inhibiting Conversion of T4 to T3.
Miscellaneous Therapies
Identification and Treatment of the Precipitating Event
Disposition
Hypothyroidism
Principles
Background
Pathophysiology
Clinical Features
History and Physical Examination
Myxedema Coma
Diagnostic Testing
Differential Diagnosis
Management
Hypothyroidism
Myxedema Coma
Disposition
Adrenal Insufficiency
Principles
Background
Anatomy and Physiology
Pathophysiology
Clinical Features
Diagnostic Testing
Differential Diagnosis
Management
Disposition
References
Chapter 120: Questions & Answers
Section Twelve: Infectious Diseases
Chapter 121: Bacteria
Diphtheria
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Disposition
Pertussis
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Acute Treatment
Vaccination
Tetanus
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Generalized Tetanus.
Localized Tetanus.
Cephalic Tetanus.
Neonatal Tetanus.
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Acute Treatment
Supportive Care.
Elimination of Unbound Toxin and Active Immunization.
Prevention of Further Toxin Production.
Vaccination
Botulism
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Disposition
Pneumococcemia
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Acute Treatment
Vaccination
Disposition
Meningococcemia
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Occult Bacteremia.
Meningococcal Meningitis.
Meningococcal Septicemia.
Fever and a Nonblanching Rash.
Chronic Meningococcemia.
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Acute Treatment
Antibiotic Prophylaxis and Vaccination
Disposition
Toxic Shock Syndrome
Principles
Background
Epidemiology
Etiology
Pathophysiology
Clinical Features
Symptoms and Signs
Complications
Diagnostic Strategies
Differential Diagnosis
Management
Disposition
References
Chapter 121: Questions & Answers
Chapter 122: Viruses
Perspective
Vaccine-Preventable Infections of Childhood
Mumps
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Measles (Rubeola)
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Rubella (German Measles)
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Viral Infections With Vesicular Rash
Herpes Simplex
Principles
Clinical Features
Oral Infection.
Genital Herpes.
Central Nervous System Infection.
Other Infections.
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Varicella-Zoster Virus
Principles
Clinical Features
Varicella.
Zoster.
Differential Diagnosis
Diagnostic Testing
Management
Varicella.
Zoster.
Disposition
Viral Infections Causing Nonspecific Febrile Illness
Epstein-Barr Virus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Cytomegalovirus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Enteroviruses
Principles
Clinical Features
Poliovirus.
Non-Polio Enteroviruses.
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Viruses Associated With Respiratory Infections
Influenza
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Neuraminidase Inhibitors.
Adamantane Antivirals.
Disposition
Coronavirus
Principles
Clinical Features
Severe Acute Respiratory Syndrome.
Middle East Respiratory Syndrome.
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Rhinovirus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Adenovirus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Parainfluenza
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Respiratory Syncytial Virus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Viruses Associated With Diarrheal Illness
Norovirus and Rotavirus
Principles
Clinical Features
Norovirus.
Rotavirus.
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Viral Infections With Neurologic Manifestations
Principles
Clinical Features
West Nile Virus
Eastern Equine Encephalitis Virus
St. Louis Encephalitis Virus
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Viral Hemorrhagic Fevers
Dengue Virus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Chikungunya Virus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Yellow Fever Virus
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Ebola
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Marburg
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Lassa Fever
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
References
Chapter 122: Questions & Answers
Chapter 123: Rabies
Principles
Epidemiology
Pathophysiology
Encephalitic Rabies
Paralytic Rabies
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Prophylaxis and Vaccination
Preexposure Prophylaxis
Postexposure Prophylaxis and Vaccination
Wound Care
Management of Human Rabies Infection
References
Chapter 123: Questions & Answers
Chapter 124: HIV Infection and AIDS
Principles
Background and Epidemiology
Pathophysiology
Risk Factors for HIV Transmission
Clinical Features
Primary HIV Infection
Chronic HIV Infection
AIDS
Initial Evaluation
Clinical Manifestations by Organ System
Cardiac Manifestations
Pulmonary Manifestations
Oropharyngeal and Gastrointestinal Manifestations
Central Nervous System Manifestations
Renal Manifestations
Rheumatologic and Orthopedic Manifestations
Hematologic Manifestations
Cutaneous Manifestations
Diagnosticconsiderations
Differential Diagnosis
Diagnostic Testing
HIV Testing
Management
Postexposure Prophylaxis
Disposition
References
Chapter 124: Questions & Answers
Chapter 125: Parasites
Overview
Travel History
Therapy
Presentations
Fever
Malaria
Clinical Features.
Diagnostic Testing.
Management.
Babesiosis
Clinical Features.
Management.
Other Parasites
Neurologic Symptoms
Cerebral Malaria
Clinical Features.
Management.
Cysticercosis
Clinical Features.
Diagnostic Strategies and Management.
Echinococcosis
Principles and Clinical Features.
Diagnostic Strategies and Management.
African Trypanosomiasis
Clinical Features.
Diagnostic Strategies and Management.
Other Parasites
Anemia
Malaria
Whipworm and Hookworm
Tapeworm
Peripheral Edema
Elephantiasis
Clinical Features.
Diagnostic Strategies and Management.
Dermatologic Symptoms
Cutaneous Leishmaniasis
Clinical Features.
Diagnostic Strategies and Management.
Dracunculiasis
Principles and Clinical Features.
Management.
Other Parasites
Visual Symptoms
Onchocerciasis
Clinical Features.
Diagnostic Strategies and Management.
Loiasis
Clinical Features.
Diagnostic Strategies and Management.
Other Parasites
Pulmonary Symptoms
Cardiovascular Symptoms
Chagas’ Disease
Clinical Features.
Diagnostic Strategies.
Management.
Other Parasites
Gastrointestinal Symptoms
Diarrhea
Abdominal Pain
Pruritus Ani
Parasitic Co-Infections in Patients With HIV Infection and AIDS
Specific Parasites
References
Chapter 125: Questions & Answers
Chapter 126: Tickborne Illnesses
Overview
Identification of Ticks
Physiology of Tick Feeding
Lyme Disease
Clinical Features
Early Lyme Disease
Acute Disseminated Infection
Neurologic Manifestations.
Cardiac Manifestations.
Arthritis.
Ophthalmic Manifestations.
Late Lyme Disease
Differential Diagnosis
Diagnostic Testing
Management
Early Disease
Early Disseminated Infection
Neurologic Disease.
Cardiac Disease.
Late Infection
Arthritis.
Neurologic Disease.
Lyme Disease and Pregnancy
Vaccination
Prophylaxis and Asymptomatic Tick Bites
Relapsing Fever
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Tularemia
Clinical Features
Presentations
Ulceroglandular Tularemia.
Glandular Tularemia.
Oculoglandular Tularemia.
Oropharyngeal Tularemia.
Typhoidal Tularemia.
Pulmonary Tularemia.
Other Considerations
Diagnostic Testing
Management
Rocky Mountain Spotted Fever
Pathophysiology
Clinical Features
Cutaneous Manifestations
Cardiopulmonary Manifestations
Neurologic Manifestations
Differential Diagnosis
Diagnostic Testing
Skin Biopsy
Serologic Studies
Isolation of Organism
Management
Supportive Care
Antibiotics
Corticosteroids
Q Fever
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Ehrlichioses
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Babesiosis
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Colorado Tick Fever
Pathophysiology
Clinical Features
Diagnostic Testing
Management
Other Tickborne Viruses
Tick Paralysis
Pathophysiology
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Tick Bite Prophylaxis With Insect Repellents
References
Chapter 126: Questions & Answers
Chapter 127: Tuberculosis
Principles
Background
Pathophysiology
Transmission
Pathogenesis
Stage 1
Stage 2
Stage 3
Stage 4
Clinical Features
History
Present Illness
Risk Factors
Physical Examination
Complications of Pulmonic Tuberculosis
Hemoptysis
Pneumothorax
Pleural Effusion
Empyema
Airway Tuberculosis
Superinfection With Fungi
Primary Tuberculous Pericarditis
Differential Diagnosis
Pulmonary Tuberculosis
Bacterial Pneumonia
Fungal and Nontuberculous Mycobacterial Infections
Pneumonias in Patients With HIV Infection
Cavitary Lesions
Mediastinal Lymphadenopathy
Extrapulmonary Tuberculosis
Lymphadenitis
Bone and Joint Infection
Renal Disease
Genital Disease
Multisystem Disease
Central Nervous System Disease
Gastrointestinal Disease
Diagnostic Testing
Laboratory Tests
White Cell Stimulation Tests
Serology
Diagnostic Imaging
Primary Tuberculosis
Postprimary Tuberculosis
Microbiologic Testing
Sputum Studies
Direct Microscopy.
Nucleic Acid Amplification Tests
Culture
Tuberculin Skin Test
Management
Initial Management in the Emergency Department
Hemoptysis
Fever or Wasting
History of Tuberculosis, Therapy Discontinued
Antituberculosis Medications
First-Line Agents
Second-Line Agents
Corticosteroids
Initial Therapy
Drug-Resistant Tuberculosis
Multidrug-Resistant Tuberculosis
Extensively Drug-Resistant Tuberculosis
Vaccines for Mycobacterium tuberculosis
Disposition
Prevention of Transmission in the Emergency Department
Early Identification
Isolation and Environmental Control
Personal Respiratory Protection
Preventive Therapy After Inadvertent Exposure
References
Chapter 127: Questions & Answers
Chapter 128: Bone and Joint Infections
Principles
Background
Anatomy and Physiology
Pathophysiology
Causes and Microbiology
Osteomyelitis
Clinical Features
History and Physical Examination
Complications
Clinical Subsets of Osteomyelitis
Osteomyelitis in Children.
Vertebral Osteomyelitis.
Posttraumatic Osteomyelitis.
Diabetic Foot Osteomyelitis.
Osteomyelitis in Sickle Cell Disease.
Chronic Osteomyelitis.
Differential Diagnosis
Diagnostic Testing
Laboratory Tests
Diagnostic Imaging
Conventional Radiography.
Radionuclide Bone Scanning.
Computed Tomography.
Magnetic Resonance Imaging.
Microbiologic Diagnosis
Management
Disposition
Septic Arthritis
Principles
Clinical Features
History and Physical Examination
Complications
Clinical Subsets of Septic Arthritis
Bites.
Infants and Children.
Gonococcal Septic Arthritis.
Lyme Arthritis.
Periprosthetic Joint Infections.
Patients With Existing Joint Disease.
Atypical Joints.
Differential Diagnosis
Diagnostic Testing
Serum and Urine Tests
Joint Fluid Analysis
Imaging
Management
Disposition
References
Chapter 128: Questions & Answers
Chapter 129: Skin Infections
Principles
Background and Importance
Anatomy and Physiology
Pathophysiology
Clinical Features
Differential Diagnosis and Diagnostic Testing
Wound Cultures
Blood Cultures
Radiographic Studies
Other Diagnostic Tests
Cellulitis
Principles and Clinical Features
Diabetic Foot Infections
Bite Wounds
Water-Borne Infections
Differential Diagnosis and Diagnostic Testing
Management
Disposition
Abscess
Principles and Clinical Features
Differential Diagnosis and Diagnostic Testing
Management
Disposition
Impetigo
Principles
Clinical Features and Differential Diagnosis
Management
Infections of the Pilosebaceous Follicle
Principles
Clinical Features and Management
Furuncles and Carbuncles
Acne
Hidradenitis Suppurativa (Acne Inversa)
Necrotizing Skin and Soft Tissue Infections
Principals and Clinical Features
Differential Diagnosis and Diagnostic Testing
Management and Disposition
Toxic Shock Syndromes
Principles and Clinical Features
Streptococcal Toxic Shock Syndrome
Staphylococcal Toxic Shock Syndrome
Staphylococcal Scalded Skin Syndrome
Differential Diagnosis and Diagnostic Testing
Management
Disposition
Other Infections With Skin Manifestations
References
Chapter 129: Questions & Answers
Chapter 130: Sepsis Syndromes
Principles
Background
Pathophysiology
Mediators of Sepsis
Organ System Dysfunction
Neurologic Impairment.
Cardiovascular Dysfunction.
Pulmonary Involvement.
Gastrointestinal Effects.
Endocrine Disorders.
Hematologic Abnormalities.
Genetic Factors
Clinical Features
Symptoms and Signs
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Laboratory Testing
Hematology.
Blood Chemistry.
Microbiology.
Special Procedures
Radiology
Management
Respiratory Support
Cardiovascular Support
Fluid Resuscitation
Vasoactive Drug Therapy
Norepinephrine.
Dopamine.
Phenylephrine.
Epinephrine.
Vasopressin.
Dobutamine.
Bicarbonate
Antibiotics
Steroid Therapy
Disposition
References
Chapter 130: Questions & Answers
Part IV: Environment and Toxicology
Section One: Environment
Chapter 131: Frostbite and Nonfreezing Cold Injuries
Frostbite
Principles
Background
Physiology
Pathophysiology
Predisposing Factors
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Prehospital
Emergency Department
Prethaw.
Thaw.
Postthaw.
Disposition
Nonfreezing Cold Injuries
Principles
Clinical Features
Immersion Injury
Pernio
Differential Diagnosis
Diagnostic Testing
Management
Immersion Injury
Pernio
Disposition
References
Chapter 131: Questions & Answers
Chapter 132: Accidental Hypothermia
Principles
Background
Physiology of Temperature Regulation
Pathophysiology
Cardiovascular System
Central Nervous System
Renal System
Respiratory System
Predisposing Factors
Decreased Heat Production.
Increased Heat Loss.
Impaired Thermoregulation.
Traumatic Factors
Clinical Features
Diagnostic Considerations
Differential Diagnosis
Diagnostic Testing
Acid-Base Balance
Hematologic Evaluation
Hypothermic Coagulation
Imaging
Management
General Measures
Volume Resuscitation
Advanced Life Support
Pharmacologic Treatment
Cardiovascular Medications
Antibiotics
Failure to Rewarm
Rewarming
Passive External Rewarming
Active Rewarming
Active External Rewarming
Active Core Rewarming.
Airway Rewarming.
Peritoneal Dialysis.
Heated Irrigation.
Endovascular Rewarming.
Diathermy.
Extracorporeal Blood Rewarming.
Disposition
References
Chapter 132: Questions & Answers
Chapter 133: Heat Illness
Principles
Background
Anatomy and Physiology
Heat Production
Conduction.
Convection.
Radiation.
Evaporation.
Heat Regulation
Thermosensors.
Central Integrative Area.
Thermoregulatory Effectors.
Acclimatization
Pathophysiology
Predisposing Factors
Fever Versus Hyperthermia
Minor Heat Illness
Prickly Heat
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Heat Cramps
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Heat Edema
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Heat Syncope
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management and Disposition
Major Heat Illness
Heat Exhaustion
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Heatstroke
Principles
Clinical Features
Heatstroke Versus Heat Exhaustion.
Classic Heatstroke Versus Exertional Heatstroke.
Differential Diagnosis
Meningitis and Encephalitis.
Thyroid Storm.
Drug-Induced Heat Illness.
Neuroleptic Malignant Syndrome.
Serotonin Syndrome.
Diagnostic Testing
Management
Cooling.
Resuscitation.
Disposition
References
Chapter 133: Questions & Answers
Chapter 134: Lightning and Electrical Injuries
Principles
Background
Electrical Injury
Lightning
Physics of Electricity
Electrical Injury
Type of Circuit.
Current.
Resistance.
Voltage.
Duration of Contact.
Pathway.
Conducted Electrical Weapons.
Lightning Injury
Clinical Features
Electrical Injury
General Tissue Effects
Skin
Cardiovascular System
Head and Neck
Extremities
Nervous System
Other Viscera
Clinical Features After Discharge of a Conducted Electrical Weapon
Lightning Injury
Cardiovascular System
Nervous System
Skin
Ears
Eyes
Other Injuries
Differential Diagnoses
Electrical Injury
Lightning Injury
Diagnostic Testing
Electrical Injury
Lightning Injury
Management
Electrical Injury
Lightning Injury
Disposition
Electric Injury
Lightning Injury
References
Chapter 134: Questions & Answers
Chapter 135: Scuba Diving and Dysbarism
Principles
Background
Pathophysiology
Clinical Features
Disorders Related to Descent
Middle Ear Barotrauma
External Ear Barotrauma
Inner Ear Barotrauma
Barosinusitis
Facial Barotrauma
Disorders Arising at Depth
Nitrogen Narcosis
Oxygen Toxicity
Contaminated Air
Disorders Arising on Ascent
Alternobaric Vertigo
Barodontalgia
Gastrointestinal Barotrauma
Pulmonary Barotrauma
Decompression Sickness
Arterial Gas Embolism
Pulmonary Edema
Differential Diagnoses
Diagnostic Testing
Management
Diving Disorders Requiring Recompression Therapy
Diving Disorders Not Requiring Recompression Therapy
External Ear Barotrauma
Middle Ear Barotrauma
Internal Ear Barotrauma
Barosinusitis
Facial Barotrauma
Nitrogen Narcosis
Pulmonary Barotrauma
Alternobaric Vertigo
Disposition
References
Chapter 135: Questions & Answers
Chapter 136: High-Altitude Medicine
Principles
Background
Epidemiology
Definitions
Environmental Considerations
Acclimatization
Pathophysiology
Acute Mountain Sickness
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Oxygen Therapy
Analgesics and Antiemetics
Acetazolamide
Dexamethasone
Disposition
Prevention
High-Altitude Pulmonary Edema
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Ultrasonography
Chest Radiographs
Electrocardiogram and Echocardiogram
Management
Oxygen Therapy
Nifedipine
Other Medications
Disposition
Prevention
High-Altitude Cerebral Edema
Principles
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Special Considerations
High-Altitude Retinal Hemorrhage
Carbon Monoxide Poisoning
Altitude and Underlying Medical Conditions
Respiratory Illnesses
Cardiovascular
Hypertension
Seizures
Sickle Cell Disease
Pregnancy
Radial Keratotomy
Acknowledgment
References
Chapter 136: Questions & Answers
Chapter 137: Drowning
Principles
Definitions
Epidemiology
Risk Factors
Pathophysiology
Clinical Features
History and Physical Examination
Prognostic Factors
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Preventive Efforts
References
Chapter 137: Questions & Answers
Chapter 138: Radiation Injuries
Principles
Radiation
Overview
Radiation Measurements
Radiation Protection
Radiation Sources
Pathophysiology
Routes of Exposure
Clinical Features
Acute Radiation Syndrome
Local Radiation Injury
Differential Diagnoses
Diagnostic Testing
Management
Prehospital Care
Emergency Department
Preparation
External Contamination
Internal Contamination
Acute Radiation Syndrome
Hematopoietic Sub-Syndrome.
Gastrointestinal Sub-Syndrome.
Neurovascular Sub-Syndrome.
Local Radiation Injury
Psychological Consequences
Disposition
Additional Resources
References
Chapter 138: Questions & Answers
Section Two: Toxicology
Chapter 139: Approach to the Poisoned Patient
Principles of Toxicity
Clinical Features
Toxicologic History and Physical
Toxidromes
Sympathomimetic
Anticholinergic
Cholinergic
Sedative/Hypnotic
Opioid
Serotonin Syndrome
Neuroleptic Malignant Syndrome
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Syrup of Ipecac
Gastric Lavage
Single-Dose Activated Charcoal
Whole Bowel Irrigation
Enhanced Elimination
Multiple-Dose Activated Charcoal
Serum Alkalinization
Intravenous Fat Emulsion (Intralipid)
Focused Therapy
Toxicology Consultation
Disposition
References
Chapter 139: Questions & Answers
Chapter 140: Substance Abuse
Principles of Toxicity
Epidemiology
Pharmacology
Clinical Features
History
Physical Examination
Complications
Differential Diagnoses
Diagnostic Testing
Management
Agitation
Drug Seeker
Disposition
References
Chapter 140: Questions & Answers
Chapter 141: Toxic Alcohols
Methanol
Principles of Toxicology
Clinical Features
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Ethylene Glycol
Principles of Toxicology
Clinical Features
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Isopropyl Alcohol
Principles of Toxicology
Clinical Features
Diagnostic Considerations
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Other Alcohols of Clinical Significance
References
Chapter 141: Questions & Answers
Chapter 142: Alcohol-Related Disease
Principles of Toxicity
Metabolism of Alcohol
Clinical Features
Alcohol Withdrawal Syndrome
Alcohol-Related Seizures
Alcohol Withdrawal Seizures
Cardiovascular Effects
Pulmonary Effects
Gastrointestinal and Hepatic Effects
Esophagus and Stomach
Gastrointestinal Bleeding
Liver Damage
Alcoholic Hepatitis
Alcoholic Cirrhosis
Pancreatitis and Malabsorption
Neurologic Effects
Neuropathy
Wernicke-Korsakoff Syndrome
Movement Disorders
Alcoholic Cerebellar Degeneration
Infectious Disease
Endocrine Effects
Metabolic Effects
Carbohydrates
Lipids
Electrolytes
Alcoholic Ketoacidosis
Hematologic Effects
Anemia
Leukocyte Abnormalities
Platelet Disorders
Hemostasis
Oncologic Effects
Hypothermia
Psychiatric Effects
Toxicologic Effects
Disulfiram and Similar Reactions
Other Considerations
Patient Groups Affected
Adolescents.
Older Patients.
Pregnant Women.
Trauma
Alcohol Withdrawal Syndrome
Clinical Features
Differential Diagnoses
Diagnostic Testing
Laboratory Tests
Alcohol Screening Questionnaires
Management Considerations
Alcohol Withdrawal Syndrome
Pharmacologic Treatment
Benzodiazepines.
Butyrophenones.
Other Agents.
Neurologic Examination
Normal Examination
New-Onset Seizures.
Prior History of Seizures During Withdrawal.
Abnormal Neurologic Examination
New-Onset Partial Seizures.
Patients Taking Phenytoin Anticonvulsant
Disposition
Acute Intoxication
Alcohol Withdrawal
Seizures
Psychiatric and Social Problems
References
Chapter 142: Questions & Answers
Chapter 143: Acetaminophen
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Risk Assessment With Acute Acetaminophen Ingestion
Risk Assessment With Chronic Ingestion
Risk Assessment in Pregnant Women
Management
Stabilization and Supportive Care
Decontamination
Enhanced Elimination
Antidote Therapy
N-Acetylcysteine
Use in Pregnancy
Duration of Therapy.
Disposition
References
Chapter 143: Questions & Answers
Chapter 144: Aspirin and Nonsteroidal Agents
Aspirin
Principles of Toxicity
Overview
Epidemiology
Salicylate Containing Products
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Stabilization and Supportive Care
Decontamination
Enhanced Elimination
Antidote Therapy
Disposition
Nonsteroidal Agents
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Stabilization and Supportive Care
Decontamination
Enhanced Elimination
Antidote Therapy
Disposition
References
Chapter 144: Questions & Answers
Chapter 145: Anticholinergics
Principles of Toxicology
Overview
Clinical Features
Differential Diagnoses
Diagnostic Testing
Laboratory
Electrocardiogram
Management
Stabilization
Decontamination
Pharmacologic Intervention and Antidote Treatment
Disposition
Observation at Home
Emergency Department Observation
Hospital Admission
Intensive Care Unit Admission
Consultations
References
Chapter 145: Questions & Answers
Chapter 146: Antidepressants
Principles of Toxicity
Monoamine Oxidase Inhibitors
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Tricyclic Antidepressants
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Selective Serotonin Reuptake Inhibitors
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Serotonin-Norepinephrine Reuptake Inhibitors and Norepinephrine Reuptake Inhibitors
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Miscellaneous Antidepressants
Bupropion
Trazodone
Nefazodone
Serotonin Syndrome
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Discontinuation Syndromes
References
Chapter 146: Questions & Answers
Chapter 147: Cardiovascular Drugs
Cardioactive Steroids (Digoxin)
Principles of Toxicity
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Fab Fragments (DigiFab)
Electrolyte Correction
Atropine
Pacing and Cardioversion
Phenytoin and Lidocaine
Pediatric Considerations
Disposition
Beta-Adrenergic Blockers
Principles of Toxicity
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Hypotension, Bradycardia, and Atrioventricular Block
Calcium
Glucagon
High-Dose Insulin
Sodium Bicarbonate
Vasopressors and Other Inotropes
Intravenous Fat Emulsion (Intralipid)
Ventricular Dysrhythmias
Extracorporeal Elimination and Circulatory Assistance
Pediatric Considerations
Sequential Approach to Beta-Blocker Poisoning
Disposition
Calcium Channel Blockers
Principles of Toxicity
Pathophysiology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Hypotension and Bradycardia
Pediatric Considerations
Disposition
Clonidine
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Nitrates and Nitrites
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
References
Chapter 147: Questions & Answers
Chapter 148: Caustics
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Special Cases
Povidone-Iodine
Phenol and Formaldehyde
Hydrogen Peroxide
Button Batteries
References
Chapter 148: Questions & Answers
Chapter 149: Cocaine and Other Sympathomimetics
Principles of Toxicity
Cocaine Formulations
Pathophysiology of Cocaine
Clinical Features
Hyperthermia
Hypertensive Emergencies
Cardiac Dysrhythmias
Other Complications
Differential Diagnoses
Diagnostic Testing
Management
Pharmacologic Sedation for Agitation
Hyperthermia
Acute Hypertensive Emergencies
Dysrhythmias
Cocaine-Related Chest Pain
Cocaine Body Packers
Body Stuffers
Levamisole-Related Complications
Disposition
Other Stimulants
Amphetamines
Methylenedioxymethamphetamine
Methamphetamine
Ephedrine and Ephedra
Khat and Methcathinone
Bath Salts
References
Chapter 149: Questions & Answers
Chapter 150: Hallucinogens
Serotonergic Agents
Principles of Toxicity
Lysergamides
Tryptamines
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Dissociative Agents
Principles of Toxicity
Phencyclidine
Ketamine
Methoxetamine
Dextromethorphan
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Marijuana and Synthetic Cannabinoids
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management and Disposition
Other Agents
Mescaline
Nutmeg
Salvia
Kratom
Ibogaine
Isoxazole Mushrooms
References
Chapter 150: Questions & Answers
Chapter 151: Iron and Heavy Metals
Iron
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Enhanced Elimination
Antidotal Therapy
Disposition
Lead
Principles of Toxicity
Clincal Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Antidotal Therapy
Children
Adults
Disposition
Arsenic
Principles of Toxicity
Clinical Features
Acute Arsenic Toxicity
Chronic Arsenic Toxicity
Arsine Gas
Differential Diagnoses
Diagnostic Testing
Management
Decontamination and Enhanced Elimination
Antidotal Therapy
Acute Arsenic Poisoning
Chronic Arsenic Poisoning
Disposition
Mercury
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 151: Questions & Answers
Chapter 152: Hydrocarbons
Principles of Toxicology
Pathophysiology
Pulmonary Pathophysiology
Central Nervous System Pathophysiology
Cardiac Pathophysiology
Other Organ Systems
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 152: Questions & Answers
Chapter 153: Inhaled Toxins
Simple Asphyxiants
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Pulmonary Irritants
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Smoke Inhalation
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Disposition
Cyanide and Hydrogen Sulfide
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Hydrogen Cyanide
Hydrogen Sulfide
Disposition
Carbon Monoxide
Principles of Toxicity
Clinical Features
Differential Diagnosis
Diagnostic Testing
Management
Simultaneous Carbon Monoxide and Cyanide Poisoning (Fire Victims)
Disposition
References
Chapter 153: Questions & Answers
Chapter 154: Lithium
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 154: Questions & Answers
Chapter 155: Antipsychotics
Principles of Toxicity
Pathophysiology
Clinical Features
Acute Overdose
Acute Extrapyramidal Syndromes
Tardive Dyskinesia
Neuroleptic Malignant Syndrome
Cardiovascular Toxicity
Agranulocytosis
Seizures
Differential Diagnoses
Diagnostic Testing
Management
General
Anticholinergic Toxidrome
Seizures
Acute Extrapyramidal Syndromes
Cardiotoxicity
Neuroleptic Malignant Syndrome
Disposition
References
Chapter 155: Questions & Answers
Chapter 156: Opioids
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Stabilization and Supportive Care
Decontamination
Enhanced Elimination
Antidote Therapy
Disposition
Withdrawal
References
Chapter 156: Questions & Answers
Chapter 157: Pesticides
Organophosphate Insecticides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Carbamate Insecticides
Chlorinated Hydrocarbons Insecticides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Substituted Phenols
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Chlorophenoxy Herbicides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Bipyridyl Herbicides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Pyrethrin and Pyrethroid Insecticides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Glyphosate
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
DEET
Principles of Toxicology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
Rodenticides
Principles of Toxicology
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Decontamination
Stabilization and Supportive Care
Enhanced Elimination
Antidote Therapy
Disposition
References
Chapter 157: Questions & Answers
Chapter 158: Plants, Mushrooms, and Herbal Medications
Plants
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Plant Categories
Anticholinergics
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Antimitotic Toxins
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Cardiac Glycosides
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Other Cardiotoxic Plants
Cicutoxin
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Other Toxic Plants
Nicotinic Toxin
Raphides
Toxalbumins
Mushrooms
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Mushroom Categories
Hepatotoxic Mushrooms
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Gyromitrin-Containing Mushrooms
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
Other Mushroom Classes
Cholinergic Agonists
Disulfiram Reaction-Inducing Mushrooms
Hallucinogenic Mushrooms
Gastrointestinal Irritants
Renal Insufficiency
Rhabdomyolysis-Inducing Mushrooms
Herbal Medications
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Disposition
References
Chapter 158: Questions & Answers
Chapter 159: Sedative Hypnotics
Barbiturates
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Gastrointestinal Decontamination
Enhanced Elimination
Disposition
Benzodiazepines
Principles of Toxicity
Pharmacokinetics
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
General
Antidote
Disposition
Benzodiazepine Withdrawal Syndrome
Special Considerations
Flunitrazepam
Buspirone
Zolpidem, Zaleplon, and Zopiclone
Eszopiclone
Chloral Hydrate
Principles of Toxicity
Clinical Features
Differential Diagnoses
Management
Disposition
Over-the-Counter Sleep Aids
Principles of Toxicity
Gamma-Hydroxybutyrate
Principles of Toxicity
Clinical Features
Differential Diagnoses
Diagnostic Testing
Management
Withdrawal
Disposition
References
Chapter 159: Questions & Answers
Part V: Special Populations
Section One: The Pediatric Patient
Chapter 160: General Approach to the Pediatric Patient
Principles
Pathophysiology
Temperature Regulation
Airway
Cardiovascular System
Musculoskeletal System
Immunologic System
Pharmacologic Considerations
Developmental Considerations
Young Infants
Infants (

Citation preview

ROSEN’S

EMERGENCY MEDICINE Concepts and Clinical Practice

9th Edition

Rosen’s

Emergency Medicine Concepts and Clinical Practice Editor-in-Chief Ron M. Walls, MD Executive Vice President and Chief Operating Officer, Brigham Health; Neskey Family Professor of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Senior Editors Robert S. Hockberger, MD

Marianne Gausche-Hill, MD, FACEP, FAAP, FAEMS

Emeritus Professor of Emergency Medicine, David Geffen School of Medicine at UCLA; Chair Emeritus, Department of Emergency Medicine, Harbor-UCLA Medical Center, Los Angeles, California

Medical Director, Los Angeles County EMS Agency; Professor of Clinical Medicine and Pediatrics, David Geffen School of Medicine at UCLA; EMS Fellowship Director, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

Editors Katherine Bakes, MD

Amy H. Kaji, MD, PhD

Associate Professor, Department of Emergency Medicine, University of Colorado School of Medicine; Clinical Director of Community Affairs, Director, At-Risk Intervention and Mentoring (AIM), Denver Health; Denver, Colorado

Associate Professor, Emergency Medicine, David Geffen School of Medicine at UCLA; Vice Chair of Academic Affairs, Department of Emergency Medicine, Harbor-UCLA, Los Angeles, California

Jill Marjorie Baren, MD, MBE, FACEP, FAAP Professor and Chair, Emergency Medicine, Perelman School of Medicine; Chief, Emergency Services, University of Pennsylvania Health System, Philadelphia, Pennsylvania

Chairman, Emergency Medicine, Brigham and Women’s Hospital Professor, Department of Emergency Medicine, Harvard Medical School; Boston, Massachusetts; Director, Harvard Humanitarian Initiative, Harvard University, Cambrige, Massachusetts

Timothy B. Erickson, MD, FACEP, FACMT, FAACT

Richard D. Zane, MD, FAAEM

Chief, Division of Medical Toxicology, Department of Emergency Medicine, Brigham and Women’s Hospital; Harvard Medical School, Boston, Massachusetts; Faculty, Harvard Humanitarian Initiative, Cambridge, Massachusetts

The George B. Boedecker Professor and Chair, Department of Emergency Medicine, University of Colorado School of Medicine; Executive Director, Emergency Services, University of Colorado Health, Aurora, Colorado

Michael VanRooyen, MD, MPH

Andy S. Jagoda, MD Professor and Chair, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai; Professor and Chair, Emergency Medicine, Mount Sinai School of Medicine, New York, New York

VOLUME 1

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

ROSEN’S EMERGENCY MEDICINE: CONCEPTS AND CLINICAL PRACTICE, NINTH EDITION 

ISBN: 978-0-323-35479-0 Part Vol 1: 9996111695 Part Vol 2: 9996111636

Copyright © 2018 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2014, 2010, 2006, 2002, 1998, 1992, 1988, and 1983. Library of Congress Cataloging-in-Publication Data Names: Walls, Ron M., editor. | Hockberger, Robert S., editor. | Gausche-Hill, Marianne, editor. Title: Rosen’s emergency medicine : concepts and clinical practice / [edited by] Ron M. Walls, Robert S. Hockberger, Marianne Gausche-Hill. Other titles: Emergency medicine Description: Ninth edition. | Philadelphia, PA : Elsevier, [2018] | Includes bibliographical references and index. Identifiers: LCCN 2016055133 | ISBN 9780323354790 (hardcover : alk. paper) | ISBN 9789996111693 (v. 1: hardcover : alk. paper) | ISBN 9996111695 (v. 1: hardcover : alk. paper) | ISBN 9789996111631 (v. 2 : hardcover : alk. paper) | ISBN 9996111636 (v. 2: hardcover : alk. paper) Subjects: | MESH: Emergencies | Emergency Medicine Classification: LCC RC86.7 | NLM WB 105 | DDC 616.02/5—dc23 LC record available at https://lccn.loc.gov/2016055133 Executive Content Strategist: Kate Dimock Senior Content Development Specialist: Deidre Simpson Publishing Services Manager: Catherine Jackson Senior Project Manager: Rachel E. McMullen Design Direction: Renee Duenow Printed in China Last digit is the print number:  9  8  7  6  5  4  3  2  1

Acknowledgments To my wife Barb, thank you for the endless love, support, and patience and for being my closest and most trusted advisor. To my children, Andrew, Blake, and Alexa, thank you for making my life so complete that I can savor fully the joy and privilege of helping others. To David and Sharon Neskey, thank you for your vision and generosity in support of me and of our specialty. To my colleagues at Brigham and Women’s Hospital and the Department of Emergency Medicine at Harvard Medical School, thank you for the constant inspiration to drive toward excellence. To Peter Rosen and John Marx, thank you for showing the way with such extraordinary determination and clarity. And to Bob, Marianne, and our superb editors, you are the best team that one could hope for. Thank you for bringing so much brilliance, energy, and commitment to make this edition so special. RMW To Peter for his inspiration and mentorship over the years; to John for sharing his friendship and commitment to excellence; to Ron for his leadership and renewed vision for the “bible” of Emergency Medicine; to Marianne for her creativity and endless enthusiasm; to Amy, Andy, Jill, Katie, Mike, Tim, and Rich for their willingness to add this burden of love to their already busy lives; to Kate and Dee for their vigilance and professionalism; and to Patty, for bringing color and meaning to my life. RSH I would like to thank my family for their continued understanding of my work to improve emergency care. My husband David and our three children Katie, Jeremiah, and Sarah provide the love, joy, and encouragement that makes participation on endeavors as important as this text worthwhile. Finally, I would like to thank Drs. Ron Walls, Robert Hockberger, and all the associate editors for their incredible leadership in the creation of a truly state of the art textbook. MGH I would like to thank my wonderful family, Peter, Sam, Jessie, and Avery, who sacrificed their time with me for the publication of this text. I would also like to thank my mentors, including Marianne Gausche-Hill and Bob Hockberger, for their constant support and positive encouragement. And finally, I would like to thank Ron Walls, my dear friend and ultimate mentor, who has looked out for me and inspired me since medical school. In many ways, my success belongs more to him that it does to me. I am eternally grateful for all of you. KB

I am forever grateful to my husband Kenneth and my two sons, Noah and Andrew, for their everlasting love and for their tolerance of my long hours and work passions. I love you all so much. Mom and Dad—thanks for such a great start in life and for continuing to tell me how proud you are. It makes a difference, no matter how old you get. I have deep appreciation for my authors and fellow editors who have enriched my knowledge of emergency medicine and strengthened my clinical practice through your outstanding contributions to this book. JMB I extend my thanks to Valerie, Camille, Isabelle, Celeste, Julian, and my parents. I also give appreciation to my mentors and colleagues in Emergency Medicine, Toxicology, Wilderness Medicine, and Global and Humanitarian Health, with special thanks to Paracelsus and Alice Hamilton. TBE To all the faculty, residents, and staff at the Mount Sinai Department of Emergency Medicine—their commitment to excellence in clinical care, teaching, and research inspires me every day. To Silvana, my wife and closest colleague, for her support and for keeping me focused on the important things in life. To Ron, for being a mentor throughout my career; and to John, whose memory lives forever. ASJ As a first-time section editor, I am grateful to Ron, Bob, and Marianne for their incredible mentorship and patience with me, and to Dee and Kate for their editorial guidance. This has been a tremendous learning experience and opportunity. Thank you! AHK With love and thanks to my family, ever patient and ever supportive. And especially to my daughter, Isabella VanRooyen, who is striving toward a career in medicine. May she be as fortunate as I was to find wonderful colleagues, inspiring mentors, and generous patients to lead her into a fulfilling career in a field that she loves. MV It is both humbling and a privilege to be associated with this text and those who started it all— Rosen, Marx, Walls, and Hockberger—the founders of our discipline. RDZ

v

Contributors Gallane Abraham, MD

Aaron N. Barksdale, MD

Assistant Professor, Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

Assistant Professor, Emergency Medicine, University of Nebraska Medical Center, Omaha, Nebraska

Michael K. Abraham, MD, MS

Christopher W. Baugh, MD, MBA

Clinical Assistant Professor, Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Attending Physician, Emergency Medicine, Upper Chesapeake Health System, Bel Air, Maryland

Director of Observation Medicine, Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Saadia Akhtar, MD Associate Dean for Graduate Medical Education and Residency Program Director, Department of Emergency Medicine, Mount Sinai Beth Israel, New York, New York

Steven E. Aks, DO Director, The Toxikon Consortium, Department of Emergency Medicine, Cook County Health and Hospitals System; Professor of Emergency Medicine, Department of Emergency Medicine, Rush University, Chicago, Illinois

James T. Amsterdam, DMD, MD, MMM, FACEP, FACPE Senior Vice-President/Chief Medical Officer, Administration, Saint Vincent Hospital Allegheny Health Network, Erie, Pennsylvania; Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Penn State University College of Medicine, Hershey, Pennsylvania; Adjunct Professor of Emergency Medicine, Department of Emergency Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania

Felix K. Ankel, MD Vice President, Health Professional Education, HealthPartners, Bloomington, Minnesota; Professor, Emergency Medicine, University Of Minnesota, Minneapolis, Minnesota

Robert T. Arntfield, MD, FRCPC, FCCP, RDMS

Bruce M. Becker, MD, MPH, FACEP Professor, Emergency Medicine and Behavioral and Social Science, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island

Rachel R. Bengtzen, MD Assistant Professor, Emergency Medicine and Family Medicine (Sports Medicine), Oregon Health and Science University, Portland, Oregon

Rachel Berkowitz, MD Attending Physician, Department of Emergency Medicine, Kaiser Permanente South San Francisco Medical Center, San Francisco, California

Kristin Berona, MD Assistant Professor of Emergency Medicine, LAC USC Medical Center, Keck School of Medicine, Los Angeles, California

Marian E. Betz, MD, MPH Associate Professor, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Michelle H. Biros, MD, MS Professor, Emergency Medicine, University of Minnesota Medical School; Attending Physician, Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota

Assistant Professor, Division of Emergency Medicine and Critical Care Medicine, Western University; Attending Physician, Emergency Medicine, Critical Care Medicine and Trauma, London Health Sciences Centre, London, Ontario, Canada

Robert A. Bitterman, MD, JD

Tom P. Aufderheide, MD

Assistant Dean, Longitudinal Clinical Education, University of South Carolina School of Medicine Greenville; Professor, Department of Emergency Medicine, Greenville Health System, Greenville, South Carolina

Professor of Emergency Medicine, Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin

Katherine Bakes, MD Associate Professor, Department of Emergency Medicine, University of Colorado School of Medicine; Clinical Director of Community Affairs, Director, At-Risk Intervention and Mentoring (AIM), Denver Health; Denver, Colorado

President, Bitterman Health Law Consulting Group, Sarasota, Florida

Thomas H. Blackwell, MD

Frederick C. Blum, BA, MD Associate Professor, Departments of Pediatrics and Emergency Medicine, West Virginia University School of Medicine, Morgantown, West Virginia

vii

viii

Contributors

Ira J. Blumen, MD, FACEP

E. Bradshaw Bunney, MD, FACEP

Professor, Department of Medicine, Section of Emergency Medicine, University of Chicago; Medical and Program Director, University of Chicago Aeromedical Network (UCanada), University of Chicago Medicine, Chicago, Illinois

Associate Professor, Residency Director, Emergency Medicine, University of Illinois at Chicago, Chicago, Illinois

Edward B. Bolgiano, MD Assistant Professor, Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Michael C. Bond, MD Associate Professor, Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Kelly Bookman, MD Associate Professor, Emergency Medicine, University of Colorado, Denver, Colorado

Joelle Borhart, MD Assistant Professor, Emergency Medicine, Georgetown University, Washington, DC

William J. Brady, MD Professor of Emergency Medicine, Department of Emergency Medicine; Professor of Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia

Michael J. Burns, MD Clinical Professor, Departments of Emergency Medicine and Medicine, Division of Infectious Diseases, University of California Irvine School of Medicine, Irvine, California; Attending Physician, Department of Emergency Medicine, University of California Irvine Medical Center, Orange, California

John H. Burton, MD Chair, Professor of Emergency Medicine, Department of Emergency Medicine, Carilion Clinic, Roanoke, Virginia

Katharine Carroll Button, BA, BS, MS, MD Clinical Fellow, Pediatric Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts

Richard L. Byyny, MD, MSc Associate Professor, Emergency Medicine, Denver Health Medical Center, Denver, Colorado; Assistant Professor, Emergency Medicine, University of Colorado, Aurora, Colorado

John D. Cahill, MD

Associate Professor, Division of Emergency Medicine; Program Director, EMS Fellowship, Washington University in St. Louis School of Medicine, St. Louis, Missouri

Senior Attending in Emergency Medicine and Infectious Disease, Global Health Fellowship Director, Emergency Medicine, St. Luke’s Roosevelt Hospital Center, New York, New York; Senior Lecturer, International Health and Tropical Medicine, The Royal College of Surgeons, Dublin, Ireland

Leah Bright, DO

Andrea Carlson, MD

Sabina A. Braithwaite, MPH

Assistant Professor, Emergency Medicine Department, Johns Hopkins Medical Institute, Baltimore, Maryland

Assistant Residency Director, Director of Toxicology, Emergency Medicine, Advocate Christ Hospital, Oak Lawn, Illinois

Aaron Brody, MD

Jeffrey M. Caterino, MD, MPH

Assistant Professor, Emergency Medicine, Wayne State University, Detroit, Michigan

Associate Professor, Departments of Emergency and Internal Medicine, The Ohio State University, Columbus, Ohio

Calvin A. Brown III, MD

Andrew K. Chang, MD, MS

Assistant Professor of Emergency Medicine, Director of Faculty Affairs, Harvard Medical School; Attending Physician, Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Vincent P. Verdile, MD Endowed Chair in Emergency Medicine, Professor of Emergency Medicine, Vice Chair of Research and Academic Affairs, Department of Emergency Medicine, Albany Medical College, Albany, New York

James E. Brown, MD, MMM

Jennifer C. Chen, MD, MPH

Chair, Department of Emergency Medicine, Wright State University Boonshoft School of Medicine, Dayton, Ohio

Jennie Alison Buchanan, MD

Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California; Clinical Assistant Professor of Medicine, School of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California

Attending Physician, Emergency Medicine, Denver Health and Hospital Authority; Staff Physician, Medical Toxicology, Rocky Mountain Poison and Drug Center, Denver, Colorado; Associate Professor, Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Rachel L. Chin, MD

Jeffrey Bullard-Berent, MD

Esther K. Choo, MD, MPH

Professor, Departments of Emergency Medicine and Pediatrics, University of New Mexico, Albuquerque, New Mexico

Professor of Emergency Medicine, Department of Emergency Medicine, UCSF School of Medicine, San Francisco General Hospital, San Francisco, California

Assistant Professor, Emergency Medicine, Warren Alpert Medical School, School of Public Health, Brown University, Providence, Rhode Island

Contributors

Richard F. Clark, MD

Daniel F. Danzl, MD

Professor, Emergency Medicine, UCSD School of Medicine; Director, Division of Medical Toxicology, UCSD Medical Center; Medical Director, San Diego Division, California Poison Control System, San Diego, California

Professor and Chair, Department of Emergency Medicine, ICAR, Zürich, Switzerland; Clinical Professor, Department of Emergency Medicine, Stanford University Medical Center, Stanford, California

Ilene Claudius, MD

Mohamud R. Daya, MD, MS

Associate Professor, Emergency Medicine, University of South Carolina Keck School of Medicine, Los Angeles, California

Professor of Emergency Medicine Department of Emergency Medicine, Oregon Health and Science University, Portland, Oregon

Wendy C. Coates, MD Professor of Clinical Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Senior Faculty/Education Specialist, Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

Jon B. Cole, MD Medical Director, Minnesota Poison Control System; Faculty, Emergency Physician, Department of Emergency Medicine, Hennepin County Medical Center; Associate Professor of Emergency Medicine, Department of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota

Robert A. De Lorenzo, MD, MSM, MSCI Professor, Department of Emergency Medicine, University of Texas Health Scinece Center at San Antonio, San Antonio, Texas; Professor, Departement of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Ken Deitch, DO Research Director, Department of Emergency Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania

Robert W. Derlet, MD

Michael Alan Cole, MD

Professor, Emergency Department, University of California, Davis, School of Medicine, Sacramento, California

Assistant Professor, Emergency Medicine, University of Michigan Medical School, Ann Arbor, Michigan

Shoma Desai, MD

Christopher B. Colwell, MD

Assistant Professor, Department of Emergency Medicine, LAC + USC Medical Center, Los Angeles, California

Chief of Emergency Medicine, Zuckerberg San Francisco General Hospital and Trauma Center; Professor and ViceChair, Department of Emergency Medicine, UCSF School of Medicine, San Francisco, California

Robert Cooper, MD Assistant Professor of Emergency Medicine, Medical Director Ohio State University Health Plan, The Ohio State University, Columbus, Ohio

Zara Cooper, MD, MSc Associate Surgeon, Division of Trauma, Burns and Surgical Critical Care, Department of Surgery, Brigham and Women’s Hospital; Assistant Professor of Surgery, Harvard Medical School, Boston, Massachusetts

Randolph J. Cordle, MD Medical Director, Division of Pediatric Emergency Medicine, Emergency Medicine, Carolinas Medical Center, Levine Children’s Hospital, Charlotte, North Carolina

Brian Niall Corwell, MD Assistant Professor, Department of Emergency Medicine and Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland

Todd J. Crocco, MD, FACEP Chief Business Development Officer, WVU Health Sciences Center; Professor, Department of Emergency Medicine, West Virginia University, Morgantown, West Virginia

Shawn M. D’Andrea, MD, MPH Instructor of Emergency Medicine, Emergency Medicine, Harvard Medical School; Attending Physician, Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Valerie A. Dobiesz, MD, MPH, FACEP Director of External Programs: STRATUS Center for Medical Simulation, Brigham and Women’s Hospital; Harvard Humanitarian Initiative, Harvard Medical School, Boston, Massachusetts

Alan A. Dupré, MD Assistant Professor, Department of Emergency Medicine, Boonshoft School of Medicine, Wright State University, Dayton, Ohio

Joshua Samuel Easter, MD, MSc Assistant Professor, Emergency Medicine, University of Virginia, Charlottesville, Virginia; Physician, Emergency Medicine, Bon Secours St. Mary’s Hospital, Richmond, Virginia

Wesley P. Eilbert, MD Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, University of Illinois, College of Medicine, Chicago, Illinois

Matthew Emery, MD, FACEP Assistant Professor, Associate Director for Academic Affairs, Department of Emergency Medicine, Lead Clerkship Director, Fourth-Year Elective in Emergency Medicine, Department of Emergency Medicine, Michigan State University College of Human Medicine; Educational Assistant for Simulation, Emergency Medicine, Grand Rapids Medical Education Partners, Grand Rapids, Michigan

ix

x

Contributors

Timothy B. Erickson, MD, FACEP, FACMT, FAACT

Jeffrey M. Goodloe, MD, NRP, FACEP

Chief, Division of Medical Toxicology, Department of Emergency Medicine, Brigham and Women’s Hospital; Harvard Medical School, Boston, Massachusetts; Faculty, Harvard Humanitarian Initiative, Cambridge, Massachusetts

Professor and EMS Section Chief, Director, Oklahoma Center for Prehospital and Disaster Medicine Department of Emergency Medicine, University of Oklahoma School of Community Medicine—Tulsa; Oklahoma Medical Director, Medical Control Board EMS System for Metropolitan Oklahoma City and Tulsa, Tulsa, Oklahoma

Madonna Fernández-Frackelton, MD Program Director, Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California; Professor of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California

Eric Goralnick, MD, MS

Associate Professor of Clinical Emergency Medicine, Indiana University, Indianapolis, Indiana

Medical Director, Emergency Preparedness, Brigham and Women’s Healthcare; Assistant Professor, Emergency Medicine, Harvard Medical School; Instructor, Department of Health Policy and Management, Harvard TH Chan School of Public Health, Boston, Massachusetts

Charles J. Fox, MD, FACS

Diane L. Gorgas, MD

John T. Finnell, MD, MSc

Chief, Vascular Surgery, Department of Surgery, Denver Health Medical Center; Associate Professor of Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, Colorado

Professor, Department of Emergency Medicine, The Ohio State University; Executive Director, Office of Global Health, The Ohio State University, Columbus, Ohio

Benjamin W. Friedman, MD, MS

Professor of Traumatology and Emergency Medicine, Emergency Medicine, University of Connecticut School of Medicine, Farmington, Connecticut; Medical Director of Quality, Performance Improvement, Associate Director of Emergency Medicine, Emergency Medicine, Hospital of Central Connecticut, New Britain, Connecticut

Associate Professor, Emergency Medicine, Albert Einstein College of Medicine; Attending Physician, Emergency Medicine, Montefiore Medical Center, Bronx, New York

Joel M. Geiderman, MD, FACEP

Louis Graff IV, MD, FACEP, FACP

Professor of Medicine, Department of Medicine, Division of Emergency Medicine, David Geffen School of Medicine at UCLA; Co-Chairman and Professor of Emergency Medicine, Department of Emergency Medicine, Cedars-Sinai Medical Center, Los Angeles, California; Medical Director, Beverly Hills Fire Department, California

Thomas J. Green, MSc, MD

Nicholas Genes, MD, PhD Associate Professor, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

Clinical Professor of Emergency Medicine, Quality Director, Department of Emergency Medicine, University of California, Davis, Sacramento, California

Carl A. Germann, MD, FACEP

Phillip F. Gruber, MD

Clinical Assistant Professor, Department of Emergency Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Eric A. Gross, MD

Associate Professor, Emergency Medicine, Tufts University School of Medicine, Boston, Massachusetts; Attending Physician, Emergency Department, Maine Medical Center, Portland, Maine

Assistant Professor of Clinical Emergency Medicine, LAC USC Department of Emergency Medicine, Keck School of Medicine of USC, Los Angeles, California

Jonathan M. Glauser, MD, MBA, FACEP

Clinical Professor, Department of Emergency Medicine, University of California San Diego, San Diego, California

Professor, Emergency Medicine, Case Western Reserve University; Faculty, Emergency Medicine Residency, MetroHealth Medical Center, Cleveland, Ohio

Steven A. Godwin, MD, FACEP Professor and Chair, Emergency Medicine, Assistant Dean, Simulation Education, University of Florida COMJacksonville, Jacksonville, Florida

Scott A. Goldberg, MD, MPH Director of Emergency Medical Services, Brigham and Women’s Hospital; Instructor of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Kama Guluma, MD

Leon Gussow, MD Lecturer, Emergency Medicine, University of Illinois; Instructor, Emergency Medicine, Rush Medical College, Chicago, Illinois

Joshua Guttman, MD, FRCPC, FAAEM Assistant Professor, Department of Emergency Medicine, Long Island Jewish Medical Center, Hofstra-Northwell School of Medicine, New Hyde Park, New York

Elizabeth J. Haines, DO Assistant Professor, Emergency Medicine and Pediatrics, New York University School of Medicine, New York, New York

Contributors

N. Stuart Harris, MD, MFA, FRCP Edinburgh

Robert S. Hoffman, MD, FAACT, FACMT, FRCP Edinburgh

Chief, Division of Wilderness Medicine, Fellowship Director, MGH Wilderness Medicine Fellowship, Department of Emergency Medicine, Massachusetts General Hospital; Associate Professor, Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Professor, Emergency Medicine and Medicine, New York University School of Medicine; Attending Physician, Department of Emergency Medicine, Bellevue Hospital Center, New York, New York

Danielle Hart, MD

Assistant Professor, Departments of Medicine, Emergency Medicine, and Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Associate Program Director and Director of Simulation, Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota

Benjamin W. Hatten, MD, MPH Assistant Professor, Emergency Medicine, University of Colorado–School of Medicine, Aurora, Colorado; Medical Toxicologist, Rocky Mountain Poison and Drug Center, Denver Health Medical Center, Denver, Colorado

Jag S. Heer, MD

Christopher Hogrefe, MD

Jeffrey A. Holmes, MD Attending Physician, Emergency Department, Maine Medical Center, Portland, Maine

Jason A. Hoppe, DO Associate Professor, Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Associate Professor of Clinical Medicine, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California; Attending Faculty Physician, Department of Emergency Medicine, Kern Medical Center, Bakersfield, California

Timothy Horeczko, MD, MSCR

Carlton E. Heine, MD, PhD Clinical Associate Professor, Elson S. Floyd College of Medicine, Washington State University, Spokane Academic Center, Spokane, Washington

Fellowship Director, Associate Medical Director, Rocky Mountain Poison and Drug Center; Director, Medical Toxicology Clinic, Section of Medical Toxicology, Department of Emergency Medicine, University of Colorado School of Medicine, Denver, Colorado

Jason D. Heiner, MD

Daniel Hryhorczuk, MD, MPH

Clinical Assistant Professor, Division of Emergency Medicine, University of Washington, Seattle, Washington

Robert G. Hendrickson, MD Professor, Department of Emergency Medicine, Oregon Health and Science University; Program Director, Fellowship in Medical Toxicology, Oregon Health and Science University; Associate Medical Director, Medical Toxicologist, Oregon Poison Center, Portland, Oregon

H. Gene Hern, Jr, MD, MS Vice Chair, Education, Emergency Medicine, Alameda Health System—Highland Hospital, Oakland, California; Association Clinical Professor, University of California, San Francisco, California

Jamie M. Hess, MD Director of Medical Student Education, Emergency Department, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Christopher M. Hicks, MD, MEd, FRCPC Staff Emergency Physician, Trauma Team Leader, Department of Emergency Medicine, St. Michael’s Hospital; Assistant Professor, Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Robert S. Hockberger, MD Emeritus Professor of Emergency Medicine, David Geffen School of Medicine at UCLA; Chair Emeritus, Department of Emergency Medicine, Harbor-UCLA Medical Center, Los Angeles, California

Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

Christopher Hoyte, MD

Director, Environmental Health, Center for Global Health, University of Illinois College of Medicine, Chicago, Illinois

Margaret G. Huang, MD Clinical Instructor, Department of Pediatric Emergency Medicine, Rady Children’s Hospital, UC San Diego Medical Center, San Diego, California; Clinical Instructor, Department of Pediatric Emergency Medicine, Rady Children’s Hospital, UC San Diego Medical Center, San Diego, California

Robert David Huang, MD Clinical Ultrasound Fellowship Director, Associate Director of Clinical Ultrasound, Assistant Residency Program Director, Clinical Instructor, University of Michigan Health System, Ann Arbor, Michigan

J. Stephen Huff, MD Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia, Charlottesville, Virginia

Christopher L. Hunter, MD, PhD Clinical Assistant Professor, Emergency Medicine, University of Central Florida College of Medicine; Attending Physician, Emergency Medicine, Orlando Regional Medical Center; Associate EMS Medical Director, Health Services, Orange County, Orlando, Florida

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Contributors

Alson S. Inaba, MD, FAAP

Julius (Jay) A. Kaplan, MD, FACEP

Associate Professor of Pediatrics, Department of Pediatrics, University of Hawaii John A. Burns School of Medicine; PEM Attending Physician, Emergency Department, Kpaiolani Medical Center for Women and Children; Course Director, Pediatric Advanced Life Support, The Queen’s Medical Center, Honolulu, Hawaii; PEM Attending Physician, Emergency Medicine Physicians (EMP), Canton, Ohio

Immediate Past-President, American College of Emergency Physicians; Vice Chair, Department of Emergency Medicine, Ochsner Health System, New Orleans, Louisiana

Kenneth V. Iserson, MD, MBA Professor Emeritus, Emergency Medicine, The University of Arizona, Tucson, Arizona

Janetta L. Iwanicki, BA, MD Medical Toxicology, Attending Physician, Department of Medical Toxicology, Rocky Mountain Poison and Drug Center; Emergency Medicine Attending Physician, Department of Emergency Medicine, Denver Health, Denver, Colorado; Assistant Professor, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Andy S. Jagoda, MD Professor and Chair, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai; Professor and Chair, Emergency Medicine, Mount Sinai School of Medicine, New York, New York

Timothy G. Janz, MD Professor, Department of Emergency Medicine, Wright State University—Boonshoft School of Medicine; Professor, Pulmonary/Critical Care Division, Department of Internal Medicine, Wright State University—Boonshoft School of Medicine, Dayton, Ohio

Alan E. Jones, MD Professor and Chair, Department of Emergency Medicine, University of Mississippi School of Medicine, Jackson, Mississippi

Emily Martin Jones, MD Assistant Professor, Departments of Medicine and Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Nicholas J. Jouriles, MD Professor and Chair, Department of Emergency Medicine, Northeast Ohio Medical University, Rootstown, Ohio; Chair, Department of Emergency Medicine, Cleveland Clinic Akron, GeneralAkron, Ohio; Past President, American College of Emergency Physicians, Dallas, Texas

Amy H. Kaji, MD, PhD Associate Professor, Emergency Medicine, David Geffen School of Medicine at UCLA; Vice Chair of Academic Affairs, Department of Emergency Medicine, Harbor-UCLA, Long Beach, California

Tarina Lee Kang, MD Associate Professor of Emergency Medicine, LAC USC Medical Center, Keck School of Medicine, Los Angeles, California

Dan Katz, MD, DTMH Attending Physician and Medical Director of Academic Affairs, Department of Emergency Medicine, Cedars-Sinai Medical Center; Assistant Professor of Clinical Medicine, Department of Medicine, Division of Emergency Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California

Stephanie Kayden, MD, MPH Chief, Division of International Emergency Medicine and Humanitarian Programs, Department of Emergency Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Ryan D. Kearney, MD Fellow, Emergency Medicine, Seattle Children’s Hospital, Seattle, Washington

Matthew P. Kelly, MD Assistant Professor, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Hyung T. Kim, MD Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, University of Southern California, Los Angeles, Los Angeles, California

Heidi Harbison Kimberly, MD, FACEP Chief, Division of Emergency Ultrasound, Brigham and Women’s Hospital; Assistant Professor of Emergency Medicine, Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Jeffrey A. Kline, MD Professor and Vice Chair of Research, Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Kristi L. Koenig, MD, FACEP, FIFEM, FAEMS Professor of Emergency Medicine and Public Health, Director, Center for Disaster Medical Sciences, Founding Director, EMS & International Disaster Medical Sciences Fellowship, Director of Public Health Preparedness, University of California, Irvine School of Medicine, Irvine, California; EMS Medical Director, County of San Diego Health & Human Services Agency, San Diego, California

Joshua M. Kosowsky, MD Attending Physician, Department of Emergency Medicine, Brigham and Women’s Hospital; Assistant Professor, Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Michael C. Kurz, MD, MS, FACEP Associate Professor, Department of Emergency Medicine, University of Alabama School of Medicine, Birmingham, Alabama

Contributors

Thomas Kwiatkowski, MD

Mark D. Lo, MD

Assistant Dean and Professor, Emergency Medicine Basic Sciences, Hofstra Northwell School of Medicine, Hempstead, New York; Attending Physician, Emergency Medicine, Long Island Jewish Medical Center, New Hyde Park, New York; Attending Physician, Emergency Medicine, North Shore University Hospital, Manhasset, New York

Department of Pediatric Emergency Medicine, Seattle Children’s Hospital, Seattle, Washington

Nicole Lazarciuc, MD, MPH Assistant Clinical Professor, Mount Sinai Icahn School of Medicine, New York, New York

Andrew W. Lee, MD Associate Vice Chair, Operations; Assistant Professor, Department of Emergency Medicine, University of Wisconsin, Madison, Wisconsin

Christopher C. Lee, MD Assistant Professor, Stony Brook University, Stony Brook, New York

Sharon E. Mace, MD, FACEP, FAAP Professor of Emergency Medicine, Cleveland Clinical Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio

Gerald E. Maloney, Jr, DO Attending Physician, Emergency Medicine, MetroHealth Medical Center; Assistant Professor, Emergency Medicine, Case Western Reserve University, Cleveland, Ohio

Patrick J. Maloney, MD Medical Director, Pediatric Emergency Services, Emergency Medicine, Mission Hospital, Asheville, North Carolina

Rebekah Mannix, MD, MPH

Jeffrey E. Lee, MD

Assistant Professor, Pediatrics, Harvard Medical School; Attending Physician, Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts

Assistant Professor, Program Director, Ophthalmology, UC San Diego, San Diego, California

Catherine A. Marco, MD

Charles Lei, MD Assistant Professor of Emergency Medicine, Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennesee

Michael D. Levine, MD Department of Emergency Medicine, Division of Medical Toxicology, Assistant Professor, Department of Emergency Medicine, Section of Medical Toxicology, University of Southern California, Los Angeles, California

Phillip D. Levy, MD, MPH Professor and Associate Chair for Research, Department of Emergency Medcicine, Wayne State University, Detroit, Michigan

Christopher S. Lim, MD Assistant Professor, Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois

Daniel Lindberg, MD

Professor, Emergency Medicine, Wright State University Boonshoft School of Medicine; Attending Physician, Emergency Medicine, Miami Valley Hospital, Dayton, Ohio

Marc L. Martel, MD Faculty, Department of Emergency Medicine, Hennepin County Medical Center; Associate Professor, Department of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota

Ryanne J. Mayersak, MS, MD Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon

Maryann Mazer-Amirshahi, PharmD, MD, MPH Assistant Professor, Emergency Medicine, MedStar Washington Hospital Center; Assistant Professor of Emergency Medicine, Georgetown University School of Medicine, Washington, DC

Maureen McCollough, MD, MPH

Associate Professor, Emergency Medicine and Pediatrics, University of Colorado, Denver, Colorado

Associate Professor of Emergency Medicine, USC Keck School of Medicine, Department of Emergency Medicine, Oliveview-UCLA Medical Center, Sylmar, California

Judith A. Linden, MD

Taylor McCormick, MD, MS

Associate Professor and Vice Chair for Education, Emergency Medicine, Boston University, Boston Medical Center, Boston, Massachusetts

Emergency Medicine Physician, Denver Health Medical Center, Denver, Colorado; Instructor, Department of Emergency Medicine, University of Colorado School Of Medicine, Aurora, Colorado

Ari M. Lipsky, MD, PhD Attending Physician, Emergency Department, Clear Lake Regional Medical Center, Webster, Texas; Research Director, Emergency Medicine, Rambam Health Care Campus, Haifa, Israel

Michael T. McCurdy, MD Associate Professor, Departments of Medicine (Division of Pulmonary and Critical Care) and Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland

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Contributors

Nathanael J. McKeown, DO

Gregory J. Moran, MD

Assistant Professor, Department of Emergency Medicine, Oregon Health and Science University; Attending Physician, Department of Emergency Medicine, Portland VA Medical Center, Portland, Oregon

Professor, Department of Clinical Emergency and Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Emergency Medicine and Division of Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, California

Jeffry McKinzie, MD Assistant Professor, Emergency Medicine; Assistant Professor, Pediatrics, Vanderbilt University, Nashville, Tennessee

Raveendra S. Morchi, MD

Kemedy K. McQuillen, MD

Associate Professor in Emergency Medicine, Department of Emergency Medicine, Harbor- UCLA Medical Center, Torrance, California

Attending Physician, Emergency Medicine, St. Mary’s Regional Medical Center, Lewiston, Maine

Robert L. Muelleman, MD

Timothy J. Meehan, MD, MPH

Professor and Chair, Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, Nebraska

Assistant Clinical Professor, Emergency Medicine and Medical Toxicology, University of Illinois Hospital and Health Science System, Chicago, Illinois

Brittany Lee Murray, MD

Instructor of Emergency Medicine, Harvard Medical School; Brigham and Women’s Hospital, Boston, Massachusetts

Assistant Professor, Division of Pediatric Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia; Honorary Lecturer, Emergency Medicine Department, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

Frantz R. Melio, MD

Mark B. Mycyk, MD

David A. Meguerdichian, MD

Director of Physician Outreach and Strategic Development, University of New Mexico Medical Group, University of New Mexico Health System, Albuquerque, New Mexico

Attending Physician, Emergency Medicine, Cook County Hospital; Research Director, Toxikon Consortium, Chicago, Illinois

Felipe Teran Merino, MD

Joshua Nagler, MD, MHPEd

Academic Chief Resident, Instructor, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

William J. Meurer, MD, MS Associate Professor, Department of Emergency Medicine, Associate Professor, Department of Neurology, University of Michigan, Ann Arbor, Michigan

Nathan W. Mick, MD Director, Pediatric Emergency Medicine, Department of Emergency Medicine, Maine Medical Center, Portland, Maine

James R. Miner, MD Chief of Emergency Medicine, Hennepin County Medical Center; Professor of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota

Alicia B. Minns, MD Assistant Clinical Professor of Emergency Medicine, Emergency Medicine, UCSD, San Diego, California

Jessica Monas, MD Clinical Assistant Professor, Emergency Medicine, University of Arizona College of Medicine, Phoenix, Arizona

Andrew A. Monte, MD Associate Professor, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Gregory P. Moore, MD, JD Faculty Emergency Medicine Residency, Madigan Army Medical Center, Tacoma, Washington

Assistant Professor, Pediatrics and Emergency Medicine, Harvard Medical School; Fellowship Director, Division of Emergency Medicine, Boston Children’s Hospital, Boston, Massachusetts

Sidhant Nagrani, MD Director of Residency Simulation, Emergency Medicine, Emory School of Medicine, Atlanta, Georgia

Anthony M. Napoli, MD Associate Professor of Emergency Medicine, Department of Emergency Medicine, The Warren Alpert Medical School at Brown University, Providence, Rhode Island

Lewis S. Nelson, MD Professor and Chair, Department of Emergency Medicine, New Jersey Poison Information and Education System, Rutgers New Jersey Medical School, Newark, New Jersey

Michael E. Nelson, MD, MS Attending Physician, Emergency Medicine, NorthShore University Health System, Evanston, Illinois; Attending Physician, Emergency Medicine, Toxicology, Cook County Hospital Stroger), Chicago, Illinois

Robert W. Neumar, MD, PhD Professor and Chair, Department of Emergency Medicine, University of Michigan Health System, Ann Arbor, Michigan

Kim Newton, MD Associate Professor, Emergency Medicine, USC, Keck School of Medicine, Los Angeles, California

Contributors

Thomas Nguyen, MD

Daniel J. Pallin, MD, MPH

Associate Program Director, Emergency Medicine, Mount Sinai Beth Israel, New York, New York

Research Director, Department of Emergency Medicine, Brigham and Women’s Hospital; Assistant Professor, Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

James R. Nichols III, DO Assistant Professor, Assistant Director of Emergency Ultrasound, Emergency Medicine, Univeristy of Mississippi Medicial Center, Jackson, Mississippi

James T. Niemann, MD Professor of Medicine, UCLA School of Medicine, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

Jenna K. Nikolaides, MD, MA Medical Toxicology Fellow, Toxikon Consortium, Chicago, Illinois

Kimberly Nordstrom, MD, JD Medical Director, Psychiatric Emergency Services, Department of Psychiatry, Denver Health Medical Center, Denver, Colorado; Assistant Professor, Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado

Richard M. Nowak, MD, MBA

Linda Papa, MD, MSc Director of Academic Clinical Research, Professor of Emergency Medicine, Orlando Regional Medical Center; Professor, Department of Medicine, University of Central Florida, Orlando, Florida; Adjunct Professor, Emergency Medicine, University of Florida, Gainesville, Florida; Adjunct Professor, Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

Ram Parekh, BA, MD Assistant Professor, Emergency Department, Icahn School of Medicine at Mount Sinai, New York, New York; Attending Physician, Emergency Department, Elmhurst Hospital Center, Elmhurst, New York

Asad E. Patanwala, PharmD Associate Professor, Pharmacy Practice and Science, The University of Arizona, Tucson, Arizona

David A. Peak, MD

Emergency Medicine, Henry Ford Health System; Professor, Emergency Medicine, Wayne State Medical School, Detroit, Michigan; Clinical Associate Professor, Emergency Medicine, University of Michigan Medical School, Ann Arbor, Michigan

Assistant Residency Director, Harvard Affiliated Emergency Medicine Residency, Emergency Medicine, Massachusetts General Hospital; Assistant Professor, Emergency Medicine (Surgery), Harvard Medical School, Boston, Massachusetts

John F. O’Brien, BS, MD

Ryan Anthony Pedigo, MD

Attending Physician, Department of Emergency Medicine, Orlando Regional Medical Center; Associate Clinical Professor, Department of Emergency Medicine, University of Central Florida, Orlando, Florida; Associate Clinical Professor, Department of Surgery, University of Florida, Gainesville, Florida

Debra Perina, MD

Adedamola A. Ogunniyi, MD Faculty, Department of Emergency Medicine, Director, Process and Quality Improvement Program, Harbor-UCLA Medical Center, Torrance, California

Director of Undergraduate Medical Education, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California; Assistant Professor of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California

Professor, Division Director, Prehospital Care, Regional Quality Director, Emergency Medicine, University of Virginia, Charlottesville, Virginia

Andrew D. Perron, MD

Kelly P. O’Keefe, MD

Professor and Residency Program Director, Department of Emergency Medicine, Maine Medical Center, Portland, Maine

Program Director, Emergency Medicine, Unversity of South Florida-Tampa General Hospital, Tampa, Florida

Shawna J. Perry, MD

Professor of Emergency Medicine and Pediatrics, Director, Division of Toxicology, University of Cincinnati College of Medicine, Cincinnati, Ohio

Associate Professor, Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida; Honorary Associate Professor, CPQI, Department of Industrial Engineering, University of Wisconsin-Madison, Madison, Wisconsin

Leslie C. Oyama, MD

Michael A. Peterson, MD

Edward Joseph Otten, MD

Associate Clinical Professor, Emergency Medicine, University of California, San Diego, San Diego, California

Patricia Padlipsky, MD, MS Associate Clinical Professor of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; Director, Pediatric Emergency Department, Harbor-UCLA Medical Center, Torrance, California

Assistant Professor, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Director, Adult Emergency Department, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

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Contributors

James A. Pfaff, MD

Robert F. Reardon, MD

Assistant Professor, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Emergency Medicine, San Antonio Military Medical Center, Staff Physician, San Antonio Uniformed Services Health Education Consortium, San Antonio Military Medical Centers, Fort Sam Houston, Texas

Professor, Department of Emergency Medicine, University of Minnesota; Faculty Physician, Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota

Camiron L. Pfennig, MD, MHPE Associate Professor, Emergency Medicine, University of South Carolina Greenville; Residency Program Director, Emergency Medicine, Greenville Health System, Greenville, South Carolina

David B. Richards, MD, FACEP Assistant Professor, Department of Emergency Medicine, University of Colorado School of Medicine; Director, Medical Student and Intern Clerkship, Department of Emergency Medicine, Denver Health Medical Center, Denver, Colorado

Ralph J. Riviello, MD, MS

Associate Professor, Emergency Medicine, University of Louisville, Louisville, Kentucky

Professor and Vice Chair of Clinical Operations, Emergency Medicine, Drexel University College of Medicine; Medical Director, Philadelphia Sexual Assault Response Center, Philadelphia, Pennsylvania

Charles V. Pollack, Jr., MA, MD

Daniel W. Robinson, MD

Professor, Emergency Medicine, Sidney Kimmel College of Medicine; Associate Provost, Associate Dean for Continuing Medical Education, Thomas Jefferson University, Philadelphia, Pennsylvania

Assistant Professor of Medicine, Section of Emergency Medicine, Department of Medicine, University of Chicago Medicine and Biological Sciences, Chicago, Illinois

Trevor R. Pour, BA, MD Assisstant Residency Program Director, Department of Emergency Medicine, Mount Sinai Hospital, New York, New York

Emergency Physician, Stormont-Vail HealthCare, Topeka, Kansas; Physician Advisor, Clinical Documentation Improvement, Baptist Health of Northeast Florida, Jacksonville, Florida

Timothy G. Price, MD

Chad E. Roline, MD

Associate Professor, Emergency Medicine, University of Louisville, Louisville, Kentucky

Department of Emergency Medicine, North Memorial Health Care, Robbinsdale, Minnesota

Michael A. Puskarich, MD

Genie E. Roosevelt, MD, MPH

Associate Professor, Research Director, University of Mississippi Medical Center, Jackson, Mississippi; Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina

Associate Professor, Emergency Medicine, Denver Health Medical Center, Denver, Colorado

Tammie E. Quest, MD

Assistant Professor of Clinical Emergency Medicine, Department of Emergency Medicine, LA County + USC Medical Center, Keck School of Medicine of the University of Southern California, Los Angeles, California

Melissa Platt, MD

Professor, Emory University School of Medicine, Department of Emergency Medicine; Director, Emory Palliative Care Center; Chief, Department of Veterans Affairs, Hospice and Palliative Medicine, Atlanta, Georgia

Elaine Rabin, MD Icahn School of Medicine at Mount Sinai, New York, New York

Ali S. Raja, MD, MBA, MPH Vice Chairman, Department of Emergency Medicine, Massachusetts General Hospital; Associate Professor of Emergency Medicine and Radiology, Harvard Medical School, Boston, Massachusetts

Rama B. Rao, MD

Howard Rodenberg, MD, MPH

Emily Rose, MD

Gabriel Rose, DO Clinical Instructor, Department of Emergency Medicine, Mount Sinai St. Luke’s-Mount Sinai West Hospitals, New York, New York

Nicholas G.W. Rose, MD, PhD, FRCPC, Dip Sports Med (CASEM) Clinical Assistant Professor, Department of Emergency Medicine,University of British Columbia, Vancouver, British Columbia, Canada

Assistant Professor, Chief, Division of Medical Toxicology, Department of Emergency Medicine, New York Presbyterian Hospital, Weill Cornell Medicine, New York, New York

Tony Rosen, MD, MPH

Neha P. Raukar, MD, MS

Anne-Michelle Ruha, MD

Assistant Professor, Emergency Medicine, Warren Alpert Medical School of Brown University; Attending Physician, Emergency Medicine, Rhode Island-Miriam Hospital; Director, Emergency Medicine, Center for Sports Medicine, Providence, Rhode Island

Fellowship Director, Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona

Instructor in Medicine, Division of Emergency Medicine, Weill Cornell Medical College, New York, New York

Contributors

Christopher S. Russi, DO

Rachel Semmons, MD

Chair, Division of Community Emergency Medicine, Department of Emergency Medicine; Assistant Professor of Emergency Medicine, Mayo Clinic, Rochester, Minnesota

Bisan A. Salhi, MD

Associate Education Director, Senior Emergency Medicine Clerkship Director, Associate Fellowship Director EMS Fellowship, Emergency Medicine, University of South Florida; Associate Department Director, Emergency Medicine, Tampa General Hospital, Tampa, Florida

Assistant Professor, Emergency Medicine, Emory University, Atlanta, Georgia

Joseph Sexton, MD, FACEP

Arthur B. Sanders, MD, MHA

Attending Physician, Emergency Medicine, Lehigh Valley Health Network, Allentown, Pennsylvania

Professor, Emergency Medicine, University of Arizona, Tucson, Arizona

Nathan I. Shapiro, MD, MPH

Genevieve Santillanes, MD

Vice Chairman of Emergency Medicine Research, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Assistant Professor, Emergency Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California

Richard J. Scarfone, MD Associate Professor, Pediatrics, Perelman School of Medicine at the University of Pennsylvania; Attending Physician, Division of Emergency Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Dag Shapshak, MD Associate Professor, Department of Emergency Medicine, University of Alabama, Birmingham, Birmingham, Alabama

Peter Shearer, MD Medical Director, Emergency Medicine, Mount Sinai Hospital, New York, New York

Carl H. Schultz, MD, FACEP

Sanjay N. Shewakramani, MD

Professor of Emergency Medicine and Public Health, Director of Research, Center for Disaster Medical Sciences; Director, EMS and Disaster Medical Sciences Fellowship, University of California Irvine School of Medicine, Irvine, California; Director, Disaster Medical Services, Department of Emergency Medicine, University of California Irvine Medical Center, Orange, California

Assistant Professor, Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio

Jeremiah D. Schuur, MD, MHS

Jan M. Shoenberger, MD

Chief, Division of Health Policy Translation, Department of Emergency Medicine; Vice Chair, Quality and Safety Clinical Affairs, Department of Emergency Medicine, Brigham and Women’s Hospital; Assistant Professor, Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Halden F. Scott, MD Assistant Professor, Pediatrics and Emergency Medicine, University of Colorado School of Medicine; Attending Physician, Section of Emergency Medicine, Children’s Hospital Colorado, Aurora, Colorado

Raghu Seethala, MD Instructor, Emergency Medicine, Harvard Medical School; Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Jeffrey A. Seiden, MD Associate Medical Director, Pediatric Emergency Medicine, CHOP at Virtua, Voorhees, New Jersey

Todd A. Seigel, MD Staff Physician, Emergency Medicine and Critical Care Medicine, Kaiser Permanente, Oakland Medical Center, Oakland, California

Lee W. Shockley, MD, MBA Attending Emergency Physician, Emergency Medicine, CarePoint; Professor, Emergency Medicine, The University of Colorado School of Medicine, Denver, Colorado Residency Director, Emergency Medicine, Los Angeles County + USC Medical Center; Associate Professor of Clinical Emergency Medicine, Emergency Medicine, Keck School of Medicine of USC, Los Angeles, California

Barry C. Simon, MD Chairman, Department of Emergency Medicine, Highland General Hospital; Professor of Emergency Medicine, University of California San Francisco, San Francisco, California

Adam J. Singer, MD Professor and Vice Chairman, Emergency Medicine, Stonybrook University, Stony Brook, New York

Aaron B. Skolnik, MD Assistant Medical Director, Banner Good Samaritan Poison and Drug Information Center, Department of Medical Toxicology, Banner-University Medical Center Phoenix; Clinical Assistant Professor, Department of Emergency Medicine, University of Arizona College of MedicinePhoenix, Phoenix, Arizona

Corey M. Slovis, MD Chairman, Emergency Medicine, Vanderbilt University Medical Center; Medical Director, Nashville Fire Department; Medical Director, Nashville International Airport, Nashville, Tennessee

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Contributors

Clay Smith, MD

Morsal Tahouni, MD

Assistant Professor of Emergency Medicine, Internal Medicine, and Pediatrics, Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

Assistant Medical Director, Department of Emergency Medicine, Boston Medical Center; Assistant Professor of Medicine, Department of Emergency Medicine, Boston University School of Medicine, Boston, Massachusetts

Kurt A. Smith, MD, FACEP Assistant Professor, Emergency Medicine, Vanderbilt University, Nashville, Tennessee

David C. Snow, MD, MSc Assistant Residency Director, Assistant Professor of Emergency Medicine, Emergency Medicine, University of Illinois at Chicago, Chicago, Illinois

Peter E. Sokolove, MD Professor and Chair, Department of Emergency Medicine, University of California San Francisco School of Medicine, San Francisco, California; Sacramento

David M. Somand, MD Assistant Professor, Department of Emergency Medicine, University of Michigan Hospital, Ann Arbor, Michigan

Benjamin Squire, MD, MPH Clinical Instructor of Medicine, David Geffen School of Medicine at UCLA, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California

Stephen C. Stanfield, M.Arch, MD

Sukhjit S. Takhar, MD Instructor, Medicine (Emergency Medicine), Harvard Medical School; Attending Physician, Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Nelson Tang, MD, FACEP Associate Professor, Emergency Medicine, Johns Hopkins Uniiversity School of Medicine; Director, Division of Special Operations, Johns Hopkins Medical Institutions; Chief Medical Officer, Center for Law Enforcement Medicine, Baltimore, Maryland

Todd Andrew Taylor, MD Assistant Professor, Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia

James L. Thea, MD Associate Professor of Emergency Medicine, Emergency Medicine, Boston University School of Medicine, Boston, Massachusetts

Jillian L. Theobald, MD, PhD

Emergency Medicine, Regions Hospital, St. Paul, Minnesota

Assistant Professor, Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin

Dana A. Stearns, MD

Molly E.W. Thiessen, MD

Associate Physician, Department of Emergency Medicine, Massachusetts General Hospital; Assistant Profesor of Emergency Medicine, Associate Advisory Dean, William Bosworth Castle Society, Harvard Medical School, Boston, Massachusetts

Assistant Emergency Ultrasound Director, Emergency Medicine, Denver Health Medical Center, Denver, Colorado; Assistant Professor, Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Michael E. Stern, MD Assistant Professor of Clinical Medicine, Division of Emergency Medicine, Weill Cornell Medical Center, New York, New York

Associate Professor, Medical Director, University Emergency Department, Emergency Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Brian A. Stettler, MD

Stephen H. Thomas, MD, MPH

J. Jeremy Thomas, MD

Michael B. Stone, MD

Professor and Chair, Hamad Medical Corporation, Department of Emergency Medicine; Chief of Service, Hamad General Hospital Emergency Department, Weill Cornell Medical College in Qatar, Doha, Qatar

Chief, Division of Emergency Ultrasound, Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

Trevonne M. Thompson, MD, FACEP, FACMT

Assistant Professor of Clinical Medicine, Division of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio

Reuben J. Strayer, MD Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, NYU School of Medicine, New York, New York

Amita Sudhir, MD Assistant Professor, Emergency Medicine, University of Virginia, Charlottesville, Virginia

Ramin R. Tabatabai, MD Assistant Professor of Clinical Emergency Medicine, Keck School of Medicine of the University of Southern California; Assistant Program Director, Department of Emergency Medicine, LAC + USC Medical Center, Los Angeles, California

Associate Professor, Emergency Medicine and Medical Toxicology, Director, Division of Medical Toxicology, Department of Emergency Medicine, University of Illinois at Chicago, Chicago, Illinois

Carrie D. Tibbles, MD Associate Director, Graduate Medical Education, Beth Israel Deaconess Medical Center; Associate Program Director, Harvard Affiliated Emergency Medicine Residency; Assistant Professor of Medicine, Harvard Medical School, Boston, Massachusetts

Glenn F. Tokarski, MD Emergency Medicine, Henry Ford Hospital, Detroit, Michigan

Contributors

Veronica Vasquez, MD

David T. Williams, MD

Assistant Professor, Department of Emergency Medicine, University of Southern California, LAC + USC Medical Center, Los Angeles, California

Attending Staff Physician, Department of Emergency Medicine, Maui Memorial Medical Center, Wailuku, Hawaii

David A. Wacker, MD, PhD

Assistant Professor, Neurosurgery, Assistant Professor, Neurology, University of Michigan, Ann Arbor, Michigan

Assistant Professor, Department of Medicine (Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine), University of Minnesota Medical School, Minneapolis, Minnesota

Craig A. Williamson, MD

Matthew D. Wilson, MD

Laura Walker, MD

Attending Physician, Emergency Medicine, Washington Hospital Center; Assistant Professor of Emergency Medicine, Georgetown University School of Medicine, Washington, DC

Clinical Instructor, Emergency Medicine, Mayo Medical School, Rochester, Minnesota

Adria Ottoboni Winter, MD

Ron M. Walls, MD

Assistant Clinical Professor, Department of Emergency Medicine, Kern Medical/UCLA, Bakersfield, California

Executive Vice President and Chief Operating Officer, Brigham Health; Neskey Family Professor of Emergency Medicine, Harvard Medical School, Boston, Massachusetts

Allan B. Wolfson, MD, FACEP, FACP

George Sam Wang, MD Assistant Professor of Pediatrics, Department of Pediatrics, Section of Emergency Medicine and Medical Toxicology, Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado

Matthew A. Waxman, MD, DTM and H

Professor of Emergency Medicine, Vice Chair for Education, Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Andrea W. Wu, MD, MMM, FACEP Core Faculty, Department of Emergency Medicine; Director, Adult Emergency Department, Harbor-UCLA Medical Center, Torrance, California

Associate Clinical Professor, Department of Emergency Medicine and Department of Medicine, Olive View-UCLA Medical Center, Los Angeles, California

Donald M. Yealy, MD

Robert L. Wears, MD, MS, PhD

Ken Zafren, MD, FAAEM, FACEP, FAWM

Professor, Emergency Medicine, University of Florida, Jacksonville, Florida; Visiting Professor, Clinical Safety Research Unit, Imperial College London, London, England

Professor and Chair, Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Lori Weichenthal, MD

Emergency Programs Medical Director, State of Alaska, Anchorage, Alaska; Clinical Professor, Department of Emergency Medicine, Stanford University Medical Center, Stanford, California; Staff Emergency Physician, Alaska Native Medical Center, Anchorage, Alaska

Professor of Clinical Emergency Medicine, Emergency Medicine, UCSF Fresno, Fresno, California

Brian J. Zink, MD

Katherine Welker, MD, MPH Attending Physician, Department of Emergency Medicine, San Diego, California; Toxicology Fellowship, Toxikon Consortium, Cook County Hospital, Chicago, Illinois

Matthew A. Wheatley, MD Assistant Professor, Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia

John M. Wightman, MD, MA, FACEP Director, Human Research Protection Program, 711th Human Performance Wing, Air Force Research Laboratory, WrightPatterson Air Force Base, Ohio; Adjunct Professor, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland; Clinical Professor, Department of Emergency Medicine, Boonshoft School of Medicine, Wright State University, Dayton, Ohio

Professor and Chair, Emergency Medicine, Alpert Medical School of Brown University; Physician-in-Chief, Emergency Medicine, Rhode Island, Newport and The Miriam Hospitals, Providence, Rhode Island

Leslie S. Zun, MD, MBA Professor and Chair, Emergency Medicine, Rosalind Franklin University of Medicine and Science-Chicago Medical School, North Chicago, Illinois; System Chair, Emergency Medicine, Sinai Health System, Chicago, Illinois

xix

Preface to the Ninth Edition When we began planning for this ninth edition, we challenged ourselves to make substantial and meaningful improvements to a book that has become the trusted standard in our field. With broad and rapid changes occurring in health care and information sciences, we recognized that relevance is not an accidental or passive concept. To advance in relevance and consolidate the book’s position as the defining reference in our specialty, we carefully and deliberately undertook bold changes that we know make the book at once fresh, directive, and current in a way we have never before dared. First, we created a substantially enhanced role for our editors, one that would demand a great deal more of their time, creativity, and energy. This helped us build a substantially different team of editors, a perfectly balanced blend of those with great experience with prior editions and those who would bring new ideas and challenge our assumptions. Ron Walls was asked to serve as Editor-in-Chief, with Bob Hockberger in his long-standing role as senior editor. Marianne Gausche-Hill, a highly respected academic emergency physician with service as editor on four previous editions, stepped up to complete our senior editorial ranks. At the editor level, Dr. Andy Jagoda returns and is joined by six brilliant new editors drawn from academic programs from coast to coast—Drs. Katherine Bakes, Jill Baren, Timothy Erickson, Amy Kaji, Michael VanRooyen, and Richard Zane. This dynamic and innovative editorial team has dramatically redrawn our text’s blueprint by preserving what has served our readers the best, such as well-written discussions of the pathophysiologic basis of illness and injury, while moving in entirely new directions in providing pithy, clear, and succinct recommendations for diagnosis and treatment. We collectively determined that all references prior to 2010 have been sufficiently long in the public domain that they no longer warrant citation. The infrequent exception to this is for guidelines that were issued in 2007 or later and have not been reissued or supplanted since. Strict adherence to our referencing policy required authors to diligently provide well-researched and detailed updates to their chapter content, based on only the most recent and relevant medical literature. In cases in which the literature is controversial or unclear, we have used the combined experience and expertise of our authors and editors to present cogent analyses of diagnostic and treatment options,

make specific recommendations, and give the reader clear indications of the preferred actions. This makes the book much more immediately relevant for emergency clinicians. We recognize that emergency medicine is practiced by specialist emergency physicians, other physicians, residents and other trainees, and a variety of nonphysician practitioners, so were careful to ensure that we are addressing all these groups with the same concise, highest quality information and recommendations. We revisited page counts for every chapter, adjusting allocations where indicated, and added new chapters on several important topics. We focused anew on consistency and redundancy, enhancing the former and minimizing the latter. We moved some chapters to online access only, allowing us to add new topics of interest, such as drug therapy for older patients, and have provided a rich array of dynamic videos and images, especially in emergency ultrasound. We substantially expanded and reorganized the pediatric emergency medicine section, introducing dedicated pediatric chapters on airway management, procedural sedation, and drug therapy. We introduced significant new material on emergencies in the pregnant woman, the patient with cancer, and a variety of other highly important clinical conditions. And, in every possible case, we insisted on adherence to referencing and writing requirements, a focus on relevant directive information, and appropriate use of prose and illustrations to provide the perfect balance of depth, breadth, and ready accessibility. We are enormously proud of the result, a different, more readable “Rosen,” preserving the gravitas earned over 30 years as the most important book in our specialty while embracing the modern era of emergency medicine practice and research and an entirely new generation of learners and practitioners. For those who have owned prior editions, we appreciate your loyalty over so many years and hope to reward it with a significantly improved and useful companion for your continuing learning and practice of this great specialty. For our newer readers, welcome, and thank you for inspiring us to make significant changes to an iconic and timeless part of our academic heritage. Ron M. Walls Robert S. Hockberger Marianne Gausche-Hill

xxi

How This Medical Textbook Should Be Viewed by the Practicing Clinician and Judicial System The editors and authors of this text strongly believe that the complex practice of medicine, vagaries of human diseases, unpredictability of pathologic conditions, and functions, dysfunctions, and responses of the human body cannot be defined, explained, or rigidly categorized by any written document. Therefore, it is neither the purpose nor intent of our textbook to serve as an authoritative source on any medical condition, treatment plan, or clinical intervention, nor should our textbook be used to rigorously define a standard of care that should be practiced by all clinicians. Our written word provides the physician with a literature-referenced database and a reasonable clinical guide combined with practical suggestions from individual experienced practitioners. We offer a general reference source and clinical road map on a variety of conditions and procedures that may confront emergency clinicians who are experienced in emergency medicine practice. This text cannot replace physician judgment, cannot describe every possible aberration, nuance, clinical scenario, or presentation, and cannot define rigid standards for clinical actions or procedures. Every medical encounter must be individualized, and every patient must be approached on a case-by-case basis. No complex medical interaction can possibly be reduced to the written word. The treatments, procedures, and medical conditions described in this text do not constitute the total expertise or knowledge base expected to be possessed by all emergency clinicians. Finally, many of the described complications and adverse outcomes associated with implementing or withholding complex medical and surgical interventions may occur, even when every aspect of the intervention has been standard or performed correctly. The editors and authors of Rosen’s Emergency Medicine: Concepts and Clinical Practice, Ninth Edition

SECTION ONE

Critical Management Principles C H A P T E R 1 

Airway Calvin A. Brown III  |  Ron M. Walls

PRINCIPLES

Failure of Ventilation or Oxygenation

Background

Gas exchange, both oxygenation and removal of carbon dioxide, is required for vital organ function. Ventilatory failure that is not reversible by clinical means or persistent hypoxemia despite maximal oxygen supplementation is a primary indication for intubation. This assessment is clinical and includes an evaluation of the patient’s general status, oxygen saturation by pulse oximetry, and ventilatory pattern. Continuous capnography also can be helpful but is not essential if oximetry readings are reliable. Arterial blood gases (ABGs) generally are not required to determine the patient’s need for intubation. In most cases, clinical assessment, including pulse oximetry with or without capnography, and observation of improvement or deterioration in the patient’s clinical condition lead to a correct decision. ABG results are rarely helpful, are time-consuming to obtain, and may be misleading, causing a false sense of security and delay in intubating a deteriorating patient. If obtained, they should be interpreted carefully in the context of the patient’s clinical status. Patients who are clinically improving despite severe or apparently worsening ABG alterations may not require intubation, whereas a rapidly tiring asthmatic may require intubation, even though ABG values are only modestly disturbed. The need for prolonged mechanical ventilation generally mandates intubation. An external mask device, continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BLPAP), have all been used successfully to manage patients with exacerbations of chronic obstructive pulmonary disease (COPD) and congestive heart failure, obviating the need for intubation (see Chapter 2) but, despite these advances, many patients who need assisted ventilation or positive pressure to improve oxygenation require intubation.1,2

Airway management is the cornerstone of resuscitation and is a defining skill for the specialty of emergency medicine. The emergency clinician has primary airway management responsibility, and all airway techniques lie within the domain of emergency medicine. Although rapid sequence intubation (RSI) is the most commonly used method for emergent tracheal intubation, emergency airway management includes various intubation techniques and devices, approaches to the difficult airway, and rescue techniques when intubation fails.

Anatomy, Physiology, and Pathophysiology The decision to intubate should be based on careful patient assessment and appraisal of the clinical presentation with respect to three essential criteria: (1) failure to maintain or protect the airway; (2) failure of ventilation or oxygenation; and (3) the patient’s anticipated clinical course and likelihood of deterioration.

Failure to Maintain or Protect the Airway A patent airway is essential for adequate ventilation and oxygenation. If a patient is unable to maintain a patent airway, the airway should be established by using airway maneuvers such as repositioning, chin lift, jaw thrust, or insertion of an oral or nasal airway. Likewise, the patient must be able to protect against the aspiration of gastric contents, which carries significant morbidity and mortality. Historically, the presence of a gag reflex has been advocated as a reliable indicator of the patient’s ability to protect the airway, but this has been definitively proven to be unreliable because the gag reflex is absent in 12% to 25% of normal adults, and there is no evidence that its presence or absence corresponds to airway protective reflexes or predicts the need for intubation. The patient’s ability to swallow or handle secretions is a more reliable indicator of airway protection. The recommended approach is to evaluate the patient’s level of consciousness, ability to phonate in response to voice command or query, which provides information about the integrity of the upper airway and level of consciousness, and ability to manage his or her own secretions (eg, pooling of secretions in the oropharynx, absence of swallowing spontaneously or on command). In general, a patient who requires a maneuver to establish a patent airway or who easily tolerates an oral airway requires intubation for airway protection, unless there is a temporary or readily reversible condition, such as an opioid overdose.

Anticipated Clinical Course Certain conditions indicate the need for intubation, even without an immediate threat to airway patency or adequacy of ventilation and oxygenation. These conditions are characterized by a moderate to high likelihood of predictable airway deterioration or the need for intubation to facilitate a patient’s evaluation and treatment. Intubation may be indicated relatively early in the course of certain overdoses. Although the patient initially may be protecting the airway and exchanging gas adequately, intubation is advisable to guard against the strong likelihood of clinical deterioration, which can occur after the initial phase of care when the patient is no longer closely observed. A patient who has sustained significant multiple traumatic injuries may require intubation, even if the patient is ventilating normally through a patent airway and has adequate oxygen levels. For example, a multiple trauma 3

4

PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

patient with hypotension, open femur fracture, and diffuse abdominal tenderness warrants early intubation, even if the patient is initially awake and alert, without airway injury or hypoxemia. Active resuscitation, pain control, need for invasive procedures and imaging outside of the emergency department (ED), and inevitable operative management dictate the need for early airway control. In addition, a patient with penetrating neck trauma may have a patent airway and adequate gas exchange. Nevertheless, early intubation is advisable when there is evidence of vascular or direct airway injury because these patients tend to deteriorate, and increasing hemorrhage or swelling in the neck will compromise the airway and confound later attempts at intubation. The common thread among these indications for intubation is the anticipated clinical course. In each case, it can be anticipated that future events may compromise the patient’s ability to maintain and protect the airway or ability to oxygenate and ventilate, and waiting until these occur may result in a difficult airway.

Identification of the Difficult Airway In most patients, intubation is technically easy and straightforward. Although early ED-based observational registries reported cricothyrotomy rates of about 1% for all intubations, more recent studies have shown a lower rate, less than 0.5%.3 As would be expected with an unselected, unscheduled patient population, the ED cricothyrotomy rate is greater than in the operating room, which occurs in approximately 1 in 200 to 2000 elective general anesthesia cases.4 Bag-mask ventilation (BMV) is difficult in approximately 1 in 50 general anesthesia patients and impossible in approximately 1 in 600. BMV is difficult, however, in up to one-third of patients in whom intubation failure occurs, and difficult BMV makes the likelihood of difficult intubation four times higher and the likelihood of impossible intubation 12 times higher. The combination of failure of intubation, BMV, and oxygenation in elective anesthesia practice is estimated to be exceedingly rare, roughly 1 in 30,000 elective anesthesia patients.4 These numbers cannot be extrapolated to populations of ED patients who are acutely ill or injured and for whom intubation is urgent and unavoidable. Although patient selection cannot occur, as with a preanesthetic visit, a preintubation analysis of factors predicting difficult intubation gives the provider the information necessary to formulate a safe and effective plan for intubation. Preintubation assessment should evaluate the patient for potential difficult intubation and difficult BMV, placement of and ventilation with an extraglottic device (EGD; see later discussion), and cricothyrotomy. Knowledge of all four domains is crucial to successful planning. A patient who exhibits obvious difficult airway characteristics is highly predictive of a challenging intubation, although the emergency clinician should always be ready for a difficult to manage airway, because some difficult airways may not be identified by a bedside assessment.5 Airway difficulty exists on a spectrum and is contextual to the provider’s experience, environment, and armamentarium of devices. Airways predicted to be difficult when using a traditional laryngoscope may not prove to be difficult when a videolaryngoscope is used. Some patients may have a single minor anatomic or pathophysiologic reason for airway difficulty, whereas others may have numerous difficult airway characteristics. Although both sets of patients represent potential intubation challenges, the latter group would likely have crossed a threshold beyond which neuromuscular blockade would be avoided because a so-called can’t intubate and can’t oxygenate failed airway may ensue. In these cases, a preferred approach would include topical anesthesia, parenteral sedation, and intubation without the use of a neuromuscular blocking agent (NBMA). Occasionally, RSI remains the preferred method, despite a concerning bedside assessment, when

it is part of a planned approach to the difficult airway. This may include use of a double setup, in which a rescue approach, such as cricothyrotomy, is simultaneously prepared in the event of intubation failure. Regardless of the results of a reassuring bedside assessment for airway difficulty, significant challenges may be encountered with intubation and bag mask ventilation and the clinician must be prepared for unanticipated difficulty.

Difficult Direct Laryngoscopy: LEMON Glottic visualization is paramount in emergency airway management. With direct laryngoscopy (DL), if the vocal cords can be seen (Cormack and Lehane [CL] grade I or II view; Fig. 1.1), the chance of intubation success is high. However, when the glottic aperture cannot be visualized (CL grade III or IV), intubation success is less likely. Very few of the difficult airway markers thought to limit DL access have been scientifically validated, yet applying them in combination can provide a reasonable assessment of anticipated airway difficulty. Videolaryngoscopy, on the other hand, rarely fails to provide adequate laryngeal visualization, so characterization of difficult videolaryngoscopy predictors may not be possible. Like DL, adequate video views are highly correlated with intubation success, although the strength of this association can depend on the device used and operator experience.3,6,7 Whether DL or videolaryngoscopy is planned, a standard screening process for difficulty should be undertaken with every patient. Our recommended approach uses the mnemonic LEMON (Box 1.1). L—Look Externally.  The patient first should be examined for external markers of difficult intubation, which are determined

Grade 1

Grade 3

Epiglottis Vocal cord Arytenoids

Grade 2

Grade 4

Fig. 1.1.  Cormack and Lehane grading system for glottic view. (Modified from Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; with permission.)

BOX 1.1 

LEMON Mnemonic for Evaluation of Difficult Direct Laryngoscopy Look externally for signs of difficult intubation (by gestalt) Evaluate 3-3-2 rule Mallampati scale Obstruction or obesity Neck mobility Adapted with permission from The Difficult Airway Course: Emergency and Walls RM, Murphy MF, eds: Manual of Emergency Airway Management, 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2012.

CHAPTER 1  Airway

1 2 3

A

1 2

B

Fig. 1.2.  Final two steps of the 3-3-2 rule. A, Three fingers are placed along the floor of the mouth, beginning at the mentum. B, Two fingers are placed in the laryngeal prominence (Adam’s apple). (Modified from Murphy MF, Walls RM: Identification of difficult and failed airways. In Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; the 3-3-2 rule copyright © 2012 by The difficult airway course: emergency; and Lippincott Williams & Wilkins, publishers, Manual of emergency airway management.)

based simply on the intubator’s clinical impression or initial gestalt. For example, the severely bruised and bloodied face of a combative trauma patient, immobilized in a cervical collar on a spine board, should (correctly) invoke an immediate appreciation of anticipated difficult intubation. Subjective clinical judgment can be highly specific but insensitive and so should be augmented by other evaluations whether or not the airway appears to be challenging. E—Evaluate 3-3-2.  The second step in the evaluation of the difficult airway is to assess the patient’s airway geometry to determine suitability for DL. Glottic visualization with a direct laryngoscope necessitates that the mouth opens adequately, the submandibular space is adequate to accommodate the tongue, and the larynx be positioned low enough in the neck to be accessible. These relationships have been explored in various studies by external measurements of mouth opening, oropharyngeal size, neck movement, and thyromental distance. The 3-3-2 rule is an effective summary of these assessments.8 The 3-3-2 rule requires that the patient be able to place three of his or her own fingers between the open incisors, three of his or her own fingers along the floor of the mandible beginning at the mentum, and two fingers from the laryngeal prominence to the underside of the chin (Fig. 1.2). A patient with a receding mandible and highriding larynx is impossible to intubate using DL because the operator cannot adequately displace the tongue and overcome the acute angle for a direct view of the glottic aperture In practice, the operator compares the size of his or her fingers with the size of the patient’s fingers and then performs the three tests. M—Mallampati Scale.  Oral access is assessed with the Mallampati scale (Fig. 1.3). Visibility of the oral pharynx ranges from complete visualization, including the tonsillar pillars (class I), to no visualization at all, with the tongue pressed against the hard palate (class IV). Classes I and II predict adequate oral access, class

Class I: soft palate, uvula, fauces, pillars visible

Class II: soft palate, uvula, fauces visible

No difficulty

No difficulty

Class III: soft palate, base of uvula visible

Class IV: only hard palate visible

Moderate difficulty

Severe difficulty

Fig. 1.3.  The Mallampati scale, classes I to IV, assesses oral access for intubation. (From Whitten CE: Anyone can intubate, ed 4, San Diego, CA, 2004; with permission.)

III predicts moderate difficulty, and class IV predicts a high degree of difficulty. A meta-analysis has confirmed that the four-class Mallampati score performs well as a predictor of difficult laryngoscopy (and, less so, of difficult intubation), but the Mallampati score alone is not a sufficient assessment tool. A Mallampati score necessitates an awake compliant patient to perform the assessment in the way in which it was originally described. Nearly 50%

5

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PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

of ED patients cannot willingly perform this assessment, but it can be improvised by using a direct laryngoscope blade as a tongue depressor in obtunded or uncooperative patients.9 O—Obstruction or Obesity.  Upper airway (supraglottic) obstruction may make visualization of the glottis, or intubation itself, mechanically impossible. Conditions such as epiglottitis, head and neck cancer, Ludwig’s angina, neck hematoma, glottis swelling, or glottic polyps can compromise laryngoscopy, passage of the endotracheal tube (ETT), BMV, or all three. Examine the patient for airway obstruction and assess the patient’s voice to satisfy this evaluation step. Although obesity alone may not be an independent marker of difficult direct laryngoscopy, it likely contributes to challenges in other areas of airway management. Nevertheless, obese patients generally are more difficult to intubate than their nonobese counterparts, and preparations should account for this and for the more rapid oxyhemoglobin desaturation and increased difficulty with ventilation using BMV or an EGD (see later).

N—Neck Mobility.  Neck mobility is desirable for any intubation technique and is essential for positioning the patient for optimal DL. Neck mobility is assessed by flexion and extension of the patient’s head and neck through a full range of motion. Neck extension is the most important motion, but placing the patient in the full sniffing position provides the optimal laryngeal view by DL.10 Modest limitations of motion do not seriously impair DL, but severe loss of motion, as can occur in ankylosing spondylitis or rheumatoid arthritis, for example, may make DL impossible. Cervical spine immobilization in trauma patients artificially reduces cervical spine mobility, but DL is still highly successful in this group of patients.7 A similar mnemonic, LEMONS, has been described, with the “S” referring to the patient’s oxygen saturation. Although not a direct contributor to difficulty with DL, a low starting oxygen saturation will result in a shorter period of safe apnea and a truncated time to perform laryngoscopy and successful endotracheal tube placement. As noted, identification of a difficult intubation does not preclude use of an RSI technique. The crucial determination is whether the emergency clinician judges that the patient has a reasonable likelihood of intubation success, despite the difficulties identified, and that ventilation with BMV or an EGD will be successful in case intubation fails (hence, the value of the BMV and EGD assessments; see Boxes 1.2 and 1.3).

redundant upper airway tissues, chest wall weight, and resistance of abdominal mass) • Advanced Age (best judged by the physiologic appearance of the patient, but age older than 55 years increases risk) • Edentulous patients (“No teeth”), which independently interferes with mask seal • Stiffness or resistance to ventilation (eg, asthma, COPD, pulmonary edema, restrictive lung disease, term pregnancy)— may contribute to increased difficulty with BMV The difficulty with BMV of the edentulous patient is the basis of the advice often cited for patients with dentures: “teeth out to intubate, teeth in to ventilate.” Another approach involves placing the mask inside the patient’s lower lip. This may limit air leak in patients without teeth and eliminates the risk of aspiration associated with dental prosthetics or rolled gauze (Fig. 1.4).11 Difficult BMV is not uncommon but, with proper technique, it usually is successful. A review by Kheterpal et al of more than 50,000 patients undergoing elective anesthesia has found that impossible BMV is exceptionally rare (0.2%) and is associated with neck changes secondary to radiation therapy, presence of a beard, male gender, history of sleep apnea, and Mallampati class III or IV airway.11a Impossible BMV was five times more likely if one of these factors was present and 25 times more likely with four or more.

Difficult Extraglottic Device Placement: RODS Placement of an EGD, such as a laryngeal mask airway (LMA), Combitube, or similar upper airway device, often can convert a can’t intubate, can’t oxygenate situation to a can’t intubate, can oxygenate situation, which allows time for rescue of a failed airway (see following section). Difficulty achieving placement or ventilation with an EGD can be predicted by the mnemonic RODS. Fortunately, if the emergency clinician has already performed the LEMON and MOANS assessments, only the D for distorted anatomy remains to be evaluated (Box 1.3). EGDs are placed blindly and have a mask or balloon structure that, when inflated, obstructs the oropharynx proximally and esophageal inlet distally, permitting indirect ventilation. Distorted upper airway anatomy can result in a poor seal and ineffective ventilation.

Difficult Cricothyrotomy: SMART Difficult cricothyrotomy can be anticipated whenever there is limited access to the anterior neck or obscured laryngeal

Difficult Bag-Mask Ventilation: MOANS Attributes of difficult BMV have largely been validated and can be summarized with the mnemonic MOANS (Box 1.2). • Mask seal compromise or difficulty • Obstruction (particularly supraglottic obstruction, but can be present anywhere in the airway) or Obesity (because of BOX 1.2 

MOANS Mnemonic for Evaluation of Difficult Bag-Mask Ventilation Mask seal Obstruction or obesity Aged No teeth Stiffness (resistance to ventilation) Adapted with permission from The Difficult Airway Course: Emergency and Walls RM, Murphy MF, eds: Manual of Emergency Airway Management, 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2012.

Fig. 1.4.  Mask ventilation in edentulous patients can be performed by placing the lower rim of the mask on the inside of the patient’s lower lip to improve mask seal. (Courtesy Dr. Tobias Barker.)

CHAPTER 1  Airway

BOX 1.3 

RODS Mnemonic for Evaluation of Difficult Extraglottic Device Placement Restricted mouth opening Obstruction or obesity Distorted anatomy Stiffness (resistance to ventilation) Adapted with permission from The Difficult Airway Course: Emergency and Walls RM, Murphy MF, eds: Manual of Emergency Airway Management, 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2012.

BOX 1.4 

SMART Mnemonic for Evaluation of Difficult Cricothyrotomy

Fig. 1.5.  End-tidal CO2 detector before application. The indicator is purple, which indicates failure to detect CO2. This also is the appearance when the esophagus is intubated.

Surgery Mass (abscess, hematoma) Access/anatomy problems (obesity, edema) Radiation Tumor Adapted with permission from The Difficult Airway Course: Emergency and Walls RM, Murphy MF, eds: Manual of Emergency Airway Management, 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2012.

landmarks and can be remembered by the mnemonic SMART (Box 1.4). Prior surgery, hematoma, tumor, abscess, scarring (as from radiation therapy or prior injury), local trauma, obesity, edema, or subcutaneous air each has the potential to make cricothyrotomy more difficult. Perform an examination for the landmarks needed to perform cricothyrotomy as part of the preintubation difficult airway assessment of the patient. Pointof-care ultrasound has been used at the bedside to locate the cricothyroid membrane, thereby allowing the emergency clinician to mark the location on the surface of the neck in high-risk cases. The emergency clinician should not avoid performing a rescue cricothyrotomy when indicated, even in the presence of predicted difficulty.

Measurement and Incidence of Intubation Difficulty The actual degree to which an intubation is difficult is highly subjective, and quantification is challenging. The CL system is the most widely used system for grading a laryngoscopic view of the glottis, which grades laryngoscopy according to the extent to which laryngeal and glottic structures can be seen (see Fig. 1.1). In grade 1 laryngoscopy, all or nearly all of the glottic aperture is seen; in grade 2, the laryngoscopist visualizes only a portion of the glottis (arytenoid cartilages alone or arytenoid cartilages plus part of the vocal cords), in grade 3 only the epiglottis is visualized and, in grade 4, not even the epiglottis is visible. Fewer than 1% of stable patients undergoing DL during elective anesthesia yield a grade 4 laryngoscopy, a finding associated with an extremely difficult intubation with. Grade 3 laryngoscopy, which represents highly difficult intubation, is found in less than 5% of patients. Grade 2 laryngoscopy, which occurs in 10% to 30% of patients, can be subdivided further into grade 2a, in which the arytenoids and a portion of the vocal cords are seen, and grade 2b, in which only the arytenoids are seen. Intubation failure occurs in 67% of grade 2b cases but in only 4% of grade 2a cases.

Fig. 1.6.  Positive detection of CO2 turns the indicator yellow, indicating tracheal placement of the endotracheal tube.

Outside of the operating room, the rate of difficulty may be higher. In a recent review of emergency adult inpatient intubations, as many as 10% were considered difficult (grade 3 or 4 CL direct view or more than three attempts required).12 The incidence of difficult ED intubations is unknown but is likely much higher Approximately 80% of all grade 2 laryngoscopies are grade 2a; the rest are grade 2b. First-attempt intubation success drops off significantly as the glottic view transitions from a grade 2a to 2b; however, a grade 1 view is associated with virtually 100% intubation success. An alternative system, POGO (percentage of glottic opening), also has been proposed and validated but has not been widely used or studied. The incidence of difficult intubation, and the predictors thereof, are largely based on the use of conventional DL and are not applicable to videolaryngoscopy.

Confirmation of Endotracheal Tube Placement Immediately after intubation, the intubator should apply an endtidal carbon dioxide (ETco2) detection device to the ETT and assess it through six manual ventilations. Disposable colorimetric ETco2 detectors are highly reliable, convenient, and easy to interpret, indicating adequate CO2 detection by color change (Figs. 1.5 and 1.6) and determining tracheal and esophageal intubation in patients with spontaneous circulation. The persistence of detected CO2 after six manual breaths indicates that the tube is within the airway, although not necessarily within the trachea. CO2 is detected with the tube in the mainstem bronchus, trachea, or supraglottic

7

8

PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

space. Correlation of ETco2 detection with the depth markings on the ETT, particularly important in pediatric patients, confirms tracheal placement. Rarely, BMV before intubation or ingestion of carbonated beverages may lead to the release of CO2 from the stomach after esophageal intubation, causing a transient false indication of tracheal intubation. Washout of this phenomenon universally occurs within six breaths. Although colorimetric ETco2 measurement is highly sensitive and specific for detecting esophageal intubation, caution is required for patients in cardiopulmonary arrest. Insufficient gas exchange may prevent CO2 detection in the exhaled air, even when the tube is correctly placed within the trachea. In patients in cardiopulmonary arrest, a CO2 level greater than 2%, which is the threshold for color change on colorimetric capnometers, should be considered definitive evidence of correct ETT placement, but the absence of such CO2 cannot be used reliably as an indicator of esophageal intubation. Recent resuscitation guidelines have suggested continuous quantitative measurement of ETco2 during cardiac arrest to gauge the efficacy of cardiopulmonary resuscitation.13 This circumstance arises in approximately 25% to 40% of intubated cardiac arrest patients. In all other patients, absence of CO2 detection indicates failure to intubate the trachea, and rapid reintubation is indicated. When ETco2 detection is not possible, tracheal tube position can be confirmed with other techniques. One approach involves point-of-care ultrasound. In live patient and cadaver studies, ultrasonography performed over the cricothyroid membrane or upper trachea has accurately confirmed ETT position in the trachea, especially during intubation.14,15 Another method of tube placement confirmation is the aspiration technique, based on the anatomic differences between the trachea and esophagus. The esophagus is a muscular structure with no support within its walls and is therefore collapsible when negative pressure is applied. The trachea is held patent by cartilaginous rings and thus is less likely to collapse when negative pressure is applied. Vigorous aspiration of air through the ETT with the ETT cuff deflated results in occlusion of the ETT orifices by the soft walls of the esophagus, whereas aspiration after tracheal placement of the tube is easy and rapid. Bulb or syringe aspiration devices may be used in patients in cardiac arrest who have no detectable CO2. Although such devices are highly reliable at detecting esophageal intubation (sensitivity > 95%), false-positives, in which a correctly placed tracheal tube is incorrectly identified as esophageal, can occur in up to 25% of cardiac arrest patients. Aspiration devices may be useful in the out-of-hospital setting when poor lighting hampers colorimetric ETco2 determination. They also are good backup devices when cardiac arrest confounds attempts to assess placement with ETco2. Detection of expired CO2 is more reliable and is the standard for confirmation of tracheal placement of an ETT and for early detection of accidental esophageal intubation. Aspiration devices have a valuable but secondary role. Also, a bougie can be placed through the center of an ETT to corroborate tube location further. A bougie that can be passed deeply through the tube, with little or no resistance, suggests an esophageal intubation because the bougie has likely passed beyond the tube and into the stomach. If the ETT is in the trachea, the tip of the bougie will become wedged after only a few inches, likely in the right mainstem bronchus, and a vibration from contact with the anterior tracheal rings may be transmitted to the operator’s fingertips. Accordingly, ETco2 detection, with aspiration, bougie, or an ultrasound technique as backup, should be considered the primary means of ETT placement confirmation. Secondary means include physical examination findings, oximetry, and radiography. The examiner should auscultate both lung fields and the epigastric area. Pulse oximetry is indicated as a monitoring technique in all critically ill patients, not just those who require intubation. Oxim-

etry is useful in detecting esophageal intubation but may not show a decreasing oxygen saturation for several minutes after a failed intubation because of the oxygen reservoir (preoxygenation) created in the patient before intubation. Although chest radiography is universally recommended after ETT placement, its primary purpose is to ensure that the tube is well positioned below the cords and above the carina. A single anteroposterior chest radiograph is not sufficient to detect esophageal intubation, although esophageal intubation may be detected if the ETT is clearly outside the air shadow of the trachea. In cases in which doubt persists, a fiberoptic scope can be passed through the ETT to identify tracheal rings, another gold standard for confirmation of tracheal placement.

MANAGEMENT Decision Making Algorithms for emergency airway management have been developed and provide a useful guide for planning intubation and rescue in case of intubation failure. The algorithm assumes that a decision to intubate has been made and outlines such an approach. The approach is predicated on two key determinations that are to be made before active airway management is initiated (Fig. 1.7). The first determination is whether the patient is in cardiopulmonary arrest or a state of near arrest and is likely to be unresponsive to direct laryngoscopy. Such a patient—agonal, near death, in

Needs intubation

Unresponsive? Near death?

Yes

Crash airway

No Predict difficult airway? From difficult airway

Yes

Difficult airway

No RSI

Attempt intubation

Successful?

Yes

Postintubation management

No Failure to maintain oxygenation?

Yes

Failed airway

No

≥ 3 attempts at OTI by experienced operator?

Yes

No

Fig. 1.7.  Main emergency airway management algorithm. OTI, Orotracheal intubation; RSI, rapid sequence intubation. (Modified from Walls RM: The emergency airway algorithms. In Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; copyright © 2012, The difficult airway course: emergency; and Lippincott, Williams & Wilkins, publishers.)

CHAPTER 1  Airway

Difficult airway predicted

Crash airway

Maintain oxygenation

Intubation attempt successful?

Forced to act? Yes

Postintubation management

No Unable to bag ventilate?

Yes

Failed airway

No

Successful?

Postintubation management

No Failure to maintain oxygenation?

Yes

Failed airway

No ≥3 attempts by experienced operator?

Yes

No Fig. 1.8.  Crash airway algorithm. IVP, Intravenous push. (Modified from Walls RM: The emergency airway algorithms. In Walls RM, Murphy  MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; copyright © 2012, The  difficult airway course: emergency; and Lippincott, Williams & Wilkins, publishers.)

circulatory collapse—is deemed a crash airway patient for the purposes of emergency airway management and is treated using the crash airway algorithm by an immediate intubation attempt without use of drugs; this can be supplemented by a single large dose of succinylcholine if the attempt to intubate fails, and the patient is thought not to be sufficiently relaxed (Fig. 1.8). If a crash airway is not present, a decision of whether the patient represents a difficult intubation, as determined by the LEMON, MOANS, RODS, and SMART evaluations is made and, if so, the difficult airway algorithm is used (Fig. 1.9). For patients who require emergency intubation but who have neither a crash airway nor a difficult airway, RSI is indicated. RSI provides the safest and quickest method of achieving intubation in such patients.3,16 After administration of RSI drugs, intubation attempts are repeated until the patient is intubated or a failed intubation is identified. If more than one intubation attempt is required, oxygen saturation is monitored continuously and, if saturation falls to 90% or less, BMV is performed until saturation is recovered for another attempt. If the oxygen saturation continues to fall, despite optimal use of BMV or EGD, a failed airway exists. This is referred to as a can’t intubate, can’t oxygenate scenario. A failed airway also is defined as three unsuccessful attempts

Failed airway

Yes PIM

No

Awake technique successful? Yes

One best attempt successful?

Give RSI drugs No

Failure to maintain Yes oxygenation?

No Attempt intubation

Yes

No

BMV or EGD predicted to be successful?

Succinylcholine 2 mg/kg IVP

Call for assistance

Yes

Yes Intubation predicted to be successful?

RSI with double setup

No Yes

Postintubation management or RSI

No ILMA Flexible endoscopy Videolaryngoscopy Cricothyrotomy BNTI

Go to main algorithm

Fig. 1.9.  Difficult airway algorithm. BMV, Bag-mask ventilation; BNTI, blind nasotracheal intubation; DL, direct laryngoscopy; EGD, extraglottic device; ILMA, intubating laryngeal mask airway; PIM, postintubation management; RSI, rapid sequence intubation. (Modified from Walls RM: The emergency airway algorithms. In Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; copyright © 2012, The difficult airway course: emergency; and Lippincott, Williams & Wilkins, publishers.)

at laryngoscopy because subsequent attempts at laryngoscopy by the same clinician are unlikely to succeed. The three failed laryngoscopy attempts are defined as attempts by an experienced clinician using the best possible patient positioning and technique. Three attempts by a physician trainee using a direct laryngoscope may not count, necessarily, as best attempts if an experienced emergency clinician is available or videolaryngoscopy has not yet been attempted. Also, if the emergency clinician ascertains after even a single attempt that intubation will be impossible (eg, grade 4 laryngoscopic view with DL, despite optimal patient positioning and use of external laryngeal manipulation), and no alternative device (eg, videolaryngoscope, intubating LMA) is available, a failed airway is present. The failed airway is managed according to the failed airway algorithm (Fig. 1.10).

Difficult Airway The perception of a difficult airway is relative, and many emergency intubations could be considered difficult. Deciding whether to treat the airway as a typical emergency airway or whether to use the difficult airway algorithm is based on the degree of perceived difficulty, operator experience, armamentarium of airway devices available, and individual circumstances of the case. The LEMON, MOANS, RODS, and SMART assessments provide a systematic framework to assist in identifying the potentially difficult airway.

9

10

PART I 

Fundamental Clinical Concepts  | 

Failed airway criteria

SECTION One 

Critical Management Principles

Call for assistance Extraglottic device may be attempted

Failure to maintain oxygenation? No

Yes

Cricothyrotomy

If contraindicated

Choose one of: Flexible endoscopy Videolaryngoscopy Extraglottic device Lighted stylet Cricothyrotomy

Cuffed ETT placed?

Yes

Postintubation management

No Arrange for definitive airway management Fig. 1.10.  Failed airway algorithm. ETT, Endotracheal tube. (Modified from Walls RM: The emergency airway algorithms. In Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; copyright © 2012, The difficult airway course: emergency; and Lippincott, Williams & Wilkins, publishers.)

When preintubation evaluation identifies a potentially difficult airway (see Fig. 1.9), the approach is based on the premise that NMBAs generally should not be used unless the emergency clinician believes that (1) intubation is likely to be successful and (2) oxygenation can be maintained via BMV or EGD should the patient desaturate during a failed intubation attempt. The one exception to this recommendation occurs in the forced to act scenario. A forced to act imperative permits RSI, even in a highly difficult airway situation in which the operator is not confident of the success of laryngoscopy or of sustaining oxygenation. This usually occurs in the setting of a rapidly deteriorating patient with an obviously difficult airway and a presumed clinical trajectory of imminent arrest. Although this is not yet a crash airway situation, the operator is forced to act—that is, there is a need to act immediately to intubate before orotracheal intubation quickly becomes impossible or the patient arrests. The patient retains sufficient muscle tone and voluntary effort (including combative behavior induced by hypoxia) to require administration of drugs before intubation can be attempted. Consider an agitated patient with rapidly advancing anaphylaxis or angioedema, a morbidly obese patient in severe, end-stage status asthmaticus, or an intensive care unit (ICU) patient with inadvertent or premature extubation, respiratory failure, and difficult airway. Within seconds to minutes, perhaps before a full difficult airway assessment can be done or preparations can be completed for an alternative airway approach (eg, flexible endoscopy), the patient’s rapid deterioration signals impending respiratory arrest. This is a unique situation in which the operator may be compelled to take the one best chance to secure the airway by rapidly administering RSI drugs, despite obvious airway difficulty, and attempting intubation before the airway crisis has advanced to the point that intubation is impossible or delay has caused hypoxic arrest. If laryngoscopy fails, the RSI drugs have optimized patient conditions for cricothyrotomy

or insertion of an alternative airway device, depending on the operator’s judgment. Therefore, in the difficult airway algorithm, the first determination is whether the operator is forced to act. If so, RSI drugs are given, a best attempt at laryngoscopy is undertaken and, if intubation is not successful, the airway is considered failed, and the operator moves immediately to the failed airway algorithm. In the vast majority of difficult airway situations, however, the operator is not forced to act, and the first step is to ensure that oxygenation is sufficient to permit a planned orderly approach to airway management. If oxygenation is inadequate and cannot be made adequate by supplementation with BMV, the airway should be considered a failed airway. Although inadequate oxygenation should be defined on a case by case basis, oxygenation saturation falling below 90% is the accepted threshold, because this represents the point at which hemoglobin undergoes a conformational change, more readily releases oxygen, and increases the pace of further desaturation. Oxyhemoglobin saturations in the mid-80s, if holding steady, might be considered adequate in some circumstances, particularly if the patient is chronically hypoxemic. When oxygenation is inadequate or dropping, the failed airway algorithm should be used because the predicted high degree of intubation difficulty, combined with failure to maintain oxygen saturation, is analogous to the can’t intubate, can’t oxygenate scenario. When oxygenation is adequate, however, the next consideration is whether RSI is appropriate, on the basis of the operator’s assessment of the likelihood of (1) successful ventilation with BMV or EGD in case intubation is unsuccessful and (2) the likelihood of successful intubation by laryngoscopy. If the operator judges laryngoscopy likely to succeed and is confident that he or she can oxygenate the patient if intubation fails, RSI is performed. In such cases, a double setup can be used in which RSI is planned and preparations are simultaneously undertaken for rescue cricothyrotomy or another rescue technique. If the operator is not confident of successful intubation by RSI and time allows, an awake technique can be used. In this context, awake means that the patient continues to breathe and, although intravenous sedation and analgesia may be administered, can cooperate with caregivers. The patient is prepared by applying topical anesthesia with atomized or nebulized lidocaine, ideally preceded by a drying agent such as glycopyrrolate. Titrated doses of a sedative and analgesic agents (or ketamine, which provides both actions) may be required for the patient to tolerate the procedure. Once this is accomplished, a number of different devices can then be used to attempt glottic visualization, although flexible bronchoscopes and videolaryngoscopes are preferable. If the glottis is adequately visualized, the patient can be intubated at that time or, in a stable difficult airway situation, the emergency clinician may proceed with planned RSI, now assured of intubation success. If the awake laryngoscopy is unsuccessful, the patient can be intubated with any of numerous techniques shown in the last box in Fig. 1.9. For each of these methods, the patient is kept breathing but is variably sedated and anesthetized. The choice among these methods depends on clinician experience and preference, device availability, and patient attributes.

Failed Airway Management of the failed airway is dictated by whether the patient can be oxygenated. If adequate oxygenation cannot be maintained with rescue BMV, the rescue technique of first resort is cricothyrotomy (see Fig. 1.10). Multiple attempts at other methods in the context of failed oxygenation only delay cricothyrotomy and place the patient at increased risk for hypoxic brain injury. If an alternative device (ie, an EGD such as an LMA or Combitube) is readily available, however, and the operator judges it to be an appropriate device for the patient’s anatomy, single attempt can

CHAPTER 1  Airway

100

90 SaO2 (%)

be made to use it simultaneously with preparations for immediate cricothyrotomy as long as initiation of cricothyrotomy is not delayed. If early indications are that an EGD is effective and oxygenation improves, cricothyrotomy can wait; however, the operator must constantly reassess EGD function and oxygenation status. If the EGD subsequently fails, cricothyrotomy must begin without delay. If adequate oxygenation is possible, several options are available for the failed airway. In almost all cases, cricothyrotomy is the definitive rescue technique for the failed airway if time does not allow for other approaches (ie, preservation of oxygenation) or if they fail. The fundamental difference in philosophy between the difficult and failed airway is that the difficult airway is planned for, and the standard is to place a definitive airway (cuffed ETT) in the trachea. The failed airway is not planned for, and the standard is to achieve an airway that provides adequate oxygenation to avert hypoxic brain injury. Some devices used in the failed airway (eg, EGDs) are temporary and do not provide definitive airway protection.

80

70

Mean time to recovery of twitch height from 1 mg/kg succinylcholine IV

60 0

10% 0

Rapid Sequence Intubation RSI is the cornerstone of modern emergency airway management and is defined as the nearly simultaneous administration of a potent sedative (induction) agent and NMBA, usually succinylcholine or rocuronium, for the purpose of tracheal intubation. This approach provides optimal intubating conditions and has long been thought to minimize the risk of aspiration of gastric contents. A systematic review of the literature in 2007 failed to prove that RSI results in a lower incidence of aspiration than other techniques, but the authors correctly noted that virtually no studies have ever been designed to measure this precise endpoint. RSI is nevertheless the most widely used technique for emergency intubation of patients without identifiable difficult airway attributes, with recent large registry data showing that it is used in 85% of all emergency department intubations.3,16 The central concept of RSI is to take the patient from the starting point (eg, conscious, breathing spontaneously) to a state of unconsciousness with complete neuromuscular paralysis, and then to achieve intubation without interposed assisted ventilation. The risk of aspiration of gastric contents is thought to be significantly higher for patients who have not fasted before induction. Application of positive-pressure ventilation can cause air to pass into the stomach, resulting in gastric distention and likely increasing the risk of regurgitation and aspiration. The purpose of RSI is to avoid positive-pressure ventilation until the ETT is placed correctly in the trachea, with the cuff inflated. This requires a preoxygenation phase, during which mixed alveolar gases (mostly nitrogen) within the lungs’ functional residual capacity are replaced with oxygen, permitting at least several minutes of apnea (see later discussion) in a healthy normal body habitus adult before oxygen desaturation to less than 90% ensues (Fig. 1.11). Use of RSI also facilitates successful endotracheal intubation by causing complete relaxation of the patient’s musculature, allowing better access to the airway. Finally, RSI permits pharmacologic control of the physiologic responses to laryngoscopy and intubation, mitigating potential adverse effects. These effects include further elevations in intracranial pressure (ICP) in response to the procedure and to the sympathetic discharge resulting from laryngoscopy (Box 1.5). RSI is a series of discrete steps, and every step should be planned (Box 1.6).

2

3

4

5

6

7 6.8

8

9 8.5

90% 10 10.2

⋅ Time of VE = 0 (min) Obese 127-kg adult Normal 10-kg child

Methods of Intubation Although many techniques are available for intubation of the emergency patient, four methods are the most common, with RSI being the most frequent approach.3,16

1

50%

Normal 70-kg adult Moderately ill 70-kg adult

Fig. 1.11.  Desaturation time for apneic, fully preoxygenated patients. Children, patients with comorbidity, and obese patients desaturate much more rapidly than healthy normal adults. The box on the lower right side of the graph depicts time to recovery from succinylcholine, which in almost all cases exceeds safe apnea time. Note also the precipitous decline of oxygen saturation from 90% to 0% for all groups. VE, Expired volume. (Modified from Benumof JL, Dagg R, Benumof R: Critical hemoglobin desaturation will occur before return to unparalyzed state following 1 mg/kg intravenous succinylcholine. Anesthesiology 87:979–982, 1997.)

BOX 1.5 

Pretreatment Agents for Rapid Sequence Intubationa Reactive airway disease: Albuterol, 2.5 mg, by nebulizer. If time does not permit albuterol nebulizer, give lidocaine 1.5 mg/kg IV. Cardiovascular disease: Fentanyl, 3 µg/kg, to mitigate sympathetic discharge Elevated ICP: Fentanyl, 3 µg/kg, to mitigate sympathetic discharge and attendant rise in ICP ICP, intracranial pressure. a Given 2–3 min before induction and paralysis.

BOX 1.6 

The Seven Ps of Rapid Sequence Intubation 1. 2. 3. 4. 5. 6. 7.

Preparation Preoxygenation Pretreatment Paralysis with induction Positioning Placement of tube Postintubation management

Preparation.  In the initial phase, the patient is assessed for intubation difficulty, unless this has already been done, and the intubation is planned, including determining dosages and sequence of drugs, tube size, and laryngoscope type, blade, and size. Drugs are drawn up and labeled. All necessary equipment is

11

12

PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

assembled. All patients require continuous cardiac and pulse oximetry monitoring. At least one and preferably two goodquality intravenous lines should be established. Redundancy is always desirable in case of equipment or intravenous access failure. Most importantly, a rescue plan for intubation failure should be developed at this time and made known to the appropriate members of the resuscitation team. Preoxygenation.  Administration of 100% oxygen for 3 minutes of normal tidal volume breathing in a normal healthy adult establishes an adequate oxygen reservoir to permit 6 to 8 minutes of safe apnea before oxygen desaturation to less than 90% occurs (see Fig. 1.11). Additional preoxygenation does not improve arterial oxygen tension. The time to desaturation to less than 90% in children, obese adults, late-term pregnant women, and patients who are acutely ill or injured is considerably shorter. Desaturation time also is reduced if the patient does not inspire 100% oxygen. Nevertheless, adequate preoxygenation usually can be obtained, even in ED patients, to permit minutes of apnea before there is oxygen desaturation to less than 90%. Preoxygenation is also essential to the no-bagging approach of RSI. If time is insufficient for a full 3-minute preoxygenation phase, eight vital capacity breaths with high-flow oxygen can achieve oxygen saturations and apnea times that match or exceed those obtained with traditional preoxygenation. Desaturation time in obese patients can be prolonged by preoxygenating with the patient in a head-up position and by continuing supplemental oxygen (via nasal cannula at a flow rate of 5–15 L/min) after motor paralysis and during laryngoscopy until the ETT is successfully placed. In obese patients, it extends the time to desaturation to 95% from 3.5 to 5.3 minutes.17,18 This so-called apneic oxygenation takes advantage of a physiologic principle termed aventilatory mass flow.19 Even though patients are paralyzed during RSI, circulation is unaltered. The constant diffusion of alveolar oxygen into the pulmonary circulation creates a natural downward gradient promoting passive oxygen movement from the patient’s upper airway into the gasexchanging portions of the lungs. Oxygen saturation monitors permit earlier detection of desaturation during laryngoscopy, but preoxygenation remains an essential step in RSI. Pretreatment.  During this phase, drugs are administered 3 minutes before the administration of succinylcholine and an induction agent to mitigate the adverse physiologic effects of laryngoscopy and intubation on the patient’s presenting condition. Pretreatment approaches have evolved over time. Periodic reappraisals of the available literature have whittled the pretreatment approach down to the bare essentials with a focus on optimizing patient physiology prior to any intubation attempts. Older practices, such as the routine use of atropine for intubation of small children, have largely been abandoned. Intubation is intensely stimulating and results in a sympathetic discharge, or reflex sympathetic response to laryngoscopy (RSRL). In patients suffering from a hypertensive emergency, sympatholysis with fentanyl (3 mcg/kg IV) administered 3 minutes before RSI can optimize the patient’s hemodynamics by attenuating spikes in blood pressure and shear forces, both of which are considered undesirable in patients with elevations of intracranial pressure (ICP), aortic disease, acute coronary syndromes and neurovascular emergencies. Patients with reactive airways disease can exhibit worsening pulmonary mechanics after intubation as a result of bronchospasm. Controversy exists regarding whether lidocaine (1.5 mg/kg IV) confers any additional benefit, beyond albuterol, and should be considered optional at best. Asthmatic patients being intubated in the ED for status asthmaticus will have received albuterol before intubation, and it is unlikely in these patients that lidocaine has any additive protective effect and is not recommended. Lidocaine

has a vanishing role in emergency airway management and may disappear completely in the near future (see Box 1.5). Paralysis With Induction.  In this phase, a potent sedative agent is administered by rapid intravenous (IV) push in a dose capable of producing unconsciousness rapidly. This is immediately followed by rapid administration of an intubating dose of an NMBA, either succinylcholine at a dose of 1.5 mg/kg IV or rocuronium, 1 mg/kg. It is usual to wait 45 seconds from when the succinylcholine is given and 60 seconds from when rocuronium is given to allow sufficient paralysis to occur. The results from two large meta-analyses have revealed that intubating conditions provided by each drug are equivalent as long as rocuronium is dosed between 1.0 and 1.2 mg/kg IV. Positioning.  The patient should be positioned for intubation as consciousness is lost. Usually, positioning involves head extension, often with flexion of the neck on the body. Although simple extension may be adequate, a full sniffing position with cervical spine extension and head elevation is optimal if DL is used.10 The Sellick maneuver—application of firm, backward pressure over the cricoid cartilage with the goal of obstructing the cervical esophagus and reducing the risk of aspiration—had long been recommended to minimize the risk of passive regurgitation and hence aspiration, but is no longer recommended. The Sellick maneuver is incorrectly applied by a variety of operators, making laryngoscopy or intubation more difficult in some patients, and aspiration often occurs despite use of the Sellick maneuver. In many patients, the cervical esophagus is positioned lateral to the cricoid ring in a relationship that is exaggerated by posterior pressure, rarely resulting in esophageal obstruction. Accordingly, we do not recommend routine use of the Sellick maneuver, and it should be considered optional, applied selectively, and released or modified early if the laryngeal view is poor or tube passage is difficult. After administration of an induction agent and NMBA, although the patient becomes unconscious and apneic, BMV should not be initiated unless the oxygen saturation falls to 90%. Placement of Tube.  Approximately 45 to 60 seconds after administration of the NMBA, the patient is relaxed sufficiently to permit laryngoscopy. This is assessed most easily by moving the mandible to test for mobility and absence of muscle tone. Place the ETT during glottic visualization with the laryngoscope. Confirm placement, as described earlier. If the first attempt is unsuccessful but oxygen saturation remains high, it is not necessary to ventilate the patient with a bag and mask between intubation attempts. If the oxygen saturation is approaching 90%, the patient may be ventilated briefly with a bag and mask between attempts to reestablish the oxygen reservoir. Postintubation Management.  After confirmation of tube placement by ETco2, obtain a chest radiograph to confirm that mainstem intubation has not occurred and to assess the lungs. If available, place the patient on continuous capnography. In general, long-acting NMBAs (eg, pancuronium, vecuronium) are avoided; the focus is on optimal management using opioid analgesics and sedative agents to facilitate mechanical ventilation. An adequate dose of a benzodiazepine (eg, midazolam, 0.1–0.2 mg/kg IV) and opioid analgesic (eg, fentanyl, 3–5 µg/kg IV, or morphine, 0.2–0.3 mg/kg IV) is given to improve patient comfort and decrease sympathetic response to the ETT. Propofol infusion (5–50 µg/kg/min IV) with supplemental analgesia is an effective method for managing intubated patients who do not have hypotension or ongoing bleeding and is especially helpful for management of neurologic emergencies because its clinical duration of action is very short ( 10% BSA

>5 days until healed

Crush injury

>5 days until healed

Denervation (stroke, spinal cord injury)

>5 days until 6 mo postinjury

Neuromuscular disease (ALS, MS, MD)

Indefinitely

Intraabdominal sepsis

>5 days until resolution

ALS, Amyotrophic lateral sclerosis; BSA, body surface area; MD, muscular dystrophy; MS, multiple sclerosis.

CHAPTER 1  Airway

dialysis) sufficient to be manifest on the electrocardiogram (ECG). Treatment for succinylcholine-induced hyperkalemia is the same as for any other hyperkalemic emergency. Masseter Spasm.  Succinylcholine has rarely been reported to cause masseter spasm, primarily in children and young adults. The clinical significance of this phenomenon is unclear, but administration of a competitive NMBA terminates the spasm. Severe persistent spasm should raise suspicion of malignant hyperthermia. Malignant Hyperthermia.  Succinylcholine has been associated with malignant hyperthermia, a perplexing syndrome of rapid temperature rise and rhabdomyolysis. Malignant hyperthermia occurs in genetically predisposed individuals who receive certain volatile anesthetic agents or succinylcholine. The condition is extremely rare and has not been reported in the context of ED intubation. Treatment consists of cessation of any potential offending agents, administration of dantrolene (1–2.5 mg/kg IV every 5 minutes, to a maximum dose of 10 mg/kg IV), and attempts to reduce body temperature by external means. A national malignant hyperthermia hotline is available for emergency consultation at 1-800-644-9737 (then dial 0). Competitive Agents.  Competitive NMBAs are classified according to their chemical structure. The aminosteroid agents include pancuronium, vecuronium, and rocuronium. Vecuronium neither releases histamine nor exhibits cardiac muscarinic blockade and is an excellent agent for the maintenance of neuromuscular blockade when this is desirable. Rocuronium is the best agent for use in RSI when succinylcholine is contraindicated. In a study of ED intubations performed with rocuronium or succinylcholine, first-pass intubation success was independent of the NMBA used.24 Rocuronium.  When a patient has a contraindication to succinylcholine, rocuronium bromide is the paralytic agent of choice. At a dose of 1.0–1.2 mg/kg IV, rocuronium achieves intubating conditions similar to those of succinylcholine, lasts approximately 50 minutes, and has been used in the ED with success.3 Intubating level paralysis may take 15 to 20 seconds longer than with succinylcholine, and the operator should allow 60 seconds to elapse before attempting intubation when rocuronium is used. There are no absolute contraindications to rocuronium. In the ED, dosing in morbidly obese patients should be based on actual TBW. Although adequate intubating conditions can be obtained when ideal body weight (IBW) is used, this concept is only pertinent to the anesthesiologist who may be titrating neuromuscular blockade to a short anesthetic time. Paralysis will be of sufficient duration, regardless of which weight-based dosing regimen is used, that the emergency clinician will need to have managed the airway successfully before spontaneous respirations return. The potential for inferior intubating conditions using IBW dosing makes this approach undesirable. However, in the subset of critically ill patients who require frequent, serial, neurologic examinations, the more prolonged duration of paralysis with rocuronium may make it less desirable than succinylcholine for routine use. Paralysis After Intubation.  After intubation, prolonged paralysis may be desired to optimize mechanical ventilation; however, current management is based on use of deep sedation and analgesia, with neuromuscular paralysis used only when necessary to maintain ventilatory control. If neuromuscular blockade is required, vecuronium (0.1 mg/kg IV) can be given, but longer term neuromuscular blockade is not to be undertaken without ensuring appropriate sedation and analgesia of the patient and a means to ensure that ongoing sedation and analgesia are adequate. Prolonged paralysis without adequate sedation occurs in up to 20% of patients following RSI in the ED.25 A sedating dose of a benzodiazepine, such as midazolam (0.1 mg/kg IV), combined with an opioid analgesic, such as fentanyl (3–5 µg/kg IV) or morphine (0.2–0.3 mg/kg IV), is required to improve patient comfort

and decrease sympathetic response to the ETT. A sedative strategy using propofol (0.1 mg/kg/min IV) is common, especially in head-injured patients, because of its beneficial cerebroprotective profile and rapid resolution of anesthesia that allows frequent neurologic reassessments. With appropriate attention to achieving optimal sedation and analgesia, ongoing use of an NMBA usually is not necessary.

Induction Agents A patient with any degree of clinical responsiveness, including reactivity to noxious stimuli, should receive a sedative or induction agent at the time of administration of any NMBA. Patients who are deeply unconscious and unresponsive may require only a reduced dose of an induction agent if the unconscious state is caused by drugs or alcohol, which are themselves general anesthetic agents. Patients who are unconscious because of a central nervous system insult should receive a full induction dose of an appropriate agent to attenuate adverse responses to airway manipulation. Induction agents also potentiate the effect of the NMBA and improve intubation conditions because the intubation is often initiated on the leading edge of paralysis, and the relaxation effects of the induction agent are additive to those of the NMBA. Etomidate.  Etomidate is an imidazole derivative that has been in use since 1972. Its activity profile is similar to that of thiopental, with rapid onset, rapid peak activity, and brief duration, but it is remarkable in its lack of adverse hemodynamic effects. Emergency clinicians have high confidence in etomidate and, over the last decade, have chosen it for more than 90% of all ED intubations.3 The induction dose is 0.3 mg/kg IV. Because etomidate is able to decrease ICP, cerebral blood flow (CBF), and cerebral metabolic rate without adversely affecting systemic mean arterial blood pressure and cerebral perfusion pressure (CPP), it is an excellent induction agent for patients with elevated ICP, even in cases of hemodynamic instability. Etomidate may cause brief myoclonus, but this is of no clinical significance when administered for RSI. A single dose of etomidate has been shown to reduce serum cortisol levels transiently and blunt the adrenal response to adrenocorticotropic hormone (ACTH) by reversibly inhibiting 11β-hydroxylase, a key synthetic enzyme in the glucocorticoid pathway. Since discovering this mechanism, much debate has emerged regarding etomidate’s impact on survival in sepsis patients. Data from retrospective studies are conflicting, but a recent meta-analysis of 18 prospective observational and controlled trials has shown no mortality effect from a single dose of etomidate in septic patients.26,27 Recent prospective randomized trials looking at undifferentiated ICU admissions and those specifically involving individuals with septic shock have shown that single-dose etomidate has no effect on outcome.28 Ironically, much of the original criticism of etomidate arose from the hypothesis that the adrenocortical response to exogenous corticotropin predicts outcome in patients with septic shock, a theory that has since been discredited.28a The most comprehensive study of the role of exogenous corticosteroids in septic shock has failed to show any benefit, casting further doubt about any possible mortality effect of a single dose of etomidate. Pending a properly constructed, prospective, randomized clinical trial, there is not sufficient evidence to support the recommendation that etomidate be avoided in patients with septic shock. In fact, etomidate’s superior hemodynamic profile makes it an excellent choice in these and other unstable patients. Ketamine.  Ketamine, a phencyclidine derivative, has been widely used as a general anesthetic agent since 1970. After an IV dose of 1 to 2 mg/kg, ketamine produces loss of awareness within 30 seconds, peaks in approximately 1 minute, and has a clinical

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Critical Management Principles

duration of 10 to 15 minutes. As a dissociative anesthetic agent, ketamine induces a cataleptic state rather than a true unconscious state. The patient has profound anesthesia but may have her or his eyes open. Protective airway reflexes and ventilatory drive usually are preserved. The principal uses of ketamine in emergency airway management are as a sedative agent for awake intubation (eg, flexible bronchoscope) and as the induction agent during RSI for patients with acute severe asthma or hemodynamic instability. Because of its superior hemodynamic profile, ketamine is an excellent alternative to etomidate for a hemodynamically unstable patient, such as a patient with sepsis or multiple trauma. Although comparative human evidence is lacking, ketamine probably has less propensity to exacerbate hemodynamic instability than any other agent, even etomidate. However, all sedative induction agents, including ketamine, can provoke further hypotension or cardiovascular collapse in patients with profound refractory shock or those with depressed myocardial contractility and catecholamine depletion. In these settings, dosages are reduced to 50% or 25% of the usual dose. In patients with status asthmaticus, etomidate, propofol, or another induction agent can be used, with the notable exception of sodium thiopental, which releases histamine. Ketamine has some bronchodilatory effects and also can cause catecholamine release, so it may be useful for intubation and intermittent administration as part of sedation for mechanical ventilation in patients with severe asthma, although no outcome studies have clearly demonstrated its superiority. Controversy exists regarding the use of ketamine in patients with elevated ICP because it may increase the cerebral metabolic rate, ICP, and CBF. The evidence that ketamine can produce harm in this way is conflicting, however, and may be outweighed in trauma patients because of its overall favorable hemodynamic profile.29 Ketamine does not appear to be harmful in children when given in procedural doses to patients with known elevated ICP and may actually lower ICP. Because it may cause release of catecholamines and increase blood pressure, ketamine should be avoided in traumatic brain injury (TBI) patients with elevated blood pressure. However, we recommend the use of ketamine or etomidate during RSI for induction of patients with TBI and hypotension or risk factors for hypotension. Ketamine may produce unpleasant emergence phenomena, especially disturbing or frightening dreams in the first 3 hours after awakening. These reactions, which are more prominent in adults than in children, in women than in men, in patients receiving larger doses, and in certain personality types, may be mitigated by benzodiazepine administration.30 Patients who undergo RSI with ketamine should receive a benzodiazepine (eg, lorazepam, 0.05 mg/kg, or midazolam, 0.1 mg/kg) as part of postintubation management. Propofol.  Propofol is a highly lipophilic alkylphenol with γ-aminobutyric acid (GABA) receptor stimulation activity. Its primary use in the emergency setting has been for postintubation sedation in head-injured patients; however, it increasingly has been used as an induction agent during RSI.3 It reduces ICP and cerebral oxygen usage and is indicated for patients with elevated ICP caused by a medical or traumatic emergency. Because of the propensity of propofol to cause hypotension through vasodilation and direct myocardial depression, the dosage is reduced or the drug is avoided altogether in hemodynamically compromised patients. The usual induction dose of propofol is 1.5 mg/kg IV, but reduced dosages should be used in older patients or those with hemodynamic compromise or poor cardiovascular reserve. Propofol is delivered in a soybean oil and lecithin vehicle and should not be used for patients with allergies to these substances. Although propofol has traditionally been avoided in patients with egg allergy, it is likely safe unless a history of anaphylaxis to egg protein

exists. Propofol causes pain at the site of administration in as many as 60% of patients. Using a proximal (antecubital) vein in lieu of a distal venous injection site is the most important preventive measure. Pretreatment with IV lidocaine, coadministration of lidocaine mixed with propofol, and pretreatment with opioids or ketamine have all been shown to limit this common adverse reaction.31 Other Induction Agents.  Given the widespread acceptance and familiarity with etomidate, propofol, and ketamine, other drug classes such as barbiturates and benzodiazepines are infrequently used as induction agents for RSI. In North America, nearly all emergency intubations are performed with one of those three agents.3 Rapidly acting barbiturates, such as thiopental, are highly lipid-soluble and readily cross the blood-brain barrier, acting on the GABA receptor neuroinhibitory complex to depress central nervous system activity. The last US-based manufacturer of sodium thiopental stopped production, and imports into the United States are severely restricted, but it is still in use in some areas outside of North America. Of the benzodiazepines, only midazolam is used as an induction agent, a role for which it is inferior to other, more commonly used agents, such as etomidate and propofol. The usual induction dose for midazolam is 0.2 to 0.3 mg/kg IV. At a dose of 0.3 mg/kg IV, midazolam produces loss of consciousness in about 30 seconds (but may take up to 120 seconds) and has a clinical duration of 15 to 20 minutes. Midazolam is a negative inotrope and should be used with caution in hemodynamically compromised and older patients, for whom the dose can be reduced to 0.1 or 0.05 mg/kg. Onset is slower at these reduced doses. Dexmedetomidine (Precedex) has gained popularity as a solo agent, or in combination with benzodiazepines, for procedural sedation and awake intubation.21 The typical loading dose is 1 mg/ kg IV over 5 to 10 minutes. At therapeutic levels, it has a minimal effect on the respiratory drive or protective airway reflexes but its use is limited by bradycardia and hypotension. It has not been studied as an induction agent during RSI, and its slow loading rate would likely keep it from being effective in that situation.

Special Clinical Circumstances This section will discuss several specific clinical scenarios that often warrant modification of the airway management plan. Pediatric airway management is discussed in Chapter 161.

Status Asthmaticus RSI is the recommended technique for intubation of a patient in status asthmaticus. Difficult airway considerations are complex in an asthmatic patient because of impending respiratory arrest and the patient’s inability to tolerate attempts at awake intubation. When a difficult airway is identified, intubation preparation should begin early, so that awake methods, such as flexible endoscopic intubation, may be retained as options. Even when a difficult airway is identified in an asthmatic patient, however, RSI usually is the intubation method of choice. Ventilation with a BMV or EGD may be difficult because of high airway resistance, and the technique should be optimized with the use of a low tidal volume and respiratory rate, with a high inspiratory flow rate. Reducing the respiratory rate to allow for adequate exhalation, even at the expense of retaining CO2, is recommended to prevent the development of auto-PEEP, known as breath stacking, which can compromise ventilation and cause barotrauma. The asthmatic patient has highly reactive airways, and steps should be taken to minimize any additional bronchospasm that may occur during intubation. The bronchoconstriction that occurs with ETT placement is thought to be neurally mediated,

CHAPTER 1  Airway

and local anesthetics, particularly lidocaine, have been studied as a way to blunt this airway reflex. We had previously recommended lidocaine to suppress the reflexive bronchospasm and coughing that occurs in response to airway manipulation in asthmatic patients, but there have been no high-level human studies supporting these beneficial effects, particularly in patients who have received a β2-agonist. High-dose, inhaled β-agonists, such as albuterol, provide maximal protection against reactive bronchospasm during intubation and are indicated for asthmatics with or without active bronchospasm. Ketamine has bronchodilatory properties and may mitigate bronchospasm in patients who are not intubated and in patients who are already intubated and are not improving with mechanical ventilation. Although studies to date have been limited, ketamine is also a reasonable induction agent for the emergency intubation of patients with status asthmaticus (Table 1.3).

Hemodynamic Consequences of Intubation Laryngoscopy and intubation are potent stimuli for the reflex release of catecholamines. This RSRL produces a modest increase in blood pressure and heart rate and is of little or no consequence in otherwise healthy patients. The RSRL is of potential clinical significance in two settings, acute elevation of ICP and certain cardiovascular diseases (eg, intracerebral hemorrhage, subarachnoid hemorrhage, aortic dissection or aneurysm, ischemic heart disease). In these settings, the reflexive release of catecholamines, increased myocardial oxygen demand, and attendant rise in mean arterial blood pressure and heart rate may produce deleterious effects. The synthetic opioids (eg, fentanyl) and β-adrenergic blocking agents (eg, esmolol) are capable of blunting the RSRL and stabilizing heart rate and blood pressure during intubation. In patients at risk from acute blood pressure elevation, administration of fentanyl (3 µg/kg) during the pretreatment phase of RSI attenuates the heart rate and blood pressure increase. The full

TABLE 1.3 

Rapid Sequence Intubation for Status Asthmaticus TIME

STEP

Zero minus 10 min Preparation Zero minus 5 min

Preoxygenation (as possible) • Continuous albuterol nebulizer • 100% oxygen for 3 min or eight vital capacity breaths, or highest flow oxygen possible

Zero minus 3 min

Pretreatment—albuterol, 2.5 mg nebulized, or lidocaine, 1.5 mg/kga

Zero

Paralysis with induction • Ketamine, 1.5 mg/kg • Succinylcholine, 1.5 mg/kg

Zero plus 30 s

Positioning

Zero plus 45 s

Placement • Laryngoscopy with intubation • End-tidal carbon dioxide confirmation

Zero plus 2 min

Postintubation management • Sedation and analgesia • NMBA only if required after adequate sedation, analgesia • In-line albuterol nebulization • Additional ketamine as indicated

Only if not already pretreated with β-agonists. NMBA, Neuromuscular blocking agent. a

sympatholytic dose of fentanyl is much higher, but limiting the dose minimizes the likelihood of precipitating or worsening hypoventilation. Because fentanyl reduces sympathetic tone, it should not be given to patients with hemodynamic compromise (eg, bleeding, volume depletion, sepsis). The administration of 3 µg/kg is safer than larger doses and can be supplemented with an additional 3 µg/kg immediately after intubation if greater sympathetic blockade is desired or hypertension and tachycardia persist. Fentanyl should be given over 60 seconds to prevent hypoventilation or apnea.

Elevated Intracranial Pressure When the ICP is elevated as a result of head injury or acute intracranial catastrophe, there are two considerations—maintaining CPP (by avoiding excessive hypotension) and minimizing supranormal surges in the mean arterial blood pressure (MAP), which can increase ICP. Normally, cerebrovascular autoregulation maintains a constant CBF over a wide range of systemic blood pressures, but this action may be lost in conditions that elevate ICP. Maintenance of the systemic MAP at 100 mm Hg or higher supports CPP and reduces the likelihood of secondary injury. Therefore, the RSI induction agent for a patient with suspected elevated ICP should be selected and dosed to minimize the likelihood of exacerbation of hypotension. In patients with suspected or documented elevation of ICP, control of RSRL is desirable to avoid further elevation of ICP. Fentanyl (3 µg/kg) given as a pretreatment drug is the best choice for this purpose in the emergency setting. Although evidence has suggested a separate reflex that increases ICP in response to laryngoscopy and intubation, and IV lidocaine was formerly recommended for this purpose, evidence is weak, and no further evidence has developed. Therefore, we no longer recommend lidocaine in this setting. Similarly, RSRL and the ICP response to intubation make blind nasotracheal intubation inadvisable for brain injury patients. In emergency patients who may have elevated ICP, the emergency clinician should choose an induction agent that balances a favorable effect on cerebral dynamics and ICP with a stable systemic hemodynamic profile. We recommend etomidate, although propofol is also a good option when there is no hemodynamic compromise (Table 1.4).

Hypotension and Shock In critically ill and injured patients, induction agents have the potential to exaggerate preexisting hypotension and, in some cases, precipitate circulatory collapse. Peri-intubation cardiac arrest, typically pulseless electrical activity (PEA), complicates up to 4% of emergency RSIs.3 Risk factors in ED populations include advanced age (>70 years), COPD, and shock on arrival.32-34 In patients with profound shock, all induction agents have the potential to exacerbate hypotension. Shock-sensitive RSI hinges on three primary management principles—volume resuscitation prior to induction (if time permits), reduced dose induction agent administration, and pretreatment with peri-intubation pressor agents (Table 1.5). When time allows, patients with hypotension should be administered isotonic fluid boluses or packed red blood cells (PRBCs) to maximize preload, increase blood pressure, and allow more pharmacologic options during RSI. Phenylephrine hydrochloride (Neo-Synephrine; 50–100 µg IV push) administered prior to the induction agent can limit hypotensive effects. In addition, induction agent selection should be limited to etomidate or ketamine only, and the dose should be reduced by 50%. Attention to these details can reduce the incidence of cardiovascular periintubation adverse events.

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Critical Management Principles

TABLE 1.4 

Rapid Sequence Intubation for Elevated Intracranial Pressure TIME

STEP

Zero minus 10 min

Preparation

Zero minus 5 min

Preoxygenation (as possible) — 100% oxygen for 3 min or eight vital capacity breaths

Zero minus 3 min

Pretreatment—fentanyl, 3 µg/kg (slowly)

Zero

Paralysis with induction • Etomidate, 0.3 mg/kg • Succinylcholine, 1.5 mg/kga

Zero plus 30 s

Positioning

Zero plus 45 s

Placement • Laryngoscopy with intubation • End-tidal carbon dioxide confirmation

Zero plus 2 min

Postintubation management—sedation and analgesia; consider propofol to permit frequent reexamination NMBA only if required after adequate sedation, analgesia

a

May substitute rocuronium, 1 mg/kg, for succinylcholine. NMBA, Neuromuscular blocking agent.

TABLE 1.5 

Rapid Sequence Intubation for Hypotension and Shock TIME

STEP

Zero minus 10 min

Preparation—isotonic fluid boluses or blood products

Zero minus 5 min

Preoxygenation (as possible)—100% oxygen for 3 min or eight vital capacity breaths

Zero minus 3 min

Pretreatment—phenylephrine hydrochloride (Neosynephrine), 50–100 µg IV push (if still hypotensive after IVFs or blood)

Zero

Paralysis with induction • Ketamine, 0.5–0.75 mg/kg OR Etomidate, 0.1–0.15 mg/kg • Succinylcholine, 1.5 mg/kg IV

Zero plus 30 s

Positioning

Zero plus 45 s

Placement • Laryngoscopy with intubation • End-tidal carbon dioxide confirmation

Zero plus 2 min

Postintubation management—continued volume resuscitation

Potential Cervical Spine Injury Historically, most patients with suspected blunt cervical spine injury were intubated orally by direct laryngoscopy with in-line cervical spine immobilization, whether done as an awake procedure or with neuromuscular blockade. However, with this approach, glottic views can be inadequate, and excessive lifting force often is required. Patients with known cervical spine fractures are optimally managed with a flexible bronchoscope to minimize cervical spine motion; however, in the emergency

setting, a videolaryngoscope should be used and, if not available, a direct laryngoscope also can be used. A videolaryngoscope provides superior laryngeal views without excessive lifting force or cervical spine movement and has higher intubation success rates when compared with conventional direct laryngoscopy. The intubating laryngeal mask airway (ILMA) also may result in less cervical spine movement during intubation than direct laryngoscopy, although the need for a blind intubation devices has been decreasing with the advent of videolaryngoscopy.3 Other devices have also shown promise for safe intubation of patients with cervical spine injury. A fluoroscopic study in which intubation with the Shikani optical stylet (SOS; Clarus Medical, Minneapolis) was compared with DL has shown significantly less cervical spine movement with the SOS but a slightly longer intubation time (28 vs. 17 seconds). Video-enhanced rigid stylets, such as the Clarus Video System (CVS) are also effective tools for patients in cervical collars.35 The Airtraq and Pentax Airway Scope are curved intubation devices that integrate an ETT channel and either a viewing lens or a video screen to facilitate intubation. Both devices have shown high levels of intubation success and minimal cervical spine motion compared with direct laryngoscopy. In the absence of a coexistent blunt traumatic mechanism or a neurologic examination indicating spinal cord injury, cervical spine immobilization for intubation of patients with penetrating head and neck trauma rarely is indicated. It is not proven whether patients with gunshot or shotgun injuries to the head or neck are at risk of exacerbation of cervical cord injury during intubation, and there is no report of such a patient, with or without clinical evidence of spinal cord injury, who was injured by intubation. In addition, cervical spine immobilization in patients with penetrating neck injuries may be harmful. A large retrospective review of more than 45,000 trauma patients with penetrating injuries has found that those in whom prehospital cervical collars were applied were two to three times more likely to die. Delays in transport and patient assessment and added difficulty for airway procedures were postulated as potential contributors.36

Airway Devices and Techniques Direct Versus Video Laryngoscopy The inherent limitations of DL make glottic visualization less likely when compared to video instruments.6,37 Videolaryngoscopes offer the ability to visualize the glottis without creating a direct line of sight, thus making irrelevant many of the issues that complicate DL. Although DL remains an acceptable technique for tracheal intubation, there is mounting evidence of the clear superiority of modern video devices, and DL increasingly is relegated to the role of a standby device.3

Videolaryngoscopes Modern laryngoscopes incorporate video imaging into specially designed laryngoscope blades to provide glottic visualization superior to that of a direct laryngoscope, without the need to create a straight-line visual axis through the mouth. Videolaryngoscopes can be separated into two large groups based on shape— those that use traditional laryngoscope geometry complemented by a video viewing device (which also can be used as direct laryngoscopes), and those with specially curved or angulated blades, designed specifically for use in a video system and not suitable for DL. This classification system is important because intubating mechanics and success differ between the two groups. Nevertheless, regardless of type, videolaryngoscopes provide superior glottic views and greater first-pass success when compared with direct laryngoscopes, particularly when the airway is difficult or when a nonexpert operator is performing the intubation.6,7,37,38

CHAPTER 1  Airway

For routine intubation of nondifficult airways by expert intubators, success rates with direct laryngoscopy often can match those obtained with a videolaryngoscope.7 Because emergency intubations are by definition emergent and cannot be rescheduled, operator experience varies, and airways are often difficult, videolaryngoscopy is the first-choice modality for emergency intubations. The GlideScope videolaryngoscope system (GVL; Verathon, Seattle) uses a modified Macintosh blade with a straightened, angulated, and elongated tip enclosing a proximally placed camera to provide a wide-angle view of the glottis and surrounding anatomy, even in patients with difficult airways. Video images are transmitted to a high-resolution display that can record still pictures and video clips. Handle and blade sizes range from neonate to obese adult. The GlideScope Ranger is an ultraportable version of the device, designed for use in the out-of-hospital environment. One large series of out-of-hospital intubations has shown that the Ranger significantly reduces the number of attempts needed to intubate compared with DL.39 The GlideScope Cobalt is a system designed for a single use, without the need for cleaning (Fig. 1.12). It consists of a flexible video wand insert that fits inside a disposable, single-piece transparent blade called a stat and comes in sizes comparable to those for the standard GlideScope. The added bulk created by the stat can make it harder to maneuver in emergency patients and may reduce intubation success compared to the standard GVL blade.40 The newest generation GlideScope handles are made of lightweight titanium, with a narrower side profile (Fig. 1.13). The placement of the camera distally along the blade to create a viewing field essentially negates the obstructive potential of the tongue, so GlideScope laryngoscopy and most other hyperangulated videolaryngoscopy is performed with the blade introduced in the midline of the mouth and advanced around the tongue, with very little lifting. A proprietary rigid, preformed stylet is available for use with the GlideScope, or a malleable stylet can be shaped to match the exaggerated curve of the GlideScope blade. The rigid stylet is less likely to deform during intubation attempts and allows the operator better ETT control on the video screen. Either stylet may be used, and data are conflicting regarding the advantage provided with a rigid stylet; however, one ED-based investigation has suggested that intubation success is higher with the rigid stylet compared with a standard malleable stylet.41,42 When compared with DL, the GlideScope provides an equivalent or superior glottic view and has a very high intubation success rate.7 Traditional predictors of difficult direct laryngoscopy likely will not apply to videolaryngoscopy because most are based on limitations of creating a direct line of sight, which is not part of videolaryngoscopy.43

Fig. 1.12.  GlideScope Cobalt system uses a high-resolution digital display, includes single-use Stats (blade sheaths) that cover the video baton, and can record still images and video clips through internal and removable storage devices. (Courtesy Verathon, Seattle.)

Although the view is universally better with all videolaryngoscopes, the GlideScope’s impact on first-pass success has been less clear. A recent large meta-analysis of more than 12 studies has shown that GVL is superior in obtaining full glottic views but, for experienced laryngoscopists, first-pass success was not superior to conventional laryngoscopy.7 In ED patients, GVL was associated with a lower first-attempt success rate than DL, although the groups were not matched.3 Single-center ED observational studies, however, have shown that the GlideScope is superior to DL for intubating ED patients, and success has increased over time.37,44 The GlideScope causes less cervical spine movement than conventional DL and provides better glottic exposure in patients with strict cervical spine precautions. The C-MAC videolaryngoscope (Fig. 1.14; Karl Storz Endoscopy, Tuttlingen, Germany)

Fig. 1.13.  GlideScope Titanium handles incorporate similar video elements in a lightweight titanium blade with a narrower side profile. Connection to the video display is made by a USB-style cord. (Courtesy Verathon, Seattle.)

Fig. 1.14.  The C-MAC videolaryngoscope (Karl Storz Endoscopy, Tuttlingen, Germany) uses an integrated complementary metal oxide semiconductor (CMOS) video chip to capture a video image from near the distal tip of an otherwise conventional laryngoscope blade. The image  is conveyed to a video screen, where it is viewed by the intubator.   (From Walls RM, Murphy MF, eds: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins; with permission.)

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Critical Management Principles

Fig. 1.16.  The Clarus Video System incorporates a curved stylet containing a CMOS chip video camera surrounding by a malleable but rigid protective metal sheath. Images are displayed on a video screen attached to the handle. The screen can swivel for optimal viewing as the stylet is inserted into the mouth. (Courtesy Clarus Medical, Minneapolis.)

Fig. 1.15.  King Vision videolaryngoscope integrates a single-use, curved video blade attached to a top-mounted display. The blades come in two versions, those with endotracheal tube channels, for advancing the endotracheal tube, and those without. (Courtesy Calvin A. Brown III, MD.)

incorporates a complementary metal oxide semiconductor (CMOS) video chip into a range of laryngoscope blades to enhance glottic views. Images are displayed on a high-resolution monitor, with image- and video-saving capabilities. The traditionally shaped C-MAC blade can be used as a direct laryngoscope by a trainee while a supervisor observes the video output, providing an excellent tool for teaching DL. One ED-based direct comparison of the C-MAC and GVL has suggested that they perform similarly during emergency intubation.45 Compared to DL the C-MAC provides better visualization of the glottic inlet, higher rates of first-pass success, and outperforms DL when rescuing a failed first attempt using DL.3,6,46 The King Vision videolaryngoscope (King Systems, Noblesville, IN) is a single-use, lightweight device with a detachable (and reusable) screen that sits on top of a disposable video blade (Fig. 1.15). There are two blade types, one with an integrated tube channel and one without; the latter requires the operator to place the ETT manually. In simulated difficult airways using cadaveric subjects, the King Vision results in higher success rates and faster tube placement compared to DL.47 The McGrath Series 5 is a cordless videolaryngoscope with an integrated screen and handle configuration. There are several other models of videolaryngoscopes with various sizes and features, such as disposable sheaths or blades, and at various price points.48,49 Individual evaluation of these devices is important in selecting the best videolaryngoscope for an individual practitioner or practice group. In 2012, videolaryngoscopes were chosen as the first device for airway management in nearly 40% of all intubations.3 Overall, videolaryngoscopy offers the promise of transforming laryngoscopy and has the potential to render DL obsolete.

Fiberoptic and Video Intubating Stylets Several semirigid fiberoptic and video intubating stylets also are available. The SOS is the most studied of these, although a newer video device (Clarus Video System, Clarus Medical, Minneapolis;

Fig. 1.17.  The Shikani optical stylet (SOS) with endotracheal tube mounted. The eyepiece and battery pack are at the right. (Courtesy Clarus Medical, Minneapolis, MN.)

Figs. 1.16 and 1.17) based on the same principles likely will perform as well as or better than its fiberoptic forerunner. The ETT is placed over a semirigid stylet, consisting of a metal sheath with a distally placed video image acquisition system, then advanced through the mouth and over the tongue in the midline and into the trachea under fiberoptic or video visualization. The SOS appears to cause less movement of the cervical spine than conventional laryngoscopy during intubation with inline stabilization (Fig. 1.16). A smaller version, the Levitan scope (Clarus Medical), uses a light-emitting diode (LED)–illuminated fiberoptic stylet to facilitate intubation by direct laryngoscopy. The device is recommended by the manufacturer to facilitate first-pass success when a limited glottic view is obtained by DL. In the only study comparing the Levitan scope with the gum elastic bougie, however, the two devices achieved similar success.

Flexible Intubating Scopes Intubation using a flexible endoscope is an important option for certain difficult airways, particularly in those with distorted upper airway anatomy, such as angioedema or blunt anterior neck trauma. These scopes long relied on fiberoptic technology, but this has largely been supplanted by miniaturized, high-quality video systems (Fig. 1.18). After appropriate patient preparation, the endoscope is passed through the vocal cords under continuous visualization, serving as an introducer for an ETT, which is then placed through the glottis. Flexible endoscopic examination also is used for airway assessment to determine whether intubation is needed, such as for patients with smoke inhalation or supraglottitis. Intubation of morbidly obese patients, those with distorted airway anatomy (eg, penetrating or blunt anterior neck injury), or those with a fixed cervical spine deformity can be achieved with the flexible endoscope with topical anesthesia and judicious sedation, thus preserving the patient’s ability to breathe until intubation has been achieved. Scopes also have been used successfully to intubate through an ILMA, and video systems likely would work well in this application also.

CHAPTER 1  Airway

Fig. 1.18.  New video flexible bronchoscopes are now available and integrate fully with the C-MAC high-resolution display. (Courtesy Karl Storz Endoscopy, Tuttlingen, Germany.)

Fig. 1.19.  The Ambu aScope is a new, fully disposable video flexible bronchoscope with an integrated suction port and working channel for suctioning and instillation of local anesthetic. Airway images are viewed via a reusable digital display. (Courtesy Calvin A. Brown III, MD.)

There is a significant learning curve for flexible endoscopic intubation, and proficiency with this device requires training and practice. Fortunately, endoscopic examination of the upper airway to the level of the vocal cords is a similar skill set as that needed to maneuver the scope through the cords to intubate. This is an important alternative method to obtain real-life experience with insertion and manipulation of the scope. Only approximately 1% of ED patients are managed with a flexible bronchoscope, possibly reflecting reluctance to select this instrument if the operator does not feel sufficiently trained or competent. Flexible bronchoscope intubations are the method of choice for most patients with upper airway obstruction.3 The role of flexible endoscopic intubation in the ED will likely expand as obesity increases in the population and, increasingly, difficult airways are handled in the ED without backup. The transition from fiberoptic to CMOS video technology will make these flexible scopes more durable and less prone to fogging, both desirable attributes for emergency intubation. Although the cost required to purchase and maintain a flexible endoscope can make it challenging for some emergency departments, single-use flexible videoscopes, such as the Ambu aScope (Ambu, Columbia, MD), provide a less costly option (Fig. 1.19). Emergency clinicians should have immediate access to flexible endoscopes and should acquire training and regular practice in their use.

providing a seal that permits ventilation of the trachea with minimal gastric insufflation. In elective anesthesia, the LMA has an extremely high insertion success rate and low complication rate, including a low incidence of tracheal aspiration. Evaluations of LMA insertion by experienced and inexperienced personnel consistently have shown ease of insertion, high insertion success rates, and successful ventilation. The LMA may be a viable alternative to endotracheal intubation for in-hospital or out-of-hospital treatment of cardiac arrest, particularly when responders are inexperienced airway managers. At a minimum, the device may serve a temporizing role equal or superior to BMV until definitive airway management can be achieved. The LMA Supreme (Teleflex Inc., Morrisville, NC) is a more robust LMA with a rigid angled tube, similar to an ILMA; it offers an orogastric tube channel and higher seal pressures than the standard LMA. This likely is the best version for general ED use. A noninflatable LMA, the i-gel (Intersurgical, Berkshire, England), has a viscous gel cuff and does not require inflation (Fig. 1.20). It is available in a variety of sizes for adults and pediatric patients. The device is placed blindly, and insertion depths are marked on the side of the device. It has an integrated bite block and channel for passage of an orogastric tube. Initial experience with the device, even with minimally trained novice users, has been promising, with high insertion success rates and shorter insertion times when compared with the LMA or laryngeal tube airway.50 The ILMA is designed to facilitate intubation through the mask after correct placement (Fig. 1.21). It differs from the LMA in two main ways. First, the mask is attached to a rigid, stainless steel ventilation tube that is curved almost to a right angle, and the mask incorporates an epiglottic elevator at its distal end. Placement of the ILMA results in successful ventilation in almost 100% of cases and successful subsequent intubation in 95%. The ILMA can also be used for ventilation and intubation in obese patients, with similarly high success rates. The ILMA has a special ETT and stabilizer rod to remove the mask over the ETT

Extraglottic Devices Laryngeal Mask Airways.  LMAs collectively include a number of commercially available ovoid, silicone mask devices designed to seal above the glottis and permit ventilation through a central channel with a standard bag. There are several models available, and attributes differ among the models, but use and success rates are very similar. The most widely used is the original LMA. Reusable and single-use configurations, conventional and intubating formats, are offered by several manufacturers. The mask is inserted blindly into the pharynx and then inflated,

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Fig. 1.20.  The i-gel mask airway (Intersurgical, Berkshire, England) does not have an inflatable cuff and is available in sizes from infant to adult. (Courtesy Dr. Calvin A. Brown, III.)

Fig. 1.21.  The intubating laryngeal mask airway is modified to facilitate insertion of an endotracheal tube after placement and ventilation have been achieved. The epiglottic elevator (arrowhead) lifts the epiglottis to allow passage of the special endotracheal tube (arrow).

after intubation has been accomplished, but intubation can be comparably successful with a conventional polyvinylchloride (PVC) ETT. The ILMA is a better device than the standard LMA for use in the ED because it facilitates rescue ventilation and intubation. Intubation through the ILMA has compared favorably in terms of success with DL and is superior in the hands of novice intubators. When the ILMA is placed, intubation can be performed blindly or guided by a lighted stylet or fiberoptic scope. The ILMA comes only in sizes 3, 4, and 5 and so is not suitable for use in patients weighing less than about 30 kg (≈66 lb). For smaller patients, the standard LMA, which has sizes down to size 1 (infant), should be used. Intubation can be achieved through the standard LMA, but the success rate is significantly less than with the ILMA. As experience with the LMA and ILMA grows, it is likely that there will be increasing adoption of the LMA as a primary airway management technique by nonhospital first responders, and the ILMA has been gaining attention as a primary rescue device in the ED. Newer

LMA-style devices, the Ambu air-Q and Aura-I, can act as standard LMAs for ventilation and oxygenation but can facilitate blind intubation with standard adult endotracheal tubes. Both work well intubating a difficult airway, especially when augmented by flexible endoscopy.51 In the ED, the primary use of the LMA or ILMA is as a rescue technique to provide a temporary airway when intubation has failed, bag ventilation is satisfactory, and the patient has been paralyzed and may require prolonged ventilation or be in need of immediate airway management. In such cases, the LMA is one of numerous acceptable devices. In the can’t intubate, can’t ventilate situation, cricothyrotomy is indicated, but an ILMA may be placed rapidly in an attempt to achieve ventilation (converting the situation to can’t intubate, can ventilate), as long as this is done in parallel with preparations for cricothyrotomy and does not delay initiation of a surgical airway. The standard LMA may also offer advantages for providing ventilation in unconventional positions, such as when the patient is lying on his or her side. In the out-ofhospital setting, where concerns about esophageal placement of ETTs have focused interest on methods used for airway management, the LMA and Combitube offer excellent placement and ventilation characteristics and may be preferable to endotracheal intubation in this setting, especially when intubation is relatively infrequently performed.53 If the patient is in a difficult position in terms of intubation access, the LMA may facilitate more rapid ventilation. Other Extraglottic Devices.  In addition to LMAs, which sit above the glottis, there are several other types of EGDs. These are inserted blindly posterior to and beyond the laryngeal inlet to provide oxygenation and ventilation through side ports while inflatable balloons occlude the pharynx above and the esophageal inlet below. Because of their positioning behind the larynx, these often are called retroglottic devices. The prototype for these devices is the esophagotracheal Combitube. The Combitube is a plastic double-lumen tube with one lumen functioning as an airway after esophageal insertion and the other lumen functioning as a tracheal airway. The tube is placed blindly into the esophagus, and proximal and distal balloons are inflated sequentially through different ports. The balloons prevent escape of ventilatory gases upward through the pharynx or downward through the esophagus. The tube is placed into the esophagus, as designed, almost 100% of the time, but both lumens are patent, so ventilation is still possible if the tube has been placed inadvertently into the trachea. It comes in two sizes and is used only in patients taller than 48 inches. The King laryngeal tube airway (King LT; King Systems) has a single port through which distal and proximal low-pressure balloons are inflated as a single step (Fig. 1.22). The distal balloon, when seated correctly, obstructs the cervical esophagus, and the larger proximal balloon obstructs the hypopharynx, preventing regurgitation of air. A newer version of the King LT has a posterior channel that accepts a nasogastric tube, which can be passed through the device into the stomach for aspiration of gastric contents. The King LT is disposable, rapidly placed, easy to use by operators of various skill levels and has seal pressures similar to those of standard LMAs.52 All extraglottic devices can be safely left in place for 4 hours without mucosal pressure damage. Another device, the Rusch EasyTube (Teleflex, Morrisville, NC), is similar in concept and appearance to the Combitube but is available in 41 Fr and a smaller 28-Fr size for smaller patients. All retroglottic devices are primarily a substitute for endotracheal intubation for non–ETT-trained personnel, but are also used by advanced airway managers as a way to oxygenate and ventilate patients during crash and failed airway scenarios. These devices should be considered temporary measures, do not protect against aspiration, and should be exchanged for a definitive airway as soon as possible.

CHAPTER 1  Airway

Fig. 1.22.  King laryngeal tube incorporates two cuffs but inflates with a single bolus of air. There is a channel in the back for passage of an orogastric tube. It is available in a variety of adult and pediatric sizes.

Surgical Airway Management Needle Cricothyrotomy With Transtracheal Jet Ventilation With the advent of newer airway devices, especially videolaryngoscopes, surgical airway management, which always has been distinctly uncommon, is required even less frequently.3 Needle cricothyrotomy, which involves the insertion of a large needle (ideally, a large catheter designed for this purpose) through the cricothyroid membrane into the airway for transtracheal ventilation, may have a limited role in pediatric airway management (see Chapter 161). However, it is rarely, if ever, the right choice for an adult airway emergency and will not be discussed further here.

Cricothyrotomy Cricothyrotomy is the creation of an opening in the cricothyroid membrane through which a cannula, usually a cuffed tracheostomy tube, is inserted to permit ventilation. The techniques and variations thereof have been well described elsewhere.53 When surgical airway management is required, cricothyrotomy is the procedure of choice in the emergency setting, where it is faster, more straightforward, and more likely to be successful than tracheotomy. Cricothyrotomy is indicated when oral or nasal intubation is impossible or fails and when BMV or EGD cannot maintain adequate oxygen saturation (the can’t intubate, can’t ventilate situation). Previous large series have established that the incidence of cricothyrotomy is approximately 1% of all ED intubations, with the highest rates seen in trauma patients.16 More recent ED-based intubation surveillance has suggested that the rate of salvage cricothyrotomy—a surgical airway performed after another technique was attempted first—has dropped and is now approximately 0.3%.3 Cricothyrotomy is relatively contraindicated by distorted neck anatomy, preexisting infection in the neck, and coagulopathy; these contraindications are relative, however, and establishment of the airway takes precedence over all other considerations. The procedure should be avoided in infants and young children, in whom anatomic limitations make it exceedingly difficult. Studies have suggested that approximately five practice cricothyrotomies on a simulator or animal model are sufficient to achieve at least baseline capability with the procedure, although training intervals for skill maintenance have not been well defined.

Fig. 1.23.  Melker universal cricothyrotomy kit. (Courtesy Cook Critical Care, Bloomington, IN.)

A number of commercial kits and devices are used to perform percutaneous cricothyrotomy. Percutaneous cricothyrotomy with the Seldinger technique appears comparable to formal open cricothyrotomy in terms of ease of learning and success rates. Patients with clear landmarks are the best candidates for this procedure because patient obesity or altered anatomy may lead to paratracheal tube placement. In patients with indistinct landmarks or for novice operators, standard open cricothyrotomy may be more successful. Bougie-assisted cricothyrotomy, during which a bougie is placed through the cricoid incision and used as a guidewire for ETT placement, may also improve surgical airway success for inexperienced practitioners. The safety and effectiveness of the many cricothyrotomy kits and devices have not been clearly established. Only two percutaneous cricothyrotomy sets currently on the market have the ability to place a cuffed tracheostomy tube. One is a dedicated Seldinger cricothyrotomy set; the other is a combination set that has all necessary equipment for a Seldinger percutaneous cricothyrotomy or standard surgical cricothyrotomy (Melker universal cricothyrotomy kit; Cook Critical Care, Bloomington, IN; Fig. 1.23).

OUTCOMES Phase II of the National Emergency Airway Registry study (NEAR II) of almost 9000 ED intubations has reported that most patients were intubated by emergency clinicians using RSI, with overall success rates of 96%.16 The NEAR classification system characterizes potentially adverse occurrences during intubation as adverse events. In the NEAR study, the overall rate of adverse events was 12%, with recognized esophageal or mainstem intubation and hypotension being the most common.7 Phase III of the NEAR project has reported on more than 17,500 adult ED intubations over an 11-year period (2002–2012).3 This latest multicenter report has revealed that first-attempt success (FPS) was 83%. However, over the course of data collection, this significantly increased from 80% in the first 3 years to 86% during the last 3 years. Emergency clinicians managed 95% of all patients, and 99% were successfully intubated within three attempts. Adverse event rates (12%) were identical to those of NEAR II, with recognized esophageal intubation and hypotension requiring IV fluids being the most common. The incidence of cricothyrotomy dropped from 0.9% to 0.5%. No studies have evaluated the long-term outcome of intubated ED patients.

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Critical Management Principles

KEY CONCEPTS • Anticipating the clinical course of the patient’s condition and assessing the likelihood of deterioration are crucial to the decision to intubate, especially if the patient is to leave the ED for a period of time (eg, interfacility transfer, diagnostic testing). • Assessment of the patient for potential difficulty with intubation, bag-mask ventilation (BMV), ventilation using an extraglottic device (EGD), and cricothyrotomy is an essential step before a neuromuscular blockers is administered. The mnemonics LEMON, MOANS, RODS and SMART can serve as useful aids. • In the absence of a crash patient (agonal, unresponsive to laryngoscopy) or difficult airway, rapid sequence intubation (RSI) is the airway management method of choice for ED patients. • Tube placement confirmation using end-tidal CO2 (ETCO2) is essential after intubation; failure to detect adequate quantities of exhaled CO2 is evidence of esophageal intubation until proven otherwise.

• Videolaryngoscopy has transformed intubation by eliminating many of the traditional anatomic barriers to direct laryngoscopy. Practitioners responsible for emergency airway management should transition their routine airway management from direct laryngoscopy to videolaryngoscopy. • Cricothyrotomy is indicated in the can’t intubate, can’t oxygenate failed airway situation and should be performed without hesitation once this has been identified. Delays may increase the likelihood or severity of hypoxic injury to the patient. • Emergency airway management is evolving, and modern intubators should be aware of these fundamental changes. Videolaryngoscopy is replacing direct laryngoscopy as the tool of choice for emergency airway management. Etomidate is used in more than 90% of all RSIs, and rocuronium use has been increasing. EGDs, such as laryngeal mask airways, are continually evolving, offering additional options for rescue oxygenation of the failed airway.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 1  Airway

REFERENCES 1. Williams TA, et al: Prehospital continuous positive airway pressure for acute respiratory failure: a systematic review and meta-analysis. Prehosp Emerg Care 17:261–273, 2013. 2. Vital FM, Ladeira MT, Atallah AN: Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev (5):CD005351, 2013. 3. Brown CA, 3rd, et al: Techniques, success, and adverse events of emergency department adult intubations. Ann Emerg Med 65:363–370, 2015. 4. Tachibana N, Niiyama Y, Yamakage M: Incidence of cannot intubate-cannot ventilate (CICV): results of a 3-year retrospective multicenter clinical study in a network of university hospitals. J Anesth 29:326–330, 2015. 5. Norskov AK, et al: Diagnostic accuracy of anaesthesiologists’ prediction of difficult airway management in daily clinical practice: a cohort study of 188 064 patients registered in the Danish Anaesthesia Database. Anaesthesia 70:272–281, 2015. 6. Sakles JC, et al: A comparison of the C-MAC video laryngoscope to the Macintosh direct laryngoscope for intubation in the emergency department. Ann Emerg Med 60:739–748, 2012. 7. Griesdale DE, et al: Glidescope® video-laryngoscopy versus direct laryngoscopy for endotracheal intubation: a systematic review and meta-analysis. Can J Anaesth 59:41–52, 2012. 8. Walls RM, Murphy MF, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott Williams & Wilkins, pp 8–21. 9. Bair AE, et al: Feasibility of the preoperative Mallampati airway assessment in emergency department patients. J Emerg Med 38:677–680, 2010. 10. El-Orbany MI, et al: Head elevation improves laryngeal exposure with direct laryngoscopy. J Clin Anesth 27:153–158, 2015. 11. Racine SX, et al: Face mask ventilation in edentulous patients: a comparison of mandibular groove and lower lip placement. Anesthesiology 112:1190–1193, 2010. 11a.  Kheterpal S1, Martin L, Shanks AM, et al: Prediction and outcomes of impossible mask ventilation: a review of 50,000 anesthetics. Anesthesiology 110(4):891–897, 2009. 12. Martin LD, et al: 3,423 emergency tracheal intubations at a university hospital: airway outcomes and complications. Anesthesiology 114:42–48, 2011. 13. Touma O, Davies M: The prognostic value of end tidal carbon dioxide during cardiac arrest: a systematic review. Resuscitation 84:1470–1479, 2013. 14. Chou HC, et al: Tracheal rapid ultrasound exam (T.R.U.E.) for confirming endotracheal tube placement during emergency intubation. Resuscitation 82:1279–1284, 2011. 15. Saglam C, Unluer EE, Karagoz A: Confirmation of endotracheal tube position during resuscitation by bedside ultrasonography. Am J Emerg Med 31:248–250, 2013. 16. Walls RM, et al: Emergency airway management: a multi-center report of 8937 emergency department intubations. J Emerg Med 41:347–354, 2011. 17. Ramachandran SK, et al: Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J Clin Anesth 22:164–168, 2010. 18. Weingart SD, Levitan RM: Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med 59:165–175, 2012. 19. Rudlof B, Faldum A, Brandt L: Aventilatory mass flow during apnea : investigations on quantification. Anaesthesist 59:401–409, 2010. 20. Weingart SD, et al: Delayed sequence intubation: a prospective observational study. Ann Emerg Med 65:349–355, 2015. 21. Hu R, Liu JX, Jiang H: Dexmedetomidine versus remifentanil sedation during awake fiberoptic nasotracheal intubation: a double-blinded randomized controlled trial. J Anesth 27:211–217, 2013. 22. Ingrande J, Lemmens HJ: Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth 105(Suppl 1):i16–i23, 2010. 23. Osta WA, et al: Nicotinic acetylcholine receptor gene expression is altered in burn patients. Anesth Analg 110:1355–1359, 2010. 24. Patanwala AE, et al: Comparison of succinylcholine and rocuronium for first-attempt intubation success in the emergency department. Acad Emerg Med 18:10–14, 2011. 25. Chong ID, et al: Long-acting neuromuscular paralysis without concurrent sedation in emergency care. Am J Emerg Med 32:452–456, 2014. 26. Dmello D, et al: Outcomes of etomidate in severe sepsis and septic shock. Chest 138:1327–1332, 2010. 27. Gu WJ, et al: Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies. Chest 147:335–346, 2015. 28. Tekwani KL, et al: A comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: a prospective, randomized study. Ann Emerg Med 56:481–489, 2010.

28a.  Sprung CL, Annane MD, Keh D, et al: Hydrocortisone therapy for patients with septic shock. N Engl J Med 358(2):111–124, 2008. 29. Ballow SL, et al: A standardized rapid sequence intubation protocol facilitates airway management in critically injured patients. J Trauma Acute Care Surg 73:1401–1405, 2012. 30. Sener S, et al: Ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial. Ann Emerg Med 57:109–114, 2011. 31. Jalota L, et al: Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ 342:d1110, 2011. 32. Heffner AC, et al: The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care 27:417.e9–417.e13, 2012. 33. Heffner AC, et al: Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation 84:1500–1504, 2013. 34. Heffner AC, et al: Predictors of the complication of postintubation hypotension during emergency airway management. J Crit Care 27:587–593, 2012. 35. Kim JK, et al: Comparison of tracheal intubation with the Airway Scope or Clarus Video System in patients with cervical collars. Anaesthesia 66:694–698, 2011. 36. Haut ER, et al: Spine immobilization in penetrating trauma: more harm than good? J Trauma 68:115–120, 2010. 37. Sakles JC, et al: Tracheal intubation in the emergency department: a comparison of GlideScope® video laryngoscopy to direct laryngoscopy in 822 intubations. J Emerg Med 42:400–405, 2012. 38. Brown CA, 3rd, et al: Improved glottic exposure with the Video Macintosh Laryngoscope in adult emergency department tracheal intubations. Ann Emerg Med 56:83– 88, 2010. 39. Wayne MA, McDonnell M: Comparison of traditional versus video laryngoscopy in out-of-hospital tracheal intubation. Prehosp Emerg Care 14:278–282, 2010. 40. Sakles JC, et al: Comparison of the reusable standard GlideScope® video laryngoscope and the disposable cobalt GlideScope® video laryngoscope for tracheal intubation in an academic emergency department: a retrospective review. Acad Emerg Med 21:408–415, 2014. 41. Jones PM, et al: A randomized comparison of the GlideRite® Rigid Stylet to a malleable stylet for orotracheal intubation by novices using the GlideScope®. Can J Anaesth 58:256–261, 2011. 42. Sakles JC, Kalin L: The effect of stylet choice on the success rate of intubation using the GlideScope video laryngoscope in the emergency department. Acad Emerg Med 19:235–238, 2012. 43. Aziz MF, et al: Routine clinical practice effectiveness of the Glidescope in difficult airway management: an analysis of 2,004 Glidescope intubations, complications, and failures from two institutions. Anesthesiology 114:34–41, 2011. 44. Sakles JC, et al: Improvement in GlideScope® Video Laryngoscopy performance over a seven-year period in an academic emergency department. Intern Emerg Med 9:789–794, 2014. 45. Mosier J, et al: A comparison of the GlideScope video laryngoscope to the C-MAC video laryngoscope for intubation in the emergency department. Ann Emerg Med 61:414–420, 2013. 46. Sakles JC, et al: The C-MAC® video laryngoscope is superior to the direct laryngoscope for the rescue of failed first-attempt intubations in the emergency department. J Emerg Med 48:280–286, 2015. 47. Murphy LD, et al: Comparison of the King Vision video laryngoscope with the Macintosh laryngoscope. J Emerg Med 47:239–246, 2014. 48. Noppens RR, et al: Evaluation of the McGrath Series 5 videolaryngoscope after failed direct laryngoscopy. Anaesthesia 65:716–720, 2010. 49. Liu L, et al: Tracheal intubation of a difficult airway using Airway Scope, Airtraq, and Macintosh laryngoscope: a comparative manikin study of inexperienced personnel. Anesth Analg 110:1049–1055, 2010. 50. Castle N, et al: Assessment of the speed and ease of insertion of three supraglottic airway devices by paramedics: a manikin study. Emerg Med J 27:860–863, 2010. 51. Jagannathan N, et al: A randomized trial comparing the Ambu® Aura-i with the air-Q intubating laryngeal airway as conduits for tracheal intubation in children. Paediatr Anaesth 22:1197–1204, 2012. 52. Burns JB, Jr, et al: Emergency airway placement by EMS providers: comparison between the King LT supralaryngeal airway and endotracheal intubation. Prehosp Disaster Med 25:92–95, 2010. 53. Vissers RJ, Bair AE: Surgical airway techniques. In Walls RM, Murphy MF, Luten RC, editors: Manual of emergency airway management, ed 4, Philadelphia, 2012, Lippincott, Williams & Wilkins, pp 193–219.

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Critical Management Principles

CHAPTER 1: QUESTIONS & ANSWERS 1.1. Which of the following is considered unreliable for assessing the need to establish an artificial airway? A. Absence of a gag reflex B. Absence of swallowing on command C. Level of consciousness D. Patient’s ability to phonate E. Pooling of secretions in the oropharynx Answer: A. The gag reflex can be absent in up to 25% of normal adults. Moreover, there is no evidence that the presence or absence of a gag reflex corresponds to a patient’s ability to protect his or her airway. It should therefore not be used as an indicator of the need for intubation. 1.2. Which of the following is the most reliable overall method for confirmation of correct tube placement after endotracheal intubation? A. Bulb aspiration B. Chest and gastric auscultation C. Chest radiography D. Detection of colorimetric or quantitative end-tidal carbon dioxide (ETco2) E. Measurement of exhaled volume Answer: D. Detection of ETco2 after endotracheal intubation is the most reliable of the options listed for the confirmation of tube placement. (A fiberoptic scope passed through the endotracheal tube, with visualization of the tracheal rings, is the gold standard but is not generally required.) Limitations of colorimetric CO2 detection should be appreciated in cardiac arrest patients. In these situations, a bulb aspiration device may provide helpful information, even though this technique is generally not as reliable as ETco2 detectors. The other listed options, traditional as they may be, are prone to failure and should not be relied on for confirmation of tube placement. 1.3. During rapid sequence intubation (RSI), what is the optimal time to wait between the administration of a pretreatment drug and administration of the induction agent and neuromuscular blocking agent? A. 1 minute B. 2 minutes C. 3 minutes D. 4 minutes E. 5 minutes Answer: C. Three minutes is considered the optimal time to wait between the administration of a pretreatment drug and administration of the induction agent. If the clinical situation does not allow for this length of time between administrations, there may still be some benefit to administration of the pretreatment agent. 1.4. In which of the following conditions is succinylcholine contraindicated? A. Acute burn < 5 days B. Acute head injury secondary to motor vehicle accident

C. Acute spinal cord injury < 5 days D. Renal failure with a serum potassium level of 4.7 mEq/L E. Stable multiple sclerosis Answer: E. Succinylcholine has been associated with severe fatal hyperkalemia when administered in specific clinical circumstances. The risk of succinylcholine-induced hyperkalemia in patients with denervation syndromes begins with the onset of disease and continues indefinitely. With respect to acute burns, trauma, stroke, spinal cord injury, and intraabdominal sepsis, the risk of hyperkalemia with succinylcholine use becomes evident 5 days after the onset of injury or disease process. Succinylcholine is not contraindicated in renal failure; however, known elevations in the potassium level may warrant use of another neuromuscular blocking agent. 1.5. Which of the following conditions prevents reliable use of colorimetric capnometers for the detection of esophageal intubation in 25% to 40% of cases? A. Acute asthma exacerbation B. Cardiac arrest C. Chronic obstructive pulmonary disease exacerbation D. Head trauma E. Pneumonia Answer: B. Colorimetric capnometers detect CO2 and can be used to confirm tracheal intubation. The absence of CO2 detection indicates failure to intubate the trachea and necessitates reintubation, except in the low-perfusion state of cardiac arrest, when quantities of CO2 returned to the lungs may be insufficient to produce a color change in the capnometer. This situation occurs in 25% to 40% of intubated cardiac arrest patients. The placement of the tube needs to be confirmed by clinical means, revisualizing placement, or the tube needs to be removed and the patient reintubated. 1.6. Until how long after an acute burn is succinylcholine considered safe to use for RSI? A. 30 minutes B. 12 hours C. 24 hours D. 48 hours E. 5 days Answer: E. Succinylcholine can produce severe (and fatal) elevations in serum potassium levels after administration in patients with burns. However, this vulnerability to succinylcholine-induced hyperkalemia is not clinically significant until at least 5 days after the acute burn. As a result, succinylcholine remains the paralytic of choice if rapid sequence intubation occurs less than 5 days after the burn.

C H A P T E R 2 

Mechanical Ventilation and Noninvasive Ventilatory Support Todd A. Seigel PERSPECTIVE Invasive and noninvasive ventilation are essential components in the management of critically ill patients. Some patients require support for respiratory failure or as part of comprehensive management of critical illness, whereas other patients require assistance primarily for airway protection. The reasons for initiating ventilatory support are varied and will influence ventilation strategy, hemodynamics, sedation strategy, and subsequent clinical course. The decision to intubate is discussed in Chapter 1 and in other chapters throughout this text in the context of individual conditions. This chapter describes the modalities and techniques of noninvasive and invasive mechanical ventilation.

PRINCIPLES OF MECHANICAL VENTILATION Physiology of Positive-Pressure Breathing Spontaneous breathing in normal patients is based on the initiation of negative intrathoracic pressure. It is mediated by contraction and relaxation of the diaphragm in concert with the intercostal muscles. Contraction of the diaphragm and intercostal muscles increases the intrathoracic volume, creating negative pressure in the chest cavity and causing inhalation, whereas relaxation of the diaphragm and recoil of the chest wall decreases intrathoracic volume, which increases pressure in the chest cavity and results in passive exhalation. The amount of force required to generate adequate inspiration is influenced by the work of breathing; when the work of breathing increases, patients may be unable to generate enough negative force to sustain successful respiration and will require ventilatory support. Unlike spontaneous breathing, invasive and noninvasive mechanical ventilation are based on the delivery of humidified air with positive pressure. The amount of positive pressure required for adequate ventilation is dependent on the patient’s respiratory effort, ranging from mild assistance to full support. Inhalation occurs by driving air into the lungs under positive pressure; air is passively exhaled when the chest wall recoils. Transition from negative-pressure breathing to positivepressure breathing affects cardiovascular and pulmonary physiology and can have significant clinical consequences. Pressure changes in the thoracic cavity directly affect pressures in the chambers of the heart. During spontaneous inspiration, decreased intrathoracic pressure augments venous return and preload. Cardiac output is increased, and there is an increased pressure gradient between the left ventricle and aorta. With the initiation of positive-pressure ventilation (PPV), the opposite occurs— venous return is diminished, cardiac output falls, and there is a decreased pressure gradient between the left ventricle and aorta. Relative hypotension can occur after ventilatory support has been initiated, and this may be exaggerated in patients with clinical hypovolemia or vasodilatory states.

Invasive Mechanical Ventilation: Control Variable and Ventilator Mode The primary considerations regarding initiation of mechanical ventilation relate to how each breath should be delivered. This includes how a breath is defined, the size, duration, and frequency of the breath, and the degree of interaction the patient has with the ventilator. How the ventilator defines a breath is referred to as the control variable. The ventilator can give breaths based on delivery of a set pressure or a set volume, referred to as pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV), respectively. The amount of time over which the breath is delivered is defined as the inspiratory time, and the speed at which air travels through the circuit is defined as inspiratory flow rate. In PCV, a set amount of pressure is applied to the airway to expand the lungs for a specified amount of time. During PCV, the target pressure and inspiratory time are set by the provider, whereas the delivered tidal volume and inspiratory flow rate vary as functions of dynamic lung compliance and airway resistance. Ability to control the pressure delivered to the lungs is particularly useful to prevent barotrauma, which is described in more detail below. In addition, because inspiratory flow is not fixed, PCV may improve ventilator synchrony in intubated patients with a high respiratory drive. A significant disadvantage of PCV is that as tidal volume changes with acute changes in lung compliance, it can neither be guaranteed nor limited. PCV offers advantages over VCV in clinical conditions in which control of airway pressure is strictly mandated. This includes patients with the potential to develop dynamic hyperinflation and intrinsic positive endexpiratory pressure (PEEP) such as patients with severe asthma or respiratory failure from chronic obstructive pulmonary disease (COPD). In VCV, a breath is defined by delivery of a set tidal volume to the lungs. Inspiratory volume and flow rate are set by the provider, and inhalation ends once a preset tidal volume has been delivered. The inspiratory time is a function of the set flow rate. Lung pressure—peak inspiratory pressures (PIPs) and end-inspiratory alveolar pressures—vary based on lung compliance and set tidal volume. The main benefit to the use of VCV is the ability to control tidal volume and minute ventilation, but VCV may cause spikes in peak pressures when compliance of the respiratory system is poor. Clinically, poor respiratory system compliance occurs in conditions that increase lung or chest wall stiffness, including pulmonary edema, acute respiratory distress syndrome (ARDS), pneumothorax, and obesity. The choice between pressure-cycled ventilation and volumecycled ventilation is driven by the underlying indication for mechanical ventilation. Volume-cycled ventilation should be used when strict control of tidal volume is mandated. Specifically, this includes patients with known ARDS, in whom low tidal volume strategies have been proven to reduce mortality. In addition, 25

26

PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

TABLE 2.1 

Features of Pressure Control Versus Volume Control SET PARAMETERS

VARIABLE PARAMETERS

CLINICAL IMPLICATIONS

CLINICAL CONDITIONS

Pressure-controlled ventilation (PCV)

Pressure target, inspiratory Tidal volume, inspiratory time, RR, PEEP flow rate

Controls airway pressure, but tidal volume becomes a function of lung compliance (no guaranteed tidal volume or minute ventilation). Allows estimation of end-inspiratory alveolar pressure based on ventilator settings. Variable inspiratory flow helpful for patients with high respiratory drive

Severe asthma COPD, salicylate toxicity

Volume-controlled ventilation (VCV)

Tidal volume, RR, inspiratory flow pattern, inspiratory time

Guaranteed delivery of tidal volume, but may result in high or injurious lung pressures. End-inspiratory alveolar pressure cannot be reliably estimated and must be measured (plateau pressure)

ARDS, obesity, severe burns

PIP, end-inspiratory alveolar pressure

ARDS, Acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; PIP, peak inspiratory pressure; PEEP, positive end-expiratory pressure; RR, respiratory rate.

patients with decreased chest wall compliance should be placed on VCV to ensure that adequate tidal volume is delivered. This includes patients with morbid obesity or severe chest wall burns. Conversely, in conditions in which strict control of airway pressure is desired, pressure-cycled ventilation should be used. As detailed earlier, this occurs most often in patients with asthma or COPD. In addition, because inspiratory flow is not limited in pressure-cycled ventilation, this strategy may be preferred to volume-cycled ventilation in patients with a high respiratory drive such as patients with salicylate overdose. For patients who do not require strict control of pressure or volume, similar ventilation mechanics can generally be achieved with pressure-cycled or volume-cycled ventilation (Table 2.1). Newer ventilators can deliver breaths that combine volume and pressure strategies, referred to as dual-control ventilation. A common dual-control method of ventilation is pressure-regulated volume control (PRVC). A variation of volume control, PRVC is set to deliver a specific tidal volume while simultaneously minimizing airway pressure. Unlike with strict volume control, pressure is measured and modulated by the ventilator with each breath to ensure the delivery of the preset tidal volume. In addition, a pressure limit is set, and the ventilator sounds an alarm when that pressure has been exceeded. Theoretically, this combines the advantages of pressure and volume control to ensure the delivery of a specific tidal volume while the airway pressure is monitored. That said, because the ventilator is set to deliver a specific tidal volume, the disadvantages of volume-cycled ventilation persist. In addition, elevations in airway pressure are still possible and must be addressed if acute changes in respiratory system compliance occur. This mode of ventilation has not been specifically studied but likely does not offer significant advantage over traditional volume- or pressure-cycled ventilation, particularly if strict parameters for airway pressure are desired. The term ventilator mode refers specifically to the amount of respiratory support provided by the ventilator. The most common ventilator modes can be categorized on the basis of how often the ventilator will initiate a breath for the patient and can be divided broadly into continuous mechanical ventilation (CMV), intermittent mechanical ventilation (IMV), and continuous spontaneous ventilation (CSV). CMV and IMV are intended to provide patients with a specific minimum number of preset breaths as defined by the ventilator and can be delivered via pressure or volume control methods. Conversely, in CSV, no mandatory breaths are delivered to a patient; the size and rate of the breaths are determined by the effort of the patient and are augmented with applied pressure to

the airway. These methods are compared in Table 2.2. Other, more complex modes of ventilation include proportional assist ventilation (PAV) and airway pressure release ventilation (APRV), although these generally are not used in the emergency department (ED). CMV is intended to provide full ventilatory support for patients with little or no spontaneous respiratory activity continuous delivery of preset breaths. However, if a patient generates negative pressure, representing respiratory effort, on CMV, that breath will be assisted by the ventilator. For this reason, CMV is also referred to as assist-control (A/C) ventilation. In this mode, patients can trigger a breath at any rate but will always receive at least the preset number of breaths. Notably, when a patient initiates a breath, the assisted breath that he or she receives is the full volume breath as set on the ventilator. For the promotion of ventilator synchrony, a spontaneous patient-initiated breath will take priority over a preset breath, meaning that if the ventilator is set to deliver 12 breaths/min, a breath is provided every 5 seconds in the absence of spontaneous inspiratory effort. When the patient makes a spontaneous effort, the ventilator provides an additional breath and the timer resets for another 5 seconds. A/C ventilation is the most useful initial mode of mechanical ventilation in ED patients, because many patients are initially paralyzed and sedated and do not interact with the ventilator. One of the biggest challenges with A/C ventilation, however, is that patient-initiated breaths are not proportional to patient effort; when inspiratory effort is detected, a full-sized breath is delivered. Clinically, this requires adequate sedation of patients when ventilated in the A/C mode to prevent spontaneous respiratory efforts that will result in hyperventilation, air trapping, hypotension, and poor ventilator synchrony.1 Synchronized intermittent mandatory ventilation (SIMV) provides intermittent ventilatory support to patients by delivering mandatory and spontaneous breaths. In SIMV, a mandatory breath is given at a preset rate, but the breath is synchronized as much as possible with spontaneous patient effort. Similar to A/C, the patient will receive at least the minimum number of preset mandatory breaths; if the patient provides no effort, the preset number of breaths will be given. If a patient has a rate of spontaneous respirations lower than the set rate, the ventilator will provide the preset number of full breaths but will deliver as many as possible in synchrony with patient effort. In these scenarios, there is little difference between A/C and SIMV. If a patient has a rate of spontaneous respirations higher than the preset rate, the patient receives all preset full breaths at the set rate, but additional

CHAPTER 2  Mechanical Ventilation and Noninvasive Ventilatory Support

TABLE 2.2 

Selecting Ventilator Strategy: Features of Potential Options MODE

PARAMETERS SET BY PROVIDER

CLINICAL SCENARIO

CONTINUOUS MECHANICAL VENTILATION (CMV) Assist-control (A/C)

Pressure or volume control, RR

Paralyzed or deeply sedated patient, sedated patients with intermittent spontaneous respiratory effort; can lead to hyperventilation

INTERMITTENT MANDATORY VENTILATION (IMV) Synchronized intermittent mandatory ventilation (SIMV)

Pressure or volume control, RR (backup rate)

Patients with regular but poor spontaneous respiratory effort; if used in deeply sedated patients, set RR will need to be higher

CONTINUOUS SPONTANEOUS VENTILATION (CSV) Pressure-support ventilation (PSV)

Level of pressure support, PEEP

Spontaneously breathing patients with good respiratory effort requiring minimal ventilatory support

Continuous positive airway pressure (CPAP)

Level of CPAP

Alert, spontaneously breathing patients with immediately reversible causes of respiratory distress; COPD and ACPE are classic indications for noninvasive ventilation

Bi-level positive airway pressure (BL-PAP)

IPAP and EPAP

Similar to CPAP

ACPE, acute cardiogenic pulmonary edema; COPD, chronic obstructive pulmonary disease; EPAP, expiratory positive airway pressure; IPAP, inspiratory positive airway pressure; PEEP, positive end-expiratory pressure; RR, respiratory rate.

breaths generated by the patient will be at a volume determined by his or her respiratory effort. Additional breaths can be given via pressure support (see later). SIMV is useful for patients who are sedated but who have weak respiratory efforts and combats some of the challenges of using A/C in awake patients. The delivery of extra breaths consistent with patient respiratory effort attenuates the effects of air trapping and hyperventilation and may promote patient comfort. CSV, in contrast to A/C or SIMV, delivers a breath only on a patient-initiated trigger. On a ventilator, the only way to eliminate mandatory delivery of preset breaths is via pressure support ventilation (PSV); therefore, CSV and PSV are essentially the same for patients who remain intubated with no intrinsic spontaneous respiratory effort. PSV is designed to support patients’ spontaneous respiratory effort by delivering an applied pressure to the airway on the trigger of a breath. The amount of pressure required to support a full breath is variable and depends on the patient’s ability to overcome the work of breathing. When inspiratory flow stops, signaling the end of inhalation, pressure support ceases and exhalation is allowed to proceed spontaneously. The level of pressure support is the only parameter determined by ventilator settings; inspiratory flow, inspiratory time, and tidal volume are determined by patient effort. This mode of ventilation most closely resembles normal spontaneous breathing and, for this reason, promotes patient control and comfort. In the ED, PSV is rarely used for intubated patients because most patients who require intubation are unable to breathe spontaneously and effectively and may have failed noninvasive support before intubation. PSV may prove to be most useful in awake and interactive patients who have been intubated for temporary airway protection rather than for respiratory failure. If PSV is used, careful monitoring and ventilatory alarms are needed to ensure against undetected hypoventilation or apnea.

Positive End-Expiratory Pressure Regardless of the ventilatory mode chosen, PEEP is often used during invasive mechanical ventilation. PEEP refers to the maintenance of positive airway pressure after the completion of passive exhalation. During acute respiratory failure, lung volumes are typically decreased; the application of PEEP increases functional

residual capacity (FRC), improves oxygenation, and decreases intrapulmonary shunting. The use of PEEP also reduces portions of nonaerated lung that may contribute to the development of ventilator-induced lung injury. Notably, PEEP increases intrapulmonary and intrathoracic pressures and may affect pulmonary and cardiovascular physiology. Potential adverse effects of PEEP include decreased cardiac output, lung overdistention, and pneumothorax. Applied PEEP must be specifically differentiated from intrinsic PEEP (iPEEP, or auto-PEEP), which may result from improper assisted ventilation when adequate time is not allowed between breaths for complete exhalation. This is discussed later.

Noninvasive Techniques Noninvasive positive-pressure ventilation (NPPV) is the delivery of CSV via sealed mask rather than endotracheal tube. As with PSV, the ventilator is set to provide a defined level of pressure when a patient takes a breath; inspiratory flow and inspiratory time are completely patient-mediated. The most common types of noninvasive ventilation in the ED are continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BLPAP). BiPAP, a term commonly used for BL-PAP, is the proprietary name of a portable device that uses this method of noninvasive ventilation rather than a term for the ventilation itself (Philips Respironics, Murrysville, PA). CPAP provides constant positive pressure throughout the respiratory cycle, whereas BL-PAP alternates between higher pressure during inspiration (IPAP) and lower pressure during expiration (EPAP). Although, strictly speaking, CPAP applies positive pressure to the airway during inspiration, the amount of inspiratory assistance is minimal. Conversely, just as with invasive mechanical ventilation, IPAP augments patient respiratory effort by decreasing the work of breathing during inspiration, whereas EPAP acts as PEEP to maintain FRC and alveolar recruitment. Notably, although PEEP, CPAP, and EPAP all represent positive airway pressure at the end of expiration, PEEP, by convention, refers to pressure applied during invasive mechanical ventilation, whereas CPAP is the application of positive pressure (invasively or noninvasively) during spontaneous breathing. The terms are occasionally used interchangeably.

27

28

PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

MANAGEMENT Decision Making: Noninvasive Versus Invasive Ventilation The decision to intubate carries significant implications for patients, including potentially life-threatening complications related to airway management and subsequent complications related to intensive care unit (ICU) care. NPPV is an appealing option for patients requiring ventilatory assistance with potentially reversible conditions when tracheal intubation is not immediately necessary or as a therapeutic adjunct for patients with “do-notintubate” directives.2 In appropriately selected patients, NPPV obviates intubation in more than 50% of cases and improves survival. Relative contraindications include decreased level of consciousness, lack of respiratory drive, increased secretions, hemodynamic instability, and conditions such as facial trauma that would prevent an adequate mask seal. Although the need for emergent intubation is generally a contraindication to treatment with noninvasive ventilation, noninvasive ventilation has been shown to improve preoxygenation prior to intubation when compared to standard methods of oxygen delivery.3,4 If NPPV is initiated, patients should be reassessed frequently for progress of therapy, tolerance of the mode of support, and any signs of clinical deterioration that would indicate a need for intubation. Patients most likely to respond to NPPV in the ED are those with more readily reversible causes of respiratory distress such as COPD exacerbation or cardiogenic pulmonary edema in which fatigue is a significant factor. Robust evidence has supported the use of NPPV for both conditions. In patients with acute COPD exacerbations, NPPV decreases the need for subsequent intubation with a number needed to treat (NNT) of 4, decreases hospital length of stay, and improves mortality (NNT = 10) when compared with standard therapy.5 Treatment failure, defined as a subsequent need for intubation, is predicted by a Glasgow Coma Scale score of less than 11, sustained arterial pH less than 7.25, and tachypnea greater than 35 breaths/min.3 A recent large study has confirmed prior findings regarding the benefit of NPPV over invasive ventilation, but highlighted the need for appropriate patient selection in that a failed trial of NPPV was associated with higher mortality when compared to patients who received immediate intubation.6 In patients with acute cardiogenic pulmonary edema (ACPE), NPPV reduces the work of breathing while simultaneously improving cardiac output. The application of NPPV causes elevations in intrathoracic pressure that decrease left ventricular (LV) ejection pressure and LV transmural pressure, which results in afterload reduction. In addition, decreases in RV preload may improve LV compliance via ventricular interdependence. Compared with standard therapy, multiple studies and several metaanalyses have confirmed a decreased need for intubation, as well as decreased mortality for patients with ACPE treated with NPPV. Benefits were found to be independent of whether patients received CPAP or BL-PAP and, despite suggestions from early clinical data, no increased rate of acute myocardial infarction occurred in patients receiving any form of NPPV.7-9 Although either modality can be used, a recent ED-based study has suggested faster clinical improvement with BL-PAP.10 Specific predictors of failure of NPPV in those with congestive heart failure (CHF) have not been systematically examined. Evidence regarding the use of NPPV in other patients with respiratory compromise, including asthma and pneumonia, is limited. Several small studies have suggested that NPPV may be beneficial for patients with acute asthma exacerbations by improving lung function, decreasing bronchodilator requirements, and shortening overall hospital length of stay, suggesting a potential role for NPPV in these patients.11,12 Studies have failed to establish

a definitive role for NPPV in pneumonia, and the presence of pneumonia has been shown to be an independent risk factor for failure of noninvasive ventilation.13 In a recent trial of NPPV for pneumonia, increased heart rate and decreased Pao2/Fio2 ratio after 1 hour of therapy predicted failure of NPPV. In addition, the duration of NPPV prior to intubation was associated with in-hospital mortality, suggesting that early intubation is preferable for patients who do not rapidly improve on noninvasive therapy.14

Approach to Initial Ventilator Settings Noninvasive Ventilation Initial settings for noninvasive ventilation should be determined by the amount of ventilatory assistance required by the patient, as well as patient comfort and cooperation with therapy. The first consideration in the use of NPPV is whether to provide support in the form of CPAP or BL-PAP. As described earlier, there is no clear benefit of one over the other. Support may be provided by a full-face (oronasal) mask or nasal mask; this choice is determined by patient comfort, ability of the patient to cooperate, and the need for the patient to cough effectively or speak. Notably, nasal masks have been associated with higher leak rate and decreased patient comfort3; therefore, I recommend a full-face mask as the first method for novice patients. Inspiratory support (IPAP) is initiated at 10 cm H2O and expiratory support (EPAP) at 5 cm H2O. Subsequent titration of these parameters is based on the patient’s clinical response, particularly pressure tolerance, respiratory rate, and oxyhemoglobin saturation. Although blood gas analysis is confirmatory, improvements in the patient’s clinical condition can be observed by decrease in work of breathing, good patient-ventilator synchrony, and patient report. If required, EPAP and IPAP can be adjusted by 1 to 2 cm H2O at a time based on the clinical response. If the work of breathing is unchanged, increases in IPAP can reduce hypercarbia by increasing tidal volume and minute ventilation, and increases in EPAP can improve oxygenation by combating atelectasis and promoting alveolar recruitment. IPAP greater than 20 cm H2O should be avoided, because it can be uncomfortable and can cause gastric insufflation.

Mechanical Ventilation of the Intubated Patient For the intubated patient, initial ventilator settings should facilitate ventilation that improves gas exchange, promotes ventilator synchrony, and minimizes the potential for complications. For an apneic or paralyzed patient, full ventilatory support is required; therefore, A/C is the recommended mode of initial ventilation for emergent patients. Specific required settings depend on whether the patient is receiving PCV or VCV, but the principles underlying the selection of settings are similar. Reasonable initial ventilator settings should deliver a tidal volume of 6 to 8 mL/kg of estimated ideal body weight (IBW) at rate of 12 to 14 breaths/min. If VCV is used, tidal volume can be set directly and, if PCV is used, tidal volume is determined by adjusting the targeted pressure to be delivered. Regardless of VCV or PCV, initial pressure targets should not exceed 30 cm H2O. The initial Fio2 should be set at 1.0 but generally can be adjusted down quickly to maintain an oxygen saturation of 90% or greater. PEEP is routinely given and is set initially at 5 cm H2O.1 Settings for specific clinical conditions such as status asthmaticus are discussed later.

Ongoing Management Mechanical ventilation requires monitoring and regular adjustment to ensure appropriate gas exchange, safe delivery of desired tidal volume, and prevention of barotrauma and acid-base

CHAPTER 2  Mechanical Ventilation and Noninvasive Ventilatory Support

derangement. Changes to ventilator settings are guided dynamically by multiple factors, including pulse oximetry, end-tidal carbon dioxide (ETco2) measurement, ventilation pressures, and blood gas levels. For the adequacy of ventilation to be monitored, capnography must be used, and arterial blood gases should be measured 15 to 20 minutes after the initiation of ventilatory support to correlate ETco2 with Pco2. Notably, venous blood gas levels generally correlate well with the pH of arterial samples, although this correlation may be unreliable in critically ill patients.15 The correlation of Pco2 between venous and arterial samples is less reliable.16,17 Although there is variation in agreement between capnography and blood gas values, capnography generally correlates well with the Pco2 of arterial samples and should be used for ventilator adjustment after initial correlation has been established. Recent data have confirmed the importance of continuous capnography, demonstrating a decrease in the use of blood gases and resultant, significant cost savings.18 If capnography is difficulty to perform or otherwise noncorrelative, arterial blood gas determination remains the definitive test for evaluating Pao2 and Pco2. Minute ventilation can subsequently be altered by adjusting the tidal volume or respiratory rate. To avoid oxygen toxicity, Fio2 should be reduced at the earliest opportunity to the lowest level that provides acceptable oxygen saturation (>90%). In many cases, increases in PEEP will allow better oxygenation for a given Fio2 but may worsen hypotension or increase intrathoracic pressure. In addition to maintaining adequate gas exchange, care should be taken to ensure that that pressure in the ventilator circuit (including the lungs) is appropriate. The two main measurements of pressure during mechanical ventilation are the PIP and plateau pressure (Pplat). The PIP measures the maximum amount of pressure in the ventilator circuit during a breath cycle. It reflects lung compliance and airway resistance, including resistance in the circuit itself. In PCV, because pressure limits are preset, the PIP is the sum of the set pressure target and PEEP. In this case, PIP also reflects the maximum amount of pressure in the alveoli, an important determinant in the development of ventilator-induced lung injury (VILI). In VCV, PIP can be influenced greatly by airway resistance and therefore is not reflective of the maximal alveolar pressure. Rather, maximal alveolar pressure is determined on the ventilator at the end of inspiration by means of an inspiratory hold. At the end of inspiration, flow in the circuit stops; therefore, there is no pressure from resistance in the circuit. Pplat is measured at that time, so it represents maximal end-inspiratory alveolar pressure in VCV. Acute increases in measured pressure indicate increased airway resistance or changes in compliance of the respiratory system (eg, those associated with pneumothorax) and can indicate potentially dangerous clinical deterioration. Notably, acute changes in resistance or compliance that are seen directly in VCV as increased pressure would manifest as an acute decreases in tidal volume if the patient were on PCV (where pressure has been previously set). Decreases in lung pressure, conversely, indicate decreased resistance or decreased airflow in the ventilatory circuit and should prompt investigation of the ventilator circuit for leaks. Large or sudden decreases in pressure suggest disconnection of the ventilator circuit or unintended extubation. For patients with underlying respiratory failure secondary to increased airway resistance such as in asthma or COPD, more gradual decreases in PIP are associated with clinical improvement.

Sedation and Analgesia of the Ventilated Patient Aside from specific ventilator management, considerations in the care of the intubated patient include analgesia and sedation, potential neuromuscular paralysis, and secretion management.

After intubation, the primary goals of care in the ED are sustained, effective ventilation and patient comfort. Intubation, mechanical ventilation, and paralysis are a significant cause of pain and anxiety for patients, and analgesia and sedation are required to promote patient comfort and patient-ventilator synchrony. In initiating sedation (see later), sedation should be titrated to comfort and therapeutic goals, avoiding oversedation and undersedation. The desired level of sedation will differ based on patient tolerance and the clinical scenario; assuming that comfort is maintained, lighter sedation may be useful in patients requiring serial neurologic examinations, whereas deep sedation is required for any patient who is paralyzed. Several clinical scales, including the Richmond Agitation-Sedation Scale (RASS), have been established and validated for this purpose. Sedation should be maintained at the highest RASS score at which the patient is comfortable (between 0 and −5) and should be serially readdressed. Any paralyzed patient should remain deeply sedated (Table 2.3). Recent ED-based data have demonstrated that the use of rocuronium during rapid sequence intubation (RSI) is associated with increased time to adequate sedation, as well as decreased overall dose of sedation, when compared to patients intubated with succinylcholine.19,20 This is likely because emergency clinicians wrongly ascribe the patient’s inability to move or respond to adequate sedation, rather than to the paralysis. When rocuronium is used for RSI, additional sedation should be immediately administered after intubation confirmation. After RSI, additional neuromuscular blocking agents (NBMAs) should generally be used only when poor ventilator synchrony interferes with ventilation sedation and analgesia. This may be particularly true in patients with ARDS, in whom the use of NMBAs has been associated with shorter duration of ventilation and improved mortality.21 With proper sedation and analgesia, however, neuromuscular blockade usually is not required. If

TABLE 2.3 

Richmond Agitation-Sedation Scale (RASS) SCORE

TERM

DESCRIPTION

+4

Combative

Overtly combative, violent, immediate danger to staff

+3

Very agitated

Pulls or removes tube(s) or catheter(s), aggressive

+2

Agitated

Frequent nonpurposeful movement, fights ventilator

+1

Restless

Anxious, but movements not aggressive or vigorous

Calm

Alert and calm

−1

0

Drowsy

Not fully alert, but has sustained awakening (>10 sec)

−2

Light sedation

Briefly awakens with eye contact to voice (5–10 days with regular dosing) will require tapering doses as their painful condition improves to prevent withdrawal. Neglecting to address this issue early in a patient’s treatment can lead to difficulties with safe and tolerable treatment termination. Addiction is a potential risk associated with prolonged opioid use and often limits use. The term addiction refers to a neurobiologic disease, with many factors influencing its development and manifestations. Addiction is characterized by compulsive drug use, continued use despite harm, and craving. The term pseudoaddiction describes patient behaviors that may occur when pain is undertreated. Patients with unrelieved pain may become focused on obtaining medications and otherwise seem to engage in inappropriate drug-seeking behaviors. Behaviors such as illicit drug use and deception can occur in the patient’s efforts to obtain relief (Box 3.4). Pseudoaddiction can be distinguished from true addiction in that it resolves when pain is effectively treated.

BOX 3.4 

Addiction Behaviors BEHAVIORS TYPICALLY SPECIFIC TO ADDICTION • • • • • • • • •

Injecting oral formulations Concurrent abuse of alcohol or illicit drugs Selling or diversion of prescription drugs Prescription forgery Obtaining drugs from nonmedicinal sources Repeated dose escalation Repeated visits to other EDs without informing prescriber Drug-related deterioration in function at work or socially Repeated resistance to changes in therapy, despite evidence of adverse drug effects

BEHAVIORS LESS SPECIFIC TO ADDICTION • • • • • • •

Aggressive complaining about the need for more drug Drug hoarding during periods of reduced symptoms Requesting specific drugs Openly acquiring drugs from other medicinal sources Occasional dose escalation or noncompliance Unapproved use of a drug to treat another symptom Resistance to change in therapy associated with tolerable side effects, with expression of anxiety related to the return of severe symptoms

ED, Emergency department.

CHAPTER 3  Pain Management

Drug-Seeking Behavior.  Some patients feign or exaggerate pain to receive opioids to abuse medications or sell them to others, defined as diversion. Opioid abuse and diversion is a growing problem, and the rapid growth in the number of opioid prescriptions has played a large role in rising rates of abuse and diversion.21-25 In recognition of diversion and abuse, many states have developed prescription monitoring programs that allow for an exchange of information among providers to detect frequent opioid prescriptions.26-33 Prescription-monitoring programs are effective in reducing the number of opioid prescriptions given to patients at risk for abuse or diversion as long as providers consider these data as a routine and integrated practice for patient care. Some states require consultation with the registry before prescribing opioids, but EDs may be exempted from this requirement because of patient flow issues. A physician’s impression of behaviors believed to be associated with patient drug-seeking is associated with a reduction in the treatment of the patient’s pain (see Box 3.3).34 Unfortunately, prescriber perceptions are often complicated by differences between the health care provider and patient in regard to factors such as socioeconomic class, ethnic and racial background, and age, making them frequent sources of bias in the treatment of pain. Care must be taken to recognize these factors and consider their impact on treatment decisions. A thorough evaluation of drug-seeking behavior for a patient includes a review of medical records, prescription registries, and contact with other providers (eg, hospitals, primary care physicians), as available and appro­ priate. Unless confirmation can be derived through such an evaluation, a patient with apparent acute pain, as from a new injury, should be given the benefit of the doubt and treated as though her or his pain is legitimate. Patients with chronic conditions that can cause acute pain, such as dental caries, some gastrointestinal (GI) syndromes, or long-standing back pain, should be offered alternative pain management approaches, such as nerve block, nonopioid analgesia, or symptomatic treatment with antispasmodic agents until they can resume care with their usual health care providers. Primary providers, chronic pain specialists, and others should note patient contracts, prescription details, and patterns of possible nontherapeutic drug-seeking behavior in the medical record, using objective terms and descriptions. Patients with repetitive episodes of drug-seeking events may benefit from a multidisciplinary review to establish specific recommendations for their care when they present to anyone other than their primary pain provider. Patients who are noncompliant with their treatment contract, and those who are known to be abusing or diverting opioid medications, should not be prescribed opioid medications from the ED. Administration of Pain Control.  The goal of opioid administration is to attain effective analgesia, with minimal adverse effects. The effects of opioids vary widely among individuals. There is no ceiling effect to their potency. There is also no standard, fixed, or weight-related dose that will consistently produce a given clinical effect. The correct dose that a particular patient requires at a particular time can only be determined by repeated assessment of the degree of pain relief and adverse effects. The use of opioids, therefore, requires titration based on frequent and accurate assessments (Fig. 3.7). The most effective and safe way to achieve pain relief is to use a deliberate IV titration. The intramuscular (IM) route of administration of opioids has several disadvantages and is not advised for the treatment of acute pain (Box 3.5). The principal limitation of the IM route is its inability to titrate specific doses to desired treatment effects effectively. The time to achieve significant pain relief from an IM injection varies substantially for each patient and offers no therapeutic advantage over an oral medication dosing strategy.

BOX 3.5 

Disadvantages of Intramuscular Opioid Administration Pain on injection Delayed onset of action Inability to predict therapeutic effect Inability to titrate dosage Diurnal variation in level achieved Disease state may affect level achieved Level dependent on intramuscular injection site

Most patients with mild to moderate pain are best treated with oral (PO) opioids. If pain is severe, or if the patient is expected to require multiple doses of an agent for management, an IV route of administration is desirable. If an IV line cannot be established, and the patient cannot tolerate PO medications, the subcutaneous (SC) route is preferable to the IM route. SC injection is less painful than IM injection, with a similar onset of pain relief. Opioids can be delivered through an oral transmucosal or intranasal mucosal route. Buprenorphine can be given via a sublingual route; whereas fentanyl is available in an impregnated sweetened matrix called Fentanyl Oralet (PO transmucosal fentanyl citrate). Nasal fentanyl, butorphanol, and sufentanil also produce rapid clinical effects via nasal mucosal absorption. The optimal use of IV opioids requires the administration of an initial loading dose followed by assessment of the analgesic effect. Frequent (every 5–15 minutes) repeated doses should be administered until analgesia is achieved, followed by doses at regular intervals to prevent the return of significant discomfort (see Fig. 3.7). Specific Agents Morphine.  IV morphine is often the first choice for treatment of acute severe pain in ED patients. Morphine is the opioid analgesic agent with which all other opioids are compared. When administered via the IV route, morphine reaches a peak of action in 15 to 20 minutes, with a half-life of 1.5 to 2 hours in healthy young adults and slightly longer in older adults. Its duration of action is 3 to 4 hours. An appropriate loading dose of morphine for acute severe pain is 0.1 to 0.15 mg/kg IV of ideal body weight, augmented by repeated doses of approximately half the initial dose every 5 to 15 minutes, depending on the severity of the pain and patient response. Morphine is effective by oral administration; however, only 20% of the ingested morphine dose will reach tissues after firstpass metabolism, requiring a dose adjustment approximately five times that of an equipotent IV dose. The formerly held belief that morphine causes more smooth muscle spasm than other opioids, rendering it inappropriate for the treatment of patients with biliary or renal colic, has been thoroughly discredited. Morphine is primarily metabolized by conjugation into a three- and six-conjugate forms in the liver. The three-conjugate form (normorphine) has no opioid analgesic activity and has rarely been associated with CNS side effects (eg, tremors, myoclonus, delirium, seizures). This risk is greatest in older patients and those with renal insufficiency, although it is generally not an issue in the ED. The six-conjugate form morphine metabolite is a strong mu and delta receptor agonist. This form plays an important role in the efficacy and duration of clinical effects. Meperidine.  Meperidine (Demerol), although once widely used, has several disadvantages compared with morphine and other parenteral opioids. Meperidine has no indication for use in the ED, and many hospitals have removed it from their

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PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

Emergency department triage analgesia algorithm Patient inclusion/exclusion criteria Include: patients with acute, traumatic, extremity pain AND site of injury between EITHER ankle to hip OR wrist to shoulder Exclude: patients with chronic or recurrent pain, OR extremity pain of nontraumatic cause

Standardized triage assessment • Severity: record pain scale assessment with 1-10 numeric rating scale • EMS: record absence or treatment by EMS with analgesia agent(s) in medical record • Dosing and therapy: in accordance with presence or absence of deformity and consideration of allergy • Ice/elevate: Ice pack and elevation of affected extremity

Presence of deformity/suspected dislocation • Place IV, saline lock; place order for patient NPO • Notify emrgency clinician; request and confirm one of the following: 1. IV morphine 0.10 mg/kg up to 4 mg 2. IV hydromorphone 0.015 mg/kg up to 1 mg 3. IV fentanyl 2-4 µg/kg up to 100 µg 4. Absence of deformity—medications may be considered If patient refuses IV and/or analgesia, RECORD IN MEDICAL RECORD and consider dosing and therapy in accordance with absence of deformity protocol

Absence of deformity • Notify emergency clinician; request and confirm one of the following: 1. PO ibuprofen 10 mg/kg up to 600 mg 2. PO acetaminophen 15 mg/kg up to 650 mg 3. PO hydrocodone suspension 0.15 mg/kg up to 5 mg 4. PO oxycodone 0.15 mg/kg up to 5-mg tablet If patient refuses PO analgesia, RECORD IN MEDICAL RECORD (ibuprofen not to be used in pregnant patients or patients > 70 years)

Standardized nursing repeat pain assessment • Severity: record pain scale assessment with 1-10 numeric rating scale q1h • Dosing and Therapy: in accordance with presence or absence of deformity after confirmation with emergency clinician Fig. 3.7.  Emergency department triage analgesia algorithm. EMS, Emergency medical services.

formularies. It should not be administered or prescribed in the ED. The greatest disadvantage of meperidine is that it is metabolized by the cytochrome P450 system to the active metabolite, normeperidine. Normeperidine can cause CNS toxicity at therapeutic meperidine doses. Normeperidine has a half-life of 12 to 16 hours and blocks muscarinic receptors, resulting in significant anticholinergic effects, including agitation and delirium. These effects may lead to seizures, hallucinations, and psychosis as the metabolite accumulates. Therefore, meperidine is never the firstline drug for any condition, and it should not be used or prescribed in the ED for the management of pain. Hydromorphone.  Hydromorphone is a semisynthetic derivative of morphine that is a potent analgesic agent, increasingly used in the management of acute pain in the ED.18,35-37 Hydromorphone is the P450 metabolite of hydrocodone and is approximately seven times more potent than morphine, with a similar duration of action. Although 7 mg of morphine is roughly equivalent to 1 mg of hydromorphone, the nursing staff is more likely to administer low milligram doses of hydromorphone to patients with acute pain than higher, equipotent doses of morphine. Care should therefore be taken not to dose hydromorphone excessively, given the propensity for staff to believe that repeated doses of 1 to 2 mg of hydromorphone are relatively benign.

Pruritus, nausea, and vomiting may occur less frequently with hydromorphone administration than with morphine at equianalgesic doses. Hydromorphone is primarily conjugated in the liver to hydromorphone-3-glucuronide (H3G), an inactive metabolite, and is excreted through the renal system. As a result, hydromorphone is better tolerated than morphine, particularly in older patients and those with hepatic impairment. Patients with renal insufficiency may be at some risk of neurotoxicity after prolonged exposure due to H3G accumulation. Patients allergic to morphine do not consistently have cross-reactivity with hydromorphone. Hydromorphone can be given via the IV, SC, PR (per rectum), or PO route. Fentanyl.  Fentanyl is a synthetic opioid that is highly lipophilic; it produces analgesia within 1 to 2 minutes following IV infusion. Fentanyl redistributes rapidly, and its duration of therapeutic action is approximately 30 to 60 minutes. Fentanyl is metabolized by the P450 system into inactive metabolites. Drug accumulation and toxicity may occur after tissue saturation following a prolonged infusion, but this is unlikely to occur during acute therapy. The short duration of action for fentanyl makes it highly titratable and ideal for use in patients who require serial examinations, such as trauma patients with possible occult head injury.

CHAPTER 3  Pain Management

Fentanyl causes less histamine release than morphine and is associated with fewer peripheral effects at an equianalgesic dose. Fentanyl is an excellent choice for treating pain in patients with bronchospastic lung disease or a history of opioid-associated pruritus. Fentanyl is more frequently associated with respiratory depression than morphine. Patients receiving fentanyl infusions should be monitored with direct observation, supplemented by pulse oximetry. The ED use of fentanyl is associated with a very low incidence (1.1%) of serious complications. High or repeated fentanyl doses may produce muscle rigidity. This side effect, so-called rigid chest syndrome, usually occurs with anesthetic doses greater than 15 µg/kg, but also has been reported during use for procedural sedation; it may be so severe that it interferes with respiration. Rigid chest attributed to fentanyl is exceedingly rare at doses typically used for acute analgesia. Chest rigidity, when observed to occur, generally responds to naloxone, but neuromuscular blockade may be necessary if naloxone reversal is not successful. Fentanyl can be administered IV, transmucosally, or transdermally. Nebulized or intranasal fentanyl has been described for the treatment of acute pain in patients without IV access at doses of 3 mcg/kg.38 Oxycodone.  Oxycodone is a strong opioid agonist that is highly bioavailable in an oral form. Oxycodone is widely sold in combination with acetaminophen or aspirin as well as by itself and is also available in long-acting PO formulations. Oxycodone for acute pain should be prescribed in the noncombination form—that is, as pure oxycodone—to allow a balance between oxycodone and a nonopioid medication. Baseline administration of a nonopioid medication, supplemented by titrated doses of oxycodone, will achieve the optimal effect, with the fewest side effects. Oxycodone bioavailability is much higher than other opioids. It is quickly and efficiently absorbed, which may be a causative factor in its high abuse potential. Oxycodone is not available in a parenteral form in the United States, although studies have demonstrated its IV form to be equianalgesic to morphine. Similar to other opioids, the analgesic effects of oxycodone are dose-dependent. A 15-mg oxycodone dose has similar efficacy to 10 mg of IV morphine. The onset of action of PO oxycodone is approximately 20 to 30 minutes. Oxycodone undergoes hepatic metabolism into oxymorphone, a strong opioid agonist that principally accounts for its analgesic effects. Similar to codeine, approximately 10% of patients do not metabolize oxycodone well and are unable to generate the functional metabolite, oxymorphone. This defect in metabolism renders these patients unable to achieve clinically meaningful pain relief with typical dosing strategies and may require very large doses to achieve analgesia. This effect can also be caused by agents that compete with oxycodone for CYP2D6 metabolism, such as neuroleptics, tricyclic antidepressants, and selective serotonin reuptake inhibitors. Cases of serotonin syndrome have been reported when serotonin reuptake inhibitors and oxycodone are given together, likely due to this metabolic interaction. Hydrocodone.  Hydrocodone is metabolized in the liver to hydromorphone and is typically given orally. Hydrocodone provides greater pain relief when combined with acetaminophen or NSAIDs than either component alone. Hydrocodone combinations are less effective than oxycodone-acetaminophen combinations. Hydrocodone clinical analgesia effects typically last 4 hours, with typical dosing of 5 to 20 mg. As with oxycodone, hydrocodone should be prescribed in pure form, not in a combination agent, to allow individual titration of opioid and nonopioid analgesics. Codeine.  Codeine is a weak opioid receptor agonist, usually prescribed in combination with acetaminophen, but has little, if any, role in the modern ambulatory treatment of pain. Codeine is

thought to exert its effects through metabolism into morphine and other active hepatic metabolites. Approximately 10% of the population metabolizes codeine poorly. The effect of this genetic trait is a reduction in active analgesic metabolites and an enhancement in deleterious side effects, including nausea, constipation, and pruritus. Although often historically prescribed for mild to moderate pain, codeine is a poor choice for analgesia due to its tendency to cause side effects, particularly nausea, cramping, and constipation, at doses that provide minimal analgesia. Despite its weak opioid receptor agonist characteristics, codeine has been widely abused. Methadone.  Methadone has several unique features that distinguish it from other opioids. It has no known neurotoxic or active metabolites and has high bioavailability. In addition to being a strong opioid agonist, methadone also has N-methyl-daspartate antagonist and serotonin reuptakeitesnguish it from othMethadone has a slow elimination half-life of 27 hours due to its lipophilicity and tissue distribution. This slow clearance of methadone is the basis for its use in maintenance therapy, given that it can delay the onset of opioid withdrawal symptoms for up to 24 hours. The duration of its analgesic effects is closer to 6 to 8 hours. The discrepancy between the duration of action of analgesia and duration of the prevention of withdrawal symptoms is due to the biphasic elimination of the drug and its redistribution. Naloxone.  Naloxone is an opioid antagonist that reverses the effects of opioids and is used in the setting of adverse, opioidinduced events, such as opioid overdose. It can precipitate physiologic withdrawal in patients who are opioid-dependent. The duration of action of naloxone is approximately 45 minutes, which is shorter than that of most opioids, and care must be taken to monitor for the recurrence of opioid adverse events following this time period. Naloxone can be given IV, IM, SC, or via an endotracheal tube, but is typically given in titrated doses of 0.2 mg IV until reversal of any adverse opioid effect is observed. In the setting of adverse events from opioid treatment, usually respiratory depression, careful titration allows for the smallest dose possible to be administered so that its analgesic effect of the opioid. Naloxone, 0.4-mg autoinjectors, are available for outpatient use to prevent overdose complications. Early results of distributing these autoinjectors to opioid-dependent patients have shown that they are effective in preventing overdose complications. Tramadol.  Tramadol is a synthetic oral analgesic that is a weak mu agonist, with some serotonin and norepinephrine reuptake qualities. Its analgesic properties are thought to be primarily due to mu receptor agonist activity. Tramadol-induced analgesia is partially reversed by naloxone, suggesting that other properties play a role in its therapeutic effects. Tramadol, as a selective mu agonist without kappa agonist effects, should not cause physiologic dependence, although tramadol use is associated with abuse. Tramadol should be used with caution in patients addicted to opioids. Tramadol is metabolized in the liver by the cytochrome P450 system. One of its metabolites, M1, has a greater mu receptor affinity than tramadol and has an elimination half-life of 9 hours. Tramadol appears to have effects on GABA, norepinephrine, and serotonin receptors and the reuptake of the neurotransmitters. These properties may serve to activate descending pain modulation pathways. Compared with traditional opioids, low-dose tramadol has a more favorable side effect profile and may present a lower risk of addiction with chronic use. The most common tramadol side effects are nausea, vomiting, dizziness, orthostatic hypotension, and sedation. These side effects are seen in as many as 17% of patients using the drug for chronic pain, with slightly lower rates in patients receiving controlled-release versions. Tramadol lowers the seizure threshold and therefore provokes isolated seizures in

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PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

selected patients. The use of tramadol with other serotonergic medications (eg, selective serotonin receptor inhibitors, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors) is associated with serotonin syndrome. Tramadol is effective at low doses. At increasing doses, it is associated with nausea and vomiting, limiting its use to low doses and effectively creating a therapeutic ceiling to its clinical use. Tramadol, 37.5 mg, combined with acetaminophen, 325 mg, appears to have similar efficacy to hydrocodone, 5 mg, combined with acetaminophen, 325 mg. As with hydrocodone and oxycodone, tramadol should be prescribed in pure form, allowing accurate dosage adjustment from other agents. Tapentadol.  Tapentadol is a mu opioid agonist and norepinephrine reuptake inhibitor. It is thought to control acute pain via both these pathways. Tapentadol has similar efficacy to oxycodone for the treatment of acute pain, with less frequent nausea and vomiting. Its dual mechanism of action makes it a potentially effective drug for use in chronic pain, although it has not been studied for this. Opioid Agonist-Antagonist Analgesic Agents.  The agonist-antagonist group of opioids was synthesized in an attempt to provide analgesia with little or no respiratory depression or abuse potential. It is believed that the analgesia provided by these agents is caused by agonist action at the kappa receptors, whereas the ceiling for respiratory depression is created by mu receptor antagonism. Agonist-antagonist agents have rates of abuse similar to those for standard opioids and a ceiling effect to their analgesia that limits their use. Clinical application of these drugs is typically in situations in which brief, limited analgesia is needed and respiratory depression is the principal adverse concern, such as in the perinatal period. Nalbuphine is a commonly used agonist-antagonist. The halflife of nalbuphine is 3.5 hours, and the effects of renal or hepatic disease on metabolism are not completely known. The usual therapeutic parenteral dose is 10 mg, which has an analgesic efficacy similar to morphine, 10 mg. As with all other opioids, the dose must be individualized for the specific patient and clinical needs. Opioid Use for Acute Abdominal Pain.  Historically, pain treatment was withheld from patients with abdominal pain to avoid confounding a diagnosis. These recommendations date from the turn of the 20th century, predating modern diagnostic techniques, and have no place in modern emergency care. Multiple studies have confirmed the safety of providing effective opioid analgesia to patients with undiagnosed abdominal pain.

Nonopioid Analgesic Agents Acetaminophen.  Acetaminophen is the first-line agent for the treatment of acute and chronic pain and is the safest pharmacologic option for pain in children and adults. It has a high toxic-to-therapeutic ratio and lacks significant drug interactions compared with other pain medications. Although acetaminophen has been in use since the 1880s, its pharmacologic mechanism of action is unknown. Acetaminophen has known analgesic and antipyretic activity, with no known peripheral antiinflammatory effects. Its activity may be due to the inhibition of prostaglandin endoperoxide H2 synthase and a cyclooxygenase isoenzyme centrally. It may also affect the activation of beta-endorphin centrally. The analgesic actions of acetaminophen are comparable in magnitude to those of NSAIDs. The analgesic effects of the combination of acetaminophen with an NSAID are additive. Acetaminophen is metabolized in the liver primarily through conjugation to a sulfate or glucuronide. A minor pathway for the

oxidative metabolism of acetaminophen produces the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI requires glutathione for detoxification and elimination. Hepatic toxicity can occur when glutathione pathways are overwhelmed by an increase in NAPQI or a decrease in glutathione levels. Hepatic toxicity is rare with ingestions less than 10 g in a 24-hour period, unless underlying liver disease exists or there is concomitant ethanol abuse. In the latter cases, therapeutic doses can cause clinical hepatotoxicity. Acetaminophen is generally well tolerated when used at therapeutic doses. Mild rashes are rarely reported, as is bone marrow suppression, manifested by neutropenia, thrombocytopenia, and agranulocytosis. Its use is associated with several important drug interactions. Many anticonvulsants, including phenytoin, barbiturates, and carbamazepine, induce hepatic microsomal enzymes. Increased conversion of acetaminophen to its toxic metabolite may occur in patients who are taking anticonvulsants, but this is rarely of clinical significance in the context of the usual doses for pain management. Although uncommon, drug interactions resulting in an increased international normalized ratio (INR) have been reported for patients taking acetaminophen and warfarin, particularly among patients taking high doses of acetaminophen (>9100 mg/ week). Chronic use of acetaminophen should be avoided in patients with hepatic or renal disease. Renal failure can worsen with acetaminophen use, but the mechanism is unknown. Patients with a history of salicylate hypersensitivity characterized by urticaria have an 11% cross-reactivity to acetaminophen, and the agent should be used with caution in this group. For mild analgesia and fever reduction, acetaminophen is the first-line agent and is a first choice for use in combination with other agents, usually opioids, in the treatment of patients with more severe pain. The recommended dose of acetaminophen for an adult is 650 to 1000 mg every 4 to 6 hours, not to exceed 4000 mg/day.

Nonsteroidal Antiinflammatory Drugs NSAIDs inhibit cyclooxygenase (COX) and, as a result, the synthesis of prostaglandin, a key mediator of inflammation. The analgesic effect of NSAIDs is peripherally mediated by decreasing prostaglandin levels and effectively raising the threshold of activation of nociceptors. NSAIDs have synergistic effects with opioids and can reduce the amount of opioids needed to achieve pain relief. Two COX isoenzymes mediate prostaglandin synthesis. COX-1 is present in all cells and plays an important role in homeostatic functions. COX-2 is induced by injury or inflammation and generates prostaglandins as part of the inflammatory process. Nonselective NSAIDs inhibit both COX-1 and COX-2, which results in multiple beneficial effects (eg, reduction of inflammation, pain, fever) but also some important undesirable effects. As a group, and because of their common use, NSAIDs are responsible for more serious drug-related side effects than any other class of analgesic drugs. The major side effects of NSAID analgesic agents are GI bleeding, renal failure, anaphylaxis, and platelet dysfunction. Most of these side effects occur in patients who are taking NSAIDs for chronic conditions. It is estimated that more than 100,000 hospital admissions and approximately 16,500 deaths each year from GI bleeding are related to NSAID use for osteoarthritis and rheumatoid arthritis. One survey has estimated that for every 100,000 people taking NSAIDs, there are 300 GI-related deaths, 5 hepatic-related deaths, 4 renal-related deaths, and some congestive heart failure–related deaths. Bone and cartilage healing and repair during NSAID use is a concern in patients with acute fractures. There is limited evidence to suggest that prostaglandins promote bone formation and that

CHAPTER 3  Pain Management

NSAIDs might inhibit the process. This issue has not been thoroughly pursued or established through properly conducted studies. There is no human subject evidence that short-term use of NSAIDs for analgesia after fracture is deleterious to healing. COX also promotes the production of prostacyclin, a vasodilator that increases GI mucosal perfusion. In the stomach, COX-1 increases bicarbonate and mucus production, important for protecting the mucosal lining. Inhibition of COX-1 compromises these protective functions, predisposing patients to ulcerations and bleeding, which are then exacerbated by concomitant NSAIDinduced platelet dysfunction. COX-1 and COX-2 affect the cardiovascular system through the production of endothelial prostacyclin (vasodilatory) and thromboxane (platelet aggregation). Inhibition of COX-1 causes antiplatelet activity that may be cardioprotective by inhibiting thromboxane production more than prostacyclin. Inhibition of COX-2 inhibits prostacyclin production more than thromboxane and may produce prothrombotic effects, increasing the risk of cardiovascular events. In the case of nonselective COX inhibitors, these two effects appear to balance each other out, resulting in few changes in cardiovascular risk in studies of these drugs. In the case of selective COX-2 inhibitors, this may result in an increase in cardiovascular risk and has limited the use of these agents. Prostaglandin produced by COX-1 causes renal vasodilation that maintains renal blood flow and the glomerular filtration rate (GFR). Inhibition of COX-1, especially in volume-depleted patients, can result in a decreased GFR and acute renal insufficiency. Sodium and water retention, hypertension, hyperkalemia, and acute renal failure may also ensue, particularly in patients with congestive heart failure. The most common adverse effect of NSAIDs is GI mucosal injury. In patients taking NSAIDs continuously for 1 year, it has been found that 10% to 60% will develop abdominal pain, dyspepsia, or nausea and 2% to 4% will develop symptomatic ulcers. Risk factors include age, concomitant use of warfarin or corticosteroids, congestive heart failure, diabetes, and coronary artery disease. There is evidence that cytoprotective agents such as misoprostol and proton pump inhibitors reduce this risk. The relative risk for GI side effects varies with various NSAIDs and treatment strategies (Table 3.5). Drug Interactions With Nonsteroidal Antiinflammatory Drugs Aspirin.  NSAIDs may impair the cardioprotective effect of aspirin, although the available evidence is unclear and the use of daily aspirin for cardiac prophylaxis should not deter the prescribing of an NSAID for acute pain or inflammation. Oral Anticoagulants.  The antiplatelet effects of NSAIDs add to the anticoagulant properties of warfarin, compounding the risk of significant bleeding complications, especially from GI ulcers. Furthermore, NSAIDs displace protein-bound warfarin and cause subsequent increases in prothrombin times at a constant warfarin dose. NSAID use is generally avoided in patients who are taking warfarin. Angiotensin-Converting Enzyme Inhibitors.  Concurrent use of NSAIDs with angiotensin-converting enzyme (ACE) inhibitors may impair renal function and impair the antihypertensive effects of ACE inhibitors. Diuretics.  Patients who are taking diuretics have a greater risk of developing renal failure due to NSAID-mediated decreased renal blood flow. Also, the natriuretic response to diuretics depends in part on prostaglandin-mediated vasodilation. Glucocorticoids.  Patients on corticosteroids have an increased risk of peptic ulcer disease. NSAIDs should generally be avoided in patients concurrently taking glucocorticoids unless closely supervised by a physician.

TABLE 3.5 

Risk of Serious Gastrointestinal Effects of Nonselective Nonsteroidal Antiinflammatory Drugs (NSAIDs) NSAID

RELATIVE RISK OF SERIOUS GI TOXICITY

COX-2 inhibitor

0.6

Ibuprofen

1.0

Diclofenac

1.8

Sulindac

2.1

Naproxen

2.2

Indomethacin

2.4

Tolmetin

3.0

Piroxicam

3.8

Ketoprofen

4.2

Ketorolac

24.7

RISK REDUCTION WHEN ADDED TO IBUPROFEN Proton pump inhibitor

0.09

Misoprostol

0.57

GI, Gastrointestinal.

Lithium.  NSAIDs enhance lithium reabsorption and may directly reduce lithium excretion, leading to increased lithium levels. CNS symptoms (eg, drowsiness, confusion, vertigo, convulsions, tremors), cardiac dysrhythmias, and QRS widening are warnings of lithium toxicity. The lithium dosage should be reduced when an NSAID is prescribed.

Nonselective Cyclooxygenase Inhibitor Selection.  NSAIDs combine analgesia and antiinflammatory effects with low abuse potential and many different side effects compared to opioid agents. Oral NSAIDs can be as effective as oral opioids for mild to moderate pain. Parenteral NSAIDs offer little advantage over their PO forms. Different patients respond differently to the beneficial effects and side effects of different NSAIDs. Therefore, some individual experimentation may be necessary to determine the best NSAID choice for a particular patient. No particular NSAID has been proven to be superior for any indication. Drug selection should depend on availability, side effect profile, convenience, and cost. Patients at risk for adverse events using NSAIDs are listed in Box 3.6. Ketorolac Tromethamine.  Ketorolac was the first nonopioid analgesic agent available for parenteral use in the United States. For acute pain management, ketorolac is rarely indicated in the patient able to receive oral medications, given that 60 mg of ketorolac administered IM is not clinically superior to 800 mg of oral ibuprofen. Additionally, NSAID agents can be administered at a fraction of the cost of parenteral routes. The main indication for ketorolac use is in the early treatment of renal colic (accompanied by a loading dose of IV morphine) because of the difficulty in colic patients receiving and tolerating of oral medications. Ibuprofen.  Ibuprofen is the most widely used agent in the NSAID class. It is available over the counter in a variety of preparations, including tablet, liquid suspension, and suppository forms. Ibuprofen is rapidly absorbed from the upper GI tract and has minimal interaction with other medications. The adult analgesic dose is 400 mg. No NSAID is more effective as an analgesic than ibuprofen, 400 mg, including ibuprofen, 600 and 800 mg.

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PART I 

Fundamental Clinical Concepts  | 

SECTION One 

Critical Management Principles

BOX 3.6 

Patients at Risk for Adverse Events During Nonsteroidal Antiinflammatory Drug (NSAID) Therapy 1. Patients with dehydration, hypovolemia or who have impaired renal function are at increased risk for decreasing renal function or renal failure. 2. Patients with liver disease or congestive heart failure—in particular, those already taking ACE inhibitors, ARBs, or diuretics—in whom liver or heart conditions may worsen. 3. Older patients are at enhanced risk for GI and renal events. 4. Patients with asthma and known aspirin hypersensitivity are increased risk of bronchospasm. 5. Women in the third trimester of pregnancy—NSAIDs may prolong gestation or prematurely close the ductus arteriosus. 6. Patients who use tobacco or ethanol with a history of gastritis or peptic ulcer disease are at increased risk for peptic ulcer or GI bleed. ACE, Angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; GI, gastrointestinal.

Skeletal Muscle Relaxants.  Skeletal muscle relaxants have been advocated as an adjunct to analgesics in the management of musculoskeletal pain with a spasm component, principally back pain. Despite the common use of skeletal muscle relaxants, little data exist supporting their role in the treatment of pain. Studies have demonstrated that muscle relaxants, such as cyclobenzaprine, are indistinguishable from ibuprofen in analgesic effect but have an increased side effect profile. Skeletal muscle relaxants should not be used in the treatment of acute musculoskeletal pain as a substitute for proper doses of effective analgesics unless there is a high degree of anxiety accompanying the pain. Benzodiazepines are not recommended for the routine treatment of musculoskeletal pain. In patients exhibiting a great deal of muscle spasm with anxiety, a benzodiazepine such as diazepam, 5 mg tid, or lorazepam, 1 mg bid, may be an effective therapeutic adjunct. Benzodiazepines have hypnotic, anxiolytic, antiepileptic, and antispasmodic properties. Muscle relaxation with these agents is probably due to GABA-mediated presynaptic inhibition at the spinal cord level. Nitrous Oxide–Oxygen Mixtures.  The analgesic and anesthetic properties of nitrous oxide were discovered more than 200 years ago and is one of the original forms of patient-controlled analgesia. Nitrous oxide–oxygen mixtures can be used in the ED or the out-of-hospital care setting to reduce anxiety in patients and manage mild to moderate pain states. Combined with oxygen, a mixture of nitrous oxide and oxygen in a 50 : 50 ratio is safe when self-administered by the patient. Nitrous oxide and oxygen administered by nasal mask have long been used by dentists for the treatment of pain and anxiety. Experience in emergency medicine with nitrous oxide–oxygen mixtures is greatest in the ratio of a 50 : 50 mixture with a selfadministered, hand-held mask. The mechanism of analgesia and anxiolysis with nitrous oxide have not been fully delineated. The nature of its analgesic effect appears to be similar to that of low-dose opioids, although some of the anxiolytic effects of nitrous oxide appear to have more in common with benzodiazepines than opioids. It has been postulated that nitrous exerts an effect on GABA receptors. Nitrous preparations are often administered in a two-tank system, with a fixed-ratio nitrous oxide–oxygen mixture delivered to the patient through a demand valve activated with inhalation

through a facemask or mouthpiece. A negative pressure of 3 to 5 cm H2O must be produced within the mask or mouthpiece to activate the flow of gas, limiting the use of these devices in very small children. Having the patient hold the mask to the face allows him or her to titrate the dose to an effective level. In 10% to 15% of patients, nitrous oxide is ineffective. It is much more potent as an anxiolytic than as an analgesic agent and can be supplemented with other analgesics. Nitrous oxide is a folate antagonist and is strictly contraindicated in pregnant patients. Advanced scavenger systems are necessary to allow the safe use of nitrous oxide in the ED to avoid accumulation and toxicity in health care workers, especially if pregnant. Nitrous oxide–oxygen mixtures are relatively or absolutely contraindicated in patients with a decreased level of consciousness who are unable to follow instructions. Patients with severe chronic obstructive pulmonary disease who retain CO2 should be given nitrous oxide–oxygen mixtures carefully, given that the mixture contains 50% oxygen, which may predispose to hypercapnia. Because nitrous oxide diffuses into body cavities, it can worsen a pneumothorax or bowel obstruction. Minor side effects of nitrous analgesic gas mixtures have been reported in 5% to 50% of patients. The most common adverse effect is lightheadedness, with paresthesias and nausea reported less frequently. No documented adverse hemodynamic effects have occurred with the self-administered forms of this agent. Side effects attributed to nitrous oxide usually resolve within minutes of discontinuation. Ketamine.  Ketamine is a drug that has typically been used primarily as a dissociative anesthetic for procedural sedation; it is one of the most effective and widely used drugs for procedural anesthesia worldwide. Ketamine has also been evaluated for lowdose use as an analgesic.39-41 Low-dose ketamine has been shown to be similar to morphine in its analgesic effect when used alone and as an additive to opioids when used in conjunction with them at doses of 0.1 to 0.3 mg/kg IV (one-tenth to one-third of a typical dose used for dissociative sedation). The principle side effects of ketamine are dysphoria, vomiting, and hypersalivation. Ketamine appears to be effective via the N-methyl-d-aspartate receptor, a different pathway from opioids, acetaminophen, or NSAIDS, giving it potential to affect analgesia when other agents are limited by their adverse effects. It is likely that the use of low-dose ketamine as an analgesic will likely increase as its role and safety are further explored.

Local Anesthesia Mechanism of Action.  Peripheral nerves are responsible for transmitting pain information from pain receptors to the spinal cord. Each fiber consists of an axon surrounded by a covering called the Schwann cell. A myelinated axon is one covered by the projection of a Schwann cell that wraps itself many times around the axon; hence, the term myelin sheath. Local anesthetics are much more effective at penetrating unmyelinated or lightly myelinated fibers than heavily myelinated ones. This difference explains the finding that local anesthetic agents provide sensory block without motor neuron effects (see Table 3.1). Local anesthetic agents reversibly block lipid membrane sodium channels and prevent the influx of sodium ions into the axon, blocking depolarization and the nerve action potential. After injection of a local anesthetic, tissue buffers increase the pH of the solution surrounding the agent, driving much of the watersoluble acidic form to its lipid-soluble nonionic form. The lipidsoluble phase of the drug is able to penetrate the axon lipid membrane, where it then ionizes and enters the sodium channel, blocking the ability of sodium to enter the cell.

CHAPTER 3  Pain Management

TABLE 3.6 

Characteristics of Common Local Anesthetic Agents AGENT

POTENCY (LIPID SOLUBILITY)

DURATION OF ACTION (min)

ONSET

COMMENTS

Procaine

1

60–90

Slow

Solutions of 0.5%–2% used in infiltration and blocks

Tetracaine

8

180–600

Slow

Topical for ophthalmic use

Lidocaine

3

90–200

Rapid

Most commonly used agent; 1.5 times as toxic as procaine

Mepivacaine

2.4

120–240

Very rapid

Less potent and less toxic than lidocaine

Bupivacaine

8

180–600

Intermediate

Long-acting agent used in infiltration and blocks

Etidocaine

6

180–600

Rapid

Twice as toxic as lidocaine; used mostly in epidurals

Adapted from Paris PM, Weiss LD: Narcotic analgesics: the pure agonists. In Paris PM, Stewart RD, editors: Pain management in emergency medicine, Norwalk, CT, 1988, Appleton & Lange.

Classes of Local Anesthetic Agents.  Local anesthetic agents are chemical compounds that consist of an aromatic and amine group separated by an ester (eg, procaine, chloroprocaine, tetracaine) or an amide (eg, lidocaine, mepivacaine, prilocaine, bupivacaine, and etidocaine) intermediate chain. Esters are unstable in solution and are metabolized in the body by the plasma enzyme cholinesterase. The amides, after absorption into the body, are destroyed by enzymes in the liver. The main considerations in the clinical use of these agents are potency, duration of anesthesia, and speed of onset (Table 3.6). The lipid solubility of an agent determines its potency. Less potent local anesthetics must be given in more concentrated forms and in larger doses to achieve an equivalent effect. The duration of anesthetic agent action is determined by its protein-binding affinity to protein in the sodium channel. The speed of onset of any local anesthetic agent is directly related to its diffusion through tissues to the nerve, as determined by its pKa (dissociation constant)—the pH at which 50% is ionized. After injection, the anesthetic agent is in two forms, ionized and nonionized. Only the nonionized form of the drug diffuses into nerves. Therefore, solutions with a low pKa have a more rapid onset of anesthesia. Low tissue pH (5 or 6) in surrounding infected tissue delays the onset of local anesthesia in cases such as abscess incision and drainage by keeping more of the agent in an ionized state. The onset of action can be hastened by the alkalinization of the solution carrying the drug, which also decreases its irritant effect (pain) on injection. This can be done clinically by adding sodium bicarbonate solution to the anesthetic at a ratio determined by the pKa of the agent. Anesthetic agents, except cocaine, are vasodilators, which tend to shorten the duration of anesthesia. Injection of the solutions into vascular tissues not only shortens the duration of anesthesia but also increases systemic absorption and the chance of systemic toxicity when larger doses are used. Therefore, epinephrine is often added to local anesthetic solutions. Allergic Reactions.  True allergies to local anesthetics are rare. When an allergy to local anesthetics is reported, the offending substance is often one of the preservatives used. Because the amide agents and amino ester agents do not cross-react and use different preservatives, a patient may be given a medication from another class if the allergy history is consistent with a specific anesthetic group. In those patients who report they are allergic to all “-caine” anesthetic agents, and the allergy is believed to be legitimate, diphenhydramine can be used as an alternate agent. Diphenhydramine may be used with 1 mL of a 50-mg/mL ampule diluted with saline to 5 or 10 mL (1%–0.5% solution) for local infiltration or nerve block. Diphenhydramine may cause direct

TABLE 3.7 

Guidelines for Maximum Doses of Commonly Used Local Anesthesia Agentsa AGENT Lidocaine HClb Mepivacaine HCl d

Bupivacaine HCl

WITHOUT EPINEPHRINE (mg/kg)

WITH EPINEPHRINE (mg/kg)

3–5

7

8

7c

1.5

3

a

All maximum doses should be reduced 20% to 25% in very young, old, and very sick patients. b A lidocaine level of 0.5 to 2.0 g/mL may be reached for every 100 mg of lidocaine infiltrated for blocks. c Epinephrine adds to the potential cardiac toxicity of this drug. d Not to be used for pudendal blocks or IV regional anesthesia; not recommended for children younger than 12 years. Adapted from Stewart RD: Local anesthesia. In Paris PM, Stewart RD, editors: Pain management in emergency medicine, Norwalk, CT, 1988, Appleton & Lange.

tissue toxicity and should be avoided in areas with poor collateral circulation. Local and Systemic Toxicity Local Toxicity.  Local anesthetic agents, depending on the concentration, can be directly toxic to tissue. Also, it is possible that the use of a vasoconstrictor in an anesthetic solution may produce a reduction in blood flow that could increase wound healing time and vulnerability of the wound to infection. However, this concept has never been formally demonstrated. Systemic Toxicity.  Systemic toxicity of local anesthetics occurs when a sufficient quantity of the drug accumulates in the body so that sodium channel blockade occurs in the heart or brain. There is a dose-related clinical progression of local anesthetic toxicity, from subtle neurologic symptoms to seizures to cardiovascular collapse. All local anesthetics produce systemic toxicity at a sufficiently high blood or CNS concentration. Each local anesthetic has a range of therapeutic safety beyond which systemic toxicity is more likely to occur (Table 3.7). Overdosage of local anesthetics may occur more commonly in patients with large wounds and in patients with a low body mass index. The more lipophilic anesthetic agents (eg, etidocaine, bupivacaine) are more cardiotoxic. Cardiac toxicity may also occur if epinephrine-containing anesthetics are inadvertently injected intravenously. Special care should be exercised in children and

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Critical Management Principles

when performing blocks known to produce high blood levels of the anesthetic agent (eg, intercostal). In pediatric patients, the maximum agent dose should be calculated before administration. A wide variety of symptoms may be experienced from local anesthetic toxicity. These include lightheadedness, headache, tinnitus, paresthesias, muscle spasm, and confusion. In addition, benzocaine has been associated with methemoglobinemia. The degree to which CNS symptoms are experienced is directly related to the blood level of the local anesthetic. CNS toxicity from anesthetic agents may result in seizures. A typical clinical progression usually begins with circumoral paresthesias, dysarthria, and a report of tinnitus or similar auditory phenomenon. These events may be followed by a decreased level of consciousness progressing to confusion, seizures, and coma. Longer acting, more potent agents (eg, bupivacaine, etidocaine) are more likely than lidocaine to cause CNS symptoms at lower blood levels. Local anesthetic-induced seizures should be treated with IV benzodiazepines and may be refractory to normal dosing of neuroleptic medications. Local anesthetic agents also have direct effects on cardiac automaticity, conductivity, contractility, and vascular tone. Management of cardiovascular collapse caused by toxic levels of local anesthetic agents should follow standard advanced cardiac life support guidelines. Unless the overdose is massive, the toxicity should be relatively short-lived, given the redistribution of the lipophilic agents. Reducing the Pain of Local Anesthetic Injection.  Many techniques can be used to reduce the pain of anesthetic injection (Box 3.7). Distraction by manual methods such as scratching, jiggling, or repetitively pinching the skin during needle puncture or injection reduces the discomfort experienced during local anesthetic injection. Injecting the agent slowly is the principle method to reduce injection pain. Injection into the edges of a wound is less painful than injection through intact skin. Warming the anesthetic and the application of a topical anesthetic agent can also decrease the initial sensation associated with needle injection. The addition of sodium bicarbonate to lidocaine prior to injection reduces anesthetic injection pain. A standard solution of sodium bicarbonate (8.4% in 50 mL) can be added to a syringe containing lidocaine in a ratio of 1 : 10 (eg, 1 mL bicarbonate to 10 mL lidocaine, or 0.5 mL to 5 mL). Buffered lidocaine can be stocked in the ED and is effective for up to 1 week.

Topical Anesthesia Topical anesthetics are generally of two types, those that can be applied to intact skin and those used on open skin. Topical agents are particularly useful in pediatric patients intimidated by needles. These agents may help decrease the intensity of superficial stimuli. The long application time and limited analgesia are the principal drawbacks for these strategies. In some patients, however, the

BOX 3.7 

Techniques to Reduce the Pain of Injection • • • • • •

Buffering of local anesthetic agents Counterirritation Slower rate of injection Use of topical anesthetics Warming of solution Distraction techniques

strategy of applying the topical anesthetic and delaying the procedure until there will be less pain can be an effective tool in controlling pain and the response to subsequent interventions. Topical Anesthetics Applied to Intact Skin Eutectic Mixture of Local Anesthetics.  A eutectic mixture

of local anesthetics (EMLA) is a mixture of lidocaine and prilocaine in an alkaline oil mixture in which the anesthetics are primarily in their nonionized form. This format allows diffusion through intact skin. The term eutectic refers to mixtures that result in a melting point higher than that of either agent alone. For clinical use, an EMLA mixture should be applied to the desired area with an occlusive dressing 30 to 60 minutes before the procedure is performed. Heating EMLA for 20 minutes improves analgesia but is less effective than a routine 60-minute application, with or without heat. The duration of action after a 60-minute application is 1 to 5 hours. Indications for the use of EMLA include venipuncture, arterial puncture, lumbar puncture, or arthrocentesis when a 30- to 60-minute delay in performing the procedure is not an impediment. EMLA can be applied in triage, particularly for pediatric patients, with an IV started later in the ED with little or no pain. Ethyl Chloride and Fluoromethane Sprays.  Ethyl chloride and fluoromethane sprays are occasionally used for superficial analgesia. The agents evaporate quickly and cool the skin, providing brief ( 4 mM/L Urine output < 0.5 mL/kg/h Arterial hypotension > 30 min duration, continuous

Regardless of cause. Four criteria should be met.

medications are administered. BP and HR correlate poorly with the cardiac index (CI) in shock and often underestimate the severity of systemic hypoperfusion. Moreover, children with hypovolemic shock frequently demonstrate a normal BP until they rapidly deteriorate. Urine output provides an excellent indicator of vital organ perfusion and is readily available with insertion of a Foley catheter. Measurement of urine output, however, requires 30 to 60 minutes for accurate determination of whether output is normal (>1.0 mL/kg/h), reduced (0.5–1.0 mL/kg/h), or severely reduced ( 38°C or < 36°C 2. Heart rate > 90 beats/min 3. Respiratory rate > 20 breaths/min or Paco2 < 32 mm Hg 4. White blood cell count > 12,000/mm3, < 4,000/mm3, or > 10% band neutrophilia Severe Sepsis SIRS with suspected or confirmed infection and associated with organ dysfunction or hypotension; organ dysfunction may include presence of lactic acidosis, oliguria, and/or altered mental status. Septic Shock SIRS with suspected or confirmed infection with hypotension despite adequate fluid resuscitation requiring vasopressor support; septic shock should still be diagnosed if vasopressor therapy has normalized blood pressure.

HEMORRHAGIC SHOCK

1. Evaluate or treat for ingestion of negative inotropic drug 2. Initiate thyroid function tests 3. Consider treatment for addisonian crisis or steroid withdrawal

Hemorrhage with Hypoperfusion Suspected bleeding with base deficit < −4 mEq/L or persistent pulse rate > 100 beats/min

Rule out pulmonary embolism

Hemorrhagic Shock Suspected bleeding, with at least four criteria listed in Box 6.2

1. Volume resuscitate 2. Emergent abdominal computed tomography or surgical consultation to evaluate for peritoneal inflammation or vascular rupture

Simple Hemorrhage Suspected bleeding with pulse rate < 100 beats/min, normal respiratory rate, normal blood pressure, and normal base deficit

CARDIOGENIC SHOCK

Cardiac Failure Clinical evidence of impaired forward flow of the heart, including presence of dyspnea, tachycardia, pulmonary edema, peripheral edema, and/or cyanosis Cardiogenic Shock Cardiac failure plus four criteria listed in Box 6.2

Treat for anaphylaxis

Fig. 6.1.  Flow diagram to classify undifferentiated shock.

emergency clinician’s ability to accurately diagnose the cause of undifferentiated shock in ED patients, and the finding of hyperdynamic left ventricular function in patients with undifferentiated shock strongly suggests sepsis.6,7 Consensus definitions of shock show the spectrum of hypoperfusion for the following three common causes of shock (Box 6.3): 1. Hemorrhagic shock. The American College of Surgeons has divided hemorrhagic shock into four stages, depending on the severity of blood loss and physiologic response to this loss, but such arbitrary divisions are of little value and are not accurate reflections of degree of hemorrhage in clinical practice.8 A more useful approach defines hemorrhagic shock as being present when systemic hypoperfusion manifests as lactic acidosis or increasing base deficit with concomitant organ dysfunction.

2. Septic shock. International consensus definitions distinguish septic shock from its precursor conditions—systemic inflammatory response syndrome (SIRS), sepsis, and severe sepsis.9 SIRS is often a precursor of shock, but the nonspecific criteria for SIRS are found in a large variety of conditions, many of which are benign, so the clinical context is vital to understanding the significance of these physiologic variations. Although a consensus definition of septic shock requires persistent hypotension after fluid resuscitation, initiation of treatment for empirically diagnosed severe sepsis or septic shock should not await the onset of hypotension. The incorporation of an indicator of tissue hypoperfusion (Box 6.4) into the clinical assessment may improve identification of hypoperfusion, particularly in subtle cases.10 3. Cardiogenic shock. Cardiogenic shock should be thought to be present whenever cardiac failure (ischemic, toxic, or obstructive) causes systemic hypoperfusion that manifests as lactic acidosis with organ dysfunction. Box 6.5 presents the general treatment approach for these three common causes of shock.

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BOX 6.4 

Variables Indicating Tissue Hypoperfusion Hypotension Tachycardia Low cardiac output Dusky or mottled skin Delayed capillary refill Altered mental state Low urine output Low central venous oxygen saturation Elevated lactate level

BOX 6.5 

Clinical Management Guidelines for Three Common Causes of Shock HEMORRHAGIC SHOCK

• Ensure adequate ventilation and oxygenation. • Provide immediate control of hemorrhage, when possible (eg, traction for long bone fractures, direct pressure), and obtain urgent consultation as indicated for uncontrollable hemorrhage. • Initiate judicious infusion of isotonic crystalloid solution (10–20 mL/kg). • With evidence of poor organ perfusion and 30-min anticipated delay to hemorrhage control, begin packed red blood cell (PRBC) infusion (5–10 mL/kg). • With suspected massive hemorrhage, immediate PRBC transfusion may be preferable as the initial resuscitation fluid. • Treat coincident dysrhythmias (eg, atrial fibrillation with synchronized cardioversion).

CARDIOGENIC SHOCK

• Ameliorate increased work of breathing; provide oxygen and positive end-expiratory pressure (PEEP) for pulmonary edema. • Begin vasopressor or inotropic support; norepinephrine (0.5 µg/ min) and dobutamine (5 µg/kg/min) are common empirical agents. • Seek to reverse the insult (eg, thrombolysis, percutaneous transluminal angioplasty). • Consider intraaortic balloon pump counterpulsation for refractory shock.

SEPTIC SHOCK

• Ensure adequate oxygenation; remove work of breathing. • Administer 20 mL of crystalloid/kg or 5 mL of colloid (albumin)/kg, and titrate infusion based on dynamic indices, volume responsiveness, and/or urine output. • Begin antimicrobial therapy; attempt surgical drainage or débridement. • Begin PRBC infusion for hemoglobin level 4 L), we recommend adding 5- to 10-mL/kg boluses of a natural colloid (eg, albumin), rather than additional isotonic crystalloid alone, until volume responsiveness is achieved.19 We do not recommend use of synthetic colloids, such as hydroxyethyl hetastarch, which have recently been demonstrated to be associated with a higher risk of renal failure.20 The infusion of hemoglobinbased blood substitutes as alternatives to packed red blood cells (PRBCs) for the resuscitation of hemorrhagic shock has been extensively studied and is associated with significant increased risk of death and myocardial infarction; we recommend against their use. Blood Products.  In the setting of hemorrhage or a critically low hemoglobin level ( upper limit of normal  Urine output < 0.5 mL/kg/h  PaCO2/FiO2 < 250 in patients without or < 200 in patients with pneumonia  Creatinine > 2.0 mg/dL  Bilirubin > 2.0 mg/dL  Platelet count < 100,000 cells/µL  Coagulopathy (INR > 1.5)

Yes No

MAP < 65 or SBP < 90 mm Hg after 30 ml/kg fluid bolus? Yes Sepsis-induced hypoperfusion

Yes

___Cardiac monitoring, pulse oximetry ___Obtain blood cultures ___Initiate broad spectrum antibiotics ___IJ or SC central line placement if vasopressors required ___O2 or mechanical ventilation to keep Sat > 94% ___Measure lactate

Volume assessment

Volume responsive

Crystalloid 500–1000-mL bolus q15–30 min until unresponsive; reassess regularly

Volume nonresponsive MAP < 65 mm Hg MAP

Arterial line placement Norepinephrine (NE) drip @ 5–40 µg/min

MAP 65–100

Reassess volume and perfusion status (One or more of the following):

MAP < 65 mm Hg And NE @ 40 µg/min

Vasopressin drip @ 0.04 U/min

Dobutamine drip @ (2.5-20 µg/kg/min)

Crystalloid 500-mL bolus



Focused exam (vital signs, cardiopulmonary, capillary refill, pulse, and skin assessment)  Measure CVP  Measure ScvO2  Bedside cardiovascular ultrasound  Dynamic assessment of fluid responsiveness

Volume responsive

Abnormal Normal Remeasure lactate (if initially elevated)

Volume nonresponsive

Volume assessment

Lactate elevated

Lactate normal Early goals achieved Reassess antibiotic coverage Fig. 6.2.  Flow diagram outlining an example of a formalized resuscitation strategy. This figure illustrates the sequential targeting of preload, afterload, oxygen supply, and demand matching for sepsis-induced hypoperfusion. The protocol outlines specific hemodynamic and physiologic parameters that the emergency clinician should seek to attain within the first 6 hours of care. This protocol is focused on resuscitation and should be used in conjunction with standard clinical care for patients with suspected infection, such as appropriate diagnostic studies, to determine the focus of infection and appropriate antimicrobial agents to treat the infection. HCT, Hematocrit; ICU, intensive care unit; IJ, internal jugular; INR, international normalized ratio; MAP, mean arterial pressure; NS, normal saline; PaCO2, partial pressure of carbon dioxide, arterial; Sat, peripheral oxygen saturation; SBP, systolic blood pressure; SC, subclavian; ScvO2 , central venous oxygen saturation; SIRS, systemic inflammatory response syndrome; WBC, white blood cell count.

CHAPTER 6  Shock

a 30-mL/kg fluid bolus generally require vasopressor support. Several randomized trials and a meta-analysis have suggested that norepinephrine (5–30 µg/min) is associated with improved efficacy and lower rates of adverse effects, making norepinephrine the vasopressor of choice for correction of hypotension in septic shock.7 In patients who remain in shock after initial crystalloid boluses, norepinephrine should be initiated at a rate of 0.05 μg/ kg/min and titrated at 3- to 5-minute intervals until the mean arterial pressure is greater than 65 mm Hg or the systolic BP is greater than 90 mm Hg. There are no clear data regarding an absolute maximum dose, but generally there is little or no additional pressor effect once a dose of 30 µg/min has been reached. Vasopressin can be added as a second vasopressor agent when norepinephrine reaches the maximum dose of 30 µg/min. Vasopressin should be administered at a fixed rate of 0.03 to 0.04 units/ min and should not be titrated. A trial of vasopressin cessation can be attempted once the patient demonstrates improving hemodynamics over at least a 6-hour period. Except in cases of a prolonged stay in the ED, vasopressors will not be stopped until the patient is in the ICU. Following vasopressor initiation, particularly in patients who require high or rapid upward titration of the vasopressor dose, patients should be reassessed for their responsiveness to additional fluid boluses through the use of dynamic variables or empirical 500-mL boluses, with careful attention to the clinical response. Vasopressor support, along with crystalloid therapy, is continued until the patient can maintain the blood pressures listed without vasopressor support, which can be tested at the bedside by weaning the vasopressor agent at a rate of 2 to 3 µg/min every 5 to 10 minutes.

Inotropes Dobutamine may also be used with norepinephrine to increase cardiac output and maintain adequate oxygen delivery in cardiogenic and septic shock. In the setting of cardiogenic shock, dobutamine may be indicated by some combination of hypotension, cool extremities, poor urine output, and elevated lactate level. In the setting of septic shock, if the lactate level does not decrease at least 10% and/or the measured ScvO2 does not reach 70%, despite fluid resuscitation and vasopressor administration (see earlier), dobutamine can be added at a dose of 2 µg/kg/min and titrated every 5 to 10 minutes, to a maximum of 20 µg/kg/min. Due to stimulation of vasodilating peripheral beta receptors, dobutamine does have the potential to decrease the BP, so careful attention to a patient’s individual response is necessary. If simultaneous BP and inotropic support is necessary for septic shock, epinephrine alone, 0.2 µg/kg/min starting dose, provides similar outcomes and adverse event rates as a combination of norepinephrine plus dobutamine. When norepinephrine is the first pressor initiated and an inotrope is indicated, we recommend the addition of dobutamine, with the ability to titrate each agent individually. However, it is acceptable as an alternative to discontinue the norepinephrine and initiate epinephrine infusion to provide vasopressor and inotropic support via a single agent.

Antimicrobial Therapy Treatment of the infection with antimicrobial therapy and, where necessary, surgical drainage (see later, “Source Control”), should be instituted as soon as practical in cases of septic shock.10 Current evidence does not support an absolute time requirement for administration but, when septic shock is the working diagnosis in the ED, we recommend initiation of appropriate antibiotics as soon as practical after the diagnosis is made, ideally within 4 hours of ED presentation. When there is no focus of infection identified in a patient with presumed septic shock, a semisynthetic penicillin with a β-lactamase inhibitor, in combination with a

fluoroquinolone and vancomycin, is a rational empirical choice. One such regimen would include piperacillin-tazobactam, 4.5 g IV every 6 hours, plus levofloxacin, 750 mg IV every 12 hours, and vancomycin, 30 mg/kg (maximum dose, 2 g) given every 12 hours, adjusted as appropriate for trough levels and renal failure. Patients with neutropenia and sepsis syndrome are at particular risk for progressive sepsis, organ failure, and death. Neutropenia can be suspected in patients who have recently undergone chemotherapy, and these patients often know that they are neutropenic. Antimicrobial administration is particularly urgent for these patients and should occur rapidly after blood cultures are obtained, in parallel with crystalloid administration. Antibiotic considerations for the neutropenic patient are discussed in Chapter 115. Chemotherapy patients with sepsis represent a special challenge because the pathophysiology may be complicated by anemia, thrombocytopenia, dehydration from vomiting, and the effects of adjunctive steroid therapy. Chemotherapy patients often have indwelling catheters, which predispose them to more unusual causes of sepsis, including gram-positive bacteria and fungi (see Chapters 115 and 187).

Corticosteroids There is no evidence for high-dose, short-course corticosteroid therapy in unselected patients with septic shock. Most current guidelines recommend that low-dose hydrocortisone be administered only to patients receiving chronic steroid replacement and in patients with refractory shock, despite adequate fluid and vasopressor support. Even this is only marginally supported, if at all, by scientific evidence. Corticotropin stimulation testing is no longer considered of value.

Special Cases Systemic thrombolytic therapy is indicated in patients with shock from pulmonary embolism (see Chapter 78) without contraindications.21 Specific treatments for shock as a result of poisoning with vasoactive medications and other toxins are discussed in the relevant chapters in this text.

Devices and Procedures Ventilation Rapid sequence intubation is the preferred method of airway control in most patients with refractory shock (see Chapter 1). Tissue hypoperfusion leads to increasing fatigue of the muscles of respiration, and respiratory failure commonly supervenes in patients with persistent shock. Intubation prevents aspiration, increases oxygenation, treats acute respiratory failure, provides initial treatment for metabolic or hypercarbic acidemia, and protects the patient who will be sent to an uncontrolled environment (eg, for testing). Intubation also reduces the work of breathing, which, in the patient with hypoperfusion, further exacerbates lactic acidemia. Strenuous use of accessory respiratory muscles can increase oxygen consumption by 50% to 100% and decrease cerebral blood flow by 50%. More importantly, if the patient has increased airway resistance (eg, bronchospasm with anaphylaxis) or a decrease in lung compliance (eg, pulmonary edema, ARDS), a more negative intrathoracic pressure must be generated to fill the lungs with each inspiration. The greater suction effect is also exerted on the left ventricle, impeding its ability to eject and increasing functional afterload. Positive-pressure ventilation removes this impedance and can improve ventricular function and cardiac output up to 30%. The use of etomidate for patients with septic shock is discussed in Chapter 1.

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Critical Management Principles

Source Control

Pericardiocentesis and Thrombectomy

Controlling hemorrhage remains the cornerstone of treating hemorrhagic shock, and evidence continues to support immediate surgery when direct vascular control cannot otherwise be obtained (see Chapters 33 and 41). Gastrointestinal bleeding may require urgent endoscopy, often in the ED or ICU, and aortic rupture requires emergency consultation by a vascular surgeon. In septic shock related to an abscess, aggressive infection (eg, necrotizing fasciitis; see Chapter 129) or wound (eg, toxic shock syndrome; see Chapter 130), removal of the infectious stimulus through surgical intervention should proceed as soon as practical.

Shock caused by mechanical obstruction can be managed by direct intervention. Large, acute pericardial effusions should be managed with pericardiocentesis. Surgical thrombectomy for massive pulmonary embolism is performed rarely. Direct thrombolysis via interventional radiology, however, has been gaining acceptance as a therapeutic option in patients with shock, particularly if systemic thrombolytics are contraindicated.

Intraaortic Balloon Pumps and Percutaneous Coronary Intervention The use of intraaortic balloon counterpulsation and percutaneous coronary intervention in selected patients with cardiogenic shock or acute cardiovascular emergencies is discussed in Chapter 68.

OUTCOMES Outcomes for patients with shock vary with the underlying cause of the shock state and the premorbid or comorbid status of the patient. Outcomes have progressively improved, with emphasis on early diagnosis and treatment. In general, persistent hypotension (refractory shock) is associated with worse outcomes. Patients meeting consensus definitions for hemorrhagic shock have a mortality rate of about 20%,1 whereas this exceeds 40% in septic and cardiogenic shock.2

KEY POINTS • Circulatory shock can occur with normal arterial blood pressure, and not all patients with arterial hypotension have circulatory shock. • A base deficit more negative than −4 mEq/L or a serum lactate level greater than 4.0 mmol/L warrants a presumptive diagnosis of shock. • Urine output is a reliable index of vital organ perfusion in patients with suspected shock. Normal urine output is 1.0 mL/kg/h. Output less than 0.5 mL/kg/h indicates severe renal hypoperfusion.

• A combination of a worsening base deficit, increasing lactate level, and low urine output represents persistent or worsening circulatory shock. • Early initiation of fluid resuscitation, with pressor support as needed, and appropriate antimicrobial therapy improve the outcomes in patients with septic shock. • The use of defined physiologic endpoints to measure systemic perfusion during resuscitation (quantitative resuscitation) improves outcomes for ED patients with shock.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 6  Shock

REFERENCES 1. Holcomb JB, Tilley BC, Baraniuk S, et al: Transfusion of plasma, platelets, and red blood cells in a 1 : 1 : 1 vs a 1 : 1 : 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 313:471–482, 2015. 2. Kaukonen KM, Bailey M, Suzuki S, et al: Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316, 2014. 3. Summers RL, Baker SD, Sterling SA, et al: Characterization of the spectrum of hemodynamic profiles in trauma patients with acute neurogenic shock. J Crit Care 28:531– 535, 2013. 4. Odom SR, Howell MD, Silva GS, et al: Lactate clearance as a predictor of mortality in trauma patients. J Trauma Acute Care Surg 74:999–1004, 2013. 5. Hasler RM, Nuesch E, Juni P, et al: Systolic blood pressure below 110 mm Hg is associated with increased mortality in blunt major trauma patients: multicentre cohort study. Resuscitation 82:1202–1207, 2011. 6. Holst LB, Haase N, Wetterslev J, et al: Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 371:1381–1391, 2014. 7. De Backer D, Aldecoa C, Njimi H, et al: Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med 40:725–730, 2012. 8. Mutschler M, Nienaber U, Brockamp T, et al: A critical reappraisal of the ATLS classification of hypovolaemic shock: does it really reflect clinical reality? Resuscitation 84:309–313, 2013. 9. Bone RC, Balk RA, Cerra FB, et al: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992. Chest 136:e28, 2009. 10. Dellinger R, Levy M, Rhodes A, et al: Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock 2012. Crit Care Med 41:580–637, 2013.

11. ProCESS Investigators, Yealy DM, Kellum JA, et al: A randomized trial of protocolbased care for early septic shock. N Engl J Med 370:1683–1693, 2014. 12. Jones AE, Shapiro N, Trzeciak S, et al: Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303:739– 746, 2010. 13. Puskarich M, Trzeciak S, Shapiro N, et al: Whole Blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest 143:1548–1553, 2013. 14. Rivers E, Nguyen B, Havstad S, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377, 2001. 15. Peake SL, Delaney A, Bailey M, et al: Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506, 2014. 16. Mouncey PR, Osborn TM, Power GS, et al: Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 372:1301–1311, 2015. 17. Yunos NM, Bellomo R, Hegarty C, et al: Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 308:1566–1572, 2012. 18. Bulger EM, May S, Kerby JD, et al: Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg 253:431–441, 2011. 19. Delaney A, Dan A, McCaffrey J, et al: The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis. Crit Care Med 39:386– 391, 2011. 20. Mutter TC, Ruth CA, Dart AB: Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev (7):CD007594, 2013. 21. Konstantinides SV, Torbicki A, Agnelli G, et al, Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC): 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 35:3033–3069, 2014.

CHAPTER 6: QUESTIONS & ANSWERS 6.1. Which of the following is considered one of the empirical criterion for the diagnosis of circulatory shock? A. Partial pressure of carbon dioxide (Paco2) < 40 mm Hg B. Partial pressure of oxygen (Pao2) < 55 mm Hg C. Serum lactate level < 4 mM/L D. Systolic blood pressure (SBP) < 100 mm Hg E. Urine output < 0.5 mL/kg/h Answer: E. Four of the following criteria should be met for the diagnosis of circulatory shock: 1. Ill appearing or altered mental status 2. Heart rate > 100 beats/min 3. Respiratory rate > 20 breaths/min or Paco2 < 32 mm Hg 4. Arterial base deficit < −4 mEq/L or lactate level > 4 mM/L 5. Urine output < 0.5 mL/kg/h 6. Arterial hypotension > 20 min duration 6.2. Which of the following, when present and in the setting of suspected or confirmed infection, helps distinguish severe sepsis from systemic inflammatory response syndrome? A. Heart rate > 90 beats/min B. Hypotension C. Paco2 < 32 mm Hg D. Temperature < 36°C E. >10% band neutrophilia Answer: B. The diagnosis of severe sepsis is made in patients who meet the criteria for systemic inflammatory response syndrome (SIRS) with suspected or confirmed infection and associated with organ dysfunction or hypotension. The organ dysfunction

mentioned may include the presence of lactic acidosis, oliguria, and/or altered mental status. The diagnosis of SIRS is made when two or more of the following are present: 1. Temperature > 38°C or < 36°C 2. Heart rate > 90 beats/min 3. Respiratory rate > 20 breaths/min or Paco2 < 32 mm Hg 4. White blood cell count > 12,000/mL, < 4,000/mL, or > 10% band neutrophilia 6.3. An 18-year-old unrestrained driver is transported to the emergency department (ED) after being thrown from his vehicle during a motor vehicle collision. He was intubated in the field and received an intravascular bolus of 3 L of normal saline before arrival to the ED. His initial Glasgow Coma Score (GCS) is 7, and his blood pressure on arrival is 80/50 mm Hg. Which of the following would be the most appropriate to initiate immediately on arrival to the ED? A. Dobutamine B. Dopamine C. Hetastarch D. Norepinephrine E. Packed red blood cell (PRBC) transfusion Answer: E. In patients with signs of hemorrhagic shock and suspected central nervous system trauma or GCS < 9, immediate PRBC transfusion should be initiated. This assists with volume expansion and oxygen delivery to the brain. Pressors and positive inotropes will be of little benefit before volume replacement, and hetastarch has no proven benefit for initial resuscitation in head injury patients.

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C H A P T E R 7 

Brain Resuscitation Craig A. Williamson  |  William J. Meurer PRINCIPLES Background Despite our recognition of the brain’s dominant role in determining the quality of life, modern medicine’s ability to intervene and reverse neuronal injury remains limited. Consequently, modern techniques of brain resuscitation are focused on restoring cerebral homeostasis and mitigating the effects of secondary brain injuries. Hypoxic-ischemic injury following cardiac arrest can be seen as a model of global ischemic disease, and recent advances in understanding of its pathophysiologic mechanisms have led to improvements in neurologic outcomes. Although hypoxic-ischemic injury represents a so-called pure form of brain ischemia, its underlying pathology has significant overlap with other cerebral injuries, such as stroke and traumatic brain injury. Thus, many of the physiologic principles of brain resuscitation following cardiac arrest are applicable to these conditions. This chapter, therefore, reviews the pathophysiology of ischemic brain injury and discusses therapies for improving neurologic recovery following cardiac arrest and other critical neurologic illnesses in which cerebral ischemia may occur.

Anatomy, Physiology, and Pathophysiology The human brain consists of 10 billion neurons, each with multiple connections to other cells, totaling an estimated 500 trillion synapses. Although the brain constitutes only 2% of body weight, it receives 15% of the body’s cardiac output and accounts for 20% of the body’s overall oxygen use. Although no mechanical or secretory work is performed by the brain, energy expenditures include the synthesis of cellular constituents (eg, an estimated 2000 mitochondria are reproduced each day by each cell) and neurotransmitter substances, axoplasmic transport of these substances, and transmembrane pumping of ions. When the brain is deprived of adequate blood flow, the resulting ischemia is characterized by a bewildering array of interrelated physiologic and cellular responses that ultimately result in neuronal cell death (Fig. 7-1).1 Although this complex cascade of events can be triggered by periods of ischemia lasting only a few minutes, the resulting neuronal death is usually delayed by hours or days. Furthermore, the biology of cerebral cell death after global cerebral ischemia follows the pattern of delayed cerebral cell death that follows stroke, traumatic brain injury, and other forms of hypoxic or toxic brain injury, with slight variations. Increased understanding of the brain’s response to injury during the period between insult and neuronal cell death will eventually allow more specific brain resuscitation therapies.

Elevated Intracranial Pressure Intracranial pressure (ICP) is an important consideration in ischemic brain injury because cerebral ischemia can directly result in ICP elevation. This occurs because the failure of oxidative phosphorylation depletes adenosine triphosphate (ATP) stores, which

results in an inability to maintain osmotic gradients actively. Increased intracellular osmolarity leads to water influx and the development of cytotoxic edema, which usually peaks 48 to 72 hours after injury. By decreasing cerebral perfusion pressure (CPP), elevated ICP is also an important contributor to secondary brain injury. This relationship is discussed in further detail below; additional information on ICP management is contained in the pharmacology, devices, and techniques sections. To understand the pathophysiology of elevated ICP, it should be noted that the skull is a rigid container whose relatively noncompressible contents include the brain (~80%), blood (~10%), and cerebral spinal fluid (CSF; ~10%). According to the MonroKellie hypothesis, any addition to the volume of one of these components—for example, increased brain volume due to cerebral edema—must be offset by a reduction in the volume of the other contents or the ICP will rise. Typically, adaptation to increased intracranial volume is initially accomplished by shifting CSF from the intracranial to spinal subarachnoid compartment. Approximately two-thirds of cerebral blood volume is contained in the cerebral veins and dural sinuses, and this venous capacitance can be reduced to accommodate increased intracranial volume further. Unfortunately, these mechanisms are sometimes quickly exhausted, resulting in decreased compliance and a significant increase in ICP. This may occur rapidly with acute cerebral injury or slowly with mass lesions such as tumors. In its final stages, uncontrolled intracranial hypertension will result in downward herniation of the cerebellar tonsils through the foramen magnum, thereby compressing critical cardiorespiratory centers in the medulla. Prior to or concurrently with this, elevated ICP can exacerbate ischemic injury by reducing cerebral blood flow. CPP is equal to the mean arterial pressure (MAP) minus ICP. As ICP increases, CPP decreases, which is compensated for by cerebral arteriolar vasodilation. Unfortunately, this vasodilation may increase cerebral blood volume, which can additionally increase ICP and further reduce CPP. This vicious cycle is one of the primary inciting factors for the prolonged periods of refractory ICP elevation known as plateau or Lundberg A waves.

MANAGEMENT Decision Making Standard management of ischemic brain damage involves restoring cerebral blood flow (CBF) and preventing secondary insult. Most treatments have not been studied in prospective, randomized, controlled trials, but have been supported by clinical experience and limited experimental data. Although proposed and experimental neuroprotectant therapies are generally aimed at specific molecular interventions in the pathophysiology of ischemic brain injuries, as yet none of these have proven effective in clinical trials. In the case of ischemic injury following cardiac arrest, the most comprehensive review and consensus guideline statement on care of patients with post–cardiac arrest syndrome 77

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Critical Management Principles

has come from the International Liaison Committee on Resuscitation and its constituent bodies, with the endorsement of the American College of Emergency Physicians, Society for Academic Emergency Medicine, Society of Critical Care Medicine, and Neurocritical Care Society.2 Improvements in post–cardiac arrest care, through an inclusive multisystem approach, can increase the

likelihood of meaningful recovery in these patients. Implementation of standardized protocols for postresuscitation care that include many or all of the following components have demonstrated increases in survival, with a favorable neurologic outcome of up to 30% in repeated (although poorly controlled) before and after studies.3,4

mGluR AMPA/KA

Glu Glu

↓ATP K+

K+

Na+

↑Na+

NMDA GABA rot Ca2+ GP Cl– Na+ PKC P ↑Ca2+ AM . ATP ↓ATP c etc ↑Na+ Cytotoxic edema Na+

Ca2+

Ca2+ ↑Ca2+

Ca2+

ADP ↓H+ Na+ ATP ↓O2

↓CBF

Depolarization Action potential

en

Glu release

Lum

A

B

ER

↓ATP 2+

Ca Cytochrome oxidase inhibition Xanthine XO Uric acid

NO

NOS

Ca2+activated oxidases

↑Ca2+ Oxidative protein damage

Damaged E.T. Oxygen free radicals

H2O2 + Fe

GABA GABA

Membrane degradation

C Fig. 7.1.  Synopsis of events contributing to neuron cell death cascade after ischemia. A, Decreased cerebral flow (CBF) and arterial oxygen content during ischemia cause decreased adenosine triphosphate (ATP) production, failure of ATP-driven ion pump efflux of potassium ions (K+), and influx of sodium ions (Na+) and calcium ions (Ca2+) through voltage-gated channels. ADP, adenosine diphosphate. B, Na+ influx causes depolarization and glutamate (Glu) release, opening Glu receptor α-amino-3-hydroxy-5-methyl-4isoxazolepropionate (AMPA) and kainate (KA) channels and exacerbating intracellular Na+ overload. Increased Na+ concentration ([Na+]i) leads to cytotoxic edema. Glu-mediated N-methyl-D-aspartate (NMDA) channels allow intracellular Ca2+ overload. Insufficient ATP causes failure of energy-dependent Ca2+ pumps, and high [Na+]i prevents removal of Ca2+ by Na+/Ca2+ exchange pumps. γ-Aminobutyric acid (GABA) release can attenuate excitatory changes by opening a receptor-gated Cl−. C, Increased [Ca2+]i is amplified by calcium-induced release of Ca2+ from the endoplasmic reticulum (ER). Mitochondria may be injured attempting to buffer increasing [Ca2+]i, resulting in further metabolic failure and diminished ATP. Ca2+ activates nitric oxide synthase (NOS), transforming it to nitric oxide (NO), which is amplified by NO activation of NOS. NO contributes to the formation of damaging oxygen free radicals and inhibits mitochondrial cytochrome oxidase function. ATP degradation to xanthine and then uric acid by xanthine oxidase (XO) yields hydrogen peroxide (H2O2), which reacts with iron to form dangerous oxygen radicals. Oxygen free radicals react with lipids in the cell membrane, which leads to membrane degradation and more free radicals. Oxygen free radicals also can damage proteins.

CHAPTER 7  Brain Resuscitation

Degradation of cytoskeleton and Membrane proteins, G proteins, and kinases

↓ATP Cytochrome ↑Ca2+ C Caspases ↑PARP DNA damage MAPK Apoptosis Oxygen free NFκB Transcription

radicals

AP-1

Calpains

↑Ca2+

↓PARP Apoptosis

IEG HSP Bax/Bcl-2 Caspases

E

D

Microglial activation

Cytokines eNOS NO NO

Endothelin Selectins and ICAM

Transcription

Activated leukocyte

MAC

F

en

Clumping

Lum

Membrane degradation Oxygen free radicals and proteases Complement

Integrins

↓CBF

Fig. 7.1, cont’d. D, Ca2+ also activates kinase transcription factors, such as mitogen-activated protein kinase (MAPK). Oxygen radicals trigger nuclear factor κB (NFκB), another transcription factor. Many genes, including immediate early genes (IEGs), heat shock protein (HSP) genes, genes for caspases, and the Bax/ Bcl-2 systems, are activated. IEG products include AP-1, another transcription factor. Mitochondrial release of cytochrome c, existing and newly formed caspases, and other factors trigger apoptosis. DNA is damaged by oxygen free radicals and by endonucleases formed in apoptosis. DNA damage activates poly(ADP-ribose) polymerase (PARP), which further depletes ATP stores. E, Ca2+ and apoptosis activate calpains, proteases that degrade a variety of structural elements (eg, cytoskeletal and membrane proteins), signaling elements (eg, G proteins, kinases), and PARP. F, Transcription and NO contribute to the neuronal expression of cytokines, chemokines, and growth factors. These intercellular signals activate complement, epithelial cells, leukocytes, and microglia. Complement can amplify chemotactic signals, activate microglia directly, or cause cellular damage by creation of the membrane attack complex (MAC). Leukocyte integrins, epithelial cell selectins, and intercellular adhesion molecules (ICAMs) allow demargination. Activated leukocytes cause neuronal injury by releasing potent oxidants and protease. Cerebrovascular resistance may be affected by the epithelial release of NO and endothelin and by leukocyte clumping. ADP, Adenosine diphosphate; [Ca2+]i, Ca2+ concentration; cAMP, cyclic adenosine monophosphate; eNOS, endothelial nitric oxide synthase; E.T., enzyme trafficking; mGluR, metabotropic glutamate receptor; PKC, protein kinase C.

Pharmacology, Devices, and Techniques Cardiopulmonary Resuscitation In the event of cardiac arrest, return of spontaneous circulation is the first priority in cerebral resuscitation. The degree of brain injury after cardiac arrest depends on the duration of complete

cerebral ischemia (the downtime, or time before the initiation of cardiopulmonary resuscitation [CPR]) and duration of relative ischemia that occurs during CPR and that may occur from cardiogenic shock preceding or subsequent to the period of cardiac arrest. Events occurring after the restoration of flow (eg, transient hypoxia, hypotension) also can exacerbate brain damage in this dynamic and important early resuscitation time period. Extensive

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SECTION One 

Critical Management Principles

clinical evidence on hospital discharge rates and neurologic recovery rates supports the concept that success in resuscitation is inversely proportional to the duration of cardiac arrest. Although duration of arrest generally predicts outcome in the population of patients with sudden cardiac death, it cannot be used reliably to predict the outcome of individual patients. Modern brain resuscitation techniques focus on avoiding further secondary cerebral injury, which also affects outcome. Neurologic outcome of survivors is influenced by patient age, comorbidity and other individual characteristics. The efficacy of closed chest CPR in generating adequate cerebral perfusion is somewhat controversial. Cardiac output during optimal standard closed chest CPR was previously estimated to be only 20% to 30% of normal, but more recent studies have suggested that higher cardiac outputs are possible in clinical practice and, unquestionably, effective CPR is essential to neurologic recovery after cardiac arrest.

Reperfusion With cerebrovascular insults due to embolic or thrombotic mechanisms, randomized clinical trials have shown a benefit of revascularization in ischemic stroke. This is discussed in detail in Chapter 91). Optimizing Perfusion and Oxygenation.  Maintaining cerebral oxygen delivery is a mainstay of therapy after ischemic brain injury. Oxygen delivery requires a sufficiently high CPP, sufficiently low cerebrovascular resistance (CVR), and adequate blood oxygen saturation. Hypotension can dangerously lower cerebral blood flow (CBF) and is associated with worse outcome following cardiac arrest and traumatic brain injury (TBI). Normally, a change in systemic blood pressure triggers corresponding changes in CVR, mediated by cerebral arterial vasodilation or vasoconstriction. This capacity, termed cerebral autoregulation, functions to maintain a constant CBF over a wide range of arterial blood pressures. Autoregulation is often lost in the injured brain and, as a result, perfusion of ischemic tissue becomes passively dependent on CPP. Consequently, hypotension can compromise CBF and result in significant additional brain damage. Therefore, low arterial pressures should be rapidly normalized, with intravascular volume administration and vasopressors used as needed. In the absence of prospective clinical trial data to guide decision making, current recommendations for cardiac arrest patients are to maintain a MAP of 65 to 100 mm Hg. Induced hypertension, once believed to enhance CPP, is not currently a standard therapy due to concerns related to disruption of the blood-brain barrier and worsening of vasogenic edema. Blood pressure goals fundamentally differ in intracerebral hemorrhage (ICH), in which elevated blood pressure at presentation is common due to a physiologic pressor response. Hypertension is a known risk factor for hematoma expansion, yet the targeted blood pressure goal in these patients remains controversial due to uncertainty regarding perfusion to the brain tissue surrounding the hematoma (ischemic penumbra). A large, multicenter, randomized controlled trial has demonstrated that rapid lowering of the systolic blood pressure (SBP) to less than 140 mm Hg is safe and may have a small but meaningful benefit on neurologic outcome.5 Consequently, we endorse immediate management with IV antihypertensives targeting an SBP less than 140 mm Hg. As in other conditions where there is a risk of secondary ischemic injury, hypotension should be diligently avoided by not allowing the MAP to drop below 65 mm Hg. CVR is a critical determinant of CBF and may be affected by hyperventilation and microvascular patency. Although the cerebral circulation may lose its ability to adjust to blood pressure

changes after ischemia, attenuated responsiveness to carbon dioxide and oxygen levels in arterial blood is generally present.3 Carbon dioxide is a potent vasoactive agent, and lowering the arterial carbon dioxide partial pressure (Paco2) by hyperventilation results in a rapid reduction of CBF of 2% for every 1-mm Hg decrease in the Paco2. Because reductions in CBF reduce total cerebral blood volume, hyperventilation quickly lowers ICP. Induced hyperventilation can transiently abort brainstem herniation in the presence of critically elevated ICP until an alternative therapy can be initiated. However, the vasoconstriction and increased CVR caused by hyperventilation can lead to dangerous reductions in CBF, with resulting cerebral ischemia.4 We recommend restricting the use of induced hyperventilation to the short-term treatment of immediately life-threatening cerebral herniation and severe intracranial hypertension that is not responsive to other measures, such as osmotic therapy. Chronic or prophylactic hyperventilation should not be used. Specific treatment for elevated ICP is described in the next section. In general, ventilation to maintain a Paco2 of 35 to 40 mm Hg is safe and appropriate, and inadvertent hyperventilation should be avoided. Normal arterial oxygen saturation following resuscitation from ischemic brain injury is a primary goal. The injured brain may not be able to compensate for hypoxia by augmenting CBF, and cerebral oxygen delivery may diminish rapidly as the oxygen content of blood decreases. Hyperoxia secondary to the use of high concentrations of oxygen, however, has also been shown to increase oxidative brain injury in animal models of cardiac arrest and resuscitation and is associated with increased mortality in stroke patients5 and in post–cardiac arrest patients.9 Normoxia or mild hyperoxia (arterial partial pressure of oxygen, Pao2, of 80–120 mm Hg with oxyhemoglobin saturation percentage maintained in the high 90s) should be maintained through use of the lowest fraction of inspired oxygen (Fio2) possible. Because hypoxia, hypocapnia, and hypercapnia must be avoided, controlled ventilation is appropriate in the period after resuscitation, with sedation and muscle relaxation if needed. Continuous oximetry and capnography, correlated with intermittent arterial blood gas determinations, will provide the information necessary to optimize ventilation parameters.

Elevated Intracranial Pressure The presence of intracranial hypertension is suggested by certain imaging findings and clinical features. Relevant computed tomography (CT) findings include compressed basal cisterns, diffuse sulcal effacement, and diffuse loss of differentiation between the gray and white matter, although ICP can be elevated without any of these findings. Suggestive clinical features include papilledema, bilateral sixth nerve palsies, and new third nerve palsy in a comatose patient. Definitive diagnosis requires invasive ICP monitoring placement. The decision to place an ICP monitor should be guided by neurosurgery whenever consultation is available. Most data on the management of elevated ICP is derived from literature on TBI, a condition in which ICP elevation commonly occurs. Although support from randomized controlled trials is lacking, the Brain Trauma Foundation has published guidelines for ICP monitor placement, which we recommend following in TBI patients whenever possible. These call for ICP monitor placement in all patients with an abnormal head CT scan and severe brain injury, defined as a Glasgow Coma Score of 3 to 8. ICP monitoring is considered appropriate in the presence of a normal head CT when two of the following are present: (1) age older than 40 years; (2) unilateral or bilateral motor posturing; and (3) SBP less than 90 mm Hg. Guidelines are not available for ICP monitoring in other conditions involving ischemic brain injury, such as stroke, where it is

CHAPTER 7  Brain Resuscitation

generally not indicated. In particular, the clinical impact of intracranial hypertension due to anoxic brain injury following cardiac arrest is unclear and has not been studied in prospective trials. When cytoxic edema severe enough to cause ICP elevation develops, it portends a very poor prognosis. Consequently, invasive ICP monitoring is not recommended in the management of global ischemic injury following cardiac arrest.2 Medical Treatment.  Medical treatment for elevated ICP has similarly not been proven effective in randomized controlled trials, and treatment protocols are primarily based on clinical experience and expert opinion. To ensure adequate cerebral perfusion, the MAP should be maintained above 65 mm Hg in all patients at risk for ICP elevation, and a CPP of 50 to 70 mm Hg should be targeted when ICP monitoring is available. Although the exact threshold for ICP treatment is unclear and may vary between individual patients, an ICP over 20 mm Hg has been associated with worse neurologic outcomes and should trigger treatment. Although there are many and somewhat diverse recommendations for the initial medical management of patients with elevated ICP, we suggest the following: 1. Position the patient with the head up by elevating the upper half of the bed or gurney to 30 degrees. 2. Maintain a neutral head and neck position to avoid jugular venous compression. 3. Treat fever. Administer antipyretics agents (eg, acetaminophen suppositories, 1000 mg every 6 hours) and use mist cooling as necessary, targeting a temperature at or below 37°C. 4. Minimize triggers of ICP increases. This is accomplished by treating and avoiding pain. We recommend titrated doses of a hemodynamically stable opioid medication, such as fentanyl 25 to 50 µg every 5 minutes, as needed. Cough or bucking of the ventilator also should be avoided; this is best accomplished by achieving adequate sedation and analgesia to permit mechanical ventilation, as described in Chapters 1 and 2. Propofol is our sedative agent of choice for this purpose because it decreases cerebral metabolic activity and thereby CBF, and rapidly clears for neurologic assessment, as needed. Propofol can cause or contribute to hypotension, which generally is avoided by dosage adjustment. 5. Initiate osmolar therapy. Osmolar therapy with mannitol or hypertonic saline can draw water across an intact blood-brain barrier and thereby lower ICP. Mannitol, 0.5 to 1 g/kg is given every 6 hours, up to a serum osmolality of 320 mOsm/kg. Treating with 30 mL of 23.4% normal saline appears to be at least as effective as mannitol at rapidly lowering ICP and reversing herniation, although a central line is necessary for safe administration; 30 to 60 mL can be given every 6 hours, up to a maximum serum sodium level of 160 meq/L. Because it is a potent diuretic, mannitol is preferred in cases of fluid overload, whereas hypertonic saline can be used as a resuscitative fluid. 6. Treat cases of refractory ICP elevation not amenable to the previous therapies. Induced coma with a barbiturate will further decrease CBF and lower ICP. Pentobarbital is started with a 10-mg/kg loading dose over 1 hour, followed by a continuous infusion of 0.5 to 5 mg/ kg/h, titrated to achieve electroencephalographic burst suppression. Barbiturate administration is frequently accompanied by hypotension, which often requires vasopressors to maintain adequate CPP. 7. Mild induced hypothermia is an additional option in highly refractory cases. Endovascular or surface cooling devices should be used to target a temperature of 32° to 36°C, titrated to achieve ICP control. Once cooled, rapid rewarming should be avoided because this may precipitate a significant ICP elevation.

Surgical Treatment.  Surgical options for the management of refractory ICP include decompressive craniectomy and evacuation of intracranial hematoma, when present, and should be guided by neurosurgical consultation. In the event of severe cytotoxic edema following middle cerebral artery stroke, there is a benefit of early ( 65 yr Male gender History of congestive heart failure History of cardiovascular disease or serious dysrhythmia History of structural heart disease Family history of early (1 error

Altered level of consciousness

No

Evidence of disorganized thinking

Abnormal attention span, mental status testing Yes

bCam positive Delirium present

Yes

Confusion, delirium ( agitation)

No Thought disorder Possible psychiatric disorder

Any errors

No errors

Fig. 14.5.  Diagnostic algorithm for confusion.

bCam negative No delirium

Suggested questions; 1) Will a stone float on water? 2) Are there fish in the sea? 3) Does 1 pound weigh more than 2 pounds? 4) Can you use a hammer to pound a nail? Command: “Hold up this many fingers” (hold up two fingers). “Now do the same thing with the other hand” (do not demonstrate). Fig. 14.4.  Brief confusion assessment method (bCAM).

more specific evaluation is recommended. The guidelines recommend a modification of the confusion assessment method, termed the brief confusion assessment method (bCAM) as a second test. This assesses four features—mental status by history or examination, further assessments of attention, level of consciousness, and orderly thinking (Fig. 14.4).

Ancillary Testing Synthesis of information from the history and physical examination guide the emergency clinician in the choice of laboratory tests most likely to yield valuable diagnostic information. Pulse oximetry may reveal hypoxia or bedside glucose testing may reveal hypoglycemia or hyperglycemia. In the presence of fever, chest radiography and urinalysis often reveal the source of the infection causing the altered mentation. In older patients, urinalysis should be performed whether or not fever or typical symptoms are present. Serum chemistry tests for liver function may help identify hepatic encephalopathy. If there are clinical findings or a history suggestive of hypothyroidism, thyroid testing is indicated (see Chapter 120). Electrocardiography is indicated in older patients because myocardial infarction may manifest atypically as confusion. The complete blood count, although commonly determined, is unlikely to provide useful diagnostic clues unless profound anemia is suspected. White blood cell counts may be elevated, normal, or low, without specificity as to the presence or nature of a disorder. Arterial blood gas testing is rarely indicated or useful unless pulse oximetry is not reliable.

If common and simple tests do not identify a cause, advanced diagnostic testing may be indicated. The clinical situation and overall condition of the patient determine the speed and direction of evaluation and whether the tests are obtained in the ED. Additional laboratory work is often of decreasing yield but serum ammonia and calcium levels and selected drug and toxicologic testing may be ordered in this second tier of evaluation. Blood and urine cultures are obtained in the febrile patient when hospital admission is anticipated and a clear infectious source is not evident. Paracentesis or thoracentesis may be appropriate if ascites or a new pleural effusion is present. Cranial computed tomography (CT) scanning is often done to screen for CNS lesions in the absence of another identified source of the confusion. Unanticipated abnormalities are uncommonly found, although focal findings on examination increase the yield of neuroimaging. Lumbar puncture may allow discovery or exclusion of CNS infection if no other source has been identified. Cerebrospinal fluid examination may clarify a diagnosis of meningitis, encephalitis, or subarachnoid hemorrhage. If the cause of confusion remains unclear, or if the patient is unable to function safely in their current environment, admission is recommended for observation, and additional evaluation with consideration of obtaining magnetic resonance imaging or electroencephalography.

DIAGNOSTIC ALGORITHM Certain critical and emergent diagnoses require prompt recognition for morbidity or mortality to be prevented (Box 14.1). The diagnosis of confusion implies the exclusion of other states of altered mental status, such as a decompensated psychiatric syndrome (Fig. 14.5). The first step in assessing a patient with confusion is to ensure that the critical reversible causes are identified and addressed (eg, hypoxia, hypercarbia, hypoglycemia; Fig. 14.6). A complete set of vital signs, including temperature and oxyhemoglobin saturation, and a bedside blood glucose level should be determined promptly. Next, an assessment for delirium is performed using the confusion assessment method (CAM) score. If delirium is suspected, the underlying medical or surgical cause must be sought, including pneumonia, urinary tract infection, other systemic infection, CNS lesion, and drug toxicity. If the patient’s CAM score is negative, a cognitive assessment should be performed, looking for evidence of an underlying dementia.

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Signs, Symptoms, and Presentations

Confusion change in baseline mental status

Substrate verification glucose, oxygen checks

Abnormal

Correct as needed

Normal

Toxidrome present?

Yes

Antidotal therapy as appropriate supportive care

No

Focal findings on neurologic examination

Yes

Stroke, tumor, subdural Immediate neuroimaging

Yes

Possible sepsis pneumonia, UTI, skin, CNS Initiate treatments

No

Fever, SIRS criteria No

Diagnosis remains uncertain Yes

ED testing directed by history and physical examination basic (CBC, electrolytes, CXR, ECG, UA) Advanced (might include cranial CT, ABG, CSF, thyroid, MRI, toxicologic studies)

Consultation or admission Coordinate advanced diagnostic testing Coordinate treatments with other providers Fig. 14.6.  Management algorithm for confusion. ABG, Arterial blood gases; CBC, complete blood count; CNS, central nervous system; CT, computed tomography; CSF, cerebrospinal fluid; CXR, chest x-ray; ECG, electrocardiogram; ED, emergency department; MRI, magnetic resonance imaging; SIRS, UA, urinalysis; UTI, urinary tract infection.

The history and physical examination search for precipitating factors underlying the onset of the confusional state. Investigations continue until the patient is stabilized, a likely diagnosis is discovered, or consultation and admission are deemed necessary. Focal neurologic findings suggesting stroke, tumor, or some other mass lesion prompt immediate neuroimaging. If the examination is nonfocal, the presence of systemic inflammatory response syndrome (SIRS) criteria or fever may lead to the discovery of an infectious cause of the confusion. Postictal confusion is common in patients with seizures but should improve within 20 to 30 minutes. If the patient remains unconscious or confused after a seizure, the possibility of ongoing or intermittent seizure activity (ie, nonconvulsive seizures) should be entertained, and neurologic consultation and electroencephalography should be considered.

If the cause of confusion remains uncertain, admission to an inpatient or observation unit is considered for further evaluation. Ideally, care is promptly coordinated with consultants and admitting physicians.

EMPIRICAL MANAGEMENT Oral or intravenous glucose therapy is indicated if an abnormally low blood glucose level is discovered. In adults, 25 g dextrose (50 mL of 50% dextrose) is commonly administered, and the bedside glucose level is checked again. Thiamine, 100 mg IV, is recommended at the time of dextrose administration. Hypoxia and hypocapnia are addressed with noninvasive or invasive strategies tailored to the patient’s presentation. If a toxidrome is present, treatment is directed toward the specific toxin or syndrome.

CHAPTER 14  Confusion

Confused or agitated patients should be protected from harming themselves or others. Close observation may need to be supplemented by medications or physical restraint. Family members may offer valuable assistance in observing and comforting the patient. Environmental manipulations such as dim lighting or providing a quiet environment may be helpful. Confinement or physical restraint may be necessary at times but should be used with careful adherence to institutional guidelines. Benzodiazepines, butyrophenones, or newer antipsychotic medications may be used if necessary to decrease agitation, but any of these might confound evaluation of the confusional state. No studies allow precise recommendation but in adults we recommend midazolam, titrated beginning with 1 to 2 mg IV or 5 mg IM.

Age-appropriate antibiotic treatment for coverage of causes of sepsis tailored to the patient’s comorbidities may be considered in ill febrile patients while a definitive evaluation is in progress. If a CNS infection is suspected, age-guided empirical antibiotic treatment without delay for lumbar puncture is recommended (see Chapter 99). In patients with a prolonged postictal period or who are suspected of being in nonconvulsive status epilepticus, empirical treatment with lorazepam, 1 mg IV, up to a maximum of 10 mg, may be considered pending consultation and additional testing (see also Chapters 15 and 92).

KEY CONCEPTS • Confusion is a symptom, not a diagnosis. • Focal cortical dysfunction, such as from tumor or stroke, typically does not cause confusion. • Any underlying clinical process that disrupts optimal central nervous system (CNS) functioning can result in confusion. • Emergent causes of confusion that need immediate detection and treatment include hypoglycemia, hypoxemia, hypotension, sepsis, and toxic ingestions.

• Assessment of attention is fundamental for the assessment of patients with confusion. • The confusion assessment method (CAM) is a validated tool for identifying patient with delirium. • Delirium often goes unrecognized unless a structured assessment tool is used. • Midazolam is useful for managing undifferentiated agitation while the diagnostic evaluation is in progress.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 14  Confusion

137.e1

REFERENCES 1. Han JH, Schnelle JF, Ely EW: The relationship between a chief complaint of “altered mental status” and delirium in older emergency department patients. Acad Emerg Med 21:937, 2014. 2. Han JH, et al: Delirium in the emergency department: An independent predictor of death within 6 months. Ann Emerg Med 56:244, 2010. 3. Young GB: Encephalopathy of infection and systemic inflammation. J Clin Neurophysiol 30:454–461, 2013. 4. O’Regan NO, et al: Attention! A good bedside test for delirium? J Neurol Neurosurg Psychiatry 85:1122–1131, 2014.

5. Han JH, et al: Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method. Ann Emerg Med 62:457–465, 2013. 6. American College of Emergency Physicians; American Geriatrics Society; Emergency Nurses Association; Society for Academic Emergency Medicine; Geriatric Emergency Department Guidelines Task Force: Geriatric emergency department guidelines. Ann Emerg Med 63:e7–e25, 2014.

CHAPTER 14: QUESTIONS & ANSWERS 14.1. A 70-year-old man with a chief complaint of confusion is brought to the emergency department by his family. Which of the following initial assessments should be included? A. All of these B. Blood pressure C. Pulse oximetry D. Rapid bedside glucose testing E. Temperature Answer: A. Confusion may result from shock states, hypoglycemia, and hypoxia. Evaluation for these conditions is a priority. Confusion is a symptom rather than a medical condition, and reversible remedial causes should be investigated. 14.2. A variety of screening tests may aid in the detection of confusion. Which of the following conditions may inhibit performance of these tests? A. Attention impairment B. Cortical blindness C. Disorientation D. Hemiparesis E. Long-term memory impairment Answer : A. Deficiency in attention span will impair performance of all tests of cognitive performance. If the patient cannot attend to simple tasks, more detailed testing is not possible. 14.3. A 30-year-old patient is brought to the emergency department for evaluation of odd behavior. Which of the

following characteristics might suggest a psychiatric cause for the behavior? A. Auditory hallucinations B. Disorientation C. Fever D. Olfactory hallucinations E. Visual hallucinations Answer: A. Auditory hallucinations are common in psychiatric illness. If hallucinations are present in organic causes of delirium, they are usually visual, tactile, or olfactory. Orientation is generally preserved with primary psychiatric disorders unless psychosis or severe impairment is present. 14.4. Postictal confusion is common in patients with seizures, but if improvement in consciousness does not occur within 20 to 30 minutes after seizure cessation, which of the following conditions should be considered? A. all of these B. electrolyte abnormalities C. head injury D. hypoglycemia E. nonconvulsive or subtle status epilepticus Answer: A. For a patient with a generalized convulsive seizure, termination of the seizure activity should be followed by improvement of mental status within a short period of time. For the patient with persistently altered consciousness or prolonged confusion, consider causes of provoked seizures with prolonged altered mental status or persistence of subtle seizures.

C H A P T E R 15 

Seizures Charles V. Pollack, Jr.  |  Felipe Teran Merino

PERSPECTIVE

Pathophysiology

Seizures are episodes of abnormal neuronal excitation and are generally a manifestation of an underlying process. The goal of the emergency clinician is to differentiate a seizure from a seizure mimic and identify causes that are reversible. Epilepsy is defined as recurrent unprovoked seizures caused by a genetically determined or acquired brain disorder; it is not an appropriate term for seizures that occur intermittently or predictably after a known insult, such as alcohol intoxication and withdrawal.1 Status epilepticus is characterized by seizures lasting more than 5 minutes or recurrent seizures, without return to baseline mental status.2 Generalized convulsive seizures are often self-limiting but, if sustained, require prompt treatment to minimize complications. Nonconvulsive seizure activity and nonconvulsive status epilepticus may be relatively obscure in their presentation and should be suspected in patients with altered behavior or coma of undetermined cause.3

Seizures occur when the abnormal, increased electrical activity of initiating neurons activates adjacent neurons and propagates via a process termed recruitment, following contiguous paths or extending along diverse integrated circuits that are deep and may cross the midline. When the abnormal impulse extends below the cortex to deeper structures, the reticular activating system in the brainstem may be affected, altering consciousness. In generalized seizures, the focus often is subcortical and midline, which explains the prompt loss of consciousness and bilateral involvement. Seizures are typically self-limited; at some point the hyperpolarization subsides and the bursts of electrical discharges from the focus terminate. This cessation may be related to reflex inhibition, neuronal exhaustion, or alteration of the local balance of neurotransmitters between the excitatory acetylcholine and the inhibitory γ-aminobutyric acid (GABA). Focal seizures may represent a similar pathophysiologic process, in which less recruitment occurs and the ictal activity does not cross the midline. Because of the more limited focus of abnormal activity, convulsive motor activity may not be the predominant clinical manifestation. Chapter 92 presents a further discussion of the pathophysiology of seizures.

Epidemiology More than 10% of the US population will experience at least one seizure during their lifetime; however, only 3% will be diagnosed with epilepsy. Alcohol and other intoxications and central nervous system pathologies, such as tumor, stroke, trauma, or infection, are common causes of seizures in adults. Seizures are classified based on cause (primary or secondary), effect on mentation, and motor activity. Primary seizures are unprovoked and not linked to an inciting event. Secondary seizures may be caused by trauma, illness, intoxications and poisonings, metabolic disturbances, and cerebral tumors.4,5 A generalized seizure is defined as abnormal neuronal activity in both cerebral hemispheres, which results in an alteration in the level of consciousness. Generalized seizures may be further divided into tonic-clonic, absence, atonic, and myoclonic. Focal seizures usually involve one cerebral hemisphere, thereby preserving consciousness, although these seizures may progress and cause an altered sensorium. Some seizures are impossible to classify because of inadequate or inaccurate description of the ictal activity.2,6 Convulsive seizures are characterized by uncontrolled, rhythmic motor movements and can affect part or all of the body. Patients with nonconvulsive seizures may manifest automatisms, confusion, altered mental status, abnormal behavior, or coma. Status epilepticus has been classically defined as at least 30 minutes of persistent seizures or a series of recurrent seizures without intervening return to full consciousness. The time criterion has been shortened to 5 minutes, with recognition that the duration of seizure activity is related to outcome and that the likelihood of achieving seizure cessation with typical treatments decreases with ictal duration.2,4 Common causes of status epilepticus in adults are shown in Box 15.1. See Chapter 92 for a more detailed discussion of seizures. 138

DIAGNOSTIC APPROACH Differential Considerations Because a diagnosis of seizure has major consequences for the patient—including loss of driving privileges and exposure to potentially toxic medicines—the first diagnostic task in the emergency department (ED) is to determine whether the patient has actually experienced a seizure.7 Once a seizure is suspected, there must be a search for underlying precipitants. New-onset seizures or a change in seizure patterns in epileptics may be the primary manifestation of serious underlying diseases, and should prompt a focused evaluation. The differential diagnoses to consider when evaluating for seizure are listed in Box 15.2. Neurogenic seizures must be differentiated from seizure mimics, which include syncope, dysrhythmia, migraine, decerebrate posturing from increased intracranial pressure, dystonic drug reactions, tetanus, strychnine poisoning, and psychogenic events. Syncope, including simple vasovagal syncope, can be associated with occasional twitching movements or even a brief, more generalized convulsion, which can be misdiagnosed as a seizure. This is referred to as convulsive syncope. Myoclonic activity is brief (usually a few seconds) and recovery is as for any other syncopal event, without any postictal altered mental status or confusion. Generalized, sustained (more than a few seconds) tonic-clonic movements, tongue biting, or postictal amnesia are rare with convulsive syncope, and should be presumed to represent a nonsyncopal generalized seizure. When put in the context of when and where the event occurred, the duration of the event,

CHAPTER 15  Seizures

BOX 15.1 

BOX 15.2 

Causes of Status Epilepticus in Adults

Differential Considerations for a Seizure or Seizure-like Event

METABOLIC DISTURBANCES Hepatic encephalopathy Hypocalcemia Hypoglycemia or hyperglycemia Hyponatremia Uremia

INFECTIOUS PROCESSES

Central nervous system abscess Encephalitis Meningitis

WITHDRAWAL SYNDROMES Alcohol Antiepileptic drugs Baclofen Barbiturates Benzodiazepines

CENTRAL NERVOUS SYSTEM LESIONS Acute hydrocephalus Anoxic or hypoxic insult Arteriovenous malformations Brain metastases Cerebrovascular accident Eclampsia Head trauma: acute and remote Intracerebral hemorrhage Neoplasm Posterior reversible leukoencephalopathy

INTOXICATION

Bupropion Camphor Clozapine Cyclosporine Flumazenil Fluoroquinolones Imipenem Isoniazid Lead Lidocaine Lithium MDMA Metronidazole Synthetic cannabinoids Theophylline Tricyclic antidepressants

type of movements, and presence or absence of a postictal state, convulsive syncope usually is easily differentiated from seizure. Migraine with an aura can be confused with nonconvulsive seizures. This is compounded by the finding that many migraine patients have abnormal electroencephalograms (EEGs). Basilar migraine can result in loss of consciousness, making the differentiation even more difficult. These patients will almost always have a history of migraine, often with similar presentation. When the event is the first that the patient has experienced, differentiation can be difficult, and the event should be presumed to be a seizure until this has been excluded by further evaluation and testing. Psychogenic seizures (pseudoseizures) are functional events with a clinical presentation mimicking neurogenic seizures. There is no corresponding alteration in electroencephalographic activ-

The following diagnoses may have presentations that can be difficult to differentiate from seizure activity:

CARDIAC

Vasodepressive (vagal) syncope Orthostatic syncope Cardiogenic syncope

NEUROLOGIC

Stroke, transient ischemic attack Atypical migraine Movement disorders Mass lesions

TOXICOLOGIC

Intoxication, inebriation Oversedation, overanalgesia Extrapyramidal symptoms

METABOLIC

Hypo-, hyperglycemia Thyrotoxicosis Delirium tremens

INFECTIOUS

CNS infections Tetanus

PSYCHIATRIC Pseudoseizure Panic attacks Cataplexy

ity. These events are often conversion reactions and are not under the patient’s conscious control. Up to 30% of patients referred to specialized epilepsy clinics for evaluations are ultimately diagnosed with psychogenic seizures, often with a delay of many years before the correct diagnosis is made. Psychogenic seizures often last longer than neurogenic events, and there usually is a brief or no postictal period. Patients can often recall events during psychogenic seizures, which would be diagnostic because this is not possible in neurogenic generalized seizures. Psychogenic seizures are classically manifested by forward-thrusting pelvic movements and head turning from side to side. Avoidance of noxious stimuli or gaze deviation away from the examiner are also suggestive that an event is psychogenic in origin. On laboratory testing, psychogenic seizure patients do not have a metabolic acidosis, which is nearly universal in those with generalized convulsive seizures.

Pivotal Findings History and physical findings can be useful in differentiating seizure from other acute medical conditions. Retrograde amnesia, lateral tongue biting, and urinary incontinence are all suggestive of a neurogenic event however they are not specific and have been also reported in psychenic seizures. Patients may experience an aura, which in essence is a focal seizure that then often generalizes. Auras are clinically defined by the area of the brain involved. Examples include alterations in sensation, autonomic deregulation such as sweating and flushing, aphasia, a sense of déjà vu, and

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SECTION Two 

Signs, Symptoms, and Presentations

automatisms, such as lip smacking, repeated swallowing or uttering verbal phrases, or picking at clothing.

Symptoms History taking in the patient with seizure is directed by two main questions. First, “Was the incident truly a seizure?” This is important because of the broad differential diagnosis for seizures (see Box 15.2) and the frequency of inaccurate descriptions of seizurelike activity from laypersons. In general, ictal events have five properties: 1. Abrupt onset: History should focus on any evidence of an aura. 2. Brief duration. Seizures rarely last longer than 90 to 120 seconds, although bystanders may overestimate the duration. Status epilepticus is the important exception. 3. Alteration of consciousness. Generalized seizures are manifest by loss of consciousness; focal seizures are often accompanied by an alteration in consciousness. 4. Purposeless activity. Automatisms and undirected tonic-clonic movements are common in ictal events. Tonic-clonic movements are rhythmic and generally do not involve head shaking. 5. Postictal state. This is an acute confusion state that typically occurs with all seizure types except focal and absence. This interval represents the transition from the ictal state back to the patient’s baseline mental status. It can last from minutes to hours, depending on which specific region of the brain triggered the seizure, seizure duration, age, and use of an antiepileptic drug (AED). The second question to direct the history is, “Does this patient have a history of seizures?” If there is a documented history of seizures, ED evaluation may be limited to identifying precipitants and obtaining an AED level, when available. The history should focus on clinical factors known to decrease the seizure threshold, such as recent illness or trauma, drug or alcohol use, sleep deprivation, potential adverse drug-drug interactions with AEDs, medication noncompliance, recent change in anticonvulsant dosing regimens, or change in ictal pattern or characteristics.

Signs The physiologic alterations associated with convulsive ictal activity include hypertension, tachycardia, and tachypnea from sympathetic stimulation. These signs typically resolve quickly after the seizure activity ceases. With more prolonged convulsions, skeletal muscle damage, lactic acidosis and, rarely, rhabdomyolysis may ensue. Autonomic discharges and bulbar muscle involvement may result in urinary or fecal incontinence, vomiting (with aspiration risk), tongue biting, and airway compromise. All these signs are helpful discriminators in the differential evaluation of seizure-like spells, although the presence or absence of these findings neither confirms nor excludes seizure occurrence. Evidence of physical injury should be sought. After the seizure activity has ceased, resting vital signs are evaluated. Fever and underlying infection can cause seizures, although there may be a low-grade temperature elevation immediately after a convulsive generalized seizure. Tachypnea, tachycardia, or an abnormal blood pressure that persists beyond the immediate postictal period may indicate toxic exposure, hypoxia, or a central nervous system lesion. Pertinent physical findings may include nuchal rigidity, stigmata of substance abuse, lymphadenopathy suggestive of human immunodeficiency virus (HIV) disease or malignancy, dysmorphic features, or skin lesions. The examination should also focus on potential adverse sequelae of convulsive seizures, such as head trauma, oral and tongue injury, posterior shoulder dislocation, or back pain. Finally, a complete neurologic examination is performed. A persistent focal deficit after a seizure (eg, Todd’s paralysis) often

indicates the focal origin of the event but also can be evidence of an underlying stroke. Hyperreflexia and a positive Babinski reflex that resolve are indications that a seizure occurred. The patient should be carefully examined for signs of ongoing subtle convulsive or nonconvulsive status epilepticus, especially when there is prolonged postictal depression of consciousness.

Ancillary Testing Laboratory Testing The serum glucose level should be determined in every seizing or postictal patient; women of reproductive age should be tested for pregnancy. If the diagnosis of seizure is uncertain, lactic acidosis may be detectable for up to 1 hour after the seizure resolves. Blood drawn in the field should be sent to the laboratory, along with blood drawn on arrival in the ED, if possible. Presence of a lactic acidosis in the field sample that resolves on ED testing supports a seizure diagnosis. Patients with a significant change in seizure pattern (eg, a substantial increase in seizure frequency despite medication compliance), or with an abnormal neurologic examination should undergo a more thorough laboratory assessment. The serum sodium level is the most important electrolyte to assess. Drug levels are appropriate in patients known or thought to be taking AEDs. Febrile patients should be evaluated for the source of the fever, including consideration of lumbar puncture. For medically ill adults (eg, those with diabetes, cancer, or liver disease or those taking medications that can affect serum electrolyte levels) and in patients with a first-time seizure or substantial change in seizure pattern, serum electrolyte levels, including calcium and magnesium, are indicated. Liver function tests may be helpful if the history or physical examination suggests hepatic disease. Directed toxicology screens should be performed if substance abuse (particularly cocaine, amphetamines, and other sympathomimetic agents) or supratherapeutic use of aspirin or acetaminophen is suspected. Many drug of abuse screening tests do not detect agents such as synthetic cannabinoids, which can cause seziures.8 Headache may be a feature of the patient’s postictal state but, otherwise, the presence of fever and headache or sudden onset of headache is an indication for computed tomography (CT), lumbar puncture, or both.

Imaging Studies An emergent cranial CT scan is indicated when a serious structural lesion is suspected on clinical grounds, including presence of a new focal deficit, persistent altered mental status, fever, recent trauma, persistent headache, history of cancer, anticoagulant use, suspicion or known history of acquired immunodeficiency syndrome (AIDS), age older than 40 years, and partial complex seizure.2,9 If magnetic resonance imaging (MRI) is readily available, it can be used instead of CT in most patients; MRI is more sensitive than CT and yields useful additional diagnostic and prognostic information. It is unlikely, however, that CT will miss a substantial CNS lesion. MRI is likely most useful in patients with a normal CT but recurrent seizure or focal electroencephalographic abnormalities.9 In the fully recovered patient without headache and with normal mental status and neurologic examination findings who has had a single brief seizure, a cranial CT scan can be performed in the ED or at a follow-up visit at the discretion of the treating physician. The literature on head CT imaging for first-time, nonfebrile seizures in children has been inconclusive.8 Emergent neuroimaging is indicated for children with medical or surgical comorbidities or in cases of focal seizures in children younger than 3 years, discussed in Chapter 174.2

CHAPTER 15  Seizures

Electroencephalography Obtaining an EEG is often logistically challenging in the ED, but can be invaluable for patients in whom the diagnosis is unclear or who remain altered. EEG is useful to diagnose nonconvulsive status epilepticus, monitor seizure activity after intubation and neuromuscular blockade, and help differentiate seizures from other nonneurologic presentations.

DIAGNOSTIC ALGORITHM In patients suspected of having had a seizure, the first step is to determine whether the history from the patient or bystander(s) supports the diagnosis. Critical causes of seizures with specialized treatments include eclampsia, toxic ingestion (eg, isoniazid, tricyclic antidepressants), hypoglycemia, hyponatremia, and increased intracranial pressure. Box 15.3 presents the critical and emergent diagnoses that must be considered; Fig. 15.1 presents a diagnostic algorithm. If the patient has a history of seizures, directed questions should be made to characterize the type of seizure. Information regarding the onset, presence of aura, type of seizure, and duration of ictal and postictal periods is key to determining whether the seizure is similar to previous seizures. If the seizure appears typical for the patient, the emergency clinician should identify if the patient is on an AED and inquire about potential triggers that can lower the seizure threshold, such as sleep deprivation, infections, and medications. If the patient is taking an AED for which a serum level can be measured (eg, phenytoin, carbamazepine, valproic acid) and found to be subtherapeutic, then additional medication can be given via the intravenous (IV) or oral (PO) route. The patient can then be discharged, with continued outpatient evaluation with the neurologist or primary care physician. If the patient does not have a history of prior seizures, the diagnostic approach is directed to assess for potential precipitants, such as toxic ingestions, history of immunosuppression, pregnancy, or head trauma. Fingerstick blood glucose, pregnancy test in women, and serum sodium level are the most helpful laboratory tests. An ECG can identify characteristic changes from some toxic ingestions and evidence of risk for dysrhythmias (eg, accessory pathways, prolonged QTc). An obviously gravid patient may increase suspicion for eclampsia, but the condition can occur up to 8 weeks postpartum. A head CT scan can identify traumatic and atraumatic lesions or signs of increased intracranial pressure.

BOX 15.3 

Critical and Emergent Diagnoses to Consider in a Patient With Seizure CRITICAL DIAGNOSES

Status epilepticus, regardless of cause Nonconvulsive status epilepticus Seizures with specialized treatments • Eclampsia • Toxic ingestion (eg, isoniazid [INH], tricyclic antidepressants) • Hypoglycemia • Hyponatremia • Increased intracranial pressure

EMERGENT DIAGNOSES

Infection Posttraumatic seizures Serious mimics of seizure activity (eg, cardiogenic syncope)

Patients who arrive at the ED with ongoing seizure activity or who experience recurrent seizures without recovering from the postictal period are in status epilepticus. These patients generally require a full metabolic evaluation, complete blood count, and head CT. Up to 15% of patients who are successfully treated for convulsive status epilepticus remain in nonconvulsive status epilepticus; therefore, there should be a low threshold for obtaining a bedside EEG, especially if the postictal period is prolonged or automatisms are noted.

EMPIRICAL MANAGEMENT Prehospital Management The prehospital management of the patient with seizures focuses on prompt recognition and treatment of hypoxia, hypotension, and hypoglycemia. Simultaneously, the patient should be protected from injury and, if possible, placed in a lateral decubitus position to reduce aspiration risk. Large retrospective reviews and expert consensus do not support the routine use of cervical spine immobilization unless there is high suspicion for head and neck trauma.1 A nasopharyngeal airway devices may optimize oxygenation. Because most seizures are of brief duration and self-limited, little intervention is generally required. Patients who are still seizing by the time of emergency medical services (EMS) arrival should be suspected to be in status epilepticus and priority should be on rapid administration of a benzodiazepine. Well-designed trials have shown the efficacy and safety of early administration of benzodiazepines during prehospital care.10,11 Intramuscular (IM) midazolam can be quickly administered; there is evidence that it is superior to IV lorazepam in adults and noninferior in children.11 Based on ease of administration and comparable outcome to IV lorazepam, we recommend IM midazolam as the first-line intervention is the field management of status epilepticus (Table 15.1 for dosing). We do not recommend the use of rectal diazepam in managing status because absorption is erratic and not as dependable as other routes.

Emergency Department Management Patients who are actively seizing in the ED should be placed in a monitored bed. Management simultaneously focuses on identifying reversible causes, such as hypoxia and hypoglycemia, and initiating pharmacologic treatment. See Table 15.1 and Fig. 15.2. For the seizing patient, ensuring central nervous system (CNS) perfusion and oxygenation is the priority. Oropharyngeal airways are contraindicated because they may induce gagging and vomiting and may damage the teeth or tongue. Oxygen may be administered to supplement immediate oxygenation and in preparation for possible rapid sequence intubation. Suction should be available but used carefully. Lorazepam is the first-line treatment unless there is no vascular access, in which case we recommend midazolam IM.12,13 If the patient continues to seize despite initial therapy with lorazepam, second-line medications should be given. These include phenytoin, 20 mg/kg IV (at a maximum rate of 50 mg/min to avoid hypotension and arrhythmias), fosphenytoin (a watersoluble prodrug of phenytoin) at 20 phenytoin equivalents (PE)/ kg IM or IV (maximum rate of 150 mg/min), and valproic acid, 20 to 40 mg/kg IV, administered at a rate of 3 to 6 mg/kg/min. If seizures continue, an additional half-loading dose of phenytoin, fosphenytoin, or valproic acid can be given.13 Although limited evidence exists, IV levetiracetam, bolus 1000 to 3000 mg over 15 minutes in adults, and 20 to 60 mg/kg, at a rate of 2 to 5 mg/ kg/min 20 to 60 mg/min over 15 minutes in children, has been recommended.12,13

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SECTION Two 

Signs, Symptoms, and Presentations

Patient presents after having a suspected seizure Does the history suggest a seizure?

Consider elements suggesting alternative diagnosis such as: • Syncope • Stroke • Atypical migraine • Pseudoseizure

Presence of aura Collateral history from witnesses Absence of additional symptoms (eg, palpitations, light-headedness, headache, speech abnormality, etc.) Yes

Yes

No

First-time seizure?

Characterize seizure Onset, aura Duration Partial vs. generalized Postictal state

Assess for potential triggers History: • Medications • Immunosuppression Physical examination: • Signs of head trauma • Focal findings on neurologic examination • Signs of intoxication Ancillary testing • Metabolic: serum glucose, electrolytes level and liver function tests • Drugs: blood alcohol level, drugs of abuse screen

No

Same as previous seizures? Yes

Check AED level and assess for factors that lower seizure threshold.

Does the patient need to be loaded (eg, on phenytoin and subtherapeutic)? Focal neurologic examination or immunosuppression

No Yes

Yes

No

Load AED to reestablish therapeutic levels. Perform CT in the ED or arrange for outpatient CT. Perform CT in the ED. Discharge and continue outpatient management. Fig. 15.1.  Diagnostic algorithm for the patient with seizure in the emergency department. AED, Antiepileptic drug; CT, computed tomography,

If seizure activity continues, a careful reassessment should be done to identify reversible underlying processes, such as bleeding, drug overdose, and metabolic abnormalities that could have been missed until this point. Preparations for endotracheal intubation and administration of third-line therapies are indicated. Concomitantly, specific seizure syndromes should be considered in patients at risk. For example, isoniazid overdose can cause prolonged seizures refractory to benzodiazepines and requires pyridoxine to terminate the seizures. In seizing female patients of childbearing age, eclampsia may be the cause, and IV magnesium is the treatment of choice. Eclamptic seizures refractory to magnesium may respond to benzodiazepines or barbiturates, with or

without phenytoin. Children and psychiatric patients at risk for water intoxication may be hyponatremic and require hypertonic saline therapy. Third-line therapies for status epilepticus include pentobarbital, 5 mg/kg IV at a rate of 1 to 5mg/kg/hr and then a 0.5 to 3.0-mg/kg/hr infusion as needed, phenobarbital, 20 mg/kg IV at 50 to 75 mg/min, midazolam, 0.2 mg/kg and then 0.1 to 0.4 mg/ kg/hr, or propofol, 2 mg/kg IV at 2 to 5 mg/kg/hr and then a 5- to 10-mg/kg/hr infusion, as needed. Patients in status epilepticus should be admitted to the intensive care unit and have continuous electroencephalographic monitoring, which will be key to titrating the dosing of sedation for seizure termination.

CHAPTER 15  Seizures

TABLE 15.1 

Medications Used in the Abortive Treatment of Ongoing Seizure Activity in the Emergency Department MEDICATION

ADULT DOSE

PEDIATRIC DOSE

COMMENTS

Diazepam

5 mg IV, up to a max of 20 mg, or 10–20 mg PR

0.2–0.5 mg/kg IV/ET or 0.5–1.0 mg/kg PR (max, 20 mg)

May repeat in 10 min; monitor respiratory status.

Lorazepam

2 mg IV at 2 mg/min, up to a max of 10 mg

0.05–0.1 mg/kg IV (max 2 mg)

Preferred IV benzodiazepine; may repeat in 10 min; monitor respiratory status.

Midazolam

5 mg, up to a max of 10 mg; IV, IM, IN

0.2 mg/kg IV, IM, IN (max, 5 mg)

Preferred IM benzodiazepine; may repeat in 10 min; monitor respiratory status.

INITIAL THERAPY

SECOND-TIER TREATMENTS Phenytoin

20-mg/kg IV infusion at 50 mg/min (25 mg/ min in patients with cardiac history)

20-mg/kg IV infusion at rate of 1 mg/kg/min

May cause hypotension and dysrhythmia; May give additional 5–10 mg/kg 10 minutes after the loading dose

Fosphenytoin

20 PE/kg IV infusion at 150 mg/min, or 20 PE/kg IM

20 PE/kg IV at rate of 3 mg PE/kg/min

May give an additional 5 PE/kg 10 min after loading dose

Valproic acid

20–40 mg/kg IV at 3–6 mg/kg/min infusion

20–40 mg/kg IV at 1.5–3 mg/kg/min infusion

May give additional dose of 20 mg/kg 10 min after loading dose

Levetiracetam

1000–3000 mg over 15 min

20–60 mg/kg at rate of 2–5 mg/kg/min

Efficacy and safety data come from small studies.

THIRD-TIER TREATMENTS Pentobarbital

5–15 mg/kg IV loading dose at 50 mg/min, then 0.5–5 mg/kg/hr infusion as needed

5–15 mg/kg loading dose at maximum rate of 50 mg/min

Titrate to EEG; intubation and hemodynamic support required

Phenobarbital

20 mg/kg IV at 50–100 mg/min

20 mg/kg IV at 50–100 mg/min

Intubation required; may give additional 5–10 mg/kg 10 min after loading dose

Midazolam

0.2- mg /kg IV loading dose, then 0.05–2 mg/kg/hr

0.2-mg/kg IV loading dose, then 0.05–2 mg/kg/hr

Titrate to EEG; monitor respiratory status

Propofol Infusion

1–2 mg/kg IV loading dose; start at 1–2 mg/kg/hr and increase rate by 0.3–0.6 mg/kg/hr every 5 min

1–2-mg/kg IV loading dose; start at 1–2 mg/kg/hr and increase rate by 0.3–0.6 mg/kg/hr every 5 min

Intubation required; use with caution in doses >4.8 mg/kg/hr

EEG, Electroencephalogram; ET, endotracheal; IM, intramuscular; IV, intravenous; IN, intranasal; PR, per rectum. Second- and third-tier treatments adapted from Brophy GM, Bell R, Claassen J, et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee: guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17:3–23, 2012.

Disposition The appropriate disposition of a patient presenting to the ED with a seizure or history of a recent seizure must be individualized according to the underlying illness, likelihood of recurrence, indications for maintenance pharmacologic therapy, and state reporting regulations. Patients may be discharged home with early referral to a neurologist if they have a normal neurologic examination findings, no significant medical comorbidities, and no known structural brain disease, do not require the use of an AED, did not

require more than one dose of a benzodiazepine in the ED, and are thought to have sufficient resources to comply reliably with follow-up instructions.14 When the diagnosis is uncertain and close follow-up is unlikely, longer observation or admission for observation should be considered. Patients discharged home from the ED should receive statespecific guidance regarding driver’s license privileges, warning about potentially dangerous activities (eg, swimming, climbing ladders and heights, operating machinery), and information for prompt follow-up with a neurologist.

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Prehospital care

SECTION Two 

Signs, Symptoms, and Presentations

• Assess airway, breathing, and circulation • Pulse oximetry • Electrocardiogram • Finger stick (give IV dextrose if glucose > horizontal > anterior)

Vestibular neuritis and labyrinthitis

Inflammation (possibly viral) of the vestibular nerve

Ménière’s disease

Endolymphatic hydrops (excessive endolymph in the inner ear)

Perilymph fistula

Abnormal opening between the middle and inner ear

BOX 16.1 

Causes of Vertigo PERIPHERAL CAUSES

Benign paroxysmal positional vertigo (BPPV) Vestibular neuritis (or neuronitis)/labyrinthitis Ménière’s disease Foreign body in ear canal Acute otitis media Perilymphatic fistula Trauma (labyrinth concussion) Motion sickness Acoustic neuroma

CENTRAL CAUSES

Vertebral basilar artery insufficiency Cerebellar hemorrhage or infarction Tumor Migrainous vertigo Multiple sclerosis Post-traumatic injury (temporal bone fracture, postconcussive syndrome) Infection (encephalitis, meningitis, brain abscess) Temporal lobe epilepsy Subclavian steal syndrome

The mechanism of nonspecific dizziness is poorly understood but is thought to result from impaired central integration of sensory signals. Patients sometimes have difficulty describing their dizziness and are often in a hypervigilant state. Their exaggeration of reactions to normal changes may induce psychological stress. Table 16.1 lists the pathophysiology for selected causes of peripheral vertigo.

DIAGNOSTIC APPROACH Differential Considerations The differential diagnosis for peripheral and central vertigo is summarized in Box 16.1. More detailed information is given on selected causes in Table 16.2. A symptom-based approach to categorizing dizziness identifies four categories: (1) vertigo, (2) near syncope, (3) disequilibrium, and (4) nonspecific dizziness. Unfortunately, this approach is imprecise and new categorization systems have been proposed. One system uses three general categories: (1) acute severe dizziness (eg, vestibular neuritis, stroke), (2) recurrent attacks of dizziness (eg, Ménière’s disease, transient

ischemic attack (TIA), and (3) recurrent positional dizziness (eg, BPPV, cerebellar tumor, multiple sclerosis). Another system uses a “timing and triggers” approach, resulting in four categories: (1) acute vestibular syndrome (eg, vestibular neuritis, cerebellar stroke), (2) spontaneous episodic vestibular syndrome (eg, Ménière’s disease, vertebrobasilar insufficiency [VBI]), (3) triggered episodic vestibular syndrome (eg, BPPV), and (4) chronic vestibular syndrome (eg, polysensory dizziness, psychiatric syndromes, posterior fossa lesions).3 Neither of these approaches has been prospectively validated or systematically studied as a diagnostic paradigm, but they provide an alternative way of thinking about dizziness and vertigo. If the patient has true vertigo, then the cause is either a peripheral lesion, such as from the vestibular system, or a central process, such as cerebrovascular disease or a neoplasm. This distinction is important because peripheral disorders are generally benign, whereas central disorders usually have serious consequences. Box 16.1 lists causes of peripheral and central vertigo. Table 16.3 summarizes the different characteristics of peripheral and central vertigo.

Pivotal Findings Symptoms Vertigo is described as the environment spinning; however, any sensation of disorientation in space or sensation of motion can qualify as vertigo. Vertigo is generally associated with some degree of nausea, vomiting, pallor, and perspiration. Peripheral vertigo is not associated with a change in mentation or syncope. A sensation of imbalance often accompanies vertigo, and this can be difficult to distinguish from true instability, disequilibrium, or ataxia, findings of which indicate a higher likelihood of a central process. The time of onset and the duration of vertigo are important clues to the cause. For example, episodic vertigo produced primarily by a change in position and lasting less than a minute suggests BPPV. A patient with BPPV often thinks his vertigo is constant, because every time he moves his head, he gets vertigo. By teasing out how long each individual episode of vertigo lasts, the physician will be led to the correct diagnosis of BPPV. Acute vestibular syndrome has an arbitrary cutoff of continuous vertigo for at least 1 day, in part to help differentiate acute vestibular syndrome from attacks of Ménière’s disease or prolonged migrainous vertigo. The presence of auditory symptoms suggests a peripheral cause of the vertigo, usually on the side of end-organ disturbance. Acoustic neuroma, which can rarely cause vertigo, is usually associated with progressive unilateral hearing loss, typically of several months’ duration. Hearing loss, vertigo, and tinnitus form the characteristic triad of Ménière’s disease. Labyrinthitis is differentiated from vestibular neuritis in that the former is associated with hearing loss. Head injury can cause vertigo occasionally from intracerebral injury and more commonly from labyrinth concussion. Neck injury can cause vertigo from vertebral artery dissection, resulting in posterior circulation ischemia. Associated neurologic symptoms such as imbalance, dysarthria, or numbness raise the likelihood of TIA and stroke. Although the vast majority of patients with isolated dizziness/ vertigo do not have TIA or stroke, they can be the only initial symptoms of cerebellar and other posterior circulation bleeds, TIAs, and infarction. In these cases, diagnostic testing is directed by assessment of risk based on the history and physical examination.4 Older age, male sex, hypertension, coronary heart disease, diabetes, and atrial fibrillation put patients at higher risk for TIA and stroke. Many medications (such as, aminoglycosides, anticonvulsants, alcohols, quinine, quinidine, and minocycline) have direct vestibulotoxicity.

CHAPTER 16  Dizziness and Vertigo

TABLE 16.2 

Selected Causes of Peripheral and Central Vertigo CAUSE

HISTORY

ASSOCIATED SYMPTOMS

PHYSICAL

1. Benign paroxysmal positional vertigo (BPPV)

Short-lived (typically less than 30 seconds), positional, fatigable episodes; more often in older adults.

Nausea, vomiting

Certain positions can precipitate vertigo. Positive result on Hallpike test (posterior semicircular canal) or supine roll test (horizontal canal).

2. Vestibular neuritis/ labyrinthitis

Vertigo may develop suddenly or evolve over several hours, usually increasing in intensity for hours, then gradually subsiding over several days but can last weeks. Can be worsened with positional change. Sometimes history of viral infection precedes initial attack. Highest incidence is found in third and fifth decades.

Nausea, vomiting

Spontaneous nystagmus beating away from the side of the lesion may be present in the first few hours. Positive head impulse test. Hearing is normal in vestibular neuritis; hearing loss for labyrinthitis.

3. Ménière’s disease

Recurrent episodes of severe rotational vertigo usually lasting hours. Onset usually abrupt. Attacks may occur in clusters. Long symptom-free remissions.

Nausea, vomiting, tinnitus, hearing loss (hearing loss required for diagnosis)

Positional nystagmus is not present; hearing loss

A. Vertebrobasilar insufficiency (VBI)

Should be considered in any patient of advanced age with isolated new-onset vertigo without an obvious cause. More likely with history of atherosclerosis. Can occur with neck trauma. May be preceded by an episode usually lasting minutes.

Often headache; usually neurologic symptoms including dysarthria, ataxia, weakness, numbness, double vision; tinnitus and hearing loss uncommon but possible

Neurologic deficits usually present, but initially neurologic examination can be normal.

B. Cerebellar hemorrhage

Sudden onset of severe symptoms.

Headache, vomiting, ataxia

Signs of toxicity. Dysmetria, true ataxia. Ipsilateral sixth cranial nerve palsy may be present.

C. Occlusion of posterior inferior cerebellar artery (Wallenberg’s syndrome)

Vertigo associated with significant neurologic complaints.

Nausea, vomiting, loss of pain and temperature sensation, ataxia, hoarseness

Loss of pain and temperature sensation on the side of the face ipsilateral to the lesion and on the opposite side of the body, paralysis of the palate, pharynx, and larynx. Horner’s syndrome (ipsilateral ptosis, miosis, and decreased facial sweating).

2. Head trauma

Symptoms begin with or shortly after head trauma. Positional symptoms most common type after trauma. Self-limited symptoms that can persist weeks to months.

Usually mild nausea

Occasionally, basilar skull fracture.

3. Migrainous vertigo

Vertigo attacks can occur during the headache (in one study of 33 patients 24% always had headache with vertigo and 67% had headache sometimes with vertigo) but often occur during the headache-free interval. Most patients have a family history of migraine. Syndrome usually begins in adolescence.

Imbalance, head motion intolerance, photophobia, phonophobia, oscillopsia

No residual neurologic or otologic signs are present after attack.

4. Multiple sclerosis

Vertigo presenting symptom in 7% to 10% and appears in the course of the disease in a third. Onset may be severe. Disease onset usually between ages of 20 and 40. Often history of other attacks with varying neurologic signs or symptoms.

Nausea and vomiting, which may be severe

May have horizontal, rotary, or vertical nystagmus. Nystagmus may persist after the vertiginous symptoms have subsided. Internuclear ophthalmoplegia (INO) highly suggestive for multiple sclerosis. INO is diagnosed when, on eye movement, the adducting eye shows little to no movement while the abducting eye moves normally.

PERIPHERAL

CENTRAL 1. Vascular disorders

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Signs, Symptoms, and Presentations

TABLE 16.3 

Characteristics of Peripheral and Central Vertigo CHARACTERISTIC

PERIPHERAL

CENTRAL

Onset

Sudden

Gradual or sudden

Intensity

Severe initially, often decreasing over time

Mild in most but can be severe in stroke and multiple sclerosis

Duration

Intermittent episodes lasting seconds to less than a minute for BPPV; continuous and lasting hours to days for vestibular neuritis

Usually weeks, months (continuous) but can be seconds or minutes with vascular causes, such as with posterior circulation TIA

Direction of nystagmus

Usually torsional and upbeat (fast phase beating toward forehead) in classic posterior canal BPPV; horizontal in horizontal canal BPPV; horizontal-torsional in vestibular neuritis/labyrinthitis

Purely vertical, spontaneous and purely torsional, direction-changing on lateral gaze, downbeating (fast phase beats toward nose)

Effect of head position

Induces vertigo (BPPV); worsens vertigo (vestibular neuritis)

Usually little change but can worsen with head position change

Associated neurologic findings

None

Usually present

Associated auditory findings

May be present, including tinnitus (Ménière’s disease) and hearing loss (labyrinthitis)

Rarely

BPPV, Benign paroxysmal positional vertigo; TIA, transient ischemic attack.

Physical Examination Vital Signs.  The vital signs, including orthostatic changes, may be the key to identifying a cardiovascular etiology or drug effect as the cause of dizziness. When subclavian steal syndrome is suspected, which also can cause VBI, the pulse and blood pressure should be checked on both sides. Head and Neck.  Carotid or vertebral artery bruits suggest atherosclerosis and risk for TIA or stroke. The vertebral artery can be auscultated in the supraclavicular region. Fluid in the middle ear as a result of a middle ear infection may cause mild vertigo, as can occlusion of the eustachian tubes associated with an upper respiratory tract infection or descent barotrauma. A perforated or scarred eardrum may indicate a perilymphatic fistula, especially if the history includes previous trauma. Examination of the eyes is critical in assessing a patient with vertigo. Pupillary abnormalities may indicate third cranial nerve or descending sympathetic tract involvement. Papilledema suggests increased intracranial pressure. Relatively subtle extraocular movement abnormalities can be the only clue to a cerebellar hemorrhage. A sixth cranial nerve palsy ipsilateral to the hemorrhage may result from early brainstem compression by the expanding hematoma. Internuclear ophthalmoplegia, which indicates brainstem pathology, is recognized when the eyes are in a normal position on straight-ahead gaze, but on eye movement the adducting eye (CN III) is weak or shows no movement while the abducting eye (CN VI) moves normally (although often displaying a coarse nystagmus). This finding indicates an interruption of the MLF on the side that demonstrates third cranial nerve weakness and is virtually pathognomonic of multiple sclerosis. Abnormal nystagmus is the cardinal sign of inner ear disease and the principal objective evidence of abnormal vestibular function. Positional nystagmus, induced by changing the position of the head, strongly suggests an organic vestibular disorder, typically BPPV. Noting the characteristics of the nystagmus can help to differentiate benign peripheral causes from serious central causes (see Table 16.3). Central causes of nystagmus are more likely when the pattern of nystagmus is purely vertical, downbeating (fast phase beating toward the nose), non-fatigable, direction changing with gaze, or spontaneous pure torsional. Severity of nystagmus is directly related to the degree of acute vestibular

hypofunction that occurs. Spontaneous nystagmus usually occurs in severe cases. In mild cases, vestibular asymmetry is less prominent, so spontaneous nystagmus may be subtle or present only for the first few hours. After that it may be only detectable when the patient looks away from the damaged ear or if the examiner performs a head impulse test. Neurologic Examination.  The presence of cranial nerve deficits suggests a space-occupying lesion in the brainstem or cerebellopontine angle, such as an acoustic neuroma, which can rarely manifest with vertigo. Cerebellar function is tested several ways. Dysmetria is the inability to arrest a muscular movement at the desired point and should be assessed with finger-to-finger or finger-to-nose pointing. Dysdiadochokinesia (an inability to perform coordinated muscular movement smoothly) is assessed with rapid alternating movements. Gait assesses ataxia, which when of recent and relatively sudden onset suggests cerebellar hemorrhage or infarction in the distribution of the posterior inferior cerebellar artery or the superior cerebellar artery. Ataxia that is slowly progressive suggests chronic cerebellar disorders. True ataxia may be difficult to discern from the unsteadiness that occurs when a patient with significant vertigo attempts to walk, although other findings (such as, nystagmus and dysmetria) can help narrow the differential diagnosis. This examination is performed when the patient is both sitting and standing, because truncal ataxia, which is seen in midline cerebellar lesions, may become obvious only when the patient has to sit, stand, or walk unaided. Any marked abnormality (eg, consistent falling or a grossly abnormal gait) should suggest a central lesion, especially in a patient whose vertiginous symptoms have subsided. Patients with an acute peripheral vestibular lesion typically can stand, although they will likely veer toward the side of the lesion. Patients with central vertigo often cannot stand without support. The main features of a cerebellar gait are a wide base, unsteadiness, irregularity of steps, tremor of the trunk, and lurching from side to side. The unsteadiness is most prominent on arising quickly from a sitting position, turning quickly, or stopping suddenly while walking. Patients with gait ataxia also cannot perform heel-to-toe walking. Positional Testing.  Positional testing can confirm the diagnosis of BPPV. The Hallpike test, also known as the Dix-Hallpike

CHAPTER 16  Dizziness and Vertigo

BOX 16.2 

Classic Findings During Hallpike Test in Posterior Canal Benign Paroxysmal Positional Vertigo Latency (delay in nystagmus and vertigo once in head-hanging position) of approximately 3 to 10 seconds, although delay can take up to 30 seconds on rare occasions Reproduction of vertigo symptoms in head-hanging position Upbeat (fast phase toward forehead) and torsional nystagmus (usually toward the downward ear) Vertigo and nystagmus escalates in head-hanging position, then slowly resolves over 5 to 30 seconds Nystagmus and vertigo may reverse direction when patient returns to sitting position Nystagmus and vertigo decrease with repeated testing (fatigability)

Fig. 16.1.  Testing for positional vertigo and nystagmus.

test or the Nylen-Barany test, confirms the diagnosis of posterior canal BPPV, which is the most common variant of BPPV.5 This test should be reserved for those patients suspected of positional vertigo, and caution should be exercised in performing it in patients with acute vestibular syndrome (acute and constant dizziness, nausea or vomiting, unsteady gait, nystagmus, and intolerance to head motion lasting more than a day) whose main differential diagnosis include vestibular neuritis and stroke.6 Some evidence indicates that provocative testing may lead to a nonspecific worsening of symptoms in these patients, which could be misinterpreted as diagnostic of a peripheral disorder before stroke has been adequately excluded. Thus, if a patient is actively experiencing vertigo during history taking and there has been no immediate prior head movement, then the Hallpike test should not be performed because this history is inconsistent with BPPV, which requires head movement to elicit symptoms. The Hallpike test is performed with the patient sitting up. The examiner turns the patient’s head 45 degrees to one side and then moves the patient from the upright seated position to a supine position with the head overhanging the edge of the gurney (Fig. 16.1). The patient is queried for the occurrence of vertigo, and the eyes are observed for nystagmus after a latency period on the order of a few seconds. In a patient with classic posterior canal BPPV, the nystagmus usually lasts 5 to 30 seconds and is combined upbeating (the fast phase beats toward the forehead) and ipsilateral torsional (the top pole beating toward the downward ear). The patient is then brought back up to the seated position, and the test is repeated with the head turned 45 degrees to the other side. Findings are summarized in Box 16.2. In general, if the patient has posterior canal BPPV, only one side should be positive during the Hallpike test, although it is theoretically possible to have otoliths inappropriately located in both right and left posterior semicircular canals. Assuming unilateral involvement, the downward ear indicates the involved side, which is the side to start with when treating with the curative bedside Epley maneuver. If the patient pre-identifies the side that causes the symptoms, we test the opposite side first, and this should result in a negative Hallpike test. We then test the other side and, if positive, continue on to complete the Epley maneuver. (The first step of the Epley maneuver is the first part of the Hallpike test, which involves turning the head 45 degrees to the involved side and then laying the patient with the head hanging over the edge of the gurney.)

If the Hallpike test is negative or seems to be positive bilaterally, one can use the supine roll test to test for the horizontal canal variant of BPPV.7,8 The patient starts in the supine position and unlike the Hallpike test, the head does not need to overhang the edge of the gurney. The head is then turned 90 degrees to each side. With a positive test, the patient will have reproduction of symptoms and horizontal nystagmus with the head turned in either direction. The side that is involved is the one with the more intense symptoms and more dramatic nystagmus. Note that the nystagmus will change direction, but this is due to a change in head position and not from a change in gaze direction and so is not concerning for a central cause of vertigo. A video of a case involving failed attempts at the barbeque roll to treat horizontal BPPV, followed by conversion to posterior canal BPPV after a Gufoni maneuver (with resultant cure using the Epley maneuver), can be found at www.youtube.com/watch?v=iOJOArGmepM. The head impulse, or head-thrust test, is used to diagnose vestibular neuritis and labyrinthitis. The physician stands face to face with the patient and places both hands on the sides of the patient’s head. The patient stares at the examiner’s nose while the examiner rapidly turns the patient’s head approximately 10 degrees to one side. Normally the patient’s eyes should keep focusing on the examiner’s nose. If there is a problem with the vestibular nerve, the eyes will temporarily move along with the head. A corrective saccade will then occur, in which the eyes jerk back toward the midline. If a saccade is seen, this denotes a positive head-thrust test result and indicates vestibular nerve dysfunction. In general, eliciting a positive head impulse test indicates a benign peripheral cause of vertigo, such as vestibular neuritis. The head must be turned rapidly because a false negative test may result otherwise, leading to incorrectly suspecting a central cause. HINTS.  HINTS (Head Impulse test, Nystagmus, Test of Skew) is a bedside oculomotor examination test that has been proposed as a way to differentiate central from peripheral vertigo in patients with acute vestibular syndrome. The majority of such patients will have vestibular neuritis, but the HINTS examination may help to identify the smaller numbers who are suffering from stroke or other central causes of vertigo. The first part of HINTS is the head impulse test and as described earlier, a corrective saccade indicates a positive test and is more reassuring for vestibular neuritis. The second part (nystagmus) refers to a direction change of nystagmus on eccentric gaze. For example, when the patient looks to the left, the fast component beats to the left; and when the patient looks to the right, the fast component beats to the right. This direction-changing nystagmus may indicate a stroke in a patient with acute vestibular

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Signs, Symptoms, and Presentations

TABLE 16.4 

Differentiating Benign Paroxysmal Positional Vertigo From Vestibular Neuritis/Labyrinthitis BENIGN PAROXYSMAL POSITIONAL VERTIGO

VESTIBULAR NEURITIS/LABYRINTHITIS

Age

More common in older adults

More common in younger patients

Hearing loss

None

None in vestibular neuritis; hearing loss in labyrinthitis

Frequency of symptoms

Episodic (occurs with certain movements of the head)

Constant

Hallpike test

Positive usually on one side only with upbeat and torsional nystagmus and reproduction of vertigo symptoms

Symptoms may be worsened in head-hanging position (Note: It is advised not to administer Hallpike test in a patient with a clinical history consistent with vestibular neuritis or labyrinthitis.)

Head impulse test

Negative (Note: It is advised not to administer head impulse test in a patient with a clinical history consistent with BPPV.)

Positive (corrective saccade seen)

Epley maneuver

Highly effective

Ineffective

Recurrence

Frequent

Rare (2% to 11%)

BPPV, Benign paroxysmal positional vertigo.

syndrome. The third part (test of skew) refers to vertical ocular misalignment during alternate cover testing and its presence is suggestive of brainstem strokes.9 Using HINTS requires experience and practice, and it should only be used in patients with a first ever episode of constant vertigo from acute vestibular syndrome as was required in the clinical studies involving the HINTS exam. For example, applying the head impulse test in a patient who is dizzy from BPPV would result in a negative test and may cause the emergency physician to incorrectly conclude that the patient’s dizziness could be from a central cause of vertigo. In general, performing both the Hallpike test and the HINTS examination on the same patient is not appropriate. Instead, BPPV and acute vestibular syndrome should be distinguished from each other by history and by the presence of spontaneous nystagmus.

Ancillary Testing Most routine laboratory testing is not helpful in the evaluation of a vertiginous patient except for a finger-stick blood glucose test. Blood counts and blood chemistries are helpful if the dizziness is described as lightheadedness. An electrocardiogram can evaluate for myocardial ischemia or dysrhythmia as a potential cause. Radiologic Imaging.  Acute vertigo by itself does not warrant urgent computed tomography (CT) or magnetic resonance imaging (MRI) in all patients, particularly patients in whom a clear picture of peripheral vertigo emerges, such as with BPPV. Risk factor assessment can be helpful in deciding which patients warrant imaging: Older age, male sex, hypertension, coronary artery disease, diabetes, and atrial fibrillation put patients at higher risk for more serious causes of dizziness and vertigo. If cerebellar hemorrhage, cerebellar infarction, or other central lesions are suspected, emergent CT or MRI of the brain is indicated. MRI, when available, has become the diagnostic modality of choice for posterior fossa (cerebellum, medulla, and pons) lesions, as well as for rare causes of vertigo, including acoustic neuroma and multiple sclerosis.

DIAGNOSTIC ALGORITHM Most cases of vertigo are of peripheral origin and are not usually life-threatening. BPPV and vestibular neuritis are likely the most common peripheral causes of vertigo encountered in the ED. However, they are diagnosed and treated very differently. Table 16.4 helps to differentiate between these two diagnoses (Fig. 16.2).

EMPIRICAL MANAGEMENT Management is based on an accurate diagnosis that distinguishes the serious central causes of vertigo from the less serious peripheral causes. Any suggestion of cerebellar hemorrhage warrants immediate imaging with CT or MRI and neurosurgery consultations. VBI should be considered in any patient of advanced age or at high risk of cerebrovascular disease who presents with isolated, new-onset vertigo without an obvious cause. Because of the possibility of progression of new-onset VBI in the first 24 to 72 hours, hospital or observation unit admission and consideration of early magnetic resonance angiography (MRA) are reasonable, even in a stable patient. Changing or rapidly progressive symptoms suggest impending posterior circulation occlusion. If CT or MRI excludes hemorrhage as the source of the patient’s symptoms, an immediate neurologic consultation, further imaging (such as, angiography), and possible anticoagulation are indicated. Canalith repositioning maneuvers, such as the Epley maneuver, are extremely effective in treating BPPV, including in the ED setting.10 The Epley maneuver, which is used to treat posterior semicircular canal BPPV, involves four to five sequential rotations of the head, holding each position for approximately 30 seconds or until the nystagmus and vertigo resolves, as demonstrated in Figure 16.3. Failure of the Epley maneuver is usually due to one of two problems: First, the head is lifted too high during the third step of the Epley maneuver, in which the patient rolls onto his side and looks toward the ground. Second, the Epley maneuver is often inappropriately applied to a patient who has vestibular neuritis, which is distinct from BPPV (see Table 16.4). The “barbecue roll” is a simple maneuver that can be used to treat the horizontal canal variant of BPPV, which is diagnosed by the supine roll test. The patient lies flat on the gurney with the head turned 90 degrees to the involved side. The head is then rotated in 45-degree intervals away from the involved side (each turn is held approximately 30 seconds or until nystagmus and vertigo resolve). Eventually the patient needs to turn over into the prone position. The maneuver is completed once the head has returned to the original starting position. The Gufoni maneuver is an alternative treatment for the horizontal canal variant (see http://careguides-videos.med.umich.edu/media/Gufoni+Left +Horizontal-Geotropic/1_3sii1rw8/20345631). Two relatively recent practice guidelines were published that included information on the use of medications to treat BPPV. One found no evidence to support a recommendation of any medication in the routine treatment of BPPV.11 The other

CHAPTER 16  Dizziness and Vertigo

Hypoglycemia Anemia Dysrhythmias Myocardial infarction Hypovolemia Vasovagal Sepsis Drug side effect

Near-syncope/ light-headedness

Gait instability

Disequilibrium

Spinning or sensation of motion

Peripheral Attacks: Sudden, severe, can last anywhere from seconds to minutes to days Nystagmus: Varies (see Table 16-2) No neurologic findings Auditory findings may be present

BPPV Short-lived, positional episodes caused by stray otoliths in semicircular canal Positive Hallpike test (posterior canal) or supine roll test (horizontal canal)

Dizziness

Vestibular neuritis/labyrinthitis Severe vertigo for days Mild persistent vertigo up to weeks and months No auditory symptoms (vestibular neuritis); positive hearing loss (labyrinthitis) Positive head impulse test

Vertigo

Central Attacks: Gradual, mild, usually continuous for weeks or months but can be sudden, severe and seconds or minutes with vascular causes Nystagmus: Varies (see Table 16-2) Can worsen with head position change Neurologic findings usually present No auditory findings

Ménière’s disease Tinnitus Hearing loss Attacks in clusters Long symptom-free intervals

Vertebrobasilar migraine Cerebellar hemorrhage Severe vertigo, headache, vomiting, ataxia Head/neck trauma Multiple sclerosis

Vertebrobasilar insufficiency Usually associated neurologic abnormalities More likely in the elderly and those with history of cardiac or cerebrovascular disease Fig. 16.2.  Diagnostic algorithm for dizziness and vertigo. BPPV, Benign paroxysmal positional vertigo.

concluded that clinicians should not routinely treat BPPV with vestibular suppressant medications.12 However, both guidelines were from specialty societies whose patients often have chronic and likely milder forms of BPPV than patients who develop acute BPPV and come to the ED. For ED patients who are actively vomiting or cannot tolerate canalith repositioning maneuvers and for those with other causes of acute vertigo (such as, vestibular neuritis), it is reasonable to administer vestibular suppressants. Most vestibular suppressants are antiemetic medications (Table 16.5), which not only suppress nausea and vomiting but also decrease the sensation of vertigo. Although promethazine (Phenergan) is likely the most effective parenteral vestibular suppressant, the U.S. Food and Drug Administration (FDA) has given intravenous use of promethazine a black box warning, and it is now recommended to be administered only in intramuscular or oral forms.13 Trials using various agents including dimenhydrinate, lorazepam, and droperidol have given mixed results. We recommend intravenous ondansetron as the first line intravenous medication for symptomatic vertigo. Patients with intractable vertigo and vomiting that are unresponsive to antiemetics can be given an intravenous benzodiazepine, such as 1 to 2 mg of intravenous lorazepam. However, it is generally not recommended to discharge patients with oral benzodiazepines, especially in patients with vestibular neuritis and labyrinthitis because these patients undergo a process of vestibular habituation, in which the vestibular system learns to adapt to the mismatch of

information it is receiving, and benzodiazepines can interfere with this process. Meclizine (Antivert) 25 mg every 4–6 hours can be given in the ED, although its time of onset is approximately 1 hour. Because it can exacerbate symptoms in patients with non-vertiginous types of dizziness, it should be reserved for patients with BPPV who have failed the Epley maneuver or for patients who have an alternative diagnosis of peripheral vertigo, such as vestibular neuritis. Transdermal scopolamine has shown disappointing results for treatment of peripheral vertigo but may be considered a thirdline option. Vestibular neuritis, which is inflammation of the eighth cranial nerve, is thought to have a similar mechanism to Bell palsy.14 Patients typically have severe vertigo for 1 to 2 days with gradual resolution over weeks to months. Nystagmus may be spontaneous during the first several hours of symptoms, and patients will have a positive head impulse test. Although the evidence is weak, corticosteroids are possibly helpful using a 22-day taper of methylprednisolone beginning with a dose of 100 mg each morning.15 Antivirals, such as valacyclovir, are not helpful in the treatment of vestibular neuritis. Until certainty is reached, we recommend steroid treatment with prednisone (or methylprednisolone) with a gradual taper over 2 to 3 weeks, although shared decision making with the patient is an acceptable alternative. Some cases of Ménière’s disease have been treated successfully with vasodilation and diuretic therapy. Diets low in sodium and

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Signs, Symptoms, and Presentations TABLE 16.5 

Medications for Acute Vertigo USUAL STARTING DOSAGE

ANTIEMETIC ACTION

Promethazine (Phenergan)

25 mg IM, PO, PR (black box warning for IV administration)

Moderate

Ondansetron (Zofran)

4 mg IV, SL/PO, IM

Prominent

Dimenhydrinate (Dramamine)

50 mg IM, IV, PO

Moderate

Prochlorperazine (Compazine)

10 mg IV, IM, PO, PR

Prominent

Droperidol (Inapsine)

2.5 mg IM (black box warning for IV administration)

Prominent

Metoclopramide (Reglan)

10 mg IV, IM, PO

Prominent

Lorazepam (Ativan)

1 mg IV, IM, PO

Mild

Diazepam (Valium)

2.5 to 5.0 mg IV, IM, PO

Mild

Meclizine (Antivert)

25 mg PO

Mild

Scopolamine (Transderm-Scop)

0.2 mg transdermal patch, IM, PO

Moderate

DRUG

A

B E

D

C (c) 2001 Northwestern University

Fig. 16.3.  A to E, The Epley maneuver for benign paroxysmal peripheral vertigo, also known as the particle repositioning or canalith repositioning procedure. (Image used with permission of Timothy C. Hain, Professor of Neurology, Feinberg School of Medicine, Northwestern University, www.dizziness-and-balance.com/disorders/bppv/bppv.html.)

caffeine and cessation of smoking also have been helpful. However, the diagnosis of Ménière’s disease requires documentation of hearing loss, so this is not a diagnosis that can be typically made during an ED visit.

DISPOSITION Documented or suspected VBI or cerebellar hemorrhage or infarction require diagnostic evaluation, treatment, and, usually, hospitalization. In patients older than age 55 with vascular risk factors, admission for observation and imaging of cerebral vasculature should be considered if the diagnosis is not certain. Most

IM, Intramuscular; IV, intravenous; PO, per os (by mouth); PR, per rectum; SL, sublingual.

younger patients with peripheral causes of vertigo can be discharged from the ED after symptoms have been controlled. Some patients with peripheral vertigo may have such severe symptoms (eg, intractable vomiting, inability to walk) despite medications that they require hospital admission for intravenous hydration, vestibular suppressants, and antiemetics. Reassessment of neurologic examination findings and response to therapy are important to ensure that the vertigo is not of central origin. Discharged patients should receive primary care, neurology, or otolaryngology follow-up, particularly if symptoms are not significantly improved within 72 hours or are worsening despite symptomatic treatment.

KEY CONCEPTS 1. Associated neurologic complaints, such as imbalance, dysarthria, or numbness raise the likelihood of TIA or stroke as the cause of a patient’s dizziness/vertigo. 2. Benign paroxysmal positional vertigo (BPPV) requires head movement to elicit symptoms. Consequently, the Hallpike test should not be performed if the patient is actively symptomatic during history taking (and the patient’s head has not been recently moved) because such a history is inconsistent with BPPV. 3. When performing the Hallpike test, the head should be turned to the side 45 degrees prior to laying the patient back into the head-hanging position. 4. A positive Hallpike test should elicit upbeating nystagmus. 5. The Epley maneuver is used to treat posterior semicircular canal BPPV, which is the most common subtype of BPPV. 6. Central causes of nystagmus are more likely when the pattern of nystagmus is purely vertical, downbeating (fast phase beating toward the nose), non-fatigable, direction changing with gaze, or spontaneous pure torsional.

7. The presence of auditory symptoms suggests a peripheral cause of the vertigo. 8. Acute vestibular syndrome is diagnosed when dizziness develops acutely; is constant; is accompanied by nausea or vomiting, unsteady gait, nystagmus, and intolerance to head motion; and persists for longer than a day. 9. Neck injury can cause vertigo from vertebral artery dissection, resulting in posterior circulation ischemia. 10. Abnormal nystagmus is the cardinal sign of inner ear disease and the principal objective evidence of abnormal vestibular function. 11. HINTS (Head Impulse test, Nystagmus, Test of Skew) is a bedside oculomotor examination test that has been proposed as a way to differentiate central from peripheral vertigo in patients with a first ever onset of constant vertigo from acute vestibular syndrome. 12. Meclizine (Antivert) has a time of onset of approximately 1 hour. 13. Do not prescribe benzodiazepines to patients with vestibular neuritis or labyrinthitis who are discharged home. Such medications can interfere with the process of vestibular rehabilitation.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 16  Dizziness and Vertigo

REFERENCES 1. Kim AS, Fullerton HJ, Johnston SC: Risk of vascular events in emergency department patients discharged home with diagnosis of dizziness or vertigo. Ann Emerg Med 57:34–41, 2011. 2. Lee CC, Ho HC, Su YC, et al: Increased risk of vascular events in emergency room patients discharged home with diagnosis of dizziness or vertigo: a 3-year follow-up study. PLoS ONE 7:e35923, 2012. 3. Edlow JA: Diagnosing dizziness: we are teaching the wrong paradigm! Acad Emerg Med 20:1064–1066, 2013. 4. Lee H: Isolated vascular vertigo. J Stroke 16:124–130, 2014. 5. Kim JS, Zee DS: Clinical practice: benign paroxysmal positional vertigo. N Engl J Med 370:1138–1147, 2014. 6. Tarnutzer AA, Berkowitz AL, Robinson KA, et al: Does my dizzy patient have a stroke? A systematic review of bedside diagnosis in acute vestibular syndrome. CMAJ 183:E571–E592, 2011. 7. Mandala M, Pepponi E, Santoro GP, et al: Double-blind randomized trial on the efficacy of the Gufoni maneuver for treatment of lateral canal BPPV. Laryngoscope 123:1782–1786, 2013. 8. van den Broek EM, van der Zaag-Loonen HJ, Bruintjes TD: Systematic review: efficacy of Gufoni maneuver for treatment of lateral canal benign paroxysmal

positional vertigo with geotropic nystagmus. Otolaryngol Head Neck Surg 150:933– 938, 2014. 9. Cohn B: Can bedside oculomotor (HINTS) testing differentiate central from peripheral causes of vertigo? Ann Emerg Med 64:265–268, 2014. 10. Hilton MP, Pinder DK: The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo. Cochrane Database Syst Rev (12):CD003162, 2014. 11. Fife TD, Iverson DJ, Lempert T, et al: Practice parameter: therapies for benign paroxysmal positional vertigo (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 70:2067– 2074, 2008. 12. Bhattacharyya N, Baugh RF, Orvidas L, et al: Clinical practice guideline: benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 139:S47–S81, 2008. 13. Amini A, Heidari K, Asadollahi S, et al: Intravenous promethazine versus lorazepam for the treatment of peripheral vertigo in the emergency department: a double blind, randomized clinical trial of efficacy and safety. J Vestibular Res 24:39–47, 2014. 14. Jeong SH, Kim HJ, Kim JS: Vestibular neuritis. Semin Neurol 33:185–194, 2013. 15. Fishman JM, Burgess C, Waddell A: Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev CD008607, 2011.

CHAPTER 16: QUESTIONS & ANSWERS 16.1. Which maneuver should be used to treat benign paroxysmal positional vertigo (BPPV) of the horizontal semicircular canal? A. Barbeque roll B. Epley maneuver C. Hallpike test D. Head impulse test Answer: A. The Epley maneuver is used to treat posterior canal BPPV. The Hallpike test is used to diagnose posterior canal BPPV. The head impulse test is used to diagnose vestibular neuritis and labyrinthitis. The supine roll test, in which the patient lies flat on the gurney and the head is turned to each side, is used to diagnose horizontal canal BPPV, whereas the barbeque roll maneuver is used to treat the horizontal variant of BPPV. 16.2. Which of the following examination findings requires further testing and/or consultation with a specialist? A. Direction changing nystagmus on change in head position B. Direction changing nystagmus on change in lateral gaze C. Positive head impulse test D. Torsional upbeat nystagmus during Hallpike test Answer: B. Direction changing nystagmus on change in gaze is concerning for a central cause of vertigo and makes up part of the HINTS test. 16.3. Internuclear ophthalmoplegia most often suggests a diagnosis of: A. Horizontal canal BPPV B. Labyrinthitis

C. Multiple sclerosis D. Vestibular neuritis Answer: C. Internuclear ophthalmoplegia is diagnosed when, on eye movement, the adducting eye shows little to no movement while the abducting eye moves normally. In a vertigo patient, this finding is virtually pathognomonic for multiple sclerosis. 16.4. Which of the following is a central cause of vertigo? A. Labyrinthitis B. Ménière’s disease C. Vertebrobasilar insufficiency D. Vestibular neuritis Answer: C. All the other causes are peripheral. 16.5. Continuous vertigo of what duration is used to define acute vestibular syndrome? A. 1 hour B. 8 hours C. 24 hours D. 1 week Answer: C. Acute vestibular syndrome has an arbitrary cutoff of continuous vertigo for at least 1 day in part of help differentiate acute vestibular syndrome from attacks of Ménière’s disease or prolonged migrainous vertigo.

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C H A P T E R 17 

Headache Christopher S. Russi  |  Laura Walker PERSPECTIVE Headache is consistently among the top reasons for visit to the emergency department (ED). The vast majority of patients who have a primary complaint of headache do not have a serious medical cause for the problem. Most common primary headache etiologies are benign, such as tension headache and migraine. A minority of headaches will be secondary to an underlying medical or surgical condition; a patient may present with headache due to a serious life-threatening disease requiring prompt diagnosis and treatment. The low incidence of serious disease can create a “needle in the haystack” phenomenon, and headache is disproportionately represented in emergency medicine malpractice claims despite widespread overuse of imaging for benign headache conditions. Although representing only 0.5% to 6% of presentations of acute headache to the ED, the most important and commonly encountered life-threatening cause of severe sudden head pain is subarachnoid hemorrhage (SAH).1 Unfortunately, this is a diagnosis that is also missed on first presentation over 25% of the time.2 The other significant, potentially life-threatening causes of headache occur even less frequently. As is the case for SAH, these other serious disorders (ie, meningitis, carbon monoxide poisoning, temporal arteritis, acute angle-close glaucoma, intracranial hemorrhage [ICH], cerebral venous sinus thrombosis, and increased intracranial pressure) can often be linked with specific historical elements and physical findings that facilitate their diagnosis.

Pathophysiology The brain parenchyma is insensitive to pain. The pain-sensitive areas of the head include the meninges, the arteries and veins supplying the brain, and the various tissues lining the cavities within the skull. The ability of the patient to specifically localize head pain is often poor. Much of the pain associated with headache, particularly with vascular headache and migraines, is mediated through the fifth cranial nerve. Such pain may proceed back to the nucleus and then be radiated through various branches of the fifth cranial nerve to areas not directly involved. Inflammation in a specific structure (eg, periapical abscess, sinusitis, or trigeminal neuralgia) is much easier to localize than the relatively diffuse pain that may be generated by tension or traction headaches. Pains in the head and neck may easily overlap. They should be thought of as a unit when complaints of headache are considered.

DIAGNOSTIC APPROACH Differential Diagnosis Considerations The differential diagnosis of headache is complex due to the large number of potential disease entities and the diffuse nature of many types of pain in the head and neck region (Table 17.1). In evaluating the patient with a primary complaint of headache, the top priority is to exclude the causes with significant morbidity and

mortality: SAH, ICH, meningitis, encephalitis, and mass lesions. Carbon monoxide is an exogenous toxin, the effects of which may be reversible by removing the patient from the source and administering oxygen. Carbon monoxide poisoning is a rare example of a headache in which relatively simple interventions may quickly improve a critical situation; however, returning the patient to the poisoned environment without a diagnosis could be lethal (see Chapter 153).

Pivotal Findings Physical findings may be minimal or nonspecific, even in serious causes of headache, so the history is the pivotal part of the evaluation (Table 17.2). 1. Determine the pattern and the onset of the pain. Patients may remember having had frequent and recurrent headaches similar to the one they have on the current ED visit; a marked variation in the headache pattern can signal a new or serious problem. A rapid and severe onset of pain (“thunderclap”) has been associated with serious causes of headache, and this warrants strong consideration of a cerebrovascular etiology.3 Slow onset of headache should not be solely relied on to rule out a potentially life-threatening cause, and the nature of the onset usually is not possible to ascertain if the headache came on during sleep. Almost all studies dealing with subarachnoid bleeding report that patients moved from the pain-free state to severe pain within seconds to minutes. The thunderclap headache is common in acute presentations of SAH but is not highly specific. If the patient with moderate or severe headache can indicate the precise activity in which he or she was engaging at the time of the onset of the headache, the suddenness of onset warrants consideration of SAH. Careful questioning about the onset of headache may lead to the correct diagnosis of SAH, even if the pain is improving at the time of evaluation. 2. The patient’s activity at the onset of the pain may be helpful. Headaches that come on during exertion have a relationship to vascular bleeding.4 Additionally, although the syndrome of postcoital headache is well known, coitus is also recognized as an activity associated with SAH, so a pattern of previous postcoital headache is key, as is understanding whether the current headache fits that pattern. Postcoital headaches require the same evaluation on initial presentation as any other exertionrelated head pain. 3. If there is a history of head trauma, the differential diagnosis shifts markedly toward epidural and subdural hematoma, traumatic SAH or intraparenchymal hemorrhage, skull fracture and closed head injuries, such as concussion and diffuse axonal injury. 4. The intensity of head pain is difficult to quantify objectively. Almost all patients who come to the ED consider their headaches to be severe. Use of a pain scale with appropriate explanation may help differentiate patients initially but has more value in monitoring their response to therapy. Rapid resolution 153

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TABLE 17.1 

Headache Etiologies and Associated Spectrum of Severity of Disease by System ORGAN SYSTEM

CRITICAL

EMERGENT

NONEMERGENT

CNS, neurologic, vessels

SAH Carotid dissection Venous sinus thrombosis

Shunt failure Traction headaches Tumor or mass Subdural hematoma Reversible cerebral vasoconstriction syndrome

Migraine, various types Vascular headache, various types Trigeminal neuralgia Post-traumatic (concussion) Post LP headache

Toxic/metabolic, environmental

Carbon monoxide poisoning

Mountain sickness

Collagen vascular disease

Temporal arteritis

Ocular/ENT

Glaucoma

Sinusitis Dental problems TMJ disease

Musculoskeletal

Tension headache Cervical strain

Allergy Infectious disease

Cluster or histamine headaches Bacterial meningitis Encephalitis

Brain abscess

Febrile headaches, non-neurologic source

Pulmonary or oxygen

Anoxic headache Anemia

Cardiovascular

Hypertensive crisis

Hypertension (rare)

Unspecified

Preeclampsia IIH

Effort-dependent or coital headaches

CNS, Central nervous system; ENT, ear, nose, and throat; IIH, idiopathic intracranial hypertension; LP, lumbar puncture; SAH, subarachnoid hemorrhage; TMJ, temporomandibular joint.

TABLE 17.2 

Signs and Symptoms of Various Headache Etiologies SYMPTOM

FINDING

POSSIBLE DIAGNOSIS

Sudden onset of pain

“Thunder clap” with any decreased mentation, any positive focal finding, meningismus or intractable pain

SAH, cervical artery dissection, cerebral venous thrombosis

Sudden onset of pain

Recurrent thunder clap episodes, may be associated with stroke-like symptoms

Reversible cerebral vasoconstriction syndrome

“Worst headache of my life”

Associated with sudden onset

SAH, cervical artery dissection, cerebral venous thrombosis

Near syncope or syncope

Associated with sudden onset

SAH, cervical artery dissection, cerebral venous thrombosis

Increased with jaw movement

Clicking or snapping; pain with jaw movement

TMJ disease

Facial pain

Fulminant pain of the forehead and area of maxillary sinus; nasal congestion

Sinus pressure or dental infection

Forehead and/or temporal area pain

Tender temporal arteries

Temporal arteritis

Periorbital or retro-orbital pain

Sudden onset with tearing

Temporal arteritis or acute angle closure glaucoma

SAH, Subarachnoid hemorrhage; TMJ, temporomandibular joint.

of pain in the ED, either from time or therapy, should not be relied on to rule out serious causes of headache.5 5. The character of the pain (eg, throbbing, pressure), although sometimes helpful, may not be adequate to differentiate one type of headache from another. 6. The location of head pain at onset and as the pain progresses is helpful when the patient can identify a specific area. It is certainly useful to direct the examination to evaluate for externally visible contributing factors, such as an infectious process.

Unilateral pain is more suggestive of migraine or localized inflammatory process in the skull (eg, sinus) or soft tissue. Muscle tension headache often starts at the base of the skull and can extend over the entire head, following the occipitalfrontal aponeurosis. Temporal arteritis, temporomandibular joint (TMJ) disease, dental infections, and sinus infections frequently have a highly localized area of discomfort. Meningitis, encephalitis, SAH, and even severe migraine, although intense in nature, are usually more diffuse in their localization.

CHAPTER 17  Headache

BOX 17.1 

Emergent Causes of Headache and Associated Risk Factors 1. Carbon monoxide poisoning a. Breathing in enclosed or confined spaces with engine exhaust or ventilation of heating equipment b. Multiple household members with the same symptoms c. Wintertime and working around machinery or equipment producing carbon monoxide (eg, furnaces) 2. Meningitis, encephalitis, abscess a. History of sinus or ear infection or recent surgical procedure b. Immunocompromised state c. General debilitation with decreased immunologic system function d. Acute febrile illness—any type e. Extremes of age f. Impacted living conditions (eg, military barracks, college dormitories) g. Lack of primary immunization 3. Temporal arteritis a. Age >50 b. Females more often than males (4 : 1) c. History of other collagen vascular diseases (eg, systemic lupus) d. Previous chronic meningitis e. Previous chronic illness, such as tuberculosis, parasitic or fungal infection 4. Glaucoma—acute angle closure a. Not associated with any usual or customary headache patterns b. History of previous glaucoma c. Age >30 d. History of pain increasing in a dark environment 5. Increased intracranial pressure a. History of previous benign intracranial hypertension b. Presence of cerebrospinal fluid (CSF) shunt c. History of congenital brain or skull abnormalities

7. Exacerbating or alleviating factors may be important. Patients whose headaches rapidly improve when they are removed from their environment or recur each time they are exposed to a particular environment (eg, basement workshop) may have carbon monoxide poisoning. Most other severe causes of head pain are not rapidly relieved or improved when patients get to the ED. Intracranial infections, dental infections, and other regional causes of head pain tend not to be improved or alleviated before therapy is given. 8. Associated symptoms and risk factors may relate to the severity of headache but rarely point to the specific causes (Box 17.1). Nausea and vomiting are nonspecific symptoms seen in both primary and secondary headaches, but they are rare in simple muscle tension headache. Migraine headaches, increased intracranial pressure, temporal arteritis, and glaucoma can all manifest with severe nausea and vomiting, as can some systemic viral infections with headache. Such factors may point toward the intensity of the discomfort but are not specific in establishing the diagnosis. Immunocompromised patients are at risk for unusual infectious causes of headache, which may present with deceptively low grade symptomatology. Toxoplasmosis, cryptococcal meningitis, and abscess are very rare but may be seen in patients with a history of human immunodeficiency virus (HIV) or other immunocompromised state. This subset of patients may have a serious central nervous system infection without typical signs or symptoms of systemic illness (eg, fever and meningismus). Another special population to considers is the pregnant and peripartum woman, in whom preeclampsia, idiopathic intracranial hypertension (IIH), and reversible cerebral

d. Female gender e. Obesity 6. Cerebral venous sinus thrombosis a. Female gender b. Pregnancy, peripartum, hormone replacement therapy or oral contraceptive use c. Prothrombotic conditions 7. Reversible cerebral vasoconstriction syndrome a. Episodic sudden severe pain, with or without focal neurological findings or seizure b. Recurrent episodes over a period up to several weeks c. Exposure to adrenergic or serotonergic drugs d. Postpartum state 8. Intracranial hemorrhage (ICH) a. Subarachnoid hemorrhage (SAH) i. Sudden and severe pain; “worst headache of life” ii. Acute severe pain after sexual intercourse or exertion iii. History of SAH or cerebral aneurysm iv. History of polycystic kidney disease v. Family history of SAH vi. Hypertension—severe vii. Previous vascular lesions in other areas of the body viii. Young and middle-aged b. Subdural hematoma i. History of alcohol dependency with or without trauma ii. Current use of anticoagulation c. Epidural hematoma i. Traumatic injury ii. Lucid mentation followed by acute altered mentation or somnolence iii. Anisocoria on physical examination

vascular syndrome should be considered, as well as the even more serious causes of headache including venous sinus thrombosis, pituitary apoplexy, cervical artery dissection, and stroke.5-7 Patients on medications containing estrogen are also at higher risk for thrombotic events, such as cavernous venous thrombosis, and this should be considered in the differential diagnosis. 9. A prior history of headache, although helpful, does not rule out current serious problems. One important consideration is the association of migraine headaches and stroke, with particular consideration of carotid dissection.8 Previous evaluation for serious disease can be useful to guide the current evaluation. Prior visits to an ED or outpatient setting, computed tomography (CT), magnetic resonance imaging (MRI), and other forms of testing can provide support for, or help rule out, a specific diagnosis. Patients with migraine, cluster, and tension headaches tend to have stereotypical recurrent patterns. Adherence to these patterns is also helpful in deciding the degree to which a patient’s symptoms are pursued.

Signs There are signs that may be elicited on physical examination that can be particularly high yield. For example, deficits of extraocular movements localizing to cranial nerves (CNs) III, IV, and VI may indicate the presence of increased intracranial pressure due to mass lesion or IIH. When headache is associated with an acutely red eye, this finding should prompt consideration of acute angle closure glaucoma and further investigation with testing of

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intraocular pressure. Any focal neurological deficit found on examination, regardless of subtlety, warrants further investigation. Not all signs associated with headache contribute greatly to final determination of diagnosis, but they may serve as cues for further consideration of a serious intracranial process. Nausea and vomiting are often associated with migraine, but they are also associated with intracranial mass, acute angle closure glaucoma, intracranial bleeding, and carbon monoxide poisoning.

Additional physical findings associated with various forms of headache are listed in Table 17.3.

Ancillary Testing The vast majority of headache patients do not require additional testing (Table 17.4). Advanced imaging should be directed toward the specific disease of concern in the differential diagnosis and not

TABLE 17.3 

Signs and Symptoms Associated With Different Headache Etiologies SIGN

FINDING

POSSIBLE DIAGNOSES

General appearance

Nonfocal mental status changes

Meningitis, encephalitis, SAH, subdural hematoma, anoxia, increased intracranial pressure, carbon monoxide poisoning Intraparenchymal bleed, tentorial herniation, stroke Increased intracranial pressure, acute-angle closure glaucoma, SAH, carbon monoxide poisoning

Mental status changes with focal findings Severe nausea, vomiting Vital signs

Hypertension with normal heart rate or bradycardia Tachycardia Fever

Increased intracranial pressure, SAH, tentorial herniation, intraparenchymal bleed, preeclampsia, reversible cerebral vasoconstriction syndrome Anoxia, anemia, febrile headache, exertional or coital headache Febrile headache, meningitis, encephalitis

HEENT

Tender temporal arteries Increased intraocular pressure Loss of venous pulsations on funduscopy or papilledema Acute red eye (severe ciliary flushing) and poorly reactive pupils

Temporal arteritis Acute angle closure glaucoma Increased intracranial pressure, mass lesions, subhyaloid hemorrhage, SAH, cerebral venous thrombosis Acute angle closure glaucoma

Neurologic

Enlarged pupil with third nerve palsy Lateralized motor or sensory deficit

Tentorial pressure cone, mass effect (aneurysm, bleed, abscess, or tumor) Stroke, subdural hematoma, epidural hematoma, hemiplegic or anesthetic migraine (rare), reversible cerebral vasoconstriction syndrome, central venous thrombosis Cervical artery dissection, acute cerebellar hemorrhage, acute cerebellitis (mostly children), chemical intoxication of various types Mass lesion, neurapraxia (post-traumatic headache), IIH

Balance and coordination deficits Extraocular movement deficits (CN III, IV, and VI)

CN, Cranial nerve; HEENT, head, eyes, ears, nose, and throat; IIH, idiopathic intracranial hypertension; SAH, subarachnoid hemorrhage.

TABLE 17.4 

Diagnostic Findings in Emergent Causes of Headache TEST

FINDING

DIAGNOSIS

Erythrocyte sedimentation rate (ESR)

Significant elevation

Temporal arteritis

Electrocardiogram (ECG)

Nonspecific ST/T wave changes

SAH Increased intracranial pressure

Complete blood count (CBC)

Severe anemia

Anoxia

Computed tomography (CT) scan: Head

Increased ventricular size Blood in subarachnoid space Blood in epidural or subdural space Bleeding into parenchyma of brain Areas of poor vascular flow Structural, mass lesion

Increased intracranial pressure SAH Epidural or subdural hematoma Intraparenchymal hemorrhage Pale infarct Traction headache secondary to mass effect

Lumbar puncture (LP) and cerebrospinal fluid (CSF) analysis

Increased opening pressure

IIH Mass lesion Shunt failure Cryptococcal meningitis Tumor or other structural lesions, infection SAH Infection Infection Infection

Increased protein Increased RBCs Increased WBCs Positive Gram’s stain Decreased glucose IIH, idiopathic intracranial hypertension; RBC, red blood cell; SAH, subarachnoid hemorrhage; WBC, white blood cell.

CHAPTER 17  Headache

as a default process in the investigation of headache in general. For example, a head CT scan is not indicated for muscle tension headache or recurrent migraine, and it may not be sufficient to assess for cerebral venous thrombosis or for a posterior circulation stroke. A CT scan performed within 6 hours of onset of headache has been shown to be sufficiently sensitive to exclude the diagnosis of SAH when using a third-generation CT scanner. Outside this window, sensitivity declines, and additional testing must be undertaken for appropriate evaluation for SAH.9 Lumbar puncture (LP) with measurement of the opening pressure and cerebrospinal fluid (CSF) analysis is indicated when assessing for an infectious process, such as meningitis or encephalitis, IIH, or SAH. Although evidence for this is scant, it is widely believed that LP may increase the likelihood of herniation in certain cases with elevated intracranial pressure caused by a mass lesion. This is the genesis of the common dictum of “CT before LP” when a mass lesion or abscess is a consideration. In reality, this concern is likely misguided, and the compelling reason to obtain a CT scan first in such patients is that it may provide the diagnosis and make the LP unnecessary.

DIAGNOSTIC ALGORITHM Key elements of the history of present illness, past medical history, and examination are used to narrow the differential diagnosis and choose the appropriate diagnostic pathway. Figure 17.1 outlines a diagnostic algorithm for assessment of headache patients.

If it is clear from the evaluation that the diagnosis is a primary headache disorder (eg, migraine) or of minor severity and gradual onset (eg, typical tension headache) with normal neurological examination findings, then symptomatic treatment is provided without need for further diagnostic evaluation. If the history or examination findings are clearly indicative of a particular etiology (eg, angle closure glaucoma), then directed testing is indicated—in this case, intraocular pressure determination. It is cases in which there are highly concerning elements of history but no definitive diagnosis that are the most challenging in terms of choosing the appropriate evaluation. Indications of patients at higher risk for serious cause of headache who are candidates for more comprehensive evaluation include (1) sudden onset of headache, (2) patient description of the headache as “the worst ever,” (3) altered mental status, (4) meningismus, (5) unexplained fever, (6) focal neurological deficit on examination, (7) symptoms refractory to appropriate treatment or worsening despite treatment, (8) onset of headache during exertion, (9) history of immunosuppression, or (10) pregnancy or peripartum state. In these potentially critically ill patients, head CT scan is indicated, and a LP often is needed for those in whom imaging does not reveal the etiology of their symptoms. Sequential evaluation of the patient’s condition and assessment of ancillary data will confirm a working diagnosis or trigger a reconsideration of alternatives, including more serious conditions (Table 17.5).

Initial assessment: H&P

Decreased mentation, focal neurologic deficit, meningismus, thunderclap

If findings of H&P reveal cause or are mild, provide supportive care, treat underlying condition (eg, CO poisoning, acute angle closure, tension HA)

LP may be performed immediately if the patient has no focal neurologic findings and normal fundoscopic examination

CT

CT+: Treat underlying condition

If meningitis suggested, initiate antibiotics as soon as possible

Beyond 6 hours onset: LP

CT-

Within 6 hours of headache onset

LP negative

Unlikely SAH, consider alternate diagnoses

LP positive: Treat as indicated by abnormal findings (blood, organisms, pressure)

Fig. 17.1.  Evaluation algorithm for presentation of headache. CO, Carbon monoxide; CT, computed tomography; H&P, history and physical examination; HA, headache; LP, lumbar puncture; SAH, subarachnoid hemorrhage.

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TABLE 17-5 

Causes and Differentiation of Potentially Catastrophic Illness Manifesting With Nontraumatic Headache DISEASE ENTITIES

PAIN HISTORY

ASSOCIATED SYMPTOMS

SUPPORT HISTORY

PREVALENCE

Carbon monoxide poisoning

Usually gradual, subtle, dull, nonfocal throbbing pain

May wax and wane as individual leaves and enters the involved area of carbon monoxide; throbbing may vary considerably

Exposure to engine exhaust, old or defective heating systems, most common in winter months

Rare

Subarachnoid hemorrhage (SAH)

Sudden onset, “thunderclap,” severe throbbing

Symptoms variable; may present from relatively asymptomatic to altered mental status or focal neurological deficit

History of polycystic kidney disease; history of HTN

Uncommon

Meningitis, encephalitis, abscess

Gradual; as general symptoms increase, headache increases. Nonfocal pain

Decreased mentation prominent, irritability prominent. With abscess, focal neurologic findings may be present

Recent infection, recent facial or dental surgery or other ENT surgery, unimmunized state

Uncommon

Temporal arteritis

Pain often develops over a few hours from mild to severe, almost always localized to temporal area(s)

Decreased vision, nausea, vomiting may be intense and confound diagnosis

Age over 50; other collagen vascular diseases or inflammatory diseases

Uncommon

Acute angle closure glaucoma

Sudden in onset

Nausea, vomiting, decreased vision

History of glaucoma; history of pain increasing in dark areas

Rare

Increased intracranial pressure syndromes

Gradual, dull, nonfocal

Vomiting, decreased mentation

History of CSF shunt or congenital brain or skull abnormality

Uncommon

CSF, Cerebrospinal fluid; ENT, ear, nose, and throat; HTN, hypertension.

Initial assessment

Suspect intracranial process

Stable

Mild to moderate pain

PO NSAID or acetaminophen for analgesia

Severe pain

Parenteral NSAID, with or without antiemetic, IV fluids

Altered/comatose

Mild to severe pain

Parenteral opioid pain medications

Neurological assessment followed by airway intervention if indicated

Continue evaluation

Primary headache (see specific management algorithm described in later chapter)

Benign secondary headache; treat underlying cause

Intracranial process; consult accordingly

Fig. 17.2.  Management algorithm. IV, intravenous; NSAID, nonsteroidal antiinflammatory drug; PO, per os (by mouth).

EMPIRICAL MANAGEMENT Headache, although a frequent chief complaint, is a nonspecific symptom. The speed and intensity of the initial evaluation and treatment are guided by the presentation and the patient’s mental status. Figure 17.2 represents a management algorithm with

immediate management pending completion of a full diagnostic evaluation. For purposes of the initial assessment, headache can be divided into two categories: (1) accompanied by altered mental status and (2) without altered mental status. Whenever a patient’s mental status is impaired, brain tissue is initially assumed to be

CHAPTER 17  Headache

compromised. The principles of cerebral resuscitation address the seven major causes of evolving brain injury: (1) lack of substrate (glucose, oxygen), (2) cerebral edema, (3) intracranial mass lesion, (4) endogenous or exogenous toxins, (5) metabolic alterations (fever, seizure), (6) ischemia, or (7) elevated intracranial pressure. Pain is mitigated as soon as possible. The pain medication of choice depends on the working diagnosis of the patient’s headache. For nonspecific mild to moderate headache, oral nonsteroidal antiinflammatory medication is appropriate in analgesic doses (eg, 500 mg of naproxen). Opioids are not first-line management for any type of headache pain, except when ICH (including SAH) is thought to be present. Other than symptomatic relief of pain, empirical treatment does not precede diagnostic studies in most cases, because the

treatment must be targeted to the specific cause of the headache. A significant exception to this is when bacterial meningitis is a consideration. Treatment of bacterial meningitis is time-sensitive, and empirical antibiotics should be administered as soon as possible and before results are available to confirm the diagnosis.

Disposition Patients who are not thought to have a serious cause for their head pain requiring hospitalization but who are without a specific diagnosis are provided with appropriate return precautions and recommendations for follow-up care. Some patients many benefit from beginning a headache journal to facilitate further outpatient evaluation.

KEY CONCEPTS • When a patient with a known headache disorder presents with a change in the pattern of the headache, evaluate for potential serious causes. • The physical examination in the headache patient focuses on cranial nerves (CNs) II, III, IV, and VI. • Opioid medication is almost never the analgesic of choice for headache. Simple headache is treated with nonsteroidal analgesic medication, and specific antimigraine therapies are used for migraine. • Most patients with headache do not require neuroimaging. When obtained, neuroimaging should be tailored to the specific elements of the differential diagnosis of concern.

• The differential diagnosis of sudden severe headache includes subarachnoid or other intracranial hemorrhage (ICH), cerebral venous thrombosis, and cervical artery dissection. • In those patients for whom there is concern for subarachnoid hemorrhage (SAH), a normal head CT scan obtained using a high resolution scanner within 6 hours of onset is sufficient to rule out SAH. Patients outside this window require lumbar puncture (LP) to achieve appropriate sensitivity in the evaluation. • Antibiotics should be given prior to LP being performed when bacterial meningitis is suspected.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 17  Headache

159.e1

REFERENCES 1. Bellolio MF, et al: External validation of the Ottawa subarachnoid hemorrhage clinical decision rule in patients with acute headache. Am J Emerg Med 33(2):244–249, 2015. 2. Burch RC, Loder S, Loder E, et al: The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache 55:21–34, 2015. 3. Devenny E, et al: A systematic review of causes of severe and sudden headache (thunderclap headache): should lists be evidence based? J Headache Pain 15:49, 2014. 4. Perry JJ, Stiell IG, Sivilotti ML, et al: Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA 310(12):1248–1255, 2013.

5. Edlow JA, et al: Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute headache. Ann Emerg Med 52:407–436, 2008. 6. Digre KB: Headaches during pregnancy. Clin Obstet Gynecol 56:317–329, 2013. 7. Coutinho JM, et al: Isolated cortical vein thrombosis: systematic review of case reports and case series. Stroke 45:1836–1838, 2014. 8. Harriott AM, Barrett KM: Dissecting the association between migraine and stroke. Curr Neurol Neurosci Rep 15:5, 2015. 9. Perry JJ, Stiell IG, Sivilotti ML, et al: Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ 343:d4277, 2011.

CHAPTER 17: QUESTIONS & ANSWERS 17.1. The most appropriate initial evaluation of a patient with nontraumatic headache is: A. CT scan of brain B. EEG C. MRI scan of brain D. Thorough neurological evaluation E. Trial of NSAIDs for pain relief Answer: D. A thorough neurological examination may reveal deficits not seen on gross evaluation, prompting expansion of the differential diagnosis to include more concerning etiologies. Depending on the history and remainder of the physical, a normal neurological examination may be reassuring and obviate need for advanced imaging studies. 17.2. In the setting of headache, the presence of nausea and vomiting are diagnostic of which of the following as an underlying cause? A. Glaucoma B. Increased intracranial pressure C. Migraine D. Temporal arteritis E. None of the above Answer: E. Nausea and vomiting are completely nonspecific. Migraine headaches, increased intracranial pressure, temporal arteritis, and glaucoma can all be manifested by severe nausea and vomiting, as can some systemic viral infections with headache. Such factors may point toward the intensity of the discomfort but are not specific in establishing the diagnosis. 17.3. Which of the following causes of headache has a constellation of risk factors that include age older than 50

years, female gender, history of lupus, and previous chronic meningitis? A. Abscess B. Encephalitis C. Increased intracranial pressure D. SAH E. Temporal arteritis Answer: E. Risk factors associated with temporal arteritis include age older than 50 years; female gender (ratio 4 : 1); history of other collagen vascular diseases, such as lupus; previous chronic meningitis; and previous chronic illness, such as tuberculosis, parasitic infection, and fungal infection. 17.4. A history of polycystic kidney disease is an associated risk factor for which of the following potentially catastrophic causes of headache? A. Cerebral venous sinus thrombosis B. Increased intracranial pressure C. SAH D. Subdural hematoma E. Temporal arteritis Answer: C. A history of polycystic kidney disease is a risk factor for SAH. Other historical details and risk factors for SAH are sudden severe pain, acute severe pain after sexual intercourse or straining, history of SAH or cerebral aneurysm, family history of SAH, severe hypertension, previous vascular lesions in other areas of the body, and being young or middle aged.

C H A P T E R 18 

Diplopia Kama Guluma PERSPECTIVE Epidemiology Diplopia, or double vision, is of two types, monocular and binocular. For patients who present to the emergency department (ED) with diplopia, most cases are binocular, with cranial nerve (especially sixth nerve) palsies being among the most common causes. The remainder (≈15%) are monocular.

Pathophysiology Monocular diplopia, or double vision that persists in one affected eye, even with the other one closed, is an ophthalmologic problem related to distortions in the light path. Binocular diplopia, or double vision that resolves when either eye is closed, is the result of a misalignment in the visual axes and has a wide range of causes. These can be organized in a progression from the eye distally to the brainstem proximally. The process responsible might involve oculomotor muscle dysfunction, cranial nerve (CN) dysfunction, or intranuclear or supranuclear lesions in the brainstem or above. In a recent, prospective observational study of 260 ED patients presenting with binocular diplopia, a secondary cause of the diplopia was delineated in 36% and, of these, the most frequent diagnoses were stroke (45%), multiple sclerosis (18%), brain tumors (12%), and cerebral aneurysms (8%).1

DIAGNOSTIC APPROACH Differential Considerations The causes of diplopia are myriad, ranging from relatively benign to significantly pathologic. The clinical approach in the ED entails sorting out those that may result in rapid and profound morbidity from those that are less acute. Table 18.1 outlines some key causes of diplopia prioritized by immediate acuity, with mechanism and distinguishing features. Binocular diplopia may be due to a mechanical orbitopathy, a palsy of one or more of the oculomotor cranial nerves, a proximal neuroaxial process involving the brainstem and related cranial nerves, or a systemic neuromuscular process. Monocular diplopia is an ophthalmologic problem related to distortions in the light path from dry eyes, a corneal irregularity, cataract or lens dislocation2 or, rarely, from retinal wrinkles involving the macula. A restrictive mechanical orbitopathy can be caused by orbital myositis, trauma, or infection (abscess), or from craniofacial masses, any of which can directly restrict movement of a single eye. A restrictive orbitopathy is identified by characteristic symptoms and signs combined with the absence of any other focal neurologic deficits. Often involving only a single extraocular muscle, orbital myositis may be a manifestation of a variety of steroid-responsive conditions such as Wegener’s granulomatosis, giant cell arteritis, systemic lupus erythematosus, dermatomyositis, sarcoidosis, rheumatoid arthritis, or idiopathic orbital inflammatory syndrome (orbital pseudotumor). 160

Graves’ orbitopathy is the most common cause of ocular myopathy in older adults, will affect at least 50% of patients with Graves’ disease,3 and is bilateral in at least 85% of cases. The patient presenting with thyroid-related diplopia will likely have a preexisting diagnosis of Graves’ disease, but may present with isolated diplopia prior to the onset of systemic symptoms (and diagnosis).3 The oculomotor (CN III), trochlear (CN IV), and abducens (CN VI) cranial nerves innervate the muscles that move the eye. With regard to an oculomotor cranial nerve palsy, CN VI is the most commonly affected, followed by CN III, and then CN IV.2 An isolated simple mononeuropathy in CN III, IV, or VI may be from a demyelinating process (eg, multiple sclerosis4), hypertensive or diabetic vasculopathy, or compression. Each nerve has characteristic predilections to which it is vulnerable. In adults, CN III is usually affected by diabetic or hypertensive vasculopathy. Aneurysms in the posterior communicating (most common), basilar, superior cerebellar, posterior cerebral, and cavernous internal carotid arteries are a close second.5 CN IV is usually affected by trauma from abutting against the tentorium, typically not an isolated symptom or finding, followed by vascular causes. Due to its length, CN VI is the most common nerve to be affected by tumors, elevated intracranial pressure, and microvascular ischemia.6 A cavernous sinus infection, mass, or vasculitis may affect CN III, IV, and VI simultaneously (orbital apex syndrome), but typically affects CN VI first because it traverses through the cavernous sinus, as opposed to within its wall, like CNs III and VI. Causes include carotid-cavernous fistula, inflammatory vasculitides such as giant cell arteritis, Tolosa-Hunt syndrome (a rare idiopathic vasculitis), or tumor or infiltration (eg, lymphoma, sarcoidosis) in the orbital apex.7 A complex palsy in the cavernous sinus may also be iatrogenic due to intravascular injection or diffusion of anesthetic along tissue planes into the pterygoid venous plexus from an intraoral dental anesthetic nerve block.8 Herpes zoster ophthalmicus is a well-described cause of orbital apex syndrome.9-11 A focal brainstem lesion may be from multiple sclerosis (as a clinically isolated syndrome, of which 68% manifest as diplopia).4 A more diffuse but localized brainstem process may be caused by brainstem tumor, brainstem lacunar stroke,2 impending basilar artery thrombosis, vertebral artery dissection, or ophthalmoplegic migraine.3 A vertebral artery dissection may present with diplopia alone, as can an impending basilar artery thrombosis, which can also result in a coma.12 A more diffuse process involving the brainstem and/or CNs III, IV, and VI may be infectious, autoimmune, neurotoxic, or metabolic, and involve other neurologic structures, resulting in additional symptoms and signs. Possibilities include basilar meningoencephalitis (cryptococcal,13 carcinomatous, or viral14), at times with the diplopia being the only symptom,15 botulism,16 an autoimmune process such as Miller-Fisher or Guillain-Barré syndrome,17 and Wernicke’s encephalopathy, in which the ophthalmologic manifestations are due to metabolically induced lesions in the pontine tegmentum, abducens nucleus, and oculomotor nucleus.18

CHAPTER 18  Diplopia

TABLE 18.1 

Important Causes of Diplopia DIPLOPIA-CAUSING ENTITY

MECHANISM AND MORTALITY

DISTINGUISHING FEATURES

Basilar artery thrombosis

Impending thrombosis of the basilar artery with brainstem ischemia; untreated mortality, 70%–90%

Vertigo, dysarthria, other cranial nerve involvement; risk factors for stroke

Botulism

Toxin inhibits release of acetylcholine at cholinergic synapses and presynaptic myoneural junctions; untreated mortality, 60%

Dysarthria, dysphagia, autonomic dysreflexia, pupillary dysfunction

Basilar meningitis

Infection; untreated mortality, close to 100% if bacterial (15%–20% if treated)

Headache, meningismus, fever

Aneurysm

Enlarging aneurysm directly compresses cranial nerve; untreated rupture risk = 1%/yr (3.5%/yr for previously ruptured); mortality, 26%–67%/rupture

CN III palsy with pupillary involvement

Vertebral dissection

Dissection causes vertebrobasilar ischemia; acute untreated mortality, 28% (2%–5% if neurologically asymptomatic)

Neck pain, vertigo; risk factors for vertebral dissection

Myasthenia gravis

Autoantibodies develop against acetylcholine (ACh) nicotinic postsynaptic receptors; untreated crisis mortality, 42% (5% if treated)

Fluctuating muscle weakness, ptosis, and diplopia worsen with activity, improve with rest

Wernicke’s encephalopathy

Thiamine-dependent metabolic failure and tissue injury; untreated mortality, 20%

Nystagmus, ataxia, altered mental status, ophthalmoplegia; alcoholism and nutritional deficiency

Orbital apex syndrome, cavernous sinus process

Inflammation or infection in the orbital apex or cavernous sinus directly affects oculomotor cranial nerves; acute mortality low unless infectious and complicated by meningitis

Combination of palsies of CN III, IV, or VI, with retro-orbital pain, conjunctival injection, possible periorbital, facial numbness

Brainstem tumor

Tumor involvement at the supranuclear level; acute mortality low (long-term mortality variable)

Skew deviation—vertical diplopia, internuclear ophthalmoplegia

Miller-Fisher syndrome

Autoantibodies develop to a cranial nerve ganglioside, GQ1b; acute mortality low (if fully differentiated from GBS; mortality, 2%–12% if GBS)

Ophthalmoplegia, ataxia, areflexia

Multiple sclerosis

Demyelinating lesions; acute mortality low

Internuclear ophthalmoplegia

Thyroid myopathy (Graves’ disease)

Autoimmune myopathy; acute mortality low in regard to ocular complaints

Proptosis, restriction of elevation and abduction of the eye, signs of Graves’ disease

Ophthalmoplegic migraine

Inflammatory cranial neuropathy; low mortality, self-limited disease

Ipsilateral headache, CN (usually III) palsy

Ischemic neuropathy

Microvascular ischemia; mortality low, self-limited disease

Isolated CN palsy (pupil-sparing if CN III)

Orbital myositis, pseudotumor

Autoimmune or idiopathic myositis; acute mortality low in regard to ocular complaints

Eye pain, restriction of movement, periorbital edema; exophthalmos and chemosis when more severe

Orbital apex mass

Tumor, infiltration, or mass effect in orbital apex or cavernous sinus directly compresses oculomotor cranial nerves; acute mortality low

A combination of palsies of CN III, IV, or VI and possible periorbital, facial numbness, with retro-orbital pain, proptosis, signs of venous congestion

TIER 1—CRITICAL

TIER 2—EMERGENT

TIER 3—URGENT

Snake envenomations and tick paralysis can, on rare occasions, present with isolated diplopia, with diplopia being an early and frequent manifestation of neurotoxicity from certain snake venoms.19 Diplopia may also be part of a paraneoplastic syndrome, but the prototypical neuromuscular cause of diplopia is myasthenia gravis. The initial symptoms are ocular in 85% of myasthenia cases, due to diplopia in 14% of cases. In addition, the symptoms of myasthenia gravis are solely ophthalmologic in almost 20% of patients.20 However, patients with myasthenia will typically present with diplopia in the setting of a preestablished diagnosis, which facilitates a determination, if not immediate recognition, of the cause.

Pivotal Findings There are four aspects of questioning the help formulate the differential diagnosis in diplopia: (1) timing of onset and symptoms; (2) directionality and orientation of the diplopia; (3) presence of pain; and 4) presence of other associated symptoms.2 In terms of the timing of onset, a truly sudden onset suggests an ischemic cause, cerebrovascular or microvascular, especially if the intensity or degree of diplopia was maximal at onset. A fluctuation of symptoms over time may suggest transient ischemic attacks or an impending stroke, but more generally implies a neuromuscular disease.2 Regarding the directionality of the diplopia, the

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SECTION Two 

Signs, Symptoms, and Presentations

directions of gaze that elicit or worsen the diplopia and the general orientation of that diplopia—that is, horizontal, vertical, torsional—should be carefully determined to localize the problem. Finally, symptoms associated with the diplopia (eg, pain, neurologic or neuromuscular symptoms) are critical to forming a differential diagnosis, if not making the diagnosis. The presence of pain suggests an inflammatory or infectious process and narrows the differential significantly. The patient complaining of diplopia should have a thorough neurologic examination, with attention to the cranial nerves and an evaluation of the six cardinal movements of gaze. Each extraocular muscle (and the nerve that supplies it) has a maximal action in a specific direction, and the evaluation of gaze should therefore specifically follow the configuration of a six-limbed asterisk, or an H (Fig. 18.1). The patient should also undergo a careful pupillary and facial examination, looking for signs of

pupillary asymmetry, ptosis, lid lag, conjunctival injection or chemosis, periorbital swelling, or proptosis and overall head positioning. The acuity of onset and presence or absence of pain can be used to prestratify diagnostic possibilities, as shown in Fig. 18.2, especially with regard to vascular, potentially ischemic events. Symptoms Monocular Cause.  This is present only if the patient complains that the diplopia persists in the affected eye with the normal eye closed. Mechanical Orbitopathy.  A structural restriction of motion of a single eye, typically gradual in onset, may cause diplopia in a single or multiple directions of gaze, depending on the type and extent of muscular involvement. A sensation of mass effect, discomfort, or pain in the culprit eye is a characteristic symptom. If

RIGHT EYE

LEFT EYE

Superior rectus CN III

Inferior oblique CN III

Lateral rectus CN VI

Medial rectus CN III

Inferior rectus CN III

Superior oblique CN IV

Inferior oblique CN III

Superior rectus CN III

Medial rectus CN III

Lateral rectus CN VI

Superior oblique CN IV

Inferior rectus CN III

Fig. 18.1.  Cardinal movements of the eyes, with the oculomotor muscles that create them and the nerves that supply those muscles. Small curved arrows denote intorsion or extorsion of the eye by the muscle indicated. CN, Cranial nerve. SUDDEN ONSET? NO

YES

Nonvascular

Vascular/ischemic

PAIN or DISCOMFORT?

PAIN or DISCOMFORT?

No

Noninflammatory

Yes

Inflammatory

No

Noninflammatory

Yes

Inflammatory

ORBITAL • Orbital mass • Monocular light path distortion

ORBITAL • Orbital myositis • Graves’ disease • Orbital abscess • Orbital infiltration

ORBITAL • N/A

ORBITAL • Microvascular ischemia

CRANIAL • Compression (mass/aneurysm) • Miller-Fisher syndrome • Botulism •Wernicke’s encephalopathy • Multiple sclerosis

CRANIAL • Cavernous sinus vasculitis • Basilar meningoencephalitis

CRANIAL • Brainstem lacune • Impending basilar artery thrombosis • Vertebral dissection

CRANIAL • Ophthalmoplegic migraine

NEUROMUSCULAR Fig. 18.2.  Prestratification of the differential diagnosis in a patient presenting with diplopia.

CHAPTER 18  Diplopia

the cause is infectious, the patient may have a history of a fever. Diplopia that is worse in the morning suggests Graves’ myopathy, presumably due to the venous congestion of the ocular muscle associated with being supine. Isolated Oculomotor Nerve Palsy.  The patient with a CN III palsy typically reports diplopia in all directions of gaze, except on lateral gaze to the affected side. A CN IV palsy resulting in rotational double vision makes descending stairs, reading, and watching television in bed difficult. Diplopia that worsens on lateral gaze to one direction implies an issue with CN VI on that side.2 A patient with diplopia from an isolated palsy of CN III, IV, or VI will typically not have other associated symptoms. Pain and speed of onset are differentiators; a sudden isolated CN III, CN IV, or CN VI palsy associated with orbital discomfort in a patient with chronic diabetes or hypertension strongly suggests that microvascular ischemia is the cause, with a caveat that with a CN III palsy, a headache frequently accompanies aneurysmal compression.21 The diplopia from a problem involving the cavernous sinus or orbital apex, unlike an isolated mononeuropathy, may manifest as a combination of any of the gaze abnormalities noted above, because more than one cranial nerve may be involved. It may be gradual in onset and associated with retroorbital pain or blurred vision due to venous congestion. Because branches of the trigeminal nerve travel though the orbital apex, the patient may have associated ipsilateral periorbital facial numbness or dysthesia.7 Neuroaxial Process Involving the Brainstem and Related Cranial Nerves.  A focal brainstem lesion (eg, in multiple sclero-

sis) may result in isolated diplopia. However, localized brainstem lesions such as those from mass effect or ischemia typically also result in so-called neighborhood symptoms and signs from anatomically contiguous involvement, of which double vision may be the most prominent and therefore the presenting complaint (see Box 18.1). It is therefore important to screen for those other symptoms and signs actively. Additional symptoms of nausea, vertigo, or slurred speech are concerning for an impending basilar artery occlusion, especially if symptoms are sudden in onset, painless, and fluctuate, or a brainstem mass, if gradual in onset and progressive over days. A young person with an ophthalmople-

BOX 18.1 

Lacunar Stroke Syndromes Presenting   With Diplopia Weber syndrome (midbrain lacune)—ipsilateral CN III palsy and contralateral hemiparesis Benedikt syndrome (midbrain lacune)—ipsilateral CN III palsy and contralateral tremor or dysmetria Claude syndrome (midbrain lacune)—ipsilateral CN III palsy and contralateral weakness, tremor, and ataxia Millard-Gubler syndrome (pontine lacune)—ipsilateral CN VI palsy, ipsilateral facial weakness (CN VII), contralateral arm and leg weakness Foville’s syndrome (pontine tegmentum)—ipsilateral CN VI palsy, ipsilateral facial weakness (CN VII), contralateral ataxia and hemiparesis One-and-a-half syndrome (CN VI nuclei, paramedian pontine reticular formation)—bilateral CN VI (abduction) palsies with a unilateral adduction palsy Adapted from Friedman DI. Pearls: diplopia. Semin Neurol 30:54–65, 2010; and Lewandowski CA, Rao CP, Silver B: Transient ischemic attack: definitions and clinical presentations. Ann Emerg Med 52:S7–S16, 2008.

gic migraine may present in a similar fashion to someone with a brainstem stroke but will typically develop an associated ipsilateral headache. Diplopia from a more diffuse neurologic syndrome that happens to involve the brainstem and cranial nerves is usually gradual in onset and manifests with various other discordant symptoms. A gradually evolving combination of double vision, slurred speech, and problems swallowing suggests foodborne botulism,16 especially if additional symptoms of dry mouth, nausea, and diffuse muscle weakness are present. Double vision, clumsiness, and altered mentation in a patient with chronic alcoholism, malnutrition, or history of bariatric surgery should raise the possibility of Wernicke’s encephalopathy.18 Diplopia and other cranial nerve symptoms, together with headache, photophobia, stiff neck, and/or fever, are suspicious for a basilar meningoencephalitis. Neuromuscular Disorder.  Diplopia that is variably triggered in multiple directions, and without a distinct structural or neuropathic cause evident, implies a neuromuscular cause such as myasthenia gravis. A mild neuromuscular manifestation of myasthenia may present with a diplopia isolated to one direction, however. Diplopia from neuromuscular disease generally fluctuates over time2 and, in myasthenia gravis, worsens with fatigue and improves with rest.22 There may be associated symptoms of proximal muscle weakness (eg, difficulty holding arms above the head or climbing stairs), shortness of breath, or difficulty swallowing. Signs Monocular Cause.  With monocular diplopia—typically a problem with abnormal refraction—the diplopia from the affected eye should resolve when a pinhole is used, unless it is due to a retinal abnormality. Mechanical Orbitopathy.  Signs of a structural orbitopathy or myositis include proptosis, periorbital swelling, edema, conjunctival or scleral hyperemia, and palpebral swelling involving a single eye. Diplopia due to a mass in the orbit may appear as a clean, ordinal mechanical diplopia, in which having the patient attempt to look in the direction of the problem induces the most diplopia, with an axis of visual image separation parallel to the direction of the gaze (as can at times be seen in patients with significant periorbital swelling from trauma). In contrast, diplopia due to a process in any of the individual extraocular muscles, except for the lateral or medial recti muscles, may present in a messy eccentric or torsional manner based on the direction of pull of and therefore restriction by each muscle (see Fig. 18.1). There is a mismatch between the primary direction of diplopia and primary direction of movement, possibly improved by head tilt. Although findings may mimic a neurogenic palsy to some extent, the signs induced on testing extraocular eye movements will not reflect the stereotyped deficits typical of palsies of the oculomotor cranial nerves. Ocular myositis can be distinguished from a neurogenic palsy in that it abruptly restricts eye movement away from the muscle, whereas a cranial nerve palsy smoothly and progressively impairs movement toward the weakened muscle. Stigmata of Graves’ disease include lid lag, diffuse conjunctival edema, and vascular injection3 and, because it typically affects the inferior and medial recti muscles first, restriction of elevation and abduction of the eye. Patients with thyroid-related diplopia may tilt their head back to accommodate for the restriction of upward gaze by the thickened inferior rectus muscle.2 Isolated Oculomotor Nerve Palsy.  Palsies from an isolated mononeuropathy of the oculomotor nerve will present with typical findings, as outlined in Fig. 18.3. CN III also innervates the levator palpebrae superioris muscle, which lifts the upper eyelid, and provides parasympathetic innervation to two intrinsic ocular muscles, the ciliary and constrictor pupillae muscles, which

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SECTION Two 

MUSCLE(S) “OFF”

Signs, Symptoms, and Presentations

SYMPTOMS

EXAMINATION FINDINGS

Normal

N/A

N/A

Oculomotor (CN III)

Medial, inferior, and superior rectii muscles • Inferior oblique muscle • Levator palpebrae (eyelid) • Ciliary and constrictor pupillae muscles (pupil)

Multidirectional horizontal and vertical diplopia, except on lateral gaze to the affected side • Eyelid “droop”

Superior oblique muscle

Rotational diplopia that worsens on looking down and toward the nose

Trochlear (CN IV)

Abducens (CN VI)

Lateral rectus muscle

Ptosis Pupillary dilation “Down and out”

Extorsion on downward gaze

Horizontal diplopia on gaze toward the affected side Lateral gaze palsy

Fig. 18.3.  Corresponding muscle dysfunction, symptoms and examination findings for each oculomotor cranial nerve palsy. CN, Cranial nerve.

constrict the pupil. An isolated CN III palsy presents with diplopia in all directions of gaze, except on lateral gaze to the affected side and an eye that is deviated down and out, with a dilated pupil, and ptosis. Typically seen in older patients with vascular risk factors such as diabetes and hypertension, diplopia due to microvascular ischemia may present with an isolated CN III palsy associated with pain, classically sparing the pupil, whereas that from compression (ie, from an aneurysm) is associated with pupillary mydriasis due to compression of pupillomotor parasympathetic fibers in the exterior of the nerve. The so-called rule of the pupil—more of a guideline than a rule—states that an otherwise complete CN III palsy (complete ptosis, completely down and out), with normal pupillary size and reactivity, rules out compression as the source. However, the presence of pupillary involvement does not rule in mechanical compression as the cause. A large case series of patients with CN III palsies revealed that over 50% of patients with diabetic microvascular ischemia had pupillary involvement, possibly from concomitant autonomic neuropathy, although pain was more common with CN III palsies from aneurysms (94% of cases) than from diabetic microvascular ischemia (69% of cases).21 A rotational diplopia that worsens on looking down and toward the nose implies a superior oblique (CN IV) palsy. An abducens nerve (CN VI) palsy may present with bilateral findings, because elevated intracranial pressure from a brain tumor or malfunction ventriculoperitoneal shunt may be the cause.23 In contrast to a mononeuropathy, the combination of ipsilateral palsies of CN III, IV, and VI from an orbital apex or cavernous sinus process will typically present with additional findings— together called orbital apex syndrome—of exophthalmos, chemosis, and injection. Sensory deficits corresponding to the ophthalmic

(V1) and maxillary (V2) divisions of the trigeminal nerve may be present, given their course through the orbital apex.

Neuroaxial Process Involving the Brainstem and Related Cranial Nerves.  Vertical diplopia without the torsional compo-

nent seen with CN IV palsy, called a vertical skew deviation, suggests a brainstem lesion. An internuclear ophthalmoplegia, suggested by an inability to adduct the eye on one side in the contralateral direction during lateral gaze that resolves during convergence, implicates a lesion in the medial longitudinal fasciculus (MLF) such as that typically found in patients with multiple sclerosis.2 In multiple sclerosis, diplopia may present alone as a clinically isolated syndrome4 or may be associated with a host of additional heterogeneous neurologic findings that typify this disorder (eg, optic neuritis, with blurred vision and eye pain, or focal motor or sensory abnormalities). A brainstem lacunar stroke may present as any of a number of identifiable syndromes (see Box 18.1). An impending basilar occlusion may present with additional symptoms of nystagmus, dysmetria, gait ataxia, and dysarthria. A brainstem or cranial neuropathy that is part of a more diffuse neurologic syndrome may present with a stereotypical assortment of additional associated deficits. With foodborne botulism, patients have a descending flaccid paralysis that begins with multiple cranial nerve palsies. There may also be autonomic signs such as dry mouth, ileus, postural hypotension, respiratory muscle weakness, and pupillary abnormalities.16 Patients with Miller-Fisher syndrome may present with an isolated ophthalmoplegia, considered a forme fruste of the disease, but more typically have the classic triad of ophthalmoplegia, ataxia, and areflexia. Muscle weakness should not be present17; if it is, the case is better classified as Guillain-Barré syndrome with

CHAPTER 18  Diplopia

ophthalmoplegia.17 Most patients with Wernicke’s encephalopathy have ocular abnormalities, including nystagmus and ophthalmoplegia (usually from a CN VI palsy), typically associated with the classic triad of nystagmus, altered mental status, and ataxia. A fever suggests the possibility of an infectious process such as basilar meningoencephalitis. Neuromuscular Disorder.  The stigmata of neuromuscular disease such as muscle atrophy or weakness may be apparent on physical examination. Patients with myasthenia gravis may have unilateral or bilateral ptosis, weakness on forced eyelid closure, and generalized muscle weakness, but with normal reflexes and no sensory abnormalities. About 50% present with isolated ocular abnormalities.22 The diplopia may represent a myasthenic crisis, possibly associated with occult respiratory muscle weakness and ventilatory insufficiency.24

Ancillary Testing The patient with monocular diplopia should undergo a slit lamp and funduscopic examination and may need an evaluation by an ophthalmologist. A monocular cause of diplopia will not typically require an extensive neuroophthalmologic evaluation. In the patient with a suspected or evident mechanical orbitopathy, a magnetic resonance imaging (MRI) scan of the orbits with gadolinium can allow an assessment for enlargement or enhancement in extraocular muscles and orbital structures, although a contrast-enhanced cranial computed tomography (CT) scan with fine cuts through the orbit can be used as a second-line option.25 The same imaging paradigm applies to localization of the process within the cavernous sinus or orbital apex, because it will highlight infiltrative, inflammatory, or compressive pathology.25 For an isolated neuropathy of CN III, IV, or VI presenting without evidence of an aneurysm, the optimal study is MRI of the brain and orbits with gadolinium, high-resolution cuts through the brainstem, and fat-suppressed orbital imaging to assess for inflammation, neoplasm, or demyelination along the course of the nerves.25 If an aneurysm is suspected, the imaging modality chosen (typically magnetic resonance angiography [MRA] and CT angiography) should be standard for that required to assess for an aneurysm; this is detailed in other chapters in this text specifically devoted to the topic. If myasthenia gravis is suspected, a bedside test that can be performed is the ice test. An ice-filled glove or bag is applied to the patient’s closed eye or eyes, held there for about 5 minutes, withdrawn, and any improvement in ptosis (typically ≈5 mm) or diplopia noted. Cold temperatures mitigate the effect of myasthenia-related acetylcholine receptor blockade by decreasing cholinesterase activity and promoting the efficacy of acetylcholine at the endplate. The bedside tests with the highest sensitivities for ocular myasthenia gravis are fatigability on sustained upgaze (sensitivity, 80%; specificity, 63%) and the ice test (sensitivity, 80%; specificity, 25%).22 An edrophonium (Tensilon) challenge can also be performed, if the drug is available.

DIAGNOSTIC ALGORITHM The critical, emergent, and urgent diagnoses applicable to each of the differential considerations noted are outlined in Table 18.1. The refinement of the differential diagnosis for the ED patient with diplopia involves determining the exact nature of the diplopia and functional location of the defect and screening for associated symptoms and findings that may suggest the underlying cause. Most of this diagnostic resolution is done at the bedside, followed by targeted neuroophthalmologic imaging, as indicated. The diagnostic challenge, in a context of cost-effective and efficient resource utilization, tends to be “Where do I look? … and

for what? … and with which tool?” This challenge can be addressed, as reflected in the diagnostic algorithm in Fig. 18.4, using a phased systematic approach that incorporates the following queries, taking into consideration the symptoms and signs described earlier (see “Pivotal Findings”): 1. Is the diplopia monocular? 2. Is the diplopia due to a restrictive, mechanical orbitopathy? 3. Is the diplopia due to a palsy of the oculomotor cranial nerves (CN III, IV, VI) in a single eye? 4. Is the diplopia due to a neuroaxial process involving the brainstem and related cranial nerves? 5. Is the diplopia due to a neuromuscular disorder? The first key assessment is to determine if diplopia is purely monocular. If it is, the evaluation essentially ends with ophthalmologic considerations. In contrast, if the diplopia is determined to be binocular, the next question is whether or not there is a simple mechanical orbitopathy, from an inflammatory, traumatic, neoplastic, or infectious mass effect directly restricting the movement of a single eye. If both eyes are involved, thyroid disease (Graves’ orbitopathy) is a consideration. If an orbital mechanical problem is clearly apparent, with no neuroophthalmologic findings (including ptosis, pupillary abnormality, and anisocoria) or neurologic findings (including cranial nerve abnormalities), the initial evaluation can proceed along these lines. If the diplopia does not appear to be strictly mechanical, the next question is whether there is a unilateral oculomotor cranial nerve palsy in the oculomotor (CN III), trochlear (CN IV), or abducens (CN VI) nerve, either as an isolated simple mononeuropathy from compression or microvascular ischemia or ipsilateral involvement of more than one of these oculomotor nerves (from mass, inflammation, or infection in the posterior orbit or cavernous sinus; orbital apex syndrome). An older diabetic patient with a classic presentation of mononeuropathy from microvascular ischemia will typically not need neuroimaging because the yield regarding another pathology is very low.6,26 If there is any equivocation, however, it would not be unreasonable to pursue this in the ED because a small percentage of patients with risk factors for microvascular ischemia (eg, hypertension, diabetes, smoking) may have a cause other than microvascular ischemia.6,27 Assuming that a unilateral process limited exclusively to the orbit or oculomotor cranial nerves is not clearly identifiable, the next option is a neuroaxial process involving the brainstem and related cranial nerves, as one of the following: (1) a focal lesion in the brainstem (eg, from multiple sclerosis); (2) a more diffuse but still localized brainstem process (eg, from a brainstem tumor, brainstem lacunar stroke, impending basilar artery thrombosis, vertebral artery dissection, or ophthalmoplegic migraine); or (3) as part of a more diffuse neurologic syndrome involving the brainstem and/or CNs III, IV, and VI due an infectious, autoimmune, neurotoxic, or metabolic process involving other neurologic structures (eg, basilar meningoencephalitis, foodborne botulism, Miller-Fisher or Guillain-Barré syndrome, Wernicke’s encephalopathy). It should be kept in mind that diplopia may be the first, primary, or only symptom of any of these, and that neuropathic signs suggesting a focal brainstem process may actually be a mild or early presentation of a diffuse neurologic syndrome. Finally, if the presentation of the diplopia does not fit into an anatomically congruent process or central nervous system (CNS), a neuromuscular cause such as myasthenia gravis or tick paralysis may be involved.

EMPIRICAL MANAGEMENT Because the treatment of diplopia depends entirely on the cause, there are few primary treatments for diplopia in the ED, as opposed to addressing whatever secondary disorder is causing it. Such approaches are outlined elsewhere in this text.

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Monocular? Persists with unaffected eye closed?

SECTION Two 

POTENTIAL DIAGNOSIS

EVALUATION

• Refraction problem in cornea, lens, vitreous; retinal wrinkle

• Slit lamp examination • Consider ophthalmology consult or referral

YES

NO Restrictive mechanical orbitopathy?

Signs, Symptoms, and Presentations

CRITICAL or EMERGENT • Orbital cellulitis or abscess YES

Involving only one eye?

YES

NO

URGENT • Orbital myositis • Idiopathic orbital inflammatory syndrome (”orbital pseudotumor”) • Maxillofacial or orbital tumor CRITICAL or EMERGENT • N/A

NO Involving both eyes

URGENT • Graves’ disease Isolated palsy of CN III, IV, or VI?

YES

Typical microvascular ischemia?

YES

• Contrast-enhanced MRI (or CT) of the orbits

• Contrast-enhanced MRI (or CT) of the orbits

• Consider discharge with neuroophthalmology referral

• Chronic diabetes or hypertension • Associated pain NO “Aneurysmal” CN III palsy?

YES

• Pupillary involvement?

Isolated palsy of CN IV or VI?

YES

URGENT • Skull base brain tumor, other lesion

NO Orbital apex syndrome or cavernous sinus? Combined palsy of CN III, IV, or VI?

YES

NO

• Retroorbital pain? • Exophthalmos? • Conjunctival injection or chemosis? • No other neurologic deficits except facial numbness?

YES

YES

Deficits isolated to the brainstem?

CRITICAL or EMERGENT • Septic cavernous sinus thrombosis • Cavernous internal carotid artery aneurysm • Carotid-cavernous fistula • Cavernous sinus vasculitis URGENT • Orbital apex mass or infiltrative process (eg, sarcoidosis)

NO

Other neurologic deficits?

• MRA/CTA/DSA brain

URGENT • Skull base brain tumor, other lesion

NO

NO

CRITICAL or EMERGENT • Intracranial aneurysm

YES

• Skew deviation? • Dysarthria? • Vertigo? • Other cranial neuropathies?

CRITICAL or EMERGENT • Impending basilar artery thrombosis • Basilar meningoencephalitis • Brainstem lacunar stroke • Vertebral artery dissection URGENT • Multiple sclerosis • Ophthalmoplegic migraine • Intracranial tumor

• MRI brain  orbits with gad  high-res cuts through brainstem  fatsuppressed orbital imaging

• Contrast-enhanced MRI (or CT) of the orbits ( brain)

• Vascular causes: MRI brain (with DWI)  MRA or CTA brain and neck • Others: MRI brain with gad  hi-res cuts through brainstem • Consider LP for meningitis

NO

NO

NO

Neuropathic syndrome with brainstem/cranial nerve involvement? • Brainstem findings  other neurologic signs?

Neuromuscular process? NO

YES

YES

CRITICAL or EMERGENT • Botulism (Dysarthria? Dry mouth? Dysphagia?...) • Wernicke’s encephalopathy (Nystagmus? Altered mental status? Malnutrition?...) URGENT • Miller-Fisher syndrome (Ataxia? Areflexia? Recent illness?...)

CRITICAL or EMERGENT • Myasthenia gravis URGENT • N/A

• Treat empirically • Consider screening MRI • Consider LP for Miller-Fisher syndrome

• Ice test • Edrophonium challenge

Consider other diagnoses

Fig. 18.4.  Algorithm for the diagnostic approach to diplopia in the ED, a guideline. CN, Cranial nerve; CNS, central nervous system; CT, computed tomography; CTA, CT angiography; DSA, digital subtraction angiography (conventional angiography); DWI, diffusion-weighted imaging; gad, gadolinium; High-res, high-resolution; LP, lumbar puncture; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging.

CHAPTER 18  Diplopia

DIPLOPIA SCREENING

Assess airway and ventilatory status

Yes

• Signs of airway compromise? • Signs of hypoventilation?

• • • • •

EMPIRICAL PREDIAGNOSTIC MANAGEMENT

Gag? Tachypnea and anxiety? NIF? End-tidal CO2? PCO2 on ABG?

• Immediate airway or ventilatory support as needed (intubation, BiPAP)

No

Assess for signs of stroke • Signs of an impending basilar artery occlusion?

Yes

• Risk factor for vertebral artery dissection or cerebrovascular disease? • Vertigo? • Dysarthria?

• IV fluid bolus • Emergent stroke evaluation for reperfusion therapy/anticoagulation

• Temperature elevation? •  Headache? •  Photophobia? •  Meningismus? •  Altered mental status?

• Emergent empirical antibiotics pending CT, LP, and confirmation of infection

• Nystagmus? • Altered mental status? • Ataxia?

• Emergent administration of thiamine

No

Assess for signs of infection • Signs of basilar meningoencephalitis?

Yes

No

Signs of Wermicke’s encephalopathy?

Yes

No

PROCEED WITH INDICATED EVALUATION AND MANAGEMENT Fig. 18.5.  Algorithm for the initial stabilization of the patient with diplopia in the ED, a guideline. ABG, Arterial blood gas; BiPAP, biphasic positive airway pressure; CO2, carbon dioxide; pCO2, partial pressure of carbon dioxide; CT, computed tomography (of the cranium); LP, lumbar puncture; NIF, negative inspiratory force.

Management Algorithm Certain emergent therapeutic measures may be indicated in the context of potentially serious underlying causes, as outlined in the algorithm in Fig. 18.5. The priority is to consider imminent threats to CNS tissue viability such as an impending basilar artery thrombosis and then consider rapidly evolving threats to CNS tissue viability such as meningoencephalitis or Wernicke’s encephalopathy and institute indicated treatments empirically as, or even before, the evaluation gets underway.

The patient with diplopia will typically require admission for further evaluation and treatment of the underlying disorder, unless diagnosed with a low-acuity condition such as microvascular ischemia. A CN III or VI palsy from microvascular ischemia is generally self-limited; the pain usually resolves after a few days, and complete spontaneous resolution is the norm, occurring in up to 95% of patients. These patients can typically be discharged home, with close outpatient follow-up.

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Signs, Symptoms, and Presentations

KEY CONCEPTS • Monocular diplopia persists in one affected eye, even with the other one closed. It is an ophthalmologic problem related to refractory distortions in the light path or from buckling of the retina. • Binocular diplopia resolves when either eye is closed and is the result of a misalignment in the visual axes. • Four lines of questioning that help formulate the differential diagnosis of binocular diplopia are as follows: (1) cadence of onset and symptoms (a sudden onset suggests an ischemic event; a fluctuation of symptoms suggests transient ischemic attacks, impending stroke, or neuromuscular disease); (2) directionality and orientation of the diplopia (horizontal, vertical, torsional); (3) presence of pain, which suggests an inflammatory or infectious process, and (4) the presence of other associated symptoms, which suggest a larger disease process (eg, infection, CNS ischemia, neuromuscular disease). • The diagnostic approach to diplopia entails a methodical consideration of (1) a monocular (refractive) problem, which, when excluded, leads to consideration of (2) a simple restrictive, mechanical orbitopathy, which, when excluded, leads to consideration of (3) a palsy of one or more of the oculomotor cranial nerves, and then (4) a more proximal neuroaxial process involving the brainstem and related cranial nerves; if all else is excluded, then (5) a systemic neuromuscular process. • An isolated CN III palsy presents with diplopia in all directions of gaze, except on lateral gaze to the affected side, and an eye that is deviated down and out, with a dilated pupil, and ptosis. Microvascular ischemia (typically seen in patients with diabetes), classically spares the pupil. A CN IV palsy results in rotational diplopia that worsens on looking down and toward the nose. A CN





• •

VI palsy results in diplopia that worsens on lateral gaze toward the problematic side. Simultaneous ipsilateral involvement of more than one of the CN III, IV, or VI nerves from mass, inflammation, or infection in the posterior orbit or cavernous sinus (orbital apex syndrome) may cause a combination of palsies and is associated with retroorbital pain or blurred vision due to venous congestion and possibly ipsilateral numbness or dysesthesia from involvement of the ophthalmic (V1) and maxillary (V2) trigeminal branches that travel though the orbital apex. Diplopia from a neuroaxial process involving the brainstem and related cranial nerves may present as (1) a focal lesion in the brainstem (eg, from multiple sclerosis), (2) a more diffuse but still localized brainstem process (eg, from a brainstem tumor or lacunar stroke, impending basilar artery thrombosis, vertebral artery dissection, or an ophthalmoplegic migraine), or (3) as part of a more diffuse neurologic syndrome involving the brainstem and oculomotor nerves (eg, from an infectious, autoimmune, neurotoxic, or metabolic process). The diplopia in myasthenia gravis is associated with ptosis, gets worse as the patient fatigues, and improves with rest or on placing ice over the eye. The empirical treatment of conditions causing diplopia, instituted even before testing for specific entities is begun, is directed toward imminent threats to airway and ventilation (eg, with botulism and myasthenia gravis), immediate threats to CNS tissue viability (eg, with basilar artery thrombosis or stroke), and rapidly evolving threats to CNS tissue viability (eg, with meningoencephalitis or Wernicke’s encephalopathy).

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 18  Diplopia

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REFERENCES 1. Nazerian P, Vanni S, Tarocchi C, et al: Causes of diplopia in the emergency department: diagnostic accuracy of clinical assessment and of head computed tomography. Eur J Emerg Med 21:118–124, 2014. 2. Friedman DI: Pearls: diplopia. Semin Neurol 30:54–65, 2010. 3. Cockerham KP, Chan SS: Thyroid eye disease. Neurol Clin 28:729–755, 2010. 4. Prasad S, Volpe NJ: Paralytic strabismus: third, fourth, and sixth nerve palsy. Neurol Clin 28:803–833, 2010. 5. Cianfoni A, Pravatà E, De Blasi R, et al: Clinical presentation of cerebral aneurysms. Eur J Radiol 82:1618–1622, 2013. 6. Tamhankar MA, Biousse V, Ying GS, et al: Isolated third, fourth, and sixth cranial nerve palsies from presumed microvascular versus other causes: a prospective study. Ophthalmology 120:2264–2269, 2013. 7. Aryasit O, Preechawai P, Aui-Aree N: Clinical presentation, aetiology and prognosis of orbital apex syndrome. Orbit 32:91–94, 2013. 8. Boynes SG, Echeverria Z, Abdulwahab M: Ocular complications associated with local anesthesia administration in dentistry. Dent Clin North Am 54:677–686, 2010. 9. Kurimoto T, Tonari M, Ishizaki N, et al: Orbital apex syndrome associated with herpes zoster ophthalmicus. Clin Ophthalmol 5:1603–1608, 2011. 10. Lee CY, Tsai HC, Lee SS, et al: Orbital apex syndrome: an unusual complication of herpes zoster ophthalmicus. BMC Infect Dis 15:33, 2015. 11. Merino-Iglesias A, Montero JA, Calabuig-Goena M, et al: Orbital apex syndrome secondary to herpes zoster virus infection. BMJ Case Rep 2014:2014. 12. Mattle HP, Arnold M, Lindsberg PJ, et al: Basilar artery occlusion. Lancet Neurol 10:1002–1014, 2011. 13. Muslikhan Y, Hitam WH, Ishak SR, et al: Cryptococcus meningitis in an immunocompetent teenage boy presented early with diplopia. Int J Ophthalmol 3:92–94, 2010. 14. Jensen MB: Diplopia secondary to West Nile virus meningitis. Webmedcentral 1:2010. 15. Rufa A, Cerase A, Annunziata P, et al: Transient supranuclear paresis of the abduction in viral encephalitis of the brainstem. Neurol Sci 31:653–655, 2010.

16. Williams BT, Schlein SM, Caravati EM, et al: Emergency department identification and critical care management of a Utah prison botulism outbreak. Ann Emerg Med 64:26–31, 2014. 17. Arányi Z, Kovács T, Sipos I, et al: Miller Fisher syndrome: brief overview and update with a focus on electrophysiological findings. Eur J Neurol 19:15–20, 2012. 18. Lough ME: Wernicke’s encephalopathy: expanding the diagnostic toolbox. Neuropsychol Rev 22:181–194, 2012. 19. Lonati D, Giampreti A, Rossetto O, et al: Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001-2011. Clin Toxicol (Phila) 52:269–276, 2014. 20. Spillane J, Higham E, Kullmann DM: Myasthenia gravis. BMJ 345:e8497, 2012. 21. Keane JR: Third nerve palsy: analysis of 1400 personally-examined inpatients. Can J Neurol Sci 37:662–670, 2010. 22. Mittal MK, Barohn RJ, Pasnoor M, et al: Ocular myasthenia gravis in an academic neuro-ophthalmology clinic: clinical features and therapeutic response. J Clin Neuromuscul Dis 13:46–52, 2011. 23. Teksam O, Keser AG, Konuskan B, et al: Acute abducens nerve paralysis in the pediatric emergency department: analysis of 14 patients. Pediatr Emerg Care 32:307–311, 2016. 24. Wendell LC, Levine JM: Myasthenic crisis. Neurohospitalist 1:16–22, 2011. 25. Wippold FJ, II, Cornelius RS, Berger KL, et al: Expert Panel on Neurologic Imaging: Orbits, vision and visual loss. . 26. Murchison AP, Gilbert ME, Savino PJ: Neuroimaging and acute ocular motor mononeuropathies: a prospective study. Arch Ophthalmol 129:301–305, 2011. 27. O’Colmain U, Gilmour C, MacEwen CJ: Acute-onset diplopia. Acta Ophthalmol 92:382–386, 2014. 28. Lewandowski CA, Rao CP, Silver B: Transient ischemic attack: definitions and clinical presentations. Ann Emerg Med 52:S7–S16, 2008.

CHAPTER 18: QUESTIONS & ANSWERS 18.1. A 65-year-old man with a long-standing history of diabetes and hypertension presents with sudden onset of persistent diplopia that began a few hours before arrival. He describes left retro-orbital discomfort, and his examination is notable for a left eye that is deviated laterally and downward, with a palsy of movement medially and upward. He also has a left-sided ptosis but no conjunctival injection, chemosis, or proptosis. His pupils are equal in size at 4 mm, round, and equally reactive to light in both a direct and consensual reflex, and his examination is otherwise unremarkable. What is the most likely cause of the diplopia? A. Brain tumor B. Cerebral aneurysm C. Microvascular ischemia D. None of these E. Orbital apex syndrome Answer: C. Based on examination, this is a patient who has a pupil-sparing CN III (third nerve) palsy. Because his pupillary examination is normal, with an otherwise complete CN III palsy, the so-called rule of the pupil applies. The palsy is very unlikely to be due to external compression from a brain tumor, aneurysm, or orbital apex process. It is a typical presentation of microvascular ischemia, to which the patient is predisposed, given his history of diabetes and hypertension. 18.2. A 56-year-old woman presents with recurrent episodes of diplopia that have been ongoing for a week. She describes double vision that gradually comes and goes, typically worse at the end of the day, with no particular direction or orientation to the diplopia. The patient’s coworker, who is present in the emergency department (ED) with her, states that the patient’s eyes “looked droopy” during an animated staff meeting they attended that afternoon but look normal now. The patient also describes waxing and waning general muscular weakness that has also been present this past week but denies any other symptoms and

states that when she rests, she feels better. With which entity are her symptoms most consistent? A. Botulism B. Hypothyroidism C. Miller-Fisher syndrome D. Myasthenia gravis E. None of the above Answer: D. The patient and coworker are describing what appears to be an activity-related diplopia, with generalized muscle weakness and lack of other focal symptoms, all very suggestive of a possible neuromuscular process (myasthenia gravis). MillerFisher syndrome would not be associated with muscle weakness and would not wax and wane. Botulism would typically have a more progressive course, with other associated bulbar symptoms. Diplopia may be associated with hypothyroidism if it is a presentation of or treatment complication of Graves’ disease but would not change so markedly with activity. 18.3. A 76-year-old man with hypertension, hypercholesterolemia, and diet-controlled diabetes presents with a sudden onset of diplopia that developed 30 minutes before arrival. Medics state that the patient’s wife reported that he suddenly began staggering around the room, unable to bear weight on his left side. On examination, the patient has normal vital signs except for mild hypertension and has a right CN III palsy, with left arm and leg weakness. He has no airway complaints and denies any pain. What is the most appropriate initial response? A. Checking blood gas levels and assess the patient’s negative inspiratory force B. Emergent treatment with botulinum antitoxin C. Initiating broad-spectrum antibiotics to cover upper respiratory pathogens D. Initiating clinical measures to address an acute ischemic stroke E. A and B

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SECTION Two 

Signs, Symptoms, and Presentations

Answer: D. The paroxysmal onset of the patient’s symptoms, with focal neurologic symptoms and signs, suggests an ischemic event. His crossed deficits and discrete CN III palsy suggest localization in the brainstem. 18.4. Which constellation of symptoms is most concerning for foodborne botulism? A. Double vision, headache, and right leg weakness B. Double vision, left eye discomfort, and periorbital swelling C. Double vision, neck pain, and vertigo D. Double vision, nystagmus, and confusion E. Double vision, slurred speech, difficulty swallowing, and dry mouth Answer: E. Double vision, slurred speech, difficulty swallowing, and dry mouth would be present with foodborne botulism. 18.5. A 45-year-old man presents with progressively worsening double vision associated with right-sided, retro-orbital pain. His examination reveals mild conjunctival injection of the right eye, palsies of CNs III, IV, and VI on that side, some ptosis, a slightly decreased visual acuity to the right

eye compared to the left, and mild sensory loss to the right infraorbital maxillary area. Which of the following initial imaging modalities should be used to evaluate the patient? A. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) of the brain and neck B. Contrast-enhanced CT or magnetic resonance imaging (MRI) of the brain, with fine cuts through the orbit C. Diffusion-weighted MRI of the brain and brainstem D. Digital subtraction angiography (DSA) E. Noncontrast computed tomography of the brain Answer: B. The combined palsy of multiple oculomotor cranial nerves on one side, with no other neurologic deficits apart from mild facial numbness corresponding to the maxillary branch of the trigeminal nerve, especially with the ocular findings and decreased visual acuity, suggests an orbital apex or cavernous sinus problem. The most optimal study would be that outlined in answer B. The risk in using the studies outlined in the other answers is that pathology might be missed because they are not dedicated to the orbits and cavernous sinus.

C H A P T E R 19 

Red and Painful Eye Alan A. Dupré  |  John M. Wightman PERSPECTIVE Epidemiology and Pathophysiology Most eye complaints are not immediately sight-threatening and can be managed by an emergency clinician; however, some require immediate recognition, emergent intervention, and consultation. Ocular injuries are one of the leading causes of visual impairment and blindness worldwide.1 More patients with postoperative complications can be expected to present to the emergency department (ED) as more outpatient ophthalmological surgeries are performed. Nontraumatic diseases, such as glaucoma and peripheral vascular disease leading to retinal ischemia, are more common with advancing age. The external and internal anatomy of the eye is depicted in Figure 19.1. The globe has a complex layer of blood vessels in the conjunctiva, sclera, and retina. Redness reflects vascular dilation and may occur with processes that produce inflammation of the eye or surrounding tissues. Eye pain may originate from the cornea, conjunctiva, iris, vasculature, or optic nerve. Each is sensitive to processes causing irritation or inflammation.

DIAGNOSTIC APPROACH Rapid and accurate triage is the most critical consideration in the approach to the red and painful eye. A few problems should be considered critical, because they can rapidly lead to progressive visual loss without immediate intervention in the ED. Emergent conditions require expeditious triage and treatment. Urgent conditions should be managed in the ED before discharge. The remainder of conditions are those, such as conjunctivitis and spontaneous subconjunctival hemorrhage, where time to treatment has little effect on patient comfort or outcome. Visual acuity has been called “the vital sign of the eye.” Only a few situations preclude early and accurate visual acuity testing. Patients with complaints of contamination with an acid, alkali, or other caustic substance; sudden visual loss, especially if unilateral and painless; and significant trauma, especially with retrobulbar hematoma causing orbital compartment syndrome, should have only a gross visual acuity examination performed as interventions are simultaneously prepared. When not being actively examined or treated, injured eyes should be protected with a rigid shield to prevent inadvertent pressure that could cause additional damage.

Differential Diagnosis Considerations The diagnostic approach to the red or painful eye typically begins with categorization into traumatic and nontraumatic causes. Patients almost always can report whether or not their eye was injured, even indirectly, such as injury from reflected sunlight. Traumatic pain and redness can be caused by caustic fluids and solid materials, low-velocity contact with a host of materials that can fall or be rubbed into the eye, higher velocity blunt-force impacts to the orbit or globe, or potentially penetrating injuries.

Caustic contamination is discussed elsewhere. Other traumatic complications that must be considered early in the course of care include retrobulbar hematoma, abscess, or emphysema with orbital compartment syndrome and suspicion of an open globe from either blunt or penetrating trauma. The first triage question for any eye complaint should be, “Did anything get in your eye?” If so, attempt to identify the nature of the substance or foreign body. Specifically, this question seeks to quickly identify eyes that may have been exposed to a caustic substance. Patients exposed to acids, alkalis, and other caustic substances require rapid decontamination before additional evaluation to potentially prevent permanent loss of visual acuity. The possibility of an open globe must be considered following any traumatic injury regardless of the mechanism. Findings may be obvious, subtle, or occult. Blunt trauma may frankly rupture the globe. Penetrating trauma can result from obvious causes identified through determining the events leading to injury, but it can also be unknown to the victim, such as walking near a person hammering metal or using a high-speed grinder yet not realizing a tiny ballistic metal fragment may have penetrated the eye. Causes of nontraumatic pain and redness are diverse but are mostly infectious and inflammatory, although these may be due to processes intrinsic to the globe and adjacent structures or be due to ocular manifestations of systemic illness (eg, giant-cell arteritis). Exposure history and review of systems may be helpful when infection is suspected (eg, concomitant upper respiratory tract infections making a viral etiology of conjunctivitis more likely). Questions related to recent surgery and contact lens wear and cleaning practices should not be overlooked. Therefore, nontraumatic eye complaints typically require a more detailed history than would be necessary following a known injury. Not all visual disturbances are due to conditions that cause ocular inflammation resulting in pain or redness. One that is critical to identify in the triage process is central or branch retinal artery occlusion. Only a rapid funduscopic examination to identify the problem and immediate intervention will afford even a chance to restore sight. This condition is readily apparent as a diffusely pale retina with indistinct or unseen retinal arteries (Fig. 19.2). Because it does not typically present with either pain or external signs (such as, redness), diagnosis and treatment are detailed in Chapter 61. Diplopia is covered in Chapter 18.

Pivotal Findings Measurement of the patient’s best corrected visual acuity (ie, with glasses on if available) with each eye individually provides vital information when evaluating eye complaints and may be prognostic in some situations. Only a few situations discussed earlier preclude obtaining visual acuity using a chart. Decreased visual acuity caused by abnormal refraction (eg, chronic myopia) can be detected by using a pinhole device during acuity testing, because central vision remains intact in refraction conditions. If there is a non-refractory problem, such as retinal edema or aqueous hemorrhage causing the acuity deficit, pinhole testing will show no improvement in the (poor) visual acuity. 169

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Signs, Symptoms, and Presentations

Pupillary margin

Superior punctum

Cornea overlying iris

Inner canthus

Sclera

Caruncle

Outer canthus Inferior punctum Iris sphincter Limbus (corneoscleral junction)

Collarette Iris crypt

Cilia (eyelashes)

A

External appearance of the eye Ciliary body Canal of Schlemm Posterior chamber Fovea Iris Optic nerve

Anterior chamber Lens Cornea Limbus Pars plana Retina

B

Cross section of the eye

Fig. 19.1.  External (A) and internal (B) anatomy. (From Ragge NK, Easty DL: Immediate eye care, St Louis, 1990, Mosby-Year Book.)

Symptoms and signs that are more likely to be associated with a serious diagnosis in patients with a red or painful eye are listed in Box 19.1.

Symptoms When the presenting complaint is pain, the first step is to characterize it: itching, burning, dull pain, sharp pain, diffuse, or localized. Two historical factors are particularly important: suddenness of onset and perception of a foreign body. Itching tends to be more often due to irritation by blepharitis, conjunctivitis, or dry eye syndrome. Burning is associated with these conditions and with other mostly superficial problems, such as irritation of a pterygium or pinguecula, episcleritis, or limbic keratoconjunctivitis. A foreign-body sensation, particularly when it can be localized, is a strong indicator of corneal origin to the pain (foreign body, corneal abrasion, ulcer, or viral or ultraviolet keratitis). Sharp pain generally results from abnormalities of the anterior eye, such as corneal origin pain and uveitis. Dull pain, which may be severe, is usually generalized throughout the eye (and may be reported as “headache”). It is typically a manifestation of increased intraocular pressure (IOP) (such as, with acute angle closure glaucoma), vitreous infection (such as, endophthalmitis), or the pain is referred from an extra orbital process (such as, sinusitis,

migraine headache, or temporal arteritis). Acute orbital compartment syndrome, caused by retro-orbital hematoma, presents with intense pain and progressive visual loss. These patients often present with head trauma that precludes them reporting pain, emphasizing the importance of physical examination. Rarely is there a chief complaint of redness that is not accompanied by pain, itching, irritation, or foreign body sensation. Completely asymptomatic “red eye” is almost always a spontaneous subconjunctival hemorrhage, which is benign but often alarming to the patient. Spontaneous subconjunctival hemorrhage may follow coughing or straining, but it most often occurs without any identifiable precipitating event and is simply noticed by the patient when looking in a mirror. Symptomatic red eye commonly causes bulbar or limbal injection of the conjunctiva. Free blood noted behind the bulbar conjunctiva (ie, subconjunctival hemorrhage) or in the anterior chamber (ie, hyphema) may be spontaneous or post-traumatic. Spontaneous subconjunctival hemorrhage is painless, and the presence of pain raises concern for a more serious cause of the hemorrhage, such as direct globe injury or a retrobulbar process. Hyphema of sufficient size to be noted by the patient or bystander usually presents with pain and blurred vision. Other subjective findings may be transient and detected only by a thorough history. The patient may have symptoms of lid

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BOX 19.2 

Past Ocular History Questions 1. Are contact lenses used? If so, what type, how are they cleaned, and how old are the lenses? How often is the lens solution changed? 2. Are glasses worn? If so, when was the last assessment for adequate refraction? Does the patient endorse a subjective change in vision? 3. Has previous eye injury or surgery occurred? 4. What is the patient’s usual state of health? Does the patient have any systemic diseases that may affect the eye? 5. What medications are being taken? 6. Are there any known or suspected allergies?

Retinal edema

Cherry-red spot

Fig. 19.2.  Key funduscopic findings in acute central retinal artery occlusion include general pallor of the retina (except for a characteristic cherryred spot where the perfused choroid shows through the thinner fovea) and attenuation of retinal arteries (possibly with retinal veins preserved as in the photograph). (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders, p 297.)

BOX 19.1 

Pivotal Findings More Likely Associated With a Serious Diagnosis in Patients With a Red or Painful Eye Severe ocular pain Persistently blurred vision Exophthalmos (proptosis) Reduced ocular light reflection Corneal epithelial defect or opacity Limbal injection (also known as, ciliary flush) Pupil unreactive to a direct light stimulus Wearer of soft contact lenses Neonate Immunocompromised host Worsening signs after 3 days of pharmacologic treatment Adapted and reprinted with permission from Trobe JD: The physician’s guide to eye care, San Francisco, 2001, Foundation of the American Academy of Ophthalmology.

swelling, tearing, discharge, crusting, discomfort on blinking, or sensitivity to light. Lid swelling can be caused by inflammatory and noninflammatory processes. Concurrent erythema and tenderness of the lid favors the former. In the absence of trauma or other external irritant (eg, contact dermatitis from eye makeup), inflammatory processes include primary lid problems, such as hordeolum (ie, stye) or blepharitis, as well as extension from concomitant conjunctivitis or cellulitis in orbital or periorbital structures. When pain is present, tearing is usually secondary. Discharge and crusting are most commonly associated with conjunctivitis, whether allergic, chemical, viral, or bacterial. Blepharitis, dacryocystitis, and canaliculitis are other inflammatory processes that may create a discharge and subsequent crusting. A history of eyelids sticking together, particularly in the morning, is commonly cited as clinical evidence of bacterial, as opposed to viral, conjunctivitis, but this is unreliable. Even when lid sticking is combined with absence of itch and lack of history of conjunctivitis, large studies have failed to show diagnostic

BOX 19.3 

Complete Eye Examination Visual acuity (best possible using correction) Visual fields (tested by confrontation) External examination Globe position in orbit Conjugate gaze Periorbital soft tissues, bones, and sensation Extraocular muscle movement Pupillary evaluation (absolute and relative) Pressure determination (tonometry) Slit-lamp examination Funduscopic examination Adapted from Wightman JM, Hurley LD: Emergency department management of eye injuries. Crit Decis Emerg Med 12:1-11, 1998.

correlation between lid sticking and bacterial infection. Similarly, in the pediatric population (younger than 18 years old), lid sticking plus mucoid or purulent discharge show only fair correlation with proven bacterial infection. The hazards of equating lid sticking with bacterial infection are underscored by the fact that viral conjunctivitis, particularly caused by subtypes of adenovirus, can cause dramatic symptoms with mucopurulent discharge, lid sticking, keratitis symptoms, and lid inflammation. In many studies, lack of viral cultures precludes consideration of copathogens or bacterial culture of nonpathogenic flora. Additional past ocular history questions are listed in Box 19.2.

Signs A complete eye examination usually includes eight components, although many patients require only a limited or directed eye examination, depending on the presentation. The mnemonic VVEEPP (pronounced “veep”) plus slit-lamp and funduscopic examinations represent these components (Box 19.3). We recommend slit-lamp examination for any complaint involving trauma and for any medical presentation involving foreign-body sensation or alteration of vision. Funduscopic examination is usually pursued if there is visual loss, visual alteration, clouding of vision, or suggestion of serious pathology in the history and initial physical examination. A thorough physical examination can be conducted in the following order.

Visual Acuity The initial determination of a patient’s visual acuity provides a baseline from which deterioration or improvement may be

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followed. It is also predictive of functional outcome after ocular trauma. Visual acuity is quantitatively assessed by use of a Snellen chart test at a distance of 20 feet (6 m) or a Rosenbaum chart at a distance of 14 inches. Young patients who cannot yet read letters and numbers should be tested with an Allen chart that depicts easily recognizable shapes. Each eye is tested separately with the opposite eye carefully covered. Patients who present without their prescribed corrective lenses may be evaluated by having them view the chart through a pinhole eye cover, which improves most refractive errors in vision. If the patient cannot distinguish letters or shapes on a chart, visual acuity must be determined qualitatively. Any printed material suffices. The result may be recorded as, for example, “patient able to read newsprint at 3 feet.” If this is not possible, visual acuity is recorded as: • Unable/able to count fingers (CF) • Unable/able to perceive hand motion (HM) • Unable/able to perceive light (LP)

Visual Field Testing Confrontation is the most common method of testing visual fields in the ED, but it is unreliable for detection of anything short of an extensive field deficit. On the other hand, visual field examination rarely adds useful information in the evaluation of the acutely red and painful eye. Detection of a scotoma usually represents a retinal problem. However, glaucoma may cause scotomata that can be crescent-shaped, involve just the binasal visual fields, or affect all peripheral vision. Hemi- or quadrantanopia is more commonly a problem of the neural pathways to the brain.

External Examination Gross abnormalities are assessed by a visual inspection of both eyes simultaneously. Findings may be more apparent if compared with the opposite side. Fractures of maxillofacial bones are associated with ocular injuries, some of which require immediate intervention by an ophthalmologist.2 Globe position is part of the external examination. Subtle exophthalmos and enophthalmos are rare and best detected by looking inferiorly, tangentially across the forehead, from over the patient’s scalp. Exophthalmos may have traumatic or nontraumatic causes but is due to increased pressure or a space-occupying lesion within the orbit, which may manifest as pain. Medical causes include cellulitis or intraorbital or lacrimal tumors. Hyperthyroidism may cause enlargement of extraocular muscles. The most important cause of exophthalmos in the ED is orbital compartment syndrome, which pushes the globe forward, stretching the optic nerve and retinal artery and increasing IOP. The resulting microvascular ischemia is sight-threatening if sufficiently severe and persistent. Orbital emphysema and inflammation caused by a retained foreign body behind the eye are other causes of exophthalmos. Other signs of orbital compartment syndrome include limited eye movement and a relative afferent pupillary defect (RAPD) described under ancillary testing. If retrobulbar hemorrhage is the cause, blood often dissects anteriorly to fill the subconjunctival potential spaces. The discovery of exophthalmos should prompt ocular tonometry measurements to determine the urgency of intervention. Trauma, particularly penetrating globe injury with extrusion of vitreous, can cause the globe to recede into the orbit, but the most common cause of enophthalmos is actually pseudo-enophthalmos when the contralateral globe is proptotic. Inspection also involves examination of the upper and lower palpebral sulci for foreign bodies or other abnormalities. The lower sulcus is easily viewed after manual retraction of the lower lid toward the cheek and having the patient gaze upward. The

Fig. 19.3.  Injection of the palpebral and bulbar conjunctiva plus hypertrophy of Bruch’s glands in the lower eyelid. (Photograph courtesy of Dr. John Wightman.)

upper sulcus is inspected by pulling its lashes directly forward and looking under the lid with white light. The lid can then be everted by pressing a cotton-tipped applicator in the external lid crease and folding the lid margin over the applicator. Conjunctivitis, with conjunctival injection and discharge, is a common diagnosis following evaluation of patients with red and painful eyes. The presence of punctate “follicles” (ie, hypertrophy of lymphoid tissue in Bruch’s glands) along the conjunctival surfaces of one or both lower lids has been touted to be relatively specific for a viral etiology (Fig. 19.3). Indeed, the “typical” viral “pink eye” used to be called acute follicular conjunctivitis.3 Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is one notable nonviral cause of this follicular hypertrophy. Any discharge present is assessed as serous, mucoid, or purulent. Both viral and bacterial infection can cause mucoid or purulent discharge, so it is not possible to clinically distinguish viral from bacterial conjunctivitis on this basis alone. A red eye in a neonate or infant is always abnormal. It is usually caused by corneal abrasion or infection. Corneal abrasions can also be a cause of inconsolable crying in an infant. Fluorescein examination helps to identify traumatic abrasions and herpes keratitis acquired from the birth canal or transmitted from a caregiver’s fingers.

Extraocular Muscle Function Limitation of ocular movement in one eye may be detected by having the patient follow the examiner’s finger or a bright light through the cardinal movements of gaze. The eyes may move in a disconjugate fashion, or the patient may admit to diplopia if asked. Diplopia on extreme gaze in one direction may indicate entrapment of one of the extraocular muscles within a fracture site, but more often is caused simply by edema or hemorrhage related to the injury and is functional rather than actual entrapment. In the absence of trauma, diplopia is rarely associated with redness or pain.

Pupillary Evaluation The pupils are inspected for abnormalities of shape, size, and reactivity. These examinations are conducted with light specifically directed into the pupil and by means of the swinging flashlight test.

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Blunt or penetrating trauma, previous surgery (eg, iridotomy for cataract extraction), and synechiae from prior iritis or other inflammatory condition are the most common causes of irregularly shaped pupils. Asymmetrically sized pupils may represent normal or pathologic conditions. Physiological anisocoria is a slight difference in pupil size that occurs in up to 10% of the population. Topical or systemic medications, drugs, and toxins may cause abnormal pupillary constriction or dilation. Pathologic reasons for failure of one pupil to constrict with a direct light stimulus include globe injury, abnormalities of afferent or efferent nerves, and paralysis of the ciliaris or sphincter pupillae muscles in the iris. Potentially serious problems, which also cause pain and redness, include uveitis and acute angleclosure glaucoma. While examining the pupils, the anterior chambers can be visually inspected for hyphema or hypopyon. Blood in the anterior chamber is usually the result of direct ocular trauma and may be associated with traumatic mydriasis or an obvious tear of the iris. If penetration and rupture can be reasonably excluded, the hyphema should be graded and IOP determined. Inability to view posterior structures through the anterior blood may necessitate radiologic or ultrasonographic imaging.

Posterior cornea

Slit-beam

Iris surface

Fig. 19.4.  Primary angle-closure glaucoma with very shallow anterior chamber and iridocorneal touch (no space between slit-beam views of cornea and iris). (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

Ancillary Testing Physical examination can be augmented by a number of additional tests to assess the relative amount of light reaching the retina or being converted into neural signals, determine the IOP, and visually inspect the anterior and posterior globe with magnification. Imaging of internal anatomy and pathology can be accomplished at the bedside or in the radiology suite.

Swinging Flashlight Test The swinging flashlight test is used to determine whether a RAPD exists (see https://youtu.be/soiKbngQxgw). It is described in Chapter 61. A RAPD may be partial or complete and due to inhibition of light transmission to the retina because of vitreous hemorrhage, loss of some or all of the retinal surface for light contact because of ischemia or detachment, or the presence of lesions affecting the prechiasmal optic nerve (eg, optic neuritis).

Pressure Determination Ocular tonometry is usually the last examination performed in the ED. Common methods of determining the IOP in the ED include use of electronic, manual (eg, Schiøtz), or applanation tonometers. IOPs in the 10 to 20 mm Hg range are considered normal. Causes of intraocular hypertension include glaucoma in its many forms, suprachoroidal hemorrhage, and space-occupying retrobulbar pathology. Acute angle-closure glaucoma is a relatively rare but an important critical diagnosis to make in the ED. Patients present with pain, the onset of which is often sudden in low-light conditions causing pupillary dilation through contraction and thickening of the iris peripherally. The iris becomes immobile and often irregular, and the pupil is commonly fixed at 5 to 6 mm in diameter. Inability of the pupil to constrict may result in photophobia, and accommodation may be affected. These reactions and the increased IOP can lead to frontal headache, nausea, and vomiting. As inflammation progresses, limbal injection of the conjunctiva is almost universally seen. Figure 19.4 demonstrates many of these findings. Patients presenting with IOPs exceeding 20 mm Hg should have ophthalmological consultation. Rapid treatment is usually not necessary unless the pressure exceeds 30 mm Hg.

Reflection from cornea

Space in which to look for particulate matter, “flare”

Reflection from lens

Fig. 19.5.  Technique of slit-lamp examination with a short, narrow light beam projected from an extreme temporal angle across the contrasting black pupil to better find cells or “flare” indicative of acute anterior uveitis. (From Ragge NK, Easty DL: Immediate eye care, St Louis, 1990, Mosby-Year Book.)

Slit-Lamp Examination The slit lamp is used to examine anterior eye structures. It permits a magnified, binocular view of the conjunctivae and anterior globe for diagnostic purposes and to facilitate delicate procedures. It allows depth perception in otherwise clear structures, such as the cornea, aqueous humor, and lens. Figure 19.5 shows the typical appearance of an angled slit beam reflecting from and passing through the cornea. Components of the slit-lamp examination are found in Box 19.4. Fluorescein examination with cobalt blue light from the slit lamp identifies corneal defects. Fluorescein is not taken up by intact corneal epithelium but concentrates in areas where corneal epithelium is breached by abrasion, foreign body, or ulcer (Fig. 19.6). If the patient cannot sit in front of a slit lamp, a Wood’s lamp may be used for magnification and an alternative light source instead. When corneal perforation is suggested, Seidel’s test can be used as described in Chapter 61 (see https://www.youtube .com/watch?v=GlFcAv0DR4c).

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Neovascularization Corneal abrasion Fig. 19.6.  Corneal abrasion demonstrating fluorescein pooling of a small inferior epithelial defect. (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

Corneal ulcer

Fig. 19.7.  Bacterial keratitis demonstrating a large, central Streptococcus pneumoniae corneal ulcer. Note the dense, white corneal infiltrate and the extreme conjunctival injection. (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

BOX 19.4 

BOX 19.5 

Slit-Lamp Examination

Causes of Inability to Visualize a Red Reflex or the Otic Fundus

1. Lids and lashes inspected for blepharitis, lid abscess (ie, hordeolum) and internal or external pointing, and dacryocystitis. 2. Conjunctiva and sclera inspected for punctures, lacerations, and inflammatory patterns. 3. Cornea (with fluorescein in some cases) evaluated for abrasions, ulcers, edema, foreign bodies, or other abnormalities. 4. Anterior chamber evaluated for the presence of cells (eg, red and white blood cells) and “flare” (diffuse haziness related to cells and proteins suspended in aqueous humor) representing deep inflammation. Hyphema from surgery or trauma, hypopyon, or foreign bodies may also be noted. 5. Iris inspected for tears or spiraling muscle fibers noted in acute angle-closure glaucoma. 6. Lens examined for position, general clarity, opacities, and foreign bodies.

Ulcers can be large and easy to visualize (Fig. 19.7) or small and difficult to detect. They are best identified under slit-lamp examination by noting a denuding of epithelium with surrounding edema. Edema, in the form of increased interstitial water, is seen as whitish clouding of the normally clear tissue in the base of and adjacent to the lesion. This is best identified without fluorescein staining.

Direct Funduscopic Examination Funduscopy is used to examine posterior eye structures. Emergency physicians most commonly perform a nondilated funduscopic examination, because there are several eye conditions in which dilation may be harmful (eg, angle-closure glaucoma). Iridodialysis, lens dislocation, and conditions requiring early intervention are usually identifiable along the visual axis. Inability to obtain a red reflex or visualize the fundus of the eye can be due to the causes listed in Box 19.5. In the absence of trauma, few posterior findings are associated with chief complaints of external redness. Findings associated

1. Opacification of the cornea, most commonly by edema secondary to injury or infection 2. Hyphema or hypopyon within the anterior chamber 3. Extremely miotic pupil 4. Cataract of the lens 5. Blood in the vitreous or posterior eye wall 6. Retinal detachment

with visual loss include pallor of the retina indicating ischemia, “cupping” of the optic disk indicating glaucoma, indistinctness of disk margins indicating papilledema or optic neuritis or neuropathy, air or plaque emboli in retinal arteries, and a host of other signs indicating more chronic ocular or systemic pathology not normally amenable to management in the ED.

Topical Anesthetics Relief of discomfort after instillation of a topical anesthetic can be used as a diagnostic test for a superficial source of pain. In general, abolition of pain by local anesthetic drops indicates pain of corneal origin. Modest but incomplete relief suggests a conjunctival process. Intraocular pain, including pain associated with uveitis, is not diminished by local anesthetic solution.

Imaging A penetrating wound that violates the sclera may be immediately obvious. In other cases, the penetration may have occurred elsewhere in the head or neck then reach the orbit posterior to the orbital septum to injure the globe. In these cases, computed tomography (CT) or plain radiography is used to determine the presence of an intraocular or intraorbital foreign body. Ultrasonography can be used in the ED when patient condition may preclude movement to the radiology suite, and it can be

CHAPTER 19  Red and Painful Eye

highly accurate in identifying ocular foreign bodies. In experienced hands, ultrasonography is an excellent bedside modality for evaluating pathology of the globe. Ultrasonography can be used to evaluate abnormalities of the anterior chamber, iris, ciliary body, lens, vitreous, retina, choroid, posterior wall, and optic nerve. Although plain radiography may directly identify facial fractures, or indirectly suggest fractures by detecting an air-fluid level in the orbit or fluid in the paranasal sinuses, CT is now considered the preferred modality for evaluating orbital trauma. Magnetic resonance imaging (MRI) clearly delineates orbital and retroorbital structures but is less rapidly obtained with no advantages over CT in trauma, is contraindicated in cases of suspected metallic foreign body, and is reserved for ocular issues felt to be of neurological origin.4,5 All imagining modalities should be considered complementary to each other when employed in appropriate settings.

Laboratory Testing Laboratory tests, such as a complete blood count, are generally not necessary in the evaluation of the red and painful eye. One notable exception is the evaluation of temporal arteritis. Temporal arteritis may present with eye pain and decreased visual acuity, but there may be no injection or other physical alteration of the eye. An erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are generally elevated in the acute phase, although one or both may be normal in up to 5% of biopsy-proven cases of temporal arteritis.6 We do recommend obtaining CRP and ESR in cases of suspected temporal arteritis. Microbiologic cultures are rarely ordered in the ED, but an ophthalmologist may request them in select circumstances.

DIAGNOSTIC ALGORITHM A recommended algorithmic approach to the patient with an acutely red or painful eye is provided in Fig. 19.8.

Critical Diagnoses Critical diagnoses require immediate intervention in the ED. Ophthalmological consultation is mandatory but should not delay potentially sight-saving procedures. Critical ophthalmologic diagnoses that do not present with redness or pain are discussed in Chapter 61. Because of its prognostic value, a quick visual acuity should be obtained while the patient is being triaged and subsequently managed. Caustic injury to the eye can rapidly lead to a destructive keratoconjunctivitis if the agent is not removed immediately (Fig. 19.9). Intervention is initiated on history alone, before any other examination is performed. Early and copious irrigation is indicated. Many patients have already undergone extensive irrigation at the job site, but when the exposure has occurred in the home, irrigation prior to arrival in the ED is uncommon. Alkaline caustic agents cause a liquefactive necrosis of the cornea by progressively reacting with the corneal layers, and destruction is severe and relentless. Acid injury causes coagulation necrosis, which tends to limit the depth of injury. Both types require copious irrigation with any clean, relatively neutral fluid (eg, tap water, normal saline, and so on). Continuous irrigation until the pH of the tears is neutral is the only effective method to terminate these chemical reactions. A normal pH and post-irrigation examination (except expected conjunctival injection) does not mandate that an ophthalmologist respond to the ED. Any other post-treatment abnormalities do necessitate the presence of an ophthalmologist. Orbital compartment syndrome can occur whenever intraorbital pressure increases to the point of causing dysfunction of the

optic nerve. IOP can be used as a surrogate measure of intraorbital pressure when this can be safely measured. Retrobulbar hematoma is usually caused by orbital trauma, but it can also occur spontaneously in patients with coagulopathy. Retrobulbar abscess or emphysema can also occur. Elevated IOP in any of these conditions implies an orbital compartment syndrome and constitutes a surgical emergency.7 Intervention in the ED requires decompressing the orbit by performing lateral canthotomy and cantholysis (see https://youtu.be/bUAagMd_Q8A) to relieve the pressure on the optic nerve, and should be performed within 2 hours of injury for the best chance of sight recovery.7 These patients should be examined by an ophthalmologist as soon as possible afterward. Patients with acute angle closure glaucoma (see earlier) require prompt medical intervention to decrease IOP in the ED and urgent ophthalmologic consultation (see Chapter 61). Follow-up can be decided based on the patient’s response to therapy and discussion with the ophthalmologist.

Emergent Diagnoses Most emergent diagnoses involve some kind of inflammation secondary to trauma, infection, or systemic disease. These include keratitis, anterior uveitis, scleritis, and endophthalmitis. Any of these may be complications of surgical procedures, and an appropriate ophthalmological history must be obtained. Consultation with an ophthalmologist is appropriate for all emergent diagnoses. If penetrating ocular trauma is confirmed, or if the possibility persists after evaluation, an ophthalmological consultation is indicated. Keratitis is treated with topical anesthesia, which provides immediate (but temporary) relief of pain, thus reinforcing the corneal origin of the process and facilitating examination and definitive diagnosis. Following thorough irrigation, thermal and chemical burns must receive a careful slit-lamp examination for potential fullthickness injury. If this is not found, superficial corneal burns may be treated similarly to abrasions. If full-thickness injury is identified, immediate ophthalmological consultation is indicated. Corneal ulcerations caused by overuse of contact lenses are treated with prophylactic antibiotics and avoidance of the lenses for at least 72 hours. We recommend follow-up with an ophthalmologist or optometrist before contact lens use is resumed. Infections of the cornea with herpes simplex virus can rapidly lead to opacification and significant visual loss. It is most commonly recognized by a characteristic dendritic pattern of fluorescein pooling under blue light (Fig. 19.10). Anterior uveitis, which includes iritis and iridocyclitis, often occurs secondary to a traumatic injury or infectious process or can be associated with serious systemic immune diseases, such as adult and juvenile rheumatoid arthritis, sarcoidosis, and ankylosing spondylitis. We recommend urgent ophthalmologic evaluation, either in the ED or by immediate evaluation in an ophthalmological clinic, for these conditions. Scleritis is commonly idiopathic, but may be associated with a systemic inflammatory process, such as a connective tissue disease, gout, or infection (eg, Lyme disease, syphilis, tuberculosis). Episcleritis is a somewhat more common, superficial, and more benign inflammation. Both are discussed in Chapter 61. Endophthalmitis usually results from an infection of structures inside the globe. It is most common following penetrating trauma but may begin after hematogenous seeding from a remote or systemic infection, particularly in immunocompromised hosts. Unless it is detected early and is responsive to antimicrobial therapy, endophthalmitis is a devastating process that frequently requires enucleation.

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Any eye complaint

Potential Diagnoses (Numbers refer to Table 19.1 for management.)

Any contaminating foreign material?

Yes

Acid, alkali, or corrosive?

Yes

Critical 1. Caustic keratoconjunctivitis

No

No Any recent blunt or Yes penetrating trauma? Critical triage questions

176

Critical 2. Orbital compartment syndrome

Exophthalmos or Yes hemorrhage?

Emergent 3. Scleral penetration

No

No

Urgent 4. Hyphema Non-urgent 5. Subconjunctival hemorrhage

Sudden loss of all or part of vision?

Yes

Emergent 6. Corneal perforation 7. Ruptured globe

See Chapter 61

Urgent 8. Corneal abrasion with or without FB

No Double vision?

Yes

Non-urgent 9. Traumatic mydriasis

See Chapter 18

No

Swelling or erythema of any external structures?

Yes

No

More than isolated lid involvement? No

Yes

Critical 2. Orbital compartment syndrome Emergent 10. Inflammatory pseudotumor 11. Orbital cellulitis Urgent 12. Periorbital cellulitis or erysipelas 13. Dacryocystitis and dacryadenitis 14. Orbital tumor Urgent 15. Hordeolum (stye) Non-urgent 16. Blepharitis 17. Chalazion

Severe pain, FB sensation, Yes or limbal injection?

Critical 18. Acute angle-closure glaucoma Emergent 4. Hyphema 19. Keratitis 20. Scleritis 21. Anterior uveitis and hypopyon 22. Endophthalmitis

No

Urgent 23. Keratoconjunctivitis 24. Episcleritis Focal injection or redness of bulbar conjunctiva?

Yes

Emergent 3. Scleral penetration Urgent 25. Inflamed pinguecula 26. Inflamed pterygium

No

Non-urgent 5. Subconjunctival hemorrhage Injection of bulbar but not limbal conjunctiva?

Yes

Urgent 27. Bacterial conjunctivitis 28. Chlamydia conjunctivitis 29. Contact dermatoconjunctivitis 30. Toxic conjunctivitis

No

Non-urgent 31. Allergic conjunctivitis 32. Viral conjunctivitis Still undiagnosed eye complaint?

Yes

See Chapter 61

Fig. 19.8.  Diagnostic algorithm for red and painful eyes. Numbers next to diagnoses correspond to Table 19.1 for management of each condition. FB, Foreign body.

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A

B Corneal alkali burn

Corneal alkali burn

Fig. 19.9.  A, Alkali burn demonstrating corneal burns and conjunctival injection on the day of the accident. B, Complete corneal tissue destruction 7 days after alkali burn. (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

Urgent Diagnoses Foreign bodies on the cornea or under the lid are removed, as described in Chapter 61. Superficial corneal abrasions, once universally patched, are now known to heal spontaneously without need for patching, prophylactic antibiotics, or prophylactic tetanus immunization. Patients with hyphema are placed with head of bed elevated to 30 degrees, and they receive systemic analgesia and, if required, antiemetics, with emergent ophthalmologic consultation (see Chapter 61). Medications affecting platelet function should be avoided. If the iris is not injured, a long-acting cycloplegic agent (eg, topical homatropine) may be recommended to prevent repetitive motion of the iris. After consultation by ophthalmology, outpatient therapy and follow-up often are sufficient for management with simple (eg, acetaminophen) analgesia for pain. We recommend a rigid shield to protect the eye during sleep, but this should not be worn during the day. Patching is not otherwise needed. The patient should see the ophthalmologist or return to the ED if the patient experiences an increase in pain or decrease in visual acuity.

Herpes simplex virus dendrite

EMPIRICAL MANAGEMENT

Fig. 19.10.  Fluorescein pooling in the dendritic-shaped lesions of herpes simplex keratitis. (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

Management of the specific entities listed in the diagnostic algorithm presented in Figure 19.8 is presented in Table 19.1. Specific management of ophthalmologic conditions is also discussed in Chapter 61. Critical and emergent conditions are treated as described earlier. All other ocular emergencies are generally diagnosable in the ED, and treatment is initiated based on the diagnosis made. Caustic exposures receive copious irrigation, but all chemical or liquid exposures should undergo irrigation unless 1 hour has passed since exposure and the patient is completely asymptomatic at the time of evaluation. Foreign bodies are removed, along with all fine particulate matter. Irrigation is advisable after foreign body removal if there is suspicion of remaining, very fine, foreign substance. After irrigation, conjunctival injection is common, but symptoms are expected to be mild. Patching is not indicated. Patients with significant symptoms after foreign body removal or with corneal abrasion may benefit from a topical nonsteroidal antiinflammatory analgesic solution or dilute topical local anesthetic drops for 24 hours.8,9 An algorithm for the treatment of acute conjunctivitis is presented in Figure 19.11. We do not recommend topical antimicrobial or corticosteroid treatment for conjunctivitis or keratoconjunctivitis (see Chapter 61). This is an area in which antibiotic

misuse is widespread. There is no good medical evidence to support the requirements of most daycare and school facilities to mandate antibiotic treatment for acute conjunctivitis before returning to activities with other children. First, some causes of “pink eye” are not infectious. Second, in patients enrolled in clinical trials for acute infectious conjunctivitis, bacteria continue to be cultured many days after treatment is started, and viruses continue to be shed for 2 weeks or more with or without antibiotics. Unless a patient with conjunctivitis might potentially expose an immunocompromised individual, there is no medical reason not to return to daycare or school with or without treatment. If bacterial, only direct eye-to-hand-to-eye exposure will result in transmission. If viral, others have likely already been exposed. Finally, regardless of etiology, complications in healthy children are extraordinarily rare.10 Topical acyclovir, 3% ointment, is indicated for herpes keratitis, in conjunction with ophthalmologic or infectious disease consultation. Azithromycin is indicated for trachoma, again with consultation. Topical antimicrobial prophylaxis is similarly not indicated for superficial epithelial defects of the cornea, although this also is Text continued on p. 182

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TABLE 19.1 

Management Algorithm for Red Eyes Extended from Diagnostic Algorithm in Figure 19.8* POTENTIAL DIAGNOSIS

MANAGEMENT

CONSULTATION

DISPOSITION

1. Caustic keratoconjunctivitis

Immediate and copious irrigation with tap water or sterile normal saline until tear-film pH = 7. Solids: Lift particles out with dry swab before irrigation Acids: Minimum of 2 L and 20 minutes Alkalis: Minimum of 4 L and 40 minutes

Ophthalmologist must come to ED if there is any abnormal visual acuity or objective finding on examination after sufficient irrigation, with exception of expected injection of conjunctiva secondary to treatment.

May discharge only if tear film pH = 7 and no findings on examination except conjunctival injection, then ophthalmologist can reevaluate next day.

2. Orbital compartment syndrome: Exophthalmos (proptosis), decreased visual acuity, painful or limited ocular mobility, and increased IOP

Measure IOP unless possibility of ruptured globe. IOP >30 mm Hg may require emergent needle aspiration or lateral canthotomy and cantholysis in ED.

IOP >20 mm Hg may be surgical emergency, may add medications used in glaucoma #18 to decrease IOP before decompression in ED. Obtain axial CT of brain and axial and coronal CT of orbits and sinuses.

Admit all cases of retrobulbar pathology causing increased IOP. Others might be candidates for discharge depending on cause of problem.

Hematoma: Correct any Retrobulbar hematoma: Occurs due coagulopathy or thrombocytopenia. to trauma, coagulopathy, or thrombocytopenia and associated with possible dissection of blood to potential space under bulbar conjunctiva Retrobulbar emphysema: Occurs with Emphysema: Antibiotic prophylaxis to cover sinus flora. forceful sneeze or occasionally happens spontaneously and associated with possible dissection of air to potential space under bulbar conjunctiva Retrobulbar abscess: Occurs with contiguous or occasionally hematogenously disseminated infection and associated with possible dissection of pus to potential space under bulbar conjunctiva

Abscess: Antibiotics as in orbital cellulitis (see #11).

3. Scleral penetration: Localized redness at site of entry plus possible teardrop pupil, blood in anterior chamber or loss of red reflex

Protect eye from further pressure, provide pain relief, and prevent vomiting. Parenteral antibiotic and tetanus prophylaxis.

Ophthalmologist must come to ED if there is any concern for globe penetration.

Admit for continuation of antibiotics and possible procedural intervention.

4. Hyphema: Pain, decreased visual acuity, gross or microscopic blood in anterior chamber, may be associated with dilated and fixed pupil following blunt trauma Graded by amount of blood: • Percentage of vertical diameter of anterior chamber when blood layers with patient in upright position • Microhyphema shows no layering and only suspended red blood cells

First rule out open globe. May require ultrasound if cannot visualize posterior structures. Measure IOP unless possibility of ruptured globe. IOP >30 mm Hg may require acute treatment as in glaucoma (see #18). If IOP >20 mm Hg and no iridodialysis, may use cycloplegic to prevent iris motion.

Discuss findings and use of ε-aminocaproic acid and steroids, other medical therapy, best disposition, and follow-up examination by ophthalmologist within 2 days. Some patients may be admitted for observation, bed rest, head elevation, and frequent medication administration.

Most patients can be discharged with careful instructions to return for any increased pain or change in vision. Patients should decrease physical activity and sleep with an eye shield in place. Eyes should be left open while awake so that any change in vision can be immediately recognized. PO NSAIDs or narcotics should be given for analgesia.

5. Subconjunctival hemorrhage: Red blood beneath clear conjunctival membrane

Exclude coagulopathy or thrombocytopenia if indicated by history.

None required if no concerns for Reassure patient that underlying ocular pathology and discoloration should resolve over no acute complications. 2 to 3 weeks.

6. Corneal perforation: Direct visualization of full-thickness injury or positive Seidel’s test

Protect eye from further pressure, provide pain relief, and prevent vomiting. Parenteral antibiotic and tetanus prophylaxis.

Ophthalmologist must come to ED to evaluate.

Admit for continuation of antibiotics and procedural intervention.

CHAPTER 19  Red and Painful Eye

TABLE 19.1 

Management Algorithm for Red Eyes Extended from Diagnostic Algorithm in Figure 19.8*—cont’d POTENTIAL DIAGNOSIS

MANAGEMENT

CONSULTATION

DISPOSITION

7. Ruptured globe: Misshaped cornea or globe following trauma

Protect eye from further pressure, provide pain relief, and prevent vomiting. Parenteral antibiotic and tetanus prophylaxis.

Ophthalmologist must come to ED to evaluate.

Admit for continuation of antibiotics and procedural intervention.

8. Corneal abrasion: History of direct trauma or foreign body plus direct visualization of defect in the corneal epithelium using white light, or fluorescein and blue light; any surrounding corneal edema indicates a concomitant keratitis (see #19)

Antibiotic prophylaxis with polymyxin-B/trimethoprim solution 1 drop every 3 hours while awake and erythromycin ointment while sleeping.

Discuss plan for follow-up in 1 to 3 days.

May discharge if no other findings. No patch.

9. Traumatic mydriasis: Nonreactive dilated pupil without any other identifiable eye abnormalities following blunt trauma

None once other abnormalities of the eye, cranial nerves, and brain have been reasonably excluded.

Discuss plan for follow-up evaluation of slowly developing hyphema and ensure resolution.

May discharge if no other findings.

10. Inflammatory pseudotumor: Nonspecific idiopathic retrobulbar inflammation with eyelid swelling, palpebral injection of conjunctiva, chemosis, proptosis, blurred vision, painful or limited ocular mobility, binocular diplopia, edema of optic disk, or venous engorgement of retina

Measure IOP. Evaluate for infection, diabetes mellitus, and vasculitis with CBC, BMP, UA, and CRP or ESR. Obtain axial CT of brain and axial and coronal CT of orbits and sinuses.

IOP >20 mm Hg may be surgical emergency, may add medications used in glaucoma #18 to decrease IOP before decompression in ED.

May discharge if no systemic problems, no findings of particular concern on CT, and IOP ≤20 mm Hg. Start high-dose PO steroids after discussion with ophthalmologist, and ensure reevaluation in 2 to 3 days.

11. Orbital cellulitis: Eyelid swelling, redness and warmth of skin overlying orbit, tenderness of skin overlying bone palpebral injection of conjunctiva, and chemosis; differentiated from periorbital cellulitis by presence of any finding of fever, ill appearance, blurred vision, proptosis, painful or limited ocular mobility, binocular diplopia, edema of optic disk, or venous engorgement of retina

Measure IOP and rule out orbital compartment syndrome. Start parenteral antibiotics with second-generation cephalosporin (eg, cefuroxime, cefoxitin, or cefotetan) or with ampicillin/ sulbactam to cover sinus and skin flora. Alternatives are ticarcillin/ clavulanate, piperacillin/tazobactam, vancomycin, or clindamycin + third-generation cephalosporin (eg, cefotaxime or ceftriaxone).

IOP >20 mm Hg may be surgical emergency, may add medications used in glaucoma #18 to decrease IOP before decompression in ED. Obtain blood cultures and start antibiotics. Axial and coronal CT of orbits and sinuses to rule out FB, retrobulbar abscess, orbital gas, subperiosteal abscess, osteomyelitis, and changes in cavernous sinus. Consider LP.

Admit all cases of orbital cellulitis.

12. Periorbital cellulitis or erysipelas: Eyelid swelling, redness and warmth of skin overlying orbit, tenderness of skin overlying bone, palpebral injection of conjunctiva, and chemosis; differentiated from orbital cellulitis by absence of any other finding listed in #11

First rule out orbital cellulitis (see #11). PO antibiotics for sinus and skin flora if not admitting.

Ophthalmologist may admit if systemically ill, case is moderate or severe, or no social support for patient.

May discharge mild cases with PO antibiotics. Ophthalmologist must reevaluate next day to ensure no orbital extension.

13. Dacryocystitis and dacryadenitis: Eye tearing and inflammation of lower eyelid inferior to lacrimal punctum finding redness and tenderness over nasal aspect of lower lid and adjacent periorbital skin

First rule out orbital cellulitis (see #11) and periorbital cellulitis (see #12). Inspect for obstruction of punctum by SLE, may express pus by pressing on sac, PO antibiotics for nasal and skin flora if not admitting.

Ophthalmologist may admit if systemically ill, case is moderate or severe, or no social support for patient. Ask about culturing before prescribing medications if admitting, and then may add medications used in glaucoma #18 to decrease IOP before decompression.

May discharge mild cases with PO analgesics and antibiotics (eg, amoxicillin/clavulanate), and instructions to apply warm compresses to eyelids for 15 minutes and gently massage inner canthal area four times a day.

14. Orbital tumor: Blurred vision, proptosis or other displacement of globe, painful or limited ocular mobility, or binocular diplopia (but can be asymptomatic)

Measure IOP. Evaluate for extraocular signs of malignancy. Obtain axial CT of brain and axial and coronal CT of orbits and sinuses.

Based on findings and IOP >20 mm Hg may be surgical emergency, prescribe to discussion with consultant. decrease IOP in ED. Ophthalmologist may want MRI, MRA, or orbital ultrasonography. Continued

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SECTION Two 

Signs, Symptoms, and Presentations

TABLE 19.1 

Management Algorithm for Red Eyes Extended from Diagnostic Algorithm in Figure 19.8*—cont’d POTENTIAL DIAGNOSIS

MANAGEMENT

CONSULTATION

DISPOSITION

15. Hordeolum (stye): Abscess in eyelash follicle or modified sebaceous gland at lid margin: external or internal based on side of lid margin that abscess is pointing

External: Warm compresses often all that is needed, may prescribe anti-Staphylococcus ointment twice daily. Internal: PO antibiotics for β-lactamase–positive Staphylococcus such as amoxicillin/clavulanate

Outpatient referral only for treatment failure after 2 weeks.

Discharge with instructions to apply warm compresses to eyelids for 15 minutes and gently massage abscess four times a day.

16. Blepharitis: Inflammation of eyelid margins often associated with crusts on awakening, FB sensation, and tearing

None except artificial tears for dry eye.

Outpatient referral only for treatment failure after 2 weeks.

Discharge with instructions to apply warm compresses to eyelids for 15 minutes four times a day and scrub lid margins and lashes with mild shampoo on washcloth twice daily.

17. Chalazion: Inflammation of meibomian gland causing subcutaneous nodule within the eyelid

None.

Outpatient referral only for treatment failure after 2 weeks.

Discharge with instructions to apply warm compresses to eyelids for 15 minutes and gently massage nodule four times a day.

18. Acute angle-closure glaucoma: Sudden-onset eye pain and blurred vision that may be associated with frontal headache, nausea, and vomiting; anterior eye may manifest shallow or closed angle between iris and cornea, pupil fixed at midsize, or limbal injection of conjunctiva

Administer medications below in ED if IOP >30 mm Hg. Decrease production of aqueous humor: • Timolol 0.5% 1 drop • Apraclonidine 1% 1 drop q8hr • Dorzolamide 2% 1 drops or if sickle cell disease or trait, then methazolamide 50 mg PO Decrease inflammation: • Prednisolone 1% 1 drop every 15 minutes four times Constrict pupil: • Pilocarpine 1%–2% 1 drop after IOP 20 mm Hg with ophthalmologist.

Based on findings and discussion with consultant, which primarily depends on speed of onset and response to treatment.

19. Keratitis (abrasion or UV injury): Pain, FB sensation, blepharospasm, tearing, photophobia, epithelial disruption on inspection under white light, or fluorescein pooling under blue light; SPK appears as stippling of corneal surface (often lower two thirds of cornea if due to light exposure); if neglected for a time, may have surrounding edema appearing as white “cloudiness” in clear tissue

First rule out corneal penetration either grossly or employing Seidel’s test. Relieve pain and blepharospasm with topical anesthetic. Inspect all conjunctival recesses and superficial cornea for any foreign material that can be removed by irrigation or manually lifted from surface.

Ophthalmologist must come to ED if there is any concern for globe penetration. Otherwise consult for follow-up examination in 1 to 2 days.

May discharge cases not infected or ulcerated. May provide topical antibiotic prophylaxis using polymyxin B combinations with bacitracin (ointment) or trimethoprim (solution). Erythromycin, gentamicin, and sulfacetamide are less desirable single-agent alternatives. PO NSAIDs or narcotics for analgesia. No patch.

CHAPTER 19  Red and Painful Eye

TABLE 19.1 

Management Algorithm for Red Eyes Extended from Diagnostic Algorithm in Figure 19.8*—cont’d POTENTIAL DIAGNOSIS

MANAGEMENT

CONSULTATION

DISPOSITION

Keratitis (ulceration): Symptoms and signs as described above; ulceration from complications of contact wear has “scooped out” epithelium with surrounding edema appearing as white “cloudiness” in clear tissue

Relieve pain and blepharospasm Discuss with ophthalmologist with topical anesthetic. any potential need to débride or culture before starting antibiotic. Staphylococcus and Streptococcus species still most common organisms, but Pseudomonas greater percentage in existing infections (especially contact lens wearer), so prescription with topical fluoroquinolone is preferred.

Keratitis (herpetic infection): Symptoms and signs as described above Look for other signs of herpes, varicella, zoster (or CMV infection in immunocompromised patient) Look for “dendritic” defects of cornea with fluorescein under blue light

Relieve pain and blepharospasm with topical anesthetic. Prescribe acyclovir 3% ointment, trifluridine 1% solution, or vidarabine ointment. Varicella-zoster and CMV not normally given antivirals if immunocompetent.

Discuss with ophthalmologist Based on findings and any potential need to débride or discussion with consultant. culture before starting antiviral. Typical vidarabine or acyclovir dosing is five times a day for 7 days, then taper over 2 more weeks. Typical trifluridine dosing is 1 drop every 2 hours for 7 days, then taper over 2 more weeks. PO NSAIDs or narcotics for analgesia. No patch.

20. Scleritis: Progressively increasing eye pain with radiation to ipsilateral face and decreasing vision, photophobia, tearing, and possible pain with eye motion

Decrease inflammation with PO NSAIDs.

Discuss findings and use of topical or PO steroids.

May discharge patient with medications recommended by ophthalmologist and ensure reevaluation in 2 to 3 days.

21. Anterior uveitis and hypopyon: Eye pain, photophobia, tearing, limbal injection of conjunctiva, and cells or flare in anterior chamber; hypopyon is layering of white cells (pus) in anterior chamber

First rule out glaucoma with IOP measurement. Prescribe in ED if IOP >20 mm Hg. Otherwise okay to dilate pupil with 2 drops of cyclopentolate 1%.

Discuss findings and use of prednisolone acetate 1% (frequency determined by ophthalmologist but range is every 1 to 6 hours).

May discharge patient with medications recommended by ophthalmologist and ensure reevaluation in 2 to 3 days. Patients with hypopyon are generally admitted.

22. Endophthalmitis: Progressively increasing eye pain and decreasing vision, diminished red reflex, cells and flare (and possibly hypopyon) in anterior chamber, chemosis, and eyelid swelling

Empirical parenteral antibiotic administration with vancomycin and ceftazidime to cover Bacillus, enterococcus, and Staphylococcus spp. Ciprofloxacin or levofloxacin are used when others contraindicated.

Ophthalmologist must admit for parenteral and possibly intravitreal antibiotics.

Admit all cases of endophthalmitis.

23. Keratoconjunctivitis: Conjunctivitis with subepithelial infiltrates in cornea causing pain and decreased vision, possibly with halos reported

Treat for conjunctivitis by likely Discuss findings and use of etiologic category (see #25 to #30). prednisolone acetate 1% (frequency determined by ophthalmologist).

May discharge patient with medications recommended by ophthalmologist and ensure reevaluation in 2 to 3 days.

24. Episcleritis: Rapid onset of localized pain, injection of episcleral vessels, and localized tenderness

Relieve irritation with artificial tears and decrease inflammation with ketorolac drops.

Outpatient referral only for treatment failure after 2 weeks.

May discharge patient with PO NSAIDs alone or in combination with topical ketorolac drops.

25. Inflamed pinguecula: Inflammation of soft yellow patches in temporal and nasal edges of limbal margin 26. Inflamed pterygium: Inflammation of firmer white nodules extending from limbal conjunctiva onto cornea

Decrease inflammation with naphazoline or ketorolac drops.

Outpatient referral only for treatment failure after 2 weeks.

Discharge to follow-up with ophthalmologist for possible steroid therapy or surgical removal.

Based on findings and discussion with consultant. Typical ciprofloxacin dosing is 2 drops q15min for 6 hours, then 2 drops q30min day and night for remainder of day 1 until seen by consultant the next day. Typical moxifloxacin dosing is 1 drop q15min for 1 hr, then 1 drop q1hr day and night until seen by consultant the next day. For large ulcerations or ulcers near the visual axis, a fortified antibiotic, such as tobramycin, may be added.

Continued

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Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

TABLE 19.1 

Management Algorithm for Red Eyes Extended from Diagnostic Algorithm in Figure 19.8*—cont’d POTENTIAL DIAGNOSIS

MANAGEMENT

CONSULTATION

DISPOSITION

27. Bacterial conjunctivitis: Hyperpurulent discharge not typical of common “pink eye” and more commonly unilateral in adults; inflammation of eyelid margins associated with lid edema, chemosis, and possibly subconjunctival hemorrhage, but usually little or no follicular “cobblestoning”

Topical polymyxin-B/trimethoprim in infants and children, because more Staphylococcus spp. Topical sulfacetamide or gentamicin clinically effective in 90% of uncomplicated adult cases. Use topical fluoroquinolone if Pseudomonas possible.

Culture drainage and ophthalmology consult in all neonates and those at risk for vision loss or systemic sepsis. Neisseria gonorrhoeae can be rapidly sight-threatening.

Discharge uncomplicated cases with 10 days of topical antibiotics in both eyes, regardless of laterality of apparent infection. Use ointments in infants and drops in others.

28. Chlamydia conjunctivitis: Often bilateral palpebral injection of conjunctiva in neonate or other individual at risk for sexually transmitted disease

Empirical PO azithromycin for Chlamydia. Consider empirical parenteral ceftriaxone for concurrent N. gonorrhoeae.

Culture drainage and consult ophthalmology in all neonates and those at risk for vision loss or systemic sepsis.

Discharge uncomplicated cases on 5 days of PO azithromycin.

29. Contact dermatoconjunctivitis: Localized lid and conjunctival redness and swelling 30. Toxic conjunctivitis: Diffuse conjunctival injection, chemosis, and lid edema

Irrigation with tap water or sterile normal saline. Decrease irritation with naphazoline drops.

Outpatient referral only for Identify offending agent and severe cases or treatment failure avoid subsequent exposure. after 2 weeks. Discharge uncomplicated cases on continued naphazoline.

31. Allergic conjunctivitis: Often bilateral palpebral injection of conjunctiva and chemosis that may be seasonal and associated with other allergic symptoms, such as rhinitis

Decrease irritation with naphazoline Outpatient referral only for drops. treatment failure after 2 weeks.

Identify antigen if possible. Consider treating other allergic symptoms with PO antihistamines.

32. Viral conjunctivitis: Often bilateral palpebral injection of conjunctiva and follicular cobblestoning of inner surface of lower lid; inflammation of eyelid margins often associated with crusts on awakening, FB sensation, and tearing

Decrease irritation with artificial tears, naphazoline, or ketorolac drops.

Ask about pregnant mothers, infants, and immunocompromised individuals in close contact. Discharge uncomplicated cases with instructions on respiratory and direct-contact contagion for 2 weeks.

Culture drainage, and consult ophthalmology in all neonates and those at risk for vision loss or systemic sepsis.

BMP, Basic metabolic profile (includes electrolytes, glucose, and renal function tests); CBC, complete blood count; CMV, cytomegalovirus; CRP, C-reactive protein; CT, computed tomography; ED, emergency department; ESR, erythrocyte sedimentation rate; FB, foreign body; IOP, intraocular pressure; IV, intravenous; LP, lumbar puncture; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; NSAID, nonsteroidal antiinflammatory drug; PO, per os (by mouth); SLE, slit-lamp examination; SPK, superficial punctuate keratitis; spp., species; UA; urinalysis; UV, ultraviolet. *Antibiotic choices should be based on current practice.

common practice despite an absence of supporting evidence. There is also no evidence supporting the practice of administering tetanus immunization to patients with superficial corneal abrasions, other than as a general public health measure. On the other hand, true open wounds of the adnexa or globe do require tetanus prophylaxis if the patient’s immunization status is not up to date. Mydriatic and cycloplegic agents are also commonly prescribed but rarely are indicated. Their use is discussed in Chapter 61. Mydriatic agents are contraindicated in patients with narrowangle glaucoma. Larger corneal lesions sometimes require a cycloplegic agent for pain relief, but this should be prescribed only for

the few patients experiencing refractory iris spasm and not prophylactically.11 Treatment of bacterial keratitis and endophthalmitis is described in Chapter 61. Most ED patients with eye complaints are candidates for discharge and, if indicated, follow-up in the ED or with an ophthalmologist in 1 to 2 days. Others may require referral only if there is lack of resolution or treatment fails. A few patients require admission for procedural intervention, parenteral antibiotic regimens, management of intractable pain, or further diagnostic evaluation. General consultation and disposition considerations for the most important entities are outlined in Table 19.1.

CHAPTER 19  Red and Painful Eye Conjunctival injection

Newborn or infant 5–7 days) in children may also be associated with Kawasaki disease.3 Patients with airway compromise often sit upright or lean forward, with the neck extended and jaw thrust forward, and appear restless and distressed. Drooling may indicate an inability to swallow oral secretions and thus inflammation or pathology in the oropharynx or hypopharynx may be present. Drooling is a sign of an advanced airway process, requiring prompt preparation for detailed evaluation and intervention. The presence of a muffled voice should prompt consideration of a supraglottic threat to airway patency. The floor of the mouth should be visualized and, when indicated, the submental region palpated as a brawny induration or tenderness in this area is classically associated with Ludwig’s angina (Table 20.1). Stridor, a high-pitched noise heard on inspiration, suggests a process involving the glottic or infraglottic structures. Stridor indicates partial obstruction, a true airway emergency except when occurring in young children (45 yr. GABHS, group A beta-hemolytic streptococci; LAD, lymphadenopathy. a

point for age >45 years). Using the criteria, the prevalence of GAS is about 50% in patients with scores of 4 or higher, one third with a score of 3, less than 20% with a score of 2, 10% with a score of 1, and near zero with a score of 0 or −1. In contrast, visualization of ulcerations, or presence of rhinorrhea, sneezing, or conjunctivitis point more to a viral cause of the pharyngitis. Unilateral swelling and contralateral uvular deviation, typically without exudates, suggest peritonsillar abscess. Involvement of the entire oropharynx indicates pharyngitis. If, however, the patient has significant symptoms and no oropharyngeal pathology on examination, evaluation for disease in the hypopharynx, especially epiglottitis, by direct or indirect visualization is indicated. Other potential sinister causes for when a patient presents with significant symptoms and a relatively normal oropharyngeal examination include retropharyngeal abscess and parapharyngeal abscess.

Ancillary Testing In the context of acute pharyngitis, diagnostic testing with the rapid antigen detection test (RADT) or culture is helpful to distinguish between GAS and non-GAS pharyngitis (particularly viral causes) for the purpose of selecting patients who may benefit from antimicrobial therapy. If the patient has a clear-cut viral cause for the pharyngitis, with oral ulcers, cough, rhinorrhea, and hoarseness, then no testing (or treatment) for GAS is indicated. Additionally, because of the rarity of GAS and rheumatic fever in children younger than 3 years, testing is also generally not indicated in this age group. Unfortunately, even with the use of the Centor criteria, clinical features alone often do not allow the emergency clinician to discriminate GAS from viral pharyngitis reliably, and the overprescribing of inappropriate antimicrobial therapy for viral pharyngitis contributes to the undesirable adverse effects of (unnecessary) antibiotics and to antimicrobial resistance. The primary reasons for treating patients with cultureproven GAS in the setting of acute pharyngitis are to decrease the risk of suppurative (eg, peritonsillar abscess, cervical lymphadenitis, mastoiditis, possibly internal jugular septic thrombophlebitis) and nonsuppurative (acute rheumatic fever) complications of GAS.5 Additionally, antimicrobial treatment may decrease the duration and severity of illness and reduce the risk of transmission to close contacts. Although many western industrialized nations, where rheumatic fever tends to be exceedingly rare, have abandoned this approach because the inaccuracy and risks of testing and treatment seem to outweigh benefits, the Centers for Disease Control and Prevention (CDC) and Infectious Disease Society of America (IDSA) guidelines of 2012 recommend a combination of clinical assessment and bacteriologic testing, with the goal of treating with antibiotics for proven or strongly suspected GAS.6 Because the sensitivity of the RADT is only approximately 70% to 90%, the IDSA recommends that for children and adolescents, a negative RADT should be followed up with a throat

culture. In contrast, a positive RADT does not warrant follow-up throat culture testing because of its high specificity (95%). The IDSA does not recommend that a negative RADT be followed up with a throat culture in adults, in whom the incidence of GAS and risk of subsequent rheumatic fever is extremely low, when compared to children and adolescents. Heterophile antibody testing for mononucleosis, testing for acute retroviral syndrome, and other possibilities may also be considered in patients with an extended clinical course, unusual features, or treatment failure, largely to exclude other causes and to ensure appropriate advice regarding issues such as contagion and activity limitations (see Chapters 62 and 122).7,8

Imaging Although radiographic imaging has long been recommended for evaluation of the epiglottis and structures in the hypopharynx, direct visualization of the structures of interest by examination is preferable, providing definitive diagnosis, assessment of airway threats, and the ability to plan for or perform endotracheal intubation. In adults with possible epiglottitis, particularly those with severe symptoms such as drooling, distress, or muffled voice, examination via nasopharyngoscopy at the bedside or via laryngoscopy in the operating room setting is the best approach. Examination of this sort, however, should occur under a so-called double setup, with availability of and preparation for an emergent rescue airway, usually cricothyrotomy, because manipulation of the irritated upper airway tissues may precipitate laryngospasm and obstruction. Endoscopic examination also allows identification of other life-threatening causes beyond infection such as foreign bodies, polyps, and angioedema. If there is concern for epiglottitis but upper airway examination by endoscopy is not possible (eg, equipment unavailable) and the patient has a stable airway, plain film radiography may be useful to assess for changes such as the thumb sign—widening of the epiglottis silhouette (Fig. 20.2).9 The approach to pediatric airway infection, including epiglottitis, is described in Chapters 167 and 168. Ultrasound is another technology with applications for the detection of neck masses from tumors and hypopharyngeal conditions, including epiglottitis. In a convenience sample of adults, the epiglottis was easily visualized and measured in males and females,10 and recent case reports, as well as a small, controlled ED study of ultrasound for epiglottitis, have suggested that this noninvasive bedside tool may prove useful.10,11 In a child or adult with signs and symptoms of a deep neck infection such as retropharyngeal abscess and whose airway security has been ensured, the most useful imaging modality is computed tomography (CT) of the neck. The lateral neck x-ray examination is a relatively sensitive test for this disease, so in lower risk patients a normal film (no widening of the prevertebral space, normal lordotic curve of the spine, and absence of soft tissue air)

CHAPTER 20  Sore Throat

BOX 20.1 

Critical and Emergent Diagnoses in Patients Presenting With Sore Throat CRITICAL DIAGNOSES

Epiglottitis causing airway compromise Retropharyngeal or parapharyngeal abscess causing airway compromise Peritonsillar abscess causing airway compromise Ludwig’s angina Angioedema Croup causing stridor at rest Lemierre’s syndrome from septic internal jugular septic thrombophlebitis Acute coronary syndrome presenting with referred throat pain

EMERGENT DIAGNOSES Fig. 20.2.  Soft tissue lateral neck x-ray demonstrating thumb sign or widening of the epiglottis silhouette (arrow).

Trauma causing a nonexpanding neck hematoma Mass lesion in the neck causing sore throat Epiglottitis, retropharyngeal, parapharyngeal, or peritonsillar abscess not causing airway compromise

URGENT DIAGNOSES

Group A streptococcal pharyngitis

Fig. 20.3.  CT scan of retropharyngeal abscess.

can be a useful risk stratification tool.12 Ultimately, however, CT is the definitive evaluation for deep neck infection (Fig 20.3). It is highly accurate at detecting infection in the deep tissues, but its ability to differentiate between cellulitis and abscess is variable.13 Also, CT may help discern tumors or hemorrhage from abscesses and delineate invasion of nearby structures. In children with a sore throat and visible inflammatory neck mass, ultrasound diagnosis can be definitive.

DIAGNOSTIC ALGORITHM Critical and Emergent Diagnoses Box 20.1 outlines critical diagnoses and emergent diagnoses that have the potential to cause airway compromise that may warrant specific intervention. For example, in patients with Ludwig’s angina, securing the airway, promptly initiating antibiotic treatment and fluid resuscitation, and obtaining prompt evaluation by an otolaryngologist may be lifesaving. If there are signs of airway compromise or impending airway compromise in addition to preparing for advanced airway management, the emergency clinician should immediately move to a detailed intraoral physical

examination, ideally while initiating any available consultations such as otolaryngology or surgical services. This examination should concentrate on the detection of masses such as sublingual edema, visible abscess, and foreign bodies. If such a mass can be visualized, disease-specific decisions about imaging, potential airway management, or surgical procedures (eg, abscess drainage) can be made. In patients without signs of airway compromise, the pace of execution can be more deliberate; a primary question is whether or not findings consistent with pharyngitis are visible. If exudates, erythema, or cobblestoning of the posterior pharyngeal wall is evident, pharyngitis is likely present. At this point, consideration of less common causes (eg, gonococcal infection, mononucleosis) should be explored by concentrating on features in the history such as recent exposures and duration, and the possibility of extremely rare entities (eg, Lemierre’s syndrome) may be entertained as well.14 In the absence of unusual features that predispose to these diagnostic possibilities, pharyngitis is likely to be viral or streptococcal in origin and may be empirically managed as such.15

EMPIRICAL MANAGEMENT Fig. 20.4 shows a clinical algorithm for the initial management of the sore throat presentation. Airway compromise and impending airway compromise, when present, must be addressed first. Infectious syndromes suggesting severe systemic illness or sepsis should be treated accordingly. Patients who clinically appear to have no potential for airway compromise and no signs of invasive or systemic disease can be managed according to presumptive causes. Usually, sore throat will be caused by viral pharyngitis, in which case pain management with acetaminophen or nonsteroidal antiinflammatory drugs (NSAIDs) is the mainstay of care and the most important initial step in empirical management. Regimented administration of these agents, rather than the use of as-needed approaches that fail to prevent or interrupt spiraling pain, is often helpful. Two recent systematic reviews have concluded that acute pharyngitis, including GAS pharyngitis, should not routinely be treated with antibiotics.16,17 It is thought that the decline of rheumatic fever may be unrelated to trends in antibiotic

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Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

DIAGNOSTIC ALGORITHM Yes: Stridor Drooling Muffled voice Sniffing position Hypoxia

Sore throat

No

Signs of airway compromise?

Visible mass? (PTA, tongue elevation, angioedema) Yes

Examination consistent with pharyngitis? Yes

No

• Disease-focused therapy • ENT, anesthesiology consultation for airway, surgical support

No

• Symptomatic treatment • Follow-up as needed • Consider antibiotics if high likelihood GABHS in endemic, epidemic settings of rheumatic fever

• ENT consultation for nasopharyngoscopy, surgical support • Consider imaging

Consider nonpharyngitis causes

A MANAGEMENT ALGORITHM Sore throat

Yes

• Prepare for potential surgical management • Maintain upright position • IV, O2, monitor • Consider empirical steroids, antibiotics • Consider surgical, anesthesiology consultation for bedside support Severe hypoxia, imminent decompensation

• Advanced airway management using difficult airway algorithm, tailored to potential obstruction

No

Signs of airway compromise?

Closer examination

Examination consistent with pharyngitis?

Yes

No

• Symptomatic treatment • Antibiotics if severely ill or endemic setting of rheumatic fever

Visible mass? (PTA, tongue elevation, angioedema)

Yes • Disease-focused therapy • ENT, anesthesiology consultation for airway, surgical support as needed

No • Consider nasopharyngoscopy • Consider advanced imaging • Consider empirical epiglottitis treatment prior imaging

B Fig. 20.4.  Clinical approach to the patient with sore throat, diagnosis and management. ENT, Ear-nosethroat; GABHS, Group A beta-hemolytic streptococci; IV, intravenous; PTA, peritonsillar abscess.

use, but rather is a result of factors associated with industrialization, including improved living conditions, access to care, hygiene, and nutrition.18 This explains the current epidemiology of rheumatic fever, a disease that is extremely rare in developed nations but continues to be an important public health threat in developing regions worldwide.19,20 Notably, adverse events caused by antibiotics are common and frequently result in ED visits, and the overuse of antibiotics for self-limiting conditions such as upper respiratory tract infections remains rampant.21 Indeed, the inappropriate prescription of antibiotics for viral pharyngitis in the United States has remained unchanged over time in recent decades, even despite extensive public health messaging to reduce

the problem.22 Thus, for public health reasons and prevention of unnecessary individual harm, antibiotics should be avoided in the management of viral pharyngitis. Education of patients, who will often expect or desire antibiotics, is a key part of management. Education should provide a careful explanation of the following: (1) the self-limited nature of viral pharyngitis; (2) the lack of symptomatic or other benefit with antibiotics; and (3) the potential harm of antibiotics (eg, individual and population resistance, fungal infections in women, rashes, gastrointestinal effects, recurrence of pharyngitis, occasionally dangerous allergic reactions). It is often most important to emphasize that symptom reduction can be achieved with the

CHAPTER 20  Sore Throat

BOX 20.2 

Antibiotic Regimens for Proven Group A Streptococcal Pharyngitis Benzathine penicillin G, intramuscular, 600,000 U for 27 kg Pencillin V oral, 50 mg/kg/day qid × 10 days Amoxicillin, 40 mg/kg/day tid × 10 days If penicillin-allergic: Clindamycin, 7 mg/kg/dose tid (maximum, 300 mg/dose) × 10 days Cephalexin, 20/mg/kg dose bid (maximum, 500 g/dose) × 10 days Azithromycin, 12 mg/kg/day (maximum dose, 500 mg) × 5 days

various interventions that target pain control—for example, NSAIDs.23 However, major organizations such as the IDSA and CDC support targeted testing and antimicrobial therapy for proven GAS pharyngitis and tonsillitis.6 Moreover, because eradicating GAS from the pharynx with appropriate antibiotic administration may reduce the duration and severity of illness, decrease the risk for suppurative and nonsuppurative complications, and reduce infectivity and transmission to close contacts, I recommend treatment with intramuscular benzathine penicillin G or a 10-day course of oral penicillin VK because of proven efficacy and low cost. See Box 20.2 for antibiotic regimens and alternative agents for those who are allergic to penicillin. For severe pharyngitis causing difficulty swallowing, corticosteroid therapy reduces pain and duration of pain, with most studies using 0.6 mg/kg (maximum dose, 10 mg) of dexamethasone, orally or parenterally, in a single dose.24 Opioid pain medication rarely is indicated, and the presence of such severe pain may indicate a more severe

syndrome such as abscess or epiglottitis, requiring additional evaluation. Proper pain management allows patients to reestablish nutritional balance, achieve and maintain a hydrated state, and ingest medications, as necessary. In the setting of clinical pharyngitis, a fluctuant unilateral peritonsillar mass should be drained whenever possible. Drainage in such cases constitutes definitive care.23 Although there are no data to support or refute the administration of antibiotics in cases of unilateral swelling and redness that appears not to be fluctuant (ie, so-called peritonsillar cellulitis), I recommend the same antibiotics that are used for GAS pharyngitis for these patients (see Box 20.2). For patients with manifestations of severe, systemic illness (ie, those requiring hospitalization or with impending airway compromise), antibiotic coverage for streptococcal and anaerobic bacteria may theoretically be helpful. I recommend the administration of parenteral clindamycin (900 mg tid) and a third-generation cephalosporin such as ceftriaxone (50 mg/kg or 1 g bid), although no firm evidence is available to support or refute this practice. Other specific empirical therapies or consultation may be necessary for severe or unusual presentations of disease. Finally, the great majority of patients will be able to manage their condition on an outpatient basis. For those with actively present or potentially impending airway threat, surgical intensive care settings are often appropriate, although this will depend on nursing ratios, local comfort level with airway management, and ability for the patient to be monitored closely in alternate settings. In such cases, as well as in cases of confirmed deep space infection (eg, neck abscess, parapharyngeal abscess, Ludwig’s angina), surgical consultation for potential operative management or for imaging modalities such as nasopharyngoscopy is generally important and helpful. Some patients with pharyngitis may also benefit from inpatient management, usually those with systemic illness who are unable to tolerate oral therapies or nutrition.

KEY CONCEPTS • Sore throat is a chief complaint that can represent life-threatening diagnoses and extreme challenges for the emergency clinician, primarily in the form of airway threats and/or deep space infections. • The five modified Centor criteria award 1 point for each of the following: (1) history of fever; (2) presence of exudates; (3) presence of anterior cervical adenopathy; and (4) absence of cough, and subtract 1 point for (5) age older than 45 years. Patients with scores of −1 to 1 are very unlikely to have GAS infection. Scores of 4 or 5 correspond to a 50% likelihood of GAS, which drops to approximately 30% with a score of 3 and below 20% with a score of 2.

• Physical examination is central to detecting airway threats and determining diagnosis. • The absence of physical findings during oropharyngeal examination in the setting of severe sore throat symptoms suggests that lower structures may be involved, and endoscopic examination of the upper airway is advisable. • Antibiotics are more harmful than helpful for patients with viral pharyngitis, which is self-limiting. • For GAS-proven pharyngitis, a single injection of penicillin or 10-day course of oral penicillin is recommended to decrease the duration of symptoms, transmission to close contacts, and prevention of the rare suppurative and nonsuppurative sequelae.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 20  Sore Throat

REFERENCES 1. Centers for Disease Control and Prevention, National Center for Health Statistics, National Health Care Surveys: National Hospital Ambulatory Medical Care Survey: 2010 emergency department summary tables. . 2. Hsiao CJ, Cherry DK, Beatty PC, et al: National Ambulatory Medical Care Survey: 2007 summary. Natl Health Stat Report 27:1–32, 2010. 3. Rowley AH: The complexities of the diagnosis and management of Kawasaki disease. Infect Dis Clin North Am 29:525–537, 2015. 4. Aalbers J, O’Brien KK, Chan WS, et al: Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score. BMC Med 9:67, 2011. 5. Kenealy T: Sore throat. BMJ Clin Evid 2014: 2014. 6. Shulman ST, Bisno AL, Clegg HW, et al: Infectious Diseases Society of America: Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 55:e86–e102, 2012. 7. Richey LE, Halperin J: Acute human immunodeficiency virus infection. Am J Med Sci 345:136–142, 2013. 8. Luzuriaga K, Sullivan JL: Infectious mononucleosis. N Engl J Med 362:1993–2000, 2010. 9. Grover C: Images in clinical medicine: “thumb sign” of epiglottitis. N Engl J Med 365:447, 2011. 10. Hung TY, Li S, Chen PS, et al: Bedside ultrasonography as a safe and effective tool to diagnose acute epiglottitis. Am J Emerg Med 29:359.e1–359.e3, 2011. 11. Ko DR, Chung YE, Park I, et al: Use of bedside sonography for diagnosing acute epiglottitis in the emergency department: a preliminary study. J Ultrasound Med 31:19–22, 2012.

12. Maroldi R, Farina D, Ravanelli M, et al: Emergency imaging assessment of deep neck space infections. Semin Ultrasound CT MR 3:432–442, 2012. 13. Rozovsky K, Hiller N, Koplewitz BZ, et al: Does CT have an additional diagnostic value over ultrasound in the evaluation of acute inflammatory neck masses in children? Eur Radiol 20:484–490, 2010. 14. Centor RM, Atkinson TP, Ratliff AE, et al: The clinical presentation of fusobacteriumpositive and streptococcal-positive pharyngitis in a university health clinic: a crosssectional study. Ann Intern Med 162:241–247, 2015. 15. Webb RH, Grant C, Harnden A: Acute rheumatic fever. BMJ 351:h3443, 2015. 16. Powell J, Wilson JA: An evidence-based review of peritonsillar abscess. Clin Otolaryngol 37:136–145, 2012. 17. Spinks A, Glasziou PP, Del Mar CB: Antibiotics for sore throat. Cochrane Database Syst Rev (11):CD000023, 2013. 18. Chang C: Cutting edge issues in rheumatic fever. Clin Rev Allergy Immunol 42: 213–237, 2012. 19. Watson G, Jallow B, Le Doare K, et al: Acute rheumatic fever and rheumatic heart disease in resource-limited settings. Arch Dis Child 100:370–375, 2015. 20. Zoorob R, Sidani MA, Fremont RD, et al: Antibiotic use in acute upper respiratory tract infections. Am Fam Physician 86:817–822, 2012. 21. Barnett ML, Linder JA: Antibiotic prescribing to adults with sore throat in the United States, 1997–2010. JAMA Intern Med 174:138–140, 2014. 22. Linder JA: Sore throat: avoid overcomplicating the uncomplicated. Ann Intern Med 162:311–312, 2015. 23. ESCMID Sore Throat Guideline Group, Pelucchi C, Grigoryan L, et al: Guideline for the management of acute sore throat. Clin Microbiol Infect 18(Suppl 1):1–28, 2012. 24. Wing A, et al: Effectiveness of corticosteroid treatment in acute pharyngitis: a systematic review of the literature. Acad Emerg Med 17:476–483, 2010.

CHAPTER 20: QUESTIONS & ANSWERS 20.1. When a patient presents to the emergency department (ED) complaining of a sore throat, which is the most valuable component of the diagnostic evaluation? A. Computed tomography (CT) evaluation of the soft tissues B. Direct visualization of the oropharynx C. Plain film radiography D. Serologic testing Answer: B. Direct visualization of the pharynx is typically the most helpful portion of the encounter. Thus, complete and unencumbered visualization of the pharyngeal structures is mandatory. Lingual resistance may require coaching or stimulation of a gag reflex, and trismus or pain will often require analgesia. If impressive tonsillar erythema or exudates are observed in a symmetric distribution, and the patient has no signs of airway involvement, acute tonsillitis is present, and further investigation is rarely warranted. 20.2. Historically, there was emphasis on determining whether infectious pharyngitis was bacterial or viral in origin. Many industrialized countries have abandoned the search for group A streptococci in the context of pharyngitis for the following reason(s): A. All of these. B. Antibiotics do not improve the symptoms associated with viral pharyngitis. C. Risks of treatment outweigh benefits. D. The prevalence of rheumatic fever is exceedingly rare in industrialized nations. Answer: A. The great majority of cases are viral in origin, and suppurative complications following streptococcal infection are easily treated and occur too rarely to justify routine use of antibiotics. Rheumatic fever is a disease that is extremely rare in developed nations. Additionally, adverse events caused by antibiotics are common and frequently result in ED visits. 20.3. A 40-year-old man presents with a complaint of sore throat. He is febrile, 102° F (39° C), reports considerable pain with swallowing, and has a moderate sensation of

tightness in his throat. On examination, you note that the patient is sitting up; you observe only mild erythema to the tonsillar tissue. What should be the next step? A. Discharging patient home with a prescription for nonsteroidal antiinflammatory drugs (NSAIDs) B. Intramuscular injection of penicillin C. Nasopharyngoscopy at the bedside D. Sending the patient to radiology for a CT scan of the neck Answer: C. The severity of his symptoms, which are disproportionate to the physical examination, is concerning for other more sinister diagnoses such as epiglottitis, parapharyngeal abscess, and retropharyngeal abscess. 20.4. A healthy 20-year-old, nonsexually active female presents with a complaint of a sore throat. She is febrile and mildly tachycardic. On evaluation, she looks uncomfortable but is in no distress. She has cervical adenopathy, and direct visualization of the oropharynx reveals symmetric tonsillar erythema and diffuse exudates. Ideal management for this patient would include which of the following? A. Ceftriaxone, 250 mg IM once B. Ibuprofen, 400 mg every 4 to 6 hours, dexamethasone (Decadron). 10 mg once, and acetaminophenoxycodone (Percocet), 5/325 mg qid PRN C. Ibuprofen 400 mg every 4 to 6 hours, penicillin G IM once D. Unasyn (Ampicillin-sulbactam), 3 g IV, and incision and drainage Answer: C. Usually, sore throat is caused by acute pharyngitis, in which case pain management with acetaminophen or NSAIDs is the mainstay of care and the most important initial step in empirical management. The Centor criteria, incorporating components of the history and physical examination to generate an estimate of group A streptococci (GAS), are listed in Table 20.2 with the results of one classic study, and this patient would be a candidate for antibiotic treatment.

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C H A P T E R 21 

Hemoptysis Calvin A. Brown III

Hemoptysis is defined as the expectoration of blood from the respiratory tract below the vocal cords. Most cases seen in the emergency department (ED) are mild episodes of small-volume hemoptysis, typically consisting of either blood-tinged sputum or minute amounts of frank blood, most often associated with bronchitis. Although hemoptysis is commonly seen in the ED, only 1% to 5% of hemoptysis patients have massive or life-threatening hemorrhage. Many definitions exist, but massive hemoptysis is generally accepted as 100 to 600 mL of blood loss in any 24-hour period, which can result in hemodynamic instability, shock, or impaired alveolar gas exchange and has a mortality rate approaching 80%. Large, contemporary series of patients with massive hemoptysis are lacking, and most causative data originate from small, often rural, studies in which tuberculosis (TB) and bronchiectasis are responsible for the majority of cases. In developed nations, cancer, cystic fibrosis, arteriovenous malformations, anticoagulant use, and postprocedural complications play more prominent roles. Pediatric hemoptysis is rare but can be caused by infection, congenital heart disease, cystic fibrosis, or bleeding from a preexisting tracheostomy. Major causes of hemoptysis are listed in Box 21.1.

Bronchiectasis, a chronic necrotizing infection resulting in bronchial wall inflammation and dilation, is one of the most common causes of massive hemoptysis worldwide. As tissue destruction and remodeling occur, rupture of nearby bronchial vessels can result in bleeding. Bronchiectasis can complicate chronic airway obstruction, necrotizing pneumonia, TB, or cystic fibrosis. Broncholithiasis, the formation of calcified endobronchial lesions following a wide array of granulomatous infections, is an uncommon problem with a similar propensity to erode nearby vessels. Hemorrhage control often requires surgical intervention. Iatrogenic hemoptysis complicates 2% to 10% of all endobronchial procedures, especially percutaneous lung biopsies. Right (pulmonary artery) heart catheterization using a Swan Ganz catheter can cause iatrogenic pulmonary artery perforation especially in patients with pulmonary hypertension. Although this complication is rare, the mortality is between 50% to 70%.1,2 Diffuse alveolar hemorrhage can be seen with autoimmune vasculitides, such as Wegener’s granulomatosis, systemic lupus erythematosus (SLE), and Goodpasture’s syndrome. An uncommon cause of hemoptysis occurs when ectopic endometrial tissue within the lung results in monthly catamenial episodes of bleeding. Less common causes include pulmonary hereditary telangiectasias and hydatidiform infections. Any episode of hemoptysis can be exacerbated by coagulopathy and thrombocytopenia.

Pathophysiology

DIAGNOSTIC APPROACH

Minor hemoptysis typically originates from tracheobronchial capillaries that are disrupted by vigorous coughing or minor bronchial infections. Conversely, massive hemoptysis nearly always involves disruption of bronchial or pulmonary arteries, which are the two sets of vessels that constitute the lung’s dual blood supply. Bronchial arteries, which are direct branches from the thoracic aorta, are responsible for supplying oxygenated blood to lung parenchyma, and disruption of these vessels from arteritis, trauma, bronchiectasis, or malignant erosion can result in sudden and profound hemorrhage. Although small in caliber, the bronchial circulation is a high-pressure system and the culprit in nearly 90% of the cases of massive hemoptysis requiring embolization. Pulmonary arteries, although transmitting large volumes of blood, do so at much lower pressures and, unless affected centrally, are less likely to cause massive hemoptysis. Nearly all causes of hemoptysis have a common mechanism— vascular disruption within the trachea, bronchi, small-caliber airways, or lung parenchyma. Modes of vessel injury include acute and chronic inflammation (from bronchitis and arteritis), local infection (especially lung abscesses, TB, and aspergillosis), trauma, malignant invasion, infarction following a pulmonary embolus, and fistula formation (specifically aortobronchial fistulae). In the 1960s, nearly all cases of massive hemoptysis were a result of TB, bronchiectasis, or lung abscess. Each of these has since decreased in frequency, whereas pneumonia and bleeding diathesis have become more prevalent.

Differential Diagnosis Considerations

PERSPECTIVE Epidemiology

190

First, the clinician should be convinced that the source of the bleeding is pulmonary. Distinguishing hemoptysis from hematemesis is accomplished by the clinician working with the patient to clarify details of the history, particularly differentiation between coughing and vomiting or spitting. Nasal, oral, or hypopharyngeal bleeding may contaminate the tracheobronchial tree, mimicking true hemoptysis. The clinician should closely inspect the nasopharynx and oral cavity to exclude this possibility. Gastric or proximal duodenal bleeding can similarly mimic hemoptysis, and differentiating a gastrointestinal (GI) source of bleeding is especially important because further evaluation and management of these two pathologies follow divergent pathways. In unclear cases, inspection and pH testing may help to distinguish GI from tracheobronchial hemorrhage. Unless an active, brisk upper GI hemorrhage is present, the acidification of blood in the stomach results in fragmentation and darkening, producing specks of brown or black material often referred to as coffee-ground emesis. Pulmonary blood appears bright red or as only slightly darker clots and is alkaline. Inflammatory disorders that secondarily involve the lungs or pulmonary vasculature include Wegener’s granulomatosis, Goodpasture’s syndrome, and SLE, and a history of these should be elicited. Any risk factors for platelet dysfunction, thrombocytopenia, and coagulopathy should be noted, as should, conversely, any

CHAPTER 21  Hemoptysis

BOX 21.1 

Signs

Differential Diagnosis of Hemoptysis

A targeted examination may suggest the location and cause of bleeding but does so in less than 50% of cases. Focal adventitious breath sounds in a febrile patient may indicate pneumonia or pulmonary abscess. A new heart murmur, especially in a febrile patient, may reflect endocarditis causing septic pulmonary emboli. A rash might hint at underlying rheumatologic disorders, such as SLE or vasculitis. Symptoms and signs of deep venous thrombosis suggest pulmonary embolism. Ecchymoses and petechiae can indicate coagulopathy and thrombocytopenia, respectively.

AIRWAY DISEASE

Bronchitis (acute or chronic) Bronchiectasis Neoplasm (primary and metastatic) Trauma Foreign body

PARENCHYMAL DISEASE Tuberculosis (TB) Pneumonia, lung abscess Fungal infection Neoplasm

VASCULAR DISEASE

Pulmonary embolism Arteriovenous malformation Aortic aneurysm Pulmonary hypertension Vasculitis (Wegener’s granulomatosis, systemic lupus erythematosus [SLE], Goodpasture’s syndrome)

HEMATOLOGIC DISEASE

Coagulopathy (cirrhosis or warfarin therapy) Disseminated intravascular coagulation (DIC) Platelet dysfunction Thrombocytopenia

CARDIAC DISEASE

Congenital heart disease (especially in children) Valvular heart disease Endocarditis

MISCELLANEOUS

Cocaine Postprocedural injury Tracheal-arterial fistula SLE

Ancillary Testing Initial laboratory studies include a complete blood count, coagulation tests, and a type and crossmatch for packed red blood cells. Renal function tests should be performed if vasculitis is suggested or contrast computed tomography (CT) is planned. Plain chest radiography plays a limited role in evaluating patients with minor hemoptysis. Although chest x-rays can screen for causes of hemoptysis (including infection and malignancy), their sensitivity is poor and often cannot identify the source of bleeding, a critical step in triage and management (see the Empirical Management section). Up to half of hemoptysis patients with a normal chest radiograph will have positive findings on chest CT. When there is massive hemoptysis, plain films localize the site of hemorrhage in as many as 80% of patients; however, highresolution CT of the chest is the principle diagnostic test for investigating both bronchial and non-bronchial causes of massive hemoptysis. A chest CT scan should be obtained in the highrisk patient (ie, smokers, oncology patients) or in any patient with moderate to severe bleeding even if the initial chest radiograph is normal. CT localization of hemorrhage can expedite bronchoscopic evaluation and guide subsequent interventional procedures. CT is diagnostically comparable to conventional angiography but less invasive and more rapidly available. Angiography is the first-line study when the cause of the hemoptysis is known (eg, malignancy), bronchial artery hemorrhage is suspected or when angiography-assisted embolization therapy is contemplated. Successful embolization rates range to 95%.

DIAGNOSTIC ALGORITHM hypercoagulable states that might contribute to venous thromboembolic disease. Primary or metastatic cancer can cause hemoptysis by erosion into pulmonary and bronchial vessels. Recent percutaneous or transbronchial procedures can cause immediate or delayed postprocedural bleeding, and any recent history of trauma should also be noted. A pertinent travel history to areas in which TB or pulmonary paragonimiasis is endemic is crucial. A history of chronic alcoholism, cancer, and pulmonary fungal infections are other critical historical elements, because these independently predict increased in-hospital mortality.3

Pivotal Findings Symptoms Although patient reports of bleeding severity can be inaccurate, an estimate of the rate, volume, and appearance of expectorated blood should be obtained. Additional pertinent history includes prior episodes of hemoptysis or parenchymal pulmonary disorders, including bronchiectasis, recurrent pneumonia, chronic obstructive pulmonary disease, bronchitis, TB, and fungal infection.

Critical Diagnoses Box 21.2 shows critical diagnoses and emergent diagnoses. Proper management hinges not only on standard resuscitative measures but also specific therapies, such as reversal of coagulopathy or emergent surgical intervention. For example, in patients with preexisting tracheostomies, new hemoptysis (especially within 3 to 4 weeks of surgery) often represents a tracheo-innominate artery fistula (TIF) for which the need for hemorrhage control is immediate and can often be accomplished in the ED. Although management decisions hinge on the volume and rate of bleeding, the initial diagnostic strategy is the same for all patients with hemoptysis (Fig. 21.1). Patients with trace hemoptysis or blood tinged sputum only and a classic story for viral bronchitis may not require laboratory or radiology investigation of any type. For all others, the initial screening test obtained in the ED is a chest x-ray. Since the advent of high-resolution CT, radiologic evaluation has had an integral role in the evaluation and treatment of patients with hemoptysis. Unless the initial chest radiograph is diagnostic or the patient is hemodynamically unstable, a chest CT should be obtained. Further management decisions should be guided by the CT results and made in conjunction with pulmonary and thoracic surgery consultants.

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Signs, Symptoms, and Presentations

Bronchoscopy Early bronchoscopy may be the right option because it facilitates both localization of bleeding and therapeutic intervention. Chest CT is as diagnostically accurate as bronchoscopy in locating bleeding peripheral vessels not accessible by a flexible bronchoscope. Chest CT can be used to identify the site of bleeding to determine whether angiography is indicated. There may be little added benefit to bronchoscopy before interventional angiography if the bleeding source has already been accurately identified on CT.

EMPIRICAL MANAGEMENT Figure 21.2 outlines the management algorithm for patients with hemoptysis. Although hemodynamic instability can occur as a result of hemorrhage, the most lethal sequela of massive hemoptysis is hypoxia, which results from the ventilation-perfusion

BOX 21.2 

Critical and Emergent Diagnoses in Patients Presenting With Hemoptysis CRITICAL DIAGNOSES

Disseminated intravascular coagulopathy (DIC) Tracheo-innominate artery fistula (TIF) Aortobronchial fistula Iatrogenic (postprocedural) hemoptysis Pulmonary embolism

EMERGENT DIAGNOSES Trauma Bronchiectasis Pneumonia Abscess/fungal infection Oral anticoagulant overdose Endocarditis

mismatch that follows submersion of the small airways and alveoli with blood. All patients with massive hemoptysis should have multiple large bore peripheral intravenous lines placed. Volume resuscitation should begin immediately for patients with ongoing bleeding or shock. Coagulopathy, in the setting of severe bleeding, should be reversed by infusing 2 to 4 units of fresh frozen plasma (FFP) and 10 mg of intravenous vitamin K. Prothrombin complex concentrates (PCCs) have been successful in reversing warfarininduced intracranial hemorrhage, but there is no information to guide the use of PCC in patients with severe hemoptysis.4 Patients with thrombocytopenia should have a platelet transfusion with a goal platelet count of 50,000 to 60,000. If a TIF is suspected, the emergency clinician should immediately attempt to overinflate the tracheostomy balloon in an effort to tamponade the bleeding. If this fails, the tracheostomy tube should be removed, the patient should be orally intubated, and the operator’s index finger should be placed through the tracheostomy hole with pressure applied at the sight of bleeding (Fig. 21.3). Aortobronchial artery fistulae are highly lethal; but if caught early, general resuscitative measures should be undertaken in addition to immediate consultation with or transfer to an endovascular surgeon. Pulmonary embolus only rarely affiliated with massive hemoptysis. When trace hemoptysis accompanies pulmonary embolism, usual care with anticoagulation is standard treatment. Hemoptysis as a complication of disseminated intravascular coagulation (DIC) should be treated following the general management guidelines for DIC. Treatment of DIC remains controversial; but when bleeding is present thrombocytopenia with platelet counts less than 50,000, transfusion is indicated. FFP and cryoprecipitate have been advocated to replace factors lost due to consumptive coagulopathy. Patients with a known or suspected lateralizing source of bleeding should be placed in the “bleeding lung-down” position such that the bleeding lung is more dependent, promoting continued protection and ventilation of the unaffected lung and improved oxygenation. If intubation is required, a large diameter

Y

Trace bleeding and viral bronchitis?

D/C home with follow-up

N CBC, PT/INR, CXR Consider: BNP, D-dimer, troponin, type and screen

CXR diagnostic?

Y

Consider oncology, CT surgery, pulmonary consult based on findings

N

Chest CT with contrast diagnostic? Y

Consider oncology, CT surgery, pulmonary consult based on findings

N

Bronchoscopy

Fig. 21.1.  The emergency department (ED) diagnostic approach to hemoptysis. BNP, B-type natriuretic peptide; CBC, complete blood count; CT, computed tomography; CXR, chest x-ray; D/C, discharge; INR, international normalized ratio; PT, prothrombin time.

CHAPTER 21  Hemoptysis

N

Massive hemoptysis?

Hemodynamic instability or hypoxia?

Y

Y

N

Hemodynamic instability or hypoxia?

Admit or OBS unit for consults and further evaluation

Consider “bleeding lung-down” positioning

Two IVs, IVFs/blood, FFP, cardiac monitor, pulse oximetry, intubation

Suspected bronchial artery hemorrhage? N Cardiothoracic surgery, pulmonary consult

Y Cardiothoracic surgery, pulmonary consult angiogram

Fig. 21.2.  The emergency department (ED) management approach to hemoptysis. IV, Intravenous; IVF, intravenous fluid; FFP, fresh frozen plasma; OBS, observation.

Fig. 21.3.  Pressure placed by the clinician’s finger through the tracheostomy hole occluding the tracheo-innominate artery.

(8.0) endotracheal tube should be used to facilitate emergent flexible bronchoscopy. If the patient has marginal hemodynamic status, the intubation should proceed with a “shock-sensitive” strategy focusing on preload maximization with isotonic fluids or blood, reduced dose induction agents and peri-intubation pressors, such as phenylephrine (Neo-Synephrine) (see Chapter 1). In selected cases of confirmed left-sided bleeding, a single-lumen right-mainstem intubation often can be successfully performed through advancement of the tube in the neutral position or use of a 90-degree rotational technique, during which the tube is rotated 90 degrees in the direction of desired placement and advanced until resistance is met. Left-mainstem intubations are more difficult but may be attempted when the bleeding site is the right lung and

simple lung-down positioning is not sufficient to stabilize the patient’s airway and oxygenation. When these measures fail or the hemoptysis is life-threatening, anesthesia consultation is sought for consideration of placement of double-lumen endotracheal tubes for lung isolation. The correct positioning of blindly placed double-lumen tubes is difficult and requires confirmation by auscultation and fiberoptic bronchoscopy, both of which are severely impaired by massive hemoptysis. Complications of double-lumen tubes include unilateral and bilateral pneumothoraces, pneumomediastinum, carinal rupture, lobar collapse, and tube malposition. Fiberoptic bronchoscopy, in addition to being one of the first diagnostic maneuvers, is a first line therapeutic option as well. Balloon and topical hemostatic tamponade, thermocoagulation, and injection of vasoactive agents can all effectively control arterial bleeding. Optimal timing for bronchoscopy remains conjectural. Although stable patients with mild to moderate bleeding may benefit from early bronchoscopy, in unstable patients or those with brisk hemorrhage, bronchoscopy may facilitate airway management but is less likely to control bleeding. Bronchial arterial embolization is an effective first-line therapy for massive hemoptysis and is the procedure of choice for patients either unable to tolerate surgery or in whom bronchoscopy has been unsuccessful. Hemostatic rates range from 85% to 98%, but as many as 20% to 50% of patients have early episodes of repeat bleeding. The risk of delayed bleeding may exist for up to 36 months. To guide therapy, initial localization of bleeding by bronchoscopy or CT is preferred. Rare complications include arterial perforation and dissection. Emergency thoracotomy, in the operating room, is reserved for life-threatening hemoptysis or for persistent, rapid bleeding that is uncontrolled by bronchoscopy and percutaneous embolization. Although lung resection for massive hemoptysis carries with it high morbidity and mortality, it is a permanent solution to ongoing life-threatening hemoptysis. Pulmonary arterial hemorrhage from tumor necrosis represents a surgical emergency. Healthy patients with blood-streaked sputum or intermittent small-volume hemoptysis in the context of an acute or subacute respiratory infection with resolved hemoptysis and normal vital signs do not require imaging beyond plain chest radiography and

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Signs, Symptoms, and Presentations

can be discharged. High-risk patients (such as, those with known lung cancer, pulmonary vascular abnormalities, or coagulopathy with minor hemoptysis) and all patients with moderate or large amounts of hemoptysis should undergo emergent chest CT scan. There is little value in obtaining a plain chest radiograph before CT, and a plain x-ray film should not be obtained if chest CT is

planned regardless of the findings on the plain film. Brief hospitalization or admission to an observation unit for bronchoscopy should be considered. All patients with massive hemoptysis require admission to an intensive care unit and expedited multidisciplinary treatment involving the emergency physician, pulmonologist, and thoracic surgeon.

KEY CONCEPTS • Hemoptysis is caused by infection, trauma, cancer, coagulopathy, or as a complication of invasive pulmonary procedures. • Plain radiographs are the initial screening test in most cases of massive hemoptysis, although CT scans are more sensitive and can supplant plain chest x-rays as the initial diagnostic test. • Bronchial artery embolization is highly effective with hemostasis rates ranging from 85% to 95%.

• With massive hemoptysis, hypoxia is the more immediate concern than volume resuscitation, and early intubation to ensure adequate oxygenation is paramount. • If a tracheo-innominate artery fistula (TIF) is suspected, then overinflation of the tracheostomy balloon or digital pressure at the site of bleeding should be performed for immediate hemorrhage control.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 21  Hemoptysis

REFERENCES 1. Booth KL, Mercer-Smith G, McConkey C, et al: Catheter-induced pulmonary artery rupture: haemodynamic compromise necessitates surgical repair. Interact Cardiovasc Thorac Surg 15(3):531–533, 2012. 2. Kalra A, Heitner S, Topalian S: Iatrogenic pulmonary artery rupture during Swan-Ganz catheter placement—a novel therapeutic approach. Catheter Cardiovasc Interv 81(1):57–59, 2013.

3. Fartoukh M, Khoshnood B, Parrot A, et al: Early prediction of in-hospital mortality of patients with hemoptysis: an approach to defining severe hemoptysis. Respiration 83(2):106–114, 2012. 4. Cabral KP, Fraser GL, Duprey J, et al: Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding. Clin Neurol Neurosurg 115(6):770–774, 2013.

CHAPTER 21: QUESTIONS & ANSWERS 21.1. What is the most common cause of trace hemoptysis (blood-tinged sputum)? A. Bronchiectasis B. Bronchitis C. Cancer D. Congestive heart failure E. Pulmonary embolism Answer: B. The most common cause of small-volume hemoptysis is bronchitis. 21.2. Disruption of which of the following vessels is responsible for the vast majority of cases of massive hemoptysis? A. Aorta B. Bronchial arteries C. Pulmonary arteries D. Pulmonary veins E. Tracheobronchial capillaries Answer: B. Massive hemoptysis almost exclusively involves one of the two sets of vessels that constitute the lung’s dual blood supply. Bronchial arteries, direct branches from the thoracic aorta, are responsible for supplying oxygenated blood to the lung parenchyma. Disruption of these vessels can result in sudden and profound hemorrhage. Although small in caliber, the bronchial circulation is a high-pressure system and the cause in nearly 90% of the cases of massive hemoptysis requiring embolization. Although they transmit large volumes of blood, pulmonary arteries are at much lower pressure and, unless affected at a very central location, are less likely to cause massive hemoptysis. Trace hemoptysis typically originates from tracheobronchial capillaries that become disrupted with vigorous coughing or minor bronchial infections. 21.3. Which of the following statements regarding the evaluation of hemoptysis is true? A. Chest computed tomography (CT) should not be obtained in patients with massive hemoptysis if this delays initiation of bronchoscopy. B. Chest CT should be obtained in any patient with moderate bleeding even if the initial chest radiograph is normal. C. Conventional angiography is the preferred diagnostic test to detect both bronchial and non-bronchial arterial causes of massive hemoptysis. D. High-resolution multidetector CT, even with recent advances in technology, remains diagnostically inferior to angiography. E. In patients with massive hemoptysis, plain films accurately localize the site of hemorrhage in less than 50% of patients. Answer: B. In patients with massive hemoptysis, plain films may localize the site of hemorrhage in as many as 80% of patients.

However, high-resolution multidetector CT of the chest is the principal diagnostic test to detect both bronchial and nonbronchial arterial causes of massive hemoptysis. CT is diagnostically comparable with, but less invasive than, conventional angiography, which currently is done as a combined diagnostic/ therapeutic modality. A chest CT scan should be obtained in highrisk patients (smokers and oncology patients) or in any patient with moderate-to-severe bleeding even if the initial chest radiograph is normal. CT localization of hemorrhage can expedite bronchoscopic evaluation or guide subsequent interventional procedures. 21.4. A 50-year-old man presents after an episode of hemoptysis. He describes coughing up several large clots of dark blood. During his evaluation, he coughs and expectorates approximately 5 mL of clotted blood. The patient’s vital signs are normal, and no abnormalities are noted on physical examination. His chest radiograph is normal. Which of the following is the most appropriate next step in the management of this patient? A. Admission to an observation unit B. Consultation for bronchoscopy C. Consultation for percutaneous embolization D. Discharge home with follow-up in 24 hours E. Obtain chest CT scan Answer: E. Since the advent of high-resolution CT, radiologic evaluation has had an integral role in the evaluation and management of patients with hemoptysis. Unless the initial chest radiograph is diagnostic or the patient is hemodynamically unstable, a chest CT scan should be obtained in most cases. Further management strategy should occur in conjunction with pulmonary and thoracic surgery consultants, guided by the CT results. 21.5. A 58-year-old man with a single lung transplant presents to the emergency department (ED) with what appears to be large-volume hemoptysis. He was just discharged from the endoscopy suite, where he had a number of surveillance biopsies performed. He looks pale and diaphoretic with an initial oxygen saturation of 71%. After placement of an intravenous line and supplemental oxygen, the next most appropriate step is: A. Blood transfusion B. Contrast-enhanced CT scan of the chest C. Intubation D. Thoracic surgery consultation Answer: C. This patient is profoundly hypoxic, will need imaging outside of the ED, and invasive procedures. All resuscitative and procedural efforts will be futile without intubation and maximal oxygenation.

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C H A P T E R 22 

Dyspnea Sabina A. Braithwaite  |  Debra Perina PERSPECTIVE Dyspnea is the term applied to the sensation of breathlessness and the patient’s reaction to that sensation. It is an uncomfortable awareness of breathing difficulties that in the extreme manifests as “air hunger.” Dyspnea is often ill defined by patients, who may describe the feeling as shortness of breath, chest tightness, or difficulty breathing. Dyspnea results from a variety of conditions, ranging from nonurgent to life-threatening. Neither the clinical severity nor the patient’s perception correlates well with the seriousness of underlying pathology and may be affected by emotions, behavioral and cultural influences, and external stimuli.1 The following terms may be used in the assessment of the dyspneic patient: Tachypnea: A respiratory rate greater than normal. Normal rates range from 44 cycles/min in a newborn to 14 to 18 cycles/min in adults. Hyperpnea: Greater than normal minute ventilation to meet metabolic requirements. Hyperventilation: A minute ventilation (determined by respiratory rate and tidal volume) that exceeds metabolic demand. Arterial blood gases (ABGs) characteristically show a normal partial pressure of oxygen (Po2) with an uncompensated respiratory alkalosis (low partial pressure of carbon dioxide [Pco2] and elevated pH). Dyspnea on exertion: Dyspnea provoked by physical effort or exertion. It often is quantified in simple terms, such as the number of stairs or number of blocks a patient can manage before the onset of dyspnea. Orthopnea: Dyspnea in a recumbent position. It usually is measured in number of pillows the patient uses to lie in bed (eg, two-pillow orthopnea). Paroxysmal nocturnal dyspnea: Sudden onset of dyspnea occurring while reclining at night, usually related to the presence of congestive heart failure.

Epidemiology Dyspnea is a very common presenting complaint among emergency department (ED) patients of every age. Causes vary widely, and range from benign, self-limited conditions to critical pathology that can produce short-term mortality and long-term morbidity.2,3

Pathophysiology The actual mechanisms responsible for dyspnea are only beginning to be specifically described. Normal breathing is controlled both centrally by the respiratory control center in the medulla oblongata and peripherally by chemoreceptors located near the carotid bodies, but there are numerous sensory inputs that affect the feeling of dyspnea, including pulmonary stretch receptors and mechanoreceptors in the diaphragm and skeletal muscles.4

Imbalances among these inputs can be perceived as dyspnea and may manifest as increased work of breathing, due to increased lung resistance or decreased compliance in asthma or chronic obstructive pulmonary disease (COPD). Alternatively, the imbalances of these inputs may also manifest as increased respiratory drive—ie, resulting from severe hypoxemia, acidosis, or centrally acting stimuli (toxins, central nervous system events).5

DIAGNOSTIC APPROACH Differential Diagnosis Considerations Dyspnea is subjective and has many different potential causes. The differential diagnosis can be divided into acute and chronic causes, of which many are pulmonary. Other causes include cardiac, metabolic, infectious, neuromuscular, traumatic, and hematologic conditions (Table 22.1).

Pivotal Findings Symptoms Patient descriptions of dyspnea vary significantly and generally correlate poorly with severity, although the complaint of dyspnea alone is predictive of mortality. Duration of Dyspnea.  Chronic or progressive dyspnea usually denotes primary cardiac or pulmonary disease.6 Acute dyspneic spells may result from asthma exacerbation; infection; pulmonary embolus; intermittent cardiac dysfunction; psychogenic causes; or inhalation of irritants, allergens, or foreign bodies. Onset of Dyspnea.  Sudden onset of dyspnea should lead to consideration of pulmonary embolism (PE) or spontaneous pneumothorax. Dyspnea that builds slowly over hours or days may represent a flare of asthma or COPD; pneumonia; recurrent, small pulmonary emboli; congestive heart failure; or malignancy. Positional Changes.  Orthopnea can result from left-sided heart failure, COPD, or neuromuscular disorders. One of the earliest symptoms seen in patients with diaphragmatic weakness from neuromuscular disease is orthopnea.7 Paroxysmal nocturnal dyspnea is most common in patients with left-sided heart failure but also occurs in COPD.6 Exertional dyspnea commonly is associated with COPD but also can be seen with poor cardiac reserve and abdominal loading. Abdominal loading, caused by ascites, obesity, or pregnancy, leads to elevation of the diaphragm, resulting in less effective ventilation and dyspnea. Anxiety or overwhelming fear, particularly if it precedes the onset of dyspnea, may point to panic attack or psychogenic dyspnea, but organic causes should be considered first. PE or myocardial infarction may cause isolated dyspnea with or without associated chest pain, particularly if the pain is constant, dull, or visceral.8 Pain that is sharp and worsened by deep breathing but not by movement may indicate pleural effusion, pleurisy, 195

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TABLE 22.1 

Differential Diagnoses for Acute Dyspnea ORGAN SYSTEM

CRITICAL DIAGNOSES

EMERGENT DIAGNOSES

NONEMERGENT DIAGNOSES

Pulmonary

Airway obstruction Pulmonary embolus Noncardiogenic edema Anaphylaxis Ventilatory failure

Spontaneous pneumothorax Asthma Cor pulmonale Aspiration Pneumonia (CAP score >70)

Pleural effusion Neoplasm Pneumonia (CAP score ≤70) COPD

Cardiac

Pulmonary edema Myocardial infarction Cardiac tamponade

Pericarditis

Congenital heart disease Valvular heart disease Cardiomyopathy

PRIMARILY ASSOCIATED WITH NORMAL OR INCREASED RESPIRATORY EFFORT Abdominal

Mechanical interference Hypotension, sepsis from ruptured viscus, bowel obstruction, inflammatory or infectious process

Psychogenic

Pregnancy Ascites obesity

Hyperventilation syndrome Somatization disorder Panic attack

Metabolic or endocrine

Toxic ingestion DKA

Renal failure Electrolyte abnormalities Metabolic acidosis

Fever Thyroid disease

Infectious

Epiglottitis

Pneumonia (CAP score >70)

Pneumonia (CAP score ≤70)

Traumatic

Tension pneumothorax Cardiac tamponade Flail chest

Simple pneumothorax, hemothorax Diaphragmatic rupture Neurologic injury

Rib fractures

Hematologic

Carbon monoxide or cyanide poisoning Anemia Acute chest syndrome

PRIMARILY ASSOCIATED WITH DECREASED RESPIRATORY EFFORT Neuromuscular

CVA, intracranial insult Organophosphate poisoning

Multiple sclerosis Guillain-Barré syndrome Tick paralysis

ALS Polymyositis Porphyria

ALS, Amyotrophic lateral sclerosis; CAP, community-acquired pneumonia; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; DKA, diabetic ketoacidosis.

or pleural irritation from pneumonia or PE. Spontaneous pneumothorax also may produce sharp pain with deep breathing that is not worsened by movement.

Signs Physical signs in dyspneic patients may be consistent with specific illnesses (Table 22.2). For example, fever suggests an infectious cause, somnolence or obtundation may indicate hypercarbia, agitation can be associated with hypoxia, and trauma may produce dyspnea through various injuries. Physical findings found in specific diseases also can be grouped according to presenting patterns (Table 22.3). Some findings have improved predictive value for specific pathologies when combined with laboratory testing in validated risk stratification tools.9-11

Ancillary Testing Specific findings obtained from the history and physical examination should be used to determine which ancillary studies are needed (Table 22.4). Bedside oxygen saturation determinations, or selective use of ABGs when oximetry is not reliable, are useful in determining the degree of hypoxia and the need for

supplemental oxygen or assisted ventilation. In patients with abnormal values, a venous blood gas (VBG) is a less painful alternative to ABG to determine pH.12 VBG is less reliable for Pco2 or accurate numeric correlation to arterial hypercapnia, although a normal venous Pco2 has a strong negative predictive value, and values greater than 45 mm Hg are highly sensitive in predicting arterial hypercarbia.13,14 The more invasive ABG is useful when an accurate Pco2 or Po2 is important. An additional resource for quickly assessing ventilatory status is noninvasive waveform capnography. End-tidal carbon dioxide (ETco2) values correlate well with arterial carbon dioxide (CO2), and the shape of the capnogram can be helpful in assessing the adequacy of ventilations, as well as underlying causes of the dyspnea (see Chapter 5).15 An electrocardiogram may be useful if history or physical examination findings suggest heart failure, ischemic cardiac disease, dysrhythmia, or pulmonary hypertension. Bedside ultrasound is useful to rapidly assess multiple parameters that can focus and guide therapy. For example, thoracic ultrasound can quickly visualize pleural effusion, pulmonary edema with B lines, pneumothorax when “sandy beach” and “comet tail” signs are absent, cardiac dysfunction by evaluating myocardial contractility and estimating ejection fraction (EF), or pericardial effusion and tamponade.16,17 Abdominal ultrasound can assess

CHAPTER 22  Dyspnea

TABLE 22.2 

Pivotal Findings in Physical Examination SIGN

PHYSICAL FINDING

DIAGNOSES TO CONSIDER

Vital signs

Tachypnea Hypopnea Tachycardia Hypotension Fever

Pneumonia, pneumothorax Intracranial insult, drug or toxin ingestion PE, traumatic chest injury Tension pneumothorax Pneumonia, PE

General appearance

Cachexia, weight loss Obesity Pregnancy Barrel chest “Sniffing” position “Tripoding” position Traumatic injury

Malignancy, acquired immune disorder, mycobacterial infection Hypoventilation, sleep apnea, PE PE COPD Epiglottitis COPD or asthma with severe distress Pneumothorax (simple, tension), rib fractures, diaphragmatic injury, flail chest, hemothorax, pulmonary contusion

Skin and nails

Tobacco stains or odor Clubbing Pallid skin or conjunctivae Muscle wasting Bruising Diffuse: Thrombocytopenia, chronic steroid use, anticoagulation Subcutaneous emphysema Hives, rash

COPD, malignancy, infection Chronic hypoxia, intracardiac shunts, or pulmonary vascular anomalies Anemia Neuromuscular disease Chest wall: Rib fractures, pneumothorax

Neck

Stridor JVD

Upper airway edema or infection, foreign body, traumatic injury, anaphylaxis Tension pneumothorax, COPD or asthma exacerbation, fluid overload or CHF, PE, cardiac tamponade

Lung examination

Wheezes Bronchospasm Rales Unilateral decrease

CHF, anaphylaxis

Chest examination

Crepitance or pain on palpation Subcutaneous emphysema Thoracoabdominal desynchrony Flail segment

Rib or sternal fractures Pneumothorax, tracheobronchial rupture Diaphragmatic injury with herniation; cervical spinal cord trauma Flail chest, pulmonary contusion

Cardiac examination

Murmur S3 or S4 gallop S2 accentuation Muffled heart sounds

PE PE PE Cardiac tamponade, pericardial effusion

Extremities

Calf tenderness, Homans’ sign Edema

PE CHF

Neurologic examination

Focal deficits (motor, sensory, cognitive)

Stroke, intracranial hemorrhage causing central abnormal respiratory drive; if long-standing, risk of aspiration pneumonia Neuromuscular disease Metabolic or electrolyte abnormality (hypocalcemia, hypomagnesemia, hypophosphatemia), anemia Hypermagnesemia Guillain-Barré syndrome

Rib fractures, pneumothorax, tracheobronchial disruption Allergic reaction, infection, tick-borne illness

CHF, pneumonia, PE Pneumothorax, pleural effusion, consolidation, rib fractures or contusion, pulmonary contusion Hemoptysis Malignancy, infection, bleeding disorder, CHF Sputum production Infection (viral, bacterial) Friction rub Pleurisy Abnormal respiratory pattern (eg, Cheyne-Stokes) Intracranial insult

Symmetrical deficits Diffuse weakness Hyporeflexia Ascending weakness

CHF, Congestive heart failure; COPD, chronic obstructive pulmonary disease; JVD, jugular venous distention; PE, pulmonary embolism.

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TABLE 22.3 

Diagnostic Table: Patterns of Diseases Often Resulting in Dyspnea ASSOCIATED SYMPTOMS

SIGNS AND PHYSICAL FINDINGS

Pulmonary embolism HPI: Abrupt onset, pleuritic pain, immobility (travel, recent surgery) PMH: Malignancy, DVT, PE, hypercoagulability, oral contraception, obesity

Diaphoresis, exertional dyspnea

Tachycardia, tachypnea, low-grade fever

Pulse oximetry, ABG (A-a gradient), D-dimer ECG (dysrhythmia, right-sided heart strain) CXR (Westermark sign, Hampton’s hump), spiral CT, MRV Pulmonary angiogram Ultrasound positive for DVT

Pneumonia

Fever, productive cough, chest pain

Anorexia, chills, nausea, vomiting, exertional dyspnea, cough

Fever, tachycardia, tachypnea, rales or decreased breath sounds

CXR, CBC, sputum and blood cultures

Bacterial

SH: Tobacco use

Viral

Exposure (eg, influenza, varicella)

Opportunistic

Immune disorder, chemotherapy

Fungal or parasitic

Exposure (eg, birds), indolent onset

Episodic fever, nonproductive cough

Pneumothorax

Abrupt onset: Trauma, chest pain, thin males more likely to have spontaneous pneumothorax

Localized chest pain

DISEASE

HISTORY (DYSPNEA)

TESTS

Pulse oximetry Waveform capnography if altered mental status; ABG if capnography unavailable and acid-base derangement or hypercarbia suspected

Decreased breath sounds, CXR: Pneumothorax, rib fractures, subcutaneous hemothorax emphysema, chest wall Ultrasound: Pneumothorax, pleural wounds or instability effusion

Simple

Ultrasound positive for pneumothorax

Tension

Decompensation of simple pneumothorax

Diaphoresis

JVD, tracheal deviation, muffled heart sounds, cardiovascular collapse

Clinical diagnosis: Requires immediate decompression. May verify via bedside ultrasound

COPD or asthma

Tobacco use, medication noncompliance, URI symptoms, sudden weather change

Air hunger, diaphoresis

Retractions, accessory muscle use, tripoding, cyanosis “Shark fin” capnograph

CXR: Rule out infiltrate, pneumothorax, atelectasis (mucus plug) Ultrasound: Distinguish from heart failure Waveform capnography

Hemoptysis

CXR, chest CT: Mass, hilar adenopathy, focal atelectasis

PMH: Environmental allergies FH: Asthma Malignancy

Weight loss, tobacco, or other occupational exposure

Dysphagia

Fluid overload

Gradual onset, dietary indiscretion or medication noncompliance, chest pain PMH: Recent MI, diabetes, CHF

Worsening orthopnea, PND JVD, peripheral edema, S3 or S4 gallop, new cardiac dysrhythmia, hepatojugular reflux

Anaphylaxis

Abrupt onset, exposure to allergen

Dysphagia

CXR and/or ultrasound: Pleural effusion, interstitial edema, Kerley B lines, cardiomegaly ECG: Ischemia, dysrhythmia BNP

Oral swelling, stridor, wheezing, hives

A-a, Alveolar-arterial; ABG, arterial blood gas; BNP, B-type natriuretic peptide; CBC, complete blood count; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CT, computed tomography; CXR, chest x-ray examination; DVT, deep vein thrombosis; ECG, electrocardiogram; FH, family history; HPI, history of present illness; JVD, jugular venous distention; MI, myocardial infarction; MRV, magnetic resonance venography; PE, pulmonary embolism; PMH, past medical history; PND, paroxysmal nocturnal dyspnea; SH, social history; URI, upper respiratory infection.

CHAPTER 22  Dyspnea

TABLE 22.4 

Ancillary Testing in the Dyspneic Patient CATEGORY

TEST

FINDINGS AND POTENTIAL DIAGNOSES

Laboratory

Pulse oximetry, selective ABG use Waveform capnography

Hypoxia, hyperventilation (muscular weakness, intracranial event) CO2 retention (COPD, sleep apnea), obstructive or restrictive pulmonary pattern Metabolic versus respiratory acidosis (DKA, ingestions) A-a gradient (PE) Elevated carboxyhemoglobin (inhalation injury or CO poisoning) WBC Increase: Infection, stress demargination, hematologic malignancy Decrease: Neutropenia, sepsis Hgb, Hct: Anemia, polycythemia Smear: Abnormal Hgb (ie, sickling), inclusions Platelets: Thrombocytopenia (marrow toxicity) Chemistry BUN, Cr: Acute or chronic renal failure K, Mg, Phos: Low levels resulting in muscular weakness Glucose: DKA D-dimer: Abnormal clotting activity BNP: Heart failure, PE Troponin: Cardiac ischemia or infarct

Complete blood count

Cardiac

ECG Echocardiogram

Ischemia, dysrhythmia, S1Q3T3 (PE), right-sided heart strain Pulmonary hypertension, valvular disorders Wall motion abnormalities related to ischemia, intracardiac shunts

Radiologic

Chest radiograph

Bony structures: Fractures, lytic lesions, pectus, kyphoscoliosis Mass: Malignancy, cavitary lesion, infiltrate, foreign body Diaphragm: Eventration, elevation of hemidiaphragm, bowel herniation Mediastinum: Adenopathy (infection, sarcoid), air Cardiac silhouette: Enlarged (cardiomyopathy, fluid overload) Soft tissue: Subcutaneous air Lung parenchyma: Blebs, pneumothorax, effusions (blood, infectious), interstitial edema, local consolidation, air bronchograms, Hampton’s hump, Westermark’s sign PE PE, intervention (thrombolysis) Mass lesion, adenopathy, trauma, PE PE, bony and soft tissue lesions, vascular abnormality Epiglottitis, foreign body Pneumothorax, pleural effusion, impaired cardiac function or pericardial effusion

Scan Pulmonary angiogram CT MRI Soft tissue neck radiograph Ultrasound Fiberoptic

Bronchoscopy Laryngoscopy

Mass lesion, foreign body Intervention (stenting, biopsy) Mass lesion, edema, epiglottitis, foreign body

A-a, Alveolar-arterial; ABG, arterial blood gas; BNP, B-type natriuretic peptide; BUN, blood urea nitrogen; CO, carbon monoxide; CO2, carbon dioxide; COPD, chronic obstructive pulmonary disease; Cr, creatinine; CT, computed tomography; DKA, diabetic ketoacidosis; ECG, electrocardiogram; Hct, hematocrit; Hgb, hemoglobin; K, potassium; Mg, magnesium; MRI, magnetic resonance imaging; PE, pulmonary embolism; Phos, phosphate;WBC, white blood cell.

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intravascular volume by quantifying inferior vena cava size and compressibility.18 Extremity ultrasound can reveal deep venous thrombosis.19 Serum electrolytes may confirm metabolic acidosis or a less common cause, such as hypokalemia, hypophosphatemia, or hypocalcemia. A complete blood count may identify severe anemia or thrombocytopenia associated with sepsis. The white blood cell count is not sufficiently sensitive or specific to be of discriminatory value. Expanded availability of specific blood biomarkers relevant to emergent evaluation of dyspnea provides improved immediate decision support and allows for short- and long-term prognostication.20,21 These include cardiac markers and D-dimer assay, which are useful in pursuing causes, such as cardiac ischemia or venous thromboembolic disease. B-type natriuretic peptide (BNP) analysis adds both diagnostic and prognostic value for several causes of dyspnea, including heart failure, PE, and ischemic cardiac disease.22 If venous thromboembolism is suspected, D-dimer testing, with or without chest computed tomographic angiography, duplex venous ultrasonography, or, rarely, ventilation-perfusion scanning, is performed on patients preselected based on clinical decision rules.23 If dyspnea is believed to be upper airway in origin, direct or fiberoptic laryngoscopy or a soft tissue lateral radiograph of the neck may be useful.

DIAGNOSTIC ALGORITHM The range and diversity of pathophysiologic conditions that produce dyspnea render a simple algorithmic approach difficult. The primary branch point is the determination of whether the dyspnea primarily is cardiopulmonary or toxic-metabolic in origin. After initial assessment, stabilization and symptom relief in critical patients, findings from the history, physical examination, and ancillary testing are collated to match patterns of disease that produce dyspnea. This process is updated periodically as new information becomes available. Table 22.3 presents recognizable patterns of disease for common dyspnea-producing conditions, along with specific associated symptoms.

Critical Diagnoses Several critical diagnoses should be promptly considered to determine the best treatment options to stabilize the patient. Tension pneumothorax is a critical condition that is diagnosed by history and physical examination. If a dyspneic patient has no breath sounds on one side, ipsilateral hyper-resonance, severe respiratory distress, hypotension, and oxygen desaturation, prompt decompression of presumptive tension pneumothorax is indicated. Jugular venous distension may or may not be apparent and its absence does not rule out the condition. Bedside ultrasonography can confirm pneumothorax in less obvious cases. If dyspnea and stridor indicate upper airway obstruction, early, definitive assessment, and intervention occur in the ED or operating room. Complete obstruction by a foreign body warrants the Heimlich maneuver until the obstruction is relieved or the patient is unconscious, followed rapidly by direct laryngoscopy for foreign body removal. Heart failure and pulmonary edema can produce dyspnea and respiratory failure and require prompt intervention to support ventilation and gas exchange if severe. Significant dyspnea and wheezing in anaphylaxis require immediate use of parenteral epinephrine in addition to supportive measures. Severe bronchospastic exacerbations of asthma at any age may lead rapidly to respiratory failure and arrest and should receive vigorous attention, including continuous or frequent administration of

a beta-agonist aerosol and steroid therapy.24 Ultrasound may also be of benefit in rapidly distinguishing between COPD and heart failure, as well as other pathologies.25,26 As mentioned earlier, waveform capnography is a valuable adjunct for assessing the severity and determining the cause of respiratory distress. Presumptive anticoagulation or even thrombolytics may be appropriate in patients with suspected significant PE even prior to diagnostic testing.

Emergent Diagnoses Asthma and COPD exacerbations can result in marked dyspnea with bronchospasm and decreased ventilatory volumes.27 Sudden onset of dyspnea with a decreased oxygen saturation on room air accompanied by sharp chest pain may represent PE. Dyspnea accompanied by decreased breath sounds and tympany on percussion on one side is seen with spontaneous pneumothorax. Dyspnea associated with decreased respiratory effort may represent a neuromuscular process, such as multiple sclerosis, GuillainBarré syndrome, or myasthenia gravis. Unilateral rales, cough, fever, and dyspnea usually indicate pneumonia. Figure 22.1 provides an algorithm for assessment and stabilization of a dyspneic patient. The initial division is based on the degree of breathing effort associated with the symptoms. The most critical diagnoses are considered first, and appropriate intervention undertaken. All patients experiencing dyspnea, regardless of possible cause, should be promptly evaluated in the treatment area. Bedside pulse oximetry readings should be obtained, and the patient placed on a cardiac monitor. If the pulse oximetry result is less than 94% on room air, supplemental oxygen either by nasal cannula or mask should be considered, depending on the degree of desaturation. In patients with somnolence or obtundation, hypercarbia and respiratory failure should be considered as possible etiologies. If necessary, ventilation should be assisted manually or mechanically, either noninvasively for the short term, or with the patient tracheally intubated for airway protection for prolonged ventilation.28 Decreased mental alertness, inability to speak in more than one-syllable words, or certain types of body positioning signal the presence of significant respiratory distress and the need for rapid intervention. After the airway has been secured, rapid assessment of the patient’s appearance and vital signs can help determine the need for further stabilization and the cause of the dyspnea can be further investigated.

Empirical Management The management algorithm for dyspnea (Fig. 22.2) outlines the approach to treatment for most identifiable diseases. Unstable patients or patients with critical diagnoses must be stabilized and may require admission to an intensive care unit. Emergent patients who have improved with ED management may be admitted to an intermediate care unit. Patients diagnosed with urgent conditions in danger of deterioration without proper treatment or patients with severe comorbidities, such as diabetes, immunosuppression, or cancer, may also require admission for observation and treatment. Most patients in the nonurgent category can be treated as outpatients if medical follow-up can be arranged. If dyspnea persists despite therapy and no definitive cause has been delineated, the preferred course of action is hospitalization for observation and ongoing evaluation. If no definitive diagnosis can be obtained and the symptoms have abated, the patient may be discharged with medical follow-up and instructions to return if symptoms recur.

CHAPTER 22  Dyspnea

Respiratory distress? (RR >24 or 33 yr • Women >40 yr Diabetes mellitus Hypertension Cigarette use or possible passive exposure Elevated cholesterol (low-density lipoprotein [LDL]) or triglyceride levels Sedentary lifestyle Obesity Postmenopausal Left ventricular hypertrophy Cocaine abuse Pulmonary embolism Prolonged immobilization Surgery >30 min in last 3 mo Prior deep vein thrombosis or pulmonary embolus Pregnancy or recent pregnancy Pelvic or lower extremity trauma Oral contraceptives with cigarette smoking Congestive heart failure Chronic obstructive pulmonary disease Obesity Past medical or family history of hypercoagulability

Ancillary Studies The two most commonly performed studies in patients with chest pain are chest radiography and 12-lead electrocardiography (Table 23.4). Electrocardiography should be performed within 10 minutes of arrival in all patients with chest pain or potential angina equivalent in whom myocardial ischemia is a possibility.3,4 This generally includes all male patients 33 years and older and female patients older than 39 years who report pain from the

Aortic dissection Hypertension Congenital disease of the aorta or aortic valve Inflammatory aortic disease Connective tissue disease Pregnancy Arteriosclerosis Cigarette use Pericarditis or myocarditis Infection Autoimmune disease (eg, systemic lupus erythematosus) Acute rheumatic fever Recent myocardial infarction or cardiac surgery Malignancy Radiation therapy to mediastinum Uremia Drugs Prior pericarditis Pneumothorax Prior pneumothorax Valsalva’s maneuver Chronic lung disease Cigarette use

umbilicus to the mandible, unless a noncardiac cause is readily apparent. Rapid acquisition of the ECG facilitates the diagnosis of acute MI and expedites the National Heart, Lung, and Blood Institute’s recommended door to treatment times from arrival to percutaneous coronary intervention (PCI) or thrombolytic therapy in acute MI. Patients with a new injury pattern on the ECG (Table 23.5) or new ischemic electrocardiographic changes should have appropriate therapy instituted at this point (Fig. 23.2; see also Chapter 68). An ECG showing right ventricular strain

CHAPTER 23  Chest Pain

TABLE 23.3 

Pivotal Findings in Physical Examination SIGN

FINDING

DIAGNOSES

Appearance

Acute respiratory distress Diaphoresis

PE, tension pneumothorax, acute MI, pneumothorax Acute MI, aortic dissection, coronary ischemia, PE, esophageal rupture, unstable angina, cholecystitis, perforated peptic ulcer

Vital signs

Hypotension

Tension pneumothorax, PE, acute MI, aortic dissection (late), coronary ischemia, esophageal rupture, pericarditis, myocarditis Acute MI, PE, aortic dissection, coronary ischemia, tension pneumothorax, esophageal rupture, coronary spasm, pericarditis, myocarditis, mediastinitis, cholecystitis, esophageal tear (Mallory-Weiss) Acute MI, coronary ischemia, unstable angina Acute MI, coronary ischemia, aortic dissection (early) PE, esophageal rupture, pericarditis, myocarditis, mediastinitis, cholecystitis PE, tension pneumothorax, pneumothorax

Tachycardia Bradycardia Hypertension Fever Hypoxemia Cardiovascular examination

Significant difference in upper extremity blood pressures Narrow pulse pressure New murmur S3-S4 gallop Pericardial rub Audible systolic “crunch” on cardiac auscultation (Hamman’s sign) JVD

Aortic dissection Pericarditis (with effusion) Acute MI, aortic dissection, coronary ischemia Acute MI, coronary ischemia Pericarditis Esophageal rupture, mediastinitis

Pulmonary examination

Unilateral diminished or absent breath sounds Pleural rub Subcutaneous emphysema Rales

Tension pneumothorax, pneumothorax PE Tension pneumothorax, esophageal rupture, pneumothorax, mediastinitis Acute MI, coronary ischemia, unstable angina

Abdominal examination

Epigastric tenderness Left upper quadrant tenderness Right upper quadrant tenderness

Esophageal rupture, esophageal tear, cholecystitis, pancreatitis Pancreatitis Cholecystitis

Extremity examination

Unilateral leg swelling, warmth, pain, tenderness, or erythema

PE

Neurologic examination

Focal findings Stroke Coronary ischemia

Aortic dissection Acute MI Aortic dissection, coronary spasm

Acute MI, coronary ischemia, tension pneumothorax, PE, pericarditis

JVD, jugular venous distention; MI, myocardial infarction; PE, pulmonary embolism.

TABLE 23.4 

Ancillary Testing of Patients With Chest Pain TEST

FINDING

DIAGNOSIS

ECG

New injury New ischemia RV strain Diffuse ST segment elevation

Acute MI, aortic dissection Coronary ischemia, coronary spasm PE Pericarditis

CXR

Pneumothorax with mediastinal shift Wide mediastinum Pneumothorax Effusion Increased cardiac silhouette Pneumomediastinum

Tension pneumothorax Aortic dissection Esophageal rupture, pneumothorax Esophageal rupture Pericarditis Esophageal rupture, mediastinitis

ABG

Hypoxemia, A-a gradient

PE

  scan Spiral CT or V/Q

High probability or any positive in patient with high clinical suspicion

PE

A-a, Alveolar-arterial; ABG, arterial blood gas; CT, computed tomography; CXR, chest x-ray examination; ECG, electrocardiography; MI, myocardial infarction; PE, pulmonary   , ventilation-perfusion. embolism; RV, right ventricular; V/Q

207

Completed initial evaluation

Initiate emergency care Cardiac monitor Oxygen therapy Aspirin Nitroglycerin IV access Laboratory tests

Stable angina— resolved

No

Suspected ACS?

Yes Discharge Acute STEMI: ST ↑ > 1 mm or new LBBB

Yes

No ED chest pain center Provocative testing

Low risk No intermediate or high risk features Non diagnostic ECG & cardiac markers Age < 70 yr

Heparin or LMWH IV nitroglycerin Consider beta blocker Revascularization: Fibrinolysis or GP IIb-IIIa inhibitor + PCI High risk Elevated troponin New ST ↓ 0.5 mm Recurrent ischemia Heart failure with ischemia Depressed LV function Hemodynamic instability PCI in last 6 months Prior CABG

Risk stratification

Intermediate risk >10 minutes rest pain – resolved T wave inversion > 2 mm Intermediate troponin elevation (TnT > 0.01 mm, < 0.1 mm)

Discharge

Ischemia-guided strategy Observation bed P2Y12 Inhibitor Heparin or LMWH IV nitroglycerin Oral beta blocker Continuous ECG monitoring Repeat ECGs at regular invervals Cardiac markers

Evidence of ongoing ischemia

Early invasive treatment P2Y12 Inhibitor Heparin or LMWH or bivalirudin IV nitroglycerin Oral beta blocker GP IIb-IIIa inhibitor Diagnostic catheterization in 12 to 48 hours

Yes

No Provocative testing

Discharge

Fig. 23.2.  Clinical guidelines for emergency department management of chest pain of myocardial ischemic origin. ACS, Acute coronary syndrome; CABG, coronary artery bypass graft; ECG, electrocardiogram; ED, emergency department; GP, glycoprotein; IV, intravenous; LBBB, left bundle branch block; LMWH, low-molecular-weight heparin; LV, left ventricular; PCI, percutaneous coronary intervention; STEMI, ST segment elevation myocardial infarction. (Adapted from Amsterdam EA, Wenger NK, Brindis RG, et al: 2014 AHA/ACC guideline for the management of patients with non-STelevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130: e344.)

CHAPTER 23  Chest Pain

pattern, in the appropriate setting, should raise the clinical suspicion for PE.5 Diffuse ST segment elevation helps confirm the diagnosis of pericarditis.6 Chest radiography is performed for patients with a possibly serious cause of chest pain. Pneumothorax, pneumonia, empyema, and pleural effusion are definitively diagnosed at this point. A wide mediastinum or ill-defined aortic knob increases the clinical suspicion for acute aortic dissection. Pleural effusion, subcutaneous air, or mediastinal air-fluid level may be seen in esophageal rupture. An increased cardiac silhouette may indicate pericarditis or cardiomyopathy. Pneumomediastinum is seen with esophageal rupture and mediastinitis. A serum D-dimer assay may help discriminate patients with PE from those with a possible gastrointestinal cause. A low serum D-dimer level in a patient without a high pretest probability of PE effectively excludes the diagnosis.7 Patients with a low pretest probability who meet certain defined criteria do not require further testing (see Chapter 78). Patients at high pretest probability for PE should undergo diagnostic imaging.8 High pretest probability warrants initiation TABLE 23.5 

Electrocardiographic Findings in Ischemic Chest Pain FINDINGS Classic myocardial infarction

ST segment elevation (>1 mm) in contiguous leads; new LBBB Q waves > 0.04-sec duration

Subendocardial infarction

T wave inversion or ST segment depression in concordant leads

Unstable angina

Most often normal or nonspecific changes; may see T wave inversion

Pericarditis

Diffuse ST segment elevation; PR segment depression

LBBB, left bundle branch block.

of anticoagulation (eg, with heparin or low-molecular-weight heparin) therapy in the ED before the imaging study in the absence of a contraindication.9 Patients with suspected thoracic aortic dissection may be evaluated by computed tomography (CT) angiography, transesophageal echocardiography, or magnetic resonance imaging. Selection of the imaging modality depends on the patient’s clinical status and availability of the test modality. A high-resolution (>64 slice) CT scanner can be used to rule out all the life-threatening causes of chest pain. Although ACS, PE, and thoracic dissection (the so-called triple rule-out) are the causes most commonly discussed, pneumothorax, mediastinitis, and pericardial effusions are also diagnosed with CT. Laboratory testing is useful in the evaluation of ACS. An elevated troponin level in the correct clinical setting is synonymous with acute MI and is embedded in the universal definition of MI. Troponins (I and T), when elevated, identify patients with ACS who have the highest risk for an adverse outcome. Sensitivity for acute MI at 4 hours is approximately 50%, rising to nearly 100% by 12 hours. Creatine kinase (CK) and CK-MB are used only if determination of the troponin level is unavailable.10

DIAGNOSTIC TABLE After the patient is stabilized and assessment is completed, the findings are matched to the classical and atypical patterns of the seven potentially critical diseases causing chest pain. This matching process is continuous while the patient is evaluated and the response to therapy is monitored. Any inconsistency in findings with the primary working diagnoses necessitates a rapid review of the pivotal findings and the potential diagnoses (Table 23.6).

EMPIRICAL MANAGEMENT The management of ACS is discussed in Chapter 68. Fig. 23.3 outlines the approach to treatment of critical noncardiac diagnoses. Patients with critical diagnoses generally are admitted to the intensive care unit. Patients with emergent diagnoses typically are

Complete initial evaluation

• Cardiac monitor • Intravenous access • Oxygen therapy

Differential diagnosis based on history, physical, and ECG Specific tests per Table 23.4

Aortic dissection

Pulmonary embolism

Tension pneumothorax

Esophageal rupture

Pericarditis

• Beta blockade • IV antihypertensive therapy • Decrease contractility • Immediate surgical consult, transfer

• IV heparin or SQ LMWH • Thrombolysis if severe cardiovascular instability

• Needle decompression • Tube thoracostomy

• IV fluid resuscitation • Analgesia • IV antibiotics • Early surgical consultation

• U/S for effusion, tamponade risk • NSAIDs • Corticosteroids • Cardiology consultation

Fig. 23.3.  Clinical guidelines for emergency department management of chest pain from potentially catastrophic nonmyocardial origins. ECG, Electrocardiogram; IV, intravenous; LMWH, low-molecular-weight heparin; NSAIDs, nonsteroidal antiinflammatory drugs; SQ, subcutaneous; U/S, ultrasound.

209

210

TABLE 23.6 

SUPPORTING HISTORY

PREVALENCE IN EMERGENCY DEPARTMENT PHYSICAL EXAMINATION

Diaphoresis, nausea, vomiting, dyspnea.

Common. May be precipitated by emotional stress or exertion. Often comes on at rest. May come on in early awakening period. Prodromal pain pattern often elicited. Previous history of MI or angina. Age >40 years, positive risk factors, and male sex increase possibility.

Unstable angina

Changes in pattern of preexisting angina with more severe, prolonged, or frequent pain (crescendo angina). Pain usually lasts >10 min. Angina at rest lasting 15–20 min or new-onset angina (duration direct

Direct>indirect

Normal/mild ↑ transaminases ↑↑↑ Alkaline phosphatase ± ↑ PT/PTT + / ↑ Amylase

↑↑↑ Transaminases Normal or ↑ alkaline phosphatase Normal or ↑ PT/PTT Normal amylase

Normal transaminases Normal alkaline phosphatase Normal PT/PTT

Suggests obstructive process

Suggests hepatocellular/cholestatic process (including fulminant hepatic failure)

Suggests hematologic process

• Choledocholithiasis • Intrinsic bile duct disease • Cholangitis • AIDS cholangiopathy • Strictures • Neoplasms • Extrinsic biliary compression • Neoplasms (pancreatic/liver)

• Viral hepatitis • Fulminant hepatic failure • Alcoholic hepatitis • AST > ALT • Ischemia • Toxins • Autoimmune hepatic disease • HELLP syndrome

• Hemolytic disorder • Hematoma resorption • Ineffective erythropoiesis • Gilbert’s syndrome*

*A benign hereditary condition characterized by hyperbilirubinemia and jaundice due to inadequate hepatic conjugation of bilirubin. Fig. 25.1.  Laboratory approach to differential diagnosis of jaundice. AIDS, Acquired immunodeficiency syndrome; ALT, alanine aminotransferase; AMS, altered mental status; AST, aspartate aminotransferase; CBC, complete blood count; HELLP, hemolysis, elevated liver enzymes, and low platelets; PT, prothrombin time; PTT, partial thromboplastin time.

of hepatic encephalopathy. Table 25.1 addresses the clinical stages of hepatic encephalopathy.

Laboratory Tests Figure 25.2 lists the laboratory tests that are helpful in the evaluation of a patient with jaundice. Serum gamma-glutamyl transpeptidase (GGT) rises in parallel with alkaline phosphatase in the setting of liver disease.1 Although alkaline phosphatase also can be elevated in diseases affecting bone or placenta, the concomitant increase in serum GGT or 5′-nucleotidase confirms a hepatic source. A reticulocyte count and evaluation of the peripheral blood smear may identify hemolysis. In cases of unexplained hepatocellular injury, a quantitative acetaminophen level may be helpful. Hepatitis serologies are indicated when the presentation suggests viral illness. Bedside stool guaiac testing should be considered assesses for the presence of gastrointestinal bleeding,

because patients with gastrointestinal bleeding will have an elevated ammonia level. This is secondary to the excess nitrogen load from the blood being converted into ammonia by the intestinal bacteria. Both glucose and ammonia metabolism can be altered in the presence of hepatocellular injury, and patients with altered mental status should have these levels determined. The degree of elevation in serum ammonia does not correlate directly with the level of hepatic encephalopathy. Ascitic fluid should be analyzed in patients with new-onset ascites and in those with established ascites but new complaints of fever, abdominal pain, gastrointestinal bleeding, hepatic encephalopathy, hypotension, or renal failure. Cell count and differential diagnosis, albumin, and total protein concentration are sufficient initial screening tests. If the etiology of the ascites is unknown, determining the serum ascites albumin gradient (SAAG) is helpful in determining the cause of ascites. The SAAG value is obtained by taking the albumin level in the ascetic fluid and subtracting it from the albumin level in

225

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Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

History • Viral prodrome • Liver disease • Alcohol/IVDU • Biliary tract surgery • Fever/abdominal pain • Pregnancy • Toxic or therapeutic ingestion • Malignancy • Recent or remote blood products • Occupational exposure • Cardiovascular disease • Recent trauma • Travel history

Physical Exam • Assess mental status • Abdominal tenderness/liver size • Hepatomegaly • Skin findings: Petechiae/purpura, caput medusae, spider angiomata • Ascites • Pulsatile mass

Lab Tests • CBC with platelets • PT/PTT • Hepatic panel: Transaminases, alkaline phosphatase, bilirubin with fractionation, amylase • ABG • Alcohol level/tox screen • Pregnancy test Fig. 25.2.  Pivotal points in the assessment of the jaundiced patient. ABG, Arterial blood gas; CBC, complete blood count; IVDU, intravenous drug use; PT, prothrombin time; PTT, partial thromboplastin time; tox, toxicology.

the serum. A value of greater than or equal to 1.1 g/dL is found in patients with portal hypertension. There are many causes of portal hypertension, including cirrhosis, liver failure, and heart failure. A value of less than 1.1 g/dL can be found in patients with lupus or pancreatitis. SAAG can diagnose portal hypertension, thereby rapidly narrowing the differential diagnosis. In the setting of suspected bacterial peritonitis, fluid culture is also necessary; Gram stain is rarely helpful. Ascites with a polymorphonucleocyte (PMN) count >250 mm3 is an indication for antibiotics (cefotaxime 2 grams). Two sets of blood cultures should be performed for patients with fever and jaundice. If there is evidence of gastrointestinal bleeding with hemodynamic instability or severe anemia, a type and crossmatch should be performed.

Imaging When indicated, abdominal imaging can help narrow the differential diagnosis of jaundice, especially in patients for whom biliary obstruction is a concern. The primary role of imaging is in the characterization of obstructive biliary disease. The first choice of study depends on the clinical presentation. Ultrasonography is generally superior for visualization of the gallbladder and ducts, but both ultrasonography and computed tomography (CT) are highly sensitive in diagnosing obstruction. The choice of imaging procedure depends on the pretest probability that there is biliary obstruction and that the obstruction is malignant. For patients with painless, progressive jaundice and without suspicion of hepatocellular injury (eg, hepatitis, alcoholism), malignant obstruction has a high pretest probability, so CT is the preferred method owing to its improved sensitivity in locating the site of the obstruction, determining resectability, and assessing for disseminated disease. Patients with a high likelihood of biliary disease and benign obstruction are best screened with ultrasonography. Ultrasonography is less expensive and less invasive than either magnetic resonance cholangiography or endoscopic ultrasound but has a lower sensitivity in identifying common bile duct stones.2 Ultrasonography with Doppler flow can detect obstruction in the hepatic, portal, and splenic veins. Sonographic features of cholecystitis are discussed in Chapter 90. In patients with low or intermediate clinical likelihood of mechanical obstruction, ultrasonography is the preferred initial modality to evaluate whether or not biliary obstruction is present. CT is preferred if the entire abdomen needs to be evaluated.

TABLE 25.1 

Clinical Stages of Hepatic Encephalopathy

DIAGNOSTIC ALGORITHM

CLINICAL INTELLECTUAL STAGE FUNCTION

NEUROMUSCULAR FUNCTION

Subclinical Normal examination findings, but work or driving may be impaired

Subtle changes in psychometric testing

Stage 1

Impaired attention, irritability, depression, or personality changes

Tremor, incoordination, apraxia

Stage 2

Drowsiness, behavioral changes, poor memory, disturbed sleep

Asterixis, slowed or slurred speech, ataxia

Stage 3

Confusion, disorientation, Hypoactive reflexes, nystagmus, somnolence, amnesia clonus, muscular rigidity

Stage 4

Stupor and coma

The differential diagnosis considerations for jaundice are broad; there are critical and emergent causes that should be ruled in or out in the ED (Table 25.2). Patients are considered in a critical state if they have jaundice and any of the following: altered level of consciousness, hypotension, fever with abdominal pain, or active bleeding. Further characterization of the cause of jaundice involves analysis of the laboratory studies (see Fig. 25.1). Indirect bilirubinemia points to a hematologic cause, whereas direct bilirubinemia indicates hepatobiliary pathology. Elevated direct bilirubin with transaminase elevation is indicative of hepatocellular inflammation or injury. Prolongation of prothrombin time (PT) indicates significant hepatocellular dysfunction. Elevated alkaline phosphatase with elevated direct bilirubin suggests extrinsic biliary obstruction. Patients with suspected biliary obstruction should undergo ultrasonography and/or CT in the ED to determine the cause and site of the obstruction. The most common causes of biliary obstruction are biliary stones, benign and malignant stenoses.3

Dilated pupils and decerebrate posturing; oculocephalic reflex

From Fitz G: Systemic complications of liver disease. In Feldman M, Sleisenger M, editors: Gastrointestinal and liver disease, Philadelphia, 1998, WB Saunders.

CHAPTER 25  Jaundice

TABLE 25.2 

Jaundice: Differential Diagnosis of Critical and Emergent Diagnoses SYSTEM

CRITICAL

EMERGENT

NONEMERGENT

Hepatic

Fulminant hepatic failure Toxin Virus Alcohol Ischemic insult Reye’s syndrome

Hepatitis of any cause with confusion, bleeding, or coagulopathy Wilson’s disease Primary biliary cirrhosis Autoimmune hepatitis Liver transplant rejection Infiltrative liver disease Drug induced (isoniazid, phenytoin, acetaminophen, ritonavir, halothane, sulfonamides) Toxin ingestion or exposure

Hepatitis with normal mental status, normal vital signs, and no active bleeding

Biliary

Cholangitis

Bile duct obstruction (stone, inflammation, stricture, neoplasm)

Systemic

Sepsis Heatstroke

Sarcoidosis Amyloidosis Graft-versus-host disease

Cardiovascular

Obstructing AAA Budd-Chiari syndrome Severe congestive heart failure

Right-sided congestive heart failure Veno-occlusive disease

Hematologic-oncologic

Transfusion reaction

Hemolytic anemia Massive malignant infiltration Inborn error of metabolism Pancreatic head tumor Metastatic disease

Reproductive

Preeclampsia or HELLP syndrome Acute fatty liver of pregnancy

Hyperemesis gravidarum

Post-traumatic hematoma resorption Total parenteral nutrition

Gilbert’s syndrome Physiologic neonatal jaundice

Cholestasis of pregnancy

AAA, Abdominal aortic aneurysm; HELLP, hemolysis, elevated liver enzymes, low platelets.

The identification of critical or emergent causes of jaundice requires the clinician to recognize patterns in the patient’s signs, symptoms, and ancillary testing. For instance, patients with a triad of jaundice, encephalopathy, and coagulopathy (international normalized ratio [INR] >1.5) have acute hepatic failure.4 Fever, right upper quadrant pain, and jaundice can indicate biliary obstruction with infection (eg, cholangitis, cholecystitis, or hepatitis). Ascites with abdominal tenderness raises suspicion for spontaneous bacterial peritonitis (SBP). Rapid onset of hepatomegaly and ascites can point to portal vein thrombosis (BuddChiari syndrome).

EMPIRICAL MANAGEMENT General supportive and specific therapies depend on the presumptive cause of the jaundice (Fig. 25.3). If coagulopathy is known or suspected, compressible sites and ultrasound guidance should be used for central venous access. Coagulopathy in the context of acute hemorrhage should be corrected with fresh frozen plasma, and blood volume repletion accomplished with packed red blood cells. If ascites is present and SBP is suspected, paracentesis is diagnostic. The presence of more than 250 polymorphonuclear cells per cubic millimeter of ascitic fluid is diagnostic for SBP. The empirical antibiotic of choice is a third-generation cephalosporin (eg, cefotaxime). If the patient has a history of cirrhosis and is taking a nonselective beta blocker, it should be discontinued because it has been shown to increase mortality in patients with SBP.5 Patients with jaundice and transaminases out of proportion to elevation of alkaline phosphatase have a hepatocellular injury

pattern. Treatment of hepatic encephalopathy is described in Chapter 90. Patients with fulminant hepatic failure should be admitted to the intensive care unit or transferred to a hospital with expertise in severe liver disease. Acetaminophen toxicity and indications for N-acetylcysteine therapy are discussed in Chapter 148. There is some evidence suggesting N-acetylcysteine offers a mortality benefit in non-acetaminophen induced acute liver failure. However, the evidence is weak and we do not recommend its use in this context.6,7 In the absence of liver failure, patients with encephalopathy, coagulopathy, or unstable vital signs should be admitted. There are no clear guidelines to indicate what level of hepatic or biliary dysfunction requires inpatient management. We recommend hospitalization or placement into observation status for patients with new-onset jaundice and transaminases approaching 1000 IU/L, bilirubin approaching 10 mg/dL, or evidence of coagulopathy, because these laboratory abnormalities suggest significant hepatic dysfunction. Patients with hepatitis or cholestatic jaundice may be managed as outpatients if they have a normal mental status, stable vital signs, ability to take oral fluids, no evidence of acute bleeding or significant coagulopathy, and no complicating infectious process. Intravenous fluids and antiemetics may be required in the ED. Alcohol and medications with potential hepatotoxicity, particularly acetaminophen, should be avoided. Fever, abdominal pain, and obstructive jaundice suggest ascending cholangitis (Fig. 25.4). Antibiotic recommendations for ascending cholangitis are discussed in Chapter 90. In addition to antibiotics, patients should be resuscitated with intravenous fluids as necessary and have any metabolic derangements corrected. Because biliary excretion of most antibiotics is compromised in the setting of obstruction, all patients will require biliary

227

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PART I 

Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

Patient with jaundice

Stabilize serious signs and symptoms

History • Viral prodrome • Alcohol/IVDU • H/O transfusion • Hepatotoxin exposure • Known hepatitis exposure • Pregnancy • Malignancy

History • Abdominal pain, fever, chills • Prior abdominal surgery • Older age Physical • High fever • RUQ abdominal tenderness • Palpable mass • Evidence of prior abd surgery

History • Trauma • Recent transfusion • Hematopoietic disorder Physical • Hematoma • Evidence of trauma • Paucity of exam findings

Physical • Hepatomegaly • Ascites • Asterixis • Encephalopathy • Spider angiomata • Caput medusae • Gynecomastia • Testicular atrophy • Excoriations Laboratory evaluation

Direct bili>indirect bili

Indirect bili>direct bili

• ± ↑ AST/ALT • ↑↑ Alk phos • ± ↑ Amylase

Suggests obstructive process

Direct bili>indirect bili • ↑↑ AST/ALT • Mild ↑ Alk phos • Normal amylase: Normal/ ↑ PT/PTT

• Normal LFT results • Abnormal hemogram

Suggests hepatocellular/cholestatic process (including fulminant hepatic failure)

Suggests hematologic process

Reassess and treat signs and symptoms

Radiographic evaluation • Ultrasonography or CT • Direct bile duct visualization • ERCP/surgical • GI and surgical consultations

• Observation • GI consultation • Remove toxins • Viral markers

• Type and crossmatch blood • Hematologic consultation

Fig. 25.3.  Management of the patient with jaundice. abd, Abdominal; Alk phos, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; bili, bilirubin; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; GI, gastrointestinal; H/O, history of; IVDU, intravenous drug use; LFT, liver function test; PT, prothrombin time; PTT, partial thromboplastin time; RUQ, right upper quadrant.

A

Systemic

Fever, leukocytosis, elevated CRP

B

Cholestasis Jaundice, abnormal liver function tests

C

Imaging Biliary dilitation, stricture, stone, stent

Diagnosis of cholangitis One item from A, B and C Fig. 25.4.  Tokyo Guidelines for diagnosis of acute cholangitis. CRP, C-reactive protein. (Redrawn from Kimura Y, Takada T, Kawarada Y, et al: Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Heptaobiliary Pancreat Surg 14: 15-26, 2007.)

CHAPTER 25  Jaundice

drainage. This generally should be done urgently but may be deferred 24 to 48 hours in stable patients. Drainage can be accomplished by endoscopic, percutaneous, or open surgical approaches. Prompt consultation with general surgery or gastroenterology is necessary to determine which approach and timing are appropriate. Patients with extrahepatic obstructive jaundice without cholangitis should also be admitted for drainage. Endoscopic retrograde cholangiopancreatography (ERCP) is therapeutic for benign obstructions, such as gallstones or strictures. Patients with obstructive jaundice caused by malignancy also benefit from biliary decompression, whether operative or endoscopic. Malignancy with jaundice heralds more advanced disease and increased morbidity and mortality. In general, patients with uncomplicated cholecystitis should receive intravenous fluids in the ED, parenteral analgesics and antiemetics as needed, and should be hospitalized. Antibiotic therapy for acute cholecystitis is discussed in Chapter 90. These patients should undergo emergent imaging and consultation with a surgeon or gastroenterologist.

Patients with confirmed or suspected choledocholithiasis, stones in the common bile duct, require admission for possible ERCP or cholecystectomy.13 Neither CT nor ultrasonography is 100% sensitive in identifying a common bile duct stone, but they are reasonably sensitive in identifying a dilated common bile duct, which is highly suggestive of obstruction. In patients with anemia, the management is based largely on the etiology. In immune-mediated hemolytic anemia, the decision to transfuse should be based on the patient’s ability to oxygenate and the ability to institute alternative treatments. An urgent hematology consultation is recommended (see Chapter 121). In the case of drug-induced hemolytic anemia, the mainstay of treatment involves removal of the offending agent. For patients with glucose-6-phosphate deficiency, blood transfusions are rarely indicated, and the focus of management should be on avoiding oxidative stressors and maintaining urine output to prevent renal failure. Patients with hemoglobinopathies rarely require transfusion therapy unless they have severe anemia without evidence of reticulocytosis. Fluids, oxygen, and analgesics can be given for an acute crisis.

KEY CONCEPTS • Clinical jaundice is usually not evident until the total serum bilirubin concentration rises above 2.5 mg/dL. • Bile metabolism may be altered when there is an overproduction of heme products (hemolysis); failure of the hepatocyte to take up, conjugate, and excrete bilirubin (hepatocellular dysfunction); or obstruction of biliary excretion into the intestine. • Unconjugated bilirubin that is not bound to albumin can cross the blood-brain barrier, causing adverse neurologic effects; conjugated bilirubin is not neurotoxic. • New-onset painless jaundice is the classic presentation for a neoplasm involving the head of the pancreas. • Jaundice is first apparent sublingually, in the conjunctiva and on the hard palate. • In cases of unexplained hepatocellular injury, a quantitative acetaminophen level may be helpful.

• If the etiology of the ascites is unknown, getting the serum ascites albumin gradient (SAAG) will aid in determining the cause of ascites and presence of portal hypertension. • Ultrasonography is the preferred initial modality to evaluate whether or not biliary obstruction is present, whereas CT is preferred if malignant obstruction is suspected or the entire abdomen needs to be evaluated. • Elevated direct bilirubin with transaminase elevation is indicative of hepatocellular inflammation or injury. • Diagnosis of spontaneous bacterial peritonitis (SBP) is >250 neutrophil count. Treatment is cefotaxime 2 grams. • Hyperemesis gravidarum can elevate liver enzymes up to 20 times the normal amount, including mildly elevated bilirubin. • Intrahepatic cholestasis of pregnancy is an idiopathic cause of jaundice that occurs in the third trimester.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 25  Jaundice

229.e1

REFERENCES 1. Lewis JR, Mohanty SR: Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci 55:560, 2010. 2. Williams EJ, et al: Guidelines on the management of common bile duct stones (CBDS). Gut 57:1004, 2008. 3. Bernal W, Auzinger G, Dhawan A, et al: Acute liver failure. Lancet 376:190, 2010. 4. Gines P, Angeli P, et al: EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis. J Heptol 53:397, 2010. 5. Mandorfer M, Bota S, Schwabl P, et al: Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology 146:1680–1690, 2014.

6. Hu J, Zhang Q, Ren X, et al: Efficacy and safety of acetylcysteine in “non-acetaminophen” acute liver failure: a meta-analysis of prospective clinical trials. Clin Res Hepatol Gastroenterol 39(5):594–599, 2015. 7. Sales I, Dzierba A, Smithburger PL, et al: Use of acetylcysteine for non-acetaminopheninduced acute liver failure. Ann Hepatol 12:6–10, 2013. 8. Maple J, et al: The role of endoscopy in the evaluation for suspected choledocholithiasis. Gastrointest Endosc 71(1):1–9, 2010.

CHAPTER 25: QUESTIONS & ANSWERS 25.1. A 56-year-old male presents with fever, distended abdomen, and a bedside ultrasound that shows ascites. A paracentesis is performed and the results indicate that the patient has spontaneous bacterial peritonitis (SBP). What daily medication should be stopped upon admission? A. Amlodipine B. Crestor C. Lactulose D. Metoprolol Answer: D. Beta Blocker use in pts with cirrhosis with SBP should be discontinued because it has been shown to increase mortality. 25.2. A 43-year-old female presents with 1 month of abdominal swelling. On examination she has a diffusely swollen abdomen with a fluid wave. The patient appears to have new onset ascites. In order to help determine the etiology, you obtain the serum ascites albumin gradient (SAAG). Which value is consistent with cirrhosis? A. 0.25 g/dL B. 0.5 g/dL C. 1 g/dL D. 1.5 g/dL Answer: D. A (SAAG) value of greater than or equal to 1.1 g/dL is found in patients with portal hypertension. There are many causes of portal hypertension, including cirrhosis, liver failure, and heart failure. 25.3. A 48-year-old male with a history of cirrhosis presents with 3 days of abdominal pain and fever. On examination, he is febrile and has an abdominal examination that is diffusely tender with guarding. The decision is made to do a paracentesis to evaluate for spontaneous bacterial peritonitis (SBP). What is the best treatment for SBP? A. Cefotaxime and discontinue beta blockers B. Ceftriaxone and dexamethasone

C. Ceftriaxone and discontinue beta blockers D. Ciprofloxacin and metronidazole Answer: A. The empirical antibiotic of choice is a thirdgeneration cephalosporin (eg, cefotaxime). If the patient has a history of cirrhosis and is taking a nonselective beta blocker, it should be discontinued because it has been shown to increase mortality in patients with SBP. 25.4. A 41-year-old male with a history of cirrhosis presents with fever, abdominal distension, and confusion. A paracentesis is performed in the evaluation of spontaneous bacterial peritonitis (SBP). What is the diagnostic criteria found in the ascetic fluid that confirms SBP? A. Neutrophil count >100 B. Neutrophil count >250 C. WBC >100 D. WBC >250 Answer: B. The presence of more than 250 polymorphonuclear cells per cubic millimeter of ascitic fluid is diagnostic for SBP. 25.5. A 55-year-old female presents with 1 month of diffuse abdominal swelling and pain. She reports a long history of alcohol use. In the evaluating this patient for jaundice, how high does the bilirubin have to be to become clinically apparent, and what area of the body does jaundice appear first? A. 2 mg/dL; nail beds B. 2 mg/dL; sclera C. 2.5 mg/dL; skin D. 2.5 mg/dL; sublingual Answer: D. Clinical jaundice is usually not evident until the total serum bilirubin concentration rises above 2.5 mg/dL. Jaundice is first apparent sublingually, in the conjunctiva and on the hard palate.

C H A P T E R 26 

Nausea and Vomiting Joshua Guttman PERSPECTIVE Nausea and vomiting are most commonly associated with primary gastrointestinal (GI) disorders but may also occur with systemic conditions. Nausea and vomiting may be of benign origin or may be associated with life-threatening conditions, and treatment is directed both at symptomatic relief and at the underlying cause. Vomiting may also result in serious sequelae (Table 26.1). Classification by duration and frequency of the vomiting (acute, recurrent, chronic, or cyclic) may assist in determination of the underlying cause.

Epidemiology Nausea and vomiting represent 4% of emergency department (ED) chief complaints and often are present in patients whose chief complaint is abdominal pain, among many other conditions. The most common causes of nausea and vomiting are GI disorders. Nausea and vomiting may also represent disorders outside the GI tract, such as hyperemesis gravidarum, intracranial lesions and infections, myocardial infarction, diabetic ketoacidosis, and drug toxicities.

Pathophysiology The act of vomiting is divided into three phases: nausea, retching, and actual vomiting. Nausea may occur without retching or vomiting, and retching may occur without vomiting. The exact neural pathways mediating nausea are not clear, but they are likely to be the same pathways that mediate vomiting. Mild activation of the pathways may result in nausea, whereas more intense stimulation results in vomiting. During nausea there is an increase in tone in the musculature of the duodenum and jejunum, with a concomitant decrease in gastric tone; this leads to reflux of intestinal contents into the stomach. There is often associated hypersalivation, repetitive swallowing, and tachycardia. Retching is characterized as rhythmic, synchronous contractions of the diaphragm, abdominal muscles, and intercostal muscles that occur against a closed glottis, without the expulsion of gastric contents. Vomiting is the forceful expulsion of gastric contents through the mouth. There is contraction of the external oblique and abdominal rectus muscles, and the hiatal portion of the diaphragm relaxes; this increases the pressure in the abdominal and the thoracic compartments. There is contraction of the pyloric portion of the stomach. Simultaneously, there is relaxation of the gastric fundus, cardia, and upper esophageal sphincter as the vomitus is brought up and out the mouth. The glottis closes to prevent aspiration. The complex act of vomiting is coordinated by the vomiting center located in the lateral reticular formation of the medulla. The efferent pathways from the vomiting center are mainly through the vagus, phrenic, and spinal nerves (Fig. 26.1). These pathways are responsible for the integrated response of the diaphragm, intercostal muscles, abdominal muscles, stomach, and 230

esophagus. The vomiting center is activated by afferent stimuli from a variety of sources. These include (1) visceral afferent impulses directly from the GI tract; (2) visceral afferent impulses from outside the GI tract, including the biliary system, peritoneum, pharynx, genitalia, and heart; (3) extramedullary central nervous system (CNS) afferents, including the vestibular system; and (4) the chemoreceptor trigger zone (CTZ) (Fig. 26.2), which is located in the area postrema, the floor of the fourth ventricle. Part of this area is located outside of the blood-brain barrier, enabling it to respond to endogenous and exogenous substances that activate vomiting (see Fig. 26.2). The discovery of various neurotransmitters and their receptor sites within the medulla has improved the understanding and development of therapeutic agents. The CTZ area is rich in dopamine D2 receptors and serotonin receptors, and the lateral vestibular nucleus is rich with cholinergic and histamine receptors. Serotonin receptors are also widely found in the GI tract. These receptor sites are targets for the various medications that are used to treat nausea and vomiting.

DIAGNOSTIC APPROACH Differential Diagnosis Considerations The differential diagnosis for nausea and vomiting is particularly broad in scope; almost any organ system can be involved. Acute vomiting is defined as episodic vomiting that occurs for less than 1 week and is associated with acute conditions, whereas chronic vomiting, which occurs for a period longer than 1 week, is associated with motility disorders, effects of systemic treatments (such as for cancer), neuropsychiatric conditions (eg, bulimia) and neurologic conditions. Discrete episodes of intractable vomiting with intervening asymptomatic periods are considered cyclic. Common causes of nausea and vomiting are outlined in Table 26.2, and a differential diagnosis is presented in Tables 26.3 and 26.4.

Pivotal Findings Symptoms A thorough history, including past medical history, medications, and social history will generally elicit the etiology of vomiting. The content and color of the vomitus may help determine its cause (Table 26.5). Although coffee ground emesis usually suggests a slower bleeding rate than bright red blood, this cannot be relied upon in all cases. The history should be directed at assessing for both the causes of vomiting, as well as its sequelae. Timing and duration of the vomiting may be important. Symptoms occurring primarily in the morning may suggest increased intracranial pressure. Delayed vomiting more than 1 hour after eating suggests gastric outlet obstruction or gastroparesis. Vomiting of material eaten more than 12 hours previously is pathognomonic for outlet obstruction. Associated symptoms are helpful: Vomiting with diarrhea is generally due to an infectious gastroenteritis but may also be

CHAPTER 26  Nausea and Vomiting

TABLE 26.1 

Potential Sequelae of Vomiting SEQUELAE

ETIOLOGY

Hypovolemia

Loss of water and sodium ions in vomitus

Metabolic alkalosis

Loss of hydrogen ions in vomitus

Hypokalemia

Loss of potassium in urine

Mallory-Weiss tears

Forceful retching or vomiting causing a 1 cm to 4 cm tear in the mucosa and submucosa; the cause of 3% of deaths from upper GI bleeds

Boerhaave’s syndrome

Perforation of the esophagus due to increased intraesophageal pressure during forceful retching or vomiting There is free passage of esophageal contents into the mediastinum, causing a chemical mediastinitis, leading to superinfection, sepsis, multiorgan failure, and death It is a surgical emergency The mortality rate is 50% if surgical repair is not performed within 24 hours

Aspiration pneumonitis and pneumonia

A concern in patients with baseline poor mental status and pulmonary findings after an episode of vomiting

GI, Gastrointestinal.

GIT receptors

Chemoreceptor trigger zone

Vestibular center

Receptors outside GIT

Vomiting center Fig. 26.1.  Vomiting process. GIT, Gastrointestinal tract.

present in mesenteric ischemia or other GI surgical emergencies. Vomiting with abdominal pain is generally caused by diseases of the GI system. Chronic headaches with nausea and vomiting should raise suspicion of elevated intracranial pressure. Vomiting without preceding nausea is typical of CNS pathology. The social history should include inquiries about alcohol or other substance use. The past medical history will reveal the presence of any GI disease or previous surgeries. Finally, a thorough medication list, including over-the-counter drugs and supplements, should be elicited. A history of similar episodes should be elicited. A history of stereotypical episodes of nausea and vomiting lasting hours to days, with symptom-free intervals may lead to a diagnosis of cyclical vomiting syndrome. In patients with a history of cyclical vomiting, heavy, chronic use of cannabis is important to elicit, because it may lead to a diagnosis of cannabis hyperemesis syndrome.1 Symptoms are similar to cyclic vomiting syndrome; however patients will note temporary relief with a hot shower.1 Onset of the syndrome is often delayed years after chronic marijuana use has begun.

Signs The examination should begin with an overall assessment of the patient’s status, including an assessment for volume depletion. The history will direct the examination to the appropriate body

systems (Table 26.6). The eye examination may reveal nystagmus, which may indicate cerebellar pathology, peripheral vertigo, or drug intoxication. Oral examination may reveal loss of dental enamel commonly seen with bulimia. Abdominal examination, with appropriate testing for occult blood in the stool, may reveal ascites, distention, hernias, abdominal tenderness and masses, or hyperactive or hypoactive bowel sounds. Neurological examination (including funduscopic examination) may be important if a central cause is considered. Provocative testing in patients with suspected benign paroxysmal positional vertigo may elicit vomiting or nystagmus, suggesting this diagnosis (see Chapter 16). Symptoms of depression or anxiety may suggest a psychiatric origin to the vomiting; however, this is a diagnosis of exclusion and rarely is made in the ED.

Ancillary Studies Testing is determined by the differential diagnosis based on the history and physical examination: • Serum electrolytes and creatinine: Measurement of serum electrolytes and creatinine is not indicated in most cases of vomiting. Patients with a history of prolonged or severe vomiting, or with clinical evidence of dehydration requiring volume replacement, should undergo electrolyte testing to assess for hypokalemia, hypochloremia, contraction alkalosis, or other sequelae of protracted vomiting. Creatinine may help assess pre-renal dysfunction. • Serum lipase: Lipase determination is indicated in cases of suspected pancreatitis, based on the patient’s complaint of (often severe) epigastric pain and the presence of tenderness. • Urine tests: A urine pregnancy test should be performed in all women of childbearing age with nausea and vomiting. A urine analysis may show leukocyte esterase and nitrites as evidence of an urinary tract infection. Ketones may support a diagnosis of diabetic ketoacidosis or prolonged starvation state. Hematuria indicates a possible renal calculus. • Liver function and ammonia tests: Liver function tests are indicated in cases of suspected hepatitis or biliary disease. Ammonia testing is useful if liver failure is suspected. • Serum drug levels: Serum drug levels may be important in determining the cause of nausea and vomiting in patients on digoxin, salicylates, or acetaminophen, especially in elders who are taking medication without supervision. Specific serum drug levels should be drawn only if knowledge of the drug level would alter the patient’s management. • Ultrasound: A bedside abdominal ultrasound evaluates for cholelithiasis, cholecystitis, renal colic, appendicitis, and small bowel obstruction (SBO). Additionally, an assessment of the inferior vena cava may be helpful in monitoring patients with suspected dehydration. • Abdominal computed tomography (CT): Abdominal CT scan is indicated in patients with a suspected SBO or surgical cause, such as appendicitis, when not diagnosed by ultrasound. • Cranial imaging: CT or magnetic resonance imaging (MRI) may be indicated to evaluate for intracranial etiologies of nausea and vomiting. When occipital headache is accompanied by hypertension and vomiting, a CT or an MRI should be obtained to evaluate for cerebellar hemorrhage. For other posterior fossa pathologies, such as cerebellar infarction, MRI is preferred. • Chest imaging: A chest x-ray may reveal subdiaphragmatic air in a patient with a perforated viscus, but abdominal CT is far superior when perforation or other serious intra-abdominal pathology is suspected. For patients with suspected Boerhaave’s syndrome, a chest radiograph is used to assess for a pneumomediastinum, but, again, CT is the preferred modality when this condition is suspected.

231

232

PART I 

Fundamental Clinical Concepts  |  GI tract Heart Testicles

Medications

SECTION Two 

Vagus and sympathetic nerves

Signs, Symptoms, and Presentations

Afferent inputs

Higher-brain centers

Pain, sights, tastes, smells

Receptors

Phenothiazines

Antihistamines

Anticholinergics

Histamine receptors

Muscarinic receptors

Dopamine

Prokinetic agents

Emetic center Brainstem Antihistamines

Histamine

Anticholinergics

Muscarinic Endogenous molecules

Serotonin agonists

Chemoreceptor trigger zone Area postrema

Vestibular nuclei

Exogenous molecules

Labyrinth

Drugs, uremia, calcium, radiation, cancer chemotherapy, bacterial toxins

5-Hydroxytryptamine3

Cannabinoids

Cannabinoid

Neurokinin antagonist

Substance P

Fig. 26.2.  Pathophysiology of nausea and vomiting. GI, Gastrointestinal.

DIAGNOSTIC ALGORITHM Patients presenting with vomiting should be rapidly assessed to ascertain if a potentially critical diagnosis is present (see Table 26.4). A diagnostic algorithm is shown in Figure 26.3. The evaluation begins by determining whether the patient is stable or unstable. If the patient is deemed to be unstable or critically ill, oxygenation is provided as needed, intravenous (IV) access and monitoring are is established, and any vital sign disturbances are addressed. A brief history and directed physical examination are performed concomitantly to determine the most likely causes, with evaluation and management prioritized to those causes.

If the patient is stable, a more thorough history and physical examination is performed. Empirical therapy, laboratory and radiologic testing are directed by results of the history and examination. Patients with volume depletion requiring IV replacement require serum electrolyte and renal function determination. In addition, patients with associated severe abdominal pain receive IV analgesics and antiemetics as needed, and have additional blood sent for liver function tests and lipase. If sepsis or shock is considered, obtain a serum lactate level. Most patients with severe pain and tenderness will require abdominal imaging. Patients with a history of abdominal surgery and decreased stool output are evaluated for SBO. Patients with severe headache or neurological deficits (not thought to be due to a primary headache disorder)

TABLE 26.2 

Disorders Commonly Associated With Vomiting CLASS

HISTORY

PREVALENCE

PHYSICAL EXAMINATION

USEFUL TESTS

COMMENTS

Nausea and vomiting of pregnancy (NVP)

Acute

Vomiting may occur in the morning or throughout the day. Associated breast tenderness. NVP typically starts in weeks 4 to 7, peaks in weeks 10 to 16, and disappears by week 20. Vomiting that begins after week 12 or continues past week 20 should prompt a search for another cause.

Very common Affects 75% of all pregnancies

Benign abdomen

Urine pregnancy test Serum electrolytes, urine ketones to exclude hyperemesis gravidarum

Consider NVP in all females of childbearing age. Prognosis for mother and infant is excellent. NVP is associated with a decreased risk of miscarriage, fetal growth retardation, and fetal mortality.

Hyperemesis gravidarum

Acute

Severe, protracted form of NVP. No universally accepted definition of the disease. Generally accepted hallmarks include 5% weight loss, ketonuria, and electrolyte disturbance. Hyperemesis is associated with multiple gestation, molar pregnancy, and nulliparity.

Uncommon Affects 55 years old, WBCs >16,000/mm3, glucose >200 dL, base deficit >4, LDH >350 IU/L, AST >250 U/L Within 48 hours—Hct drop of 10%, BUN >2 mg/dL, PO2 4 L

Appendicitis

Acute

Abdominal pain classically begins in periumbilical region and later moves to right lower quadrant. Anorexia is common.

Common

Localized tenderness over right lower WBCs quadrant. Ultrasound Low-grade fever may be present. Abdominal CT

Early appendicitis can be a difficult diagnosis to make. It is still frequently missed on the first physician encounter.

Bowel obstruction

Acute Chronic

Classically, abdominal pain consists of intermittent cramps occurring at regular intervals. The frequency of the cramps varies with the level of the obstruction; the higher the level, the more frequent the cramps. The location of the pain also varies with the level of the obstruction; high obstruction causes epigastric pain, midlevel obstruction causes periumbilical pain, colonic obstruction causes hypogastric pain.

Common

Abdominal distention, mild diffuse tenderness, and high-pitched “tinkling” bowel sounds may be present. Thorough search for hernias should be performed.

Electrolytes Lactate Abdominal ultrasound Abdominal CT

Adhesions, hernias, and tumors account for 90% of bowel obstructions. Other causes include intussusception, volvulus, foreign bodies, gallstone ileus, inflammatory bowel disease, stricture, cystic fibrosis, and hematoma.

Carbon monoxide (CO) poisoning

Acute

Headache is usually present. CO poisoning often occurs during winter months when furnaces are turned on. Family members may have similar symptoms if they also have been exposed.

Uncommon

No reliable signs of early CO poisoning

CO level

Because CO is a tasteless, odorless gas, patients may not realize they have been exposed. It is important to keep a high index of suspicion during the cold months.

Boerhaave’s syndrome

Acute

Patients may have neck, chest, or epigastric pain. Forceful, protracted vomiting usually causes the tear. Most cases follow a bout of heavy eating and drinking. Other reported causes include childbirth, defecation, seizures, and heavy lifting.

Uncommon

Tachypnea, tachycardia, and hypotension may be present. Escaped air from the esophagus may produce subcutaneous emphysema. Air in the mediastinum produces a “crunching” sound as the heart beats (Hamman’s sign).

CXR may show pleural effusion, widened mediastinum, pneumothorax, or pneumomediastinum. Esophagogram with water-soluble contrast is definitive.

The classic presentation includes forceful vomiting, severe chest pain, subcutaneous emphysema, and multiple CXR findings. There is a growing body of evidence that most cases do not have this “classic” picture. In more subtle presentations, the diagnosis can be difficult to make.

AST, Aspartate aminotransferase; β-hCG, beta-human chorionic gonadotropin; BUN, blood urea nitrogen; CT, computed tomography; CXR, chest radiography; ECG, electrocardiogram; ETOH, ethyl alcohol; Hct, hematocrit; LDH, lactate dehydrogenase; LFT, liver function test; NSAID, nonsteroidal antiinflammatory drug; PO2, partial pressure of oxygen; RUQ, right upper quadrant; VBG, venous blood gases; WBC, white blood cell.

Signs, Symptoms, and Presentations

COMMENTS

“Fruity” breath odor results from serum acetone. Tachypnea occurs with attempts to “blow off” carbon dioxide to compensate for metabolic acidosis. Signs of dehydration may be present. Severe cases often manifest with altered mental status or coma.

SECTION Two 

USEFUL TESTS

Common Polydipsia and polyuria occur early. Without treatment, altered mental status and coma may develop. In patients with long-standing diabetes, DKA may be triggered by infection, change in medication trauma, MI, or surgery.

Fundamental Clinical Concepts  | 

PHYSICAL EXAMINATION

Diabetic Acute ketoacidosis (DKA)

PART I 

DISORDER

CHAPTER 26  Nausea and Vomiting

TABLE 26.3 

TABLE 26.4 

Causes of Nausea and Vomiting

Differential Diagnosis of Nausea and Vomiting

ACUTE

CHRONIC

EPISODIC

CYCLICAL

Ischemic bowel

Chronic pancreatitis

Cholelithiasis

Cyclical vomiting syndrome

Ruptured viscus

Gastroparesis

IBD

Cannabinoid hyperemesis syndrome

Cholangitis

PUD

IBS

Cholecystitis/ cholelithiasis

Gastritis

Gastritis

Bowel obstruction

Gastric outlet obstruction

BPPV

Appendicitis

CNS tumor

Motion sickness

Peritonitis

Raised ICP

Chemotherapy

Acute pancreatitis

Migraine

DKA

PUD

Drug toxicity

Uremia

Gastroenteritis

Bulimia

Pregnancy

Hepatitis

Carbon monoxide

Food poisoning

Pregnancy

ETIOLOGIC CATEGORY

Gastrointestinal Boerhaave’s (GI) syndrome Ischemic bowel GI bleeding Ruptured viscus Cholangitis

Neurologic

Intracerebral bleed Meningitis

Drug withdrawal

Sepsis

Meningitis CNS tumor

Pregnancy

Drug toxicity

Thyroid disorder Adrenal insufficiency Uremia Hyperemesis Nausea and gravidarum vomiting of pregnancy

Acetaminophen Aspirin

Digoxin Theophylline

Therapeutic drug use

Aspirin Antibiotics Erythromycin Ibuprofen Chemotherapy

Carbon monoxide Alchohol intoxication

Drugs of abuse

Alcohol Narcotics withdrawal Narcotic withdrawal Alcohol

Alcohol withdrawal BPPV, Benign paroxysmal peripheral vertigo; CNS, central nervous system; DKA, diabetic ketoacidosis; IBD, inflammatory bowel disease; IBS, inflammatory bowel syndrome; ICP, intracranial pressure; PUD, peptic ulcer disease.

will have neuroimaging performed, and patients with suspected myocardial infarction will have an electrocardiogram (ECG) and cardiac enzyme testing. If an emergent cause of nausea and vomiting is confirmed or highly suspected based on the initial evaluation and ancillary testing, then appropriate management is undertaken. Patients who are generally well and have a low likelihood of a serious cause, whose symptoms are controllable, but for whom the diagnosis is still unclear, should have follow-up arranged within 24 to 48 hours for reevaluation if symptoms persist or more urgently if symptoms worsen or a new, concerning symptom, such as blood in the stool or vomit, fever, or localized pain, develops. Patients who have a suspected or confirmed nonemergent diagnosis are treated with antiemetic medications, with specific

Migraine

DKA

Pyelonephritis Myocardial infarction

Gastric outlet Gastritis obstruction Pancreatitis Gastroparesis Cholecystitis Peptic ulcer disease Bowel Inflammatory obstruction bowel disease or ileus Biliary colic Appendicitis Hepatitis Peritonitis Gastroenteritis Food poisoning Inflammatory bowel syndrome Spontaneous bacterial peritonitis

Endocrine

Renal colic Gonadal torsion

NONEMERGENT DIAGNOSES

Cerebellar infarct Raised ICP BPPV Suppurative labyrinthitis

Cerebellar infarct Drug toxicity

EMERGENT DIAGNOSES

Vestibular

Intracerebral bleed Meningitis

CRITICAL DIAGNOSES

Genitourinary

Gonadal torsion

Urinary tract infection Nephrolithiasis

Miscellaneous

Myocardial infarction Sepsis Organophosphate poisoning

Carbon monoxide Electrolyte disorders

Motion sickness Labyrinthitis

BPPV, Benign paroxysmal peripheral vertigo; CNS, central nervous system; DKA, diabetic ketoacidosis; ICP, intracranial pressure.

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236

PART I 

Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

TABLE 26.5 

TABLE 26.6 

Differential Diagnosis Based on Content of Vomitus

Physical Examination of the Patient With Nausea and Vomiting

COLOR/CONTENT OF VOMITUS

DIAGNOSES

Bright red blood

Peptic ulcer Gastritis Esophageal varices Aortoenteric fistula Esophageal rupture Duodenal or gastric tumors Mallory-Weiss syndrome Dieulafoy’s lesion Foreign body

Coffee grounds

Peptic ulcer Gastritis Esophageal varices Duodenal or gastric tumors Mallory-Weiss syndrome

Undigested food

Gastric outlet obstruction Achalasia Esophageal stricture Foreign body

ORGAN SYSTEM

FINDING

SUGGESTED DIAGNOSES

General

Poor skin turgor Dry mucous membranes

Dehydration

Vital signs

Fever

Gastroenteritis, cholecystitis, appendicitis, hepatitis Bowel perforation Dehydration

Tachycardia, orthostatic changes HEENT

Nystagmus

Papilledema

Labyrinthitis Vertebrobasilar insufficiency Cerebellar infarct or bleed CPA tumor Increased ICP from CNS tumor or bleeding

Neck

Goiter

Thyroid disease

Lungs

Rales

Pneumonia

Feces

Small bowel obstruction Large bowel obstruction

Heart

Arrhythmia Murmur

Acute myocardial infarction or other cardiac pathology

Bilious (adults)

Small bowel obstruction Large bowel obstruction

Abdomen

Abdominal distention

Bowel obstruction, gastroparesis Gastric outlet obstruction Bowel obstruction

management directed at the underlying cause. Patients with cyclical or recurrent vomiting syndromes do not require any particular diagnostic testing in the ED and should be managed in consultation with the patient’s primary care physician. However, care should be taken to avoid anchoring on the patient’s previous diagnosis of cyclical vomiting syndrome and should seek corroborative information from the patient, the medical record, family members, or the primary physician to ensure that the pattern of the presentation fits the patient’s syndrome and to exclude alternate emergent causes of vomiting.

Peristaltic waves High-pitched bowel sounds Decreased bowel sounds Hernias or surgical scars Peritoneal signs Neurologic

Abnormal mental status Cerebellar findings Cranial nerve findings

Ileus Possible bowel obstruction Appendicitis, cholecystitis Perforated viscus CNS pathology

CNS, Central nervous system; CPA, cerebellopontine angle; HEENT, head, eyes, ears, nose, throat; ICP, intracranial pressure.

EMPIRICAL MANAGEMENT Symptomatic relief of nausea, vomiting, or pain should not await identification of the underlying cause. Decreased oral intake with concomitant fluid loss (by vomiting) causes dehydration. If the patient is mildly or moderately dehydrated and is able to take oral liquids, a solution containing sodium, carbohydrate, and water is recommended. Many sports drinks contain the proper balance of these elements. Patients who are severely dehydrated or in whom intake of oral fluids is not possible or is contraindicated should be given IV crystalloid solution (usually normal saline) and electrolyte abnormalities corrected. Placement of a nasogastric tube is not indicated, except in patients with bowel obstruction. The need for antiemetics and the response to therapy may be measured with scales similar to those used for pain assessment, such as the visual analog scale and the verbal categorical scale. Patients presenting to the ED with nausea or vomiting may have a known etiology with specific treatment aimed toward treating the underlying cause. These are discussed in the Specific Situations section. For the patient with either non-obstructive GI causes or undifferentiated nausea and vomiting, there is very limited evidence to support one agent over another. A large, randomized trial of ED patients with undifferentiated nausea and vomiting found no

difference in the primary outcome of reduction of symptoms between metoclopramide 20 mg IV, ondansetron 4 mg IV, or saline placebo.2 There was a decreased need for rescue antiemetics in patients who received metoclopramide; however, these patients also had more side effects. These findings were similar to previous smaller trials, where various commonly used medications were compared and no statistically significant difference between the various medications were found.2-3 Children, pregnant patients, and hemodynamically unstable patients were excluded from all studies. When comparing the raw data of all the randomized controlled trials, decreased nausea scores were associated with increasing amount of IV saline given.2 Although this has not been formally studied, IV fluids alone may be an effective treatment for nausea and vomiting. The pharmacologic management of patients with nausea and vomiting is outlined in Table 26.7, and a management algorithm is shown in Figure 26.4. To allow the physician to tailor the appropriate choice for each patient, the pharmacologic therapies available may be classified into serotonin antagonists, histamine antagonists, muscarinic antagonists, and dopamine antagonists. The serotonin antagonists, particularly ondansetron, are considered first line therapies for most cases of nausea and vomiting in the ED, except in specific situations discussed later. Other

Vital signs, primary survey, basic history

Unstable or catastrophic cause likely

Severe abdominal pain or tenderness

Consider ICH, posterior CVA, meningitis, drug ingestion

Consider raptured viscus, mesenteric ischemia, ectopic pregnancy, SBO, DKA

Airway protection CT head; consider LP if CT head normal

Fingerstick glucose electrolytes, pregnancy test, lactate, emergent early surgical consultation

Obtain comprehensive history and physical

Chest pain or SOB

Consider MI or Boerhaave's

Recurrent

Chronic

ECG troponins portable CXR

Consider CVS or CHS electrolytes consultation with PCP

History of regurgitating stomach contents

Acute (see Fig 26.3B)

Consider imaging for gastric outlet obstruction

A Fig. 26.3.  A and B, Approach to the patient with nausea and vomiting. BMP, Basic metabolic panel; CT, computed tomography; CVA, Cerebrovascular accident; CVS, cyclical vomiting syndrome; CXR, chest x-ray; DKA, diabetic ketoacidosis; ECG, electrocardiogram; ICH, intracranial hemorrhage; LFT, liver function test; LP, lumbar puncture; MI, myocardial infarction; PCP, phencyclidine; SBO, small bowel obstruction; SOB, shortness of breath; US, ultrasound; VBG, venous blood gas. Continued

CHAPTER 26  Nausea and Vomiting

Neurological deficits or comatose

Stable

237

238 PART I 

Testicular pain

Cranial imaging if central cause likely

ECG troponin CXR

Pregnant

Flank pain

Urinalysis, BMP, HCG levels, consider ultrasound

Drug ingestion

Drug level, VBG, electrolytes, LFT

Obstipation, decreased bowel movements, distention, abdominal tenderness

Abdominal tenderness

Neurological symptoms or signs

Cranial imaging of considering causes other than migraine

Diarrhea with mild or no abdominal pain

Urinalysis

US or CT if nephrolithiasis considered

B

Abdominal pain

Image for SBO, consider early surgical consultation Fig. 26.3., cont’d

Electrolytes, LFTs, consider abdominal imaging

No workup needed if simple gastroenteritis; consider electrolytes if severe

Adnexal pain or tendered

Pregnancy test Ultrasound

Signs, Symptoms, and Presentations

Chest pain or SOB

SECTION Two 

Ultrasound Urology consultation

Vertigo

Fundamental Clinical Concepts  | 

Acute

CHAPTER 26  Nausea and Vomiting

TABLE 26.7 

Commonly Used Medications for the Treatment of Nausea and Vomiting MEDICATION

CLASS

SITE OF ANTIEMETIC ACTION DOSAGE

ADVERSE EFFECTS

Ondansetron (Zofran)

Serotonin antagonist

5-HT3 receptor at CTZ and vagus Adult: Usual: 4 to 8 mg IV May cause headache, dizziness, and nerve terminal in GIT single dose, may go up to 16 musculoskeletal pain.

Metoclopramide (Reglan)

Dopamine and serotonin antagonist

D2 and 5-HT3 receptors in CTZ. D2 in stomach and LES

Prochlorperazine (Compazine)

Promethazine (Phenergan)

Adult: 10 to 20 mg IM or IV, may repeat every 6 hours

May cause dystonic reactions, tardive dyskinesia (black box warning), neuroleptic malignant syndrome, restlessness, drowsiness, diarrhea.

Dopamine antagonist D1 and D2 receptor in CTZ

Adult: 5 to 10 mg IM or PO; 2.5 to 10 mg IV every 4 hours as needed; 25 mg by rectum every 12 hours as needed

May cause lethargy, hypotension, extrapyramidal effects, dystonic reactions, sedation, and feelings of restlessness. Rarely neuroleptic malignant syndrome, blood dyscrasias, and cholestatic.

Antihistamine

H1 receptor in CTZ, minimal D2

Adult: 12.5 to 25 mg IV, IM, PO, or by rectum every 4 hours as needed

Extravasation may cause severe tissue injury (black box warning). May cause sedation, dry mouth, dizziness, blurred vision.

H1 receptor in GIT and CTZ

25–50 mg IV, IM, or PO every 6 hours as needed

Drowsiness, light-headedness.

Dimenhydrinate Antihistamine (Dramamine, Gravol)

CTZ, Chemoreceptor trigger zone; GIT, gastrointestinal tract; IM, intramuscularly; IV, intravenously; LES, lower esophageal sphincter; PO, per os (by mouth).

serotonin antagonists (such as, granisetron) are available but have not been studied in the ED and therefore cannot be recommended over ondansetron. The initial dose of ondansetron is 4 to 8 mg IV. A single dose of up to 16 mg is considered safe in the non-elderly population. In the elderly, it is recommended that the initial dose should not exceed 8 mg infused over at least 15 minutes. Ondansetron at higher doses and faster infusion rates may cause QT prolongation in older patients.4 For most patients, there are few or no side effects of the serotonin receptor antagonists and, if they occur, are mild. If the patient is known to have a long QT or is at risk of developing long QT syndrome, then it is best to reserve ondansetron as a second line agent. Ondansetron has also been associated with serotonin toxicity when given concurrently with other serotonergic agents.5 Metoclopramide (Reglan) is the other first line agent for use in the ED. Metoclopramide is an excellent general-purpose antiemetic. As a prokinetic agent, it is useful in patients with gastroparesis and other dysmotility syndromes. The initial dose of metoclopramide is 10 to 20 mg IV/intramuscular (IM). The phenothiazines, prochlorperazine (Compazine) and promethazine (Phenergan), have historically been first-line agents and are still widely used as general-purpose antiemetics. In one study, prochlorperazine was found to be a superior to promethazine. Although both of these agents are sedating, promethazine is more sedating than prochlorperazine and is associated with more extra-pyramidal effects. Due to increased side effects, these medications are considered third line in the ED. The anti-psychotic medication, droperidol, is also considered effective in the treatment of nausea and vomiting. In one randomized control trial, droperidol was found to be superior to other first-line agents.6 Droperidol has generally fallen out of favor in the ED due to the black box warning on QT prolongation. An ECG should be performed prior to administration to check for QT prolongation. A dose of 1.25 mg IV is sufficient in most patients. The dose may be repeated in 60 minutes if needed. For patients with undifferentiated nausea and vomiting or those without specific causes listed in the special situations below, start with ondansetron 4 mg IV. It is inexpensive and generally

well tolerated. IV crystalloid should also be given if there are no contraindications. A repeat 4 mg IV dose should be given initially if there is no response. If there is there is still an inadequate response, than metoclopramide 10 mg IV should be given, with a repeat dose of metoclopramide after 30 minutes, if needed. A poor response to the above antiemetics should prompt the clinician to consider an underlying mechanical GI obstruction inducing the symptoms, and this should be addressed if present. If ondansetron and metoclopramide have not been effective and a mechanical obstruction is unlikely, consider using droperidol in a patient at low risk of adverse effects from the droperidol. Begin with 1.25 mg IV, and the dose may be repeated if no effect is seen within 30 minutes. If droperidol is not considered safe, then the next drug of choice should be prochlorperazine. A single dose of 10 mg IV is appropriate. If sedation is desired, promethazine may be given prior to trying prochlorperazine. For most patients, begin with promethazine 12.5 mg IV, which may be repeated in 30 minutes if tolerated. In patients who may not tolerate sedation, such as elderly patients, those with underlying respiratory diseases, or those with other sedating medications, begin at 6.25 mg IV, which may be incrementally increased as tolerated. Dimenhydrinate may be given instead of promethazine, but they should not be given together due their sedating effects. Finally, patients who remain highly symptomatic after these medications should be admitted to the hospital for continued management and evaluation for the etiology of the vomiting.

Special Situations Opioid-Induced Vomiting Antiemetic medications are frequently used in the mistaken belief that they reduce the incidence of nausea and vomiting when opioid analgesics are administered in the ED for pain control. Studies have demonstrated that the incidence of nausea and vomiting related to opioid administration in the ED is low and that these medications have little efficacy in reducing nausea and vomiting.

239

240 PART I 

Basic history, primary survey, vital signs

Fundamental Clinical Concepts  | 

Constable IV fluids, airway protection, metoclopramide IV or ondansetron IV, treat underlying cause

Stable

Diagnosis known

Diagnosis unknown

SECTION Two 

CVS or CHS

Pregnant

Migraine, IV fluids, metoclopramide IV or prochlorperazine IV, consider droperidol

IV fluids, electrolyte replacement, analgesics, antiemetic, benzodiazepine Hyperemesis gravidarum

NVP

IV fluids, ondansetron IV or metroclopramide IV, electrolyte replacement

Vitamin B6 ginger metoclopramide PO or ondansetron PO

Chemotherapy induced

Pediatric gastroenteritis

IV fluids, electrolyte replacement, IV ondansetron

Mild to moderate dehydration

Severe dehydration

Oral rehydration, ondansetron PO

IV fluids, IV ondansetron

Other causes; consider IV fluids, antiemetic with consideration of cost and side effects

Fig. 26.4.  Management algorithm for the patient with nausea and vomiting. CHS, cannabinoid hyperemesis syndrome; CVS, cyclical vomiting syndrome; IV, intravenous; NVP, nausea and vomiting of pregnancy; PO, per os (by mouth).

Vertigo

Meclizine, dimenhydrinate (IV/PO) or benzodiazepene (IV/PO)

Signs, Symptoms, and Presentations

Consider IV fluids; antiemetic based on cost and side effect profile

CHAPTER 26  Nausea and Vomiting

Headache Patients with nausea or vomiting associated with a headache should be given metoclopramide as the first line agent. Metoclopramide will treat the both the headache, as well as the nausea and vomiting. Ondansetron may cause headache and therefore is not appropriate as a first line agent. If metoclopramide is ineffective, then prochlorperazine may be used a second line agent, because it has also shown to be effective in the treatment of headaches. Finally, droperidol is effective for headaches and for nausea and vomiting and should be considered if the first two agents fail.

Pregnancy Many agents, both pharmacologic and non-pharmacologic have been evaluated in the treatment of nausea and vomiting of pregnancy and hyperemesis gravidarum. A recent Cochrane review concluded that there was insufficient high quality evidence to recommend one agent over another. Agents that have shown to be more effective when compared to placebo include ginger, vitamin B6 (pyridoxine), vitamin B6 combination products (such as, doxylamine with pyridoxine), ondansetron, and metoclopramide. Studies comparing ondansetron to metoclopramide have not shown a difference in effectiveness.7 Although the quality of the evidence is poor, there may be an association between ondansetron use and fetal malformations in the first trimester.8 In pregnant patients presenting with nausea and vomiting, metoclopramide 10 mg IV should be the first line agent. Ondansetron should be reserved as a second line agent. If the pregnant patient is discharged from the ED, then a vitamin B6 combination product should be prescribed if her symptoms return.

Chemotherapy Chemotherapy-related nausea and vomiting may be seen in ED patients. The chemotherapy-induced nausea and vomiting may be acute (up to 24 hours) or delayed (after 24 hours). Ondansetron is the first line agent and should be given at repeated doses. Start with 4 mg IV and repeat every 30 minutes up to 16 mg IV. A single dose of dexamethasone 10 mg IV should be added if the vomiting is refractory to the ondansetron.

Cyclical Vomiting Patients with cyclical vomiting syndrome may be difficult to manage. They should receive IV hydration and may require high doses of an antiemetic medication, although once again, none of

which has been deemed superior to another. Benzodiazepines are recommended in this condition, because inducing sleep often terminates the episode, especially if antiemetic therapy fails to abort the episode and admission is considered.9 Although the evidence is primarily anecdotal, patients with cannabis hyperemesis syndrome should be treated with IV fluids, an antiemetic medication, and frequent hot showers. Patients should be advised to abstain from marijuana use, because that is the only known cure. Patients with a history of cannabis hyperemesis syndrome have been shown to relapse if they resume marijuana use, even after a long period of abstention.

Vertigo Antihistamines are useful in nausea and vomiting associated with motion sickness and vertigo. Agents such as dimenhydrinate (Gravol, Dramamine) and meclizine (Antivert) directly inhibit vestibular stimulation and vestibular-cerebellar pathways. Their anticholinergic effect also may contribute to their effectiveness in vertigo and motion sickness. Antihistamines have some role as general antiemetics but are better used in the prevention of motion sickness. The most common side effects of antihistamines are drowsiness, blurred vision, dry mouth, and hypotension.

DISPOSITION Hospital admission is appropriate when the patient has a significant underlying disease, has an unclear diagnosis and responds poorly to fluid and antiemetic therapy, continues to experience uncontrolled emesis refractory to medication, or is at the extremes of age with poor response to treatment. More difficult disposition decisions are related to patients in whom the diagnosis is unclear and prospects for timely follow-up are poor. Discharge may be considered if no serious underlying illness is present, the response to fluid and antiemetic therapy is good, the patient is able to take clear liquids before discharge, and the prospects for follow-up and observation at home are favorable. Close follow-up often is advisable for discharged patients, preferably with their primary care physician, in 24 to 48 hours. At discharge, the patient is prescribed medications as needed and is advised to restart oral intake with small feedings of a liquid diet with gradual return to a normal diet. Clear instructions are given to return to the ED if there is a recurrence, change, or deterioration in symptoms. Causes for nausea and vomiting frequently remain undiagnosed. Some cases declare themselves or resolve over time; reevaluation and close follow-up are fundamental in the care for patients with continuing symptoms.

KEY CONCEPTS • Nausea and vomiting can result from a primary problem in the GI tract but can also be secondary to problems in the neurological, vestibular, urogenital, and cardiac systems. • Associated symptoms and a medication/drug history are the most helpful in narrowing the differential diagnosis in the acutely vomiting patient. • Laboratory studies are not required in all patients who vomit. Patients with severe or protracted vomiting, sufficient to require IV rehydration, should have their electrolytes and renal function determined and corrected.

• In a patient with undifferentiated nausea or vomiting or vomiting due to non-obstructive GI disease, ondansetron is the first line antiemetic. • Although evidence is limited, metoclopramide is the antiemetic of choice in hyperemesis gravidarum and vomiting associated with headache; ondansetron is the drug of choice in chemotherapy induced vomiting. • Antiemetics should not be prescribed routinely in patients receiving opioid analgesia.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

241

CHAPTER 26  Nausea and Vomiting

241.e1

REFERENCES 1. Nicolson SE, et al: Cannabinoid hyperemesis syndrome: a case series and review of previous reports. Psychosomatics 53(3):212–219, 2012. 2. Egerton-Warburton D, et al: Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Ann Emerg Med 64(5):526–532, 2014. 3. Barrett TW, et al: A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults. Am J Emerg Med 29(3):247–255, 2011. 4. Chae J, Taylor DM, Frauman AG: Tropisetron versus metoclopramide for the treatment of nausea and vomiting in the emergency department: a randomized, doubleblinded, clinical trial. Emerg Med Australas 23(5):554–561, 2011. 5. Health Canada: Zofran (Ondansetron)—dosage and administration of intravenous ondansetron in geriatrics (>65 years of age)—for health professionals. Available at

. Accessed February 3, 2015. 6. U.S. Food and Drug Administration: Serotonin-3 (5-HT3) receptor antagonists. Available at . Accessed September 2, 2015. 7. Matthews A, et al: Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev (3):CD007575, 2014. 8. Danielsson B, Wikner BN, Kallen B: Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol 50:134–137, 2014. 9. Hejazi RA, McCallum RW: Review article: cyclic vomiting syndrome in adults— rediscovering and redefining an old entity. Aliment Pharmacol Ther 34(3):263–273, 2011.

CHAPTER 26: QUESTIONS & ANSWERS 26.1. Which of the following metabolic derangements is most likely in a patient with severe, protracted vomiting? A. Hypochloremic, hypokalemic, metabolic alkalosis B. Hypochloremic, hypokalemic, metabolic acidosis C. Hyperchloremic, hypokalemic, metabolic alkalosis D. Hyperchloremic, hypokalemic, metabolic acidosis E. Hyperchloremic, hyperkalemic, metabolic acidosis Answer: E. Severe, protracted vomiting can cause a hypochloremic, hypokalemic, metabolic alkalosis. The metabolic alkalosis is produced by loss of hydrogen ions in the vomitus. Many factors serve to maintain the alkalosis including volume contractions, hypokalemia, chloride depletion, shift of extracellular hydrogen ions into cells, and increased aldosterone. Hypokalemia is produced primarily by loss of potassium in the urine. The metabolic alkalosis leads to large amounts of sodium bicarbonate being delivered to the distal tubule. Secondary hyperaldosteronism from volume depletion causes reabsorption of sodium and excretion of large amounts of potassium in the urine. 26.2. Antihistamines would most effectively control the nausea and vomiting caused by which of the following conditions? A. Chemotherapy administration B. Digoxin ingestion C. Gastritis D. Gastroparesis E. Labyrinthitis Answer: E. Antihistamines are useful in nausea and vomiting associated with labyrinthitis, motion sickness, and vestibular disorders by directly inhibiting vestibular stimulation and vestibularcerebellar pathways. Their anticholinergic effect may also contribute to their effectiveness in vertigo and motion sickness. 26.3. A 35-year-old man is given 10 mg of IV prochlorperazine for treatment of nausea. Fifteen minutes after the administration of medication, he displays protrusion of his tongue, difficulty speaking, intermittent contractions of his facial muscles, and anxiety. Which of the following would be the most appropriate next step in the management of this patient? A. Administer benztropine mesylate B. Administer haloperidol C. Five-point physical restraints

D. Rapid sequence intubation E. Repeat dose of prochlorperazine Answer: A. The described patient is experiencing a dystonic reaction to prochlorperazine (Compazine). Drug-induced dystonic reactions most commonly occur with antipsychotic, antidepressant, and antiemetic medications. Administration of an anticholinergic medication such as benztropine mesylate (Cogentin) or diphenhydramine (Benadryl) is the treatment of choice and typically aborts the reaction. Benzodiazepine administration may occasionally be necessary if the previously mentioned medications are ineffective. Artificial airway placement and use of restraints are rarely required. Further dopamine receptor blockade with haloperidol or additional doses of the offending agent would not prove useful. 26.4. Where is the principal site of action of the serotonin receptor antagonist ondansetron? A. Area postrema B. Basal ganglia C. GI tract D. Hypothalamus E. Vestibular system Answer: A. The serotonin receptor antagonists such as ondansetron, granisetron, and tropisetron are a class of agents that have generated much interest secondary to their effect on chemotherapyinduced emesis. Their principal site of action is the area postrema, which is located in the lateral reticular formation of the medulla. They also exert some effect on receptors of the GI tract; however, this is secondary to their effect in the area postrema. 26.5. What is the most common cause of nausea and vomiting in the adult population? A. Acute gastroenteritis B. Drug side effects C. Febrile systemic illness D. Motion sickness E. Pregnancy Answer: B. In adult medicine, nausea and vomiting are caused most often by medications. When considering the entire population (pediatrics and adults), the three most common causes of nausea and vomiting are acute gastroenteritis, febrile systemic illnesses, and drug effects.

C H A P T E R 27 

Gastrointestinal Bleeding David A. Meguerdichian  |  Eric Goralnick PERSPECTIVE Upper and lower gastrointestinal bleeding (GIB) are defined based on their location relative to the ligament of Treitz in the terminal duodenum, so esophagus, stomach, and duodenum origin bleeds are upper and all others are lower. Upper GIB (UGIB) mortality rates have remained constant at about 15% over the past 2 decades despite advances in medical therapy, intensive care unit (ICU) management, endoscopy, and surgery. This is most likely due to the increasing proportion of older patients, who may die due to comorbid conditions, and increases in cirrhotic and variceal patients. The lower GIB (LGIB) mortality rate is approximately 4%. Predictors include age older than 70 years, intestinal ischemia, comorbid illness, coagulation defects, transfusion of packed red blood cells, and male gender.

DIAGNOSTIC APPROACH Differential Considerations The characteristics of the GIB, age of the patient, and social factors can all help determine the cause. UGIB can routinely manifest as bloody or coffee-ground–like vomit termed hematemesis or as dark, tarry stools termed melena. In older adults, peptic ulcer disease, esophagitis, and gastritis account for most cases. Younger patients typically present with Mallory-Weiss tears, GI varices, and gastropathy (Table 27.1). As a whole, peptic ulcer disease makes up more than 50% of all acute cases of UGIB seen in the emergency department (ED).1 In pediatric patients, gastric and duodenal ulcers, esophagitis, gastritis, esophageal varices, and Mallory-Weiss tears account for most cases of UGIB, in descending order of frequency. LGIB usually produces bright red or maroon blood per rectum, termed hematochezia. LGIB may be classified according to pathophysiologic cause—inflammatory, vascular, oncologic, traumatic, or iatrogenic. Anorectal sources, such as hemorrhoids, are the most common causes of LGIB in all age groups. In adults, the most common sources of hematochezia are colonic diverticula and angiodysplasia. Other noteworthy causes include colitis caused by ischemia, infection, and inflammatory bowel disease. Among older patients with cardiovascular disease, ischemic colitis as a cause for LGIB has been increasing. Although uncommon, a brisk UGIB may present as hematochezia and be mistaken for a bleed from a lower GI source. Up to 14% of bleeds characterized as hematochezia are due to such lesions and are associated with higher transfusion rates, surgical interventions, and mortality. Major causes of LGIB in children include anorectal fissures and infectious colitis. Bleeding can also be caused by intussusception and Meckel’s diverticulum in infants and toddlers. Despite diagnostic advances for all ages, the source of GIB is not identified in nearly 15% of patients. Death from exsanguination resulting from GIB is rare. However, there are two causes of GIB that may rapidly cause death if not recognized and mitigated, esophageal varices and aortoenteric fistula. The former, which typically arises from portal hypertension usually caused by alcoholic cirrhosis, is the single 242

most common source of massive UGIB and has a mortality rate of 30%. The latter is caused when an abdominal aortic aneurysm or, more commonly, an aortic graft adheres to and erodes through a bowel wall. Aortoenteric fistula is a rare but rapidly fatal cause of GIB, with the mortality of an untreated fistula of nearly 100%. Aortoenteric fistula is a primary consideration in patients with GIB and known abdominal aortic aneurysms or aortic grafts until an alternative bleeding source is identified. Prompt surgical consultation is warranted when aortoenteric fistula is a likely diagnosis. Finally, in the differential considerations, one must determine whether the blood is actually of GI origin. Epistaxis, dental bleeding, or red food coloring can mimic the appearance of hematemesis. Bismuth-containing medications and iron supplements can create melanotic-appearing (but guaiac-negative) stools. Vaginal bleeding, gross hematuria, and red foods (eg, beets) can all be mistaken for hematochezia (Box 27.1). Unless an alternative diagnosis is clearly evident, the appropriate approach is to continue with the evaluation for GIB.

Pivotal Findings The history centers on the GI tract and on the timing, quantity, and appearance of the bleeding. Relevant comorbid conditions should be reviewed as well (Box 27.2). The extent of the history will be dictated by the severity of the complaint and hemodynamic stability of the patient on ED arrival. Reviewing the patient’s vital signs, appearance of the stool, and basic laboratory studies will help identify the bleeding source and guide treatment.

Symptoms A useful starting point for the emergency clinician is to determine the time of onset, duration of symptoms, and relevant supporting historical facts. Often, the degree of bleeding is better gauged by assessing symptoms associated with significant intravascular loss, such as weakness, shortness of breath, angina, orthostatic dizziness, confusion, palpitations, and report of cool extremities. Blood loss more than 800 mL will usually result in the onset of these complaints, with severe symptoms being described at a threshold greater than 1500 mL. Such symptoms indicate a decreased oxygen-carrying capacity that often accompanies significant blood loss and should prompt a thorough and expeditious evaluation and resuscitation. The context of the bleeding can help explain its cause. For example, if a patient complains of bright red blood per rectum after several days of constipation and straining, that presentation suggests an anorectal source. Alternatively, a patient with hematemesis after several earlier episodes of retching would lead one to suspect an esophageal tear. Finally, a patient with easy bruising and recurrent gingival bleeding might suggest an underlying coagulopathy. Efforts should be made to quantify the amount of blood lost during the bleeding event. Patients may describe the passage of large clots, blood changing the toilet bowl water red, or simply streaks of blood on the toilet paper. The patient’s recollection of

CHAPTER 27  Gastrointestinal Bleeding

TABLE 27.1 

BOX 27.3 

Common Causes of Gastrointestinal (GI) Bleeding in Adults and Children

Key Historical Information for Patients With Gastrointestinal Bleeds (GIBs)

CAUSE

ADULTS

CHILDREN

Common causes of upper GI bleeds

Peptic ulcers (gastric more than duodenal) Gastric erosion Esophagogastric varices Mallory-Weiss tears Esophagitis Gastric cancer

Duodenal ulcers Gastric ulcers Esophagitis Gastric erosion Esophageal varices Mallory-Weiss tears

Common causes of lower GI bleeds

Diverticular disease Angiodysplasia Colitis (inflammatory, infectious, ischemic) Anorectal sources Neoplasm Upper GI bleeding

Anorectal fissure Infectious colitis Inflammatory bowel disease Juvenile polyps Intussusception Meckel’s diverticulum

BOX 27.1 

Alternative Diagnoses or Mimics of Gastrointestinal Bleeding Melena • Ingestion of bismuth medications • Ingestion of activated charcoal Hematemesis • Nasopharyngeal bleeding (eg, nosebleeds, dental bleeding) • Ingestion of red drinks or food Hematochezia • Vaginal bleeding • Gross hematuria • Partially digested red food (eg, red beets, red grapes)

BOX 27.2 

Characteristics of Patients With High-Risk Gastrointestinal Bleeds Medication use • Aspirin • Nonsteroidal antiinflammatory drugs • Steroids • Anticoagulants (warfarin, heparin) • Chemotherapeutic agents History of peptic ulcer disease Known liver disease, cirrhosis Advanced age (>60 yr) Alcoholism Current smoker Chronic medical comorbidities • Congestive heart failure • Diabetes • Chronic renal failure • Malignancy • Coronary artery disease History of abdominal aortic aneurysm graft

• • • •

Events prior to or leading up to the bleeding episode Severity, frequency, and quantity of the bleeding episode Appearance and color of the bleed Medical history, including risk factors for GIB: • Prior bleeding episodes and any identified source • Medication use that may increase the risk of GIB • Social factors that may increase the risk of GIB • Symptoms patient is experiencing with the bleeding episode

the bleed and its amount is usually poorly quantified and inaccurate. Classifying the blood as hematemesis, melena, or hematochezia provides the initial clue to the source of bleeding. Vomiting of fresh blood or blood with the appearance of coffee grounds strongly suggests a UGI source. The passage of melena, dark digested stools, also suggests likely UGIB. In contrast, the presence of hematochezia, bright red or maroon stools, usually signifies LGIB. There are exceptions, however. In a hemodynamically unstable patient, bright red blood per rectum can represent brisk UGIB. Hematemesis rarely can arise from a source in the LGI tract that is proximal to an obstruction. Although the definitive cause and location of the bleed will usually be determined by the gastroenterologist, the emergency clinician uses the history to make a reasoned determination of the likely source and help guide the initial diagnostic evaluation.

Relevant Medical History A review of the patient’s relevant medical history and risk factors for bleeding should note whether a patient has had similar bleeding before and the location of the causative lesion (Box 27.3). This is especially important with UGIB because most of these presentations are caused by rebleeding of previously identified sources. Next, identification of relevant comorbid diseases helps riskstratify these patients in the context of their bleed. Patients with GIB and a history of coronary artery disease, congestive heart failure, liver disease, or diabetes have a higher mortality and therefore may require earlier or more extensive interventions. A review of the patient’s medications should pay particular attention to gastrotoxic substances, anticoagulants, and antiplatelet drugs. Medications such as nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, warfarin, clopidogrel, corticosteroids, and certain chemotherapeutic agents are known to increase the risk of GIB by as much as threefold. In addition, reviewing the patient’s social history can identify activities that increase risk for GIB. Alcohol abuse is associated with gastritis and peptic ulcer disease. It can also result in cirrhosis, portal hypertension and, ultimately, esophageal variceal bleeding. Smoking cigarettes results in slower healing and greater recurrence of ulcers. These two social habits are also closely associated with GI malignancy— another, albeit rare, risk factor for GIB.

Signs Hypotension and tachycardia can suggest moderate hypovolemia and can be the early indicators of impending shock. Normal vital signs do not preclude the possibility of a severe bleed. Orthostatic vital signs, although frequently used historically, are insufficiently sensitive or specific to be of value in determining volume status in the context of acute blood loss.

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244

PART I 

Fundamental Clinical Concepts  | 

SECTION Two 

Signs, Symptoms, and Presentations

Mental status is evaluated for signs of poor cerebral perfusion. Generalized pallor in a hemodynamically stable patient might indicate the anemia of a subacute or chronic GIB; in the unstable patient, pallor might reinforce the impression of malperfusion caused by massive blood loss. Cold clammy skin on the extremities signal significant volume loss consistent with hemorrhagic shock. Ecchymoses or petechiae suggest a coagulopathy. Finally, jaundice, palmar erythema, or spider angiomata suggests the possibility of UGIB from esophageal varices. The abdomen is carefully examined for subtle findings that can help identify the source of bleeding. Hyperactive bowel sounds are a nonspecific finding, but might indicate UGIB, because intraluminal blood is a known cathartic that can stimulate peristalsis. Tenderness to palpation can be seen in many cases of peptic ulcer disease. Severe diffuse tenderness on examination warrants the consideration of bowel ischemia, mechanical obstruction, ileus, or bowel perforation. Evidence of peritonitis merits a rapid surgical consultation for possible operative management. The abdominal examination may also show further signs of portal hypertension with the presence of hepatomegaly, ascites, or caput medusae. The rectal examination helps determine the type of bleeding and should be performed in most patients with GIB. The examination should include evaluation of the external anus, digital rectal examination and, when local bleeding is thought to be the cause, anoscopy for hemorrhoids, polyps, or fissures.

Absorption of digested blood breakdown products into the circulatory system from the gut causes elevation of BUN levels. The BUN level can also be elevated from prerenal azotemia in the setting of hypovolemia. A BUN-to-creatinine ratio greater than 36 when the patient does not have renal failure has a sensitivity of 90% in predicting GIB, but specificity is very low, at 27%.3 Coagulation studies, particularly prothrombin time, monitor for coagulopathy in the context of blood loss and replacement. This becomes especially important in patients with liver disease or those taking therapeutic anticoagulants such as warfarin. Other laboratory tests rarely are useful in patients with GIB. Electrolyte abnormalities may be present in patients with repeated or prolonged episodes of vomiting or diarrhea. Leukocytosis often is present because of the stress response to acute blood loss and should not be considered to represent underlying infection unless other indications of infection are present. The serum lactate level is elevated when circulatory shock is present or, much less commonly, from gut ischemia, if that is the cause of the GI blood loss. Blood is sent to the blood bank for a type and screen if the patient is stable and for crossmatching if blood loss is brisk or the patient is hemodynamically unstable or has significant comorbidities, especially heart disease. If the patient is highly unstable, transfusion of non–crossmatched blood may be necessary.

Ancillary Testing

Electrocardiography

Occult Blood and Guaiac Bedside Testing

Because GIB and its subsequent anemia can reduce the oxygencarrying capacity of blood, patients should be screened for signs of myocardial ischemia. We recommend obtaining an electrocardiogram for all patients older than 40 years, those with any symptoms of ischemia, and those with known coronary artery disease who are at higher risk for ischemic events. Electrocardiographic findings consistent with myocardial ischemia likely represent demand ischemia rather than coronary thrombosis and are treated with restoration of adequate circulatory volume, including blood, if needed.

In patients with suspected UGIB, guaiac testing can be performed at the bedside to evaluate for occult blood, even when stool appears normal. The test makes use of the pseudoperoxidase activity found in hemoglobin. When hydrogen peroxide is dripped onto the guaiac paper containing the stool sample, an oxidative reaction rapidly turns the paper blue. The test can actually be positive for up to 2 weeks after an acute bleed and thus is more useful for diagnosing chronic occult bleeding. Uncommonly, false-positive results can be triggered by ingestions of red meat, turnips, horseradish, vitamin C, methylene blue, and bromide preparations. Iron- and bismuth-containing medications can cause dark stools that will be guaiac-negative. Similar testing is available for gastric contents but testing of UGI aspirates and vomitus is less reliable than testing of an LGI sample, and we do not recommend it. The clinical impression of an UGIB should override any testing. The diagnostic and prognostic limitations of nasogastric (NG) tube insertion are discussed below.

Laboratory Studies Laboratory studies can assist in the risk stratification of GIB. Minimum testing should include evaluation of the patient’s hemoglobin and blood urea nitrogen (BUN) levels, coagulation studies, and platelets. The hemoglobin level does not immediately decline in the setting of an acute bleed, because whole blood is lost. Changes in hemoglobin levels are typically seen after 24 hours, when there is hemodilution from shifting extravascular fluids and intravenous (IV) hydration with crystalloid. Nevertheless, acute hemoglobin levels less than 10 g/dL have been positively correlated with higher rates of rebleeding and mortality. Blood transfusion is indicated in a patient with GIB when their hemoglobin level is acutely less than 7 to 8 g/dL, they are experiencing vigorous blood loss, or they require further resuscitation beyond 2 L of crystalloid due to unstable vital signs. An even lower threshold for transfusion is indicated in older adults and those with significant comorbidities, such as coronary artery disease.2

Imaging Emergent imaging of the chest or abdomen in the ED setting is rarely indicated in the patient with acute GIB. When bowel perforation is suspected on the basis of peritoneal findings on examination, abdominal computed tomography (CT) is the imaging test of choice. Abdominal plain radiographs are of no value for patients with GIB, except in the rare case where bowel obstruction is strongly suspected. In the absence of clinical findings consistent with perforation or bowel ischemia, CT of the solid abdominal organs is not indicated and does not alter the acute management and disposition of the patient with a GIB. When endoscopy is not possible or cannot locate the hemorrhage source, CT angiography (CTA) is the principle diagnostic imaging tool and has the benefit of allowing for therapeutic options via embolization. CTA has a sensitivity of 85% and specificity of 92% for detecting acute GIB. Conventional angiography is indicated in a very small proportion of cases of GIB and requires a hemorrhage rate of greater than 0.5 mL/min to detect the bleed. Although also potentially therapeutic, angiography has a high complication rate, including acute renal failure, contrast reactions, and bowel infarction. Angiography has a sensitivity of 46% and specificity of 100% for acute bleeds (Fig. 27.1). Tagged red blood cell imaging or nuclear scintigraphy involves erythrocyte injection to detect indolent or elusive bleeding and is primarily useful in the inpatient setting. Scanning must be performed within 2 hours of injection to localize bleeding accurately3 (Fig. 27.2).

CHAPTER 27  Gastrointestinal Bleeding

Fig. 27.1.  Axial and coronal images from CT angiograms demonstrating extravasation of contrast material within the colon from a bleeding diverticulum. (Courtesy Wendy B. Landman, MD; Department of Radiology Brigham and Women’s Hospital.)

17

18

19

20

TABLE 27.2 

American College of Radiology Appropriateness Rating Scalea TREATMENT OR PROCEDURE Fig. 27.2.  Technetium 99m-labeled red blood cell scintigraphy demonstrating focus of increased activity in the ascending colon with antegrade transit into the hepatic flexure and transverse colon. (Courtesy Wendy B. Landman, MD; Department of Radiology Brigham and Women’s Hospital.)

With numerous approaches available, the American College of Radiology has developed an appropriateness rating scale to help guide emergency clinicians in the use of specific interventions and imaging modalities for patients presenting with GIB (Table 27.2).

DIAGNOSTIC ALGORITHM The diagnostic approach to the GIB patient involves a number of key decision points. First, the emergency clinician should assess the patient’s general appearance, vital signs, and volume status. This initial assessment can help categorize the patient as stable or unstable. If the patient is unstable, resuscitation begins with the immediate placement of two large-bore IV catheters (18 gauge or larger) or central venous catheter placement and crystalloid infusion, with the aim of establishing and maintaining adequate tissue perfusion. This does not equate to restoration of normal blood pressure, however, and maintaining a systolic blood pressure in the range of 100 mm Hg is a good initial resuscitative goal. Endpoints of adequate resuscitation would include evidence of adequate perfusion of skin, urine output greater than 1 mL/kg/hr, and normal mental status. The second decision point involves use of the history and physical examination findings to determine if the patient has UGIB or LGIB. These details will help risk-stratify the GIB patient further and establish the differential diagnosis. Once the presumptive origin of the bleed has been determined, the emergency clinician should consider the anticipated hospital course of the patient.

RATING COMMENTS

Transcatheter arteriography, intervention

8

Allows for embolization if positive on arteriography

Diagnostic, therapeutic colonoscopy

4

Challenging in an unstable patient

Surgery

5

Appropriate if bleeding site localized

Nuclear medicine scan

1

More appropriate for hemodynamically stable patient

CTA abdomen

5

Continuing to emerge as an appropriate option when the bleeding source is unknown

MRI abdomen

1

Not appropriate in hemodynamically unstable patients

NOTE: Rating scale from 1 to 9, with 1 = least appropriate and 9 = most appropriate. a For evaluation and treatment of LGIB in an actively hemodynamically unstable patient. From Millward S: ACR Appropriateness Criteria on treatment of acute nonvariceal gastrointestinal tract bleeding. J Am Coll Radiol 36:2667–2774, 2008.

The third decision point relies on the severity of the UGIB or LGIB to determine the ED management and disposition. A later section of this chapter (see “Disposition”) discusses risk stratification and hospitalization recommendations. In general, patients who are young, reliable, and hemodynamically stable, with a clear source of bleeding (eg, a minor bleed in a clear context of a Mallory-Weiss tear), can be discharged after an observation period of 12 hours in the ED or ED observation unit. The patient who has been properly resuscitated in the ED and remains hemodynamically stable will require urgent GI consultation, so admission to a medical inpatient unit or observation unit for further evaluation and management is indicated. LGIB patients who are hemodynamically stable, are reliable, have no significant risk factors, and have a clearly visualized source of bleeding on

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examination can be safely discharged to follow-up with their outpatient provider. Unstable UGIB will require emergent gastroenterology consultation, consideration of intubation if shock or hemorrhage is severe, and admission to an ICU for continued resuscitation and emergent endoscopy. Unstable LGIB patients require emergent surgical consultation. Management initially centers on proper resuscitation with fluids, blood products, and admission to the ICU.

MANAGEMENT Empirical Treatment Rapid identification of the bleeding source (ie, upper vs. lower GI tract), risk stratification, resuscitation, consultation, and disposition are the integral elements of this process. Massive bleeding, active hematemesis, hypoxia, severe tachypnea, and/or altered mental status may mandate tracheal intubation for protection and to supplement tissue oxygenation. Fig. 27.3 presents a combined diagnostic and management algorithm.

Resuscitation Hemodynamic instability and estimated volume loss should guide initial resuscitation efforts. Patients should be placed on pulse oximetry and should receive supplemental oxygen with prompt crystalloid resuscitation through two peripheral, large-bore IV catheters. Cardiac telemetry should be initiated because demand ischemia and myocardial infarction may occur in patients with significant GIB.

Blood Product Transfusion Continued hemodynamic instability or ongoing hemorrhage dictate the need for blood transfusion. Factors such as age, comorbidities (eg, ischemic heart disease, peripheral vascular disease, heart failure), baseline hemoglobin and hematocrit levels, and evidence of cardiac, renal, or cerebral hypoperfusion should be considered when determining transfusion quantity. Blood transfusion is immediately indicated in patients with GIB who have a hemoglobin level acutely less than 7 to 8 g/dL, are experiencing vigorous blood loss, or require further resuscitation beyond 2 L of crystalloid to maintain a systolic blood pressure in the range of 100 mm Hg. Coagulopathy, especially in patients with underlying liver disease or those requiring massive transfusions, should be corrected promptly. We recommend either a 1 : 1 : 1 or a 1 : 1 : 2 ratio of plasma to platelets to packed RBC.4

Nasogastric Aspiration and Lavage NG tube placement with aspiration or gastric lavage is not indicated for the evaluation of GIB.5 Despite its long time role, with advocates citing diagnostic and prognostic value, evidence has confirmed that it is not useful for either of these purposes. The sensitivity of NG aspiration and lavage for predicting later recurrence or worsening of UGIB is low, and the negative likelihood ratio in patients with melena or hematochezia without hematemesis is poor.6 Up to 15% of patients without blood or coffee-ground material in NG aspirates have been found to have high risk lesions on endoscopy. NG tube placement is not a benign procedure and has been associated with complications, including pain, aspiration, pneumothorax, pharyngeal or esophageal perforation, and gastric lesions. Occasionally, a consulting gastroenterologist may wish to place an NG tube in hopes of improving endoscopic visibility (and accuracy) by evacuating gastric contents and blood

but, absent such an indication, we do not recommend placement of an NG tube in patients with suspected UGIB.

Sengstaken-Blakemore Tube A bedside balloon tamponade should only be considered in exsanguinating patients with likely variceal bleeding when endoscopy is not immediately available. Complications are common and significant, but tube placement is indicated in the appropriate patient population due to the high mortality of uncontrolled bleeding. Insertion of these tubes is a rarely performed procedure, and emergency clinicians have resorted to novel approaches, including indirect laryngoscopy with a GlideScope, to aid placement.7

Pharmacologic Agents Several medications may improve GIB outcomes. Proton pump inhibitor (PPI) infusions have long been a staple of acute GIB therapy, but evidence has contradicted their necessity in the emergent setting. A recent systematic review has found no evidence to suggest that PPI therapy affects clinically important outcomes such as mortality, rebleeding, or subsequent surgery.8 However, the infusion of high-dose PPIs before endoscopy has been proven to accelerate the resolution of signs of bleeding in ulcers and reduce the need for endoscopic sclerotherapy and thermocoagulation. Therefore, we recommend initiating IV dosing of an 80-mg bolus of omeprazole, followed by 8 mg/hr by continuous IV infusion for 3 days. High-dose oral PPIs, such as esomeprazole, 40 mg bid, have been shown in Asian populations to reduce the risk of rebleeding, need for surgery, and risk of death, but additional data are needed to determine whether those findings are generalizable to Western patients. If oral therapy proves equivalent to IV therapy, oral PPI therapy would decrease cost, dosage, and supply shortfalls.9 Somatostatin and octreotide, synthetic analogues, are splanchnic vasoconstrictors that reduce portal hypertension and the risk of persistent bleeding, rebleeding, and transfusion requirements in patients with variceal bleeding. Octreotide should be empirically administered to patients presenting with an acute GIB and history of significant liver disease, variceal bleeding, or alcoholism or with abnormal liver function tests. Octreotide is given as a 50-µg bolus followed by 50 µg/hr continuous IV infusion. Octreotide is not indicated for presumed nonvariceal bleeding. Although an older meta-analysis purported to show benefit for patients with nonvariceal GIBs who were treated with somatostatin, the individual studies were poor, and there is insufficient evidence to support its use. Vasopressin, administered by continuous IV infusion, also reduces splanchnic blood flow and portal hypertension. However, we do not recommend its use due to the risk of significant complications, including myocardial and mesenteric ischemia and infarction.

Definitive Management Consultation Patients with hemodynamic instability and severe bleeding of a presumed upper GI source should have emergent gastroen­ terology consultation. Severe LGIB warrants emergent surgical consultation.

Endoscopy Upper endoscopy is the most effective diagnostic and therapeutic intervention for UGIB, achieving hemostasis in greater than 90% of cases. Endoscopic hemostasis decreases rates of rebleeding,

CHAPTER 27  Gastrointestinal Bleeding

Chief complaint GI bleed

Triage, vital sign assessment Stable or unstable?

Stable patient

Resuscitate • Two large-bore IVs • Crystalloid infusion • Consider transfusion.

Unstable patient • Abnormal vital signs • Shock

History

Physical examination

Ancillary studies

Gastric contents/stool examination Hematemesis

Melena

Hematochezia

Upper GI bleed

Massive upper GI bleeding

Airway management • Intubate as needed to protect airway from aspiration of hematemesis.

Emergent GI consult with ED endoscopy to identify and stabilize bleed

Lower GI bleed

Stable vitals and no massive bleeding or severe hematemesis

Anoscopy

Does the patient meet the following criteria?

Does the patient meet the following criteria? • Young patient ( 12, BUN < 18, no coagulopathies) • Reliable patient with prompt outpatient follow-up

Yes

• Bleeding source visualized • Stable vital signs within normal limits • No comorbidities • No coagulopathy • Young patient (12 to 40 years), the differential diagnosis includes diverticulitis and colitis. Urolithiasis may also manifest as lateral pelvic pain, especially when the stone is at the ureterovesicular junction, or as pain radiating to the labia or vaginal area. Central pelvic pain usually is caused by processes involving the uterus, bladder, or both adnexae. Pain radiating to the rectum may be secondary to pooling of fluid or blood in the cul-de-sac. Diffuse pain may occur with a central or bilateral process such as PID or with diffuse peritonitis from infection or intraabdominal hemorrhage. Information regarding the onset and duration of pain may be useful. Patients with uncomplicated appendicitis (without

The female pelvis contains the vagina, uterus, fallopian tubes and ovaries, ureters and urinary bladder, and sigmoid colon and rectum, as well as components of the vascular and musculoskeletal systems. Although pelvic pain often originates from the reproductive organs, it may arise from any structures that lie adjacent to or course through the pelvis. Visceral pain afferents supplying the pelvic organs have common innervation with the appendix, ureters, and colon. Their significant overlap makes accurate localization difficult for both patient and emergency clinician. Pain may be initiated by inflammation, distention, or ischemia of an organ, or by spillage of blood, pus, or other material into the pelvis. Pain may become more localized when the afferent nerves in the parietal peritoneum adjacent to an affected organ are stimulated. 262

Pivotal Findings It is unlikely that any particular finding on history or physical examination, summarized in Table 30.1, is reliable enough to make or exclude a particular diagnosis conclusively, so ancillary testing beyond a pregnancy test is commonly required in the evaluation of patients with acute pelvic pain. The pelvic examination may at times provide crucial information. However, some findings on bimanual examination are subjective and may be unreliable; they are perhaps most helpful in localizing the process to one side or the other or in helping to plan the initial evaluation. There are not sufficient data to select reliable women in whom the pelvic examination need not be performed, although the pelvic examination may be deferred in patients who are planned to undergo immediate imaging (usually ultrasound) for a suspected critical condition such as ruptured ectopic pregnancy. Depending on imaging results, a subsequent speculum or bimanual pelvic examination may or may not be necessary. A sequential approach can progressively narrow the diagnostic possibilities until a reasonable provisional diagnosis is reached.

Symptoms

CHAPTER 30  Acute Pelvic Pain

BOX 30.1 

Causes of Pelvic Pain in Women REPRODUCTIVE TRACT

Ovarian torsion Ovarian cyst Pelvic inflammatory disease Salpingitis Tubo-ovarian abscess Endometritis Endometriosis Uterine perforation Uterine fibroids Dysmenorrhea Neoplasm

PREGNANCY-RELATED

First Trimester Ectopic pregnancy Threatened abortion Nonviable pregnancy Ovarian hyperstimulation syndrome Second and Third Trimesters Placenta previa Placental abruption Round ligament pain Labor or Braxton-Hicks contractions Uterine rupture

INTESTINAL TRACT Appendicitis Diverticulitis Ischemic bowel

perforation or abscess) typically are seen within 48 hours of symptom onset. Sudden-onset pain suggests acute intrapelvic hemorrhage, cystic rupture, ovarian torsion, or ureterolithiasis. Gradual-onset pain is more consistent with inflammation such as in PID or appendicitis. PID-associated pain generally begins gradually during or immediately following menses, whereas ovarian cyst pain peaks at midcycle and, if associated with rupture, is of sudden onset. Ovarian cyst pain may also fluctuate through several menstrual cycles before rupture. Chronic or recurrent pain is consistent with endometriosis, recurrent ovarian cysts, or persistent ovarian mass. The quality of pain may differentiate the crampy intermittent pattern of muscular contractions along a hollow viscus (arising from uterine, ureteral, or bowel pathology) from the steady progressive pain associated with inflammatory or neoplastic causes. Fever and chills are more common with an infectious process. Nausea and vomiting occur more frequently when the process originates within the gastrointestinal tract but may also accompany any pain of visceral origin such as ovarian torsion, ureteral colic, and pregnancy or any severe pain. Dysuria occurs in many local vulvar and vaginal processes such as herpesvirus infection, candidiasis, and other types of vulvovaginitis, but urinary urgency typically signals an irritated bladder or urethra and should focus attention on the urinary tract. Information about the patient’s last menstrual period, pattern of menses, and sexual activity pattern may be useful but does not necessarily exclude pregnancy. In a pregnant patient, the obstetric history may provide some helpful diagnostic clues. Recurrent spontaneous abortion or previous ectopic pregnancy increases the

Perforated viscus Bowel obstruction Incarcerated or strangulated hernia Fecal impaction or constipation Inflammatory bowel disease Gastroenteritis Irritable bowel syndrome

URINARY TRACT Pyelonephritis Cystitis Ureteral stone

VASCULAR

Septic pelvic thrombophlebitis Ovarian vein thrombosis Sickle cell disease Pelvic congestion syndrome

MUSCULOSKELETAL

Muscular strain or sprain Hernia Abdominal wall hematoma Pelvic fracture

NEUROLOGIC OR PSYCHIATRIC Depression Domestic violence Sexual abuse Abdominal migraine Herpes zoster

likelihood of these conditions, respectively. Patients who are actively undergoing infertility treatment are at increased risk for ectopic pregnancy, heterotopic pregnancy, ovarian torsion, and ovarian hyperstimulation syndrome. Round ligament pain is usually noted in the second trimester. Postpartum patients are at increased risk for endometritis. The presence, quantity, and duration of associated vaginal bleeding should be ascertained (see Chapters 31 and 178). In a nonpregnant patient, bleeding may be associated with abnormal uterine bleeding (eg, from PID, ovulatory dysfunction, cancer) or trauma (eg, vaginal laceration due to pelvic fracture, direct vaginal irritation or trauma). In a pregnant patient, bleeding may also be associated with a subchorionic hemorrhage in an otherwise viable pregnancy, ectopic pregnancy, nonviable intrauterine pregnancy (IUP) (which may continue to cause bleeding after expulsion of the uterine contents, especially if any products of conception are retained), or later in pregnancy with placenta previa or abruption. In some cases, the amount of bleeding may be substantial enough to necessitate blood transfusion and surgical intervention. The presence of vaginal discharge (color, consistency, odor) should also be ascertained. Sexual history is important, with emphasis on recent sexual contact and previous history of sexually transmitted disease. A history of any recent gynecologic procedures should be obtained because the onset of pelvic pain shortly after uterine instrumentation increases the possibility of uterine perforation or infection. All women should be interviewed in private to permit disclosure of sensitive information such as sexual history, pregnancy, recent abortion, and abuse.

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Differentiation of Common or Potentially Catastrophic Causes of Pelvic Pain ASSOCIATED SYMPTOMS

SUPPORTING HISTORY

Ectopic pregnancy Classically severe, sharp, (critical if ruptured) lateral pelvic pain, but severity, location, and quality highly variable

Vaginal bleeding (often mild, can be absent)

Missed period; history Common of previous ectopic pregnancy, infertility, pelvic surgery, PID, or IUD use

Ruptured ovarian cyst Abrupt moderate to (emergent—critical severe lateral pain with significant hemorrhage; otherwise, urgent)

Light-headedness if bleeding is severe; rectal pain arises from fluid in cul-de-sac.

Ovarian torsion (emergent)

Acute onset of moderate to severe lateral pain

Nausea and vomiting

Appendicitis (emergent)

Duration often First trimester

First trimester

Unilateral symptoms/ signs?

Urinary complaints and/or positive urinalysis

UTI Ureteral stone

No

No

Abdominal tenderness?

No

Yes

Yes Placental abruption Placenta previa SAB Round ligament pain Labor

Definite IUP on ultrasound?

Yes

Torsion Salpingitis, TOA Ruptured ovarian cyst Mittelschmerz

PID Endometritis Dysmenorrhea Fibroids Endometriosis

Appendicitis Diverticulitis Enteritis, colitis IBS Other

Musculoskeletal Abuse Depression

No

Threatened abortion Corpus luteum cyst

Ectopic pregnancy Spontaneous abortion Early pregnancy Molar pregnancy Fig. 30.1.  Diagnostic algorithm for acute pelvic pain; see text for details. H&P, History and physical; IBS, irritable bowel syndrome; IUP, intrauterine pregnancy; PID, pelvic inflammatory disease; SAB, spontaneous abortion; TOA, tubo-ovarian abscess; UTI, urinary tract infection.

abuse or have depression. Vascular or neuropathic causes of pain are possible but less common. If the available data do not make sense or conflict with the clinical gestalt, the following three steps should be considered; 1. Ensure that emergent, life-threatening diagnoses have been addressed (eg, ectopic pregnancy). 2. Reassess whether the presentation may be atypical (eg, reconsider appendicitis). 3. If emergent causes are unlikely and sufficient consideration was given to less likely disorders without uncovering a cause, address the possibility of depression or abuse. Follow-up planning for all patients is recommended.

EMPIRICAL MANAGEMENT An algorithm for the management of patients with acute pelvic pain is presented in Fig. 30.2. Patients in extremis are most likely hemorrhaging, although on occasion septic shock may be the cause. Ectopic pregnancy, placental abruption, and hemorrhagic ovarian cyst may cause life-threatening hemorrhage, with no or minimal vaginal bleeding. Patients with these disorders need rapid treatment with fluid and blood products and may require

surgical intervention before stabilization can be achieved. A bedside ultrasound generally will help the emergency clinician reach these presumptive diagnoses expediently. Septic shock may be a consequence of abdominal or pelvic processes and may require general surgical and gynecologic consultations, as well as admission to an intensive care setting. We recommend early administration of analgesia for patients with significant pain, a practice that greatly improves patient comfort and the reliability of the physical examination, which is otherwise hampered by the patient’s extreme pain, tenderness, or both. For severe pain, intravenous opioids such as morphine or hydromorphone are rapid and effective, titratable, and generally considered safe in pregnancy. After critical and emergent diagnoses have been excluded, well-appearing patients for whom a definitive or reasonable provisional diagnosis is reached may be discharged with close follow-up and appropriate treatment and precautions. Pregnant patients at a stage of fetal viability (20 weeks’ gestation or as per institutional guidelines) should be referred to the obstetric service for fetal monitoring before discharge. Pregnant patients who have suffered abdominal trauma, especially those later in pregnancy, should undergo monitoring before discharge (see Chapter 182).

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Monitor, IV access, O2 Volume resuscitation Bedside Hgb; call for blood if Hgb low, or with obvious bleeding.

Yes

Critical?

SECTION Two 

No

Undifferentiated right lower quadrant pain

Analgesia indicated Use medications safe in pregnancy until ruled out.

Urinalysis positive?

Consider UTI and/or ureterolithiasis. If not convincing, continue with algorithm. If pregnant at 3 months) will experience persistence or a recurrence within 12 months.9,11 In an ED population, there is substantial morbidity and ongoing analgesic use at 1 week and 3 months after the initial visit, greatest in those with chronic back pain and greater baseline disability.12,13

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BOX 32.1 

BOX 32.2 

Key Clinical Findings in the History and Physical Examination

Differential Considerations in Acute Low Back Pain

HISTORICAL INFORMATION

EXTRASPINAL CAUSES

Recent significant trauma History of cancer Anticoagulant use Intravenous drug use History of prolonged glucocorticoid use History of osteoporosis History of abdominal aortic aneurysm Patient > 50 yr Unrelenting night or rest pain Unexplained weight loss Recent bacterial infection Immunocompromised status Failure to improve after 6 wk of conservative therapy

PHYSICAL EXAMINATION

Abnormal vital signs—hypotension, hypertension, tachycardia, fever Unequal blood pressure readings in the upper extremities Murmur of aortic insufficiency Pulse deficit or circulatory compromise of the lower extremities Pulsatile abdominal mass Urinary retention Urinary or stool incontinence Loss of rectal sphincter tone Severe or progressive neurologic deficit Focal lower extremity weakness New ataxia or difficulty walking

II. DIAGNOSTIC APPROACH Differential Considerations The emergency clinician should evaluate for potentially lifethreatening and disabling causes of back pain. These can be broken down into two main categories: (1) spinal causes, such as epidural abscess or compressive mass, spinal column injury with cord or root compression, and cauda equina syndrome; and (2) extraspinal causes, such as thoracic aortic dissection and ruptured AAA (Box 32.2).

Pivotal Findings A careful, thorough history and physical examination are invaluable. Technologically sophisticated radiologic and laboratory studies are not a substitute for a detailed history and physical examination. This approach will help categorize patients into stable and unstable categories (Fig. 32.1). Certain findings will guide the additional evaluation for patients with neurologic deficits and more serious spinal or visceral sources (Table 32.1). The most important elements of the history, physical examination, and diagnostic testing are to answer two questions: • Is there evidence of extraspinal or systemic disease? • Is there evidence of neurologic compromise?

Symptoms As with any patient who complains of pain, symptoms should be characterized by the basic historical elements of the episode, such as the intensity, onset, character, severity, location, presence of radiation, exacerbating and alleviating factors, and presence of key clinical finding signs and symptoms (see Box 32.1). Most episodes

Chest—aortic dissection, bacterial endocarditis, pulmonary embolism, pneumonia, pleural effusion Abdominal—ruptured or expanding aortic aneurysm, esophageal disease, penetrating peptic ulcer disease, pancreatitis, pancreatic cancer, biliary colic, cholecystitis, cholangitis Genitourinary—renal colic, prostatitis, perinephric abscess, pyelonephritis, ovarian torsion or tumor, pelvic inflammatory disease, endometriosis Musculoskeletal—acute muscle strain, acute ligamentous injury Other—herpes zoster, retroperitoneal hemorrhage, psoas abscess, nonspecific low back pain

SPINAL CAUSES

Cauda equina syndrome, spinal epidural abscess or hematoma, spinal fracture, transverse myelitis, traumatic fracture, pathologic fracture, vertebral osteomyelitis, infectious diskitis, ankylosing spondylitis, spondylolysis or spondylolisthesis, disc herniation, degenerative disease (discs, facet joints), isolated sciatica, spinal stenosis

of lower back pain will resolve or significantly improve within 4 to 6 weeks11; therefore, lack of significant improvement in 6 to 8 weeks is also a warning sign. Presence of an individual key clinical finding does not necessarily correspond to a specific pathology; rather, it prompts the emergency clinician to a more serious underlying condition that may require further investigation. Many of these key clinical findings have poor or untested diagnostic accuracy and have meaning only in the context of the complete history and findings in a particular patient. Blindly allowing the presence of these individual findings to guide diagnostic treatment will lead to potentially unnecessary, misleading, and costly investigations in most patients. In one study, 80% of patients with back pain had at least one of these key clinical findings, despite a prevalence of serious disease of less than 1%. On the other hand, if there are no key clinical findings, one can be 99% confident that serious spinal disease had not been missed.14 Presence of multiple key clinical findings often is an indication for further investigation, which may be initiated in the ED or on an ambulatory basis, depending on the patient. In an ED population, four of the important variables associated with serious outcomes include (1) pain worse at night, (2) decreased lower extremity sensation, (3) use of anticoagulants, and (4) pain persisting despite appropriate treatment.15 Different causes of acute low back pain have different distinguishing characteristics (see Table 32.1). Typical nonspecific back pain is unilateral. Pain may radiate to the buttocks or posterior thigh but not past the knee, implying muscle or ligamentous strain or disk disease without associated nerve involvement. Pain is increased with movement and is relieved by rest, and there are no complaints of numbness, weakness, or bowel or bladder dysfunction. Inflammatory back pain (spondyloarthritis) is insidious in onset, affects younger patients (50, 64, or 70 years, depending on the guideline), prolonged steroid use, and substantial trauma.14,17,18 Disk herniation is unusual in those younger than 18 years and is rare in the fibrotic disks of older adults. In older patients, typically those older than 60 years, spinal stenosis is suggested by lower back pain with radiculopathy that is worsened with walking and prolonged standing (back extension). This is because erect posture narrows the cross-sectional area of the central canal and neural foramina. It is relieved by forward flexion (shopping cart sign), which increases spinal canal diameter, temporarily relieving the stenosis. Spinal stenosis causes diffuse intermittent burning, cramping pain in the back, motor weakness, reflex changes, and radiating pain in the buttocks, thigh, and legs, with associated paresthesias. This symptom constellation is termed neurogenic claudication (also called pseudoclaudication) and is caused by neurologic compression, unlike vascular claudication, which is caused by arterial insufficiency, may have abnormal pulses, and is relieved by rest. Immunocompromised patients, diabetics, intravenous drug users (IVDUs), those with recent spinal instrumentation or indwelling devices (eg, epidural catheters, spinal stimulators, vascular access) and those with a recent bacterial infection (eg, pneumonia, urinary tract infection) are at increased risk of a spinal bacterial infection. Recent gastrointestinal or genitourinary procedures may also cause a transient bacteremia, leading to an infectious cause of the patient’s back pain. A patient with current or recent IVDU and back pain should be assumed to have an abscess or vertebral osteomyelitis until proven otherwise. Patients with cancer also represent another high-risk group. Spinal epidural metastasis can be the initial presentation of malignancy or may occur in patients with a known primary malignancy. Spinal metastases usually arise in the posterior aspect of the vertebral body, with subsequent invasion of the epidural space. The spine is the third most common site for metastatic disease, most often involving the thoracic (70%) and lumbar spines (20%). The most common metastatic diseases affecting the spine are those of the lung, breast, prostate, kidney, and thyroid, lymphoma, and multiple myeloma. Patients present with back pain that can be intermittent and often responsive to nonsteroidal antiinflammatory drugs (NSAIDs) initially, but worsens over time. History may also reveal pain at night, rest pain, pain in multiple areas of the spine, or unexplained weight loss.17,19 Sudden severe pain raises concern for a pathologic fracture. Back pain associated with pain in other locations should prompt consideration of an extraspinal cause. Association with

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TABLE 32.1 

Classic Findings in Selected Serious Causes of Acute Back Pain FINDINGS

IMPORTANT PHYSICAL EXAMINATION FINDINGS ANCILLARY TESTING

DIAGNOSES

HISTORY

Aortic dissection

Associated diaphoresis, Often sudden-onset, unstable vital signs; tearing, severe pain; hypertension common; associated nausea, unequal upper extremity vomiting, acute anxiety blood pressure; common; syncope and new-onset aortic chest pain can occur. insufficiency murmur; central and peripheral neurologic deficits secondary to ischemia Pain may radiate to back, Pulsatile abdominal mass, flank, or testicle; abdominal bruits; syncope may be hypoperfusion present.

COMMENTS

CRITICAL Vascular

Abdominal aortic aneurysm (ruptured, expanding)

Infectious

Spinal epidural abscess

At-risk population with diabetes, chronic renal failure, IV drug use, alcoholism, cancer, recent spinal surgery, trauma, recent bacterial infection, bacteremia as risk factors

Fever (50%), back pain (75%); focal neurologic deficits are late findings (100 mL) indicate a denervated bladder and suggest significant neurologic compromise. If bladder catheterization is performed, one can test for trigone sensitivity by gently pulling on the catheter, which should produce the urge to micturate. This can help distinguish those with a true neurologic deficit from those with pain-associated retention.16 Straight leg raise (SLR) tests for disk herniation causing nerve root compression (sensitivity, 72%–97%; specificity, 11%–66%). SLR has a positive predictive value (PPV) of 67% to 89% and a negative predictive value (NPV) of 33% to 57% in patients with a high probability of having a disk herniation versus a PPV of 4% in patients with a low probability based on the absence of neurologic symptoms or sciatica. To perform this test, the patient is positioned supine, with the legs fully extended. The emergency clinician places one hand under the ankle and the other hand on the knee (to maintain leg extension). With the patient relaxed, the emergency clinician slowly lifts the patient’s leg by flexing the leg at the hip until pain is elicited or end range is reached. Test each leg separately. A positive test causes or reproduces radicular pain below the knee of the affected leg when the leg is elevated between 30 and 70 degrees. Care should be taken that the patient is not actively helping in lifting the leg and that the knee remains straight throughout the examination. A further positive finding occurs if radicular symptoms are elicited when the leg is then lowered until pain is eased and the ipsilateral ankle is dorsiflexed (Braggard’s sign). Pain at less than 30 degrees, more than 70 degrees, or with reproduction of pain only in the back, hamstring, or buttock region, does not constitute a positive test result. Pain referred to the affected leg when the opposite asymptomatic leg is tested, called a positive crossed SLR, is highly indicative of nerve root irritation from a herniated disk (specificity, 85%–100%; sensitivity, 29%).20 In cases where the patient is reluctant or unwilling to lie supine for SLR testing, the seated SLR or slump test should be attempted. The patient sits at the edge of the examination table and slumps forward while flexing the neck and trunk. This is followed by knee extension and ankle dorsiflexion. A positive test reproduces radicular pain. Waddell’s examination findings can aid in distinguishing between true pathologic back pain and nonorganic back pain; it can be remembered by the mnemonic DORST—distraction, overreaction, regional disturbances, simulation tests, tenderness). Waddell’s signs, especially if three or more are present, correlate with malingering and functional complaints (physical findings without anatomic cause). Superficial, nonanatomic, or variable tenderness during the physical examination suggests a nonorganic cause. Provocative maneuvers such as axial loading of the head or passive rotation of the shoulders and pelvis in the same plane should not elicit low back pain. There may be a discrepancy between the symptoms reported during the supine and seated SLR tests. The seated version of the test, sometimes termed the distracted SLR, can be performed while distracting the patient or appearing to focus on the knee. Furthermore, radicular pain elicited at a leg elevation of less than 30 degrees is suspicious because the nerve root and surrounding dura do not move in the neural foramen until an elevation of more than 30 degrees is reached. Sensory and motor findings suggestive of a nonorganic cause include stocking, glove, or nondermatomal sensory loss or weakness that can be characterized as “give-way,” jerky, or cogwheel

CHAPTER 32  Back Pain

weakness. Finally, gross overreaction is suggested by exaggerated, inconsistent, painful responses to a stimulus. These signs can be used in the evaluation of select patients and are merely a component of a comprehensive physical examination. They should never be used independently because they lack the sensitivity and specificity to rule out true organic pathology.

ANCILLARY TESTING Ancillary testing is not indicated in the absence of concerning findings, and routine (nonemergent) use of computed tomography (CT), magnetic resonance imaging (MRI), or laboratory testing should be discouraged. Blind diagnostic testing may lead to false-positive results and further unnecessary evaluations and interventions.

Laboratory Tests Laboratory testing, consisting of the determination of the white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level is indicated for clinical suspicion of infection or malignancy, new-onset back pain with a history of malignancy, or multiple risk factors for cancer. In cases of spinal infection, the sensitivity of an elevated WBC count is poor (35%–61%), but the ESR (76%–95%) and CRP (82%–98%) are more sensitive and may help guide further evaluation or consideration of other entities. Incorporation of ESR and CRP values into an ED decision guideline may improve diagnostic delays and help distinguish patients in whom MRI may be performed on a nonemergent basis.21 Infection is very unlikely in patients with an ESR less than 20 mm/h. An elevated ESR (>20 mm/h) is nonspecific for infection, however, and also may indicate occult malignancy (sensitivity, 78%; specificity, 67%). Urinalysis (UA) may be useful in suspected cases of renal disease with referred back pain (eg, nephrolithiasis, pyelonephritis, urinary tract infection). Blood cultures may be sent when there is a significant concern for an infectious cause, such as an epidural abscess, but this will not affect immediate decision making.

Imaging Imaging, like laboratory testing, is not indicated in the absence of concerns for malignancy, fracture, infection, or epidural compression syndrome. Although the added diagnostic value of modern neuroimaging is significant, unnecessary imaging only serves to increase the cost of the visit and length of stay and subject the patient to unnecessary radiation. Multiple evidence-based clinical practice guidelines have recommended avoiding routine spinal imaging for nontraumatic acute lower back pain in the absence of severe or progressive neurologic deficits or signs and symptoms that suggest a serious underlying condition. Although patient satisfaction is reportedly higher when imaging is performed, this is likely because the negative imaging provided a reassuring explanation for the patient, one that could, instead, have been provided by a thoughtful reassuring discussion by the emergency clinician. Early imaging is not useful and does not affect outcomes for pain, function, quality of life, or overall patient-related improvement. Across all age ranges, including older adults, imaging does not change the management of uncomplicated mechanical low back pain compared with usual care being provided without routine imaging.22,23 Despite this, a substantial portion of ED patients with lower back pain undergo nonindicated imaging.23 Plain films are rarely of use in the evaluation of nontraumatic back pain unless pathologic fracture is suspected. Most patients who require imaging will undergo CT or MRI. Plain films are indicated for new onset of lower back pain in a patient with a history of cancer, strong clinical suspicion for cancer, risk factors

for pathologic vertebral fracture, and trauma. Anteroposterior (AP) and lateral films provide reasonable detail in showing fractures, particularly in the lumbar spine. Additional views are only indicated if spondylolysis or spondylolisthesis is suspected. If evidence of neurologic emergency exists, bypass plain films and proceed directly to CT or MRI. For example, only a small minority of patients with malignant spinal cord compression will have the level of compression correctly identified on plain radiographs. In general, CT provides superior imaging of bone and only moderate detail of soft tissue, whereas MRI gives excellent detail of soft tissue and only moderate detail of bone. CT is increasingly used as a primary screening modality for moderate to severe spine trauma because it is superior to plain film for the detection of vertebral fractures and other bony pathology, especially fractures involving posterior spine structures, bone fragments within the spinal canal, or spinal malalignment. CT provides reasonable contrast resolution and can identify root compressive lesions, such as disk herniations, in the vast majority of cases. CT with myelography (or with intravenous [IV] gadolinium) may be used if there is concern for epidural abscess, epidural compression, or vertebral osteomyelitis in patients who are otherwise unable to have a MRI. CT cannot identify intrathecal pathology and is less sensitive than MRI in the detection of early inflammatory or infectious processes, neoplasm, or paraspinal soft tissue lesions. With the exception of the evaluation of acute trauma, MRI will identify almost all pathologic states that could benefit from surgical management. MRI is the modality of choice for evaluation of spinal infectious lesions (sensitivity and specificity > 90%), malignancy (sensitivity, 90%; specificity, 95%), disk herniation, and epidural compression syndrome (sensitivity and specificity > 90%).18 MRI in the ED is indicated for those patients with lower back pain in whom spinal infection, cauda equina syndrome, and/ or severe or progressive neurologic deficits are suspected. Without these clinical indications, MRI does not improve clinical outcomes (eg, pain, daily function, health status) and may actually worsen them, resulting in increased rates of subsequent interventions (eg, lumbosacral injections, back surgery) and increased health care expenditures.14,24-27 MRI is too sensitive and not specific enough to screen for other presentations of back pain in the ED and has no role in the evaluation of chronic lower back pain without strong clinical consideration of emergent pathologic causes. In patients with chronic, nonradicular back pain, MRI findings are not related to disability or pain intensity.28 Disk disease is a component of normal aging and is a very nonspecific finding. In fact, one in four asymptomatic persons younger than 60 years and one in three older than 60 years will have MRI findings of a herniated disk. Over 50% of asymptomatic patients are identified as having a bulging disk on MRI. Furthermore MRI studies have shown that almost twothirds of herniated disks regress or resolve over 6 months. Thus, imaging can reveal pathoanatomic abnormalities that have little or no correlation with patient symptoms.29

DIAGNOSTIC ALGORITHM Critical Diagnoses Following the history and physical examination, patients with acute low back pain can be divided into three main categories: (1) those with extraspinal causes (chest, abdominal, or retroperitoneal); (2) those with critical or emergent spinal pathology (eg, from tumor, infection, or epidural compression syndrome); and (3) those with nonspecific lower back pain, sciatica, or spinal stenosis. (see Box 32.2) The first priority is to rule out nonspinal pathology, such as an AAA. The next step is to exclude the presence of serious spinal pathology, such as epidural compression syndrome or abscess. The final priority is to decide whether the

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patient has musculoskeletal or nerve root pain. In the absence of radicular pain, the pain is classified as nonspecific low back pain. Most patients seen in the ED will have nonspecific low back pain, and no laboratory testing or imaging is indicated. A smaller group of patients will have radiculopathy or spinal stenosis. In the absence of key clinical findings or progressive neurologic symptoms, treatment will generally mirror that of nonspecific low back pain, and MRI can be delayed for 4 to 6 weeks and coordinated by the PCP if they are candidates for surgery or interventional pain management (eg, epidural steroid injections). Most patients with sciatica recover without surgery. Following the history and physical examination, the minority of patients who have multiple key clinical findings or a moderate to high probability of a critical or emergent condition will require further urgent evaluation and management aimed at identifying and treating the underlying cause. This care is started in the ED and usually consists of an MRI evaluation. The degree of neurologic impairment, duration, and rate of worsening dictate whether these tests are performed on an urgent or emergent basis. If the motor loss in a muscle segment is rapidly progressive or 3/5 or less, MRI and spine surgery consultation should be undertaken emergently. If motor loss is subacute, stable, and with 4/5 strength, it is possible to wait 1 or 2 days for imaging, with surgical follow-up soon after. This should be arranged with the PCP, radiologist, and surgeon. The patient is instructed to return immediately if worsening weakness occurs. Spinal epidural abscess remains a very challenging diagnosis to make. Almost 50% of patients are initially misdiagnosed and average two ED visits before admission. Do not rely on the classic triad of fever, back pain, and neurologic deficits because all three components are present only 15% of the time and fever is only present in 50% to 66% of patients at presentation. ESR and CRP values may help in risk stratification. Perform MRI when a moderate to high pretest probability exists (eg, use of IV drugs with new back pain and unexplained fever), regardless of a normal WBC count and neurologic examination and the absence of fever.18 Preoperative neurologic function is a good predictor of final outcome. Those with few to no risk factors, normal WBC, ESR, CRP, and plain films, and a normal neurologic examination can be managed with close follow-up and appropriate discharge instructions. Like spinal epidural abscess, cord compression (eg, cauda equine syndrome) is another critical condition in which delayed diagnosis is common, and neurologic function at the time of diagnosis is the primary determinant of the ultimate outcome. Unfortunately, no constellation of symptoms or examination findings is 100% sensitive. No single symptom predicts the radiographic finding of cauda equina syndrome with an accuracy greater than 65%.30 The probability of significant epidural spinal compression without urinary retention is highly unlikely, although it should be noted that postvoid residual volume can be increased in patients on opioid analgesics. MRI of the lumbosacral spine should be ordered from the ED if there is moderate to high suspicion. Contrast enhancement is not necessary in most cases, but when an infiltrative cause is suspected, such as from infection or metastasis, contrast may be useful. The MRI should include the entire spine to evaluate for falsely localizing sensory levels because clinically silent multilevel involvement is common, and there is a 10% risk of distant asymptomatic metastasis, which may affect subsequent treatment (eg, cervical lesion causing a thoracic sensory level). Fewer than 25% of patients with malignant spinal cord compression have a sensory level within three vertebrae of the true compression level, as demonstrated on an MRI scan. Early initiation of glucocorticoids in consultation with the treating spinal surgeon should follow when the diagnosis is suspected, rather than waiting hours for confirmatory testing. Neoplastic epidural spinal cord compression is a true emergency and requires

prompt diagnosis and treatment for the best possible patient outcome. ED management includes early MRI, pain control, and high-dose corticosteroids, with specialty consultation for radiation therapy and/or surgical decompression. A systematic approach to the patient with cancer and back pain is accomplished by categorizing patients into two groups based on signs and symptoms: 1. Patients with sudden or rapid change in their back pain, development of new or progressive signs or symptoms suspicious for epidural compression (eg, bowel or bladder incontinence, weakness, loss of reflexes, multiroot findings), especially the development of bilateral severe sciatica. These patients are at high risk for rapid deterioration and should be evaluated and treated as previously discussed for possible emergent epidural compression syndrome in the ED. 2. Patients with back pain but without changes in neurologic status should have plain films and ESR and CRP determinations in the ED. If these are abnormal, or any change in neurologic status occurs, obtain an MRI scan within 24 hours (inpatient or outpatient). If there is any bony pathology, advanced imaging with MRI or CT is indicated on an outpatient basis within the next several days. If plain films are normal, further evaluation is not emergent. Patients must be closely followed by their PCP for improvement and lack of progressive symptoms. A follow-up appointment should occur within 1 week. Finally, some patients without known cancer have key clinical findings suggestive of malignancy, such as unexplained weight loss or back pain that is worse at night. As previously discussed, these patients require further risk stratification with plain radiographs and laboratory testing, including a WBC count, ESR, and CRP.18 With normal test results, these patients can be referred to their PCP for further evaluation. With abnormal diagnostic results, such as a bone lesion on plain film or an extremely elevated ESR, urgent MRI should be performed on an outpatient basis within the next week.

Empirical Management In general, the recommended role of the emergency clinician in the management of acute lower back pain is to identify whether significant pathology is present, and establish a correct diagnosis while avoiding excessive investigation. Subsequent goals include initiating appropriate treatment, providing analgesia, and educating the patient. The initial empirical management of acute back pain depends on the presenting vital signs and the patient’s overall appearance. Figure 32.2 details the specific management considerations for treatment. Show support by acknowledging the patient’s pain and providing reassurance that back pain is very common, the pain does not indicate ongoing harm or serious pathology, and most patients eventually experience spontaneous improvement. Care should be taken to avoid negative or confusing messages. An example of this would be avoiding language that might frighten the medically naïve patient (eg, ruptured disk) and imply a serious abnormality when none exists.31,32 Provide a full explanation of the diagnosis, evaluation, treatment plan, and expected time course for recovery in terms that the patient understands. Patients should be educated about why they are not undergoing laboratory or radiographic studies and should be reassured of the likely benign course of the pain. Most patients can be convinced by education and an explanation of radiation dosing and associated deleterious effects. This approach will help avoid misperceptions of substandard care or subsequent unnecessary return visits within 48 hours when symptoms are still present. For some patients, chronic, recurrent back pain is a long-term issue, and they may visit the ED during an acute exacerbation. These patients still require a thorough

CHAPTER 32  Back Pain

New, progressive neurologic abnormalities (bowel/ bladder incontinence, saddle anesthesia, multi–nerve root involvement)

Emergent MRI and consultation

Consider ultrasound or CT for emergent extraspinal causes

Associated with chest, abdominal, or flank symptoms

Fracture risk • Substantial trauma • Prolonged steroids • Older age • Osteoporosis

Low back pain (LBP) • History/physical • Red flags

Infection risk

Moderate to high suspicion • Fever • Abnormal neuro exam • IVDU • Recent bacterial infection • Immunocompromised • Recent spinal instrumentation or indwelling devices

No red flags/ reassuring H&P – no need for ancillary testing • Nonspecific LBP • Single nerve root involvement (sciatica) • Spinal stenosis

Plain film +/CT

Cancer risk

Low suspicion (other red flags)

Low suspicion (other red flags)

Risk-stratify with: ESR, CRP, plain film

Risk-stratify with: ESR, CRP, plain film

Abnormal

Abnormal

MRI

Moderate to high suspicion for neoplastic process • History of cancer • Multiple cancer risk factors

MRI

Fig. 32.2.  Management of acute low back pain. AAA, Abdominal aortic aneurysm; ADLs, activities of daily living; ASAP, as soon as possible; CBC, complete blood count; CRP, C-reactive protein; CT, computed tomography; ECG, electrocardiogram; echo, echocardiogram; ED, emergency department; ESR, erythrocyte sedimentation rate; exam, examination; H&P, history and physical examination; IVDU, intravenous drug use; MRI, magnetic resonance imaging; neuro, neurologic; NSAIDs, nonsteroidal antiinflammatory drugs.

examination and review of key clinical findings to risk-stratify them better and guide ED evaluation. Labelling these patients without performing a thorough investigation can have dangerous consequences. For example, cauda equina syndrome is often seen in those with a prior history of back pain or sciatica. One of the most important goals of treatment is to provide an acceptable level of analgesia while the underlying condition resolves, or ameliorate the suffering of those patients who await definitive therapy. Emergency clinicians also should be alert to racial bias in treatment of back pain.33 Despite numerous studies and recommendations, few if any treatments have been proven effective for the management of low back pain. Patients’ expectations are known to influence the outcome of treatment, and this process can begin in the ED. Advice and information about back pain, carefully selected and presented, can have a positive effect on patients’ beliefs and clinical outcomes.32 Setting a goal that a pain-free expectation is less realistic than pain improvement may be beneficial. Avoid making unnecessary presumptive diagnoses, and avoid the medicalization of benign conditions by ordering unnecessary tests. This behavior, coupled with the overprescription of analgesics, particularly opioids, fosters a belief on the part of the patient of the existence of serious pathology for an otherwise benign condition.

Nonpharmacologic analgesia can include the use of heat or cold externally applied to the lower back. There is better evidence for the benefits of heat than ice for the treatment of lower back pain. First-line pharmacologic therapy includes nonopioid analgesics (eg, acetaminophen, NSAIDs). Some studies have called into question the efficacy of acetaminophen for acute lower back pain, despite its universal recommendation as a first-line analgesic.34-36 When using acetaminophen, dosing should start at the maximal recommended doses. There is little to no benefit of adding high-dose acetaminophen to NSAID therapy. Parenteral NSAID analgesia is rarely indicated and is no more effective than an equivalent dose of an oral NSAID. Lidocaine transdermal patches (Lidoderm) are a safe, nonsedating, effective treatment option for acute and subacute back pain. Despite claims to the contrary, there is no convincing evidence for the benefit of so-called muscle relaxants, such as cyclobenzaprine and carisoprodol, for acute back pain, and we do not recommend their use.37 These medications have a high incidence of significant side effects, such as anticholinergic effects, dizziness, and sedation, thereby limiting their use. When simple analgesia is not sufficient, despite a reasonable trial with proper dosing, and the patient has prominent symptoms of sleep disturbance and anxiety related to the pain, a benzodiazepine may be prescribed

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Signs, Symptoms, and Presentations

as an adjunct to nonopioid analgesia. Their effect, if any, likely is based on their anxiolytic and sedative properties, which may promote sleep and synergize pain relief. Sleep quality is related to subsequent lower back pain intensity,38 so benzodiazepines may be beneficial, with limited side effects, when taken at bedtime. There is no clear benefit of oral glucocorticoids prescribed in the ED in regard to low back pain (with or without sciatica), activity level, or ability to return to work.39 If the pain is severe, IV opioids such as morphine or hydromorphone are the preferred analgesic and should be given in a titrated fashion. However, opioids should be considered a secondline alternative and are best used for those experiencing severe acute back pain with inadequate control with nonopioid analgesics.40 When administering opioids, frequently reassess the patients until an adequate response is reached, and then transition to oral agents in preparation for discharge. Despite back pain being the most common indication for opioid prescription in an ED population, routine use of opioids for acute or chronic back pain is not recommended.41 Also, although opioids are effective for relieving pain, they do not improve functional status. When prescribed, opioids should be combined with NSAIDs, taken on a fixed dosing schedule at the lowest dose possible, and taken only for a limited, clearly defined period (eg, 20 mph) impact • Motorcycle crash > 20 mph No Assess special patient or system considerations

Step four

• Older adults – Risk of injury/death increases after age 55 years – SBP < 110 might represent shock after age 65 years – Low-impact mechanisms (eg, ground level falls) might result in severe injury • Children – Should be triaged preferentially to pediatric-capable trauma centers • Anticoagulants and bleeding disorders – Patients with head injury are at high risk for rapid deterioration • Burns – Without other trauma mechanism: triage to burn facility – With trauma mechanism: triage to trauma center • Pregnancy > 20 weeks • EMS provider judgment No Transport according to protocol When in doubt, transport to a trauma center

Fig. 33.5.  Triage decision scheme. EMS, Emergency medical services. (Adapted from American College of Surgeons, Committee on Trauma: Resources for the optimal care of the injured patient, Chicago, 2012, American College of Surgeons.)

CHAPTER 33  Multiple Trauma

hypotension, mean arterial pressure (MAP) is restored to a goal of approximately 50 mm Hg. Data have shown that this strategy leads to less blood product use, less bleeding, and lower incidence of coagulopathy.11,12 Permissive hypotension is contraindicated in the management of traumatic brain injury because of the risk of hypoperfusion.13-15 Rather than any particular MAP target, restoration of adequate tissue perfusion, with normal mentation or, more importantly, normalization of tissue oxygen saturation (Sto2) monitoring, is the clinically relevant endpoint in the resuscitation of the trauma patient.67-69 The role of ED thoracotomy (EDT) has become more selective to limit futile resuscitation efforts and minimize risk to providers. Patients with penetrating trauma who undergo cardiac arrest while in transport or in the ED are most likely to benefit from EDT. In contrast, cardiac arrest patients with blunt trauma, prolonged cardiopulmonary resuscitation (CPR), or delayed transport times generally have dismal outcomes that are not altered by EDT.70 Most institutions have protocols in place outlining criteria regarding when EDT should be performed. The National Association of EMS Physicians and ACS Committee on Trauma have published guidelines for withholding or terminating resuscitation efforts in out-of-hospital traumatic cardiac arrest patients. As a result, these guidelines often limit the transport of patients who would not likely benefit from EDT. Patients who may not be transported include any blunt trauma patient without vital signs at the scene, apneic or pulseless penetrating trauma victims without other signs of life, patients undergoing more than 15 minutes of CPR, and patients with transport times of more than 15 minutes after arrest.71-73 Suggested algorithms for the application of EDT are outlined in Figs. 33.5, 33.6, and 33.7. EDT is discussed further in Chapter 38. When EDT is performed, the goal is to manage rapidly correctable traumatic injuries and allow for transfer to the operating room for definitive intervention. To assess disability, a rapid assessment of the patient’s neurologic status is necessary early in the ED course. If intubation is necessary early in the patient’s treatment, perform a brief neurologic examination, including level of consciousness, tone and motor ability for all four extremities (eg, spontaneous, purposeful, withdrawal to pain), anal sphincter tone (if obtunded or evidence of paralysis), and any lateralizing signs, prior to administration of the paralytic and induction agent.

DISPOSITION The decision to admit the patient or transfer to a tertiary care facility should be coordinated based on available resources, consultation with the trauma surgeon, and consideration of institutional and regional guidelines. The ultimate disposition is dictated by a number of factors, including the patient’s condition, nature of the injury, and availability of surgeons, subspecialists, and anesthesiologists. Possible dispositions include transfer to the operating room, admission to the surgical service, limited observation in the ED, and transfer to another hospital. The level of care and monitoring established in the ED should be maintained throughout transfer. All equipment and medications needed for resuscitation and maintenance of vital functions should be

Signs of life on arrival in emergency department? (any one of five equals signs of life) Blood pressure OR Pulse OR Cardiac rhythm OR Respiratory effort OR Echo cardiac activity or tamponade

Yes

No

Echo evidence for tamponade?

Yes

No

Signs of life at scene?

Full resuscitation Consider thoracotomy

Yes

Yes

No

Paramedic CPR 3) O = Obstruction (presence of any condition such as epiglottitis, peritonsillar abscess, trauma) N = Neck mobility (limited neck mobility) a

Patients in the difficult intubation group have higher LEMON scores.

Fig. 35.20.  Ultrasound image of a globe rupture with lens dislocation. At the top of the image, the cornea is visible, and just below that is the dislocation, with hemorrhage visible posteriorly.

or anesthesiology-assisted intubations with the use of adjuncts such as the GlideScope or lighted stylet.44-51 Control of local bleeding is the other significant out-of-hospital consideration in facial trauma. In many areas, external compression is sufficient to control bleeding during transport. Epistaxis and significant intraoral bleeding can be more difficult to treat. Even in the setting of significant nasal trauma, the soft portions of the nares can be compressed to stop anterior nasal bleeding. In an awake alert patient with intraoral bleeding, 4- × 4-inch gauze packing may be placed into the buccal space to provide control. If these maneuvers are insufficient, and the patient’s injuries require spinal immobilization, intubation may be a necessary first step to control intraoral or nasopharyngeal bleeding. After

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General Concepts and System Injuries

intubation, large amounts of gauze can be placed via the mouth into the oropharynx and nasopharynx to obtain control via direct pressure. If out-of-hospital personnel suspect a ruptured globe, special protection against compression of the eye (eg, eye cup, noncontact shielding) should be provided in the field. Avulsed parts, including the ears, tip of the nose, teeth, or completely avulsed flaps, should be transported with the patient in saline-soaked gauze. Completely avulsed teeth should be removed and carried with the patient during transport. Neurologically normal, nonintoxicated patients may be able to carry avulsed teeth in their mouths, held between the gum and buccal mucosa. Patients who are not neurologically normal, are intoxicated, require cervical spine immobilization, are nauseated, or cannot be transported upright should not be transported with avulsed teeth held in the mouth. In such cases, the risk of aspirating the teeth outweighs any other concerns, and the teeth should be transported in a container with sterile saline. Incompletely avulsed teeth should be left in place and not manipulated.

Emergency Department Treatment General Measures The initial evaluation in the ED should re-address the question of intubation. In the setting of significant distortion of the mouth, oropharynx, or upper neck by avulsion or hematoma, the awake fiberoptic method may optimize the chances of a successful intubation. When there is significant distortion of the oropharynx or larynx, a laryngeal mask airway may not achieve a sufficiently tight fit to allow ventilation. Emergent cricothyroidotomy is the procedure of choice if endotracheal intubation is impossible. Unless there is life-threatening hemorrhage from the face, facial injuries can be safely left to the secondary survey after the airway has been secured. The emergency clinician should avoid being distracted by a facial injury and search intensively for head, neck, chest, abdominal, pelvic, and extremity injuries. In-depth ocular examinations and other special testing should not be performed until other serious injuries have been managed emergently. Significant bleeding can often be controlled by compression. If compression fails, hemostasis can be achieved in the ED by ligation of the relevant vessel. Great care should be taken, however, not to clamp or tie structures blindly deep within the face because serious iatrogenic injury of nerve or ductal structures could result. Massive uncontrollable bleeding from facial fractures occurs rarely and is best treated with arterial embolization, if available.52

Intraarterial vasopressin has recently been suggested as an option for hemostasis.52 Tranexamic acid may also show promise in controlling hemorrhage from facial trauma.53 In the rare case of a patient acutely exsanguinating from a facial wound, the external carotid artery can be emergently ligated. This ligation is best accomplished with surgical assistance. Bite wounds, gross contamination, or significant tattooing from foreign bodies should be addressed definitively as soon as possible, given the needs of the patient’s other injuries. Definitive treatment of simple soft tissue injuries can be left for 24 hours, if needed, after irrigation and temporary approximation. Ideally, facial fractures are treated early, before significant swelling occurs, or after several days, when return of more normal facial contours can aid in the repair. The need for tetanus prophylaxis should be considered for all open wounds. If the injury is an animal bite, the need for rabies prophylaxis should be considered. Because the rabies virus is transmitted to the brain along nerve axons, and symptomatic disease theoretically may occur sooner with wounds of the head, face, and neck, initiating rabies treatment within 5 days of the injury is recommended. Because lead poisoning has been reported from the ingestion of shotgun pellets in patients with primarily facial injuries, consideration should be given to looking for the presence of pellets in the gastrointestinal tracts of these victims. A plain x-ray film of the abdomen suffices. Early endoscopic removal of the pellets should limit future toxicity. The final part of the physical examination when dealing with facial trauma is the importance of documentation. Facial injuries may be evidence of assault, domestic violence, or child abuse. Careful documentation of findings, including photographs, drawings, or both, not only communicates initial findings to other practitioners but also can provide crucial legal evidence because many of these cases have forensic implications or result in litigation.

DISPOSITION The decision to discharge or admit patients with facial trauma depends on their associated injuries, general injury severity, and plans for treatment. In general, the emergency clinician can handle the initial resuscitation and stabilization of patients with facial trauma. It is recommended that early consultation with the appropriate surgical specialists happen once the patient has been stabilized. Antibiotics should be considered in cases of severe facial trauma or open fractures. Patients with isolated facial trauma that has been repaired or stabilized and with no airway issues are usually discharged with close follow-up.

KEY CONCEPTS The face is central to the patient’s ability to breathe, eat, and communicate. Injuries to the face can have serious psychological and psychosocial consequences. • Facial injuries may be prevented by the appropriate use of seat   belts, child restraints, air bags, helmets, and mouth and face   guards. • The epidemiology of facial injury is changing, with an increasing proportion of injuries occurring as a result of interpersonal violence. A careful history is required, and the possibility of abuse should be considered for every patient.

• Shock from facial trauma is rare and results only from obvious external bleeding. Facial injuries should not distract the emergency clinician from aggressively searching for other causes of shock. • Assertive management of the airway is indicated in a patient with significant facial injuries. Surgical management (cricothyroidotomy) may be required, particularly with gunshot wounds. • Directed facial CT scanning is the best imaging technique in patients with obvious injuries. • Definitive treatment may be delayed, if necessary, to allow other serious injuries to be addressed.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 35  Facial Trauma

REFERENCES 1. Rankin M, Borah GL: Appearance is a function of the face. Plast Reconstr Surg 125:873–878, 2010. 2. De Sousa A: Psychological issues in acquired facial trauma. Indian J Plast Surg 43:200–205, 2010. 3. Prashanth NT, Raghuyee HP, Kumar D, et al: Anxiety and depression in facial injuries: a comparative study. J Int Oral Health 7:94–100, 2015. 4. Prashanth NT, Raghuyeer HP, Kumar RD, et al: Post-traumatic stress disorder in facial injuries: a comparative study. J Contemp Dent Pract 16:118–125, 2015. 5. Glynn SM: The psychosocial characteristics and needs of patients presenting with orofacial injury. Oral Maxillofac Surg Clin North Am 22:209–215, 2010. 6. Glynn SM, Shetty V: The long-term psychological sequelae of orofacial injury. Oral Maxillofacial Surg Clin North Am 22:217–224, 2010. 7. De Sousa A: Psychological issues in acquired facial trauma. Indian J Plast Surg 43:200–205, 2010. 8. Islam S, Cole JL, Walton GM, et al: Psychiatric outcomes in operatively compared with non-operatively managed patients with facial trauma: is there a difference? J Plast Surg Hand Surg 46:399–403, 2012. 9. Gironda M, Lui A: Social support and resource needs as mediators of recovery after facial injury. Oral Maxillofac Surg Clin North Am 22:251–259, 2010. 10. Marshall GN: Screening for psychiatric problems in the orofacial trauma setting. Oral Maxillofacial Surg Clin North Am 22:225–229, 2010. 11. Grant AL, Ranger A, Young GB, et al: Incidence of major and minor brain injuries in facial fractures. J Craniofac Surg 5:1324–1328, 2012. 12. Mukherjee S, Revington P: Cervical spine injury associated with facial trauma. Br J Hosp Med 75:331–336, 2014. 13. Tholpady SS, DeMoss P, Murage KP, et al: Epidemiology, demographics, and outcomes of craniomaxillofacial gunshot wounds in a Level 1 trauma center. J Craniomaxillofac Surg 42:403–411, 2014. 14. Rahman SA, Chandrasala S: When to suspect head injury or cervical spine injury in maxillofacial trauma. Dent Res J (Isfahan) 11:336–344, 2014. 15. Mulligan RP, Friedman JA, Mahabir RC: A nationwide review of the associations among cervical spine injuries, head injuries, and facial fractures. J Trauma 68:587–592, 2010. 16. Khonsari RH, Fleuridas G, Arzul L, et al: Severe facial rubber bullet injuries: less lethal but extremely harmful weapons. Injury 41:73–76, 2010. 17. Caputo ND, Raja A, Shields C, et al: Re-evaluating the diagnostic accuracy of the tongue blade test: still useful as a screening tool for mandibular fractures? J Emerg Med 45:8–12, 2013. 18. Prosser J, Vender J, Solares C: Traumatic cerebrospinal fluid leaks. Otolaryngol Clin North Am 44:857–873, 2011. 19. McCudden CR, Senior BA, Hainsworth S, et al: Evaluation of high resolution gel β(2)-transferrin for detection of cerebral spinal fluid leak. Clin Chem Lab Med 51:311–315, 2013. 20. Crecelius C: Soft tissue trauma. Atlas Oral Maxillofac Surg Clin North Am 21:49–60, 2013. 21. Sabatino F, Moskovitz JB: Facial wound management. Emerg Med Clin North Am 31:529–538, 2013. 22. Singer AJ, Kinariwala M, Lirov R, et al: Patterns of use of topical skin adhesives in the emergency department. Acad Emerg Med 17:670–672, 2010. 23. Talan DA, Krishnadasan A, Gorwitz RJ, et al: Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients, 2004 and 2008. Clin Infect Dis 53:144–149, 2011. 24. Yeroshalmi F, Sidoti EJ, Jr, Adamo AK, et al: Oral electrical burns in children—a model of multidisciplinary care. J Burn Care Res 32:25–30, 2011. 25. Lauder A: Antibiotic prophylaxis in the management of complex midface and frontal sinus trauma. Laryngoscope 120:1940–1945, 2010. 26. Zilinskiene L, Idle MR, Colley S: Emergency radiology: maxillofacial and skull-base trauma. Trauma 16:243–255, 2014. 27. Uzelax A, Gean AD: Orbital and facial fractures. Neuroimag Clin North Am 24: 407–424, 2014.

28. Krishnan DG: Systematic assessment of the patient with facial trauma. Oral Maxillofacial Surg Clin North Am 25:537–544, 2013. 29. Gelesko S, Markiewicz MR, Bell R: Responsible and prudent imaging in the diagnosis and management of facial fractures. Oral Maxillofacial Surg Clin North Am 25: 545–560, 2013. 30. Kellman RM, Tatum SA: Pediatric craniomaxillofacial trauma. Facial Plast Surg Clin North Am 22:559–572, 2014. 31. Schmidt RS, Dodson KM, Goldman RA: Prophylactic antibiotic therapy for fractures of the maxillary sinus. Ear Nose Throat J 94:170–177, 2015. 32. Veeravagu A, Joseph R, Jiang B, et al: Traumatic epistaxis: skull base defects, intracranial complications and neurosurgical considerations. Int J Surg Case Rep 4:656– 661, 2013. 33. Patel PB, Stanton D, Granquist EJ: Common dental and orofacial trauma. Med Clin North Am 98:1261–1279, 2014. 34. Patil S, Patil R: Dental trauma and replantation of avulsed teeth. Nat J Integr Res Med 4:166, 2013. 35. Petrovic B, Marković D, Peric T, et al: Factors related to treatment and outcomes of avulsed teeth. Dent Traumatol 26:52–59, 2010. 36. Murray J: Mandible fractures and dental trauma. Emerg Med Clin North Am 31:553–573, 2013. 37. McTigue D: Overview of trauma management for primary and young permanent teeth. Dent Clin North Am 57:39–57, 2013. 38. Morris LM, Kellman RM: Complications in facial trauma. Facial Plast Surg Clin North Am 21:605–617, 2013. 39. Roth FS, Koshy JC, Goldberg JS, et al: Pearls of orbital trauma management. Semin Plast Surg 24:398–410, 2010. 40. Nace SR: Cerebrovascular trauma. Neuroimaging Clin N Am 24:487–511, 2014. 41. Emmett KP, Fabian TC, DiCocco JM, et al: Improving the screening criteria for blunt cerebrovascular injury: the appropriate role for computer tomography angiography. J Trauma 70:1058–1065, 2011. 42. Theoret J, Sanz GE, Matero D, et al: The “guitar pick” sign: a novel sign of retrobulbar hemorrhage. CJEM 13:162–164, 2011. 43. Adeyemo W, Akadiri O: A systematic review of the diagnostic role of ultrasonography in maxillofacial fractures. Int J Oral Maxillofac Surg 40:655–661, 2011. 44. Lock R: Managing the difficult airway in craniomaxillofacial trauma. Craniomaxillofac Trauma Reconstr 3:151–159, 2010. 45. Barak M, Bahouth H, Leiser Y, et al: Airway management of the patient with maxillofacial trauma: review of the literature and suggested clinical approach. Biomed Res Int 2015:724032, 2015. 46. Vidya B, Cariappa KM, Kamath AT: Current perspectives in intraoperative airway management in maxillofacial trauma. J Maxillofac Oral Surg 11:138–143, 2012. 47. Osinaike B, Gholahan O, Olusanya A: Intra-operative airway management in patients with maxillofacial trauma having reduction and immobilization of facial fractures. Niger J Surg 21:26–30, 2015. 48. Jaisani M, Pradhan L, Bhattarai B, et al: Intubation techniques: preferences of maxillofacial trauma surgeons. J Maxillofac Oral Surg 14:501–505, 2015. 49. Jacoment A, Tasman A: Airway management in facial trauma patients. Facial Plast Surg 31:319–324, 2015. 50. Dong Y, Li G, Wu W, et al: Lightwand-guided nasotracheal intubation in oromaxillofacial surgery patients with anticipated difficult airways: a comparison with blind nasal intubation. Int J Oral Maxillofac Surg 42:1049–1053, 2013. 51. Robertson CG, Doucet JC: Helping anesthesiologists understand facial fractures. Oral Maxillofac Surg Clin North Am 25:561–572, 2013. 52. Boswell KA: Management of facial fractures. Emerg Med Clin North Am 31:539–551, 2013. 53. Dakir A, Ramalingam B, Ebenezer V, et al: Efficacy of tranexamic acid in reducing blood loss during maxillofacial trauma surgery—a pilot study. J Clin Diagn Res 8:ZC06–ZC08, 2014.

CHAPTER 35: QUESTIONS & ANSWERS 35.1. Stensen’s duct enters the mouth most closely to which tooth? A. First lower molar B. First upper molar C. First upper premolar D. Second lower molar E. Second upper molar

They surround the ducts draining the submandibular glands (Wharton’s ducts). The body of the submandibular gland is folded around the mylohyoid muscle so that a portion lies within the floor of the mouth and a portion lies external to it. The submandibular (Wharton’s) ducts run from the external portion of the gland to empty into the mouth on either side of the frenulum of the tongue.

Answer: E. The salivary system consists of the parotid, sublingual, and submandibular glands. The parotid is the largest of these glands, lying just anterior to the ear and wrapping around the mandible. The parotid is superficial to the masseter muscle and drains via Stensen’s duct, a 5-cm tube that curves around the anterior edge of the masseter to enter the mouth opposite the second upper molar. The sublingual glands lie entirely within the floor of the mouth and drain into the mouth via ductules.

35.2. Which term is used to describe bilateral transverse fractures through the maxilla above the roots of the teeth? A. Craniofacial disjunction B. Le Fort I fracture C. Le Fort II fracture D. Le Fort III fracture E. Trimalar fracture

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Answer: B. Tripod (or trimalar) fractures are among the simplest fractures of the midface and include fractures of three bones—the lateral orbit, zygoma, and maxilla. More complex fractures of the midface are classified using the Le Fort system, although many complex fractures defy classification with this system. A Le Fort I fracture involves a transverse fracture through the maxilla above the roots of the teeth and may be unilateral or bilateral. Patients may complain of malocclusion, and the maxilla may be mobile when the upper teeth are grasped and rocked. A Le Fort II fracture is typically bilateral and pyramidal in shape. It extends superiorly in the midface to include the fracture of the nasal bridge, maxilla, lacrimal bones, orbital floor, and rim. In these cases, the nasal complex moves as a unit with the maxilla when the teeth are grasped and rocked. Le Fort III fractures involve fracturing the connections between the elements of the skull and face (craniofacial disjunction). These fractures start at the bridge of the nose and extend posteriorly along the medial wall of the orbit (ethmoids), along the floor of the orbit (maxilla) and through the lateral orbital wall, and finally break through the zygomatic arch. Intranasally, they extend through all the lesser bones to the base

of the sphenoid and frequently are associated with a cerebrospinal fluid (CSF) leak. 35.3. Treatment for a patient with a blowout fracture can include all the following recommendations except which one? A. Application of cold compress to reduce swelling B. Appropriate oral antibiotic C. Discouraging nose blowing to avoid creating or exacerbating any orbital emphysema D. Use of decongestants to help keep the sinuses clear of any draining fluid E. Use of steroid eye drops to help decrease any inflammation in the affected eye Answer: A. The use of steroid eye drops should not be initiated by the emergency clinician for a blowout fracture. Antibiotic prophylaxis against the potential sequelae of sinusitis, orbital cellulitis, and other more malignant intracranial infections is appropriate, as would be the use of decongestants and the avoidance of any activities that would exacerbate orbital emphysema.

C H A P T E R 36 

Spinal Injuries Amy H. Kaji  |  Robert S. Hockberger

PRINCIPLES Background and Importance According to the National Spinal Cord Injury Statistical Center, motor vehicle collisions (MVCs) account for 37% of all spinal injuries.1 Speeding, alcohol intoxication, and failure to use restraints are major risk factors. The next most common cause of spinal cord injury (SCI) is falls, followed by acts of violence (primarily gunshot wounds) and sporting activities. Approximately 80% of victims are male, and the average age at injury is 42.6 years. The lifetime cost to care for SCI victims ranges from $1 million if older than 50 years, with incomplete motor function, to over $4 million for those younger than 25 years, with complete paraplegia. The total cost to society from lifelong medical expenses and lost productivity for all ages and types of spinal injuries is estimated to be more than $5 billion. The devastating emotional and psychological impact is incalculable. Injuries of the soft tissues supporting the cervical spine can result in chronic pain and disability. The term whiplash-associated disorder (WAD) has been used to describe these injuries because of the flexion-extension movement of the neck that results from rear-end MVCs, the most common cause of a WAD. Due to the large number of people sustaining these injuries, the annual costs associated with a WAD exceed $230 billion, which is more than the combined costs associated with spinal cord and brain injuries caused by MVCs.2

Anatomy and Physiology The human spine consists of 33 bony vertebrae—7 cervical, 12 thoracic, 5 lumbar, 5 sacral (fused into one), and 4 coccygeal (usually fused into one; Fig. 36.1). These 26 individual units are separated from one another by flexible intervertebral disks and connected to form a single functioning unit by a complex network of ligaments (Fig. 36.2). The vertebral column protects the spinal cord, which extends from the midbrain to the level of the second lumbar vertebra. Spinal injuries involve fractures in 85% of cases. Of these, 10% are ligamentous injuries without fracture, and 5% are SCIs without a radiographic abnormality (SCIWORA), in which the spinal cord is injured directly without radiographic evidence of bony or ligamentous injury. Stability of a spinal injury refers to the resistance to displacement of fracture fragments or, in the case of ligamentous injury, the entire vertebral unit. There are several classification systems for assessing the stability of subaxial spinal column injuries, including the Allen Ferguson classification, Association for Osteosynthesis classification, Dennis Classification, and thoracolumbar injury classification and severity score for thoracolumbar injuries. According to a survey of the members of Spine Trauma Study Group of the International Spinal Cord Society, practical implementation is evenly distributed among the classification systems.3 The three parallel vertical column model proposed by Denis2 depicts the anterior column as being formed

by alternating vertebral bodies and intervertebral disks surrounded by the annulus fibrosus capsule and anterior longitudinal ligament. The middle column consists of the posterior part of the annulus fibrosus and posterior vertebral wall, posterior longitudinal ligament, spinal cord, paired laminae and pedicles, articulating facets, transverse processes, nerve roots, and vertebral arteries and veins. The posterior column consists of the spinous processes, nuchal ligament, interspinous and supraspinous ligaments, and ligamentum flavum. Disruption of a single column usually preserves stability but does not preclude an SCI from displaced fracture fragments. Disruption of two columns results in an injury that is stable in one direction but unstable in another (eg, stable in flexion but unstable in extension). Disruption of all three columns produces a highly multidirectional unstable injury.

Pathophysiology Classification of Spinal Column Injuries Acute spinal injuries are classified according to the mechanism of trauma—flexion, flexion-rotation, extension, and vertical compression (Table 36.1). Flexion.  Pure flexion injuries involving the C1-C2 complex can cause unstable atlanto-occipital or atlantoaxial joint dislocation, with or without an associated fracture of the odontoid (Fig. 36.3). The basion-axial interval (BAI) and basion-dens interval (BDI) are normally less than 12 mm. A value greater than 12 mm is suggestive of an atlantoaxial joint dislocation (Fig. 36.4). Calculating the ratio of the distance from the basion to midvertical portion of the posterior laminar line of the atlas over the distance from the opisthion to midvertical portion of the posterior surface of the anterior ring of the atlas (Fig. 36.5) indicates subluxation if the ratio is greater than 1. These injuries are considered unstable because of their location and the relative lack of muscle and ligamentous support. In pure flexion injuries below C2, a longitudinal pull is exerted on the strong nuchal ligament complex, which usually remains intact. Most of the force is expended on the vertebral body anteriorly, causing a simple wedge fracture. Radiographically, there is a diminished height and increased concavity of the anterior border of the vertebral body, increased density of the vertebral body resulting from bony impaction, and prevertebral soft tissue swelling (Fig. 36.6). Because the posterior column remains intact, this injury is usually stable. However, spinal instability may occur with severe wedge fractures (loss of more than half the vertebral height) or multiple adjacent wedge fractures. A flexion teardrop fracture results when severe flexion forces cause anterior displacement of a wedge-shaped fragment (resembling a teardrop) of the anteroinferior portion of the involved vertebral body (Fig. 36.7). This injury, which is associated with neurologic injury, is highly unstable because the anterior and posterior ligaments are commonly disrupted. Text continued on p. 350 345

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General Concepts and System Injuries

Cervical Spinous process Spinal canal

1 2

1 2 3 4 5 6 7 1 2 3

Lamina Gutter for nerve

3 4 5 6 7

7 Cervical vertebrae

Transverse process

Pedicle

Body

Body

1

Thoracic

2 3

4

Superior articular facet Lamina

4

5

Spinous process

Lamina

5

6

6

7

12 Thoracic vertebrae

7

8

8

9

9

10

Superior articular facet

Transverse process

Body

Pedicle

10

Spinal canal

11

11

Inferior articular facet

Body

12

12

1

1

Lumbar

2 2 3

5 Lumbar vertebrae

3 4

4

5

5

Spinous process

Superior articular facet

Transverse process Pedicle Body

Coccyx View from above Back view

Side view

Superior articular facet Transverse process

Lamina

Spinal canal

Sacrum

A

Lamina

B

Fig. 36.1.  A, Vertebral column. B, Typical vertebrae.

Body Lamina

Inferior articular facet View from side

CHAPTER 36  Spinal Injuries

Anterior longitudinal ligament

Annulus

A

Posterior complex: 1. Nuchal ligament

Posterior longitudinal ligament

Capsular ligament

2. Supraspinous ligament 3. Infraspinous ligament

Ligamentum flavum

4. Interspinous ligament

B Fig. 36.2.  A, Ligaments of the anterior column. B, Ligaments of the posterior column.

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General Concepts and System Injuries

Type II odontoid fracture

A

B Fig. 36.3.  A, B, Odontoid fracture with anterior dislocation. Mechanism—flexion with shearing; stability— unstable.

TABLE 36.1 

Classification of Spinal Injuries MECHANISM OF SPINAL INJURY

Basion

STABILITY

FLEXION Wedge fracture

Stable

Flexion teardrop fracture

Extremely unstable

Clay shoveler’s fracture

Stable

Subluxation

Potentially unstable

Bilateral facet dislocation

Always unstable

Atlanto-occipital dislocation

Unstable

Anterior atlantoaxial dislocation with or without fracture

Unstable

Odontoid fracture with lateral displacement fracture

Unstable

Fracture of transverse process

Stable

(mm) (mm)

Tip of dens Posterior axial line

Fig. 36.4.  The basion-axial interval (BAI) and basion-dens interval (BDI) are normally less than 12 mm.

FLEXION-ROTATION Unilateral facet dislocation Rotary atlantoaxial dislocation

Stable Unstable

EXTENSION Posterior neural arch fracture (C1)

Unstable

Hangman’s fracture (C2)

Unstable

Extension teardrop fracture

Usually stable in flexion; unstable in extension

Posterior atlantoaxial dislocation, with or without fracture

Unstable

VERTICAL COMPRESSION Bursting fracture of vertebral body

Stable

Jefferson fracture (C1)

Extremely unstable

Isolated fractures of articular pillar and vertebral body

Stable

B

D Opisthion

Basion A Anterior arch of atlas

C Posterior arch of atlas

Fig. 36.5.  The Power’s ratio.

CHAPTER 36  Spinal Injuries

Fig. 36.6.  A, Lateral view of a wedge fracture of C5 with angulation. Mechanism—flexion; stability— mechanically stable. B, Note the anterior wedging of the C4 vertebral body and angulation of C4 on C5.

Flexion teardrop fracture

Fig. 36.7.  A, B, Lateral view of a teardrop fracture. Mechanism—flexion; stability—unstable. The fractured fragment off the C5 body resembles a teardrop.

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General Concepts and System Injuries

deceleration MVCs that result in forced neck flexion. Because this injury involves only the spinous process, it is stable and requires no treatment beyond symptomatic care. Pure spinal subluxation occurs when the ligamentous complexes rupture without an associated bony injury. This injury begins posteriorly in the nuchal ligament and proceeds anteriorly to involve other ligaments (Fig. 36.9). Although rarely associated with neurologic damage, this injury is potentially unstable.

The clay shoveler’s fracture is an oblique fracture of the base of the spinous process of one of the lower cervical vertebrae (Fig. 36.8). The injury derives its name from the fracture caused by the abrupt head flexion that clay miners experienced when lifting a heavy shovelful of clay and having the clay stick to the shovel. This force, transmitted through the supraspinous ligament, results in an avulsion fracture of the spinous process. Today, this fracture is seen after direct trauma to the spinous process and after sudden

B

A Fig. 36.8.  A, B, Clay shoveler’s fracture. Mechanism—flexion; stability—mechanically stable. Note the avulsed fragment off the tip of the C7 spinous process in an underpenetrated lateral view (arrow).

C5 on C6 subluxation with bilateral perched facets

A

B Fig. 36.9.  A, B, Subluxation with bilateral perched facets at C5 and C6. Mechanism—flexion; stability— unstable. Lateral view shows severe subluxation of C5 on C6.

CHAPTER 36  Spinal Injuries

Bilateral facet dislocations occur when a greater force of flexion causes soft tissue disruption to continue anteriorly to the annulus fibrosis of the intervertebral disk and anterior longitudinal ligament, resulting in extreme instability. The forward movement of the spine causes the inferior articulating facets of the upper vertebra to pass upward and over the superior facets of the lower vertebra (Fig. 36.10), resulting in anterior displacement of the spine above the level of injury. Shear Injury.  Trauma to the head directed in an anteroposterior (AP) direction may result in fracture of the odontoid process above the transverse ligaments (type I) or, more commonly, at the base of the odontoid process where it attaches to C2 (type II; Fig. 36.11). Slight angulation of the force may result in extension of the fracture into the body of C2 (type III; Fig. 36.12). Type I odontoid fractures are usually stable because they are an avulsion injury to the odontoid tip. However, if traction forces injure the apical and alar ligaments, the fracture may be unstable. Type II odontoid fractures are, by definition, unstable and are often complicated by nonunion. Type III odontoid fractures are

also mechanically unstable because they can extend laterally into the superior articular facet of the atlas. Flexion-Rotation.  Rotary atlantoaxial dislocation is an unstable injury visualized best on open-mouth odontoid radiographs (Fig. 36.13) or a computed tomography (CT) scan. When the x-ray image reveals symmetric basilar skull structures, a unilateral magnified lateral mass confirms a C1-C2 dislocation. A unilateral facet dislocation is caused by both flexion and rotation. The rotational component of this injury occurs around one of the facet joints, which acts as a fulcrum. Simultaneous flexion and rotation cause the contralateral facet joint to dislocate, with the superior facet riding forward and over the tip of the inferior facet and coming to rest within the intervertebral foramen. In this position, the dislocated articular mass is mechanically locked in place, making this a stable injury even though the posterior ligament complex is disrupted. Any cervical fracture or dislocation may cause torticollis however torticollis may also be caused by a benign process such as a muscle spasm. It may be difficult to differentiate the two

Facets of C6 lie anterior to those of C7 with severe subluxation of C6 on C7

A

B Fig. 36.10.  A, B, Bilateral facet dislocation. Facets of C6 lie anterior to those of C7, with severe subluxation of C6 on C7.

Fracture at base of odontoid process (type II odontoid fracture)

A

B

Fig. 36.11.  A, B, Odontoid fracture with lateral displacement. Mechanism—flexion; stability—unstable. The tip of the odontoid process is laterally displaced in this lateral flexion injury.

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Type III odontoid fracture

A

B

Fracture of C2 extending diagonally into body of C2 (type III) (red leader) with severe cord contusion (blue leader)

C

D

F

E Fig. 36.12.  A–F, Odontoid fracture, type III.

CHAPTER 36  Spinal Injuries

A Asymmetry in relation of lateral masses of C1 to odontoid process

B Fig. 36.13.  A, B, Rotatory subluxation of C1 on C2. Mechanism—rotation; stability—unstable. There is marked asymmetry in the relationship of the lateral masses of C1 to the odontoid process. Rotation causes the right lateral mass to appear slightly larger (farther from the x-ray film) than the left (closer to the  x-ray film).

which articular processes are large and nearly vertical, unilateral facet dislocation is rare. Instead, one or both articular processes fracture, and the upper vertebra swings forward. Commonly seen in the thoracolumbar and lumbar regions, this rotation fracturedislocation is unstable (Fig. 36.16).

Fig. 36.14.  Unilateral facet dislocation on CT.

and in the setting of trauma, CT (Fig. 36.14) or oblique radiographs may be necessary to demonstrate the dislocated facet joint (Fig. 36.15). Due to the varying shapes of the articular processes, different types of flexion-rotation injuries result. In the cervical region, where articular processes are small and almost horizontal, unilateral facet dislocations occur, whereas in the lumbar region, in

Extension.  Fracture of the posterior neural arch of the atlas (C1) results from compression of the posterior elements between the occiput and spinous process of the axis (C2) during forced neck extension (Fig. 36.17). Although the anterior arch and transverse ligament remain intact, this fracture is potentially unstable because of its location. The hangman’s fracture, or traumatic spondylolysis of C2, occurs when the cervicocranium—the skull, atlas, and axis functioning as a unit—is hyperextended as a result of abrupt deceleration. Bilateral fractures of the pedicles of the axis occur with or without dislocation (Fig. 36.18). Although unstable, cord damage is often minimal because the AP diameter of the neural canal is greatest at C2, and the bilateral pedicular fractures permit spinal canal decompression. Originally described in victims of hanging injury, today it is most often the result of head-on MVCs. The extension teardrop fracture occurs when abrupt extension of the neck causes the anterior longitudinal ligament to pull the anteroinferior corner of a vertebral body away from the remainder of the vertebra, producing a triangular fracture that is radiographically similar to the flexion teardrop fracture. Often occurring in lower cervical vertebrae (C5–C7) from diving accidents, this injury may be associated with a central cord syndrome (see later) and is caused by the ligamentum flavum buckling into the spinal cord. Because the posterior elements remain intact, this injury is stable in flexion but potentially unstable in extension.

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General Concepts and System Injuries

Superior articular facet (dislocated)

Superior articular facet (anatomic) C6 C7

A

Bow tie deformity

B

C4 Lamina

C5

Apophyseal joint C6

Lamina C7

C

E

D

F Fig. 36.15.  Unilateral facet dislocation. Mechanism—flexion and rotation; stability—stable. A, B, Lateral view showing one dislocated articular facet of C5 lying anterior to the corresponding facet of C6 and creating a bowtie deformity. The C5 vertebral body is subluxed anteriorly on C6. C, D, Oblique view of unilateral facet dislocation with the lamina of C6 projecting into the neural foramen. E, F, CT scan showing facet dislocation. The inferior facet (arrow) lies posterior to the superior facet.

CHAPTER 36  Spinal Injuries

Thoracic fracture with anterior subluxation and compression of spinal cord posteriorly

A

B Fig. 36.16.  A, B, MRI scan showing fracture-dislocation of the thoracic spine.

Fracture of bilateral pedicles of C2

Fig. 36.17.  A, B, CT scan of posterior neural arch fracture of C1. Mechanism—extension; stability— unstable. The fracture line is well visualized.

Fracture through posterior neural arch

Odontoid process

Fig. 36.18.  Hangman’s fracture. Mechanism—extension; stability— unstable. Fracture lines extending through the pedicles of C2 are well visualized. Retropharyngeal soft tissue swelling is apparent.

Vertical Compression.  Vertical compression injuries occur in the cervical and lumbar regions, which are capable of straightening at the time of impact. When forces are applied from above (skull) or below (pelvis or feet), one or more vertebral body endplates may fracture. The nucleus pulposus of the intervertebral disk is forced into the vertebral body, which is shattered outward, resulting in a burst fracture (Fig. 36.19). Sagittal CT cuts and a lateral radiograph will demonstrate a comminuted vertebral body, and there will typically be greater than 40% compression of the anterior vertebral body, which helps differentiate it from the simple wedge fracture. Coronal CT cuts and a frontal radiograph demonstrate a characteristic vertical fracture of the vertebral body. This is a stable fracture because all the ligaments remain

355

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General Concepts and System Injuries

Burst fracture of L1 (appearing very similar to a compression fracture)

A

B

Comminuted fracture of L1

C

D Fig. 36.19.  Burst fracture of a vertebral body. Mechanism —vertical compression and flexion; stability— unstable. in the right place? A, B, Lateral CT scan showing a burst fracture of L1, appearing very similar to a compression fracture. Mechanism—flexion; stability—usually stable. C, D, CT scan of L1 in the same patient showing comminution of the fracture and retropulsion of fragments into the spinal canal.

intact. However, fracture fragments may impinge on or penetrate the ventral surface of the spinal cord and cause an anterior cord syndrome (Fig. 36.20). An extremely unstable injury, the C1 Jefferson fracture occurs when a vertical compression force is transmitted through the occipital condyles to the superior articular surfaces of the lateral masses of the atlas, driving the lateral masses outward, disrupting the transverse ligament and resulting in fractures of the anterior and posterior arches of the atlas (Fig. 36.21). The lateral film may demonstrate a widening of the predental space between the anterior arch of C1 and the odontoid, or dens. The open-mouth view will demonstrate a bilateral offset of right and left lateral masses of C1 relative to the lateral masses of C2. A fracture should be diagnosed when the sum of the offset distances from the right and left sides exceeds 7 mm. However, when the fragments are minimally displaced, the Jefferson fracture is difficult to recognize.

Rarely, vertical compression fractures may result in isolated fractures of the articular pillar or vertebral body, exhibiting vertical and oblique lines of fracture.

Classification of Spinal Cord Injuries Primary Spinal Cord Injury.  The spinal cord may be injured by three broad categories of injury patterns. First, penetrating trauma or massive blunt trauma with disruption of the vertebral column causes transection of neural elements. Because neurons within the central nervous system do not regenerate, such injuries are irreversible. Less severe blunt trauma may have similar effects resulting from a displaced bony fragment or herniated disk injuring the cord. Second, when patients with cervical osteoarthritis and spondylosis, particularly older adults, are subjected to forcible cervical

CHAPTER 36  Spinal Injuries

MRI showing compression fracture of C7 with disruption of spinal cord and posterior elements

A

B Fig. 36.20.  A, B, MRI scan showing a burst fracture of C7 with complete spinal cord disruption.

spine extension, the spinal cord may be injured secondary to compression between an arthritically enlarged anterior vertebral ridge and a posteriorly located hypertrophic ligamentum flavum (Fig. 36.22). This injury frequently results in a central cord syndrome. The third mechanism is primary vascular damage to the spinal cord. The spinal cord may be compressed by an extradural hematoma, particularly in patients who are on anticoagulants or have bleeding disorders. Vascular injuries should also be suspected when there is a discrepancy between the clinically apparent neurologic deficit and known level of spinal injury. For example, a lower cervical dislocation may compress the vertebral arteries as they travel within the spinal foramina of the vertebrae, resulting in thrombosis of the anterior spinal artery that originates from both vertebral arteries at C1 (Fig. 36.23). On physical examination, such an injury may erroneously appear to be localized to the level of C1 or C2. Also, the great radicular artery of Adamkiewicz, originating from the aorta and entering the spinal canal at the level of L1, sends branches as cephalad as T4. Therefore, a lumbar fracture or dislocation can produce a neurologic deficit as high as T4. Secondary Spinal Cord Injury.  The maximum neurologic deficit after blunt spinal cord trauma is often not seen on initial examination and may, instead, progress over many hours. Studied extensively in animal models, the histopathology of secondary SCI is now thought to be due to a complex cascade of biochemical events that result in progressive ischemia of gray and white matter during the postinjury period (Fig. 36.24). Other factors, such as hypoxia, hypotension, hyperthermia, and hypoglycemia, also affect the ultimate extent of SCI.

Classification of Cervical Soft Tissue Injuries Blunt force trauma can injure one or more of the soft tissues of the neck, including ligaments, muscles, intervertebral disks, zygapophysial facet joints, dorsal root ganglia, and vertebral artery. Although injuries of these tissues have been documented in

TABLE 36.2 

Quebec Task Force Classification of WhiplashAssociated Disorders GRADE

DESCRIPTION

0

Whiplash injury but no pain, symptoms, or signs

1

Delayed neck pain, minor stiffness, nonfocal tenderness only, no physical signs

2

Early onset of neck pain, focal neck tenderness, spasm, stiffness, radiating symptoms

3

Early onset of neck pain, focal neck tenderness, spasm, stiffness, radiating symptoms and signs of neurologic deficit

4

Neck complaint (grade 2 or 3 above) and fracture dislocation

(Adapted from Sterling S: Physiotherapy management of whiplash-associated disorders [WAD]. J Physiother 60:5–12, 2014.)

biomechanical, animal, and human autopsy studies, a validated diagnostic test is only available for facet injuries.4,5 The cardinal symptom of a WAD is neck pain, but neck stiffness, neck and arm paresthesias, and dizziness are commonly reported. Table 36.2 shows the Quebec Task Force classification of WADs, the most common classification used worldwide.2

CLINICAL FEATURES Neurologic Evaluation The initial neurologic evaluation of a patient with a suspected spinal injury should begin with observation. Careful inspection, beginning with the head and proceeding downward, may reveal signs of possible spinal involvement. Significant head and facial trauma have a 5% to 10% incidence of associated cervical spine injuries. Scapular contusions suggest a rotation or flexion-rotation injury of the thoracic spine. Chest and neck abrasions from

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General Concepts and System Injuries Lateral masses of C1 splayed outward (red leaders) and no longer articulate with pillars of C2 (blue leaders)

A

Multiple fractures in ring of C1

C

B

Fig. 36.21.  Jefferson fracture. Mechanism— vertical compression; stability— unstable. A, B, Bilateral lateral displacement of the lateral masses of C1 with respect to the articular pillars of C2 confirms a Jefferson fracture and differentiates it from fracture of the posterior neural arch of C1 on an anteroposterior view. C, CT scan of C1 showing two fracture sites in the ring of C1, with lateral displacement of the lateral mass on the left.

automobile shoulder belts and lower abdominal markings from lap belts indicate possible blunt carotid and vertebral injuries, as well as spinal, intrathoracic, and intra-abdominal injuries. As occurs with falls from considerable heights, injuries to the gluteal region, calcaneal fractures, and severe ankle fractures suggest a compression type of spinal injury. Because the diaphragm is innervated by the phrenic nerve, which originates at C3-C4, an abdominal breathing pattern may provide an important clue to an upper cervical injury. The presence of Horner’s syndrome, characterized by unilateral ptosis, miosis, and anhidrosis, may result from disruption of the cervical sympathetic chain, usually between C7 and T2. Priapism may occur with severe SCI, and it is often associated with spinal shock, which is a transient reflex depression of the spinal cord below the level of the injury. The emergency clinician should speak with the patient during the examination because it provides the patient with reassurance and the emergency clinician with valuable information. Patients may experience pain in the sensory dermatome corresponding to the injured spinal level. For example, a C2 lesion may cause

occipital pain, whereas discomfort in the trapezius muscle, particularly in the absence of signs of local trauma, suggests a C5 injury. The past medical history is important because certain conditions predispose patients to cervical injury. For example, Down syndrome patients are predisposed to atlanto-occipital dislocation, whereas rheumatoid arthritis patients are prone to rupture of the C2 transverse ligament. Palpation of the entire spine and paraspinal musculature may reveal areas of tenderness, deformity, or muscle spasm. A step-off may be appreciated with severe subluxation. Widening of an interspinous space indicates a tear in the posterior ligament complex and a potentially unstable spinal injury. The motor activity of the body is complex. Because a single motion is often governed by muscles innervated by multiple spinal segments, localizing a spinal lesion based solely on motor function is extremely difficult. Testing the presence and strength of those motions outlined in Table 36.3, however, provides a rapid baseline assessment. When a deficit is noted, the motor and neurologic examination should be repeated because progression of dysfunction may occur. Even the most minimal of motor

CHAPTER 36  Spinal Injuries

Note: buckling of ligamentum flavum into cord Arthritically enlarged vertebral bodies

Fig. 36.22.  Older patients subjected to extension forces can sustain cervical spinal cord injury as a result of compression of the spinal cord between the posterior hypertrophic ligamentum flavum and arthritically enlarged anterior vertebral bodies.

Anterior spinal artery

TABLE 36.3 

Basilar artery

Spinal Motor Examination

Posterior inferior cerebellar artery

Atlas C2 C3 C4 Compressed vertebral artery

Normal position of C5

Abnormal position of C5 C6 C7 Vertebral artery

Fig. 36.23.  Mechanism of vascular injury of the spinal cord resulting from cervical vertebral injury.

a

LEVEL OF LESION

RESULTING LOSS OF FUNCTION

C4

Spontaneous breathing

C5

Shrugging of shoulders

C6

Flexion at elbow

C7

Extension at elbow

C8-T1

Flexion of fingers

T1-T12

Intercostal and abdominal musclesa

L1-L2

Flexion at hip

L3

Adduction at hip

L4

Abduction at hip

L5

Dorsiflexion of foot

S1-S2

Plantar flexion of foot

S2-S4

Rectal sphincter tone

Localization of lesions in this area is best accomplished with the sensory examination.

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Kinin release

Dynorphin release

Phospholipid hydrolysis

Excitatory amino acid release

Free radical production

Free radical production

Eicosanoid production

Lipid peroxidation

Membrane damage

[Na+]i

+

[Ca2+]i

Vascular permeability

Edema

Inflammation

Decreased ATPase activity

Cell swelling

Increased protease activity

Decreased energy metabolism

Ischemia

Cell death Fig. 36.24.  Speculative paradigm of secondary pathophysiologic events after primary traumatic injury to the spinal cord. Ca2+, Calcium ion; Na+, sodium ion.

TABLE 36.4 

Spinal Reflex Examination LEVEL OF LESION (AT OR ABOVE)

RESULTING LOSS OF REFLEX

C6

Biceps

C7

Triceps

L4

Patellar

S1

Achilles

response should be elicited and documented, because any response improves prognosis. A slight toe flicker in an otherwise paralyzed individual indicates that the patient may again eventually walk unassisted. The presence of cord-mediated deep tendon reflexes can be helpful as a localizing diagnostic aid (Table 36.4). Typically, muscle paralysis associated with intact deep tendon reflexes indicates an upper motor neuron (spinal cord) lesion, whereas paralysis associated with absent deep tendon reflexes indicates a lower motor neuron (nerve root or cauda equina) lesion. This differentiation

is important because the latter condition may be caused by a surgically correctable lesion. After the initial period of areflexia, reflexes gradually return after 1 to 3 days and, after 1 to 4 weeks, patients with SCI will manifest characteristic hyperreflexia and spasticity. Reflexes are typically absent during the initial phase of spinal shock in the emergency department (ED), however. Sensory function can be quickly evaluated through the use of a structured approach (Table 36.5) or graphic dermatome chart (Fig. 36.25). After locating an area of hypesthesia, one should move the sensory stimulus from areas of decreased sensation outward, rather than the reverse, because patients are more sensitive to the appearance of sensation than to its disappearance. This test should be performed first with a cotton swab to assess sensitivity to light touch, a posterior column function. A pin should be used to assess pain, which is an anterior spinothalamic tract function. Even in the presence of complete motor paralysis, the presence of islands of preserved sensation within an affected dermatome or below the level of dysfunction indicates potential for functional recovery. An accurate baseline sensory examination is imperative because cephalad progression of hypesthesia is the most sensitive indicator of deterioration. When this is observed in the cervical region, one should anticipate impending respiratory failure and preemptively secure the airway.

CHAPTER 36  Spinal Injuries

TABLE 36.5 

Spinal Sensory Examination LEVEL OF LESION

RESULTING LEVEL OF LOSS OF SENSATION

C2

Occiput

C3

Thyroid cartilage

C4

Suprasternal notch

C5

Below clavicle

C6

Thumb

C7

Index finger

C8

Small finger

T4

Nipple line

T10

Umbilicus

L1

Femoral pulse

L2-L3

Medial aspect of thigh

L4

Knee

L5

Lateral aspect of calf

S1

Lateral aspect of foot

S2-S4

Perianal region

Spinal Cord Lesions Complete Spinal Cord Lesions A complete spinal cord lesion is defined as total loss of motor power and sensation distal to the site of an SCI. Functional motor recovery is rare with a complete cord syndrome that persists for longer than 24 hours. Before making the diagnosis of a complete cord syndrome, however, two points should be considered. First, any evidence of minimal cord function, such as sacral sparing, excludes the patient from this group. Signs of sacral sparing include perianal sensation, preserved rectal sphincter tone, and flexor toe movement. Any of these signs indicates a partial lesion, usually a central cord syndrome, and the patient ultimately may have substantial functional recovery, including bowel and bladder control and eventual ambulation. Second, a complete spinal cord lesion may be mimicked by a condition termed spinal shock, which may persist for a few weeks. Spinal shock results from a concussive injury to the spinal cord that causes total neurologic dysfunction distal to the site of injury. The end of spinal shock is heralded by the return of the bulbocavernosus reflex, which is a normal cord-mediated reflex elicited by placing a gloved finger in the patient’s rectum and then squeezing the glans penis or clitoris or by tugging gently on the Foley catheter. An intact reflex results in rectal sphincter contraction. Absence of this reflex indicates the presence of spinal shock, during which time the patient’s prognosis cannot be accurately assessed.

Incomplete Spinal Cord Lesions Approximately 90% of incomplete spinal injuries can be classified as one of three clinical syndromes—the central cord syndrome, Brown-Séquard syndrome, and anterior cord syndrome (Fig. 36.26). The most common is the central cord syndrome, often seen in patients with degenerative arthritis who suffer neck hyperextension. The ligamentum flavum buckles into the cord, resulting in a concussion of the central gray matter in the pyra-

midal and spinothalamic tracts. Because fibers innervating distal structures are located in the spinal cord periphery, the upper extremities are more severely affected than the lower extremities. The prognosis is variable, but more than 50% of patients with central cord syndrome become ambulatory and regain bowel and bladder control, as well as some hand function. The Brown-Séquard syndrome, or hemisection of the spinal cord, usually results from penetrating trauma but may also be seen after lateral mass fractures of the cervical spine. Patients with this lesion have ipsilateral loss of position and vibration sense, as well as motor paralysis, but also have contralateral loss of pain and temperature sensation distal to the level of injury. Because the fibers of the lateral spinal thalamic tract cross at a different level, the pain and temperature loss may be found variably one or two segments above the lesion. Virtually all patients maintain bowel and bladder function and unilateral motor strength, and most become ambulatory. The anterior cord syndrome results from hyperflexion injuries causing cord contusion by the protrusion of a bony fragment or herniated disk into the spinal canal or by laceration or thrombosis of the anterior spinal artery. This syndrome is characterized by paralysis and hypalgesia below the level of injury, with preservation of posterior column functions, including position, touch, and vibratory sensations. Suspicion for an anterior cord syndrome warrants prompt neurosurgical consultation because it is a potentially surgically correctable lesion. After surgical intervention, patients have variable degrees of recovery during the first 24 hours but little improvement thereafter. Several less common spinal cord syndromes may result from direct injury to the cervicomedullary junction and upper cervical segments or from vertebral artery occlusion resulting from severe hyperextension (Fig. 36.27). The posteroinferior cerebellar artery syndrome may produce dysphagia, dysphonia, hiccups, nausea, vomiting, dizziness or vertigo, and cerebellar ataxia. The Dejeune onion skin pattern of analgesia of the face is caused by damage to the spinal trigeminal tract. Horner’s syndrome results from damage to the cervical sympathetic chain and is characterized by ipsilateral ptosis, miosis, and anhidrosis. Injuries below the L2 level can result in an acute cauda equina syndrome, characterized by perineal or bilateral leg pain, bowel or bladder dysfunction, perianal anesthesia, diminished rectal sphincter tone, and lower extremity weakness. The syndrome of SCIWORA is seen primarily in younger children but may occur in any age group. In fact, there is increasing evidence that SCIWORA has been underreported in adults.6 The mechanism is unclear but has been ascribed to the increased ligamentous elasticity seen in the young, leading to transient spinal column subluxation, stretching of the spinal cord, and vascular compromise. Patients often experience a brief episode of upper extremity weakness or paresthesias followed by neurologic deficits that appear hours to days later. The prognosis for patients with SCIWORA is variable, depending on the degree of neurologic impairment and rate of resolution

DIFFERENTIAL DIAGNOSIS The differential diagnosis of spinal injuries includes peripheral nerve injuries that may mimic sensory or motor deficits from a central lesion. For example, compression of the superficial peroneal nerve from a fibular fracture may result in a foot drop, but impingement of a lumbar spinal nerve root from a lumbar vertebral fracture could also result weakness in dorsiflexion. As noted, ligamentous injury in SCIWORA is also a consideration, especially if no fractures are found on imaging. Muscle contusions and strains around the neck, thorax, and lumbosacral regions would also be part of the differential diagnosis. Finally, a diagnosis of exclusion, conversion disorder can result in apparent

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C2 C3 C2

C4 C5 C6 C7 C8 T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 L1 L2 L3 L4 L5

C3 C4 C5 T1 T2 T3 T4

C5 T1

T5 T6 T7 T8 T9

C6 C7

T10 T11 T12 C6 C8

S2 S3 S4 S5

S1

362

L1

S2 S3

C6

L2

C7

C7

C8

L3

L1 L2

L4

S1 S2 L3 L5 L4

S1

L5

L4

Fig. 36.25.  Sensory dermatomes.

manifestations of sensory and motor deficits that may initially be confused and attributed to spinal injuries.

DIAGNOSTIC TESTING Radiographic Evaluation Indications Emergency clinicians have historically taken a liberal approach to imaging the cervical spine in the setting of trauma because failure to recognize an SCI may result in devastating neurologic consequences. In an effort to standardize clinical practice and guide emergency clinicians to be more selective in radiographic imaging

without jeopardizing patient care, two clinical decision rules have been developed. Use of selective but safe imaging modality may decrease overall health care costs, reduce radiation exposure, and decrease complications (eg, aspiration and pressure trauma to skin) associated with the patients lying flat on a backboards with a rigid collar. The first rule to be developed, the National Emergency X-Radiography Utilization Study (NEXUS) Low-Risk Criteria (NLC), was based on a multicenter prospective observational study involving almost 35,000 trauma patients seen at 21 EDs in the United States. The decision instrument required patients to meet five criteria to be classified as having a low probability of injury: (1) no midline cervical tenderness; (2) no focal neurologic deficit; (3) normal alertness; (4) no intoxication; and (5) no painful, distracting injury. The decision rule identified all but 8 of

CHAPTER 36  Spinal Injuries

CROSS SECTION OF CERVICAL SPINAL CORD

Lateral corticospinal tract (voluntary motor function)

Rim of foramen magnum

Posterior white columns (position and vibration)

Occipital condyle Vertebral artery

Dorsal sensory root

Lateral spinothalamic tract (pain and temperature)

C1 nerve root

Motor root CENTRAL CORD SYNDROME

Area of cord injury

Vertebral artery compressed with cervical hyperextension

ANTERIOR CORD SYNDROME

Fig. 36.27.  Mechanism of vertebral artery injury in extension injuries of the cervical spine.

Area of cord injury

BROWN-SÉQUARD SYNDROME Area of cord injury

Fig. 36.26.  Incomplete spinal cord syndromes.

the 818 patients who had spinal injuries. Two of these patients had a clinically significant injury, only one of whom required surgical stabilization, and neither sustained a permanent neurologic injury. Sensitivity, specificity, and negative predictive value of the NLC were 99.6%, 12.9%, and 99.8%, respectively. Owing to concerns about the low specificity of the NLC, the Canadian C-Spine Rule (CCR) was developed using 25 selected clinical predictor variables associated with spine injury. In 2003, the CCR was prospectively studied and compared with the NLC

in nine Canadian tertiary care hospitals. Of 8283 patients, 162 were found to have clinically significant injuries, and the sensitivity, specificity, and negative predictive values of the CCR were, respectively, 99.4%, 45.1%, and 100%.The CCR is composed of the following three questions: 1. Are there any high-risk factors that mandate radiography? 2. Are there any low-risk factors that allow safe assessment of range of motion? 3. Is the patient able to rotate his or her neck actively 45 degrees to the left and right? According to the CCR, patients with no high-risk factors, any low-risk factor, and the ability to rotate the neck do not require radiographic evaluation. High-risk factors include age older than 65 years, a dangerous mechanism of injury (eg, fall from a height >1 m, axial loading injury, high-speed MVC [>100 km/hr], rollover, ejection, motorized recreational vehicle or bicycle collision), or the presence of paresthesias. Low-risk factors include simple rear-end vehicle crashes, to a sitting position in the ED, ambulatory at any time, delayed onset of neck pain, and absence of midline neck tenderness. Although the NEXUS criteria are more widely used in the United States, there is controversy regarding which of the two rules to implement; a systematic review demonstrated better diagnostic accuracy for the CCR.7 There are methodologic differences in the respective study designs, such as different inclusion and exclusion criteria.8 Nonetheless, both rules have been well-validated and are sensitive, and the use of either rule decreases the number of unnecessary radiographs while rarely missing clinically significant injuries.

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General Concepts and System Injuries

Cervical Plain Radiographs Due to the widespread availability and superior test characteristics of CT in the United States, spinal plain radiographs are now rarely obtained, especially when CT is ordered to visualize a different body part. Furthermore, plain radiographs have been shown to be inadequate to visualize the entire cervical spine in up to 72% of cases, thus necessitating CT. However, plain radiographs are often used outside the United States, and there is increasing concern regarding cost and exposure to medical radiation from CT. When compared to plain radiographs, CT respectively confers a 10to14-fold increase in radiation exposure to the skin and thyroid. Thus, in light of cost and radiation exposure, plain radiographs of the cervical spine may be preferentially obtained in patients who sustain a relatively minor mechanism of injury but fail the NLC and CCR criteria, and do not warrant CT of the head or other body parts. On plain radiographs, the C7-T1 vertebrae may be obscured in muscular or obese patients, as well as in patients with spinal lesions causing paralysis of the muscles that act to depress the shoulders. In this case, a swimmer’s view of the lower cervical vertebrae, or CT, is often needed. The cross-table lateral view of the cervical spine is the most helpful x-ray, but its inadequacy as the sole view is well documented. The diagnostic yield is significantly increased when the AP and odontoid views are included. The NLC has shown that a technically adequate threeview trauma series will fail to diagnose significant spinal injury in only 0.07% of patients with injuries and in only 0.008% of patients with unstable injuries. Note that once CT is performed, however, plain radiographs do not add any further clinically relevant information and should not be obtained. Cross-Table Lateral View.  The inspection of the lateral cervical spine film should be methodical and complete. It is helpful to remember the ABCs of interpreting the lateral film, where A stands for alignment, B for bony abnormalities, C for cartilage space assessment, and s for soft tissues. To check alignment, two imaginary lines are drawn that connect the anterior and posterior margins of the vertebral bodies, the anterior and posterior contour lines. A third line, the spinolaminal line, connects the bases of the spinous processes extending to the posterior aspect of the foramen magnum (Fig. 36.28). All

three lines should form a smooth, continuous lordotic curve, and any disruption of these lines suggests a bony or ligamentous injury. An exception to this rule is the pseudosubluxation of C2 and C3, which is commonly seen in infants and children. This phenomenon is attributed to immature muscular development and a hypermobile spine. Thus, if a high cervical injury is suspected in a child, the posterior cervical line, which connects the points bisecting the bases of the spinous processes of C1 and C3, should be used (Fig. 36.29). If the base of C2 lies more than 2 mm anterior or posterior to the posterior cervical line, an injury at that level should be suspected. On the lateral view, the predental space, which is the distance between the anterior aspect of the odontoid process and posterior aspect of the anterior ring of C1, should not exceed 3 mm in an adult or 5 mm in a child (Fig. 36.30). A widening of this space may indicate a Jefferson fracture of C1. Subtle signs of cervical subluxations and dislocations can be identified through cartilage space assessment. A slight anterior or posterior widening of the intervertebral or interspinous space may be the only clue to an unstable dislocation. Finally, the soft tissues of the retropharyngeal space should be assessed for prevertebral swelling and hemorrhage, often the only radiographic signs of spinal injury. The retropharyngeal space, measured from the anterior border of the body of C2 to the posterior wall of the pharynx, should not exceed 6 mm in children or adults. At the level of C3 and C4, this should not exceed 5 mm or should be less than half the width of the vertebral body at that level (see Fig. 36.30). Below the level of C4, the prevertebral soft tissue space is widened by the esophagus and cricopharyngeal muscle. The retrotracheal space, measured from the anterior border of the body of C6 to the posterior wall of the trachea, should not exceed 22 mm in adults or 14 mm in children younger than 15 years. In children younger than 2 years, the retropharyngeal space may normally appear widened during expiration; therefore, inspiratory films should be obtained. Air in the prevertebral space may indicate rupture of the esophagus or some portion of the respiratory tree, and anterior bulging of the prevertebral fat stripe is an excellent sign of an underlying bony or soft tissue injury. Odontoid View.  The open-mouth or closed-mouth view of the atlas and axis can be helpful in diagnosing Jefferson and odontoid fractures. Nonfusion of the odontoid in children and congenital anomalies of the odontoid in adults may mimic fractures. Anteroposterior View.  The AP spinal film completes the spinal series. Connecting imaginary dots placed at the base of each spinous processes should form a straight line, and the laryngeal and tracheal air shadows should be midline. The regular outline of the lateral masses should be verified, and the pedicles viewed

Predental space Posterior cervical line

Spinolaminal line Posterior contour line

Anterior contour line

Fig. 36.28.  Normal structural relationships of the lateral cervical spine.

Fig. 36.29.  Posterior cervical line of a normal lateral spine.

CHAPTER 36  Spinal Injuries

Retropharyngeal space C2

Interspinous spaces Intervertebral spaces

Laminae

C6

A

B

Prevertebral fat stripe

Retrotracheal space

C

Fig. 36.30.  A, Normal structural relationships of the cervical spine laminae in an oblique view form a so-called shingles on a roof appearance. B, In the lateral view, the intervertebral spaces and interspinous spaces should be compared with the spaces above and below for asymmetry and important clues in flexion and extension injuries. The retropharyngeal and retrotracheal soft tissues are measured at the C2 and C6 levels for swelling. C, Normal relationship between soft tissues and bony structures of the cervical spine in the lateral and anteroposterior (AP) views. C, In the AP view, the tracheal and laryngeal air shadows should be within the midline. A straight line should connect points bisecting the spinous processes. If such is not the case, rotatory injuries are suspected.

end-on can be checked for fracture. Widening of the interpedicular distance compared with adjacent vertebrae suggests a burst fracture (Fig. 36.31). Bulging of the mediastinal stripe may be the only evidence of a thoracic vertebral body fracture, which may cause hemorrhage that produces mediastinal widening on the chest x-ray. Flexion and Extension Views.  Flexion-extension (F/E) views are rarely indicated in the acute evaluation of a patient presenting to the ED after acute trauma, but may be useful when there is concern for ligamentous injury and magnetic resonance imaging (MRI) is not available. F/E views should be obtained only in patients who are alert and able to articulate the presence of pain, numbness, or paresthesias, because such symptomatology may indicate instability. The NEXUS investigators demonstrated that 86 of 818 patients(10.5%) ultimately found to have cervical injury underwent F/E testing. Although two patients had bony injuries and four patients had subluxations demonstrated only on F/E views, all six patients had other injuries apparent on routine radiographs. F/E views are also deemed inadequate for interpretation in nearly one-third of studies.8 A more recent review of 1000 F-E radiographs revealed that 80% of the films did not demonstrate the C7-T1 junction or had less than a 30-degree range of motion.9 In the acute setting, F/E radiographs have been reported to have unacceptably high false-positive and false-negative rates because of concomitant muscle spasm. Delayed F/E views obtained 1 week after injury may be helpful, but they have little value in the ED when the CT scan is negative.10 Thus, we do not recommend obtaining F/E radiographs in the ED unless there is concern for ligamentous instability in an alert evaluable patient, and MRI is not available. Such evaluation should occur in consultation with,

and images should be obtained under the supervision of, a spine or trauma surgeon.

Advanced Imaging: Computed Tomography and Magnetic Resonance The CT scan is the technique of choice for the evaluation of acute cervical spine trauma because of its superior test characteristics and time efficiency in the radiology department when compared to plain radiography. CT permits examination without moving the patient from the supine position and is thus preferable in terms of fracture stabilization, airway control, and other life support measures. CT can also identify bony fragments, acute disk herniation, foreign body, paraspinal hematoma, or extramedullary hematoma. Thus, routine plain radiographs in many centers are reserved for the alert patient with minor trauma. In addition to those undergoing CT imaging of other body parts, CT may be preferred when plain radiographs are difficult to interpret because of abnormal anatomy, such as in older adults with degenerative disease or the patient with rheumatoid arthritis. Additionally, rotational and distraction injuries resulting in atlanto-occipital dislocations may be missed on plain x-ray. For patients who have a severe mechanism of injury, unless CT is not available, we support the practice guidelines from the Eastern Association for the Surgery of Trauma, which recommend that CT from the occiput to T1 be used as the primary screening. Because fractures in contiguous and noncontiguous vertebrae are fairly common, CT scans should be obtained to visualize the entire cervical spine. Fractures involving the transverse foramina or C1-C3 are associated with vertebral artery dissection or thrombosis in up 22% of cases, as well as basilar artery stroke. When such fractures are identified, we recommend further study by magnetic

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General Concepts and System Injuries

Pedicles of L1 are spread wider than those above or below, indicating burst fracture of vertebral body

A

B Fig. 36.31.  A, B, Burst fracture of L1. An anteroposterior radiograph shows increased distance between the pedicles of L1 in comparison to adjacent vertebrae. An intravenous pyelogram showed renal injury on the left.

A

B

C

Fig. 36.32.  Normal sagittal magnetic resonance images of the cervical spine. A, T1-weighted and flip angle (B) scans. C, Cervical spine.

resonance angiography (MRA), CT angiography (CTA), or fourvessel angiography. Vertebral images reconstructed from CT scans of the abdomen and pelvis obtained for the evaluation of chest and abdominal injuries provide sufficient data to screen for spinal fractures. CT is also thought to be adequate to clear cervical spines, even in the obtunded blunt trauma patient; in fact, a meta-analysis of 10 studies involving 1850 obtunded trauma patients has demonstrated a negative predictive value and specificity greater than 99%,11 whereas a single-center cohort study of 83 patients demonstrated a sensitivity and specificity of 100% for CT in detecting unstable cervical spine injuries compared to MRI.12,13

Although CT has a higher sensitivity than MRI to detect fractures and dislocations at the craniocervical junction, as well as fractures of the posterior elements, MRI, with its superior resolution and lack of ionizing radiation, has the primary advantage of the ability to image nonosseous structures directly, including intramedullary and extramedullary spinal abnormalities that potentially cause neurologic deficit (Fig. 36.32). Its major impact has therefore been in demonstrating potentially surgically correctable lesions, including acute disk herniation, ligamentous injury, bony compression, epidural and subdural hemorrhages, and vertebral artery occlusion. MRI can identify three separate patterns of SCI, including acute cord hemorrhage, cord edema or

CHAPTER 36  Spinal Injuries

contusion, and mixed cord injury. Patients with cord edema or contusion show significant neurologic improvement, whereas those with cord hemorrhage (Fig. 36.33) fare far worse. MRI can also diagnose a developing intramedullary (posttraumatic) syrinx or subarachnoid cystic changes (Fig. 36.34). MRI is also the best diagnostic imaging modality for SCIWORA. Thus, a patient who demonstrates neurologic deficit or persistent neck pain suggesting ligamentous injury or an occult spine injury, should undergo an expedited MRI, regardless of a normal CT scan or plain radiograph (Fig. 36.35). There are risks to performing an MRI, however, such as aspiration, secondary brain injury, and the difficulty of monitoring and resuscitation in the MRI suite. In addition, MRI cannot be used when MRI-incompatible life support, monitoring systems, pacemakers, cerebral aneurysm clips, and cervical traction devices are

used, although MRI-compatible support systems exist. In the obtunded or unreliable patient, MRI may not be necessary to exclude unstable injuries if the CT scan is normal. A recent prospective study of the use of cervical spine CT in 402 obtunded patients reported a sensitivity of greater than 99%.14

MANAGEMENT Spinal injury should be suspected in all trauma victims with an unknown or suggestive mechanism of injury associated with complaints of neck or back pain, evidence of significant head or facial trauma, spinal tenderness, signs of focal neurologic deficit, impaired consciousness, potentially distracting injuries, or unexplained hypotension (Fig. 36.36).

Spinal Column Stabilization Out-of-Hospital Care Prehospital personnel are well versed in the care of the patient with a potentially traumatized spine, and all emergency medical services (EMS) incorporate these principles. The traditional approach to immobilization requires the use of a backboard, rigid cervical collar, and supportive blocks on both sides of the head. In the past, a concerning mechanism of injury called for automatic and routine initiation of such spinal immobilization at the scene. However, it has been noted that many trauma patients are unnecessarily immobilized by EMS, and immobilization is not a benign intervention. For example, in addition to resulting in prolonged on-scene time and delayed transport to definitive care, the backboard can lead to pressure ulcers, increased pain, and decreased functional respiratory residual capacity. Also, the cervical collars can hide other injuries, such as lacerations and hematomas, and have even been found to result in worsening vertebral distraction injuries.15 There is also ample evidence that EMS providers can safely apply spinal assessment guidelines, such as NEXUS.

Emergency Department

Edema from anterior longitudinal ligament disruption

Hemorrhagic area (white) in center of spinal cord

Fig. 36.33.  MRI scan showing a small area of central cord hemorrhage and anterior and posterior ligamentous disruption.

Trauma victims are assessed as described in Chapter 33 while maintaining immobilization. If the patient’s spine can be clinically cleared by use of the NEXUS criteria or CCR, the immobilization device may be removed. If the trauma victim was wearing a helmet and the helmet was not removed in the field, the face mask, helmet, and any sports padding (eg, shoulder pads on hockey or football players) may be carefully removed while immobilization is maintained. Ideally, at least two or three providers should be present to perform the task of helmet removal. Once the helmet and shoulder pads have been removed, a rigid collar should be placed if the patient’s cervical spine cannot be cleared by use of the NEXUS criteria or CCR. Patients with probable spinal injury who are conscious and cooperative should be immobilized until imaging has been performed. Patients who are uncooperative because of head injury, drug or alcohol intoxication, hypotension, or presence of multiple painful injuries require a deliberate approach, including the use of chemical and mechanical restraints. Suspected thoracic and lumbar spinal injuries are best managed by keeping the patient supine and immobile. The goal of stabilization in cervical spine trauma is to immobilize the neck and body because any movement may extend the initial injury. If the patient is not already immobilized on a backboard, the torso should be firmly anchored to the examining table by straps or rolled sheets. Sedation, druginduced paralysis, and intubation may be required for patients who pose a danger to themselves because of excessive movement and whose injuries otherwise will likely require intubation. Paralysis and intubation are not used simply to control patient

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SECTION One 

General Concepts and System Injuries

Ligamentous injury with dislocation, soft tissue and spinal cord edema, and hemorrhage

Fig. 36.34.  MRI scan showing posttraumatic syrinx of the spinal cord.

movement or lack of cooperation. Spinal precautions should be maintained in patients with an altered sensorium until the presence of an injury can be excluded clinically or radiographically. Suctioning should be readily available to prevent aspiration. Vomiting patients should be placed on their side by logrolling while spinal alignment is maintained.

Airway Management Cervical spine injuries often require early intubation as part of the resuscitation. Lesions above C3 may rapidly progress to respiratory paralysis, and the spread of edema from a lower injury may cause delayed phrenic nerve paralysis, as well as ascension of the neurologic injury above the level of C3. Cervical injuries may be associated with airway obstruction from retropharyngeal hemorrhage or edema or maxillofacial trauma. Airway management of the trauma patient, including those with suspected spine injury, is discussed in Chapter 1.

Spinal Shock

Fig. 36.35.  Anteroposterior longitudinal ligament disruption. A sagittal MRI scan demonstrates ligamentous disruption between C4 and C5, with blood tracking in the anterior spinal canal.

Spinal shock is characterized by the temporary loss of neurologic function and autonomic tone below the level of an acute spinal cord lesion. Patients usually exhibit flaccid paralysis with loss of sensation, deep tendon reflexes, and urinary retention, along with bradycardia, hypotension, hypothermia, and intestinal ileus. Recovery from spinal shock, which may last from less than 24 hours to more than 2 weeks, is heralded by the return of the bulbocavernosus reflex. Neurogenic hypotension, caused by loss of vasomotor tone and lack of reflex tachycardia, is a diagnosis of exclusion in the trauma victim. It should not be considered the cause of hypotension

CHAPTER 36  Spinal Injuries

is persistent hypotension despite fluids, we recommend vasopressor support with norepinephrine to be started at 0.05 µg/kg/min and titrated upward to a maximum dose of 1 µg/kg/min to achieve an MAP of 85 mm Hg.16

Immobilize spine

Stabilize airway and support circulation

Pharmacologic Treatment for Incomplete Cord Injury

Assess associated injuries

Surgical consultants as indicated

Assess spine and neurologic status

Abnormal

Normal

1. Consider steroid administration 2. Obtain AP, lateral, and odontoid spine films 3. Call neurosurgeon or transfer patient to nearest spine center

Obtain AP, lateral, and odontoid spine films

Abnormal

Normal

Consult neurosurgeon

Severe neck pain or spinal tenderness?

Yes

No

1. CT scan 2. Flexionextension spine films

Abnormal

Disposition based on associated injuries

Normal

Fig. 36.36.  Approach to a patient with suspected cervical spine injury. AP, Anteroposterior; CT, computed tomography.

unless the patient is flaccid and areflexic, reflex tachycardia and peripheral vasoconstriction are absent and, most important, the possibilities of coexisting hemorrhagic shock, cardiac tamponade, or tension pneumothorax have been eliminated. Although there is no evidence for an optimal mean arterial pressure (MAP), we recommend initiating the resuscitation of hypotensive trauma victims with a balanced crystalloid fluid infusion, as outlined in Chapter 33. Most cases of pure neurogenic hypotension are mild (eg, systolic blood pressure > 90 mm Hg) and may not require fluid resuscitation or will respond to modest amounts of fluid. Severe neurogenic hypotension(eg, systolic blood pressure < 70 mm Hg), seen in 20% to 30% of cases, usually occurs with high cervical injuries associated with total or neartotal loss of neurologic function. Because hypotension can lead to hypoperfusion and secondary spinal cord ischemia, prolonged severe hypotension (systolic blood pressure < 70 mm Hg) should be prevented and treated. Fluid resuscitation is often ineffective in such patients and may result in fluid overload. Thus, when there

Delayed biochemical damage contributes to ongoing tissue loss and worsening neurologic function in SCI. Thus, numerous neuroprotective and neuroregenerative treatment strategies, including pharmacologic treatment, hypothermia, and decompression,17-19 have been investigated in laboratory animal studies and human clinical trials. Substantial media attention was prompted by case reports of athletes, such as the Buffalo Bills tight end Kevin Everett, who underwent therapeutic hypothermia and was subsequently able to walk just 3 months after his treatment. Since 2010, there has been one prospective case series of 20 patients,17 two retrospective case series,20,21 and one case report.19 In all these studies, the patients had surgical decompression in addition to the hypothermia treatment (32°–34° C [89.6°–93.2° F) for 6 to 48 hours and, although there appeared to be some association of hypothermia with improvement in the American Spinal Injury Association Impairment Scale, this cannot be considered evidence in support of the use of therapeutic hypothermia for acute spinal cord injury. Reported complications from hypothermia induction include pneumonia, thrombocytopenia, and atrial fibrillation. The Miami Project to Cure Paralysis is a phase 1 study currently being conducted at the University of Miami and should be able to help delineate the risks and benefits better, as well as the duration of hypothermia.22 At this time, hypothermia should be considered experimental. Methylprednisolone, once widely recommended for use on the basis of extremely weak evidence, has been found to have no benefit and is likely, on balance, to be harmful. It is no longer recommended or used for acute spinal cord injury.

Associated Injuries Cardiopulmonary Although cardiopulmonary deterioration in a trauma victim is usually the result of hemorrhagic shock or direct injury to the heart or lungs, pulmonary edema may also occur in response to brain injury and SCI. Spinal cord trauma stimulates an intense sympathetic discharge with two subsequent effects. First, pulmonary capillary endothelial cells are disrupted, leading to the pulmonary capillary leak syndrome, in which pulmonary edema occurs in the presence of normal pulmonary artery pressures (18 mm Hg) from ventricular dysfunction. Excessive fluid resuscitation can also contribute to pulmonary edema. Later in the recovery period, many SCI patients suffer from alternating episodes of low and high blood pressure, often with labile heart rates, termed autonomic dysreflexia.23 The treatment for this is primarily supportive by addressing causative factors, such as bladder distention, pain, and hydration status.

Gastrointestinal and Genitourinary If SCI renders the abdominal examination unreliable, an abdominal CT scan or ultrasound is often necessary. In the acute stages of SCI, the gastrointestinal tract and bladder become atonic. Thus, a nasogastric tube should be placed to prevent gastric distention and a Foley catheter inserted to prevent bladder distention and monitor fluid output. Because gastrointestinal bleeding from

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SECTION One 

General Concepts and System Injuries

stress ulcers occurs in 2% to 20% of spinal trauma patients, ulcer prophylaxis with histamine H2 receptor antagonists or proton pump inhibitors should be initiated.

Skin Denervated skin is extremely susceptible to pressure necrosis, and sores can develop in less than 1 hour on unpadded spinal carts. Therefore, backboards should be removed as soon as possible. Padding pressure areas with sheepskin or foam can help minimize decubitus ulcers.

Definitive Treatment and Prognosis The role of prompt surgical intervention in the management of spinal injuries is currently limited to relieving spinal cord impingement caused by foreign bodies, herniated disks, bony fracture fragments, or epidural hematoma. Surgery may be necessary later to stabilize severe bony injuries or reduce spinal dislocations. The timing of surgical intervention is controversial because there are no well-designed studies that have determined whether early ( 5.5/10 Initial disability levels: NDI > 29% Symptoms of posttraumatic stress Negative expectations of recovery High pain catastrophizing Cold hyperalgesia

FACTORS WITH CONSISTENT EVIDENCE OF NOT BEING PROGNOSTIC INDICATORS • Accident-related features (eg, collision awareness, position in vehicle, speed of accident) • Findings on imaging • Motor dysfunction

FACTORS WITH INCONSISTENT EVIDENCE • • • •

Older age Female gender Neck range of movement Compensation-related factors

NDI, Neurological Disability Index.

Adapted from Sterling S: Physiotherapy management of whiplash-associated disorders (WAD). J Physiother 60:5–12, 2014.

the prognostic indicators of poor functional recovery in patients with a WAD.

Minor Fractures Most patients with spinal fractures require hospitalization. Patients with isolated cervical vertebral body compression or spinous process fractures may be managed as outpatients if there is no evidence of neurologic impairment or associated ligamentous instability, and the degree of patient distress is not severe. Appropriate follow-up should be arranged for all patients because even minor spinal injuries may be associated with prolonged disability from chronic pain. For patients with minor wedge fractures (99%

Pain, bleeding

Infection, copper allergy, uterine anomalies

Single 0–120 h IUD

NOTES Consider in IPV where recurrent assault more likely (effective up to 10 yr) Most effective, but often not feasible or desirable from the ED after assault Less effective if >72 h or BMI > 26

Levonorgestrelb Plan B, Plan B 1.5 mg One-Step, Next Choice

0–72 h (may be used with decreased efficacy up to 120 h)

85%

Nausea, vomiting, headache, menstrual changes

Ulipristal acetatec

0–120 h

85%

Nausea, vomiting, Renal, hepatic impairment, More effective than LNG headache, uncontrolled asthma, at 72–120 h menstrual breast-feeding More effective for BMI changes 26–35 (less effective in BMI > 35)

Ella, Ella One

30 mg

BMI, Body mass index; ED, emergency department; IUD, intrauterine device; IPV, intimate partner violence; LNG, levonorgestrel. a There are no absolute contraindications to ED, except for an established pregnancy, because they will not be effective. b Levonorgestrel is not an abortifacient and is not teratogenic. c Ulipristal acetate is not an abortifacient. It has not been tested adequately in human studies in pregnancy or breast-feeding; animal studies showed increased pregnancy loss. Adapted from Glasier AF, Cameron ST, Fine PM, et al: Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 375:555–562, 2010; and Glasier A, Cameron ST, Blithe D, et al: Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception 84:363–367, 2011.

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SECTION Four 

Violence and Abuse Substantial exposure risk

≤72 hours since exposure

Negligible exposure risk

>72 hours since exposure

Source patient known to be HIV positive

Source patient of unknown HIV status

nPEP recommended

Case by case determination

Substantial risk for HIV exposure Exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percuteneous contact With blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood When the source is known to be HIV-infected

nPEP not recommended

Negligible risk for HIV exposure Exposure of vagina, rectum, eye, mouth, or other mucous membrane, intact or nonintact skin, or percutaneous contact With urine, nasal secretions, saliva, sweat, or tears if not visibly contaminated with blood Regardless of the known or suspected HIV status of the source

Fig. 58.18.  CDC algorithm for HIV prophylaxis and for the evaluation and treatment of possible nonoccupational HIV exposure. nPEP, Nonoccupational postexposure prophylaxis.

Consultation Center offers online information and telephone consultation for providers who do not have access to a local HIV expert (nccc.ucsf.edu/clinician-consultation/pep-post-exposure -prophylaxis/).

Disposition Most sexual assault patients will be discharged from the ED. There are myriad websites that can assist the emergency clinician who is caring for the sexual assault patient (Box 58.3). If available in the ED, social services and a rape crisis advocate can help formulate a safe discharge plan. Victims of attempted strangulation, especially those with loss of consciousness, bowel or bladder incontinence, or persistent shortness of breath or voice changes, should be admitted for observation. If safe house resources are unavailable, consider admitting patients who do not have a safe place to go. The discharge instructions should include the number of the forensic kit when the examination is performed. Patients should be encouraged to follow up with their local rape crisis center, primary care provider (or other medical provider), and mental health provider, as needed. Medical follow-up should include any needed completion of the hepatitis B series, repeat pregnancy testing, STI testing (if they did not get treated), and repeat HIV testing (at 6 weeks). If they received HIV prophylaxis, they should follow up with the local HIV expert or clinic to have follow-up laboratory testing, monitoring for side effects, and compliance with medications.

BOX 58.3 

Useful Websites for Sexual Assault • Tonic Immobility: Neurobiology of sexual assault. nij.gov/ multimedia/presenter/presenter-campbell/pages/welcome.aspx. • Centers for Disease Control and Prevention: 2015 STD treatment guidelines—sexual assault and abuse STD guidelines. www.cdc.gov/std/tg2015/sexual-assault.htm. • Clinician Consult Center: PEP: post-exposure prophylaxis. nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis. • U.S. Department of Justice, Office on Violence Against Women: A national protocol for sexual assault medical forensic examinations. www.ncjrs.gov/pdffiles1/ovw/241903.pdf. • American College of Emergency Physicians: Evaluation and management of the sexually assaulted or sexually abused patient. www.acep.org/forensicsection. • Training Institute on Strangulation Prevention: www.strangulationtraininginstitute.com. • National Sexual Violence Resource Center: www.nsvrc.org. • Rape, Abuse, and Incest National Network (RAINN): www.rainn.org. (Hotline: 1-800-656-HOPE [4673])

CHAPTER 58  Sexual Assault

BOX 58.4 

Steps in Court Testimony PREPARATION FOR TRIAL

1. Respond to the subpoena in a timely fashion; a delay can result in criminal charges for you. 2. Notify and consult with the institutional legal counsel. 3. Update your CV and be able to recite dates of education and certification. 4. Ask to meet with the prosecutor to review the medical records, evidence collection kit, and a list of questions the prosecutor plans to ask the emergency clinician.

DAY OF THE TRIAL

1. The day of the trial may change due to motions and order of witnesses. 2. Arrive early and dress in professional attire—a suit is preferred, rather than a white coat. 3. Before testifying, the emergency clinician will be sworn in and seated in the witness box. There are three parts to the testimony—questioning by the prosecution (testimony), crossexamination by the defense attorney, and redirect by the prosecution.

Patients may experience subsequent symptoms of PTSD or rape trauma syndrome (RTS). Symptoms may include depression, anxiety, flashbacks, and difficulty sleeping and interacting with friends and loved ones. Acute pain after sexual assault is common and often undertreated, sometimes involving areas that were not traumatized.54,55 Delayed or worsening pain in many regions of the body has been shown to occur in up to 60% of sexual assault survivors at 6 weeks and 3 months postassault.54

Testifying in Court Although good medical care is the primary goal of ED treatment, the emergency clinician may at times be responsible for collecting sexual assault evidence. In this case, the emergency clinician may be called on to testify in court. The key to com-

4. In general, the emergency clinician should look at the prosecution or defense attorney when being questioned and the jury when answering questions; this is the provider’s opportunity to educate the judge and jury. 5. Responses to questions should be brief and answer only the question; do not add information and explanations unless asked, and resist using medical jargon such as ecchymosis in favor of clearly understood terms such as bruising. 6. All answers should be verbal, taking care not to nod in response. The line of questioning will often start with asking the provider to state her or his name and then describe training and certification, including how long he or she has been practicing emergency medicine. 7. Do not refer to the patient as the “victim.” 8. If an answer cannot be recalled, then just simply state, “I cannot recall.” 9. Documents can be reviewed in court (eg, medical or evidentiary kit records) on request. 10. If the question is not understood, the emergency clinician can ask the attorney to repeat the question or clarify it prior to answering.

petent testimony is preparation and knowledge of the court process. In most cases, the emergency clinician will be called on as a fact witness or as someone who testifies to what the patient said or did, as well as findings on physical examination. Occasionally, the emergency clinician may be called on as an expert witness. An expert witness has specific training and may be called on to provide an explanation or educate the jury, even if he or she did not actually care for the patient. Box 58.4 outlines the steps in court testimony and includes some helpful suggestions for the emergency clinician in preparation for such a trial. Although testifying is anxiety-provoking, being prepared, appearing professional, remaining calm, and taking the opportunity to educate the judge and jury will help the emergency clinician feel more confident in his or her testimony.

KEY CONCEPTS • Sexual assault is more common in women, but can happen in gay and heterosexual men, and in lesbian, gay, bisexual, transgender, and gender-nonconforming individuals. • Sexual assault often results in no physical signs of injury. • Optimal care includes creating a safe confidential environment while incorporating the principles of trauma-informed care. The patient should be included in decision making and ultimately decide treatment. Options include injury evaluation, treatment to prevent pregnancy and STIs, support and trauma counseling, evidence collection, and comprehensive toxicology testing if within jurisdictional time limits. • The sexual assault evidence collection examination is an intensive, protocol-driven, multistep process, best performed by a certified sexual assault examiner. • Adult sexual assault patients should be treated empirically according to CDC guidelines to prevent STIs (including gonorrhea, syphilis, chlamydia, trichomonas, HIV, and hepatitis B), where appropriate. Children and adolescents should be tested and, if symptoms develop, treated for STIs. • All adolescent and adult female sexual assault patients should be offered pregnancy prophylaxis.

• HIV postexposure prophylaxis should be offered if the assailant is known to be HIV-positive or if multiple assailants are involved or, if the HIV status of the assailant is unknown, offered on a case by case basis. • Alcohol and drugs may have been ingested voluntarily or involuntarily by the patient. If the patient consents, comprehensive toxicology testing may be appropriate. • A strangulation attempt with loss of consciousness, bowel and bladder incontinence, persistent voice changes, difficulty swallowing, or shortness of breath should be comprehensively evaluated in the ED. Evaluation options include a chest x-ray, flexible laryngoscopy, and CTA or MRI of the neck. Admission should be considered for persistent symptoms. • Many victims will not have obvious physical injuries; this does not imply consent or refute a sexual assault. • The emergency clinician should not determine if a sexual assault happened but should record observations, statements, and findings objectively that were gathered during the course of ED treatment.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 58  Sexual Assault

REFERENCES 1. Black MC, Basile K, Breiding M, et al: The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 summary report. Atlanta, 2011, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. 2. Deleted in review. 3. Deleted in review. 4. Linden JA: Clinical practice. Care of the adult patient after sexual assault. N Engl J Med 365:834–841, 2011. 5. Zinzow HM, Resnick HS, Barr SC, et al: Receipt of post-rape medical care in a national sample of female victims. Am J Prev Med 43:183–187, 2012. 6. Deleted in review. 7. Deleted in review. 8. Beck AJ, Berzofsky M, Caspar R, et al: Sexual Victimization in prisons and jails reported by inmates, 2011-12. NCJ 241399, Washington DC, 2013, Bureau of Justice Statistics, US Department of Justice. 9. Haydon AA, McRee AL, Tucker Halpern C: Unwanted sex among young adults in the United States: the role of physical disability and cognitive performance. J Interpers Violence 26:3476–3493, 2011. 10. Krebs CP, Lindquist CH, Warner TD, et al: College women’s experiences with physically forced, alcohol- or other drug-enabled, and drug-facilitated sexual assault before and since entering college. J Am Coll Health 57:639–647, 2009. 11. Rothman EF, Exner D, Baughman AL: The prevalence of sexual assault against people who identify as gay, lesbian, or bisexual in the United States: a systematic review. Trauma Violence Abuse 12:55–66, 2011. 12. Mouilso ER, Fischer S, Calhoun KS: A prospective study of sexual assault and alcohol use among first-year college women. Violence Vict 27:78–94, 2012. 13. Deleted in review. 14. Laitinen FA, Grundmann O, Ernst EJ: Factors that influence the variability in findings of anogenital injury in adolescent/adult sexual assault victims: a review of the forensic literature. Am J Forensic Med Pathol 34:286–294, 2013. 15. White C: Genital injuries in adults. Best Pract Res Clin Obstet Gynaecol 27:113–130, 2013. 16. Anderson JC, Sheridan DJ: Female genital injury following consensual and nonconsensual sex: state of the science. J Emerg Nurs 38:518–522, 2012. 17. Lincoln C, Perera R, Jacobs I, et al: Macroscopically detected female genital injury after consensual and non-consensual vaginal penetration: a prospective comparison study. J Forensic Leg Med 20:884–901, 2013. 18. Astrup BS, Ravn P, Lauritsen J, et al: Nature, frequency and duration of genital lesions after consensual sexual intercourse—implications for legal proceedings. Forensic Sci Int 219:50–56, 2012. 19. Deleted in review. 20. Campbell R: The neurobiology of sexual assault. . 21. Volchan E, Souza GG, Franklin CM, et al: Is there tonic immobility in humans? Biological evidence from victims of traumatic stress. Biol Psychol 88:13–19, 2011. 22. Deleted in review. 23. Humphreys KL, Sauder CL, Martin EK, et al: Tonic immobility in childhood sexual abuse survivors and its relationship to posttraumatic stress symptomatology. J Interpers Violence 25:358–373, 2010. 24. Lima AA, Fiszman A, Marques-Portella C, et al: The impact of tonic immobility reaction on the prognosis of posttraumatic stress disorder. J Psychiatr Res 44:224–228, 2010. 25. Sledjeski EM, Delahanty DL: Prior peritraumatic dissociative experiences affect autonomic reactivity during trauma recall. J Trauma Dissociation 13:32–50, 2012. 26. Larsen ML, Hilden M, Lidegaard O: Sexual assault: a descriptive study of 2500 female victims over a 10-year period. BJOG 122:577–584, 2015. 27. Morgan L, Dill A, Welch J: Sexual assault of postmenopausal women: a retrospective review. BJOG 118:832–843, 2011. 28. Deleted in review. 29. Cavness S, Choudhury A, Sensabaugh G: Hospital wet mount examination for the presence of sperm in sexual assault cases is of questionable value. J Forensic Sci 59:729–734, 2014.

30. Centers for Disease Control and Prevention: 2015 sexually transmitted diseases treatment guidelines. . 31. Deleted in review. 32. Du Mont J, Macdonald S, Rotbard N, et al: Drug-facilitated sexual assault in Ontario, Canada: toxicological and DNA findings. J Forensic Leg Med 17:333–338, 2010. 33. Le Blanc-Louvry I, Papin F, Vaz E, et al: Cervical arterial injury after strangulation—different types of arterial lesions. J Forensic Sci 58:1640–1643, 2013. 34. Sethi PK, Sethi NK, Torgovnick J, et al: Delayed left anterior and middle cerebral artery hemorrhagic infarctions after attempted strangulation: a case report. Am J Forensic Med Pathol 33:105–106, 2012. 35. McClane GE, Strack GB, Hawley D: A review of 300 attempted strangulation cases. Part II: clinical evaluation of the surviving victim. J Emerg Med 21:311–315, 2001. 36. Stapczynski JS: Strangulation injuries. Emerg Med Rep 31:193–203, 2010. 37. American College of Emergency Physicians. Evaluation and management of the sexually assaulted or sexually abused patient. . 38. American College of Emergency Physicians: Selective triage for victims of sexual assault to designated exam facilities. . 39. Carr M: Evidence collection beyond the 72-hour rule. J Forensic Nurs 7:49, 2011. 40. Carr ME, Moettus AL: Developing a policy for sexual assault examinations on incapacitated patients and patients unable to consent. J Law Med Ethics 38:647–653, 2010. 41. Sommers MS, Brown KM, Buschur C, et al: Injuries from intimate partner and sexual violence: Significance and classification systems. J Forensic Leg Med 19:250–263, 2012. 42. Astrup BS, Ravn P, Thomsen JL, et al: Patterned genital injury in cases of rape—a case-control study. J Forensic Leg Med 20:525–529, 2013. 43. Kelly DL, Larkin HJ, Cosby CD, et al: Derivation of the Genital Injury Severity Scale (GISS): a concise instrument for description and measurement of external female genital injury after sexual intercourse. J Forensic Leg Med 20:724–731, 2013. 44. Larkin HJ, Cosby CD, Kelly D, et al: A pilot study to test the differential validity of a genital injury severity scale, in development for use in forensic sexual assault examinations. J Forensic Nurs 8:30–38, 2012. 45. Zink T, Fargo JD, Baker RB, et al: Comparison of methods for identifying ano-genital injury after consensual intercourse. J Emerg Med 39:113–118, 2010. 46. Jones JS, Dunnuck C, Rossman L, et al: Significance of toluidine blue positive findings after speculum examination for sexual assault. Am J Emerg Med 22:201–203, 2004. 47. Newton M: The forensic aspects of sexual violence. Best Pract Res Clin Obstet Gynaecol 27:77–90, 2013. 48. Eldredge K, Huggins E, Pugh LC: Alternate light sources in sexual assault examinations: an evidence-based practice project. J Forensic Nurs 8:39–44, 2012. 49. Planty M, Langston L, Krebs C, et al: Female victims of sexual violence, 1994-2010, Washington, DC, 2013, Department of Justice, Office of Justice Programs, Bureau of Justice Statistics. 50. McLean IA: The male victim of sexual assault. Best Pract Res Clin Obstet Gynaecol 27:39–46, 2013. 51. Dosekun O, Fox J: An overview of the relative risks of different sexual behaviours on HIV transmission. Curr Opin HIV AIDS 5:291–297, 2010. 52. Boily MC, Baggaley RF, Wang L, et al: Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 9:118–129, 2009. 53. Klot JF, Auerbach JD, Veronese F, et al: Greentree white paper: sexual violence, genitoanal injury, and HIV: priorities for research, policy, and practice. AIDS Res Hum Retroviruses 28:1379–1388, 2012. 54. Ulirsch JC, Ballina LE, Soward AC, et al: Pain and somatic symptoms are sequelae of sexual assault: results of a prospective longitudinal study. Eur J Pain 18:559–566, 2014. 55. McLean SA, Soward AC, Ballina LE, et al: Acute severe pain is a common consequence of sexual assault. J Pain 13:736–741, 2012.

CHAPTER 58: QUESTIONS & ANSWERS 58.1. Which of the following statements best describes hepatitis B infection prevention for victims of sexual assault? A. Give HBIG and hepatitis B vaccine if the patient has not been immunized. B. Give HBIG only if the patient has not been immunized. C. Give hepatitis B vaccination if patient is unimmunized or uncertain. D. Give hepatitis B vaccine only if serologic testing shows that the patient is not adequately immunized. E. Serologic testing is always required, followed by hepatitis B immunoglobulin (HBIG). Answer: C. Give hepatitis B vaccination if the patient is unimmunized or uncertain. Follow-up doses should be given at 1 to 2 months and 4 to 6 months (total of three doses). This strategy,

which avoids the need for serologic testing, has been shown to be effective. HBIG is not recommended by the CDC after sexual assault (although it is recommended in body fluid exposures in unimmunized health care workers). 58.2. Which of the following empirical antibiotic regimen is indicated for sexual assault patients to prevent sexually transmitted infections? A. Cefixime, 400 mg PO B. Cefixime, 400 mg PO once, plus doxycycline, 100 mg PO bid for 10 days C. Ceftriaxone, 1 g IM (intramuscularly) D. Ceftriaxone, 1 g IM, plus azithromycin, 2 g orally (PO) E. Ceftriaxone, 250 mg IM, plus metronidazole, 2 g PO, plus azithromycin, 1 g PO

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Trauma  | 

SECTION Four 

Violence and Abuse

Answer: E. Ceftriaxone is given to cover gonorrhea, azithromycin to cover chlamydia, and metronidazole (Flagyl) to cover Trichomonas. Ceftriaxone is preferred over oral cefixime to cover incubating syphilis and due to increasing gonorrhea resistance. Many providers opt to give the metronidazole to take at home because it increases the risk of nausea and vomiting, a common side effect of many of the medications (including emergency contraception and HIV postexposure prophylaxis). 58.3. Which of the following statements best describes sexual assault in males? A. Ejaculation should not occur in the victim during male sexual assault. B. Males are more likely to overreport sexual assault. C. Males are more likely to require sexually transmitted infection (STI) prophylaxis. D. Males do not require referral to rape crisis centers. E. Males may require anoscopy to detect anogenital injuries. Answer: E. Males may actually suffer more anogenital injuries than woman; injury detection can be aided or enhanced by using an anoscope. Males underreport the crime, do not seek medical attention, and absolutely need referral to rape crisis centers for post-rape care and counseling. Males are not more likely to require STI prophylaxis because the risk of transmission per act does not change based on gender. Ejaculation may occur during sexual assault due to prostatic stimulation and fear arousal. This should not be taken to infer that the assault was consensual. 58.4. Sexual assault often leads to injury. Which of the following statements best describes the rate of sexual assault injury in females? A. Genital injury can be seen following consensual and nonconsensual intercourse. B. Nongenital injury is uncommon and rarely seen. C. Resistance of the victim and force used do not influence the risk of genital injury. D. The precise location of genital injury can be used to confirm sexual assault. E. The presence of genital injury confirms that a sexual assault occurred. Answer: A. Genital injury can be seen following consensual and nonconsensual intercourse; its presence or location of injury does not confirm that a rape occurred. Nonconsensual intercourse (sexual assault) is more likely to result in more injuries that can be more severe. Other bodily injury can be commonly seen and may be more common than genital injury. Injury can be influenced by age, virginal status, resistance, force, number of assailants, and relationship of the assailant to the victim. 58.5. Which of the following factors reduces the likelihood of finding genital injury during the sexual assault examination? A. Digital penetration B. Increased time since sexual assault occurred C. Penile penetration D. Use of foreign object during the assault E. Victim sexual immaturity

Answer: B. The genital structures heal quickly, so the longer the time since the sexual assault occurred, the less likelihood of finding evidence of injury on examination. All the other factors increase the likelihood of finding genital injury at the time of the sexual assault examination. 58.6. A 25-year-old woman presents 4 days after vaginal penetration. Her body mass index (BMI) is 35. Which of the following is true about emergency contraception (EC)? A. A pregnancy test is mandatory prior to offering EC. B. She should be offered levonorgestrel because it is more effective in this situation. C. She should be offered ulipristal. D. She should have an intrauterine device (IUD) inserted because this is the most effective form of EC for her. E. She should not receive EC because it will likely be less effective due to her BMI. Answer: C. Emergency contraception should be offered up to 5 days after vaginal assault. Ulipristal, levonorgestrel, and high-dose birth control pills are options. Ulipristal is more effective after 72 hours and in women with a BMI greater than 26. At a BMI above 35, both forms of oral EC are less effective, but should still be administered if there is no alternative. IUD placement is the most effective form of EC; it can be placed up to 5 days after assault. IUD placement allows for ongoing birth control in situations where there is likely to be loss of reproductive control (intimate partner assault), but is often less desirable after assault. IUD placement is most often not available in a timely manner. A pregnancy test is not mandatory prior to giving EC because it will not harm an existing pregnancy. A pregnancy test is suggested prior to ulipristal administration, given the lack of large studies in pregnant women. 58.7. A 28-year-old woman presents following sexual assault, during which the assailant strangled her, and she passed out. Which of the following is true concerning this patient’s injury? A. Nonfatal strangulation has little impact on the risk of future injury in the domestic violence victim. B. Regardless of her symptoms, no additional imaging is needed. C. The hyoid bone is commonly fractured during an attempted strangulation. D. The signs and symptoms of nonfatal strangulation are usually caused by arterial or venous blood flow occlusion or blockage of air entry through the trachea. E. There must be physical evidence of injury for it to be a proven case of nonfatal strangulation. Answer: D. Strangulation leads to hypoxia by jugular vein occlusion, carotid artery occlusion, or blockage of the airway. The hyoid bone is rarely injured. A large percentage of patients may have no physical findings and may require imaging, depending on the signs and symptoms present. In intimate partner violence (IPV) relationships, nonfatal strangulation increases the risk of future homicide sevenfold.

C H A P T E R 59 

Intimate Partner Violence and Abuse Esther K. Choo  |  Judith A. Linden PRINCIPLES Background and Importance Intimate partner violence (IPV)1 has been defined by the Centers for Disease Control and Prevention (CDC) as the threat or infliction of physical, psychological, or sexual harm by a current or former intimate partner or spouse.1 Physical violence includes aggressive behaviors, such as pushing, hitting, slapping, punching, kicking, biting, burning, strangulation, and using objects and weapons with the potential to cause death, disability, injury, or other harm. Psychological or emotional violence includes words and behaviors meant to intimidate, degrade, humiliate, or isolate the victim from family and friends, threats, controlling access to clothing, transportation, money, and other basic needs, and limiting professional and social activities. Sexual violence includes using physical force to attempt sexual acts or sexual contact against the victim’s will, or on a victim not able to consent, whether or not the sexual act is completed. Although not explicitly included in the CDC definition, sexual abuse may also include prevention of or interference with the use of birth control (so-called reproductive coercion)2 and refusal to use condoms to prevent the transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV).3 Threats of physical or sexual harm are also considered IPV. According to the CDC’s 2010 National Intimate Partner and Sexual Violence Survey (NISVS), 35.6% of women will experience IPV over their lifetimes, only considering physical violence, rape, and stalking. One in three victimized women experiences multiple forms of IPV.4 Obtaining accurate national estimates of IPV prevalence among emergency department (ED) patients or even of ED visits directly related to IPV injuries is hampered by poor documentation and coding practices. In the National Hospital Ambulatory Medical Care Survey (NHAMCS), IPV is a recorded diagnosis in less than 0.25% of visits. However, in individual ED studies, observed IPV prevalence in women is disproportionately high compared to the general population, with estimates of recent (6–12 month) prevalence ranging from 12% to 19% (≈8–12 times that of the general population) and of lifetime prevalence from 44% to 54% (≈1.4–1.7 times that of the general population). IPV commonly occurs against men as well as women. In the CDC’s 2010 NISVS, one in four men reported lifetime physical abuse, stalking, or rape by an intimate partner, and 35% of them reported associated physical or psychological sequelae of abuse.4 Data from the Behavioral Risk Factor Surveillance System, another nationally representative CDC survey, have reinforced that men experience all forms of IPV and its mental and physical health sequelae.5 The high prevalence of abuse among men may be partly understood by the fact that IPV is frequently bidirectional. IPV researchers have described two distinct forms of IPV, intimate terrorism and situational couple violence.6 The two forms are differentiated based on the use of power to control. Intimate terrorism is defined as “the attempt to dominate one’s partner and to exert general control over the relationship,” whereas situational couple violence is “violence that is not connected to a general 758

pattern of control.” Situational couple violence is usually less injurious or severe and more likely to be engaged in by either member of the couple. Intimate terrorism is characterized as more injurious, more frequent, and more often perpetrated by men against women. Overall, women continue to be the primary targets of violence and to experience high rates of health sequelae. Therefore, health care responses to IPV, as well as community resources for survivors, are largely directed toward women. IPV affects other aspects of health and is associated with risky health behaviors, such as cigarette smoking, heavy alcohol and drug use, and physical inactivity, as well as mental illness (eg, depression, anxiety, posttraumatic stress disorder [PTSD], suicidality).4,7-11 IPV is associated with increased rates of cervical cancer.12 IPV patients often have poor maintenance of chronic medical conditions such as asthma, diabetes, and chronic pain syndromes.4 Pregnant IPV victims tend to seek prenatal care late and are at risk for termination of pregnancy, placental abruption, preterm delivery, and low infant birth weight.13-16 IPV is responsible for most intentional injuries experienced by women, accounting for 38% of all female homicides globally.17-19 IPV fatalities do not usually occur as a freak event in an otherwise happy family; IPV is a precursor to the homicide in 65% to 75% of cases.19 Many IPV homicide victims see a health care provider within the year before their death. ED visits represent an opportunity to identify IPV and those at high risk for future severe injury or death. The annual economic cost in the United States has been estimated at more than $4.8 billion dollars for direct medical and mental health services and an additional $1.8 billion in lost earnings and productivity,20 above and beyond those without IPV. Encouragingly, health care use has been observed to return to normal rates several years after the cessation of IPV,21 suggesting that interventions against IPV may have a positive overall effect on health.

Causes and Natural History of Intimate Partner Violence IPV is a complex multifactorial phenomenon, influenced by multiple, interconnected societal, community, relationship, and individual factors (Fig. 59.1). Individual-level risk factors include childhood exposure to IPV, presence of a physical or mental disability, and use of alcohol or drugs.22-27 Relationship factors that may influence IPV occurrence include the couple’s communication and conflict resolution skills28 and socioeconomic stressors; IPV appears to occur at increased rates in relationships among those with lower income, job or housing instability, and male unemployment. Housing instability also increases the risk of sequelae, such as PTSD, depression, and increased ED use in IPV victims.29 Lack of social support for women and delinquent peer associations for men have been associated with victimization and perpetration, respectively, whereas bolstering social supports can decrease violence.30 Finally, the individual, family, and community all function within an overarching society or culture with its laws, attitudes,

CHAPTER 59  Intimate Partner Violence and Abuse

Ideology

Manlfestations Distinct gender roies and hierarchy Male sexual entitlement

Processes

Influencing Factors

Enforcement of hierarchy and punishment of transgressions Low leveis of education of women

Male superiority

Few public roles for women Low social value and power of women

Lack of family and social and legal support for women Lack of economic power for women

Ideas of manhood linked to control of women

Crisis of masculinity and crisis resolution

Lack of economic opportunities for men and inequality with women

Relationship conflict

Heavy alcohol consumption

Intimate partner violence

Culture of violence

Violence usual in conflict

Witnessing and experiencing violence: mother abused and beatings in childhood

Fig. 59.1.  Multifactorial causes of intimate partner violence.

norms, and biases, including overall societal tolerance toward violence. The predominant cultural theory regarding the cause of IPV is so-called feminist theory, which states that violence against women results from gender inequity, both ideologic (belief, norms, values) and structural (access to and positions within social institutions). In some ways, IPV fits a chronic disease model because it tends be a lifelong condition that recurs in cyclic patterns within a relationship. Additionally, children who have experienced family violence tend to enter future violent relationships. Care for IPV requires systematic screening and multidisciplinary care, with the need for long-term physical and mental health care, counseling and advocacy, legal aid, and long-term strategies for financial and social independence. Approaching IPV as a chronic disease underscores the importance of population-wide screening efforts. In addition to providing acute medical care, emergency clinicians should connect patients who screen positive with primary care physicians and/or domestic violence community agencies to ensure continuity of care for what is typically a long-term, recurring problem. This chronic disease model is in contrast to traditional clinical thinking about IPV, which is focused around a crisis event, such as injury. A significant body of older literature was dedicated to patterns of injury that might be considered classic signs of IPV. However, physical findings have demonstrated poor sensitivity and specificity for IPV and thus are not amenable to clinical decision rules. IPV can present with any number of symptoms, usually without any injury at all.31 For this reason, the US Preventive Services Taskforce (USPSTF) has recommended routine screening for IPV in women of childbearing age, even in the absence of overt injuries.32

Despite USPSTF recommendations and Joint Commission requirements for robust health system responses to IPV, there are a number of barriers to its identification and management. Emergency clinicians generally receive little training and thus have low confidence in their ability to respond effectively to revelations of abuse. In busy clinical settings such as the ED, the high volume of patients and acuity of disease may preclude screening and more in-depth discussions of partner abuse. Given the complex psychosocial issues that may accompany IPV, emergency clinicians may also fear opening a Pandora’s box, uncovering a range of needs. Staff may be uncertain about whose responsibility it is to screen for IPV, discuss positive screens with the patient, and provide necessary counseling and referrals. Overall, current screening and intervention practices fail to identify women who are at risk for future IPV. Incorporating screening into triage processes, including into electronic medical record documentation, routine training of clinical staff, and use of newer modalities, such as self-administered, computer-based screening, may aid EDs and emergency clinicians in improving the detection of IPV.

CLINICAL FEATURES Classic injury patterns (eg, maxillofacial injuries, multiple injuries, extremity fractures) have demonstrated limited predictive value in screening for IPV. Most IPV victims present to the ED with noninjury visits, including gynecology-related complaints, mental health and substance abuse complaints, pain syndromes, and uncontrolled medical illnesses. Elements of the history that may suggest IPV include a delay in seeking medical care, noncompliance with medications, and/or missed medical appointments; all these may reflect the fact that an abuser is controlling the patient’s

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access to care. Unless probed about the presence of IPV, these patients may not be identified. If the injury is a result of IPV, the patient may be reluctant to divulge the information. Additional historical clues that an injury may be a result of IPV are a vague or changing history, a history that is inconsistent with the injuries, a statement by the patient that he or she is accident-prone, and a past history of injuries. IPV is often considered in women who present with injuries or assault, but should also be considered in male victims of assault. Although men do report being victims of IPV, reported injuries are commonly abrasions, and the mechanism is often scratching, punching, or being hit with a blunt object.33

Injury Presentations Emergency clinicians should ask patients presenting with injuries if they were intentionally inflicted and specifically if injuries were caused by IPV. If the patient attributes the injuries to IPV, the identity of the other person, as well as that person’s relationship to the patient, should be ascertained and documented. Not only is noting the nature of the relationship important for ensuring the accuracy of diagnostic coding, but a victim who is living with an assailant requires different resources compared to a victim of a stranger assault. IPV patients may come to the ED with acute injuries, or injuries may be an incidental finding discovered during the physical examination for medical complaints. The emergency clinician should look for clues that an injury may be intentional in nature—a central location (eg, trunk, breasts), bilateral injuries (both arms or both legs), defensive injuries (eg, ecchymoses on the back of the hand from protecting the face), and patterned injuries (having the markings of an object such as the sole of a shoe or a burn with the imprint of an iron). Common locations for IPV injuries are the head, face, mouth, and neck. Types of injuries may include facial contusions, lacerations, fractures, traumatic alopecia, concussion, skull fractures, intracranial hemorrhages, and strangulation. Extremity injuries with grab marks (fingertip contusions) to the upper arms are suggestive of IPV. Emergency clinicians should document injury location, size, swelling, tenderness, coloration, evidence of healing, and presence of a pattern. Certain traumatic injuries are more commonly associated with IPV, such as injuries to the face, head, neck, thorax, and abdomen.34 Some studies have considered differentiating IPV versus non–IPV-related assaults presenting to the ED. Assaults that

occur in the home are more likely to be IPV-related in men and women, and assaults involving a head injury were more likely to be IPV-related in women.35 While inquiring about who assaulted the patient is important, discovering where the assault occurred can give clues for IPV. Patients given an e-code of IPV are likely to have traumatic diagnoses such as contusion and facial fractures and are also more likely to present with complications of pregnancy.36

Gynecologic-Related Presentations IPV victims commonly present to the ED with obstetric and gynecologic complaints.37 Presentations related to IPV may include unintended pregnancy, requests for emergency contraception and termination of pregnancy, and frequent sexually transmitted infections.38-40 IPV survivors report increased rates of STIs and other gynecologic disorders, such as cervicitis and vulvovaginitis.40-42 Unintended pregnancy and STIs may be a consequence of loss of reproductive control and/or sexual assault. Sexual violence is a common tactic used for intimidation and control in IPV; 46% to 68% of abused women admit to sexual assault in the context of abuse. The sequelae of intimate partner sexual abuse are at least as serious as those of stranger sexual assault. Victims of intimate partner sexual abuse are more likely to sustain more serious nongenital injuries than victims of stranger assault. Many validated IPV screening tools (Table 59.1) omit questions about sexual abuse or reproductive coercion.2 Women who are sexually assaulted by an intimate partner or family member are more likely to present in a delayed manner or not present to the ED at all for evaluation. Emergency clinicians should ask all sexual assault victims about IPV and safety at home. IPV patients may not consider themselves raped or sexually assaulted if the perpetrator was their partner, husband, or boyfriend. Thus, emergency clinicians should ask whether the patient has been forced to perform sexual activities rather than having been “raped.”

Mental Health Presentations IPV victims frequently experience depression, suicidal ideation, homicidal ideation, PTSD, insomnia, eating disorders, and alcohol and drug misuse.4,9-11,43,44 Mental health presentations including substance abuse, therefore, should prompt suspicion for possible IPV. IPV survivors are also more likely to report depression, anxiety, and PTSD and use mental health resources.20

TABLE 59.1 

Sample of Brief Intimate Partner Violence and Abuse Screening Tools TOOL

QUESTIONS

SENSITIVITY

SPECIFICITY

HITS

How often does your partner: • Physically hurt you? • Insult you or talk you down? • Threaten or harm you? • Scream or curse at you?

30%–98%

83%–97%

PVS

• Have you been hit, kicked, punched, or otherwise hurt by someone in the past year? If so, by whom? • Do you feel safe in your current relationship? • Is there a partner from a previous relationship who is making you feel unsafe now?

65%–71%

80%–84%

STaT

Have you ever been in a relationship where your partner has: • Slapped or pushed you? • Thrown, broken, or punched things? • Threatened you with violence?

96% (cutoff >1%) 89% (>2%) 64% (>3%)

75% (cutoff >1%) 100% (>2%, >3%)

CHAPTER 59  Intimate Partner Violence and Abuse

Alcohol and Drug Use and Intimate Partner Violence Whether in the perpetrator or recipient of abuse, alcohol and drug misuse place women at greater risk for physical and sexual intimate partner victimization.44 Alcohol and drug use may be a coping response to the emotional and physical sequelae of IPV, but can also lead to abuse.22,44 Explanations for this include conflicts over substance use—women who misuse alcohol or drugs are more likely to choose partners who use alcohol and drugs—or that alcohol or drugs impedes the victim’s ability to recognize escalating aggressive behavior, navigate tensions, and resolve conflict within a relationship. Overall, alcohol and drug misuse increase women’s vulnerability to IPV victimization and reduces the likelihood that they will be screened for these problems.45 Those with coexisting problems not only face mental and physical health problems of greater complexity,26,44,46 but must contend with additional challenges to recovery; for example, few substance use treatment programs address violence, and few domestic violence agencies are equipped to address active substance misuse.26

Chronic Medical Conditions IPV patients may seek care for chronic conditions that are a result of previous injuries or are comorbid medical conditions of the abuse.4,47 These include psychosocial disorders (substance abuse, depression, anxiety, tobacco use), musculoskeletal disorders (degenerative joint disease, low back pain, joint trauma, cervical pain, acute sprains), reproductive complaints (menstrual disorders, vulvovaginitis, sexually transmitted infections), and others (confusion, headaches, urinary tract infections, abdominal pain, chest pain, respiratory infections, reflux disease, and lacerations). Other common medical presentations of IPV patients include cardiorespiratory illnesses (palpitations, chest pain, asthma exacerbations, shortness of breath), gastrointestinal disorders (functional bowel disease), and general constitutional complaints (weakness, fatigue, dizziness, chronic pain).

having control over another person, for the purpose of exploitation.” Exploitation includes, at a minimum, “the exploitation of the prostitution of others or other forms of sexual exploitation, forced labor or services, slavery or practices similar to slavery, servitude, or the removal of organs.”50 Trafficking of victims can occur across or within national borders. HT victims can be of any age or gender, but are usually women and children, who are often from a poverty situation and are previous victims of sexual or physical abuse. Victims are lured by promises of money, love, or opportunities for success. HT victims are often held in bondage and required to pay large amounts of money in return for transportation, favors, or food and shelter. They are paid little or nothing, and thus are unable to pay back this debt. Trafficking victims often have no autonomy, and access to health care or reproductive control and may be forced to sleep behind locked doors or not allowed to leave their place of employment. They may present to the ED with STIs, pregnancy, injuries, and medical and mental health conditions. HT victims often experience the initiation and forced use of drugs or alcohol, as well as physical, emotional, and sexual violence. They are often controlled with addiction to alcohol or drugs and may present as victims of an overdose or in alcohol and drug withdrawal. Trafficking victims can also present with medical complaints, such as headaches, stomach pain, memory problems, back pain, loss of appetite, and tooth pain.51 Many victims report fatigue, headaches, back pain, weight loss, mental health symptoms such as depression and anxiety, and sexual and reproductive health problems.52 The severity of symptoms appears to increase with the duration of trafficking. To date, there has been very little research on the health effects and presentations of HT, and most studies have concentrated on young female HT victims. Clues in a patient’s presentation that may suggest trafficking rather than IPV are included in Box 59.1. Although the emergency clinician may suspect HT, most victims will not be identified in the ED. There are many reasons why a victim of HT might not disclose in the ED which are similar to IPV—shame, embarrassment and self-blame, lack of trust or familiarity with the provider, isolation with lack of economic and

Pain Syndromes IPV should be in the differential diagnosis as a co-occurring condition and possible contributing factor in patients who present with chronic pain.48,49 Chronic pain, including headache, abdominal pain, back pain, and bone and joint pain are common in IPV survivors, and disability and pain symptoms may persist for years after being separated from the abuser. Those with a history of more severe abuse, sexual abuse, and childhood abuse report more symptoms. Asking about and identifying past abuse may decrease unnecessary testing and inappropriate medication administration and facilitate referral to critical resources.

DIAGNOSTIC CONSIDERATIONS Differential Diagnosis Human Trafficking A victim of human trafficking (HT) can be mistaken for a victim of IPV. HT is a form of modern slavery and can present in a similar manner as IPV. HT, however, entails very different dynamics, challenges, and approaches to intervention and resources. The World Health Organization has defined human trafficking as “the recruitment, transportation, transfer, harboring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability, or of the giving or receiving of payments or benefits to achieve the consent of a person

BOX 59.1 

Presentations Prompting Consideration of Human Trafficking • Delay in seeking medical care • Stated age older than visual appearance • Evidence of lack of care for previously identified or obviously existing medical conditions • Discrepancy between stated history and clinical presentation or observed pattern of injury • Scripted, memorized, or mechanically recited history • A patient who is overly concerned with the time, contacting their “partner,” leaving the ED • Subordinate, hypervigilant, or fearful demeanor • Reluctance or inability to speak on one’s own behalf • Companion who refuses to leave • Lack of identification documents, or documents in possession of another party • Accompanied by individual who answers questions for patient and attempts to control encounter, including insisting on providing interpretation (may be “grandmotherly” type) • Has tattoos or other marks or insignias that may indicate a claim of “ownership” by another, unwilling or uncomfortable talking about the tattoo • Evidence of any type of physical violence, including torture • Frequent relocations

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BOX 59.2 

Questions to Identify Human Trafficking • • • • •

Do you get paid for the work you do? Are you able to leave when you want to? Are there locks on the outside of your doors and windows? Can you come and go as you want? Have you been threatened if you leave your job?

social supports, fear of reprisal from the captor, lack of recognition of being trafficked, constant surveillance with intimidation, and confiscation of documents or identification (often under the guise of “keeping them in a safe place”). There may be a language or cultural barrier, fear of deportation, and distrust of authorities for those brought in from other countries. Victims of sex trafficking may be relocated frequently, often to areas where there are large sports or entertainment venues, such as the Super Bowl and other national sporting events. When an emergency clinician suspects that his or her patient is a HT victim, it is important to interview the patient in private, using a medical interpreter when appropriate. HT victims may be accompanied by a “grandmotherly” figure who is actually a captor. As with IPV, HT survivors note that they are more likely to disclose their situation if they perceive that the emergency clinician is knowledgeable and nonjudgmental about HT and when there is a trusting relationship. An advocate or social worker who is knowledgeable about the dynamics of HT can be helpful. Box 59.2 provides helpful questions for the patient who is willing to make a disclosure. Even if the patient does not disclose, the emergency clinician can send an important message that the hospital is a safe place to come to for help. Institutions should institute safe, culturally sensitive, and responsive resources through staff training and community partnerships. Community resources may include law enforcement task forces, safe houses, and legal remedies for undocumented immigrants (eg, special visas). Many state medical societies have developed educational materials for physicians.50

Diagnostic Testing Diagnostic testing for specific injuries and illnesses related to IPV follows general medical, trauma, and injury guidelines.

Screening IPV survivors use the ED at high rates. One study of law enforcement–involved survivors has found that 64% had used the ED in the year prior to police identification, and 82% used the ED in the 2 years surrounding law enforcement involvement.53 Many of these were not identified on review of the ED records, and most of the ED visits (71%) were non–injury-related. Directed screening for IPV involves questioning patients who present with illnesses and conditions that are more frequently associated with IPV (eg, chronic pain, multiple ED visits, STIs, unintended pregnancy, mental health issues such as depression, anxiety, PTSD, and suicide, alcohol and drug presentations). Universal screening includes screening those who are asymptomatic. The Institute of Medicine has recommended screening for IPV as a preventive health measure,54 the USPSTF has recommended routine screening of asymptomatic women of childbearing age for IPV in the health care setting, with referral to intervention services,32 and the American College of Emergency Physicians has endorsed assessing for family violence in all forms.53 The USPSTF’s recommendation has a B grade, indicating that there is high certainty that the net benefit is moderate to substantial and there

is little evidence of harm, based on a systematic review. Although studies have shown an increase in identification, proving a decrease in violence and increase in quality of life is challenging. A systematic review has found evidence of benefit from screening in certain populations.55 The task force does not indicate where this screening should happen, but given that survivors use the ED at high rates, and IPV is often missed, the ED seems an appropriate place to screen. Screening in the ED has been found to be safe. When surveyed in the ED, 26% of women in a past-year relationship screened positive and, at follow-up at 1 week and 3 months, there was no report of increased violence or harm as a result of screening. Although many authorities have recommended screening for IPV, and screening has been found to be acceptable to patients, barriers to screening have been identified, such as time constraints, lack of institutional protocols, policies, and procedures for screening, and negative attitudes and perceptions.56 Screening is often included in the triage section of the medical record and is often performed by a nurse in a hectic and sometimes public triage area. This approach puts privacy and security at risk because IPV survivors may be accompanied by their abusive partner. This approach also precludes developing a rapport with the provider, an important catalyst for disclosure. Providers should further question intoxicated patients after they are sober, because patients who present with alcohol and drug misuse are less likely to be screened on presentation due to their altered level of consciousness.45 Some examples of validated IPV screening tools are presented in Table 59.1. Triage screening should be followed up privately, after all visitors have been asked to step out of the room. When asking about IPV, framing statements are helpful to normalize and destigmatize IPV. Such statements may include the following: • “Because violence is so common in the lives of my patients, I ask all patients if they are being hurt or threatened by a current or ex-partner.” or • “I have found that many of my patients experience violence at home, so I like to ask my patients if they feel stress, or feel threatened at home.” The word “stress” may prompt recall of abuse that may not be perceived as IPV by the patient, but that may represent psychological or sexual abuse. Using inclusive terms such as partner will make those in a same sex or gender nonconforming relationships feel more comfortable about disclosing their situation. The emergency clinician should ask open-ended questions to give patients a chance to tell their story. Data have shown that when emergency clinicians asked at least one additional related question, patients were more likely to disclose abuse. Other methods of screening for IPV include electronic and paper surveys filled out by the patient while in the waiting room. Patient should be informed about state-specific reporting requirements that may accompany disclosure of IPV.

MANAGEMENT An overview of management and documentation considerations is provided in Table 59.2. ED screening for IPV should be combined with a strong, coordinated, institutional response.57,58 This should include ED staff training, development of institution-wide written and easily accessible policies and protocols, and in-person resources, including a social worker with IPV expertise or a domestic violence advocate. Components associated with high provider efficacy in screening include screening protocols, institutional support, initial and ongoing training, and access to IPV expert referrals.57,59 A strong, hospital-based IPV response includes systems for screening, provider training and maintenance of skills in identification and immediate response, social services, mental

CHAPTER 59  Intimate Partner Violence and Abuse

TABLE 59.2 

Intervention Strategies Based on Intimate Partner Violence (IPV) Exposure and Risk Level PATIENT TYPE BASED ON ASSESSMENT

INITIAL INTERVENTION STEPS

CRITICAL DOCUMENTATION FOR THE ENCOUNTER

No history of IPV or suspicion of abuse

Provide basic message that IPV is a health problem.

“No history of IPV; no suspicion of IPV”

Prior history of IPV but no current exposure

Assess for sequelae of prior abuse; provide educational message that patient is at risk of future IPV relationship.

Add history of IPV to problem list (can be coded as a V code); describe medical and mental health impact and any referrals made.

Recent or current abuse but no injuries and no elements on danger assessment

Assess for sequelae of abuse; provide referrals to IPV resources.

Add IPV to problem list; describe health sequelae from abuse; note referral for urgent follow-up provided to patient.

Recent or current abuse with injuries or positive findings on danger assessment

Crisis bedside consultation by social services or IPV advocate; discuss possibility of an order for protection; notify police if required by law.

Add IPV to problem list; describe health sequelae; summarize follow-up plan as outlined by social services or IPV advocate; complete mandatory reports; describe injury findings using narration, diagrams, and photographs.

Suspicion of current abuse but patient denies IPV

Provide basic message that IPV is a health problem; request bedside consultation by social services or IPV advocate; provide referrals to IPV resources.

Document IPV as a suspected health problem; note that bedside consultation was done and resources were provided; if injured, describe injury findings using narration, diagrams, and photographs.

health and substance abuse staff knowledgeable about IPV, and specialized IPV intervention programs. For institutions that lack a hospital-based IPV program, partnering with a local domestic violence agency or shelter increases resources and facilitates coordination of care. A tool developed by the Agency for Healthcare Research and Quality is available to assess system readiness.59a This assesses hospital policies and procedures, physical environment, cultural environment, emergency clinician education, screening and safety assessment, program evaluation and quality improvement, and collaborative agreements. A trauma-informed approach is critical when working with survivors of IPV. This approach recognizes the effect of past and present trauma on an individual and how this influences her or his care. It emphasizes the strengths of the survivor, rather than emphasizing the traumatic effects, recognizes the unique expertise that the individual has regarding the situation, and determines which interventions are most helpful at a given point in time.

Intervention Once a patient has disclosed IPV, the emergency clinician only needs to follow a few simple steps (Box 59.3). The emergency clinician should do the following: (1) acknowledge the abuse experience, commend the patient for disclosing, and explain how this information will facilitate good medical care; (2) validate the patient’s experience and emphasize that no one deserves to suffer physical, psychological, or sexual abuse; and (3) address the risk of acute danger to the patient or their children, determine readiness to take steps to increase safety, and provide specific means to increase safety. Individualized safety planning is complex and time-consuming and is best done by an experienced social worker or advocate in the ED or at follow up. See Fig. 59.2 for a sample template safety plan that can be used when a social worker or advocate is not immediately available. Possible management options for patients experiencing IPV may include support groups, legal remedies (eg, orders for protection, custody, pressing charges), shelter placement, or ongoing plans for follow-up with community advocates. A discussion about past strategies and what has been successful can help guide future management. Discussing the scope and consequences of

BOX 59.3 

Simple Steps for Discussing Intimate Partner Violence After Patient Has Identified 1. Acknowledge abuse and thank the patient for sharing. 2. Validate the patient. Explain that no one deserves to be treated in an emotionally, physically, or sexually abusive manner. 3. Explain that you would like to help them today. Ask permission to get an advocate or social worker involved. Ask how else staff can help today. 4. Safety and danger assessment—assess immediate safety concerns; have further discussion and planning with the social worker or advocate. 5. Make a plan for follow up. Reinforce that IPV is a health care problem and that the patient can return for assistance.

abuse on the patient and his or her children can help the patient decide which actions are most appropriate. Orders for protection have been shown to be effective in decreasing future violence, but also have the potential to increase violence.60 Abusers who do not have respect for the law or act in public are less likely to respect protection orders. Although survivors may make undesirable decisions, the provider should support the survivor and encourage her or him to continue to speak with health care providers and contact IPV agencies in the future. If children are present in the home, have experienced violence, or are at risk for becoming targets of violence, the emergency clinician may be mandated by law to report this to child protective services. Reporting to child protective services should be done in collaboration with the patient, explaining that this is done to increase resources to help keep the children safe; such a discussion may mitigate the fears of victims that disclosures of violence in the home would risk loss of custody of the child. A brief discussion about the long-term health effects of violence on children may be helpful. If the patient has not disclosed, but the emergency clinician suspects IPV, a disclosure should not be forced. It is more

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Trauma  | 

SECTION Four 

Violence and Abuse

Fig. 59.2.  Sample safety planning brochure. (From Look to End Abuse Permanently (LEAP): Safety plan. www.leapsf.org/pdf/LEAP-Safety-Plan-bro-10_05_09_ENG-OUTSF-B&W-low-res-for-web.pdf.)

important to express concern for the patient, explain how the condition may be related to stress (if this is true), and offer support, community domestic violence resources, and the opportunity to return for assistance.

Danger Assessment Campbell and colleagues have developed a 20-item danger assessment tool (Fig. 59.3) that was developed and validated based on reviews of IPV-related homicides across 11 cities.61 This study

identified factors that were more often correlated with IPV violence leading to homicide and can be used to assess immediate risk for future severe violence and lethality in IPV survivors. The tool is somewhat complex to score and requires familiarity. A self-administered version of this tool is available as a downloadable application on iTunes (Fig. 59.4). A brief, five-item version of this tool (Box 59.4) has been evaluated in an ED population of identified IPV survivors at risk for severe or potentially lethal assault, with a “yes” answer to at least three of the questions as the threshold for high risk (sensitivity, 83%). This five-item tool is

CHAPTER 59  Intimate Partner Violence and Abuse

Fig. 59.3.  Danger assessment tool.

more rapidly and easily administered, but has not been externally validated.

Mental Health Screening Given the increased prevalence of mental health disorders, including depression, anxiety, and suicide in IPV survivors, providers should conduct a brief mental health evaluation. Houry and associates have devised and validated a brief screening tool for use in this population (Fig. 59.5).62 A score of 4 or higher has a positive predictive value (PPV) of 96% for depression, 84% for PTSD symptoms, and 54% for suicidal ideation.

BOX 59.4 

Brief Danger Assessment 1. Has the physical violence increased in frequency or severity over the past 6 months? 2. Has he ever used a weapon or threatened you with a weapon? 3. Do you believe he is capable of killing you? 4. Have you ever been beaten by him while you were pregnant? 5. Is he violently and constantly jealous of you?

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SECTION Four 

Violence and Abuse

Privacy and Confidentiality Considerations Privacy is a concern for many IPV survivors. Any referrals or records should be released only after permission is obtained from the survivor. IPV should not be reported to police without the consent of the survivor unless mandated by law in cases of coexisting child, elder, or disabled abuse or based on state-specific reporting statutes (eg, burns or injuries inflicted by weapons). If reporting is mandated, the provider should make every effort to involve the patient. However, concerns for Health Insurance Portability and Accountability Act (HIPAA) violations do not apply in this circumstance; the privacy rule contains a provision allowing disclosure of protected health information to law enforcement in the case of reporting required by law.

Documentation

Fig. 59.4.  Downloadable assessment.

SmartPhone

application

with

danger

When a patient does disclose IPV, documentation in the medical record can help other health care providers and the survivor when seeking legal remedies, such as custody or restraining orders. Medical records are often admitted into a court of law as an exception to the hearsay rule, which states that someone cannot testify about something that someone else said. These statements are accepted because they are often made in the usual course of medical care or when the patient is upset and may have less impetus to fabricate. Patient statements should be documented with quotes whenever possible, or with a preceding statement— “patient states. …” Injuries should be described, recording the size or length, type of injury (eg, bruise, incised wound, abrasion), and location. EDs should have protocols for digitally photographing injuries and wounds so that they are obtained consistently, with

Brief Mental Health Screen

Feel sad? 0 1 2 3

I do not feel sad. I feel sad. I am sad all of the time and can’t snap out of it. I am so sad or unhappy that I can’t stand it.

Have you experienced a traumatic event (rape, car accident, domestic violence, death in the family, et cetera) in the past year? 0 No 1 Yes Wish to live 0 1 2

I have a medium to strong wish to live. I have a weak wish to live. I have no wish to live.

Wish to die 0 1 2

I have no wish to die. I have a weak wish to die. I have a medium to strong wish to die.

Total Score: _______

(A score of 4 or higher considered positive, with the need for further mental health referral.) Fig. 59.5.  Brief mental health screen. (From Houry D, Kemball RS, Click LA, Kaslow NJ: Development of a brief mental health screen for intimate partner violence victims in the emergency department. Acad Emerg Med 14:202–209, 2007.)

CHAPTER 59  Intimate Partner Violence and Abuse

adequate quality for legal use. Photographs should follow the rule of 4:1 long-range picture, which includes the face for identification, one medium range, and two close range, and one with and one without a ruler (or an object for comparison, such as a coin). All photographs should be stored in tamper-resistant CDs and labeled with the name of the patient, medical record, date, and signature of the person taking the photograph. The presence of photographs should be documented in the medical record. Referrals should also be recorded in the medical record. The diagnosis of IPV or suspected IPV should be documented for the medical record for possible use in legal proceedings, as well as for purposes of research and epidemiology.

TABLE 59.3 

ICD-10 Coding Categories Used for Intimate Partner Violence ICD-10 CODE

DESCRIPTION

995.8_

Maltreatment (abuse)

995.81

Physically abused adult

995.82

Adult emotional and psychological

995.83

Adult sexual

995.84

Adult neglect

Intimate Partner Violence Coding and Diagnosis

995.85

Other, multiple forms

International Classification of Diseases (ICD)–10 coding provides increased specificity for the coding of IPV (Table 59.3). New codes added to the primary category allow the provider to include adult maltreatment and neglect. Other codes added include suspected IPV (T codes) and past IPV and counseling (V codes). Similar to ICD-9, ICD-10 also includes E codes, which are used to describe the nature of the cause of the injury—for example, “Who committed the act of violence” (E967.0–E967.9), the nature of the abuse (E960–E968), the intent of the abuse or neglect (E904.0– E968.4), and the intentionality of the abuse (E980–E989).

E

Who, intentionality, nature of abuse

T4

Suspected abuse

T7

Confirmed abuse

V

Past history of abuse

DISPOSITION Most ED patients with IPV will be treated and discharged. Patients who are victims of potentially life-threatening injuries, particularly attempted strangulation, are at great danger of future violence and should have safe plans for discharge or be offered temporary admission for safety.63 Although shelters are one option, they are an extreme solution, typically removing the survivor from friends and family and sometimes requiring them to leave their place of

ICD, International Classification of Diseases.

employment and their children’s school. Furthermore, shelters are not always an available option; they are often full and may not accept patients with substance abuse issues, teenage male children of survivors, or male or transgender survivors. All survivors who are being discharged should receive resources for domestic violence, mental health, substance abuse, and social services. The emergency clinician may not agree with the choices made by the survivor but should always respect these decisions and offer encouragement and validation. This approach will increase the chances of a positive interaction and increase the likelihood of further help-seeking behavior.

KEY CONCEPTS • Intimate partner violence encompasses a pattern of controlling behaviors, including intentional physical assault, sexual assault, psychological violence, and financial control. • Treatment and intervention in intimate partner violence may be compared to a chronic disease model, whereby intervention happens over time, and relapses may be a part of the cycle. It is also critical to remember that although intervention is often offered to the survivor, responsibility for the behavior should be placed on the abusive partner. • Treatment and intervention in IPV requires a coordinated approach, including physician training, an integrated system that includes social work and IPV counselor availability, and a close relationship with area IPV service provider groups.

• Routine screening for IPV in women of childbearing age is recommended by the USPSTF; screening methods may include paper-based, computer-based, face to face (by nurse or physician), or combination of screening methods. • Sequelae of IPV include chronic pain, mental health issues (eg, depression, PTSD, substance abuse), STIs and unintended pregnancy, and worsening of medical problems (eg, diabetes, asthma). • Attempted strangulation in IPV is associated with a sevenfold increased risk of an attempted or completed lethal attack, and patients should be encouraged to seek protection from further incidents. • Some cases of IPV presenting to the ED may actually be cases of human trafficking. Cases of human trafficking have a very different dynamic and require specialized interventions.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 59  Intimate Partner Violence and Abuse

REFERENCES 1. Saltzman L, Fanslow J, McMahon P, et al: Intimate partner violence surveillance: uniform definitions and recommended data elements, version 1.0, Atlanta, 2002, Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. 2. Clark LE, Allen RH, Goyal V, et al: Reproductive coercion and co-occurring intimate partner violence in obstetrics and gynecology patients. Am J Obstet Gynecol 210(42):e1–e8, 2014. 3. ACOG Committee Opinion No. 518: intimate partner violence. Obstet Gynecol 119(Pt 1):412–417, 2012. 4. Black MC, Basile KC, Breiding MJ, et al: The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 summary report, Atlanta, 2011, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. 5. Breiding MJ, Black MC, Ryan GW: Prevalence and risk factors of intimate partner violence in eighteen U.S. states/territories, 2005. Am J Prev Med 34:112–118, 2008. 6. Johnson MP, Leone JM, Xu Y: Intimate terrorism and situational couple violence in general surveys: ex-spouses required. Violence Against Women 20:186–207, 2014. 7. Bosch J, Weaver TL, Arnold LD, et al: The impact of intimate partner violence on women’s physical health: Findings from the Missouri behavioral risk factor surveillance system. J Interpers Violence 2015. Advance online publication. 8. Dichter ME, Gelles RJ: Women’s perceptions of safety and risk following police intervention for intimate partner violence. Violence Against Women 18:44–63, 2012. 9. Lagdon S, Armour C, Stringer M: Adult experience of mental health outcomes as a result of intimate partner violence victimisation: a systematic review. Eur J Psychotraumatol 5, 2014. 10. Devries KM, Mak JY, Bacchus LJ, et al: Intimate partner violence and incident depressive symptoms and suicide attempts: a systematic review of longitudinal studies. PLoS Med 10:e1001439, 2013. 11. McLaughlin J, O’Carroll RE, O’Connor RC: Intimate partner abuse and suicidality: a systematic review. Clin Psychol Rev 32:677–689, 2012. 12. Cesario SK, McFarlane J, Nava A, et al: Linking cancer and intimate partner violence: the importance of screening women in the oncology setting. Clin J Oncol Nurs 18:65–73, 2014. 13. Alhusen JL, Lucea MB, Bullock L, et al: Intimate partner violence, substance use, and adverse neonatal outcomes among urban women. J Pediatr 163:471–476, 2013. 14. Leone JM, Lane SD, Koumans EH, et al: Effects of intimate partner violence on pregnancy trauma and placental abruption. J Womens Health (Larchmt) 19:1501– 1509, 2010. 15. Hess KL, Javanbakht M, Brown JM, et al: Intimate partner violence and sexually transmitted infections among young adult women. Sex Transm Dis 39:366–371, 2012. 16. Hall M, Chappell LC, Parnell BL, et al: Associations between intimate partner violence and termination of pregnancy: a systematic review and meta-analysis. PLoS Med 11:e1001581, 2014. 17. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention: 10 leading causes of death, by age group, 2011, all races, all females— United States, 2011. . 18. Parks SE, Johnson LL, McDaniel DD, et al: Surveillance for violent deaths—National Violent Death Reporting System, 16 states, 2010. . 19. Stöckl H, Devries K, Rotstein A, et al: The global prevalence of intimate partner homicide: a systematic review. Lancet 382:859–865, 2013. 20. Rivara FP, Anderson ML, Fishman P, et al: Healthcare utilization and costs for women with a history of IPV. Am J Prev Med 32:89–96, 2007. 21. Fishman PA, Bonomi AE, Anderson ML, et al: Changes in health care costs over time following the cessation of intimate partner violence. J Gen Intern Med 25:920–925, 2010. 22. Gilbert L, El-Bassel N, Chang M, et al: Substance use and partner violence among urban women seeking emergency care. Psychol Addict Behav 26:226–235, 2012. 23. Breiding MJ, Armour BS: The association between disability and intimate partner violence in the United States. Ann Epidemiol 25:455–457, 2015. 24. Hahn JW, McCormick MC, Silverman JG, et al: Examining the impact of disability status on intimate partner violence victimization in a population sample. J Interpers Violence 29:3063–3085, 2014. 25. Mitra M, Mouradian VE: Intimate partner violence in the relationships of men with disabilities in the United States: relative prevalence and health correlates. J Interpers Violence 29:3150–3166, 2014. 26. Weaver TL, Gilbert L, El-Bassel N, et al: Identifying and intervening with substanceusing women exposed to intimate partner violence: phenomenology, comorbidities, and integrated approaches within primary care and other agency settings. J Womens Health (Larchmt) 24:51–56, 2015. 27. Bazargan-Hejazi S, Kim E, Lin J, et al: Risk factors associated with different types of intimate partner violence (IPV): an emergency department study. J Emerg Med 47:710–720, 2014. 28. Markman HJ, Stanley SM, Bloomberg SL: Fighting for your marriage, San Francisco, 2010, Jossey-Bass. 29. Rollins C, Glass NE, Perrin NA, et al: Housing instability is as strong a predictor of poor health outcomes as level of danger in an abusive relationship: findings from the SHARE Study. J Interpers Violence 27:623–643, 2012. 30. Taft AJ, Small R, Hegarty KL, et al: MOthers’ AdvocateS In the Community (MOSAIC)—non-professional mentor support to reduce intimate partner violence and depression in mothers: a cluster randomised trial in primary care. BMC Public Health 11:178, 2011. 31. Rhodes KV, Kothari CL, Dichter M, et al: Intimate partner violence identification and response: time for a change in strategy. J Gen Intern Med 26:894–899, 2011. 32. Moyer VA: Screening for intimate partner violence and abuse of elderly and vulnerable adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 158:478–486, 2013. 33. Carmo R, Grams A, Magalhaes T: Men as victims of intimate partner violence. J Forensic Leg Med 18:355–359, 2011.

34. Wu V, Huff H, Bhandari M: Pattern of physical injury associated with intimate partner violence in women presenting to the emergency department: a systematic review and meta-analysis. Trauma Violence Abuse 11:71–82, 2010. 35. Yau RK, Stayton CD, Davidson LL: Indicators of intimate partner violence: identification in emergency departments. J Emerg Med 45:441–449, 2013. 36. Davidov DM, Larrabee H, Davis SM: United States emergency department visits coded for intimate partner violence. J Emerg Med 48:94–100, 2015. 37. Hoelle RM, Elie M-C, Weeks E, et al: Evaluation of healthcare use trends of high-risk female intimate partner violence victims. West J Emerg Med 16:107–113, 2015. 38. Decker MR, Miller E, McCauley HL, et al: Recent partner violence and sexual and drug-related STI/HIV risk among adolescent and young adult women attending family planning clinics. Sex Transm Infect 90:145–149, 2014. 39. Fantasia HC, Sutherland MA, Fontenot HB, et al: Chronicity of partner violence, contraceptive patterns and pregnancy risk. Contraception 86:530–535, 2012. 40. Fontenot HB, Fantasia HC, Lee-St John TJ, et al: The effects of intimate partner violence duration on individual and partner-related sexual risk factors among women. J Midwifery Womens Health 59:67–73, 2014. 41. Spiwak R, Afifi TO, Halli S, et al: The relationship between physical intimate partner violence and sexually transmitted infection among women in India and the United States. J Interpers Violence 28:2770–2791, 2013. 42. Hall M, Chappell LC, Parnell BL, et al: Associations between intimate partner violence and termination of pregnancy: a systematic review and meta-analysis. PLoS Med 11:e1001581, 2014. 43. Ahmed AT, McCaw BR: Mental health services utilization among women experiencing intimate partner violence. Am J Manag Care 16:731–738, 2010. 44. Devries KM, Child JC, Bacchus LJ, et al: Intimate partner violence victimization and alcohol consumption in women: a systematic review and meta-analysis. Addiction 109:379–391, 2014. 45. Choo EK, Nicolaidis C, Jenkinson RH, et al: Failure of intimate partner violence screening among patients with substance use disorders. Acad Emerg Med 17:886–889, 2010. 46. El-Bassel N, Gilbert L, Witte S, et al: Intimate partner violence and HIV among drug-involved women: contexts linking these two epidemics—challenges and implications for prevention and treatment. Subst Use Misuse 46:295–306, 2011. 47. Bonomi AE, Anderson ML, Reid RJ, et al: Medical and psychosocial diagnoses in women with a history of intimate partner violence. Arch Intern Med 169(18):1692– 1697, 2009. 48. Wuest J, Ford-Gilboe M, Merritt-Gray M, et al: Pathways of chronic pain in survivors of intimate partner violence. J Womens Health (Larchmt) 19:1665–1674, 2010. 49. Humphreys J, Cooper BA, Miaskowski C: Occurrence, characteristics, and impact of chronic pain in formerly abused women. Violence Against Women 17:1327–1343, 2011. 50. Massachusetts General Hospital, Human Trafficking Initiative; Massachusetts Medical Society, Committee on Violence Intervention and Prevention: Human trafficking: guidebook on identification, assessment, and response in the health care setting. . 51. Oram S, Ostrovschi NV, Gorceag VI, et al: Physical health symptoms reported by trafficked women receiving post-trafficking support in Moldova: prevalence, severity and associated factors. BMC Womens Health 12:20, 2012. 52. Oram S, Stockl H, Busza J, et al: Prevalence and risk of violence and the physical, mental, and sexual health problems associated with human trafficking: systematic review. PLoS Med 9:e1001224, 2012. 53. American College of Emergency Physicians: Domestic family violence. . 54. Institute of Medicine: Clinical preventive services for women: closing the gaps, Washington, DC, 2011, National Academies Press. 55. Nelson HD, Bougatsos C, Blazina I: Screening women for intimate partner violence: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med 156:796–808, 2012. 56. Hamberger LK, Rhodes K, Brown J: Screening and intervention for intimate partner violence in healthcare settings: creating sustainable system-level programs. J Womens Health (Larchmt) 24:86–91, 2015. 57. O’Campo P, Kirst M, Tsamis C, et al: Implementing successful intimate partner violence screening programs in health care settings: evidence generated from a realistinformed systematic review. Soc Sci Med 72:855–866, 2011. 58. Ghandour RM, Campbell JC, Lloyd J: Screening and counseling for Intimate Partner Violence: a vision for the future. J Womens Health (Larchmt) 24:57–61, 2015. 59. Feder G, Davies RA, Baird K, et al: Identification and Referral to Improve Safety (IRIS) of women experiencing domestic violence with a primary care training and support programme: a cluster randomised controlled trial. Lancet 378:1788–1795, 2011. 59a.  . 60. Kothari CL, Rhodes KV, Wiley JA, et al: Protection orders protect against assault and injury: a longitudinal study of police-involved women victims of intimate partner violence. J Interpers Violence 27:2845–2868, 2012. 61. Campbell JC, Webster DW, Glass N: The danger assessment: validation of a lethality risk assessment instrument for intimate partner femicide. J Interpers Violence 24:653–674, 2009. 62. Houry D, Kemball RS, Click LA, et al: Development of a brief mental health screen for intimate partner violence victims in the emergency department. Acad Emerg Med 14:202–209, 2007. 63. Glass N, Laughon K, Campbell J, et al: Non-fatal strangulation is an important risk factor for homicide of women. J Emerg Med 35:329–335, 2008.

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767.e2

CHAPTER 59: QUESTIONS & ANSWERS 59.1. By state law, you are a mandated reporter for intimate partner violence (IPV). You are concerned about violating the Health Insurance Portability and Accountability Act (HIPAA). Which of the following is correct? A. Patients are always free to act of their own free will. B. Reporting should be done without telling the patient, because you cannot report if the patient objects. C. When reporting is required by law, it does not require patient consent. D. You need a signed consent to make the report. E. You should call the legal department before reporting. Answer: C. IPV patients are not always free to act of their own will in health care decision making. Some states have laws that require reporting to local authorities. Reporting of health conditions required by local laws are exempted from HIPAA regulations. Fear may be so profound in the IPV survivor that decision making is impaired, thus jeopardizing informed consent. 59.2. Which of the following is not suspicious for intentional injury from IPV? A. Bilateral injuries B. Ecchymosis of lower extremity C. Injuries to the breasts or abdomen D. Injuries to the hands and extensor surface of the forearms E. Pattern injuries Answer: B. Signs of an intentional injury include a central location (ie, trunk and breasts), bilateral injuries (both arms or both legs), defensive injuries (ie, ecchymoses on the back of the hand as a result of protecting the face), and patterned injuries (having the markings of an object, such as the sole of a shoe or a burn with the imprint of an iron). 59.3. Which of the following about a woman should alert the provider that the patient may be a victim of human trafficking, rather than IPV? A. Appears much younger than her stated age and does have not identification with her B. Is accompanied by her partner who will not leave her side

C. Is easily startled D. Is evasive in answering questions about her injuries E. Presents with a traumatic injury at night Answer: A. Most of these situations apply to the IPV survivor and victim of human trafficking. Presentations that should alert the provider that the patient may be a victim of human trafficking rather than IPV include a person who looks much younger than her stated age (she often is younger). Other clues include a victim that does not have identification papers (the “employer” often takes these from the victims under the guise of “keeping the documents safe”), but this also prevents the victim from leaving without these documents. Untreated sexually transmitted infections (STIs, including pelvic inflammatory disease), malnourishment, and addiction to drugs and alcohol. It is important for the provider to consider the presentations of human trafficking, because although the victim may not be identified in the ED—for a number of reasons, including lack of trust and familiarity with the ED provider, the resources that may be helpful are somewhat different than those used by IPV survivors. 59.4. Key management steps after identifying a patient experiencing IPV include which of the following? A. Creating a detailed and comprehensive safety plan B. Emphasizing the importance of leaving the abuser immediately C. Keeping the patient in the ED until she agrees to contact police and have a restraining order issued D. Providing validation about disclosing the abuse E. Reinforcing the importance of secrecy about the abuse until the woman has left the home Answer: D. Emergency clinicians should validate the disclosure of abuse, emphasize that the victim is not at fault, and encourage future discussions with IPV community agencies or other health care providers. Immediate safety should be assessed, but most patients will not want to leave the abuser immediately; however, a positive initial conversation may begin the process of ending the abusive relationship. A templated list will allow the ED staff to create a basic safety plan with the patient; an individualized plan is best done in conjunction with trained domestic violence advocates, typically in follow-up.

SECTION ONE

Head and Neck Disorders C H A P T E R 60 

Oral Medicine Ryan Anthony Pedigo  |  James T. Amsterdam INTRODUCTION Dental concerns are a common chief complaint in the emergency department (ED). The spectrum of oral disease ranges from bothersome to emergently life-threatening. This chapter covers disorders of the tooth, gingiva and periodontium, dental procedure-related issues, odontogenic and deep infections of the head and neck, traumatic dental emergencies, as well as temporomandibular joint disorder (TMD) and dislocation.

DISORDERS OF THE TOOTH Principles Anatomy Humans have 20 deciduous (primary) teeth and 32 permanent (secondary) teeth, which are supported and maintained in the maxilla (upper teeth) and mandible (lower teeth) by the periodontium. The tooth that is normally visible in the mouth is considered the crown, whereas the tooth that is under the gingival line is the root (Fig. 60.1). The crown of the tooth has three layers; from outside to inside they are the enamel, dentin, and pulp. The enamel is the only part of the tooth that is visible in the absence of pathology (eg, fractures, caries) and is a hard coating that protects the tooth. The next layer deep to the enamel is the dentin, which is an intermediate layer between the enamel and the pulp (for the crown) and between the cementum and the pulp (for the root). Yellow in appearance, dentin is comprised of porous microtubules, supports the enamel, and acts as a cushion during mastication. If dentin is exposed from caries or trauma, the patient will have tooth sensitivity and/or pain. The deepest layer is the pulp cavity, which houses its neurovascular supply. The normal primary, or deciduous, dentition (“baby teeth”) consists of 10 mandibular and 10 maxillary teeth (Fig. 60.2). The lower central incisor is the first tooth to erupt at approximately 6 months of age; all primary teeth should be present by 3 years of age. The permanent dentition begins to erupt at approximately 5 to 6 years of age with the appearance of the first molar. The permanent dentition consists of 32 teeth; there are 8 teeth per quadrant (eg, right upper, right lower, left upper, left lower). From medial to lateral, the names of the teeth in each quadrant are: the central incisor, lateral incisor, canine, two premolars (also called bicuspids), and three molars (also called tricuspids). The third molars (“wisdom teeth”) are the last to erupt, appearing at approximately 16 to 18 years of age. The permanent dentition are numbered from 1 to 32, starting with the upper right third molar (1) and moving to the upper left third molar (16), to the lower

left third molar (17), and to the lower right third molar (32). The starting point for this numbering system can be recalled by the mnemonic “upright.” It is often easier to name the tooth or teeth involved; for instance, if tooth 8 is injured, the clinician could describe the tooth as the “right maxillary central incisor” or the “right upper central incisor.” If multiple teeth are involved, numbering is more concise. Specific terminology is also used to describe the various surfaces in the mouth. The facial (also referred to as labial or buccal) surface faces outside the oral cavity; the oral (also referred to as palatal for upper teeth, or lingual for lower teeth) surface faces the tongue; the mesial surface is toward the midline; and the distal surface is toward the ramus of the mandible. The interproximal surface refers to the contacting area of adjacent teeth, and the occlusal surface refers to the biting area. Finally, apical is in the direction of the root, whereas coronal is toward the crown of the tooth.

Pathophysiology Dental caries are caused by breakdown of the teeth secondary to bacterial activity. Bacteria generate acid as a byproduct from cellular metabolism of food left on the tooth surface, subsequently demineralizing the enamel. Once the enamel is breached, the microporous dentin is able to transmit saliva, byproducts of the bacteria, and the bacteria to the pulp. The pulp initially reacts with a hyperemic response, which continues to an inflammatory state termed pulpitis, which can be reversed. Untreated, pulpitis can further progress to total degeneration and necrosis (irreversible pulpitis). Cracked tooth syndrome (CTS) is a condition that generally affects adults 30 to 60 years old and is defined as “a fracture plane of unknown depth and direction passing through tooth structure that may progress to communicate with the pulp and/or periodontal ligament.”1 These fractures can occur due to either excessive forces on a normal tooth (eg, accidentally biting on a hard object, such as metal or bone), or normal forces on a weakened tooth (eg, a carious tooth or one that has undergone dental procedures previously). Because of the mechanism of injury, teeth subjected to larger forces (such as the mandibular molars) are most commonly affected. If misdiagnosed, the fracture may propagate into the pulp or periodontal ligament and compromise viability of the tooth.

Clinical Features Dental caries is the most common cause of odontogenic pain. The patient may give a variable history of a sudden or gradual onset of a sharp to dull, throbbing pain. In most cases, the patient can 771

772

PART III 

Medicine and Surgery  | 

SECTION One 

Head and Neck Disorders

Enamel Crown

Dentin Pulp cavity Gingival sulcus Gingiva

Periodontal ligament Alveolar bone

Root

Periodontium Attachment apparatus

Cementum Root canal

Fig. 60.1.  The anatomy of the tooth and associated attachment apparatus.

indicate the specific tooth involved, but pain may be generalized. Early (reversible) pulpitis is sensitive to changes in temperature and pressure; irreversible pulpitis can have pain without any stimulus. CTS patients may provide a history of preexisting dental procedures or disease, or they may have a history of occlusive trauma. Presenting symptoms are similar to those of dental caries.

Physical Examination The physical examination described here is applicable to all sections of this chapter. Ideally the patient should be placed in a dental or ear, nose, and throat chair or on a bed at a 45-degree angle with adequate lighting. Pediatric patients often are examined while sitting in the parent’s lap. Pediatric patients may require anxiolysis or sedation to permit adequate oral assessment and treatment of a painful condition. Pediatric procedural sedation is described in Chapter 162. A complete examination includes inspection of the oral cavity, gingiva, teeth, and surrounding structures (eg, throat, neck, sinuses) if indicated. Assess teeth for caries or cracks. Localization of the involved tooth may be accomplished by percussing the teeth or by having the patient bite on a tongue blade. Exquisite pain to percussion suggests an underlying periapical abscess (discussed in the section Odontogenic and Deep Neck Infections). Examine the nares and sinuses for discharge and pain, respectively, to evaluate for sinusitis. Palpate the temporomandibular joint (TMJ) with opening and closing of the jaw to assess for “clicks” or “pops,” which may indicate the etiology of pain as TMJ disorder. In older individuals, palpate the temporal artery for tenderness and prominence.

Differential Diagnoses Most dental pain in the ED is odontogenic, the most common being pulpitis due to caries. Tooth pain is not always odontogenic, however. Unilateral upper tooth pain (usually the posterior teeth) can be related to maxillary sinus dysbarism or inflammation. Trigeminal neuralgia can present as tooth pain, but it is usually lancinating and may not be related to temperature changes or mastication (see Chapter 95). Atypical odontalgia is a centralized

trigeminal neuropathy localized in a tooth or teeth. Frequentlymisdiagnosed, patients will often undergo multiple dental procedures with worsening of their pain.2 Atypical odontalgia causes persistent throbbing or burning pain that does not fulfill diagnostic criteria for another disorder and therefore is a diagnosis of exclusion. Older patients with temporal (giant cell) arteritis may have pain with mastication because of jaw claudication.

Diagnostic Testing No laboratory or radiographic testing is routinely indicated.

Management Management of dental caries with pulpitis and CTS is aimed at treating the patient’s pain and referring to a dentist for definitive care. Severe pain can be treated with supraperiosteal infiltration of local anesthetic to provide temporary relief (Fig. 60.3). To perform this, dry the area with gauze, apply a topical anesthetic to the gingiva (eg, 20% benzocaine or 5% lidocaine) and allow it to sit for 5 minutes. Inject 1 to 2 mL of local anesthetic (eg, 2% lidocaine) through the mucobuccal fold of the affected tooth with the bevel facing the tooth. Alternatively, an inferior alveolar nerve block may be used when multiple lower teeth are affected on one side. The patient can be discharged with ibuprofen 400 to 600 mg tablets every 4 to 6 hours. Nonsteroidal antiinflammatory drugs (NSAIDs) given at scheduled times (rather than as needed) are more effective than opioid analgesics for these conditions.3 However, for severe odontalgia, a short course of opioid analgesics in addition to scheduled NSAID administration is reasonable. Opioid analgesics should not be prescribed for long-standing dental problems, such as well-established caries.

Disposition The patient with odontalgia from dental caries or CTS should follow-up with a dentist within the week. Those with CTS should be instructed to avoid chewing on the affected side to avoid further trauma and fracture propagation.

CHAPTER 60  Oral Medicine

10

RIGHT

LEFT

11

Canine First premolar Second premolar

12 13

First molar 14 15 1

16

OPEN MOUTH VIEW

32

Supraperiosteal

Central incisor Lateral incisor

PERMANENT TEETH

Maxillary (upper) teeth

Individual dental nerve

Second molar Third molar

17 18

31

Mandibular (lower) teeth

19 30

20

29 27

C

A

21 22

28 26 25 24 23

Central incisor Lateral incisor Canine

PRIMARY TEETH E F D G H

First molar I

B

Second molar A

J

T

K S

L R

Mandibular (lower) teeth

M Q

P

O

Bevel facing the tooth

Maxillary (upper) teeth

N

Fig. 60.2.  Identification of teeth, adult and child. Conventional numbering starts with the upper right third molar 1 to the upper left third molar 16; lower left third molar 17 to the lower right third molar 32. For the primary dentition, A to J and K to T. (Modified from Roberts J: Roberts & Hedges’ clinical procedures in emergency medicine, ed 6, Philadelphia, 2014, Elsevier, Fig. 64.2, p 1344.)

DISORDERS OF THE GINGIVA AND PERIODONTIUM Principles Anatomy The periodontium serves to hold the teeth in place, as well as protect the root from bacteria. Surrounding the root of the tooth instead of enamel is cementum, which helps fix the tooth to the alveolar bone by attaching to the periodontal ligaments. Collectively, the periodontal ligament, alveolar bone, and cementum comprise the attachment apparatus. The attachment apparatus plus the gingiva (“gums”) is referred to as the periodontium. The gingiva consists of the mucosal tissue that overlies the mandible and maxilla inside the mouth and, in the normal state, acts as a barrier to infection and injury.

B Fig. 60.3.  A and B, Supraperiosteal nerve block for anesthesia of individual teeth. (From Roberts J: Roberts and Hedges’ clinical procedures in emergency medicine, ed 6, Philadelphia, 2014, Elsevier, Fig. 30.5.)

Pathophysiology Gingivitis and Periodontitis.  Periodontitis is inflammation of the supporting structures of the teeth (gingiva, alveolar bone, cementum, periodontal ligament). Degradation of the support structure leads to loss of alveolar bone and subsequent loosening or loss of teeth. In necrotizing periodontal diseases, polymicrobial bacteria (with a predominance of Fusobacterium and spirochetes) invade the tissue and cause pain, bleeding, and destruction. These diseases include necrotizing gingivitis (acute necrotizing ulcerative gingivitis [ANUG], or “trench mouth”) if only the gingiva are involved, necrotizing periodontitis if the attachment apparatus in addition to the gingiva is involved, and necrotizing stomatitis if the disease further extends into the surrounding oral mucosa (Fig. 60.4). Infection of the tonsils and pharynx is termed Vincent’s angina. The most diffuse necrotizing disease is termed noma (cancrum oris, fusospirochetal gangrene) where the entire mouth is involved and is often fatal; this disease is most commonly encountered in young children in developing countries (Fig. 60.5). Pericoronitis.  The gingiva and surrounding tissue can also become inflamed due to a condition known as pericoronitis. As teeth start to erupt, debris and bacteria can accumulate between

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A

Fig. 60.4.  Necrotizing stomatitis. The gingiva has classic papilla necrosis but the oral mucosa is also involved, making this condition necrotizing stomatitis and not simply necrotizing gingivitis. (From Smith J: HIV and AIDS in the adolescent and adult: an updated for the oral and maxillofacial surgeon. Oral Maxillofac Surg Clin North Am 20(4):535–565, 2008, Fig. 8.)

B Fig. 60.6.  Pericoronitis. A, Illustration of pericoronitis with swollen and inflamed operculum. B, Picture of pericoronitis of the third molar with erythema and inflammation of the surrounding tissue. (A, From Buttaravoli P, Leffler SM: Minor emergencies, ed 3, St Louis, 2012, Elsevier,  Fig. 46.1; B, From Neville BW, Damm DD, Allen CM, et al: Oral and maxillofacial pathology, ed 4, St Louis, 2016, Elsevier.)

TABLE 60.1 

Medication Classes and Their Risk of Drug-Induced Gingival Overgrowth CATEGORY Fig. 60.5.  Noma (cancrum oris, fusospirochetal gangrene) is usually found in children in developing countries and can be disfiguring or even fatal. Noma represents the most severe end of the necrotizing periodontal disease spectrum. (From Farrar J, Hotez PJ, Junghanss T, et al, editors: Manson’s tropical diseases, ed 23, London, 2014, Saunders/Elsevier,  Fig. 29.1.)

the tooth and the surrounding soft tissue (this “gum flap” overlying the tooth is called the operculum; Fig. 60.6). The third molar (“wisdom tooth”) is most commonly implicated, and symptoms typically occur in the second or third decade of life. This condition is more common with teeth that are malerupted or impacted. As the tissue becomes enlarged due to inflammation, the problem is worsened by trauma to the area during mastication. Gingival Hyperplasia.  Gingival hyperplasia can occur secondary to medications. The most commonly-associated drug classes are anticonvulsants, calcium channel blockers, and immunosuppressants (Table 60.1).

PHARMACOLOGIC AGENT

PREVALENCE

Anticonvulsants

Phenytoin Sodium valproate (valproic acid) Carbamazepine

50% Rare

Immunosuppressants

Cyclosporine

25% to 30% (adults) 70% (children)

Calcium channel blockers

Nifedipine Felodipine Amlodipine Verapamil Diltiazem

6% to 15% Rare Rare 2 cm2) defects of the orbital floor/medial wall; pediatric trapdoor fractures; and when CT evidence of entrapment is associated with symptomatic diplopia, gaze restriction, or a non-resolving oculocardiac reflex.24 Outside of these indications, persistent diplopia and cosmetic concerns (such as, enophthalmos) are generally not addressed until swelling subsides after 7 to 10 days. Patients can be discharged for reevaluation by an ophthalmologist in 1 to 2 weeks. Children with orbital wall fractures are a special consideration, because they are more predisposed to “green-stick” fractures of the orbital wall and develop fibrosis and shortening of the affected muscle within a couple of days, affecting ocular function; thus, children with orbital wall fractures should be seen by an ophthalmologist in 1 to 2 days.23 Retrobulbar Hemorrhage.  The loss of vision associated with a retrobulbar hematoma is irreversible within 60 to 100

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Fig. 61.11.  The “swinging flashlight test” for an afferent pupillary defect (APD), which is otherwise known as a Marcus Gunn pupil. Normally (panel on left), both pupils constrict regardless of which eye is illuminated, due to intact afferent stimulus into the direct and consensual pupillary light reflexes. With an APD (panel in the middle), the pupils dilate upon “swinging” the flashlight to the pathological eye with dysfunction in the retina or optic nerve (dashed circle), because of a sudden loss of afferent stimulus into light reflexes. With a fixed and dilated or damaged pupil (panel on the right), the same will hold true, except that the damaged pupil may not react due to an intrinsic problem, regardless of the presence of an APD. In each condition, whether normal or with an APD, the pupillary findings will reverse on swinging the flashlight back across to the other eye. The flashlight should be held over each eye for at least 3 seconds to ensure time for a response.

loss. In the meantime, IOP-lowering agents (such as, intravenous [IV] carbonic anhydrase inhibitors, topical beta-blocker, alpha agonists, and in some cases 1 to 2 g of IV mannitol per kilogram) can be used. However, once ischemia and vision loss sets in, time is of the essence, and—depending upon the availability of an ophthalmologist in this time frame—a lateral canthotomy may need to be performed by the emergency clinician as a temporizing, vision-saving measure before definitive decompression (Fig. 61.13).25

Fig. 61.12.  Facial computed tomography (CT) scan showing left inferior orbital fracture with blood in maxillary sinus. (Courtesy University of  Iowa Department of Ophthalmology, http://webeye.ophth.uiowa.edu/ eyeforum/Images/floorfx_08232004.jpg.)

minutes after the onset of ischemia. Emergent ophthalmologic consultation for decompression is therefore indicated, keeping in mind that the clock does not start with the injury but at the time at which the intraorbital compartment pressure from the hematoma reached a pressure critical enough to start to cause vision

Optic Nerve Injury.  Once the determination of the type and degree of optic neuropathy is determined, treatment options can be considered. Surgical decompression of orbital canal fractures that impinge the nerve is not clearly beneficial, and steroids for traumatic optic neuropathy in general do not provide any additional benefit over observation.26 In both cases, an ophthalmologist should be consulted in the ED for potential therapy options.

Chemical Exposures and Glues Clinical Features In addition to blunt or penetrating trauma, the eye can also be injured by chemical exposures. Chemical burns can lead to devastating vision loss. Acids burns precipitate and do not penetrate as deeply into tissue (due to coagulative necrosis, in which the

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A

1

2

3

4

B Fig. 61.13.  A, Lateral canthotomy. B, 1, Preoperative view of orbit. 2, Incision for lateral canthotomy. 3, Identification and incision of inferior canthal tendon, completing cantholysis. 4, View after lateral canthotomy and inferior cantholysis, creating maximal immediate decompression by allowing eyeball and orbital contents to move anteriorly. (B, From Ramakrishnan VR, Palmer JN: Prevention and management of orbital hematoma. Otolaryngol Clin North Am 43:789–800, 2010.)

precipitation of tissue proteins limits the depth of the injury). The one exception to this is hydrofluoric acid, which may rapidly pass through cell membranes and enter the anterior chamber.27 Alkaline burns are more severe because they produce a liquefactive necrosis (because damaged tissues then secrete proteolytic enzymes as part of an inflammatory response), leading to cataract formation, damage to the ciliary body and trabecular meshwork, and irreversible intraocular damage in as little as 5 to 15 minutes.27 Another chemical exposure that may present in the ED is superglue to the eye. Cyanoacrylate is often used in ophthalmological surgical procedures and is relatively nontoxic to the eye. The main issues arising from superglue exposure are adhesion of eyelashes, which is difficult to reverse, and concurrent conjunctival and corneal abrasion.28

Differential Diagnosis It is important to treat all unknown chemical exposures as an acidic or alkali exposure until proven otherwise. Certain substances, such as detergents and solvents, can lead to epithelial injury and anterior chamber inflammation, which then should be treated based on their particular findings (abrasion/iritis). Signs

of a potent chemical exposure include periorbital edema and erythema, de-epithelialized skin, and loss of eyelashes and eyebrows, corneal and conjunctival epithelial defects, chemosis, corneal cloudiness, sterile ulceration, edema, and perforation. Elevated IOP may result from damage and/or inflammation of the trabecular meshwork. Although a determination of the pH of the solution involved is the most important consideration, other factors in the exposure (such as, temperature, amount, impact force, concentration, osmolarity, and redox potential) can greatly influence the pathophysiology of chemical tissue damage.28a Accessing the material safety data sheet (MSDS) of the agent involved or consulting with a Poison Center can greatly facilitate identification of the offending agent and guide the appropriate treatment. If the exposure occurred as a result of explosion, penetrating globe injury may also be present.

Diagnostic Testing Treatment of a chemical exposure should begin as soon as possible with copious irrigation, even prior to arrival to the ED. The initial basic ophthalmic examination should pay attention to an inspection of the fornices, to ensure that there is no remaining chemical

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Corneal alkali burn

B

Corneal alkali burn

Fig. 61.14.  A, Alkali burn demonstrating corneal burns and conjunctival injection on the day of the accident. B, Complete corneal tissue destruction 7 days after alkali burn. (From Kaiser PK, Friedman NJ, Pineda R II: The Massachusetts Eye and Ear Infirmary illustrated manual of ophthalmology, ed 2, Philadelphia, 2004, WB Saunders.)

gel or solid material (such as, alkaline lime or plaster), as well as screening for ocular trauma, facilitated with the use of a topical anesthetic for patient comfort.27 With known chemical exposures, irrigation should be continued for a minimum of 10 minutes until a quick evaluation can be performed. This should include a pH measurement (Nitrazine paper dipped in lower lid fornix) to evaluate for acidity or alkalinity. If the pH is not in the neutral 7 to 7.5 range, irrigation should be continued. Superglue exposure represents a special circumstance, and there are two main principles in the evaluation: (1) to separate the lids so that a detailed eye examination can be performed and to remove visible superglue, and (2) to identify any corneal abrasion with fluorescein staining.28

Management and Disposition For acid or alkaline burns, irrigation of the eye should be performed immediately. The longer irrigation is delayed, more irrigation volume will likely be required because the chemical can deposit within the tissue.27 It may take up 20 L or more to change the pH to a physiologic level (a goal pH of 7 to 7.5). Based on animal studies, traditional isotonic saline irrigation solutions may be relatively ineffective at neutralizing a significant exposure to an alkaline agent (such as, sodium hydroxide) within the 20 minute time frame required to reduce injury and that buffered irrigation products specially designed for the task are significantly more effective.29,30 This being said, initiation of irrigation with whatever solution is most readily available should not be delayed while such a solution is being obtained. Surprisingly, tap water is more effective than saline at normalizing pH, specifically for alkali burns.29 It is also better tolerated than saline and is therefore recommended in situations in which a buffered product is not available. Use of topical anesthesia (see Table 61.1) and assistive devices, such as a Morgan lens and an eyelid retractor, can aid in delivering the irrigation more effectively. Emergent ophthalmological consultation is warranted in significant acid burns, and all alkaline burns, especially those in which irrigation to a pH of 7 required copious irrigation.29 In chemical exposures deemed to have a low risk of significant injury (an assessment of facilitated by contact with a local poison center) with no signs of immediate ocular injury (such as, corneal burns), the patient can be treated and referred for follow-up with an ophthalmologist in 24 to 48 hours. For more significant chemical injuries, cycloplegics, antibiotics (ointments are usually preferred because they also provide comfort), and occasionally steroid drops are indicated (see Table 61.1 for agents and dosing). After the acute treatment has been completed, obtaining additional history (such as, the nature of the substance) can be useful in determining prognosis; substances with pH ranging from 2 to 12 with limited contact time tend to

have a better prognosis. However, at the time of presentation, the severity and complications of the injury may not be completely assessed because the full extent of the injury has not yet occurred. These complications can include permanent corneal injury (Fig. 61.14), glaucoma, palpebral and conjunctival adhesions, cataracts, and retinal injury. In the case of superglue, cyanoacrylate does not bond well to wet surfaces, and an exposure into the eye typically results in a forceful blink and extrusion of the glue onto the dry surfaces of the lid margins.28 Gentle traction will often separate glued eyelashes; if not, trimming with Westcott scissors can help. Examination by slit lamp can help determine which lashes can be more readily separated. Time will help loosen the adhesions and allow for removal of the glue. If there is eyelid malposition, cutting the lashes can often allow for normalization of the eyelid position. Attempts to dissolve the glue with other substances (especially acetone) should be avoided, because they may cause ocular damage. Ophthalmology consultation in the ED is recommended for cases in which the above measures fail to separate the lids to enable an examination, if there is residual eyelid mal-positioning, or if there is a suspected corneal abrasion from the hardened glue. If separating eyelids reveals no evidence of subsequent lid malpositioning and no sign of conjunctival involvement or injury, the patient can be referred to an ophthalmologist for follow-up as an outpatient in the next day.

INFLAMMATORY CONDITIONS Principles Inflammatory conditions of the eye tend to present as a “red eye,” which is a general term that encompasses a variety possible etiologies in the conjunctiva, cornea, globe and surrounding orbit. The clinical approach to the red eye in general (which includes not just inflammatory processes but also infectious processes) is described in detail in Chapter 19.

The Conjunctiva and Cornea: Keratitis, Pterygium and Pinguecula Clinical Features and Differential Diagnosis Conjunctival and corneal inflammatory conditions present in a somewhat stereotyped fashion and include allergic conjunctivitis, superficial punctate keratitis, ultraviolet (UV) keratitis (radiation keratitis), and pterygium and pinguecula. Allergic conjunctivitis, although technically an inflammatory process, is similar enough in presentation to infectious conjunctivitides that it is considered together with the infectious processes outlined later this chapter.

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Superficial punctate keratitis presents with pain or foreign body sensation, photophobia, and redness due to poor lubrication of the corneal surface from any one of several etiologies, including dry eyes, drug toxicity, and contact lens overuse. UV keratitis is a specific form of keratitis that presents when prolonged exposure to UV light (from a source such as a tanning booth, reflection from snow or water, or a welder’s arc) causes a direct injury to the corneal epithelium, at times severe enough to cause ulceration. There is a latency of 6 to 10 hours before symptoms arise, at which point patients have a significant degree of pain and discomfort, photophobia, and mild conjunctival injection. Another set of conjunctival inflammatory conditions, somewhat similar in appearance to one another, are pterygium and pinguecula. A pterygium is a chronic fibrovascular growth of conjunctiva triggered by chronic exposure to UV light that grows temporally from the nasal side of the eye (or vice versa), eventually covering the cornea. A pterygium can get acutely inflamed, whereupon patients experience foreign body sensation, dry eyes, and redness, but they should not have loss of vision unless the process has started to infringe upon the visual axis (a very gradual and chronic process). A pinguecula is of similar pathology and pathophysiology to a pterygium, resulting in similar symptoms, except that it stops at the limbus and does not enter the cornea or visual axis.

Diagnostic Evaluation Examination with a slit lamp is an integral part of the diagnostic evaluation of conjunctival and corneal inflammatory conditions. With superficial punctate keratitis and UV keratitis, multiple punctate epithelial erosions are seen upon fluorescein staining. A patient with a pterygium or pinguecula will have a visible, opaque conjunctival overgrowth on the conjunctiva of one or both eyes, typically triangular or pie-shaped, with the apex of the triangle pointing towards the pupil.

Management and Disposition Superficial Punctate Keratitis and Radiation Keratitis.  Determination of etiology of the keratitis is important for definitive treatment. In general, however, care is supportive. The treatment considerations for superficial punctate keratitis and UV keratitis are the same as with corneal abrasion (because both entail an injury to the corneal epithelium and superficial cornea, see Corneal Abrasions) and include limited use of topical anesthetics and topical antibiotics administered for 3 to 5 days only if infection is a concern (see Table 61.1). UV keratitis will typically resolve in about 24 hours or so, and given the nature of the injury, patients should be instructed to avoid damaging UV rays.31 Ophthalmologic follow-up in 24 hours is recommended if symptoms have not resolved. Pterygium and Pinguecula.  Treatment of pterygium and pinguecula are similar, and it includes UV protection, lubrication, and treatment of acute inflammation with topical NSAIDs (see Table 61.1). The inflammation of a pterygium or pinguecula is usually self-limited, and encroachment into the visual axis from a pterygium is typically very gradual; non-emergent referral to an ophthalmologist is recommended for surgical treatment of severe cases, and for evaluation of the rare coexistence of an ocular surface squamous neoplasia.

The Globe: Uveitis, Scleritis, and Episcleritis

immune uveitis, or the sclera, as a scleritis. Three noninfectious, inflammatory considerations causing a painful red globe are uveitis, scleritis, and episcleritis. Uveitis is an autoimmune inflammation of the uvea, the part of the middle layer of eye that includes the highly vascularized and pigmented iris, ciliary body, and choroid.32 The iris and ciliary body are most commonly involved, a condition called iritis or anterior uveitis, but uveitis may rarely involve the intermediate and posterior chambers as a rare panuveitis. No cause is identified in 60% to 80% of people, although uveitis is one of the most frequent extra-articular features in seronegative arthritides (including ankylosing spondylitis, psoriatic arthropathy, arthritis from inflammatory bowel disease [ie, Crohn’s], and reactive arthritis [ie, Reiter’s syndrome]). The typical patient with an acute anterior uveitis will present with a very painful red eye, often with photophobia, and occasionally with decreased visual acuity.33 Scleritis is a similar autoimmune inflammatory process, but involving the sclera (the tough connective tissue layer that begins at the limbus and surrounds the eye) instead of the uvea.34 It is divided into anterior scleritis and the less frequent posterior scleritis (inflammation of the sclera posterior to the insertion of the rectus muscles). Scleritis can also be infectious, treated much in the same way an endophthalmitis would be (see The Globe: Endophthalmitis). Episcleritis, which can be confused with scleritis, is caused by inflammation in the episcleral layer of the eye rather than the deeper scleral layer. Episcleritis, unlike scleritis, is not visionthreatening and is not associated with as much discomfort.

Diagnostic Evaluation On slit-lamp examination, uveitis will typically reveal conjunctival injection, ciliary flush in the peri-limbal area, and cells and flare in the anterior chamber. Episcleritis can be distinguished from scleritis in that it is associated with more peri-limbal injection and has a redness that described as salmon pink as opposed to the deeper purple hue seen in scleritis; instillation of 10% phenylephrine drops will constrict and blanch injected superficial episcleral vessels in episcleritis but will not do so to the injected deeper vessels involved in scleritis.34 Scleritis is often more severe than episcleritis and has a much higher association with systemic diseases, such as Wegener granulomatosis, rheumatoid arthritis, and connective tissue disease (an evaluation that can be deferred to outpatient follow-up).

Management and Disposition Treatment of both uveitis and scleritis typically involves topical corticosteroid drops (and cycloplegics for symptoms of iridospasm; see Table 61.1), with a transition to systemic corticosteroids and immunosuppressants if these treatments fail. NSAIDs are helpful for scleritis, although systemic steroids may be more useful in severe cases.35,36 Decisions about treatment are typically made in concert with an ophthalmologist, and patients should be referred to an ophthalmologist for close follow-up in the next day or so; scleritis has a higher association with ocular complications, including keratitis, increased IOP, and vision loss.35

The Orbit: Orbital Pseudotumor, Orbital Apex Syndrome, and Thyroid Orbitopathy

Clinical Features and Differential Diagnosis

Clinical Features, Differential Diagnosis, and Diagnostic Evaluation

The globe itself can on rare occasion be afflicted by a variety of autoimmune conditions, typically involving the uvea as an auto-

The orbit may be affected by typically idiopathic, noninfectious inflammatory processes that lead to diffuse eye pain, redness,

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swelling, and potentially disordered vision. Considerations include orbital inflammatory pseudotumor and orbital apex syndrome (which are unilateral), as well as thyroid myopathy (which is usually bilateral). Orbital inflammatory pseudotumor (also known as idiopathic orbital inflammation syndrome, orbital pseudotumor, or orbital inflammatory syndrome) presents as an acute to subacute tumorlike inflammation consisting of a pleomorphic cellular response and a fibrovascular tissue reaction, and it is associated with various rheumatologic disorders, including Wegener’s granulomatosis, giant cell arteritis, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis.37 In orbital apex syndrome, the apex of the orbit (through which the cavernous sinus drains the eye and orbit, and cranial nerves [CNs] III, IV, and VI travel) may be selectively affected by a cavernous sinus mass or vasculitis. Etiologies include infection, carotid-cavernous fistula, inflammatory vasculitides (such as, giant cell arteritis), Tolosa-Hunt syndrome (a rare idiopathic vasculitis), or tumor or infiltration (eg, sarcoidosis). Both orbital inflammatory pseudotumor and orbital apex syndrome may result in proptosis, chemosis, and/or conjunctival injection; and with orbital apex syndrome, there may be palsies of CNs III, IV, and VI (see Chapter 18). Inflammatory thyroid orbitopathy from Grave’s disease is the most common cause of ocular myopathy in older adults, and it presents with oculomotor muscle swelling and restriction that may be bilateral in 85% of cases. It classically affects the inferior and medial recti muscles first, leading to restriction of elevation and abduction of the eye with orbital muscle dysfunction and misalignment of the visual axes.38 The examination may reveal stigmata of the underlying disease process, such as lid lag or periorbital swelling or proptosis, as well as diffuse conjunctival edema, and vascular injection near the insertions of the rectus muscles. The diagnostic evaluation of a suspected orbital inflammatory process primarily involves imaging of the orbit. Options include a magnetic resonance imaging (MRI) scan of the orbits with gadolinium, which can allow an assessment for enlargement or enhancement in extraocular muscles and orbital structures, or— as a likely more readily available second-line option—a contrastenhanced orbital CT (with fine cuts through the orbit).39

Management and Disposition The mainstay of therapy (assuming infection is excluded) for orbital pseudotumor and orbital apex syndrome is systemic corticosteroid therapy, although there is increasing use of antimetabolites, cytotoxic agents, and other immunosuppressive agents.37 Treatment choices will typically be made in concert with an ophthalmologist. For thyroid orbitopathy, the treatment of the underlying Graves’ disease will address the ophthalmological issues but may involve immunosuppressive medications, radiation, or surgery.

The Conjunctiva: Allergic, Viral and Bacterial Conjunctivitis, and Ophthalmia Neonatorum Clinical Features, Differential Diagnosis, and Diagnostic Testing Symptoms of conjunctivitis—which may be allergic, toxic, or infectious—include redness, discharge, foreign body sensation, photophobia, and blurry vision. The most common form of conjunctivitis is thought to be allergic conjunctivitis. This is not infectious per se, but it is considered in the differential diagnosis here because it is sometimes a challenge to distinguish from a viral conjunctivitis. Allergic conjunctivitis is a type 1 histaminergic hypersensitivity reaction with red itchy eyes, clear discharge, and is classically bilateral, associated with pollen and dust. In more severe cases, moderate to severe injection with glassy chemosis is observed. A toxic conjunctivitis (from topical ocular medications) may appear similar to allergic conjunctivitis; a contact dermatitis (from a trigger like eye makeup) should be suspected if there is an associated lichenified, eczematous periorbital dermatitis and edema. Of the infectious etiologies, viral causes are most common. Viral conjunctivitis is classically preceded by a viral infection with upper respiratory symptoms, with sequential involvement of both eyes, but many viral conjunctivitis episodes have no preceding upper respiratory infection (URI) syndrome. It is most commonly by adenovirus, easily spread by contact with fomites. The conjunctival discharge with viral infections tends to be more watery and less purulent than that in bacterial conjunctivitis, with signs such as preauricular lymphadenopathy and follicular changes of the conjunctiva (Fig. 61.15). Viral conjunctivitis, and keratoconjunctivitis, however, can present with impressive purulence, including having the eyelids stuck shut when awakening from sleep. Such findings do not distinguish bacterial from viral causes. Viral infections typically last 1 to 3 weeks. Epidemic keratoconjunctivitis is a highly contagious and more virulent viral conjunctivitis often presenting in epidemics, with which the patient may also complain of foreign body sensation and have a mild keratitis. Bacterial conjunctivitis is significantly less common than viral. The organisms involved include Staphylococcus organisms, as well as Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae and rarely Neisseria gonorrhoeae, with an increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA) conjunctivitis over the last decade.40 Conjunctivitis from gonorrhea classically presents with copious purulent discharge (Fig. 61.16) and carries a high risk for corneal involvement and

INFECTIOUS CONDITIONS Principles A critical clinical distinction that comes into play in a patient with a red, irritated, or painful eye is whether or not there is an infectious process in play. This is based on clinical features, keeping in mind that the globe of eye and the encompassing tissues of the orbit represent a pristinely organized and functional arrangement of tissue planes and glandular structures, and that any disruption to these structures, whether from minor trauma, prior surgery, or inflammation, can predispose to an infectious process.

Fig. 61.15.  Conjunctival injection resulting from viral conjunctivitis. (Courtesy www.tedmontgomery.com.)

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(but may take up to 20 days). The infant should be carefully examined for any evidence of a systemic gonococcal infection.

Management and Disposition

A

B Fig. 61.16.  Purulent discharge and conjunctival hyperemia suggest bacterial conjunctivitis. (From Goldman L, Schaefer AI, editors: Goldman’s Cecil medicine, ed 24, Philadelphia, 2012, Saunders.)

subsequent corneal perforation.40 A gram stain and culture (or a polymerase chain reaction [PCR] test as done for genital samples) can aid in the diagnosis.41 Distinguishing a viral from a bacterial conjunctivitis can sometimes be a challenge in the ED. A systematic review found that redness of the conjunctival membrane that is intense enough to obscure the tarsal vessels (likelihood ratio [LR], 4.6; 95% confidence interval [CI], 1.2 to 17.1), physician-observed purulent discharge (LR, 3.9; 95% CI, 1.7 to 9.1), and matting of both eyes in the morning (LR, 3.6; 95% CI, 1.9 to 6.5) increase the probability of a bacterial cause, whereas inability to discern that the patient’s eye is red from 20 feet away (LR, 0.2; 95% CI, 0 to 0.8) and absence of morning matting of either eye (LR, 0.3; 95% CI, 0.1 to 0.8) decrease the probability of a bacterial cause.42 What appears to be an infection of the conjunctiva may actually represent an infection of the cornea, and therefore a slit-lamp examination is important; if signs of corneal involvement are present, a keratitis is in play (see Diagnostic Evaluation in The Conjunctiva and Cornea: Keratitis). Epidemic keratoconjunctivitis may have some mild punctate keratitis on fluorescein staining. A consideration specific to neonates is ophthalmia neonatorum, which is a neonatal conjunctivitis developing the first 30 days of life. It can be from allergic or chemical causes but most concerning are bacterial and viral causes, presenting with tearing and discharge followed by scarring and blindness. The evaluation involves gram stain and cultures geared to infections such as N. gonorrhoeae, Chlamydia, and herpes simplex virus (HSV) that are transmitted from mother to infant through the birth canal. HSV may have associated corneal microdendrites and lid edema. Infection with N. gonorrhoeae manifests within 2 to 4 days after birth

Allergic and Viral Conjunctivitis.  Allergic conjunctivitis and viral conjunctivitis are usually self-limited, and can be treated with supportive measures, such as cool compresses (nature’s antiinflammatory). Topical antibiotics should be avoided unless there is concern for a bacterial superinfection. For allergic conjunctivitis, the patient should be counseled to avoid the offending agent and can be prescribed topical and systemic anti-allergy medications (see Table 61.1 for choices and dosing of topical options). Medications with preservatives in them should be avoided, because they may exacerbate symptoms. Presumed viral conjunctivitis rarely requires a culture. If symptoms and findings of either allergic or viral conjunctivitis worsen after 2 to 3 days, other etiologies should be considered. If inflammation is severe (with pseudomembranes, bleeding), then an ophthalmology evaluation in the ED for steroid treatment is recommended, otherwise patients can be discharged with a referral to an ophthalmologist if they worsen or if they do not improve by 7 to 10 days. Children with viral conjunctivitis should usually be kept out of school until symptoms have resolved, which will be 3 to 5 days, keeping in mind that communicability is estimated to last up to 10 to 14 days. Bacterial Conjunctivitis.  Although bacterial conjunctivitis is typically self-limited, most resolving in 1 to 2 weeks without treatment, topical antibiotics shorten the time to resolution.43 Ointment is preferred given the smoothing effect on the eye and ease of instillation (patients know if ointment was applied or not and have to do it less frequently). The prescribed antibiotics (see Table 61.1 for options) should cover the organisms mentioned previously and be taken for at least 1 week; those with the highest level of evidence for the treatment of bacterial conjunctivitis are tobramycin, ciprofloxacin, moxifloxacin, ofloxacin, azithromycin, and trimethoprim/polymixin B.40 Gentamicin and neomycin should be avoided due to toxicity. Contact lens wearers should have coverage for Pseudomonas (see Table 61.1). Treatment of a bacterial conjunctivitis suspected to involve N. gonorrhoeae consists of ceftriaxone 1 g intramuscularly once, and saline irrigation of the affected eye(s), with concomitant empirical treatment for Chlamydia trachomatis infection (either 1 mg of azithromycin orally once, or doxycycline 100 mg orally bid for 7 days). Ophthalmia Neonatorum.  Hospitalization of neonates with blood and cerebrospinal fluid examination may be indicated for ophthalmia neonatorum. N. gonorrhoeae conjunctivitis in a neonate is typically treated with single dose of ceftriaxone 25 to 50 mg/kg up to a total dose of 125 mg intramuscularly, topical erythromycin or polymyxin B–bacitracin ointment, and saline washes of the affected eye. Potential ocular chlamydial infection is often simultaneously treated with topical erythromycin ointment and oral erythromycin syrup 50 mg/kg/day divided into four doses per day for 14 days. HSV should be treated with acyclovir IV 45 mg/kg/day plus vidarabine 3% ointment five times per day for 14 to 21 days. Evaluation for systemic involvement is indicated and ophthalmology consultation in the ED is warranted.

The Cornea: Corneal Ulcers, Herpes Simplex Keratitis, and Herpes Zoster Keratitis Clinical Features and Differential Diagnosis What appears to be conjunctivitis may actually represent an infection of the cornea. A corneal ulcer (Fig. 61.17) is an infectious and/

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Fig. 61.17.  This corneal ulcer caused by Pseudomonas aeruginosa occurred in a young man who wore decorative contact lenses without professional supervision. (From Yanoff M, Duker JS, editors: Ophthalmology, ed 3, Philadelphia, 2008, Mosby.)

or inflammatory erosion, “ulcerative keratitis,” of both the outer epithelial cell layer and the underlying stromal layer (which is the bulk of the cornea). Corneal ulcers present with pain and redness of the eye, tearing, sensitivity to light, and blurred, hazy, or otherwise decreased vision. There can also be discharge or a foreign body sensation. A corneal abrasion can become an ulcer if secondarily infected, which in turn lead to corneal perforation if severe and untreated. Although corneal ulcers are due to infection, most of the resulting corneal injury is due to the secondary inflammation. The most common bacterial pathogens are Staphylococcus, Streptococcus, Mycobacterium, and Pseudomonas, which is associated with contact lens wear. Fungal pathogens are typically seen in users of corticosteroid drops, and in agricultural workers and others who may have contamination of the eye with vegetable matter or soil. The cornea can also be infected by viruses. Herpes simplex keratitis, one of the most common causes of viral keratitis, can produce recurrent corneal ulcers similar to recurrent herpes labialis or herpes genitalis. Herpes simplex may be either primary or reactivation of preexisting disease. Symptoms are similar to corneal ulcers. Herpes zoster keratitis can occur in the setting of herpes zoster ophthalmicus. Herpes zoster is re-activated along the ophthalmic division of the trigeminal nerve, and eye involvement is possible. Patients will typically present with a dermatomal rash over the forehead and upper eyelid and sometimes along the nose (branch of the nasociliary nerve—called Hutchinson’s sign), or even have a local Horner’s syndrome.

Diagnostic Testing The foundation of the diagnostic evaluation of corneal lesions is a careful examination and biomicroscopy with the slit lamp and fluorescein staining to evaluate corneal epithelial surface disruptions. On slit-lamp examination, a corneal ulcer may appear to have more “heaped up” edges (seen with tangential lighting) than those seen with a corneal abrasion; this finding, combined with stromal edema or infiltration (whitening of the underlying or surrounding cornea), helps red-flag the process as an ulcer instead of an uncomplicated abrasion. A corneal ulcer from herpes simplex keratitis may present with classic “dendritic” lesions on slit-lamp examination (Fig. 61.18), or with an amoeba-shaped ulceration, or have nonspecific findings such as punctate epithelial erosions, stromal whitening, and thinning of the cornea, possibly with classic herpetic vesicles located on the lids or conjunctiva. Herpes zoster keratitis may appear somewhat similar but will have signs of a dermatomal

Fig. 61.18.  Herpes simplex keratitis infection. Note typical dendritic pattern on cornea. (Courtesy www.tedmontgomery.com.)

vesicular rash, and it is frequently associated with iritis, uveitis, and choroiditis.44 Viral cultures of tissue can help direct therapy.

Management and Disposition Corneal Ulcers and Infiltrates.  Topical anti-microbial therapy for corneal ulcers and infiltrates is appropriate, although in some severe cases, systemic antibiotics may be warranted. The fluoroquinolones (see Table 61.1) have particularly good ocular penetration; doxycycline and other tetracyclines have good anticollagenase properties that help preserve corneal integrity. Steroids may be used to decrease inflammation but must be used with caution, because they may exacerbate the clinical situation (and if a herpetic process is suspected, steroids may have to be avoided, or antivirals concurrently used). Ophthalmology consultation in the ED is important for management of corneal ulcers, because they can rapidly progress. Herpes Simplex Keratitis.  Herpes simplex keratitis is the most common cause for corneal transplants in the United States. Emergent ophthalmologic consultation is advised, because the severity of disease will dictate treatment. Herpes simplex keratitis is treated with topical antiviral agents, such as topical acyclovir trifluridine 1% nine times a day for 14 days. Topical prophylactic antibiotics, such erythromycin ointment, and a cycloplegic agent if there are symptoms of iritis can be considered (see Table 61.1). Topical steroids should be avoided because they worsen infection.40 Systemic therapy should be considered (acyclovir 400 mg five times daily or valacyclovir 500 mg three times daily for 7 to 10 days) if topical treatment is not available or if the process is severe; admission will typically not be needed, but close follow-up with an ophthalmologist within 1 to 3 days is important. Herpes Zoster Keratitis.  Herpes zoster ophthalmicus accounts for approximately 10% to 20% of all zoster cases and necessitates emergent ophthalmologic consultation. If not treated and recognized immediately, herpes zoster ophthalmicus may result in permanent vision loss. Systemic therapy is the standard of care (unlike HSV, topical antivirals have little effect). If retinal involvement occurs or the patient is immunocompromised, inpatient treatment is recommended. Higher dose antiviral agents (acyclovir 800 mg five times daily, valacyclovir 1000 mg three times daily, or famciclovir 500 mg three times daily, all for 7 to 10 days40) are used, and occasionally topical steroid agents and systemic antibiotics may be added. Topical antibiotics are used to prevent bacterial superinfection of skin and lid lesions.

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Early treatment with antiviral therapy within 72 hours of the onset of the rash has been shown to reduce acute pain and ocular complications. Additional consideration for therapy includes pain management and aggressive lubrication to maintain a healthy ocular surface.

The Eyelids and Periorbital Area: Hordeolum, Chalazion, Dacryocystitis, Blepharitis, and Cellulitis Clinical Features and Differential Diagnosis The tissues of the eyelids and periorbital area are susceptible to any of a number of types of infections, which include those related to glandular or ductal structures, such as a hordeolum, chalazion, or dacryocystitis, or more diffuse involvement of tissue, such as blepharitis or periorbital cellulitis. Hordeola and chalazia, also known as styes of the eyelid, are inflamed oil glands of the eye. A hordeolum is caused by acute inflammation of a gland of Zeis or hair follicle. It is typically painfully tender, erythematous, associated with swelling, and can be infected. On the other hand, a chalazion is a chronic sterile, granulomatous inflammation of a meibomian gland (and may evolve from a hordeolum), which results in localized swelling that is usually not acutely painful (Fig. 61.19). Dacryocystitis is an infection of the lacrimal sac, usually resulting from a nasolacrimal duct obstruction. It is more common in females. Symptoms and signs include pain, tenderness, swelling, and erythema over the lacrimal sac medial to the eye (Fig. 61.20). Pressure over the sac may express purulent material from the puncta. The lacrimal gland itself can also become infected, appearing as a focal area of periorbital erythema, swelling and tenderness lateral to and above the upper eyelid. Patients with blepharitis typically describe itching and burning of the eyelids with associated tearing and crusting of the eyelids. The eyelids become diffusely inflamed and thickened, with erythematous margins, and telangiectasias surrounding the eyelid margin. Blepharitis can be distinguished from a pre-septal cellulitis in that it is isolated to just the eyelid margin. Blepharitis has an association with atopic dermatitis, rosacea, and eczema. Any one of the aforementioned focal infections, but especially dacryocystitis and blepharitis, may be complicated by a more diffuse, associated cellulitis. Cellulitis frequently presents, however, as an individual entity, and it has to be carefully distinguished as either pre-septal (also called periorbital) or post-septal (also called orbital). Pre-septal and post-septal are the most useful terms

because (1) they incorporate the most impactful clinical distinction in the ED and (2) remove any chance of confusion as to what is being referred to in communications with consultants. Preseptal cellulitis is limited to the tissue anterior to the orbital septum, whereas a post-septal cellulitis implies spread of the infection beyond the septum, which is concerning because it can lead to involvement of valuable orbital structures. Pre-septal cellulitis will present with lid erythema, warmth, tenderness, swelling, and even a low-grade fever. Post-septal cellulitis will present with the same but may also have more alarming symptoms including proptosis, ophthalmoplegia, pain with eye movement, chemosis, and systemic signs of infection. In very severe cases, visual loss can occur. In children, pre-septal cellulitis is often more difficult to differentiate from a post-septal cellulitis because of an incomplete orbital septum.

Diagnostic Testing For hordeolum, chalazion, dacryocystitis, blepharitis, and a cellulitis that is clearly pre-septal, the diagnosis is established on the clinical examination alone, and no additional diagnostics are needed. CT imaging is, however, indicated in cases concerning for an orbital abscess or in which localization of an infection (preseptal or post-septal) is difficult. In such cases, a complete blood count (CBC) may also be helpful. The primary diagnostic decision for the ED patient with a cellulitis around the eye is deciding who needs further evaluation with a CT scan. Symptoms and signs of proptosis, ophthalmoplegia, pain with eye movement, and chemosis easily suggest the possibility that a cellulitis is post-septal,

A

B Fig. 61.19.  Chalazion .tedmontgomery.com.)

of

the

upper

eyelid.

(Courtesy

www

Fig. 61.20.  A and B, Dacryocystitis. (Courtesy Jeffrey Lee, MD, University of California San Diego.)

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but upward of 50% of confirmed cases may not have these symptoms.45,47 In these “no orbital symptom” cases, a peripheral absolute neutrophil count (ANC) of >10 000 cells/µL, moderate-to-severe periorbital edema (extending beyond the eyelid margins), absence of conjunctivitis as the presenting symptom, older than 3 years old, and recent antibiotic use have been shown to be predictors of an orbital abscess—specifically in the pediatric population.45 In addition, a sudden onset is more typical of a post-septal orbital cellulitis.47 The absence or presence of a fever has little discriminatory utility. Cultures obtained from swabs of the eyes are discouraged due to the risk of misleading results from inoculation with commensal organisms, and blood cultures have little diagnostic utility.46

Management and Disposition Hordeolum and Chalazion.  Often, hordeola and chalazia are self-limited and can resolve on their own when the glands become unobstructed. Conservative treatment to normalize flow of the obstructed oil glands is the primary goal. This includes warm compresses for 10 to 15 minutes, 3 to 5 times a day. Treatment of an underlying blepharitis may be indicated. Referral to an ophthalmologist is recommended for incision and drainage or additional management and evaluation in nonresponsive cases. Progression to an infected oil gland may indicate need for antibiotics, depending whether the process takes the form of a blepharitis or a cellulitis (see treatment of each in the following sections). Dacryocystitis.  The most common causative organisms in dacryocystitis are S. aureus, S. pneumoniae, H. influenzae, Serratia marcescens, and Pseudomonas aeruginosa, with an emerging prevalence of MRSA.47 Treatment consists of massage, warm compresses, and systemic antibiotics selected so as to include coverage of MRSA. An attempt should be made to obtain a culture by applying gentle pressure to the nasal lacrimal duct and expressing fluid. In infants, acute dacryocystitis represents a medical emergency, because it can lead to complications including post-septal orbital cellulitis. Admission is warranted for severe cases. Occasionally, drainage of the sac is required; however, this can lead to fistula formation. Dacryocystorhinostomy is the definitive treatment, but the optimal time for surgery is when the infection is controlled. Discharged patients should follow-up with an ophthalmologist in 24 to 48 hours. Blepharitis.  The initial treatment of blepharitis is conservative, designed to remove residual oils and scurf, and entails warm massage with a moist washcloth about for 10 to 15 minutes, three to five times a day, and cleaning the lid margins twice a day with a cotton swab soaked in mild baby shampoo. Because blepharitis arises as a result of an inflammatory process, there is potential for bacterial overgrowth and superinfection (Staphylococcus epidermidis primarily, but also Propionibacterium acnes, and corynebacteria), and—if there is a concern for infection—topical azithromycin, erythromycin, or levofloxacin (see Table 61.1) can be considered.47,47a Uncomplicated cases can be discharged to follow-up with an ophthalmologist within a week or so, or within 1 to 3 days if there is concern for infection. Periorbital Cellulitis.  If pre-septal cellulitis with no other underlying medical conditions is diagnosed with certainty, the patient can be discharged on an oral antibiotics directed toward the most common organisms, Streptococcus and Staphylococcus, keeping in mind that orbital cellulitis tends to be polymicrobial.47 Although many practitioners empirically cover for MRSA, this organism is actually very rare when it comes to orbital cellulitis (at least in published series involving primarily children).48 An option is a beta-lactam antibiotic, such as oral amoxicillin-

clavulanate, 875 mg two times daily for 10 to 14 days for adults (or 20 to 40 mg/kg divided into three doses for 10 to 14 days for children). Close follow-up, with a re-examination within a day at a primary care provider’s office or with an ophthalmologist is important to assure response to treatment. In more severe cases of pre-septal cellulitis, or with any concern of post-septal cellulitis, hospitalization with IV antibiotics is indicated to avoid complications, such as subperiosteal abscess, orbital abscess, meningitis, osteomyelitis, and cavernous sinus thrombosis. In children, the difficulty in localizing the spread of the infection dictates more aggressive management of any periorbital infection. An IV second- or third-generation cephalosporin, such as cefuroxime or ceftriaxone, is recommended. Other IV antibiotic options include ampicillin/sulbactam (Unasyn), or a combination of a first-generation cephalosporin with metronidazole.47

The Globe: Endophthalmitis Clinical Features, Differential Diagnosis, and Diagnostic Testing Endophthalmitis is an infection involving the globe itself. Pain and decreased vision are the primary symptoms. Examination findings include decreased visual acuity, chemosis, and hyperemia of the conjunctiva, intraocular inflammation (evidenced by hypopyon) (Fig. 61.21). The most common etiology of endophthalmitis is recent intraocular surgery. Other etiologies include previous perforated globe and endogenous infection. Early diagnosis and management is imperative for improved prognosis. The diagnosis is primarily clinical, and will typically have to be done in consultation with an ophthalmologist, because endophthalmitis can be difficult to distinguish from a uveitis, and the two have vastly different treatments and acuity.49 An ultrasound of the eye (done in much the same way as to evaluate for retinal detachment) can be used to augment the evaluation; and with endophthalmitis, it may reveal numerous stands and membranes in a vitreous that would otherwise be uniformly hypoechoic.49

Management and Disposition Endophthalmitis is a medical emergency that must be promptly treated. Systemic antibiotics are not effective, and therefore— although IV antibiotics can be considered (their effect is unknown)—intravitreal antibiotics must always be given.50 The evaluation and treatment should be done in consultation with an ophthalmologist who can administer the intravitreal antibiotics at the bedside and perform a vitrectomy (removal of infected vitreous akin to draining an abscess) in the operating room if

Fig. 61.21.  Eye with endophthalmitis, illustrating a hypopyon (pus in the anterior chamber). (Courtesy Kama Guluma, MD, University of California San Diego.)

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needed. The typical bacterial pathogen varies with the likely cause; coagulase-negative staphylococci are most common in post-cataract endophthalmitis, Bacillus cereus is a major cause of post-traumatic endophthalmitis, and S. aureus and streptococci are important causes of endogenous endophthalmitis associated with endocarditis.50

ACUTE ANGLE-CLOSURE GLAUCOMA Principles Aqueous humor provides structural support to the eye and delivers oxygen and nutrients to the avascular lens and cornea. It is produced by the ciliary processes, passes from the posterior chamber to the anterior chamber through the pupillary aperture, and then is transported into the trabecular meshwork located at the anterior chamber angle formed by the junction of the root of the iris and the peripheral cornea. This trabecular meshwork serves as a one-way valve and filter for the aqueous humor into the canal of Schlemm, which in turn drains into episcleral veins. IOP is determined by the rate of aqueous humor production relative to its outflow and removal, and it is normally between 10 to 20 mm Hg.

Clinical Features, Differential Diagnosis, and Diagnostic Testing Glaucoma is an acquired chronic optic neuropathy. It is characterized by an enlarged ratio of the diameter of the optic cup to the diameter of the optic disc (termed cupping) and visual field loss. Glaucoma usually but not always is associated with elevated IOP. The two most common and important forms of glaucoma are primary open-angle glaucoma and acute angle-closure glaucoma. Primary open-angle glaucoma is a chronic condition characterized by asymptomatic elevated IOP (but IOP may not always be elevated), and an enlarged ratio of the diameter of the optic cup to the diameter of the optic disc (termed cupping) and peripheral visual field loss. Patients may be on chronic topical ophthalmic medications designed to improve aqueous outflow. It is not typically a cause for an urgent visit to the ED (and therefore not discussed further), although it can lead to complete blindness over time. Acute angle-closure glaucoma is the entity that typically precipitates an acute ED visit, at times in a patient with no prior knowledge or history of chronic glaucoma. A variety of rare conditions (such as, tumors, neovascular processes) can predispose a patient to this, but the more common predisposed patient has an anatomically shallow anterior chamber that further narrows with aging as the lens enlarges. Acute symptoms are often precipitated by pupillary dilation from being in a low-light environment (eg, movie theater) or taking an anticholinergic or sympathomimetic medication. This transient contraction of the iris crowds the angle (“pupillary block”), and continued formation of aqueous leads to an increased IOP, causing the iris to bulge forward, further inhibiting outflow, and eventually compromising arterial flow into the eye. The patient with acute angle-closure glaucoma typically presents with severe unilateral eye pain, redness, and blurred vision with “halos,” as well as nausea and vomiting. On examination, the pupil may be moderately dilated and unreactive to light, the anterior chamber shallow when illuminated from the side with a penlight, the conjunctiva injected, and the cornea cloudy (steamy) (Fig. 61.22). The IOP is significantly elevated, and ischemia to intraocular structures, particularly the optic nerve, retinal nerve fiber layer, and the avascular anterior portion of the lens (which is sustained by aqueous humor) may occur. Sustained elevation in IOP can cause permanent corneal and optic nerve damage, and cause the peripheral iris to adhere to the trabecular

Fig. 61.22.  Acute angle-closure glaucoma. (From Yanoff M, Duker JS, editors: Ophthalmology, ed 3, Philadelphia, 2008, Mosby.)

meshwork, forming anterior synechiae and an irreversible occlusion that only can be corrected by surgery.

Management and Disposition Treatment of acute angle-closure glaucoma begins with medications used to lower the IOP and then proceeds to definitive treatment of the anatomical abnormality that led to the elevated pressure in the first place.51 Emergent ophthalmology consultation is necessary, and the treatment paradigm in the ED is as follows: • Drugs that may be used to reduce production of aqueous humor: • Topical beta-blocker (timolol 0.5%—1 to 2 gtt) • Carbonic anhydrase inhibitor (acetazolamide 500 mg IV or orally) • Systemic osmotic agent (mannitol 1 to 2 g/kg IV over 45 minutes, to minimize cerebral effects, and typically reserved if topical medications and acetazolamide do not work within 1 hour) • Drugs that may be used to increase outflow: • Topical alpha-agonist (phenylephrine 1 gtt) • Miotics (pilocarpine 1% to 2%) • Topical steroid (prednisolone acetate 1%—1 gtt every 15 to 30 minutes four times, then every hour) • Definitive treatment—laser peripheral iridotomy within 24 to 48 hours

PRIMARY DISORDERS OF VISION Principles The process of visual perception is an orchestration of light refraction by the cornea and lens, signal transduction by the retina to generate electrical impulses, and transmission of those impulses through the optic nerve to be processed in each occipital cortex, being split and crossed at the chiasm along the way (Fig. 61.23). Primary disorders of vision can be caused by a derangement in any component in this process and may present as blurred vision, a focal disturbance somewhere in the visual field (in the form of dark objects or floaters, flashing lights (photopsia), or a visual field cut), or frank vision loss. Double vision has a very distinct presentation and is comprehensively addressed in Chapter 18. The history enables a tailored approach to the evaluation of a patient with an atraumatic visual disturbance but may be fraught with challenges. One is the potential for a patient to use the term blurred vision to actually describe double vision, and vice versa. Another is that the patient with a cortical visual field cut may not

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(1) Lesion in left superior temporal retina causes a corresponding field defect in the left inferior nasal visual field. Left visual field Right visual field

(2) Total blindness right eye. Complete lesion of right optic nerve.

Left nasal retina 1

3

Left optic nerve 4 Lateral (4) Right incongruous geniculate body hemianopia due to a lesion of the left optic tract (least common site of hemianopia). 6

2

(3) Chiasmal lesion causes bitemporal hemianopia. Right temporal retina Right optic tract 5

Corpus colliculi

Left occipital lobe

(5) Right homonymous superior quadrantanopia due to lesion of inferior optic radiations in temporal lobe. Geniculocalcarine tract

7 (6) Right homonymous inferior quadrantanopia due to involvement of optic radiations (upper-left optic radiation in this case). (8) Right homonymous hemianopia due to a lesion of the left hemisphere. The pupillary light reflex is not impaired if it is beyond the tract.

(7) Right congruous incomplete homonymous hemianopia.

Fig. 61.23.  Topographic diagnosis of visual field defects. (From Bradley WG, Duroff RB, Fenichel GM, et al: Neurology in clinical practice, ed 5, Oxford, 2007, Butterworth-Heinemann.)

even be aware there is a visual field deficit, being “blind to the blind spot.” In addition, a patient may not notice a chronic problem in one eye until a problem finally develops in the remaining functioning eye. Finally, a patient may report what was actually a binocular defect of both visual fields on one side as a monocular issue involving a single eye on that side (a discrimination of which will be lost if the visual disturbance was transient and the patient did not check if the problem persisted with one eye or the other closed). The elements of a screening ED ophthalmological examination are described in detail in Chapter 19 and should carefully incorporate a visual field and a neurological examination, in addition to the elements of visual acuity, pupillary examination, extraocular muscle movement, and examinations of the anterior and posterior segment (with a slit-lamp examination and a funduscopic examination). It should be kept in mind that a patient with a visual field defect or a retinal detachment may have a normal visual acuity, due to sparing of the macula. An etiology of the visual loss occurring beyond the retina can be considered neuro-ophthalmologic and can be further divided into prechiasmal, chiasmal, and post-chiasmal (see Fig. 61.23). Patients with prechiasmal visual loss have monocular decreased

visual acuity or visual field loss, typically from dysfunction of the optic nerve on that side, with an APD on the side involved on swinging flashlight test (see Fig. 61.11), and a visual field defect that does not respect the vertical midline and is often localized to the center of the visual field. Patients with chiasmal and post-chiasmal visual loss will typically have preserved visual acuity, and a visual field loss in both eyes that respects the midline (see Fig. 61.23).

Blurred Vision: Optic Neuritis, Toxic and Metabolic Disturbances, and Papilledema Clinical Features and Differential Diagnosis Any disturbance in the refraction of light may cause the symptom of blurred vision. Considerations include corneal infiltrates (from infections), significant pupillary dilation (which results in an increase in the scattered of light rays reaching the lens), and changes in the refractive properties of the lens or vitreous (due to edema from rapid osmotic changes). Blurred vision may also result from transductive dysfunction from retinal or optic nerve inflammation or edema. Considerations in the differential diagnosis of blurred vision include optic neuritis (which is usually

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monocular) and toxic and metabolic visual disturbances (usually binocular), and papilledema from raised intracranial pressure (also usually binocular). Optic neuritis is a primary, autoimmune inflammatory process of the optic nerve, affecting mostly young patients (range, 15 to 45 years old), has an association with multiple sclerosis, and is the presenting symptom of multiple sclerosis in 25% of cases.52 The patient with optic neuritis typically presents with monocular blurring or fogginess of vision evolving over hours or days, mild pain with movement of the involved eye if the lesion is within the orbit, and at times bright, fleeting flashes of light with eye movement, as well as worsening of vision with small increases in body temperature (from exercise, hot baths, or hot weather).52 The natural history of optic neuritis is for visual acuity to reach its poorest within 1 week and then slowly improve over the next several weeks. Approximately 30% of patients with acute optic neuritis develop multiple sclerosis within 5 years. Approximately 30% of patients with optic neuritis have a recurrence within 10 years of initial presentation. With regards to toxic visual disturbances, perhaps the most characterized toxidrome presenting with acute visual change is methanol toxicity.53 Orally ingested methanol (the toxicity of which is described in entries dedicated to it elsewhere in this text) is metabolized to formic acid, which accumulates in the optic nerve and leads to edema and compromised axoplasmic flow; in addition, it leads to widespread electrophysiological dysfunction that also affects photoreceptors in the retina, leading to visual loss. Other potential causes of a toxic visual disturbance are barbiturates, chloramphenicol, emetine, ethambutol, ethylene glycol, isoniazid, and heavy metals. In terms of metabolic visual disturbances, any rapid osmolar shift in the cornea, lens, or even retina has the potential to cause visual changes. A representative scenario is acute hyperglycemia. A rapid elevation in blood glucose (or a rapid correction of severe hyperglycemia), as seen in poorly controlled diabetics, may cause an acute hyperopia (far-sightedness), presumably due to changes in refraction in the lens.54 It may alternatively cause acute myopia when the rise in intracellular glucose levels in the lens overwhelms the normal glucose metabolic pathway such that it is converted to less absorbable sorbitol and fructose, generating an acute hyperosmolar state and stromal swelling. This may be followed by acute bilateral cataract formation within a matter of hours to days. Metabolic visual disturbances can also be from a nutrition-related optic neuropathy from causes such as thiamine deficiency and pernicious anemia. Papilledema may be seen on examination and refers to the changes in the optic disc from increased intracranial pressure. The subarachnoid space of the brain is continuous with the optic nerve sheath. Any increase in the cerebrospinal fluid pressure (such as, from pseudotumor cerebri syndrome [otherwise known as idiopathic intracranial hypertension], cryptococcal meningitis in HIV/AIDS patients, or hydrocephalus or intracranial mass) can be transmitted to the optic nerve, resulting in swelling of the optic nerve head. Although visual symptoms may be isolated on rare occasion, patients with these entities will typically present with headache, which will provoke their consideration. That being said, a small percentage of patients with pseudotumor cerebri present with isolated subjective visual loss, blurred vision, or enlargement of the physiologic blind spot as the initial presenting symptom of the disease, and rapid deterioration may occur over days in severe cases.55 Swelling of the optic disc and blurring of the disc margins, hyperemia, and loss of physiologic cupping are present (Fig. 61.24A). There may be obliteration of spontaneous venous pulsations. Flame-shaped hemorrhages and yellow exudates may appear near the disc margins as the edema progresses (see Fig. 61.24B). Visual acuity may be affected as the swelling becomes severe. Papilledema is typically bilateral but may be asymmetrical.

There are conditions with optic nerve swelling (such as, ischemic optic neuropathy [ION], optic disk vasculitis, and diabetic papillitis) that may mimic papilledema.

Diagnostic Testing, Management, and Disposition In the diagnostic evaluation of blurred vision, a standard ophthalmological assessment including visual acuity and a slit-lamp examination is important, but funduscopy (so as to screen for retinal or optic nerve edema or pathology) and an assessment of visual fields (to screen for associated sectoral abnormalities in retinal or optic nerve transduction) are critical. Optic Neuritis.  With optic neuritis, visual acuity will usually be abnormal (with the primary complaint of blurred vision), and the patient may have variable visual field defects (central, altitudinal, arcuate, hemianopic), with central defects being more common than peripheral ones.52 An APD is usually present, and direct ophthalmoscopic examination reveals a normal or swollen disk (Fig. 61.25). An orbital MRI of the optic nerves with gadolinium is the mainstay of diagnosis, revealing optic nerve lesions in 95% of cases. A lumbar puncture can be done, which may show CSF pleocytosis and a raised protein concentration.52 For treatment, steroids for optic neuritis has a long track record of investigation but with no demonstrated long-term effect on visual outcome.55a Some still recommend high-dose methylprednisolone (either 500 mg per day orally for 5 days or 1 g per day IV for 3 days), due to mild short-term benefits; plasmapheresis and IV immunoglobulins are also options.52 Toxic and Metabolic Visual Disturbances.  A key component in the diagnostic approach to blurred vision from toxic and metabolic disturbances is recognizing the existence of a cause. These processes are bilateral, progressive, and symmetrical and may manifest with a drop in visual acuity, evident haziness in the lenses, or retinal edema on funduscopy. Visual loss can be severe and visual field testing reveals central defects. In each case, the treatment is aimed at the underlying toxin, metabolite, or deficiency involved (described in entries dedicated to them elsewhere in this text). Blurred vision due to hyperglycemia typically reverses when hyperglycemia is treated, although cataracts may sometimes be permanent. Papilledema.  The diagnostic evaluation and management of specific disease processes that result in bilateral papilledema can be found in entries specifically dedicated to them elsewhere in this text. An important part of the assessment is a funduscopic eye examination, with an assessment of the optic disc. Early or mild papilledema may be difficult to detect with the direct ophthalmoscope, and if the suspicion of such a process is high, consultation with ophthalmologist in the ED for stereoscopic viewing of the optic discs with indirect ophthalmoscopy is recommended, and patients should undergo neuroimaging (either with MRI or contrast-enhanced CT).55

Visual Field Disturbances: Floaters, Flashes, and Field Deficits Clinical Features and Differential Diagnosis Visual field disturbances may take the form of floaters (seeing objects in the field of vision, caused by material obstructing the light path), photopsia (flashing lights, caused by aberrant stimulation of the retina), or field deficits (focal areas of visual loss, caused by dysfunction in the transport or processing of impulses sent by the retina). Photopsia may be unilateral or bilateral, depending on the cause. The most common causes of unilateral

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A

B Fig. 61.24.  A, Papilledema. Note the blurred disk margins. B, Papilledema. Note the blurred disk margins, exudates, and hemorrhages.

Fig. 61.25.  Optic disk swelling (papillitis) associated with acute optic neuritis. (From Yanoff M, Duker JS, editors: Ophthalmology, ed 3, Philadelphia, 2008, Mosby.)

photopsia are vitreous or retinal detachment (see later), with which abnormal mechanical stimulation of the retinal photoreceptors leads to a cascade of action potentials that the visual system interprets as flashes of light. A less common cause of unilateral photopsia is uveitis involving the choroid. The most common cause of bilateral (and homonymous) photopsia is migraines, although scintillating scotomata is much more frequent. Less common causes of bilateral homonymous photopsia include lesions of the visual cortex with release hallucinations or epileptic seizures. Considerations in the differential diagnosis of these visual field disturbances include intraocular (monocular) entities such as vitreous hemorrhage, vitreous and retinal detachment, and extraocular (binocular) entities at the optic chiasm and beyond. Vitreous hemorrhage results from bleeding into the pre-retinal space or into the vitreous cavity. The most common causes are diabetic retinopathy and retinal tears. Additional causes include neovascularization associated with branch vein occlusion, sickle cell disease, retinal detachment, posterior vitreous detachment, trauma, age-related macular degeneration, retinal artery microaneurysms, trauma, and intraocular tumor. Symptoms begin with dark floaters or “cobwebs” in the vision and may progress over a few hours to painless visual loss. Floaters, described by the patient as dark or black dots or strands moving in the visual field in the direction of the preceding eye movement, are caused by vitreous blood.

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Vitreous detachment is a common occurrence in patients older than 60 years old. With aging, the vitreous gel desiccates, shrinks, and pulls away from the retina, leading to symptoms similar to those of vitreous hemorrhage and retinal detachment. Retinal detachment can occur by three mechanisms: (1) rhegmatogenous, (2) exudative, and (3) tractional. The retina has two layers—the inner neuronal retina layer and the outer retinal pigment epithelial layer—that can be separated by fluid accumulation. A retinal tear in the retinal membranes may or may not lead to a retinal detachment. A rhegmatogenous retinal detachment occurs as a result of a tear in the neuronal layer, allowing fluid from the vitreous cavity to leak between and separate the two retinal layers. It occurs in patients older than 45 years old, is more common in men, and is associated with degenerative myopia. Trauma can cause this type of detachment at any age, with patients with severe myopia being at greater risk. An exudative retinal detachment occurs as a result of fluid or blood leakage from vessels within the retina and is associated with hypertension, pre-eclampsia, central retinal venous occlusion, glomerulonephritis, papilledema, vasculitis, and choroidal tumor. Finally, a tractional retinal detachment is a consequence of contraction of a fibrous band that has formed in the vitreous. With retinal detachment, patients typically note flashes of light related to the traction on the retina, floaters related to vitreal blood or pigmented debris, and visual loss. The visual loss is commonly described as filmy, cloudy, or curtain-like in appearance, and is painless. If a visual field disturbance is binocular, then a chiasmal or cortical disorder should be considered. Chiasmal disease is most commonly caused by chiasmal compression from pituitary tumors, craniopharyngiomas, or meningiomas. Visual loss is gradual and progressive. Beyond the optic chiasm, the most common causes of visual disturbances are infarctions, tumors, arteriovenous malformations, and migraine disorders. Patients report difficulty in performing a certain task, such as reading. Lesions can be located from the immediate post-chiasmal optic tract to the occipital cortex.

Diagnostic Testing, Management, and Disposition In the diagnostic evaluation of visual field disturbances, the history should be specific enough to ascertain if the problem is an issue of an absence of vision (ie, a “blind spot,” or visual field deficit, as seen in chiasmic or cortical etiologies), or of an obstruction of vision (ie, “floater,” as seen in vitreous detachment or hemorrhage, or retinal detachment). In addition, a visual field examination should be detailed enough to determine if the disturbance is monocular or binocular and whether it respects the midline. Funduscopy is especially important to enable an assessment of the vitreous and retina, and ocular ultrasound is a helpful adjunct. With this approach, the considerations outlined earlier can be differentiated and addressed. Vitreous Hemorrhage and Detachment.  With a vitreous hemorrhage, direct ophthalmoscopy reveals a reddish haze in mild cases and a black reflex in severe cases. Details of the fundus are usually difficult to visualize. There is a diminished red reflex and an inability to visualize the fundus clearly with the direct ophthalmoscope. Ocular ultrasound, which will reveal echogenic debris in the vitreous, can be an effective diagnostic screening tool (Fig. 61.26A). A vitreous hemorrhage or detachment usually does not cause an APD by itself, and if an APD is present, an occult retinal detachment may be present. A hemorrhage may be evenly distributed throughout the vitreous, or—if trapped in the subhyaloid space as a pre-retinal hemorrhage—may be focal, with a boat shape (see Fig. 61.26B). Ophthalmologic consultation in the ED, or a same-day evaluation by an ophthalmologist, will typically be needed to character-

A

B Fig. 61.26.  A, Ocular ultrasound showing vitreous hemorrhage (white arrow). B, Boat shaped pre-retinal vitreous hemorrhage (A, Courtesy Douglas Brunette, MD. B, Courtesy Jeffrey Lee, MD.)

ize the extent and complications of any suspected vitreous hemorrhage or detachment and manage vision-threatening complications. The management of a vitreous hemorrhage is otherwise largely expectant, with limitation of activity, avoidance of anticoagulants, and sleeping with the head of bed elevated to allow blood to settle and optimize visualization of the retina on subsequent examinations. Surgery is typically required if there is an associated retinal detachment. The same consideration applies for a posterior vitreous detachment, for which no specific emergent treatment is indicated unless accompanied by a retinal tear, vitreous hemorrhage, or retinal detachment. Retinal Detachment.  With a retinal detachment, visual acuity can range from minimally changed to severely decreased. Visual field deficits relate to the location of the retinal detachment, and an APD occurs if the detachment is large enough. When the detachment is visible on ophthalmoscopy, the retina appears out of focus at the site of the detachment. In large retinal detachments with large fluid accumulation, a bullous detachment with retinal folds can be seen (Fig. 61.27A). Retinal detachment cannot be ruled out by direct funduscopy. Indirect ophthalmoscopy is needed to visualize the more anterior portions of the retina. Bedside ED ultrasonography can be a useful tool in screening for a retinal detachment (see Fig. 61.27B).56 It will reveal a billowing hyperechoic line that may undulate with side-to-side movements of the eye.

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erations, which include occipital infarction, neoplasm, an inflammatory process, or an infectious process (such as, encephalitis).

Sudden Vision Loss: Retinal Artery and Vein Occlusion, and Ischemic Optic Neuropathy Clinical Features and Differential Diagnosis

A

B Fig. 61.27.  A, Retinal detachment. Note large portion of retina billowing forward. B, Bedside emergency department (ED) ultrasound showing retinal detachment (white arrow). (A, Courtesy www.tedmontgomery.com. B, Courtesy Nicholas Connors, MD, and Sophia Lin, MD, New York Presbyterian-Weill Cornell Medical Center.)

Any patient suspected of having a retinal tear or detachment requires immediate ophthalmologic consultation, because treatment with tamponade or retinopexy can prevent a retinal detachment that does not involve the macula (a “macula-on” retinal detachment) from progressing to involve the macula (“maculaoff ”) and significantly degrade visual acuity. The duration of macular detachment, measured from the reported time of the loss of central visual acuity, is inversely related to final visual acuity. Even though the literature suggests that there is almost a day’sworth of leeway in the timing of repair of a “macula-on” detachment, and a fair amount of visual acuity is recoverable if a “macula-off ” detachment is repaired early enough, a “macula-on” detachment that is close to the macula is at risk of converting to “macula-off ” with even a few hours delay.56-59 Chiasmal and Cortical Disturbances.  Although formal visual field testing may be necessary to stage the condition, the diagnosis of a chiasmic or cortical etiology to a visual field disturbance can usually be made by confrontation visual field testing. The classic defect for a lesion in or compression of the optic chiasm (chiasmal) is a bitemporal hemianopsia; however, tumors often compress the chiasm and optic nerves asymmetrically, resulting in combined central and temporal defects. When a visual field defect respects the vertical midline, the lesion is out of the globe and likely either chiasmal or post-chiasmal (see Fig. 61.23). The classic visual field defect in post-chiasmal (cerebral or cortical) disease is a homonymous hemianopsia, a visual field loss on the same side of both eyes (see Fig. 61.23). Patients with such lesions have a focal neurologic deficit and need to be evaluated and treated based on the primary neurological diagnostic consid-

Sudden onset of atraumatic, vision loss is usually due to a vascular process, such as infarction (although nonvascular processes, such as from retinal detachments and hemorrhages affecting the macula, are possible). Binocular processes include a sudden homonymous hemianopia from an infarction of the visual pathways in the temporal, parietal, or occipital lobes; and sudden total blindness in both eyes due to a basilar artery territory infarction of both occipital lobes. Central nervous system (CNS) processes (such as, ischemic stroke) that underlie these binocular events are discussed in entries specific to them elsewhere in this text. This section is, therefore, dedicated to sudden onset of painless monocular vision loss, which is ophthalmological and is usually due to a vascular process, such as infarction in either the retina or the optic nerve; the differential diagnosis primarily includes central retinal artery occlusion (CRAO), central retinal vein occlusion (CRVO), and ischemic optic neuropathy (ION). These typically present with sudden vision loss that is painless, severe, and develops over seconds, and may be permanent, or transient (amaurosis fugax). In a CRAO, acute retinal ischemia develops from a sudden embolic, thrombotic, vasculitic or vasospastic occlusion of a branch of the retinal artery (a branch retinal artery occlusion [BRAO]) or the central retinal artery itself (a CRAO). A CRAO may be (1) non-arteritic and permanent (over two-thirds of all CRAO cases, due to platelet fibrin thrombi and emboli from atherosclerotic disease), (2) non-arteritic and transient (with transient monocular blindness, a transient ischemic attack [TIA] of the retina, related to transient vasospasm due to serotonin release from platelets on atherosclerotic plaques), or (3) arteritic (due to temporal arteritis and rare).60 It generally has a poor visual prognosis with spontaneous resolution occurring in 1% to 8% of cases. Most commonly occurring in patients 50 to 70 years old, CRAO risk factors include hypertension, carotid artery disease, cardiac disease, diabetes, collagen vascular disease, vasculitis, cardiac valvular abnormality, and sickle cell disease. Patients with increased orbital pressure from acute glaucoma, retrobulbar hemorrhage, and endocrine exophthalmos are also at risk. A CRVO leads to congestion of venous blood and fluid in the intraretinal space that may lead to secondary retinal ischemia. It is typically characterized as either non-ischemic or ischemic; a non-ischemic CRVO is associated with dilatation of retinal vessels and edema only, whereas an ischemic CRVO presents with the sudden onset of painless vision loss in one eye. Predisposing factors include hypertension, hyperlipidemia, diabetes mellitus, vasculitides, hyperviscosity, and smoking. ION falls into two primary types, anterior ischemic optic neuropathy (AION; involving the optic nerve head) and posterior ischemic optic neuropathy (PION; involving the rest of the optic nerve). AION can further be divided into arteritic anterior ischemic optic neuropathy (A-AION; due to temporal arteritis) and—more commonly—non-arteritic anterior ischemic optic neuropathy (NA-AION; due to noninflammatory causes).61 Patients with A-AION may have concurrent symptoms of temporal arteritis (giant cell arteritis), such as weight loss, malaise, jaw pain, headache, scalp tenderness, polymyalgia rheumatica, and low-grade fever; in up to 25%, however, the acute vision loss is the only symptom.60 Vision loss can be preceded by episodes of amaurosis fugax. Untreated it may progress to involve both eyes. Temporal arteritis is extremely rare in people younger than 50

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years old, and the incidence rises with each subsequent decade. Vision loss has been shown to be unilateral in 46%, sequential in 37%, and simultaneously bilateral in 17%. Patients with the much more common NA-AION lack the classic symptoms of temporal arteritis and tend to be younger with systemic vascular disease, diabetes, or hypertension. This is an acute ischemic event affecting the anterior optic nerve that typically occurs in patients over the age of 50 (typically 60 to 70 years old), at times associated with precipitant anemia, hypovolemia, dehydration, systemic hypotension, or fluctuations in blood pressure (especially that associated dialysis).61 A sudden complete loss of vision due to a vascular cause can be transient, whereupon it is called amaurosis fugax, and can be a manifestation of any of the aforementioned processes. It has been found in 2% of CRAO, 14% of BRAO, 5% of CRVO, just over 3% in NA-AION, and in 32% of patients with temporal arteritis who have ocular involvement.62 Amaurosis fugax may also implicate proximal cerebrovascular disease and be a form of transient ischemic attack.

Diagnostic Testing, Management, and Disposition Central Retinal Artery Occlusion.  With CRAO, the examination reveals a markedly reduced visual acuity with a prominent APD, and an edematous with a pale gray-white retina with a cherry-red spot representing the fovea seen on funduscopy (Fig. 61.28). Patients younger than 50 years old should have a hypercoagulability evaluation, whereas older patients at risk for temporal arteritis should have an evaluation appropriate for that consideration.60 A number of interventions geared toward dislodgement of the embolus (via direct digital pressure through closed eyelids for 10 to 15 seconds and followed by a sudden release), dilation of the

artery to promote forward blood flow (by increasing intra-arterial carbon dioxide level [pCO2] with an inhaled mixture of 95% oxygen/5% carbon dioxide [carbogen]), and reduction of IOP (such as, with glaucoma, even using anterior chamber paracentesis) to increase in perfusion gradient have been recommended, but there is little evidence to support the benefit of any of these treatments.62a Other options in include hyperbaric oxygen. Overall, the efficacy of the above therapies varies between 6% and 49%, with a mean visual improvement rate of 15% to 21%.60 A CRAO may be amenable to the use of thrombolytic agents, with the caveat that it is usually an atheromatous embolic event, and thrombolysis is designed to lyse the fibrinoplatelet occlusion in a non-arteritic CRAO.59 Studies are heterogenous, using different agents, dosing regimens, and time-windows in largely retrospective case series with different findings, but it appears that intra-arterial thrombolytic therapy might be effective if given less than 6 hours from onset.60,63 IV thrombolysis might be effective if given less than 4.5 hours from onset, with a post-thrombolysis major hemorrhage rate significantly lower than that seen with ischemic stroke (none documented with tissue-plasminogen activator or urokinase).64 Until a large randomized controlled trial of the safety and efficacy of thrombolysis for CRAO is performed, management should be tailored to individual patient circumstances in consultation with an ophthalmologist. Central Retinal Vein Occlusion.  A CRVO is differentiated from CRAO based on findings on funduscopic examination. Appearance can vary but classically includes dilated and tortuous veins, retinal hemorrhages, and disk edema (Fig. 61.29). Branch retinal vein occlusion is an incomplete CRVO and carries about better prognosis. Neovascular glaucoma and macular edema are the major complications of ischemic CRVO. Over 80% of patients with a non-ischemic CRVO will have an ultimate visual acuity that is better than 20/200, whereas less than 10% of patients with ischemic CRVO will have an ultimate visual acuity better than 20/200. Treatment of CRVO includes treating the underlying etiology and monitoring for potential sequelae. Ophthalmology should be consulted in the ED to secure timely initiation of therapy, which largely centers around treating the macular edema associated with the occlusion. Treatment involves anti-vascular endothelial growth factor (antiVEGF) pharmacotherapies, intravitreal corticosteroid injection with a dexamethasone intravitreal implant or triamcinolone, as well as retinal photocoagulation, normalization of IOP, and cyclocryotherapy.65 The use of antithrombotic therapy, in particular the use of low–molecular-weight heparin, has also shown recent promise.65a Underlying medical disease should be managed;

A

B Fig. 61.28.  Central retinal artery occlusion (CRAO). A, Note the cherryred spot representing the fovea. B, Note whitening of the retina, with a less prominent cherry red spot. (B, Courtesy Jeffrey Lee, MD, University of California San Diego.)

Fig. 61.29.  Central retinal vein occlusion (CRVO). Note the “blood and thunder” appearance. (Courtesy www.tedmontgomery.com.)

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the prognosis depends on the degree of obstruction and resultant complications. Ischemic Optic Neuropathy.  Examination findings are similar in A-AION and NA-AION, and include a large APD, visual loss, and a visual field defect that may respect the horizontal (as opposed to vertical) midline, with a pale and swollen optic disc on funduscopy. The diagnosis of a temporal arteritis underlying an A-AION is outlined in entries specific to it elsewhere in this text, and it may include an erythrocyte sedimentation rate (ESR). Patients with NA-AION, on the other hand, do not have an elevated ESR, and an MRI may reveal abnormalities to the optic nerve head. Temporal arteritis with evolving vision loss or amaurosis fugax from A-AION—as opposed to just headache alone—represents a distinct clinical emergency. Untreated, vision loss becomes bilateral in days to weeks in at least 50% of cases.61 Patients should therefore be admitted for high-dose IV methylprednisolone (typically 500 mg to 1 g daily for 3 days) before transition to oral medications.66 Patients treated with high-dose IV methylprednisolone are more likely to have visual improvement (a 34% chance of improvement) and are less likely to develop fellow eye involvement than those receiving oral prednisone. The visual loss in NA-AION is less severe than with temporal arteritis, and improvement occurs in one-third of patients. There is no known treatment (intravitreal and systemic steroids have been tried without success, as have anti-VEGFs). Emergent ophthalmological consultation in the ED is warranted for any apparent ION to aid with differentiation of the type and extent of the process and management.

Functional Vision Loss Clinical Features, Differential Diagnosis, Diagnostic Testing, Management, and Disposition Functional (or factitious) vision loss may be a hysterical conversion reaction (a non-deliberate, imagined visual loss in a patient with a relatively flat affect) or malingering (a vision loss for secondary gain in a patient who somewhat dramatically demonstrates blindness). Although the evaluation may require collaborative consultation with an ophthalmologist, neurologist, and a psychiatrist, some tests can be performed in the ED that will suggest a functional overlay, given that the most common presentation of functional vision loss is a decreased visual acuity.67,68 They include (1) rotating an optokinetic drum or rocking a mirror slowly back and forth in front of the patient (which will induce nystagmus or eye movements in the functional patient, but not in the truly blind patient), (2) rapidly moving the examiners hand toward the eye in question (which will induce a blink to a visual threat in the functional patient, but not in the truly blind patient), (3) checking for an APD as in Figure 61.11 (which will be absent in the functional patient but not in the truly blind patient with an optic nerve problem), (4) having the patient raise his or her arms and touch both index fingers together (which a functional patient will feign inability to do, but a truly blind patient will be able to do, given that the test is actually one of proprioception and not vision). The other presentation of functional visual loss is a defect in the visual field, typically with a central scotoma.67,68 This can be identified as functional by having the patient sit in front of a picture (or grid) and describe the extent of a visual field defect vis-à-vis what is missing, and then moving him or her further away and asking for another description of what is missing. The functional patient may describe same missing elements in the picture (in an effort to convince the examiner that the defect is stable), whereas the patient will a real visual field deficit will notice that more elements in the picture (or grid) are missing.

DIPLOPIA Chapter 18 provides a comprehensive overview of the approach to diplopia in the ED expounding on a methodological consideration of whether a binocular diplopia is due to an due to (1) a simple restrictive, mechanical orbitopathy from inflammatory or infectious mass-effect directly restricting of the movement of the eye, (2) a palsy of one or more of the oculomotor CNs, (3) a more proximal neuro-axial process involving the brainstem and related CNs, or (4) a systemic neuromuscular process.

ANISOCORIA Principles Dilation (mydriasis) of the pupil is controlled by the dilator muscle, innervated by sympathetics that exit spinal cord at the level of C8, T1, and T2, and then come back up under the subclavian artery and over apices of the lungs, enter the superior cervical ganglion, then the internal carotid plexus, and finally the ophthalmic division of CN V (the trigeminal nerve), whereupon they reach the eye through the superior orbital fissure. This sympathetic innervation serves a largely inhibitory role, facilitating pupillary dilation in darkness. Constriction (or miosis) of the pupil is controlled by the pupillary sphincter muscle, innervated by parasympathetics that originate in the nuclei of CN III. This parasympathetic innervation is the primary means of regulating pupillary size in response to different intensities of light. Afferent input from the retina of each eye bifurcates to innervate the Edinger Westphal nuclei of each CN III, and each nucleus in turn provides efferent output to its pupillary constrictor muscle, underlying the direct and consensual pupillary light reflexes. Anisocoria, or a difference in pupillary size, can result from a process affecting the nuclei or the innervation pathways or from pharmacological interference at the neural endplates in the pupillary muscles.

Clinical Features and Differential Diagnosis The differential diagnosis of anisocoria include an Adie’s or Argyll Robertson pupil, pharmacologic mydriasis and miosis, a thirdnerve palsy, Horner’s syndrome, and a physiologic or headacheassociated anisocoria.

Adie’s and Argyll Robertson Pupils An Adie’s tonic pupil results from dysfunction or lesion of the ciliary ganglion or short ciliary nerves, and may be idiopathic (seen more frequently in women than men), for from local ocular or orbital damage from surgery, trauma, procedures, infection, inflammation, or ischemia. An Adie’s tonic pupil may also be part of a condition causing systemic autonomic dysfunction, such as diabetes, dysautonomia, neurosyphilis, amyloidosis, or sarcoidosis. These patients present with a large pupil, sensitivity to light in that eye, and blurred vision when looking at things near them (but may be asymptomatic, with the pupil noticed incidentally). The Argyll Robertson pupil is typically smaller than an Adie’s and similarly constricts poorly to direct light, but it briskly constricts when a target within reading distance is viewed. It is attributable to a dorsal midbrain lesion (such as from neurosyphilis) that interrupts the pupillary light reflex pathway but spares the more ventral pupillary near reflex pathway.

Pharmacologic Mydriasis and Miosis Anisocoria can be caused by a variety of accidental medication and plant exposures. Parasympathomimetic miosis may be

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induced by exposures to organophosphate esters, pilocarpine drops, or dust containing cholinesterase inhibitor from a dog’s flea collar. Parasympatholytic mydriasis may be seen with anticholinergic medications (such as, transdermal scopolamine), aerosolized ipratropium administered through ventilator masks, cycloplegics (such as, homatropine, cyclopentolate, or tropicamide), and plants containing anticholinergic agents, such as Jimsonweed (Datura stramonium) and Angel’s trumpet (Datura suaveolens).69-70 Sympathomimetic mydriasis may occur from sprays containing phenylephrine (Neo-Synephrine) and from apraclonidine (a glaucoma medication).

Third-Nerve Palsy CN III innervates the medial, inferior, and superior recti muscles, the inferior oblique muscle, and the levator palpebrae superioris muscle, which lifts the upper eyelid. It also provides parasympathetic innervation to two intrinsic ocular muscles, the ciliary and constrictor pupillae muscles, which constrict the pupil. A CN III palsy, therefore, results an eye that appears deviated “down and out” with a dilated pupil and ptosis. The parasympathetic fibers that affect pupillomotor constriction are located peripherally and on the superomedial surface of CN III, where compression from an aneurysm or other source may cause pupillary involvement before other oculomotor signs, such as ptosis or diplopia, develop.

Horner’s Syndrome Horner’s syndrome presents with ptosis, miosis, and facial anhidrosis resulting from a disruption of sympathetic innervation anywhere along the chain of sympathetic innervation.71 The presence of associated symptoms may help localize etiology, as outlined in Table 61.2.72 In children, the most common cause of acquired Horner’s syndrome is a neuroblastoma of the paravertebral sympathetic chain, although it may be from a mediastinal tumor. Horner’s syndrome can also be congenital, suggested by heterochromia or hypopigmentation of the ipsilateral iris.71

Physiologic and Headache-Associated Anisocoria In physiological anisocoria, the difference in pupil size will typically be 1 mm or less. A more prominent transient mydriasis (benign episodic unilateral mydriasis) may occasionally accom-

pany a migraine headache, either from sympathetic hyperactivity, or—with an ophthalmoplegic migraine—parasympathetic hypoactivity from CN III dysfunction.73,74 A non-migrainous benign episodic unilateral mydriasis can occur without headache, ptosis, or ocular motility disorder, in episodes lasting minutes, hours, or even days and is also thought to be caused by over-activity of sympathetic innervation to the pupil. Patients are typically female, relatively young, and episodes last a median duration of 12 hours. Patients can also present with a “tadpole pupil,” in which the pupil becomes distorted and pulled in one direction like the tail of a tadpole, possibly occurring several times a day for several days and then resolving. This is likely the result of a sectoral spasm of the dilator muscle, thought to be benign, and has been associated with strenuous exercise. If, on the other hand, the patient has a baseline anisocoria and the tadpole pupil manifests in the smaller of the pupils, testing for Horner’s syndrome is recommended.

Diagnostic Testing, Management, and Disposition Determination of the potential etiology of an anisocoria can be facilitated by the approach outlined in the explanatory algorithm in Figure 61.30. Assuming no damage to the iris (implying a purely structural problem) is evident on slit-lamp examination, the strategy is to differentiate a benign cause of anisocoria (eg, physiological or pharmacological) from one that requires additional neuro-ophthalmological consultation (eg, Horner’s syndrome) or emergent neuro imaging (eg, CN III compression potentially due to an aneurysm). The first step is to determine which pupil—the larger or the smaller—is the pathological one, keeping in mind that that parasympathetic innervation constricts a pupil in bright light, whereas sympathetic stimulation helps dilate a pupil in the dark. The subsequent steps incorporate the principles that an abnormally large pupil may be due to either a decrease in parasympathetic stimulation or an augmentation of sympathetic stimulation, and an abnormally small pupil may be due to either a decrease in sympathetic stimulation or an augmentation of parasympathetic stimulation. The type of response to a topical application of cocaine (which specifically blocks norepinephrine uptake) can be diagnostic of Horner’s syndrome, in that with no norepinephrine available to block the re-uptake, the Horner’s pupil will typically not dilate. Other medications, such as hydroxyamphetamine (an

TABLE 61.2 

Potential Locations of Lesion Causing a Horner’s Syndrome, Based on Symptoms and Signs SYMPTOMS AND SIGNS

POTENTIAL LESION LOCATION

POTENTIAL LESION TYPE

Brainstem symptoms (vertigo, ataxia, diplopia, and focal sensory and motor deficits)

Pontine or midbrain

Infarction or neoplasm

Myelopathic symptoms (paraparesis, sensory deficit, bowel or bladder symptoms, or hyperreflexia)

High spinal cord

Neoplastic or demyelinating process

Arm pain, weakness or numbness, neck lymphadenopathy (especially with hoarseness from recurrent laryngeal nerve compression)

Brachial plexus or cupula of the lung

Neoplastic process, such as a Pancoast tumor

Ipsilateral ear or neck pain (especially with symptoms of phrenic or vagus nerve involvement)

Carotid sheath

Carotid dissection; inadvertent injection of an anesthetic into the sheath during dental or line-placement procedures

Hearing loss and ear pain; trigeminal nerve dysautonomia (ipsilateral facial pain, rhinorrhea, conjunctival injection, and tearing)

Skull base

Neoplasm; inflammatory or infectious mass effect

Flaherty PM, Flynn JM: Horner syndrome due to carotid dissection. J Emerg Med 41(1):43-46, 2011. Davagnanam I, Fraser CL, Miszkiel K, et al: Adult Horner’s syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (Lond) 27(3):291-298, 2013.

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Fig. 61.30.  The approach to anisocoria in the emergency department (ED), an explanatory algorithm. *Some authors advocate that a marked response to low concentration (0.1% or 0.125%) pilocarpine is more consistent with an Adie’s pupil and can be used to differentiate it from an acute third nerve palsy (which may require the more concentrated 1% to elicit a reaction). This approach may be impractical, however, as a sole means to rule out a third nerve palsy from something like an aneurysm.

CHAPTER 61  Ophthalmology

indirect-acting adrenergic mydriatic that causes endogenous norepinephrine to be released from sympathetic nerve endings without directly stimulating the effector cells75), as well as direct adrenergic agonists, such as a phenylephrine or 1% apraclonidine, can be used with ophthalmological consultation to perform a secondary evaluation of a Horner’s pupil. Pilocarpine is a direct is a cholinergic receptor agonist and is used to differentiate hypoparasympathetic conditions (see Fig. 61.30). Once one of the typical presentations of anisocoria is identified, the evaluation progresses based on the clinical indications. Examination of an Adie’s pupil typically reveals poor reaction to light with sectoral palsy of the iris sphincter, and a lack of (or slow) constriction with near accommodation (at least in the acute phase; later on, with re-innervation, the pupil will constrict strongly, and will thus be a “tonic” pupil).76 Slit-lamp examination may reveal sectoral palsies of the iris, and a weak cholinergic agent (pilocarpine 0.1%) causes an intense pupillary constriction (compared to the patient’s normal pupil) as a result of the cholinergic supersensitivity in the affected pupil. These patients should be referred non-emergently to an ophthalmologist for further evaluation. The Argyll Robertson pupil, like the Adie’s pupil, will demonstrate segmental, slow, or little iris sphincter constriction with light, but normal constriction with near accommodation (“light-near dissociation,” which distinguishes it from an acute Adie’s pupil). A patient with bilateral Argyll Robertson pupils should be screened for neurosyphilis as per standard (please refer to entries dedicated to syphilis elsewhere in this text). The patient with a new-onset Horner’s syndrome should undergo an evaluation to determine the cause and will typically require targeting imaging based on the diagnostic considerations outlined in Table 61.2, with MRI for brain, skull-base, and spinal cord lesions, and computed tomography angiography (CTA) for chest and neck/ carotid pathology.72 The cadence of the evaluation (and which components are done in the ED) will be dictated by the acuity of the primary considerations in the differential diagnosis, with aneurysm, dissection, brainstem stroke, and a rapidly progressive myelopathic process evaluated emergently in the ED and a more subacute or chronic process (such as, a tumor) being worked up urgently as an outpatient. The diagnostic evaluation and management of a third nerve palsy is covered in Chapter 18 and Chapter 95. With regards to pharmacologic mydriasis and miosis, most of the exposures and their effects will be self-limited and transient, and the specific management will dictated by the toxicological sequelae expected. The first-time clinical presentation of physiological and headache-associated anisocoria (mydriasis) may provoke a neuro-imaging evaluation for the presence of aneurysmal or mass compression of CN III; although this is being excluded, treatment can be rendered along lines that are standard for migraine headache. Physiological and headache-associated anisocoria is otherwise self-limited and will not typically require urgent ophthalmology referral unless persistent.

NYSTAGMUS Principles Three specific mechanisms keep an object of visual interest on the fovea: (1) fixation, wherein the visual system detects retinal drifts and programs corrective eye movements; (2) the vestibulo-ocular reflex (VOR), which keeps the eyes on target despite head movements; and (3) eccentric gaze-holding, which requires ongoing signals from the brainstem and cerebellum to overcome the natural elastic pull of orbital tissues when the eyes are deviated away from the mid-position to fixate on a target.76 Dysfunction in any of these three mechanisms removes the visual target from the fovea and may result in nystagmus and oscillopsia (a subjective sense of movement of the visual field).

Nystagmus is a repetitive horizontal, vertical, or torsional back and forth movement of the eyes that may appear as an equal “to and fro” motion (pendular nystagmus), or demonstrate an alternating, slow phase followed by a corrective fast phase (jerk nystagmus). In jerk nystagmus, although the slow phase is the abnormal one, the directionality of the nystagmus is described as that of the fast phase. Gaze-evoked nystagmus (GEN) is an ability to hold the eyes in a fixed position at the eccentric extremes of gaze. Nystagmus can be physiologic or pathologic and congenital or acquired. Patients may have an incidental nonspecific physiological nystagmus with a very small amplitude and a very fast velocity, non-sustained (less than three beats), only elicited in extreme eccentric gaze, only horizontal and symmetric, and without other signs or symptoms of cerebellar system dysfunction.77 A patient may also have congenital nystagmus, typically identified as chronic or present since birth, which requires no acute intervention in the ED. The focus in the ED is therefore on acquired pathological nystagmus, of which the etiologies can be classified as either (1) peripheral (such as, seen with benign peripheral vertigo or vestibular neuronitis), (2) central (such as, seen with ischemic stroke or CNS mass lesions), or (3) toxic and metabolic (such as, that induced by medications, alcohol or illicit drugs). The clinical priority is to distinguish a peripheral (which is relatively benign and can be treated as an outpatient) from central (which may imply focal CNS pathology and require targeted neuro-imaging) from toxic or metabolic etiologies (which may imply toxic levels of a medication, or an underlying illicit drug intoxication).

Clinical Features, Differential Diagnosis, Diagnostic Evaluation, Management, and Disposition Peripheral Nystagmus and Central Nystagmus Because peripheral and central nystagmus from lesional processes (eg, from otoconia, vestibular neuronitis, posterior circulation stroke, brain tumor, and so on) present with prominent vertigo, a detailed discussion of these entities is deferred to the entries on vertigo and dizziness in Chapter 16. Table 61.3 highlights the specific features of the nystagmus associated with these conditions. The key clinical goal in the ED with regards to nystagmus caused by a lesion somewhere is differentiating more subtle presentations of a central cause from benign peripheral one. This can achieved along the lines of (1) the direction of the nystagmus, (2) how its intensity changes with extremes of gaze, and (3) how it is affected by visual fixation, as outlined in Table 61.3.

Toxic and Metabolic Nystagmus Nystagmus from drug or medication toxicity may be suggested by a concurrent toxidrome and, depending on the agent and the degree of toxicity, a lack of prominent vertigo or ataxia (keeping in mind that the specificity of nystagmus findings as an indicator of toxicity is unknown). Drug-induced GEN, although symmetric, is different from physiological nystagmus in that it has a larger amplitude and slower velocity and beats in the direction of the gaze (ie, upbeat nystagmus with the patient looking up, rightward nystagmus with the patient looking to the right, and so on). GEN from a focal cerebellar or brainstem lesion may look similar to that which is drug-induced, but it is characterized by a sustained asymmetric and rebound nystagmus in which, although the slow phase is directed toward primary position where the eyes are deviated, a few slow phases may be directed toward the prior gaze direction after the eyes return to the primary position.77,78 The management is targeted toward the overall toxicological profile of the specific offending agent.

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TABLE 61.3 

Forms and Causes of Nystagmus TYPE OF NYSTAGMUS

PRESUMED AREA OF DYSFUNCTION

CHARACTER/ PRIMARY DIRECTION

SUPPRESSES ON VISUAL CHANGES TRIGGERED FIXATION ON DIRECTION WITH BY HEAD MOVEMENTS? AN OBJECT? GAZE?

SUSTAINED?

Yes

No, just gets more pronounced the further the patient looks away from dysfunctional nerve

Yes

PERIPHERAL NYSTAGMUS Labyrinthitis or vestibular neuronitis

Labyrinthine dysfunction Horizonto-rotatory, one or viral infection of direction only, slow the superior portion of phase towards the vestibular nerve dysfunctional nerve trunk

Yes

Benign paroxysmal Otolithic, posterior canal positional (most common) vertigo (BPPV)

Torsional combined with vertical, one direction only

Yes, raising the Yes head from horizontal to vertical

No

No

Benign paroxysmal Otolithic, other canals positional vertigo (BPPV)

Horizonto-rotatory, one direction only, slow phase toward dysfunctional canal

Yes, turning head side-to-side

Yes

No, just gets more pronounced the further the patient looks away from dysfunctional canal

No

Vestibulocerebellum Pure vertical, with fast Drugs: Lithium, phenytoin, component carbamazepine, downward alcohol, toluene, felbamate, lamotrigine, phencyclidine (PCP), ketamine Nutritional deficiencies: magnesium, vitamin B12 or thiamine

No

No

No, just more pronounced on looking down

Yes

Upbeat nystagmus Pontomesencephalic or pontomedullary junction, or the superior vestibular nucleus and tracts Nutritional deficiencies: Thiamine (Wernicke’s)

Pure vertical, with fast component upward

No

No

No, just more pronounced on looking up

Yes

Torsional

Cerebellum or brainstem Drugs: PCP, ketamine

Pure rotary, with bidirectional fast component

No

No

Yes

Yes

Horizontal

Cerebellum or brainstem Drugs: PCP, ketamine

Bi-directional

No

No

Yes, fast component Yes beats in direction of gaze, and gets worse with more extreme deviation

Gaze-evoked nystagmus (GEN)

Cerebellum or brainstem Drugs: Phenytoin, alchohol

Multi-directional, but asymmetric intensity

No

No; in fact Yes, fast component Yes, specifically if vision is worsens on beats in direction eccentrically eccentric of gaze, and gets fixated on fixation worse with more an object extreme deviation

CENTRAL NYSTAGMUS Downbeat nystagmus

CHAPTER 61  Ophthalmology

TABLE 61.3 

Forms and Causes of Nystagmus—cont’d TYPE OF NYSTAGMUS

PRESUMED AREA OF DYSFUNCTION

CHARACTER/ PRIMARY DIRECTION

SUPPRESSES ON VISUAL CHANGES TRIGGERED FIXATION ON DIRECTION WITH BY HEAD MOVEMENTS? AN OBJECT? GAZE?

SUSTAINED?

OTHER MISCELLANEOUS CENTRAL NYSTAGMUS PRESENTATIONS Acquired pendular nystagmus

Paramedian pontine tract (seen in multiple sclerosis) Drugs: Phenytoin

Oblique or elliptical movements, can even be monocular

No

No

No

Yes

Periodic alternating nystagmus

Nodulus and ventral uvula Horizontal nystagmus of the with a slow phase vestibulocerebellum that changes Drugs: Phenytoin direction every 1 to 2 min

No

No

No

Yes

Superior oblique myokymia

Possible cranial nerve (CN) disorder

Torsional oscillopsia, in one eye

No

No

No

Yes

See-saw nystagmus

Parasellar mass, or stroke to mesodiencephalic regions

Elevation with intorsion No of one eye, with simultaneous depression and extorsion of the other eye

No

No

Yes

Oculopalatal myoclonus

Dentate, red, and inferior olivary nuclei in brainstem

No Vertical-torsional or pure vertical (with one eye being more prominent), associated with palatal myoclonus

No

No

Yes

From Baier B, Dieterich M: Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions. Neurology 76:361-365, 2011; Ehrhardt D, Eggenberger E: Medical treatment of acquired nystagmus. Curr Opin Ophthalmol 23(6):510–516, 2012; Shaikh AG: Fosphenytoin induced transient pendular nystagmus. J Neurol Sci 330 (1-2):121-122, 2013.

KEY CONCEPTS • Routine prophylactic topical antibiotics are not indicated for the treatment of corneal abrasions, and eye patches are not recommended because they can mask a worsening infection. • Eyelid lacerations that may require referral to a plastic or ophthalmic surgeon include those with lid margin lacerations, a canalicular laceration, or levator or canthal tendon injuries. • Alkaline burns to the cornea and conjunctiva need to be copiously irrigated until a neutral pH is attained, because they produce a liquefactive necrosis that penetrates and dissolves tissue. • Admission should be considered for traumatic hyphema patients with sickle cell trait, uncontrolled elevations in intraocular pressures (IOPs), hyphema of greater than 50%, and concern for re-bleeding. • Any manipulation, palpation, or tonometry on a suspected globe rupture should be avoided, pending ophthalmological consultation and further examination. • Scleritis, an autoimmune inflammatory process involving the sclera, can be confused with episcleritis, caused by inflammation in the more superficial episcleral layer of the eye. Episcleritis, unlike scleritis, is associated with much less discomfort, a pinker and more pronounced peri-limbal injection, and has injected superficial episcleral vessels that—unlike the deeper injected scleral vessels in scleritis—will vasoconstrict and blanch with 10% phenylephrine. Treatment of both involves topical corticosteroid drops. • Endophthalmitis is an infection of the eye itself, and the most common etiology is recent intraocular surgery. Intravitreal antibiotics are indicated for endophthalmitis.

• Herpes zoster keratoconjunctivitis can complicate herpes zoster ophthalmicus, and necessitates emergent ophthalmologic consultation and treatment with systemic antiviral agents. • The acute treatment of acute angle-closure glaucoma uses a two-armed approach: (1) reducing the production of aqueous humor with a topical beta-blocker (timolol 0.5%—1 to 2 gtt), a carbonic anhydrase inhibitor (acetazolamide 500 mg IV or PO), and a systemic osmotic agent (mannitol 1 to 2 g/kg IV); and (2) increasing the outflow of aqueous humor with a topical alpha-agonist (phenylephrine 1 gtt), miotic drops (pilocarpine 1% to 2%), and topical steroids (prednisolone acetate 1%, 1 gtt every 15 to 30 minutes four times, then every hour). • With anisocoria, the following considerations help in the determination of which pupil—the larger or the smaller—is the pathological one: (1) parasympathetic innervation constricts a pupil in bright light, whereas sympathetic stimulation helps dilate a pupil in the dark; (2) an abnormally small pupil may therefore be due to a either a decrease in sympathetic stimulation or an augmentation of parasympathetic stimulation—but likely the former (eg, Horner’s syndrome); (3) an abnormally large pupil may therefore be due to a either a decrease in parasympathetic stimulation or an augmentation of sympathetic stimulation—but likely the former (eg, partial third-nerve palsy from compression, Adie’s pupil, pharmacological mydriasis); or (4) the abnormally small pupil will usually look worse in the dark, whereas the abnormally large pupil will usually look worse in the light.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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Hayreh SS, Zimmerman MB: Amaurosis fugax in ocular vascular occlusive disorders: prevalence and pathogeneses. Retina 34(1):115-122, 2014. 62a.  Rudkin AK, Lee AW, Aldrich E, et al: Clinical characteristics and outcome of current standard management of central retinal artery occlusion. Clin Experiment Ophthalmol 38:496-501, 2010. 63. Chen CS, Lee AW, Campbell B, et al: Efficacy of IV tissue-type plasminogen activator in central retinal artery occlusion: report from a randomized, controlled trial. Stroke 42(8):2229-2234, 2011. 64. Schrag M, Youn T, Schindler J, et al: Intravenous fibrinolytic therapy in central retinal artery occlusion: a patient-level meta-analysis. JAMA Neurol 72(10):1148-1154, 2015. 65. Yeh S, Kim SJ, Ho AC, et al: Therapies for macular edema associated with central retinal vein occlusion: a report by the American Academy of Ophthalmology. Ophthalmology 122(4):769-778, 2015. 65a.  Squizzato A, Manfredi E, Bozzato S, et al: Antithrombotic and fibrinolytic drugs for retinal vein occlusion: a systematic review and a call for action. Thromb Haemost 103:271-276, 2010. 66. Dasgupta B, Borg FA, Hassan N, et al: BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford) 49(8):1594-1597, 2010. 67. Bruce BB, Newman NJ: Functional visual loss. Neurol Clin 28(3):789-802, 2010. 68. Incesu AI: Tests for malingering in ophthalmology. Int J Ophthalmol 6(5):708-717, 2013. 69. Lee DT, Jenkins NL, Anastasopulos AJ, et al: Transdermal scopolamine and perioperative anisocoria in craniofacial surgery: a report of 3 patients. J Craniofac Surg 24(2):470-472, 2013. 70. Camkurt MA, Ay D, Akkucuk H, et al: Pharmacologic unilateral mydriasis due to nebulized ipratropium bromide. Am J Emerg Med 29(5):576.e5-576.e6, 2011. 71. Pollard ZF, Greenberg MF, Bordenca M, et al: Atypical acquired pediatric Horner syndrome. Arch Ophthalmol 128(7):937-940, 2010. 72. Davagnanam I, Fraser CL, Miszkiel K, et al: Adult Horner’s syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (Lond) 27(3):291-298, 2013. 73. Maggioni F, Mainardi F, Malvindi ML, et al: The borderland of migraine with aura: episodic unilateral mydriasis. J Headache Pain 12(1):105-107, 2011. 74. Patel R, Davis C, Sivaswamy L: Anisocoria—not always cause for alarm. J Pediatr 164(6):1497, 2014. 75. Smit DP: Pharmacologic testing in Horner’s syndrome—a new paradigm. S Afr Med J 100(11):738-740, 2010. 76. Kelly-Sell M, Liu GT: “Tonic” but not “Adie” pupils. J Neuroophthalmol 31(4):393395, 2011. 77. Ehrhardt D, Eggenberger E: Medical treatment of acquired nystagmus. Curr Opin Ophthalmol 23(6):510-516, 2012. 78. Baier B, Dieterich M: Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions. Neurology 76:361-365, 2011.

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Medicine and Surgery  | 

SECTION One 

Head and Neck Disorders

CHAPTER 61: QUESTIONS & ANSWERS 61.1. A 23-year-old male presents with left periorbital pain after being struck with a fist. On examination, there are no globe injuries but marked periorbital swelling is noted. Computed tomography (CT) of the face reveals an orbital floor fracture. Which of the following would be the most likely physical findings? A. Cheek anesthesia, enophthalmos, and limitation of upward gaze B. Cheek anesthesia, ptosis, and limitation of inferior gaze C. Forehead anesthesia and afferent papillary defect D. Forehead anesthesia, diplopia, and limitation of lateral gaze E. Ptosis, miosis, and ipsilateral anhydrosis Answer: A. An orbital floor fracture may entrap the inferior rectus and inferior oblique muscles, resulting in diminished upward gaze. Other findings may include ptosis, enophthalmos, ipsilateral cheek/lip anesthesia, and orbital emphysema. Ten percent to 25% of such patients have associated globe injuries. Option E describes Horner’s syndrome, which is not a typical finding. 61.2. A 20-year-old male presents with periorbital pain and swelling after a blow to the eye by a softball. Physical examination reveals proptosis with blurred vision and limitation of ocular motion in all planes. Tonometry reveals an intraocular pressure (IOP) of 35 mm Hg. Which of the following should be the first indicated maneuver? A. Acetazolamide 500 mg IV, mannitol 20 g IV, and topical timolol B. Computed tomography (CT) scan of the head and face C. Endotracheal intubation and hyperventilation D. Immediate lateral canthotomy and cantholysis E. Ophthalmologic consultation Answer: D. These findings should make one suspect retrobulbar hemorrhage. All of these interventions are likely indicated. Intraocular hypertension may compromise central retinal artery flow. Although immediate ophthalmologic consultation and pressurelowering maneuvers are indicated, lateral canthotomy and cantholysis will provide the most rapid temporizing measure to preserve vision. 61.3. A 43-year-old male presents with acute ocular pain after a splash injury from drain cleaner. What should be the sequence of interventions? A. Copious irrigation for 10 minutes, pH testing, cyclopentolate cycloplegia, topical antibiotics/ intraocular pressure (IOP) measurement B. Intravenous (IV) analgesia, cyclopentolate cycloplegia, IOP measurement, isotonic irrigation C. IOP measurement, analgesia, head-up position, cycloplegia D. Phenylephrine cycloplegia, isotonic irrigation for 10 minutes, pH testing, slit-lamp examination for foreign bodies E. Phenylephrine cycloplegia, slit-lamp examination for foreign bodies, isotonic irrigation for 10 minutes, pH testing Answer: A. Copious irrigation, ideally beginning at the scene, is the cornerstone of management. Nitrazine pH testing after 10 minutes should guide the need for continued irrigation. Cycloplegia, IOP measurement, and topical antibiotics come after pH

normalization. Phenylephrine is contraindicated for cycloplegia in these cases because of its vasoconstrictive properties. 61.4. A 17-year-old girl who wears contact lenses presents with a 24-hour history of right eye pain. Physical examination reveals a right corneal abrasion at the six-o’clock position of the limbus. Appropriate treatment consists of which of the following? A. Cessation of contact lens wear, eye irrigation (qid) with isotonic saline solution, followed by instillation of undiluted topical tetracaine for 5 days B. Emergent ophthalmology consultation C. Tetanus prophylaxis, eye patching for 48 hours, antibiotic ointment, and a 24-hour recheck D. Tetanus prophylaxis, topical nonsteroidal antiinflammatory drugs (NSAIDs), cessation of contact lens wear, and a 24-hour recheck E. Topical nonsteroidal medications, topical antipseudomonal antibiotic, and a 24-hour recheck Answer: E. Tetanus prophylaxis is not indicated for corneal abrasion unless there is corneal perforation or contamination with organic material. Topical NSAIDs reduce corneal abrasion pain. Antipseudomonas coverage with cessation of contact lens wear is appropriate. Eye patching is not indicated. Administration of undiluted topical anesthetics for more than 24 hours is untested and may be dangerous. Oral analgesics may be needed. 61.5. How do patients with subconjunctival hemorrhage most commonly present? A. Asymptomatic blood in the eye, noticed in the mirror or by a friend B. Decreased visual acuity C. Foreign body sensation D. Modest pain E. Photophobia Answer: A. Any significant symptoms, such as pain, decreased vision, foreign body sensation, or photophobia, should spark the search for more serious pathology. Bilateral hemorrhage in the absence of a clear cause (eg, severe vomiting) should raise suspicion for coagulation issues. 61.6. A 38-year-old man presents with unilateral left-sided visual loss after a motor vehicle collision (MVC). The only clinical finding is a left-sided hyphema rising to 50% of the height of the anterior chamber. Intraocular pressure (IOP) is 17 mm Hg in the unaffected eye and 29 mm Hg in the affected eye. Appropriate management should include which of the following? A. Cycloplegia, intravenous (IV) mannitol, ophthalmology consultation B. IV analgesia and antibiotic, immediate ophthalmologic consultation for decompression resulting from intraocular hypertension C. Oral acetazolamide, patch and shield, antiemetics, 24-hour recheck D. Topical beta-blocker, patch and shield, modest analgesia, admission E. Topical beta-blocker, topical nonsteroidal antiinflammatory drugs (NSAIDs) for pain, patch and shield, 24-hour recheck Answer: D. Significant hyphema is an indication for admission. The presence of elevated IOP requires urgent treatment (which might also include topical alpha-agonists or IV acetazolamide,

CHAPTER 61  Ophthalmology

and so on), patch and shield, elevation of the head, and cautious use of systemic analgesics. Any form of platelet inhibition would be contraindicated (ie, NSAIDs). 61.7. What is the major complication of hyphema? A. Detached retina B. Glaucoma C. Horner’s syndrome D. Rebleeding E. Vitreous hemorrhage Answer: D. Rebleeding typically occurs 2 to 5 days later as the clot retracts. It is most common in patients with elevated intraocular pressures (IOPs), hyphema greater than 30% of the anterior chamber, and with delayed presentation. Rebleeding may lead to glaucoma and synechia formation. 61.8. A 48-year-old woman presents with right eye pain, photophobia, and decreased vision after a motor vehicle collision (MVC). Physical examination reveals an irregularly shaped pupil and a small hyphema. Photophobia, decreased acuity, minimal pupil reactivity, and bloody chemosis are seen on examination. What is the most likely diagnosis? A. Acute angle–closure glaucoma B. Blunt ciliary injury C. Iridodialysis D. Scleral rupture E. Traumatic miosis Answer: D. Scleral rupture occurs either at the insertion of the extraocular muscles or at the limbus, where the sclera is the thinnest. A “teardrop” pupil is often seen and may be accompanied by bloody chemosis or severe subconjunctival hemorrhage. Brownish black pigment prolapse may also be seen. Intraocular pressure (IOP) may be low, but tonometry is generally contraindicated in cases of suspected globe injury. 61.9. A 26-year-old man presents with a 3-day history of right eye pain, decreased vision, and photophobia. He reports a history of left eye trauma 6 weeks prior, with hyphema, traumatic iritis, and persistent decreased vision. He is otherwise healthy. Physical examination reveals

photophobia in the right eye with bilateral decreased vision. Before the past 3 days, the vision in the right eye had been perfect. What is the most likely explanation for his right eye symptom? A. Collagen vascular disease B. Post-traumatic conjunctivitis C. Post-traumatic retinal tear D. Spontaneous vitreal hemorrhage E. Sympathetic ophthalmia Answer: E. Sympathetic ophthalmia is an autoimmune inflammatory response in the unaffected eye, days to months after uveal trauma in the opposite eye. Pain, photophobia, and decreased vision are common. This patient had no findings consistent with conjunctivitis or collagen vascular disease, and a retinal tear would not typically be painful. 61.10. Oral antibiotics are indicated for which of the following? A. Blepharitis B. Chalazion C. Dacryocystitis D. Endophthalmitis E. Hordeolum Answer: C. Dacryocystitis is an infection of the lacrimal sac from nasociliary duct obstruction. Warm compresses are also recommended and may be helpful, although evidence is lacking. Warm compresses and topical antibiotics are appropriate for the other conditions. Intravitreal antibiotics are indicated for endophthalmitis. 61.11. Emergency department (ED) bedside ocular ultrasonography can provide useful information for which of the following conditions? A. Lens dislocation B. Retinal detachment C. Vitreous hemorrhage D. All of the above Answer: D. A displaced lens can be seen in the relatively hypoechoic vitreous. Vitreous hemorrhage and retinal detachment can both be diagnosed with ED bedside ultrasonography.

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C H A P T E R 62 

Otolaryngology* James A. Pfaff  |  Gregory P. Moore OTITIS MEDIA Principles Otitis media is broadly defined as inflammation of the inner ear and is a continuum of disease. Acute otitis media is defined as the signs and symptoms of an acute infection, with evidence of effusion; this has also been called acute suppurative or purulent otitis media. Otitis media with effusion (OME) includes effusion without signs or symptoms of an acute infection; additional descriptive terms include serous, mucoid, nonsuppurative, and secretory otitis media. Chronic otitis media or chronic suppurative otitis media refers to chronic discharge from the ear through perforation of an intact membrane. Recurrent otitis media is defined by three or more episodes over 6 months or four episodes in 1 year. Acute otitis media (AOM) is one of the most common diseases affecting preschool children in the United States and represents the most common indication for antibiotic usage and pediatric outpatient visits.1 More than 80% of children will have at least one episode of AOM during their lifetime and, by 3 years of age, up to 40% will have had at least three episodes. In 2011, there were 6.21 million patient visits with a diagnosis of otitis media.2 The financial repercussions are enormous, with one estimate that it adds $2.88 billion to annual health care expenses.1 Male gender, daycare attendance, parental smoking, pacifier use, family history of middle ear disease, premature birth, and lower socioeconomic status have been implicated as risk factors. Children with anatomic abnormalities, such as cleft palate and Down syndrome, have a higher rate of OM, probably because of eustachian tube abnormalities. Some immunocompromised patients, including patients with human immunodeficiency virus (HIV) infection, may have recurrent OM as an initial symptom of their underlying disease. OM and upper respiratory infections occur primarily in the winter. Breast-feeding seems to be protective. Immunizations for pneumococcus and influenza provide some protection but the decrease in overall episodes of otitis media is multifactorial. These factors include improved diagnosis, public education campaigns, and decreasing exposure to secondhand smoke. AOM is much less common in adults and is treated with the same antibiotics as for younger populations. OME is also less common in adults and is frequently associated with sinus disease, smoking-induced nasopharyngeal lymphoid hyperplasia, adult-onset adenoidal hypertrophy, and head and neck tumors such as nasopharyngeal carcinomas.3

Anatomy and Pathophysiology Eustachian tube dysfunction is the central theme of most theories of AOM pathogenesis. The eustachian tube, between the middle ear cavity and nasopharynx, ventilates the middle ear to equilibrate pressure, allows for middle ear drainage, and provides *The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. 820

protection from nasopharyngeal secretions. In young children, the eustachian tube is short and horizontal. As individuals age, the eustachian tube widens, doubles in length, becomes more vertically oriented, and stiffens, which may explain the decreased incidence of AOM in adults. Normally, the tube is collapsed, but it opens during yawning, chewing, and swallowing. The eustachian tube may become mechanically or functionally obstructed, decreasing middle ear ventilation. Examples of mechanical obstruction include inflammation from an upper respiratory infection, hypertrophied adenoids, and a cleft palate. Functional obstruction from persistent tubal collapse occurs primarily in young children, who have less fibrocartilage support of the medial eustachian tube than older children or adults. There is general consensus that AOM occurs as a consequence of an upper respiratory infection resulting in eustachian tube dysfunction and subsequent negative middle ear cavity pressure, causing a transudate of fluid that combines with the reflux of nasopharyngeal secretions and bacteria. As such, there is a proliferation of bacteria and viruses. The advent of reverse transcriptase polymerase chain reaction technology and other techniques for viral identification has led to improvements in diagnosis, and thus the number of viral agents identified in the middle ear has increased. In pediatric patients, middle ear cultures have been positive for viruses 48% to 70% of the time, with viral and bacterial coinfection occurring between 45% and 66% of the time. Respiratory syncytial virus is the most common virus, but parainfluenza virus, influenza virus, rhinovirus, and adenovirus have also been found in the middle ear aspirates of children. Viruses contribute to a poor treatment outcome by increasing middle ear inflammation, decreasing neutrophil function, and decreasing antibiotic penetration into the middle ear. The most common causes of bacterial infection in children are Streptococcus pneumoniae, Haemophilus influenzae (primarily nontypeable), and Moraxella (Branhamella) catarrhalis. Streptococcus pyogenes, Staphylococcus aureus, and gram-negative bacteria are much less common. The widespread use of the pneumococcal seven-valent conjugate vaccine (PCV-7) and subsequent pneumococcal 13-valent conjugate vaccine (PCV-13) have changed the frequency of these common organisms, with H. influenzae increasing in frequency, particularly in persistent AOM and treatment failures. In young children, it was previously believed that gramnegative organisms and S. aureus were the causative organisms. Although these bacteria may be the causes in intubated patients or patients in the neonatal intensive care unit, healthy newborns tend to be infected by the same pathogens as healthy older children. Bullous myringitis produces bullae on the tympanic membrane (TM) in up to 5% of cases of OM in children younger than 2 years. Although it was previously thought to be caused by Mycoplasma pneumoniae, M. pneumoniae is uncommon; a culture of middle ear aspirates in this condition generally grow the usual organisms that cause AOM in all age groups. Bullous myringitis is therefore treated with the same antibiotics. More than 70% of children with purulent conjunctivitis may have OM, a symptom complex described as the otitis-conjunctivitis syndrome, which is predominantly caused by H. influenza. Other

CHAPTER 62  Otolaryngology

less likely organisms that can cause AOM include Mycobacterium tuberculosis (primarily in children) and Chlamydia trachomatis (most commonly seen in children 39°C (102.2°F) in the past 48 hr, or if there is uncertain access to follow-up after the visit. c This plan is initial management and provides an opportunity for shared decision making with the child’s family for those categories appropriate for additional observation, if offered; a mechanism must be in place to ensure follow-up and begin antibiotics if the child worsens or fails to improve within 48–72 hr of AOM onset. Adapted from Lieberthal AS, Carroll AE, Chonmaitree T, et al: Clinical Practice Guideline: the diagnosis and management of acute otitis media. Pediatrics 131:e964–e999, 2013. b

does not worsen recovery but may be associated with transient worsening of a child’s condition.10 The observation option has been restricted to healthy children older than 6 months. In children between 6 months to 2 years of age, treatment recommendations are based on the certainty of the diagnosis and severity of illness. In patients with unilateral AOM without otorrhea, observation is an option if the diagnosis is uncertain. In children older than 2 years, treatment is necessary only for patients with severe illness, defined as severe otalgia or temperature higher than 39°C (102°F) or patients with otorrhea. Children older than 2 years can be treated or clinically observed. Table 62.1 summarizes the AAP recommendations. Observation recommendations are also based on the reliability of the caregivers and ability for close follow-up. Providers should involve the parents in the discussion, with shared decision making. If there is concern about the ability to get follow-up, give parents a safety net prescription to be filled if the patient’s condition does not improve within 48 hours. Several studies in the emergency department (ED) have shown success with use of this approach. An analysis from the National Ambulatory Medical Care Survey has revealed that management without antibiotics has not increased since the guidelines were published, although children who did not receive antibiotics were more likely to have mild infections.11 There are no data on the use of observation in adult patients, so they should be treated with amoxicillin, 500 mg tid for 10 days. The decision to treat is balanced against the medication’s adverse effects, which may include allergic reactions, gastric upset, accelerated bacterial resistance, and unfavorable changes in the bacterial flora. Several large systematic reviews have revealed that antibiotics are modestly more effective than no treatment, but 4% to 10% of children experience adverse effects from the treatment itself.12 Two randomized controlled trials comparing amoxicillinclavulanate versus placebo in a total of 610 patients have reported modestly improved time to resolution of symptoms and otoscopic findings but with more side effects, with diarrhea being the most common.13,14 Although some authorities believe that these studies settled the treatment controversy, the studies were far from conclusive. Observation in children from 6 months to 2 year of age with unilateral AOM without otorrhea, or children older than 2 years with a nondraining ear or lacking severe symptoms, remains an acceptable and recommended treatment. Amoxicillin’s cost, efficacy, safety profile, and palatability justify its recommendation as the first-line agent in the non– penicillin-allergic patient. It can be given at a dose of 90 mg/kg bid. This higher dose is preferred because it is effective against susceptible and intermediately resistant strains of S. pneumonia, and because 15% to 20% of children have poor gastrointestinal absorption of amoxicillin. In patients with reported allergies, a distinction should be made between types I and II hypersensitivity. There is only

minimal cross-reactivity to cephalosporins for patients with penicillin allergy, and the use of a second- or third-generation cephalosporin is generally considered safe, unless the child has a previous adverse reaction to cephalosporins. In patients with type II hypersensitivity, alternate treatment options include cefdinir (14 mg/kg per day in one or two doses), cefuroxime (30 mg/kg per day in two divided doses), cefpodoxime (10 mg/kg once daily), and intramuscular ceftriaxone (50 mg/kg per day) IV or IM for 1 to 3 days. Patients with type I sensitivity are problematic in that macrolides have poor sensitivity against S. pneumoniae and H. influenzae, and clindamycin has poor sensitivity against H. influenzae. In patients with severe allergy, we recommend azithromycin, 10 mg/kg, as a first dose, followed by 5 mg/kg for days 2 through 5 or clindamycin, 30 to 40 mg/kg per day tid. Children who have taken amoxicillin in the previous 30 days, those with concurrent conjunctivitis, or those for whom coverage with β-lactamase–positive H. influenzae and M. catarrhalis is desired should be initially treated with high-dose amoxicillinclavulanic acid (90 mg/kg per day amoxicillin and 6.4 mg/kg/day clavulanate) tid.12 Patients should be reevaluated in 3 days if there is no improvement. Treatment failure is defined by lack of clinical improvement in signs and symptoms, such as ear pain, fever, and TM findings of redness, bulging, or otorrhea. The reasons for treatment failure may include the wrong initial diagnosis or antibiotic resistance.15 In these cases, treatment includes agents effective against the β-lactamase–producing organisms H. influenzae and M. catarrhalis. Recommended agents include amoxicillin-clavulanate (80–90 mg of the amoxicillin component/kg per day) and intramuscular ceftriaxone (50 mg/kg for 1–3 days). Table 62.2 summarizes the AAP guidelines for antibiotic treatment. Patients with AOM for whom treatment with a conventional β-lactam antibiotic has failed and β-lactam–allergic patients for whom macrolide therapy has failed should be referred to a pediatric infectious disease specialist or otolaryngologist. These patients may need a myringotomy and treatment with a fluoroquinolone, which is not US Food and Drug Administration (FDA)–approved for children. Response to antibiotics is only one of a number of factors that affect clinical outcome. Other factors include eustachian tube function, coinfection with nonbacterial pathogens, and host immune response. Local practice patterns and antimicrobial sensitivities may also play a role in the type of treatment given. Treatment historically involved a 10-day course. Numerous studies have compared traditional treatment courses with shorter therapy, which is most appropriate for uncomplicated AOM. Patients younger than 2 years, those with TM perforations, or those with chronic or recurrent infections should be treated with a 10-day course. Children older than 2 years with a first-time infection and an intact TM can be treated with a 5- to 7-day course. The antibiotic treatment of AOM in adults is the same as for children. There is no indication for the use of

CHAPTER 62  Otolaryngology

TABLE 62.2 

Recommended Antibiotics for Initial or Delayed Treatment and for Patients Who Have Failed Initial   Antibiotic Treatment INITIAL IMMEDIATE OR DELAYED ANTIBIOTIC TREATMENT

ANTIBIOTIC TREATMENT AFTER 48–72 H OF FAILURE OF INITIAL ANTIBIOTIC TREATMENT

Recommended First-Line Treatment

Alternative Treatment (if Penicillin-Allergic)

Recommended First-Line Treatment

Amoxicillin (80–90 mg/kg/day in two divided doses)

Cefdinir (14 mg/kg/day in one or two doses)

Amoxicillin-clavulanatea (90 mg/kg/day of amoxicillin, with 64 mg/kg/day of clavulanate in two divided doses)

Ceftriaxone, 3 days Clindamycin (30–40 mg/kg/day in three divided doses), with or without third-generation cephalosporin

or

Cefuroxime (30 mg/kg/day in two divided doses)

or

Failure of second antibiotic

Amoxicillin-clavulanatea (90 mg/kg/day of amoxicillin, with 64 mg/kg/day of clavulanate [amoxicillin to clavulanate ratio, 14 : 1] in two divided doses)

Cefpodoxime (10 mg/kg/ day in two divided doses)

Ceftriaxone (50 mg IM or IV for 3 days)

Clindamycin (30–40 mg/kg/day in three divided doses) plus third-generation cephalosporin

Alternative Treatment

Tympanocentesisb Consult specialistb

Ceftriaxone (50 mg IM or IV/day for 1 or 3 days)

a

May be considered for patients who have received amoxicillin in the previous 30 days or who have otitis-conjunctivitis syndrome. Perform tympanocentesis and drainage if skilled in the procedure or seek a consultation from an otolaryngologist for tympanocentesis and drainage. If the tympanocentesis reveals multidrug-resistant bacteria, seek and infectious disease specialist consultation. c Cefdinir, cefuroxime, and ceftriaxone are highly unlikely to be associated with cross-reactivity with penicillin allergy on the basis of their distinct chemical structures. Adapted from Lieberthal AS, Carroll AE, Chonmaitree T, et al: Clinical Practice Guideline: the diagnosis and management of acute otitis media. Pediatrics 131:e964–e999, 2013. b

antihistamines, decongestants, steroids, or tympanostomy tubes for an acute episode of AOM. After a 10-day treatment with antibiotics, 50% of children may exhibit OME, but 90% of OME cases resolve within 3 months. However, about 30% to 40% of children have recurrent OME, and 5% to 10% of cases last 12 months or longer. The treatment of OME is controversial, with one large systematic review suggesting that tympanostomy tubes decrease effusion and improve hearing over a short period without affecting speech, language, or other functional outcomes.16 There is little benefit from antibiotics, and they should not be used. Antihistamines, decongestants, steroids, or surgical procedures are not beneficial for patients with OME. Myringotomy and tympanostomy tubes may be beneficial in children who have had OME for more than 4 months with persistent hearing loss, those with hearing loss greater than 40 dB, children with structural damage to the TM or middle ear, and children with persistent OM who are at risk for speech, language, or hearing problems. Tonsillectomy is not beneficial, but adenoidectomy may be helpful for older children who have a specific indication, such as nasal obstruction or chronic adenoiditis. Emergency clinicians may encounter three types of otitis media associated with a perforation of the TM: 1. Acute otitis media complicated by perforation of the tympanic membrane, presenting as otorrhea 2. Otitis media in patients with tympanostomy tubes 3. Chronic suppurative otitis media defined as tympanic membrane perforation with chronic inflammation of the middle ear and persistent otorrhea for 2 weeks to 3 months. As noted earlier, tympanic membrane perforation is a known complication of AOM and, in most cases, will heal spontaneously. Patients presenting with AOM and otorrhea should be treated with oral high-dose amoxicillin, as if the TM were not ruptured. There is no advantage to adding topical therapy. Tympanostomy tubes have also been used in recurrent AOM unresponsive to prophylactic antibiotics, for complications of AOM, and for complications of eustachian tube dysfunction, including TM retraction with hearing loss, ossicular erosions, and retraction pocket formation. Thus, tympanostomy tube insertion

is one of the most common operative procedures for children in the United States, and emergency clinicians will frequently encounter patients with drainage from these tubes. In general, increased drainage from these tubes is as a result of an acute infection. The organisms involved are the same ones that cause AOM, particularly in children younger than 2 years, but Pseudomonas aeruginosa, S. aureus, and Staphylococcus epidermidis are also implicated. Fluoroquinolone drops are the only medications FDA-approved for use in patients with a nonintact tympanic membrane. In the acute setting, topical antibiotic administration with 5 ofloxacin drops to the affected ear bid or 4 drops of ciprofloxacin-dexamethasone bid for 7 days is an effective treatment. Systemic treatment (usually with amoxicillin-clavulanate, 45 mg/kg bid) should be reserved for patients showing signs of complicated or invasive infections or signs of systemic disease. Chronic suppurative otitis media (CSOM) is one of the most common childhood infectious disease worldwide and is the most common cause of hearing impairment in the developing world, although it is infrequently seen in the developed world.1 Again, P. aeruginosa and S. aureus are the most common organisms. Because of the tympanic membrane perforation, we recommend topical treatment with quinolone antibiotics.

Disposition Patients should be seen in 48 to 72 hours if there is no improvement. Children who improve can be followed up in 8 to 12 weeks to ensure resolution of any residual effusion. Patients with complications need ear, nose, and throat (ENT) referral. Adults who have persistent OME warrant ENT referral to rule out nasopharyngeal carcinoma.

OTITIS EXTERNA Principles External otitis is an inflammation of the external auditory canal. The external auditory canal is lined with squamous epithelial cells

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Medicine and Surgery  | 

SECTION One 

Head and Neck Disorders

and cerumen glands that provide a protective lipid layer. This protective layer may be disrupted by high humidity, increased temperature, maceration of the skin after prolonged exposure to moisture, and local trauma (eg, cotton swabs or the use of hearing aids), resulting in the introduction of bacteria. Otitis externa (OE) is usually caused by P. aeruginosa and S. aureus but can also be polymicrobial. Occurring most often in the summer and in tropical climates, it is also known as swimmer’s ear or tropical ear.

Clinical Features The diagnosis is made clinically. The external auditory canal may be initially pruritic and may become erythematous and increasingly swollen. Symptoms include otalgia and ear fullness, as well as possible hearing loss or jaw pain. Physical findings include erythema or edema of the canal; pulling on the auricle or tragus classically reproduces the discomfort. There may be associated lymphadenitis, TM erythema, or local cellulitis. The disease may progress to a chronic form, with itching, eczema, and flaking of the epithelium, which may be from a bacterial, fungal, or dermatologic condition. In children, it is usually secondary to chronic OM.

Differential Diagnoses It may be difficult to distinguish OE from OM with drainage from a ruptured TM, particularly in children. The TM may be erythematous in both conditions, and the edema may preclude diagnosis. The discharge may be from OE or a perforated TM and, in equivocal cases, it is prudent to treat for both conditions. Otomycosis or fungal infection can occur as a primary or secondary infection and accounts for 10% of cases of OE. Itching is the prominent symptom, often with minimal pain or otorrhea. Aspergillosis is the cause in most cases. Otomycosis usually appears in individuals in tropical climates, diabetics, and immunocompromised patients. Treatment involves cleansing and the use of acidifying and antifungal ear drops, such as acetic acid, or a topical antifungal such as clotrimazole. Furunculosis is a small, erythematous, and well-circumscribed infection of the cartilaginous portions of the external canal, usually caused by S. aureus. There is usually no drainage; treatment involves incision, drainage, and oral antibiotics effective for cellulitis based on local sensitivity. Cellulitis of the auricle and canal may cause erythema, induration, and other systemic signs. Clindamycin, 450 mg qid, will cover S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). Skin conditions such as eczema, seborrhea, and contact dermatitis can all mimic otitis externa. A careful history about possible skin diseases, as well as medication and exposure history, should be elicited. Exposure to reactive metals such as nickel from devices such as hearing aids and chemicals from cosmetics and shampoos are also possible culprits. Herpes zoster oticus, also known as the Ramsay Hunt syndrome, is a viral manifestation of disease affecting the auricle, with resulting facial paralysis that may involve multiple cranial nerves. It initially causes pain, erythema, and swelling, with vesicles developing approximately 3 to 7 days later. Treatment consists of analgesia and antivirals (acyclovir, 800 mg five times/day, famciclovir, 500 mg, or valacyclovir, 1000 mg tid), but there is little evidence supporting its efficacy.

Diagnostic Testing OE is a clinical diagnosis. No additional testing is indicated.

Management Treating OE involves cleaning the canal and treating the infection. The external canal may be cleaned with a small cotton swab or

combination of gentle suctioning and irrigation, depending on the amount of obstructing exudates and whether there is an intact TM. Cleansing solutions include tap water, sterile saline, 2% acetic acid, and Burow’s solution. Topical antibiotics are highly effective for OE treatment, with clinical cure rates of 65% to 80% within 10 days. A combination of polymyxin B, neomycin, and hydrocortisone (Cortisporin) can be given at a dose of 3 or 4 drops to the affected ear qid, although occasionally patients develop cutaneous sensitivity to the neomycin. Ofloxacin (5 drops) or ciprofloxacin with hydrocortisone (3 drops) bid may result in improved patient compliance. The addition of steroid drops may decrease inflammation and the formation of granulation tissue in the canal, but this has not been proven. Care should be taken if there is a concern for TM perforation. As noted, quinolone drops have a better safety profile than neomycin-containing drops, which are ototoxic, especially after prolonged or repeated use.17,18 Having the patient lie down for 5 minutes after the solution has been placed may obviate the need for packing. Commercially available wicks made of compressed cotton or hydroxycellulose facilitate medication delivery. The wick is placed 10 to 12 mm into the canal, moistened with antibiotic drops, and left in place for 2 to 3 days. The wick generally falls out or, if left in place, may become a foreign body in the ear. Therefore, a patient should follow up with her or his primary care physician. There is no evidence that systemic antibiotics alone or in combination with topical preparations improve treatment outcome compared with topical antibiotics alone, but systemic medication, such as ciprofloxacin (500 mg bid), are indicated for immunocompromised patients with diabetes or HIV infection or for those with infections involving the skin and periauricular areas.17 OE can be extremely painful, and severe symptoms may require opiate analgesia. Topical anesthesia, such as benzocaine with or without antipyrine, may also be used for pain relief.

Disposition Patients with otitis externa rarely require admission. If it does not respond to therapy in 2 to 3 days, other conditions such as necrotizing external otitis should be considered. Patients who have a wick placed should be evaluated in 2 to 3 days to ensure improvement of the condition and that the wick is removed.

NECROTIZING (MALIGNANT) EXTERNAL OTITIS Principles Previously known as malignant otitis externa because of its associated high mortality rate, necrotizing external otitis (NEO) is an extremely form of OE. Patients affected include older diabetics, those with acquired immunodeficiency syndrome (AIDS) and, rarely, immunocompromised children. Pseudomonas is the predominant pathogen, but S. aureus, S. epidermidis, Proteus mirabilis, Klebsiella, Aspergillus, and Salmonella have all been described as causative organisms. The infection begins in the external canal and progresses through the periauricular tissue and cartilaginous bony junction of the external auditory meatus. It then spreads into the adjacent tissues along clefts in the floor of the meatus known as the fissures of Santorini. It may spread to the base of the skull at the temporal bone, with a resultant skull-base osteomyelitis, another term often used to describe this entity. The facial nerve is the first cranial nerve affected, but other nerves may also be involved. The pathogenesis is uncertain but may be related to vascular insufficiency or immune dysfunction.

CHAPTER 62  Otolaryngology

Clinical Features Patients may have persistent otorrhea unresponsive to topical medications, severe otalgia, headache, and periauricular pain and swelling. The diagnosis should be considered in patients at risk who have a prolonged course of OE. The characteristic clinical finding is granulation tissue on the floor of the ear canal at the bony cartilaginous junction. Cranial nerve VII is most commonly involved; involvement manifests with facial paralysis, which occurs when the stylomastoid foramen is involved. Further extension can result in involvement of the glossopharyngeal, vagal, spinal accessory, hypoglossal, trigeminal, and abducens nerves. Cranial nerve involvement is not associated with increased mortality rates. Additional complications include meningitis, brain abscess, and thrombosis of the sigmoid sinus.

Differential Diagnoses Patients with necrotizing otitis will present with severe ear pain. Other differential considerations include severe otitis externa, otitis media, otitis media complications, trauma, and referred pain from the teeth, sinuses, throat or temporal mandibular joint.

Diagnostic Testing There is no single diagnostic criterion for necrotizing external otitis. The diagnosis is made from a range of clinical, laboratory, and radiographic findings. The C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) may be elevated, but they are nonspecific markers. In the ED, computed tomography (CT) is the initial study of choice and, in most cases, will identify bony erosion and soft tissue abnormalities. Magnetic resonance imaging (MRI) is better at delineating responses to therapy. This disease should be considered in all patients with risk factors who have failed to respond to antimicrobial therapy for temporal bone inflammation and otalgia.19

Management If NOE is suspected, consultation should be made with an otolaryngologist. The patient presentation will determine disposition. Patients who appear ill require admission for IV fluoroquinolones, such as ciprofloxacin, 400 mg IV q8h, to ensure that there is an adequate clinical response. The patient can then be switched to oral ciprofloxacin, given its bioavailability and penetration to bone. Treatment may be required for 6 to 8 weeks. Although extensive surgical treatment was previously required, its use is now limited to diagnostic confirmation or débridement of granulation tissue. Although some have recommended hyperbaric treatment for advanced disease with significant skull base or intracranial involvement, there is little evidence of its effectiveness.

Disposition The decision for admission versus outpatient management should be made in consultation with an otolaryngologist.

as a complication of leukemia, mononucleosis, sarcoma of the temporal bone, and Kawasaki disease. Acute mastoiditis is a natural extension of middle ear infections because the mastoid air cells are generally inflamed during an episode of AOM. The aditus ad antrum is a narrow connection between the middle ear and mastoid air cells. If this connection becomes blocked, a closed space is formed, with the potential for abscess development and bone destruction. The infection may spread from the mastoid air cells by venous channels, resulting in inflammation of the overlying periosteum. Progression results in the destruction of the mastoid bone trabeculae and coalescence of the cells, resulting in acute mastoid osteitis or coalescent mastoiditis. The resulting pus may track through many routes: (1) through the aditus ad antrum, with resultant spontaneous resolution; (2) laterally to the surface of the mastoid process, resulting in a subperiosteal abscess; (3) anteriorly, forming an abscess below the pinna or behind the sternocleidomastoid muscle of the neck (often called a Bezold abscess); (4) medially to the petrous air cells of the temporal bone, resulting in a rare condition known as petrositis; and (5) posterior to the occipital bone, resulting in osteomyelitis of the calvaria or a Citelli abscess. Chronic mastoiditis is generally a complication of chronic OM. There may be extensive invasion of granulation tissue from the middle ear into the mastoid air cells. Another entity, latent or masked mastoiditis, also has been described. It is indolent in nature, with minimal signs and symptoms, little or no fever, and a history of otalgia. The TM may be intact or perforated. Suspicion should be raised by the presence of intracranial complications without an apparent source. Patients at risk include newborns and immunosuppressed patients (eg, those who have undergone recent chemotherapy or steroid administration, diabetic or geriatric patients). S. pneumoniae continues to be the leading cause of acute mastoiditis in the post–heptavalent pneumococcal vaccine era.20 The introduction of the pneumococcal conjugate vaccine has resulted in an increase of a particularly virulent strain, serotype 19A, although the PCV-13 included this serotype. Other organisms include group A streptococci, S. aureus, H. influenzae, and P. aeruginosa.21 Chronic mastoiditis also often has mixed cultures, with P. aeruginosa being the predominant organism.

Clinical Features Clinical findings in acute mastoiditis include fever, headache, otalgia, and erythema. Pain is universally present. There are no specific diagnostic criteria, but the most common physical findings are postauricular erythema and tenderness, protrusion of the auricle, and an abnormal TM. The TM is similar to that in AOM— erythema, bulging, and decreased mobility—but may be normal in 10% of cases. Suspicion should be heightened if symptoms of AOM have lasted longer than 2 weeks. In chronic mastoiditis, symptoms include persistent drainage through the perforated TM, redness, edema, and retroauricular sensitivity.

Differential Diagnoses

MASTOIDITIS

The differential diagnosis includes severe otitis media, external otitis, skull fracture, lymphadenopathy or lymphadenitis, and deep space neck infections.

Principles

Diagnostic Testing

Mastoiditis is the most frequent suppurative complication of OM, although the incidence of acute and chronic mastoiditis has decreased significantly since the advent of antibiotics. Although it is still associated primarily with AOM, some patients have not had a preceding episode of OM. Mastoiditis also has been described

Although the diagnosis of mastoiditis can be made clinically in patients with typical findings, a CT scan is indicated in patients with neurologic symptoms, when an intracranial complication is suspected, or there is failure to improve with conservative therapy.22 Fig. 62.1 is a CT scan of acute mastoiditis.

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Clinical Features The physical examination includes a thorough inspection of the external canal and TM integrity.

Differential Diagnoses The differential for hearing loss is broad and can be differentiated into causes that involve the outer, middle, or inner ear. Outer ear causes include cerumen impaction and OE. Middle ear causes include otitis media and tympanic membrane perforation. Inner ear causes include medications, barotrauma, and autoimmune disease.

Diagnostic Testing

Fig. 62.1.  CT scan of mastoiditis. (From McWhorter AJ, Limb CJ, Niparko JK: Otologic and skull base emergencies. In Eisele DW, McQuone SJ, editors: Emergencies of the head and neck, St. Louis, 2000, Mosby, p 384.)

Weber’s test for hearing and Rinne’s test may help in distinguishing conductive versus sensorineural deficits. A comprehensive neurologic examination, including cranial nerve and cerebellar testing, may localize brainstem involvement. Laboratory testing and CT scanning are not indicated in the ED evaluation unless the physical examination points to a space-occupying lesion (ie, focal neurologic deficits not referable to the ear). MRI of the brain with gadolinium is the study of choice to identify retrocochlear pathology but should be performed in consultation with an otolaryngologist.

Management

Management

The initial treatment of choice in the emergency department is the administration of antibiotics, such as vancomycin, 15 to 20 mg IV bid, and a third-generation cephalosporin such as ceftriaxone (50 mg/kg per day). Surgical procedures may range from myringotomy and tympanostomy tube placement (for drainage and identification of the offending organism) to mastoidectomy and drainage for more extensive disease progression.

A tapered dose of oral steroids is the most common treatment, although their efficacy is unproven. The dose is 1 mg/kg, up to 60 mg, tapered over 10 to 14 days.24 Additional treatments have included intratympanic steroids, hyperbaric oxygen, antiviral therapy, zinc,25 vasoactive and hemodilution therapies, dextran, and magnesium, all with mixed results. Given the lack of treatment options for this condition, we recommend that a steroid taper be offered.

Disposition Hospitalization is usually necessary for the administration of IV antibiotics. Early otolaryngologic referral is also recommended for possible aspiration and drainage of the middle ear, as well as the management of any potential complications.

SUDDEN HEARING LOSS Principles Sudden sensorineural hearing loss (SSNHL), defined as the idiopathic loss of hearing of 30 dB over at least three test frequencies occurring over a period of less than 3 days, is considered an otolaryngologic emergency. Any age group can be affected, but the peak incidence occurs in the fifth or sixth decade of life, with an equal gender distribution. The overall incidence ranges from 5 to 20/100,000 people/year. Its severity ranges from difficulty with conversation to complete hearing loss. SSNHL is idiopathic in 70% of cases, infectious in 13%, and related to otologic disease, trauma, vascular disease, hematologic disorders, or neoplasm in the vast majority of other cases.23 A delay in diagnosis is common because the patient may report ear fullness that is often attributed to cerumen impaction or congestion from upper respiratory infections. Tinnitus is a common finding. The likelihood of recovery is related to the severity of the hearing loss, age of the patient, and associated vestibular symptoms. A history should include the time of onset, history of trauma or recent illnesses, medications, and presence of otologic and neurologic symptoms.

Disposition Patients should get expeditious ENT referral on discharge from the ED.

EPISTAXIS Principles Epistaxis is a common otolaryngologic problem, with 60% of people experiencing it in their lifetime, although only 6% require medical treatment.26 It accounts for about 1 in 200 emergency room visits,27 with less than 0.2% ultimately requiring hospitalization.28 There is a bimodal distribution of children younger than 10 years and adults older than 50 years. Epistaxis is more common in colder seasons and in northern climates because of decreased humidity and subsequent drying of the nasal mucosa.29 Nasal bleeding is a frightening condition for patients but is seldom lifethreatening. A solid understanding of physiology and treatment allows for prompt and efficient management of the disorder. Anterior epistaxis accounts for 90% of all nosebleeds and usually involves Kiesselbach’s plexus on the anteroinferior nasal septum. Epistaxis is unilateral and can be controlled with anterior packing. Accounting for 10% of nosebleeds, and usually arising from a posterior branch of the sphenopalatine artery, posterior epistaxis differs from anterior bleeding in that it is more severe and occurs mostly in older adults with multiple comordities.30 Three arteries with anastomoses between them supply the nasal area. The sphenopalatine artery supplies the turbinates and

CHAPTER 62  Otolaryngology

Anterior ethmoidal artery

Posterior ethmoidal artery

Kiesselbach's area

BOX 62.1 

Causes of Epistaxis LOCAL CAUSES

Nasopalatine (septal) branch of sphenopalatine artery

Septal branch of superior labial artery

Greater palatine artery Fig. 62.2.  Arterial supply to the medial wall of the nose.

meatus laterally and the posterior and inferior septum medially. The anterior and posterior ethmoidal arteries from the ophthalmic branch of the internal carotid artery supply the superior mucosa medially and laterally. The superior labial branch of the facial artery provides circulation to the anterior mucosal septum and anterior lateral mucosa (Fig. 62.2). There are many reasons for epistaxis, but the most common are an upper respiratory infection with concomitant mucosal congestion and vasodilation and trauma, either accidental or iatrogenic (ie, nose picking; Box 62.1).

Clinical Features A past medical history with particular emphasis on trauma, medical conditions, and medications that could cause epistaxis should be elicited. Patients often are anxious and hypertensive. An elevated blood pressure is usually from stress and anxiety and resolves with treatment. Hypertension has never been shown to cause epistaxis, although it can worsen the bleeding when present.31 Sedation with a benzodiazepine or narcotic may help these patients.

Differential Diagnosis The differential diagnosis includes nasal trauma, infections, nasal foreign bodies, and bleeding disorders.

Diagnostic Testing Identifying the source of the bleeding is often difficult. If the nose is actively bleeding, the patient should clear clots by blowing the nose and then applying bilateral pressure on the nasal septum by compressing the cartilaginous part of the nose for 10 to 15 minutes. Spraying oxymetazoline into each nare twice before applying pressure will optimize hemostasis and facilitate inspection after the pressure is released. This simple maneuver also educates the patient on how to self-manage further episodes. It is important to optimize the examination. The floor of the nose should be parallel to the room floor. If the head is tilted, only the anterior and upper aspect of the nares can be visualized. The nasal speculum should be opened in a vertical direction rather than side to side in the nares, so as not to obscure the septum, which is the area of greatest interest. During this time, materials for illumination, suction, visualization, and treatment should be assembled. Discharge without identification and treatment of the bleeding site often results in recurrences. Anterior clots may give the appearance of posterior epistaxis if the blood runs posteriorly. Persistent bleeding should be controlled with pledgets soaked in cocaine, lidocaine-epinephrine, or oxymetazoline to promote

Nasal or facial trauma Upper respiratory tract infections Nose picking Allergies Low home humidity Nasal polyps Foreign body in the nose Environmental irritants Nasopharyngeal mucormycosis Traumatic internal carotid artery aneurysm Chlamydial rhinitis neonatorum Neoplasms Septal deviation Surgery (postoperative epistaxis)

IDIOPATHIC EPISTAXIS Habitual Familial

SYSTEMIC CAUSES

Atherosclerosis of nasal blood vessels Anticoagulant therapy Pregnancy Barotrauma Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) Blood dyscrasias (eg, hemophilia, leukemia, lymphoma, polycythemia vera, anemias, idiopathic thrombocytopenic purpura, granulocytosis, inherited platelet disorders, acquired platelet disorders [ie, aspirin use]) Hepatic disease Rupture of internal carotid artery aneurysm Diabetes mellitus Alcoholism Vitamin K deficiency Folic acid deficiency Chronic nephritis Chemotherapy Blood transfusion reactions Migraine headache Chronic use of nasal vasoconstrictors Cocaine use Drug induced thrombocytopenia

vasoconstriction and anesthesia. Routine laboratory testing is usually unnecessary unless the patient is anticoagulated or has an underlying condition.

Management Identify and treat the source of bleeding, because the most significant risk factor for recurrent bleeding is not identifying the bleeding point.32 Application of silver nitrate chemically cauterizes the area but is often unsuccessful during active bleeding, so hemostasis should be secured first. With 4 to 5 seconds of application, nitric acid is formed and coagulates tissue. Coagulation should never be maintained longer than 15 seconds because septal damage may occur. The area should be cauterized from the periphery to the center and superiorly to inferiorly to avoid blood, which renders the silver nitrate sticks ineffectual. Bilateral application of silver nitrate to the septum is not advised because it may deprive the septum of a blood supply and theoretically could lead to necrosis.

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If cautery is unsuccessful, topical thrombogenic agents, such as absorbable gelatin sponge (Gelfoam) and absorbable knitted fabric (Surgicel), can be tried. Tranexamic acid may be an option if bleeding continues. Tranexamic acid works by irreversibly binding and blocking the lysine binding sites on plasminogen molecules, resulting in inhibition of plasminogen activator and fibrinolysis. It has also been successfully used in 109 patients and resulted in much quicker resolution of bleeding and faster ED discharge when compared to nasal packing.33 The injectable solution (500 mg in 5 mL) is applied to a 15-cm nasal pledget and applied to the anterior nares.33 If bleeding persists, the next step is the use of a nasal tampon. Nasal tampons work by three mechanisms: direct pressure, decreased bleeding from mucosal irritation from the foreign body, and indirect pressure from further surrounding clot formation. Cutting them to fit the contour of the nares and lubricating them with an antibiotic ointment makes the application easier. For large noses, a second tampon may be required. Occasionally, for uncontrolled bleeding despite the presence of a tampon, a second tampon should be inserted into the opposite nare. If bleeding still continues, a nasal balloon catheter with fibrin colloid material, such as Rapid Rhino (Smith & Nephew, Austin, TX), may be used. These devices are moistened with saline, so lubricants are unnecessary. They are placed in the floor of the nose and inflated with air. The fibrin colloid forms a hemostatic dressing. A second balloon in the opposite nose may be required if one side is unsuccessful. Toxic shock syndrome (TSS) due to S. aureus has been reported in patients with nasal packing. Although many providers prophylactically give antibiotics after nasal packing, no study has shown that antibiotics are preventive for TSS or sinusitis, and the incidence of TSS is rare (16/100,000 population). We do not recommend routine antibiotic prophylaxis after nasal packing. Packing is uncomfortable and the patient may require opioids in the ED and on discharge. The packs are left in for 48 hours to minimize rebleeding and removed at 48 hours to avoid tissue necrosis associated with prolonged placement. Posterior epistaxis is suggested when bleeding occurs with a properly placed anterior nasal pack. In this case, a posterior pack is necessary with a Foley catheter or commercially available balloon. A standard Foley catheter may be inserted into the nasopharynx, partially inflated with 5 to 7 mL of water, and then pulled anteriorly, creating pressure posteriorly with an additional 5 to 7 mL of water added to the balloon, but caution should be exercised to avoid pressure necrosis. Water, rather than saline, should be used because saline can crystallize and cause problems with balloon deflation. Vaseline gauze should be packed firmly around the catheter anteriorly. Fig. 62.3 shows how the Foley catheter is placed. The commercially available devices have anterior and posterior balloons. Similar to Foley placement, the device is placed into the nose, inflated, and pulled anteriorly. Once seated, the anterior balloon should be slowly inflated to the point that the patient can tolerate. If these techniques do not provide successful control, otolaryngologic consultation is necessary. Surgical ligation has been the treatment of choice for intractable bleeding but endovascular embolization has emerged as a treatment alternative. The decision to choose surgery over embolization is influenced by factors such as patient comorbidity, presence of anticoagulation, institutional experience, patient preference, and health care costs.27,34,35 Transnasal endoscopic surgery has advantages in that it visualizes bleeding location, improves the diagnosis of other causes, and is associated with lower health care costs and complications such as blindness. The advantages of embolization include avoiding general anesthesia, improving the diagnosis of vascular pathology, and causing less trauma to the nasal mucosa.30 In one national survey, patients who underwent endovascular embolization had

higher rates of head and neck cancer, hereditary hemorrhagic telangiectasia, and arteriovenous malformation compared with patients who underwent surgical ligation.34

Disposition There has been concern that patients with posterior nasal packs may develop hypoxia as a result of a nasopulmonary reflex. However, there is little evidence to support this theory.36 Adverse respiratory events are due to a combination of factors such as sedation, underlying cardiovascular or pulmonary disease, and severe obstructive sleep apnea.37 Most patients with posterior nasal packing can be admitted to a setting with continuous pulse oximetry, but patients with serious comorbidities such as heart disease or obstructive sleep apnea may require a higher level of care.38

SIALOLITHIASIS Stones of the salivary glands occur in 1% of the population. They are usually found in those between 30 and 50 years of age. The most common gland affected is the submandibular (submaxillary) gland, accounting for 80% to 95% of cases. Stones are found less commonly in the sublingual and parotid glands. Sialolithiasis is uncommon in children, occurring in only 3% to 5% of the population.37 The exact causative mechanism is unclear, but sialolithiasis is thought to be due to increased viscosity of the saliva and the long upward curvature of the submandibular (Wharton’s) duct. Stasis and inflammation result in precipitation of calcified stones after a nidus of a complex glycoprotein combines with calcium and phosphate. Risk factors include dehydration, diuretic or anticholinergic medications, trauma, gout, and a history of smoking.39

Clinical Features Leading to swelling and pain, obstruction by a sialolith is usually associated with mealtime, when salivary secretion is enhanced.40 Patients generally present with pain, swelling, and tenderness of the gland. If the gland is infected, the patient may have systemic symptoms, such as fever or chills. The area may be erythematous, with purulence coming from the duct, a condition termed sialadenitis.41 S. aureus, Streptococcus viridans, S. pneumoniae, and H. influenzae predominate in bacterial infections. Children differ in that they have a shorter duration of symptoms, and their stones present more distally in ducts than those found in adults.37

Differential Diagnosis The differential diagnosis includes salivary gland pathology, lymph node disease, granulomatous process, soft tissue mass, and neoplastic lesion.

Diagnostic Testing CT without contrast is very sensitive for calculi of all sizes and remains the gold standard, although there is the associated risk of ionizing radiation. Although there have been reports of ultrasonography recognizing up to 90% of stones larger than 2 mm, it does not allow reliable exclusion of small salivary calculi.42 Both modalities may help identify other causes of inflammation, such as an abscess or cellulitis.

Management If the stone is palpable, gently massage the gland in an attempt to extract the stone. Additional measures include sialogogues (tart

CHAPTER 62  Otolaryngology

EPISTAXIS MANAGEMENT: POSTERIOR PACKING WITH INFLATABLE DEVICES A 1

2

3

Inflate the balloon halfway (5–7 mL) Insert a 12-Fr Foley catheter through the naris and into the posterior pharynx.

4

Look into the mouth to confirm that the catheter is properly positioned.

5

Inflate the balloon halfway with about 5–7 mL of water.

6

Clamp here

Traction

Slowly pull the catheter into the posterior nasopharynx up against the posterior aspect of the middle turbinate.

Foley catheter in proper position in the posterior nasopharynx. Inflate the balloon with another 5–7 mL of water.

While maintaining traction, place anterior packing with layered gauze. Packing of the opposite side may be required to prevent septal deviation. Place a piece of gauze on the exposed catheter and secure with an umbilical clamp.

B 1

Posterior balloon

2

Anterior balloon

Place gauze here to avoid maceration

Airway tube

Double-balloon epistaxis catheters have both an anterior and posterior balloon, and some have an integral airway tube. These devices serve as an anterior and posterior pack. They are easily inserted and are often successful in the temporary control of posterior epistaxis in the ED.

3

Insert the lubricated device along the nasal floor as far back as possible. Inflate the posterior balloon halfway with air, apply traction to pull the balloon up against the middle turbinate, and then complete the inflation. Maintain the position of the balloon and then inflate the anterior balloon with 30 mL of air.

This patient with posterior epistaxis was successfully treated in the ED and discharged. Historically, most patients with posterior packs were admitted to the hospital; however, the ease and safety of balloon devices allow selected patients to be treated as outpatients. Consider admission for older adults and those with pulmonary or cardiovascular disease.

Fig. 62.3.  Management of epistaxis—posterior packing with inflatable devices. A, Foley catheter technique. B, Dual-balloon tamponade catheter. (Adapted from Riviello RJ: Otolaryngologic procedures. In Roberts JR: Roberts and Hedges’ clinical procedures in emergency medicine, Philadelphia, 2013, Elsevier/ Saunders, p 1330.)

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hard candies to promote glandular secretions), analgesia with antiinflammatory medications, or opioids. When infection is present, antibiotics covering the affected organisms, such as cephalexin, 500 mg qid, or clindamycin, 450 mg tid (in the penicillinallergic patient), are appropriate.

Disposition Stones larger than 5 mm or stones located within the gland or in the proximal duct are often resistant to conservative measures. These may require surgical or minimal invasive treatment by an otolaryngologist or oral surgeon.43

NECK MASSES Principles Neck masses are a relatively common clinical finding, with a multitude of causes. The differential diagnosis can generally be broken down into three categories—inflammatory, congenital, or neoplastic. Children and young adults are more likely to have benign disorders, such as inflammatory or congenital abnormalities, including thyroglossal or branchial cleft cysts. Adult neck masses are more likely to be neoplastic. In general, 80% of nonthyroid neck masses in adults are neoplastic, of which 80% are malignant. In children, however, more than 80% of neck masses are benign. This is often referred to as the rule of 80, or the 80% rule. Risk factors that may predispose patients to ENT malignancies include alcohol and tobacco use, viruses such as herpes, genetics, diet, and excessive exposures to ultraviolet sunlight, dust, or chemicals. Identifying the parotid and submandibular glands, thyroid cartilage, thyroid gland, and lymph nodes can help distinguish normal structures from other masses (Fig. 62.4). The neck is divided into cervical triangles, with the sternocleidomastoid

I

IV

III

II

muscle as the common boundary. The anterior portion is bordered by the midline of the neck, inferior aspect of the mandible superiorly, and anterior border of the neck posteriorly. Lesions of the skin, scalp, oral cavity, oropharynx, hypopharynx, larynx, and tongue may manifest here. The posterior triangle is bordered by the sternocleidomastoid anteriorly, posteriorly by the trapezius muscle, and inferiorly by the clavicle. Lesions in this area may include those from the nasopharynx and metastatic lesions from the lung and gastrointestinal and genitourinary tracts.

Clinical Features Important associated symptoms include dysphagia, odynophagia, otalgia, stridor, speech disorders, and globus phenomena. Dysphagia, or difficulty swallowing, may be caused by physical obstruction or neurologic disorders. Odynophagia is pain on swallowing and can have a number of causes, such as tonsillitis or carcinoma of the pharynx. In an adult, a sore throat that lasts for several weeks should raise the suspicion of a neoplastic process. Otalgia is pain felt in the ear that may be referred from the larynx, pharynx, or cranial nerves V, IX, or X. Referred ear pain is an ominous sign in adults and should be presumed to be cancer until proved otherwise. Similarly, unilateral OME in adults should be considered nasopharyngeal carcinoma until proven otherwise. Stridor, specifically inspiratory stridor, is diagnostic of upper airway obstruction. It localizes a lesion to above or at the level of the larynx. In adults, the presence of stridor with a neck mass increases the possibility of carcinoma. Speech disorders, particularly so-called hot potato speech, are suggestive of space-occupying lesions above the oropharynx, such as a peritonsillar abscess. Globus is the symptom of having a lump in the throat. It has occurred in almost everyone at one time or another, is localized to the pharynx, and is often a functional complaint. Hoarseness is a fairly common complaint, with a myriad of causes ranging from viral pharyngitis to laryngeal cancer. Also, similar to the term dizziness, the term hoarseness has many descriptions, including breathiness, muffling, harshness, scratchiness, and unnatural deepening of the voice. Hoarseness lasting longer than 2 weeks should be investigated further. Additional history about the location of the mass, rate of growth, presence of pain, and constitutional symptoms, such as fever, night sweats, and weight loss, are also helpful. The head and neck examination may identify masses, lesions, mucosal ulcerations or discolorations, and cranial nerve abnormalities. The mass itself should be palpated for location, size, and consistency. Benign lymph nodes are generally mobile, soft, fleshy, and smaller than 1 to 1.5 cm, so any hard nodes larger than 1.5 cm with decreased mobility should be considered abnormal and as warning signs of malignancy.

Differential Diagnoses V

Box 62.2 lists common possibilities for the differential diagnosis of neck masses.

VII VI VIII

Fig. 62.4.  Major lymph node groups in the head and neck. I, Parotid nodes; II, submental nodes; III, submandibular nodes; IV, jugulodigastric nodes (superior jugular nodes); V, midjugular nodes; VI, lower jugular nodes; VII, spinal accessory nodes; VIII, subclavian nodes. Groups VI and VII are often termed scalene nodes. (Adapted from Moloy PJ: How to [and how not to] manage the patient with lump in the neck. In American Academy of Otolaryngology–Head and Neck Surgery Foundation: Common problems of the head and neck region, Philadelphia, 1995, WB Saunders, p 134.)

Diagnostic Testing The diagnostic strategy is tailored to results of the history and physical examination. Patients with hoarseness lasting longer than 2 weeks should be referred to an otolaryngologist for a flexible endoscopic examination unless they have developed acute stridor, dyspnea, or sense of acute deterioration. These patients should have otolaryngologic consultation in the ED, and most will need flexible endoscopic examination of the upper airway. In the ED, chest radiography is an initial test to identify possible lung pathology as a source. CT of the neck with contrast is the initial study of choice to delineate significant neck masses better.

CHAPTER 62  Otolaryngology

BOX 62.2 

Differential Diagnosis of Neck Masses INFLAMMATORY

Adenitis Bacterial (Streptococcus, Staphylococcus) Viral (HIV, EBV, HSV) Fungal (coccidioidomycosis) Parasitic (toxoplasmosis) Cat scratch disease Tularemia Local cutaneous infections Sialoadenitis (parotid and submaxillary glands) Thyroiditis Mycobacterium avium-intracellulare Mycobacterium tuberculosis

CONGENITAL OR DEVELOPMENTAL Brachial cleft cyst Thyroglossal duct cyst Dermoid cyst Cystic hydromas Torticollis Thymic masses Teratomas

Ranula Lymphangioma Laryngocele

NEOPLASTIC

Benign Mesenchymal tumors (eg, lipoma, fibroma, neural tumor) Salivary gland masses Vascular abnormalities (eg, hemangioma, AVM, lymphangioma, aneurysm) Malignant Primary tumors Sarcoma Salivary gland tumor Thyroid or parathyroid tumors Lymphoma Metastasis From primary head and neck tumors From infraclavicular primary tumors (eg, lung or esophageal cancer)

AVM, Arteriovenous malformation; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; HSV, herpes simplex virus.

Management and Disposition Most masses in children are inflammatory. Thus, it is a reasonable strategy to start the patient on antibiotics, with a 2-week follow-up. If inflammation is thought to be the cause of the neck mass in an

adult, a similar strategy can be used. However, adults need ENT referral if the mass does not resolve in 2 weeks, is enlarging or fixed, or is associated with matted cervical lymph nodes, or if the masses are noted in the parotid or thyroid gland.

KEY CONCEPTS • Most cases of AOM resolve spontaneously. Nontoxic children from 6 months to 2 years of age with unilateral AOM and those older than 2 years with unilateral or bilateral AOM may be observed for 3 days to determine whether antibiotics are required. When indicated, amoxicillin is the initial choice for treatment of AOM, 80 to 90 mg/kg per day. • Otitis externa is treated with topical antibiotic drops. Only fluoroquinolone drops are FDA-approved for use when a tympanic perforation may be present. Necrotizing OE should be considered in immunocompromised patients who have persistent otitis externa. • Patients with epistaxis with posterior nasal packing should be admitted to the hospital.

• Bullous myringitis is caused by the usual organisms that cause otitis media. • Adult patients with AOM should be treated with amoxicillin, 500 mg tid. • The diagnosis of AOM is made by a bulging TM and signs and symptoms of acute infection. • Acute hearing loss is most often idiopathic. A 10- to 14-day steroid taper is usually prescribed but is not known to provide benefit. • Hoarseness or an unexplained neck mass that persists for longer than 2 weeks requires ENT referral.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 62  Otolaryngology

REFERENCES 1. Ahmed A, Shapiro NL, Bhattacharyya N: Incremental health care utilization and costs for acute otitis media in children. Laryngoscope 124:301, 2014. 2. Dickson G: Acute otitis media. Prim Care 41:11, 2014. 3. Qureishi A, Lee Y, Belfield K, et al: Update on otitis media-prevention and treatment. Infect Drug Resist 7:15, 2014. 4. Laine MK, Thatiinen PA, Ruuskanen O, et al: Symptoms or symptom base scores cannot predict acute otitis media at otitis prone age. Pediatrics 125:e1154, 2010. 5. Shaikh N, Hoberman A, Rosckett HE, et al: Development of an algorithm for the diagnosis of otitis media. Acad Pediatr 12:214, 2012. 6. Block S: Improving the diagnosis of acute otitis media: seeing is believing. Pediatr Ann 42:485, 2013. 7. Daniero JJ, Clary MS, OReilly RC: Complications of otitis media. Infect Disord Drug Targets 12:267, 2012. 8. Colpaertr C, Van Rompaey Vanderveken O, et al: Intracranial complications of acute otits media. B-ENT 9:151, 2013. 9. Lieberthal AS, Carroll AE, Chonmaitree T, et al: The diagnosis and management of acute otitis media. Pediatrics 131:e964, 2013. 10. Tahtinen PA, Laine MK, Ruuskanen O, et al: Delayed versus immediate antimicrobial treatment for acute otitis media. Pediatrics 131:e964–e999, 2013. 11. Coco A, Vernacchio L, Horst M, et al: Management of acute otitis media after publication of the 2004 AAP and AAFP clinical practice guideline. Pediatrics 125:214, 2010. 12. Coker TR, et al: Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review. JAMA 304:2161, 2010. 13. Hoberman A, et al: Treatment of acute otitis media in children under 2 years of age. N Engl J Med 363:114, 2011. 14. Tähtinen PA, et al: A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med 364:116, 2011. 15. Nesbit CE, Powers MC: An evidence-based approach to managing otitis media. Pediatr Emerg Med Pract 10:1, 2013. 16. Wallace IF, Nerkaman ND, Lohr KN, et al: Surgical treatments for otitis media with effusion: a systematic review. Pediatrics 133:296, 2014. 17. Rosenfeld RM, Schwarz SR, Cannon CR, et al: Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg 150:S1, 2014. 18. Winterstein AG, Liu W, Dandan X, et al: Sensorineural hearing loss associated with neomycin eardrops and nonintact tympanic membranes. Otolaryngol Head Neck Surg 148:277, 2013. 19. Jacobsen LM, Antonelli PJ: Errors in diagnosis and management of necrotizing otitis externa. Otolaryngol Head Neck Surg 143:506, 2010. 20. Giannakopoulos P, Chrysovergis A, Xirogiannni A, et al: Microbiology of acute mastoiditis and complicated or refractory acute otitis media among hospitalized children in the postvaccination era. Pediatr Infect Dis J 33:111, 2013. 21. Harrison WL, Shargorodsky J, Gopen Q: Clinical strategies for the management of acute mastoiditis in the pediatric population. Clin Pediatr (Phila) 49:110, 2010. 22. Cheney J, Black A, Choo D: What is the best practice for acute mastoiditis in children? Laryngoscope 124:1057, 2014.

23. Chau JK, Lin JR, Atashband S, et al: Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss. Laryngoscope 120:1011, 2010. 24. Stachler RJ, Chandrasekhar SS, Archer SM, et al: Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg 146(Suppl):S1, 2012. 25. Yang CH, Ko MT, Peng JP, et al: Zinc in the treatment of idiopathic sensorineural loss. Laryngoscope 121:617, 2011. 26. Shargorodsky J, Bleier BS, Holbrook EH, et al: Outcome analysis in epistaxis management: development of therapeutic algorithm. J Otolaryngol Head Neck Surg 149:390, 2013. 27. Rudmik L, Smith TL: Management of intractable spontaneous epistaxis. Am J Rhinol Allergy 25:55, 2012. 28. Villwock JA, Jones K: Recent trends in epistaxis management in the United States 2008–2010. JAMA Otolaryngol Head Neck Surg 139:1279, 2013. 29. Purkey MR, Seeskin Z, Chandra R: Seasonal variation and predictors of epistaxis. Laryngoscope 124:2028, 2014. 30. Rotenberg B, Tam S: Respiratory complications from nasal packing: systematic review. J Otolaryngol Head Neck Surg 39:606, 2010. 31. Kikidis D, Tsioufis K, Papanikolaou V, et al: Is epistaxis associated with arterial hypertension? A systematic review of the literature. Eur Arch Otorhinolaryngol 271:237, 2014. 32. Ando Y, Limura J, Arai S, et al: Risk factors for recurrent epistaxis: importance of initial treatment. Auris Nasus Larynx 41:41, 2014. 33. Zahed R, Moharamzadeh P, AlizadehArasi S, et al: A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med 31:1389, 2013. 34. Brinjikji W, Kallmes DF, Clof HJ: Trends in epistaxis embolization in the United States: a study of nationwide inpatient sample 2003–2010. J Vasc Interv Radiol 24:969, 2013. 35. Krajina A, Chrobok V: Radiological diagnosis and management of epistaxis. Cardiovasc Intervent Radiol 37:26, 2014. 36. Banglawala SM, Gill MS, Dhillion N, et al: Nasal packing after septoplasty cardiopulmonary impact. JAMA Otolaryngol Head Neck Surg 140:253, 2014. 37. Corrales CE, Goode RL: Should patients with posterior nasal packing require ICU admission? Laryngoscope 123:2928, 2013. 38. Murphy CM, Franzen DS: Sialolith in a two-year-old. J Emerg Med 43:e199, 2010. 39. Medina J, Corey N, Hahn B: Acute Wharton’s duct sialadenitis and submandibular infection. J Emerg Med 44:e125, 2012. 40. Delli D, Spijkervet FK, Vissink A: Salivary gland disease: infections, sialolithiasis and mucoceles. Monogr Oral Sci 24:135, 2014. 41. Kanekar SG, Mannion K, Zacharia T: Parotid space: anatomic imaging. Otolaryngol Clin N Am 45:1253, 2012. 42. Terraz S, Poletti PA, Dulguerov P, et al: How reliable is sonography in the assessment of sialolithiasis? AJR Am J Roentgenol 201:W104, 2013. 43. Hoffman B: Sonographic bedside detection of sialolithiasis with submandibular gland obstruction. Am J Emerg Med 29:e574, 2011.

CHAPTER 62: QUESTIONS & ANSWERS 62.1. Which of the following clinical symptoms is most useful in diagnosing acute otitis media (OM)? A. Cough B. Decreased appetite C. Ear pain D. Fever E. Vomiting Answer: C. Although all the symptoms of acute OM are nonspecific, ear pain appears to be the most useful. 62.2. A 56-year-old man presents with sudden onset of hearing loss in his left ear. He also complains of tinnitus. His neurologic examination is otherwise unremarkable. What should be the next step in the patient’s management? A. Consult a neurologist. B. Consult an otolaryngologist. C. Obtain a head computed tomography (CT) scan. D. Obtain a magnetic resonance imaging (MRI) scan with gadolinium. E. Start a steroid taper. Answer: B. Sudden sensorineural hearing within 72 hours is considered an otolaryngologic emergency. The evaluation and potential treatment options, including steroids, hyperbaric oxygen, and antiviral agents, are best performed in consultation with an otolaryngologist.

62.3. A 30-year-old woman presents with onset of a severe right posterior occipital headache and low-grade fever. Her physical examination reveals an area of erythema and swelling posterior to the right ear and a nonmobile tympanic membrane in that ear. What is the most appropriate next diagnostic step? A. ENT referral STAT to the operating room (OR) B. CT scan C. Lumbar puncture D. MRI with gadolinium E. No further diagnostic evaluation necessary Answer: B. Clinical findings in acute mastoiditis may include fever, headache, otalgia, and posterior auricular erythema and tenderness. Although there are no specific diagnostic criteria, an initial step would be a CT scan to identify mastoid inflammation and possible bony erosion. MRI would be indicated if there is concern for intracranial extension. 62.4. All the following are implicated as risk factors in OM except: A. Children with cleft palate B. Daycare attendance C. Female gender D. Immunocompromised patient E. Parental smoking

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Answer: C. Male gender appears to be a risk factor for middle ear disease, as well as daycare attendance, parental smoking, immunocompromised patients, and children with anatomic abnormalities such as cleft palate or Down syndrome. Breast-feeding appears to be protective. 62.5. An 18-month-old boy returns to the emergency department (ED) 4 days after being diagnosed with left OM. He was prescribed amoxicillin, 90 mg/kg/day, and the parents reported compliance. He has continued ear tugging, fever, and irritability. He is tolerating PO nutrition with no vomiting or diarrhea. Physical examination reveals an alert crying male with oral temperature 101.5°F, heart rate 136 beats/min, and respiratory rate 24 breaths/min. His physical examination is otherwise negative except for severe erythema of the left tympanic membrane, with obscure landmarks and loss of mobility. What is the most appropriate next step in this patient’s management? A. Admit for intravenous antibiotics. B. Change therapy to an oral cephalosporin. C. Draw blood cultures and continue current amoxicillin regimen. D. Intramuscular ceftriaxone is given. E. Lumbar puncture is performed. Answer: D. Otitis media treatment failures at 3 days should receive intramuscular ceftriaxone. Continued use of a failing regimen would not be indicated. The child exhibits no signs or symptoms warranting a lumbar puncture and no immediate criteria for hospital admission. 62.6. A 13-year-old diabetic girl presents with left otalgia, left facial palsy, and fever. Physical examination reveals a left peripheral seventh nerve palsy, intense left otitis externa, diffuse tenderness of the pinna, and mild weakness of the left trapezius muscle. What is the most likely diagnosis? A. Acute mastoiditis B. Left temporal brain abscess resulting from left-sided otitis C. Malignant otitis externa D. Meningitis E. Sigmoid sinus thrombosis

Answer: C. Necrotizing (malignant) otitis externa is a result of chronic otitis externa often seen in immunocompromised patients. The facial nerve is the cranial nerve usually affected, but the glossopharyngeal, vagal, accessory, abducens, and trigeminal nerves may also be involved. When otoscopic view permits, granulation tissue in the floor of the external canal at the bone–cartilage junction is characteristic. CT is the imaging technique of choice and is able to indicate bony erosions and abscess formation. Ciprofloxacin is the antibiotic of choice. All the other choices are recognized complications. 62.7. The management of anterior and posterior epistaxis is similar regarding which of the following? A. Antibiotic requirements after packing B. Duration of packing C. Indications for hospitalization D. Surveillance for secondary complications E. Value of topical cauterization Answer: C. Strong evidence for postpacking of antibiotics are lacking in both situations. Anterior packs are left in place for approximately 48 hours, whereas posterior packs may require 3 to 5 days. Patients requiring posterior nasal packs for epistaxis typically need hospitalization for supplemental oxygen and surveillance for pack expulsion with rebleeding, dysrhythmias, bradycardia, aspiration, and stroke. 62.8. Which of the following statements is true regarding inspiratory stridor? A. It implies a palatal or uveal obstruction. B. It is diagnostic of tracheal pathology. C. It is typically accompanied by hoarseness. D. It localizes a lesion at or above the vocal cord. E. It may be seen with extremely severe asthma exacerbations. Answer: D. Inspiratory respiratory distress (stridor) implies an extrathoracic flow obstruction. This may be laryngeal, epiglottis, or pharyngeal. Asthma, emphysema, and aspirated foreign bodies all have expiratory airflow limitations. Inspiratory stridor may or may not directly involve the larynx and may not be accompanied by hoarseness.

SECTION TWO

Pulmonary System C H A P T E R 63 

Asthma Richard M. Nowak  |  Glenn F. Tokarski PRINCIPLES Background and Importance The word asthma, derived from the Greek ασυµα, signifies panting and was used initially as a synonym for “breathlessness.” In 1698, Floyer published A Treatise of the Asthma, in which he attempted to differentiate asthma more clearly from other pulmonary disorders. Subsequent definitions of asthma highlight concepts of airway hyperresponsiveness, bronchospasm, reversible airway obstruction, and inflammation, emphasizing the many facets of this complex disease. Asthma is a chronic respiratory disease characterized by periods of variable and recurring symptoms, airflow obstruction, and bronchial hyperresponsiveness that manifests clinically as attacks of impaired breathing.1,2 Asthma is an inflammatory disease; repetitive episodes of acute superimposed on chronic airway inflammation are responsible for alterations in airway function and result in irreversible structural airway changes. Control of asthma symptoms ultimately depends on ameliorating airway inflammation. Genetic, social, physiologic, and environmental factors influence the expression and control of asthma symptoms. Asthma is thus a complex interaction of the immune system, the environment, and genetic predispositions, which combine to alter airway structure and function. Successful emergency department (ED) management of asthma must address the multiple factors that result in airway dysfunction. In 2013, it was estimated that 39.5 million Americans had been diagnosed with asthma by a health professional within their lifetime.3 Asthma is more prevalent in children than adults, in females than males, and in African Americans than whites or Hispanics (Fig. 63.1).4 In the United States, asthma is more prevalent in impoverished and obese persons, cigarette smokers, and those residing in nonmetropolitan locales (Fig. 63.2).5 The northeastern states have the highest asthma prevalence.6 African American adults had an ED visit rate nearly twice that of whites and a hospitalization rate 2.3 times greater (Fig. 63.3). Over 3500 deaths due to asthma were reported in 2013 in the United States.7 The female death rate from asthma was 1.03 times higher than males. African Americans were two to three times more likely to die from asthma than whites, Hispanics, and other races. Decreases in asthma death rates have been noted from 1999 to 2010 (Fig. 63.4). The highest death rate is reported among adults 65 years old and older and the lowest among children 0 to 4 years old. The estimated financial burden of asthma totaled $56 billion in the United States in 2013 with approximately 89% attributable to direct costs (hospital care and physician services).5 In 2008, asthma accounted for an estimated 14.2 million lost work days and 10.5 million lost school days.3

Developed nations have higher rates of asthma, which suggests that urbanization and westernization are correlated with increased asthma prevalence. Migrants who move from an area of low asthma prevalence to an area of high asthma prevalence assume increased asthma prevalence, suggesting that environmental factors play a role. Urban areas in the United States (New York City, Los Angeles, and Chicago) have high mortality rates associated with asthma, indicating that poverty and lack of access to medical care may also be major determinants of asthma complications. Factors that contribute to asthma morbidity and mortality include under-treatment; of acute episodes by emergency clinicians; overuse of prescribed or over-the-counter medications leading to delays in seeking treatment; failure of emergency clinicians to consider previous ED visits, hospitalizations, or lifethreatening episodes of asthma; and failure to initiate corticosteroid therapy early in the course of an exacerbation. Cost of asthma care is a barrier to asthma management; African American and Hispanic adults identify costs related to seeking asthma care with a primary care physician and/or an asthma specialist and the cost of asthma medications are significant impediments.8 Over-reliance on emergency facilities for all asthma care and lack of access or compliance with ongoing asthma care are other important factors contributing to morbidity and mortality from asthma.

Anatomy and Physiology Asthma is a complex immunologically mediated condition involving a variety of cellular and airway alterations; airway inflammation and remodeling are the final common pathways that result in bronchospasm and limitation of airflow. Compared with healthy individuals, patients with asthma show bronchial hyperreactivity (hyperresponsiveness) in response to various environmental and infectious stimuli (eg, methacholine). Allergens (eg, environmental, viruses, occupational) and non-allergic stimuli (eg, exercise, aspirin-induced and menstrualrelated asthma) induce bronchoconstriction via release of mediators and metabolic products from inflammatory cells. Edema, inflammation, mucus production, and airway smooth muscle hypertrophy result in bronchoconstriction, airway obstruction, and airflow limitation. Recurrent episodes of airway inflammation result in permanent structural airway remodeling that also contributes to airway obstruction and hyperresponsiveness and decreases in the response to therapy. Necropsies of patients with fatal asthma reveal grossly inflated lungs that may fail to collapse on opening of the pleural cavities. Histologic examination reveals luminal plugs consisting of inflammatory cells, desquamated epithelial cells, and mucus. Marked thickening of the airway basement membrane, submucosal inflammatory cells, increased deposition of connective tissue, 833

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mucous gland hyperplasia, and hypertrophy of airway smooth muscle are also observed. Reports of slow-onset asthma fatalities reveal greater bronchial eosinophilia and basement membrane thickening when compared with rapid-onset fatal asthma. Reports of rapid-onset fatal asthma describe a greater number of degranulated mast cells and less mucus in the airway lumens, suggesting

that terminal events may be dominated by bronchoconstriction without excessive luminal plugging.

Pathophysiology

14 12 10 8

Age

Sex

Hispanic 5.9%

Black 9.9%

White 7.4%

Female 8.3%

0

Male 6.2%

2

Child 8.3%

4

Adult 7.0%

6

Race/Ethnicity

Fig. 63.1.  Asthma prevalence percentages in 2013 by age, sex, and race/ethnicity in the United States. (From Centers for Disease Control  and Prevention: Asthma: data, statistics, and surveillance. Available at www.cdc.gov/asthma/asthmadata.htm.)

Evidence that inflammation is a component of asthma physiology was initially derived from autopsy findings in patients with fatal asthma. The airways revealed infiltration by neutrophils, eosinophils, and mast cells and the presence of subbasement membrane thickening, loss of epithelial cell integrity, goblet cell hyperplasia, and mucous plugs. Ante mortem bronchial biopsy findings in patients with even mild degrees of asthma also demonstrate inflammatory changes in the central and peripheral airways that correlate with disease severity. Inflammatory and chemotactic cytokines produced by both resident airway and recruited inflammatory cells are identified in bronchoalveolar lavage washings and pulmonary secretions. Asthma has been divided into allergic and non-allergic types based on the presence or absence of immunoglobulin E (IgE) antibodies to common environmental antigens (pollen, dander, mites) and microbiologic antigens (bacteria, viruses). Exposure to microbes and allergens during childbirth, infancy, and childhood may confer a protective effect against atopy and suppress expression of the asthma phenotype later in life (known as the hygiene hypothesis).9 Regardless of the asthma type, a common feature is the presence of airway T-helper cells that release cytokines (eg, interleukin [IL]-4, IL-5, and IL-13) that stimulate basophil, eosinophil, mast cell, and leukocyte migration to the airways and enhance IgE production. The result is amplification of the airway

Did not graduate from high school

10.0

High school graduate

8.8

Some college

9.6

College graduate

7.5

1.5–2 L) are usually associated with malignancy but also can arise in the setting of heart failure and other conditions of volume overload. Massive effusions restrict respiratory movement, compress the lung parenchyma, and result in intrapulmonary shunting. In extremely rare cases, tension hydrothorax can develop, with a mediastinal shift and circulatory collapse.

Clinical Features Small pleural effusions often are entirely asymptomatic. Pleural inflammation, with or without effusion, is heralded by typically pleuritic pain (ie, worse with deep breathing) or pain referred to the shoulder. It is generally not until the volume of pleural fluid in an adult reaches at least 500 mL that dyspnea becomes apparent. Physical findings also depend on the size of the effusion. A pleural friction rub may be the only finding in a patient with isolated pleurisy, whereas with massive effusions, signs of cardiopulmonary compromise may be present. Classic physical signs of pleural effusion include diminished breath sounds, dullness to percussion, and decreased tactile fremitus. The simple technique of auscultatory percussion (ie, percussing the chest while listening for dullness with the stethoscope) may be even more sensitive and specific for the physical diagnosis of pleural effusion. Egophony and enhanced breath sounds are often appreciated at the superior border of the effusion because of underlying atelectatic lung tissue.

Differential Diagnosis The differential diagnosis of pleural effusion includes a wide variety disease processes characterized by dyspnea and/or chest pain, ranging from congestive heart failure and volume overload to pneumonia, PE, and pericardial effusion. Of note, many of these conditions are associated with and may coexist with pleural effusion. In any case, the presence of pleural effusion requires thoughtful consideration of the underlying disease process. Specifically, an unexplained pleural effusion should raise concern for malignancy and requires follow-up.

Diagnostic Testing When clinically suspected, the diagnosis of pleural effusion should be confirmed by chest radiography. A volume of approximately

200 mL is required before pleural effusion can be reliably demonstrated on an upright, frontal chest radiograph; a lesser amount of fluid may be visible in the posterior costophrenic gutter on a lateral projection. The classic radiographic appearance of a pleural effusion is blunting of the costophrenic angle. With larger effusions, the hemidiaphragm may be completely obscured, typically with an upwardly concave pattern, because pleural fluid tends to layer higher laterally than centrally. Pleural fluid can also extend up a major fissure and appear as a homogeneous density in the lower portion of the lung field. Massive pleural effusions can completely opacify the hemithorax (so-called white-out). In the recumbent patient, free pleural fluid gravitates superiorly, laterally, and posteriorly and thus may not be clearly discernible on a supine radiograph. If the effusion is large enough, diffuse haziness or partial opacification of a hemithorax may be seen. Other findings on the supine radiograph may include apical capping, obscuring of the hemidiaphragm, and/or a widened minor fissure. Some pleural effusions can be challenging to diagnose on plain radiographs. Clues to the presence of a subpulmonic effusion include an apparent shift of diaphragmatic dome toward the lateral chest wall and, when located on the left side, a radiodense gap between the gastric bubble and aerated lung. Loculated fluid in a pleural fissure may assume a fusiform appearance and can simulate a mass (Fig. 67.5A and B). The lateral recumbent view, although historically useful for demonstrating small loculated effusions, has been largely replaced by ultrasound or CT. Thoracic ultrasound is more sensitive than chest radiography in diagnosing and estimating the size of pleural effusions.15 Sonographically, pleural effusions typically appear as hypoechoic fluid above the diaphragm and are best visualized with a curvilinear probe in the midaxillary line (see Fig. 67.5C). Not all pleural fluid is hypoechoic; hemothorax and pyothorax may appear heterogeneous. Often, compressed lung or pleural adhesions can be visualized within the effusion, and careful observation of these findings, as well as the location of the diaphragm, liver, or spleen, can aid in the correct localization for thoracentesis or tube thoracostomy. If available in the ED, ultrasound-guided thoracentesis should be performed to decrease the risk of complications such as pneumothorax.16 CT can detect as little as 3 to 5 mL of pleural fluid and is the gold standard for the diagnosis of small pleural effusions. CT is particularly useful in distinguishing between pleural and parenchymal disease to help identify an underlying cause (eg, PE, malignancy), quantify the volume of pleural effusion, and guide thoracentesis.17 Most patients with pleural effusion should undergo diagnostic thoracentesis at some point to determine the nature of the effusion (ie, transudate, exudate) and identify an underlying cause (eg, malignancy).18 The exception to this rule would be an effusion associated with an obvious diagnosis such as heart failure or a known underlying condition such as connective tissue disease. In the ED, the clearest indication for diagnostic thoracentesis is to evaluate a life-threatening condition immediately, such as empyema or esophageal rupture in a toxic patient; in most other cases, diagnostic thoracentesis to distinguish between transudative and exudative processes can be deferred. Although numerous classification schemes have been proposed, Light’s criteria remain the most widely accepted means of differentiating transudates and exudates (Box 67.3).19 A pleural fluid pH less than 7.3 is associated with parapneumonic effusions, malignancies, rheumatoid effusions, tuberculosis, and systemic acidosis. A pH less than 7.0 strongly suggests empyema or esophageal rupture and is generally taken to be an indication for tube thoracostomy. In the case of a parapneumonic effusion, Gram staining and culture of pleural fluid are routinely performed but rarely change management.

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A

B

Diaphragm Pleural effusion

Liver

Lung

C Fig. 67.5.  A and B, Radiographs of pleural effusion along major and minor fissures. C, Ultrasound image of the right upper quadrant demonstrating the typical hypoechoic appearance of a pleural effusion.

BOX 67.3 

Light’s Criteria for Differentiating Transudates From Exudates Pleural fluid is considered an exudate if one or more of the following conditions are met: 1. Pleural fluid protein level/serum protein level exceeds 0.5. 2. Pleural fluid lactate dehydrogenase (LDH) level/serum LDH level exceeds 0.6. 3. Pleural fluid LDH level exceeds two-thirds of the upper limit of normal for the serum LDH level. From Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr: Pleural effusions: The diagnostic separation of transudates and exudates. Ann Intern Med 77:507–513, 1972.

In the absence of a traumatic tap, bloody fluid suggests trauma, neoplasm, or pulmonary infarction. If the hematocrit of the pleural fluid exceeds that of the peripheral blood by 50%, the effusion is, by definition, a hemothorax. Atraumatic hemothorax is relatively rare but can occur with spontaneous rupture of a tumor or blood vessel.

If the diagnosis of a malignant pleural effusion is being considered, pleural fluid should be submitted for cytologic examination. Contrary to popular belief, the sensitivity for diagnosis of pleural malignancy does not depend on the volume of pleural fluid extracted during thoracentesis.20

Management Most pleural effusions do not require emergent drainage, and there are few indications for therapeutic thoracentesis in the ED. For patients with massive effusions (ie, >1.5–2 L), urgent thoracentesis may stabilize respiratory or circulatory status. Patients with empyema require timely chest tube drainage in the ED or operating room to prevent complications. In most other cases, the timing of therapeutic thoracentesis can be individualized. For example, therapeutic thoracentesis would be reasonable to perform in the ED for an oncology patient with a recurrent effusion if symptomatic relief will allow the patient to be discharged. Relative contraindications to thoracentesis include coagulopathy and other bleeding disorders. Consider the risks and benefits of a procedure prior to initiating in the ED. Pleural adhesions are also a relative contraindication to thoracentesis because of the

CHAPTER 67  Pleural Disease

potential for pneumothorax, but this risk can be minimized with use of ultrasound guidance. Following a diagnostic or therapeutic thoracentesis, a chest radiograph should be obtained to evaluate for iatrogenic pneumothorax. Other potential complications of thoracentesis include hemothorax, lung laceration, shearing of the catheter tip, infection, and transient hypoxia due to ventilation-perfusion mismatch. Postexpansion pulmonary edema is a rare occurrence, except when large volumes (>1500 mL) are drained in one session. Hypotension can occur after the removal of a large volume of fluid, particularly in patients who are already intravascularly volume-depleted.

Disposition The natural history of pleural disease is determined largely by the underlying diagnosis, and the decision to admit a patient with pleural disease to the hospital must be individualized, taking into account the patient’s respiratory and hemodynamic status and predicted clinical course. For example, small pleural effusions are common after abdominal surgery and in the postpartum state, but they almost always resolve spontaneously within a few days. Viral pleuritis, with or without effusion, is generally self-limited and resolves without specific treatment. In patients with congestive

heart failure, pleural effusions generally respond well to diuretic therapy, but may persist in patients with poorly compensated disease. In nearly 20% of pleural effusions, no definitive diagnosis can be established, even after extensive investigation. A sizable percentage of these effusions are probably caused by viral infections, and most of these resolve spontaneously without sequelae. Parapneumonic effusions contribute significantly to morbidity and mortality. For this reason, the presence of a parapneumonic effusion is an indication to hospitalize a patient with communityacquired pneumonia.21 Empyema will develop in 5% to 10% of patients with a parapneumonic effusion, and early surgical drainage results in better outcomes than conservative management.22 Pleural effusions associated with malignancy are a marker of significant morbidity. The presence of a malignant effusion indicates disseminated disease, and most of the malignancies that cause pleural effusions—such as lymphoma and carcinoma of the lung, breast, or ovary—are not curable at this stage. Therapeutic thoracentesis can relieve dyspnea in the short term, but malignant effusions tend to be recurrent, often rapidly so. That said, control of pleural effusions can improve quality of life in these patients. Strategies for managing recurrence include chemical or mechanical pleurodesis to obliterate the pleural space and placement of a permanent catheter or pleuroperitoneal shunt to provide continual drainage.

KEY CONCEPTS • Point of care thoracic ultrasound can be used to rule out pneumothorax with greater sensitivity than a portable supine chest x-ray examination. Chest CT is the gold standard for diagnosis of pneumothorax but is reserved for cases in which pneumothorax is highly suspected and the chest x-ray is negative. • For healthy young patients with a small (~6-12 hrs

STEMI identification ACS identification CAD identification

Focused exam & ECG Serial exam, ECG, & biomarkers Potential cardiac imaging

Fig. 68.24.  The process of evaluation of the chest pain patient suspected of acute coronary syndrome (ACS) occurs through three distinct phases of care, including ST segment elevation myocardial infarction (STEMI) recognition, rule-out (R/O) acute coronary syndrome (ACS), and consideration of significant coronary artery disease (CAD) phases.

process. Staff, resources, and space are often dedicated for a CPC, but the unit can be part of an ED observation unit or a virtual decision unit located near or within the ED. By virtual, it is meant that the process of a rule-out MI can be performed in an appropriate ED bed location and not require a specific geographic location in the ED. A CPC protocol should rapidly direct patients with possible ACS into an appropriate treatment area where electrocardiography and a clinical examination can be performed within the first 10 minutes. Patients with STEMI who require immediate reperfusion therapy, with UA who need further intervention, or are experiencing other cardiorespiratory complications of ACS can be identified quickly. This goal can be combined with an efficient ED evaluation of patients with a low to moderate risk of ACS. The greatest medical benefit from the CPC is the early identification of patients with ACS, particularly STEMI; the most significant financial impact is the reduction of low-yield hospital admissions. There are multiple CPC models, but all emphasize expedited assessment and initiation of ACS care. The benefit of this standardization is magnified when we look at time-sensitive care, such as a target door to drug time of less than 30 minutes or a door to balloon time of less than 90 minutes (where percutaneous

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MANAGEMENT An understanding of the pathophysiology of ACS allows the emergency clinician to select the most appropriate therapies for the ACS patient. ACS pathophysiology includes the following: (1) endothelial damage through plaque disruption, irregular luminal lesions, and shear injury; (2) platelet aggregation; (3) thrombus formation causing partial or total lumen occlusion; (4) coronary artery vasospasm; and (5) reperfusion injury caused by oxygen free radicals, calcium, and neutrophils. In patients with noninfarction ACS, spontaneous fibrinolysis of the thrombus occurs rapidly, minimizing ischemic insult; persistence of the occlusive thrombus, however, often results in more serious forms of ACS, including NSTEMI and STEMI.

Time-Sensitive Nature of Acute Coronary Syndrome Therapy Early patency resulting in myocardial salvage is the key benefit of emergent reperfusion therapy, using fibrinolysis or PCI. Timely

treatment within the first hours after symptom onset may result in substantial, if not complete, myocardial salvage. Delivered later, from 2 to 12 hours after STEMI onset, treatment may result in a more modest, but significant, benefit. The opening of the occluded artery causes less adverse ventricular modeling, reduces occurrence of ventricular aneurysm, increases blood flow to the myocardium, and improves electrophysiologic stability. It has been well established that preserved left ventricular function and mortality at the 24-hour and 30-day endpoints are directly related to angiographic patency at 90 minutes. The relationship between rapid revascularization and mortality has been clearly demonstrated, and it has been shown that with each additional 30 minutes of delay to PCI, the relative 12-month mortality risk increases by 7.5%. Fig. 68.25 depicts the relationship between time to reperfusion and benefit in STEMI. Prehospital delay factors occur from the time the patient decides to seek medical attention until the patient arrives at the ED. It is not uncommon for patients to delay treatment significantly by calling their primary care physician, attempting to transport themselves or waiting for transport by other nonmedical professionals. For slightly less than 50% of patients with suspected AMI, the EMS system is the point of first medical contact.40 Wide variations in the availability of EMS systems and their varied levels of integration into their local ED and hospital ACS identification and evaluation processes can further complicate and delay care. EMS system resource is related to patient care ability; in systems with advanced and robust local resource, very comprehensive state of the art care is possible.41

TIME TO REPERFUSION VERSUS DEGREE OF BENEFIT

Maximal benefit

Definite benefit

Timedependent through myocardial salvage

Time-independent, possibly through open artery and collateral development

100

80

Benefit (%)

procedures are available) for patients with typical and uncomplicated presentations of STEMI. The CPC may have assigned nursing personnel who rapidly evaluate the patient with chest pain with a 12-lead ECG, as well as screening vital signs and cardiac monitoring, and deliver the ECG directly to an emergency clinician capable of making a decision about activation of the catheterization laboratory or administration of fibrinolytic therapy. The CPC may also be used as an observation and evaluation unit where patients with chest pain and a low to intermediate clinical likelihood of ACS can be monitored with electrocardiography, ST segment trending, serial 12-lead ECGs, and sequential serum markers. In addition, many CPCs now use further ACS evaluation with stress testing, echocardiography, or myocardial scintigraphy before disposition. Significant cost savings occur through the expedited evaluations and avoidance of unnecessary admissions, with typical charges and actual costs ranging from 20% to 50% of the costs for the usual inpatient approach. Previous studies have prospectively compared a CPC with the traditional hospital admission to rule out MI and showed a reduction in hospital admissions by almost 50%, with no adverse events in CPC patients with a negative stress test. A chest pain–accelerated diagnostic protocol approach to lowto intermediate-risk patients can be feasible, safe, and effective. Many accelerated diagnostic protocols have been validated to shorten the length of ED evaluation needed in the lower risk patient populations and, as troponin assays have increased in sensitivity, the length of time of serial testing has decreased dramatically in these protocols. The HEART Pathway Randomized Trial has demonstrated that the use of a clinical decision tool—the HEART score—plus troponin measurements at 0 and 3 hours was safe and effective in ACS evaluation in patients presenting to the ED with ACS-associated symptoms without ST elevation on the ECG. The HEART Pathway has demonstrated shorten length of stays, increased early discharges, a trend toward decreased objective cardiac testing at 30 days, and no adverse cardiac events in the early discharge group at 30 days of follow-up.39 Approximately 80% of patients with chest pain can be safely evaluated in the ED with ultimate discharge to home. The resources required for a successful CPC-based operation, in which patients undergo rapid exclusion of ACS through serial testing, continuous monitoring, and immediate provocative stress testing, are considerable. Although studies have suggested that CPCs decrease the number of admissions, they may increase the number of patients seen in the ED for chest pain, and emergency clinicians may overuse the CPC-accelerated diagnostic protocol approach in patients whom they would otherwise have discharged.

60

40

20

0 0

1

2

4

6

8

10

12

Time to treatment reperfusion agent (hr)

Fig. 68.25.  Relationship between time to reperfusion and benefit STEMI This figure depicts combined human and animal data and represents the time-dependent benefit anticipated, depending on the length of the interval between coronary artery occlusion and reperfusion. (Adapted from Tiefenbrunn AJ, Sobel BE: Timing of coronary recanalization. Paradigms, paradoxes, and pertinence. Circulation 85:2311, 1992; and from U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute [NIH Publication No. 93-3278], September 1993, p 8. Copyright ©1992 American Heart Association.)

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Further delays can occur between the time a patient arrives at the hospital and initiation of acute revascularization therapy. Although studies have shown that the average time to fibrinolysis ranges from 45 to 90 minutes, the AHA recommends that all patients with STEMI receive fibrinolytic therapy within 30 minutes of arrival or undergo primary PCI (ie, device across the culprit artery) no later than 90 minutes after arrival.6 STEMI patients who receive hospital-based reperfusion therapies (eg, fibrinolytic agent, PCI) progress through a sequence of steps that can define process time points. Within each interval, various impediments to timely care can occur. Reducing delay times is applicable to all time points in the ED by addressing the four Ds: door (events before arrival at the ED), data (obtaining the ECG), decision (arriving at the STEMI diagnosis and deciding on therapy), and drug (administering the fibrinolytic agent or passing the angioplasty catheter across the culprit lesion for PCI candidates).42 Prehospital notification to the ED of the impending arrival of a patient with a suspected STEMI, particularly when ST segment elevation is suspected, has become standard practice in many established EMS systems. A field 12-lead ECG may assist in diagnosis and decrease the reperfusion time by initiating the hospitalbased sequence of necessary events to occur in parallel, as opposed to serially. Some systems have been able to bypass the ED in selected prehospital notifications of STEMI, and these patients go directly from the ambulance to the CCL for PCI. Although these systems have shown significant decreases in door to reperfusion times, however, they were unable to demonstrate any improvement in clinical outcomes, including mortality.43 Self-transported patients with possible ACS should be evaluated by the triage nurse immediately and an ECG acquired within 5 to 10 minutes of arrival. The development of hospital-based protocols and system response plans for identifying and rapidly treating patients reduces the amount of time to treatment. When

using fibrinolysis in uncomplicated cases, the emergency clinician should activate the hospital-based system for reperfusion. Checklists of inclusion and exclusion criteria for fibrinolytic therapy should be available, and those fibrinolytic agents should be stored and administered in the ED. In a system in which fibrinolysis is the sole reperfusion therapy, the decision to administer that therapy rests solely with the emergency clinician. Nonconsultative communications with family physicians, internists, or cardiologists before administration of the agent may result in unnecessary delays. Consultative discussions should only be required in complicated situations before the administration of therapy. If the hospital offers primary PCI, many hospitals activate so-called STEMI alert responses when an STEMI patient is identified prehospital or in the ED. Analogous to the trauma alert, the cardiologist and catheterization laboratory personnel are immediately mobilized. Prehospital or emergency clinician activation of the catheterization laboratory demonstrates very high rates of accurate STEMI diagnosis, with very low rates of false activation (ie, the STEMI mimicker) while markedly reducing the time to definitive therapy.43-45 Interhospital transfer of STEMI patients for PCI when they are also candidates for fibrinolysis should be discouraged if definitive therapy (ie, catheter placement across the culprit lesion) is likely to be delayed beyond 120 minutes, except in cases of hemodynamic shock (see later) or in patients for whom fibrinolysis is contraindicated.7

Pharmacologic Intervention A range of medications can be used in the patient with ACS (Table 68.7). These agents range from the basic to the complex, including oxygen, IV fluids, antiplatelet and anticoagulant agents, nitroglycerin, opioid analgesics, β-adrenergic blocking agents, and fibrinolytic agents.

TABLE 68.7 

Medications Used in Emergency Department Management of Acute Coronary Syndrome (ACS) MEDICATION AND MEDICATION CLASS

EXAMPLES

INDICATIONS

RISK ISSUES

Nitroglycerin

Nitroglycerin (sublingual, topical, IV)

Chest pain, pulmonaryedema medication, blood pressure medication

Hypotension

Opiates

Morphine, fentanyl

Chest pain

Hypotension, respiratory suppression Hypotension, bradycardia, cardiogenic shock

β-ADRENERGIC BLOCKERS • IV

Metoprolol, labetalol, esmolol

Blood pressure agent, dysrhythmia agent

• Oral

Metoprolol

None; inpatient use

ACE inhibitors

Captopril, enalapril, lisinopril, ramipril

None; inpatient use

Statins

Lovastatin, atorvastatin, simvastatin, pravastatin

None; inpatient use

Calcium channel blockers

Diltiazem

None; inpatient use

Aspirin

Aspirin

Chest pain

Hemorrhage, gastric irritation

Other antiplatelet agents

Clopidogrel, ticagrelor, prasugrel, ticlopidine

ACS (with objective confirmation)

Hemorrhage

Antithrombin agents

Heparin, enoxaparin, bivaliruden

ACS (with objective confirmation)

Hemorrhage, heparin-induced thrombocytopenia (for heparins)

Fibrinolytic agents

Streptokinase t-PA r-PA Tenecteplase

STEMI

Hemorrhage

CHAPTER 68  Acute Coronary Syndrome

Oxygen Oxygen is considered a medication, a medication with significant potential to benefit and harm the patient with ACS. A brief mention of the most appropriate strategy for oxygen treatment in the ACS patient is warranted. Respiratory compromise can occur during ACS, usually as a result of acute pulmonary edema or chronic pulmonary disease. Suspected ACS patients with respiratory distress, demonstrated by physical examination and/or oxygen saturations, should receive supplemental oxygen as standard therapy. The rationale for this standard oxygen therapy is that maximization of oxygen saturation may improve the delivery of oxygen to the tissues and thus reduce the ischemic process and related negative outcomes. There is limited evidence regarding the use of supplemental oxygen therapy in the suspected ACS patient with normal oxygen saturation and no other evidence of respiratory compromise. The practice of administering oxygen to all patients, regardless of their oxygen saturation, is based on rational conjecture and research performed prior to the current reperfusion era in acute coronary care. More recent studies of this issue are limited46 but have suggested that excessive oxygen therapy can increase the rate of adverse outcome in the ACS patient, particularly involving STEMI. Hyperoxia, developing as a result of excessive supplemental oxygen therapy, can potentiate coronary vasoconstriction and increase oxidative stress, worsening outcome in these patients.47 Recently, the AVOID trial demonstrated that oxygen therapy, delivered to patients suspected of STEMI who also had normal oxygen saturations and no other evidence of respiratory compromise, likely increased early myocardial injury and was associated with a larger size of the infarction. Furthermore, re-infarction and cardiac dysrhythmia were also increased in the oxygen therapy group.47 In other patient groups, such as resuscitated cardiac arrest patients, hyperoxia has been associated with worse outcomes as compared with normoxia. Thus, in suspected or confirmed ACS patients, supplemental oxygen therapy is appropriate for patients demonstrating respiratory compromise, noted by physical examination or oxygen saturations less than 94%. Conversely, in patients without respiratory compromise, oxygen therapy can be withheld.

Nitroglycerin Nitrates decrease myocardial preload and, to a lesser extent, afterload. Nitrates increase venous capacitance and induce venous pooling, which decreases preload and myocardial oxygen demand. Direct vasodilation of coronary arteries may increase collateral blood flow to the ischemic myocardium. Nitroglycerin has been used for decades in patients with suspected or known ACS. Most studies of IV NTG in the setting of ACS, however, are from the prefibrinolytic era. Although the data from multiple trials originally noted a 35% mortality reduction with IV NTG in the setting of AMI, this study preceded the modern era of aggressive reperfusion therapies coupled with potent anticoagulant and antiplatelet agents. No contemporary evidence (ie, in the reperfusion era of acute cardiac care) has shown improved outcomes with the routine use of any form of nitrate therapy in patients with AMI. In the ACS patient, it must be noted that the use of NTG in any formulation is another management option, yet its use is not mandatory. In situations in which hypoperfusion is present or is anticipated to occur, it is very appropriate to withhold NTG in all formulations. Patients with possible ACS and a systolic blood pressure greater than 90 mm Hg can receive a sublingual NTG tablet (0.4 mg [400 µg]) on presentation. If symptoms and pain are not fully relieved with three sublingual tablets, IV NTG can be considered. With bradycardia, hypotension, inferior wall STEMI, and right

ventricular infarction, a sudden decrease in preload associated with NTG can result in profound hypotension. An initial infusion rate of 10 µg/min is titrated to pain symptoms. The emergency clinician can increase the infusion at regular intervals, allowing a 10% reduction in the mean arterial pressure if the patient is normotensive and a 20% to 30% reduction if hypertensive.

Morphine and Other Opioid Analgesic Agents Morphine is a potent opioid analgesic with weak sympathetic blockade, systemic histamine release, and anxiolysis. If a patient with possible ACS is unresponsive to NTG or has recurrent symptoms despite maximal antiischemic therapy, administration of morphine sulfate is a reasonable analgesic. The relief of pain and anxiety decreases oxygen consumption and myocardial work. Some vasodilatory effects are also noted with preload reduction. Standard doses of morphine sulfate are 2 to 4 mg IV, repeated every 5 to 30 minutes as necessary. Caution is advised with morphine use in this setting. Although appropriate, it must be remembered that morphine is a potent medication with significant vasodilatory effects and profound sedation, with respiratory depression. In addition to allergic reactions, the most significant adverse effect of morphine sulfate administration is hypotension, which is managed with IV crystalloid as a bolus. Its use in modest amounts is reasonable. In addition to its analgesic properties, it is also an anxiolytic agent, a valuable feature in certain ACS patients. Withholding morphine and other analgesic agents is not inappropriate if the emergency clinician is concerned about the potential for iatrogenic hypoperfusion, sedation, or respiratory depression. Other opioid agents, such as fentanyl, are reasonable for use in the ACS patient. The same caveats and general recommendations apply with other opioid agent administration in the ACS patient.

β-Adrenergic Blockers Historically, β-adrenergic blocking agents have been effective in ameliorating catecholamine-induced tachycardia, including ventricular fibrillation, increased contractility, and heightened myocardial oxygen demand during the infarction period. Although beta blockade was shown to decrease mortality for patients with AMI, these observations occurred when adjunctive therapies were few and β-adrenergic blockade was essentially monotherapy in AMI. Contemporary management strategies include highly effective reperfusion therapies coupled with potent anticoagulant and antiplatelet agents; thus, their widespread use must be reconsidered. Multiple studies have suggested that the widespread intravenous use of β-adrenergic blockade should be reconsidered. The use of the early IV β-adrenergic blocking agents in these studies was associated with higher rates of death, heart failure, cardiogenic shock, recurrent ischemia, and pacemaker use as compared to patients who received early oral administration. These increases occurred despite the exclusion of patients with obvious contraindications, including preexisting hypotension, bradycardia, or heart failure. Large studies followed that evaluated patients with suspected STEMI, comparing early IV β-adrenergic blocking agent use followed by continued oral therapy versus placebo. These studies found no significant difference between the two groups in terms of mortality; however, the group receiving β-adrenergic blockers demonstrated a minimal reduction of re-infarction and ventricular fibrillation. This was at the expense of a significantly higher rate of cardiogenic shock and increased rates of development of heart failure requiring treatment, persistent hypotension, and bradycardia.. The early IV use of β-adrenergic blocking agents, when coupled with contemporary therapy in the setting of ACS, does not appear

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to offer significant benefit and is associated with an increased rate of adverse events. Therefore, their IVs use in the ED in the ACS patient is discouraged. Conversely, oral administration to ACS patients without contraindications during the first 24 hours of management is a class I recommendation from the ACC/AHA and can be accomplished after admission has occurred. This strategy allows for stabilization of the patient while additional clinical data are obtained to determine appropriateness of this therapy.5 Empirical therapy in the ED, however, should be reserved for only those patients who have adverse effects from significantly elevated blood pressure or significant tachydysrhythmia, despite application of other appropriate medications.

Angiotensin-Converting Enzyme Inhibitors Angiotensin-converting enzyme (ACE) inhibitor agents benefit patients with CHF. ACE inhibitors may also reduce morbidity and mortality after AMI. In particular, patients treated with ACE inhibitors experience a reduction in cardiovascular mortality, decreased rates of significant CHF, and fewer recurrent AMIs. These benefits increase when ACE inhibitors are used in conjunction with other agents, such as aspirin and fibrinolytic agents. The mechanism of action regarding a reduction in recurrent AMI is unknown but may involve a reduction in plaque rupture related to decreased intracoronary shear force or neurohumoral influences. Therapy should be initiated within the first 24 hours following an ACS event, although ED administration is not indicated.5

HMG–Coenzyme A Reductase Inhibitors (Statins) A number of investigations have demonstrated a reduction in inflammation and reinfarction, angina, and lethal arrhythmia with the administration of statin drugs in the first few days after an ACS event. Although there is no indication for statin therapy in the ED management of ACS, initiation of this therapy should occur within the first 24 hours5 or should continue if patients are already undergoing statin therapy, because discontinuation during hospitalization is associated with an increase in near-term mortality and adverse events. The administration of statin therapy before elective or urgent PCI for ACS is reasonable to decrease the incidence of a periprocedural AMI; however, there are no specific risk or safety data regarding its use in this setting.

Calcium Channel Blockade As with beta blockade, the primary benefit of calcium channel blockers appears to be in regard to symptom resolution. Unfortunately, these agents may be accompanied by a significant vasodilatory effect, resulting in hypotension and potentiation of the coronary ischemic process. Like beta blockers, calcium channel blockers have a substantial negative inotropic effect. AV nodal blockade is also a significant side effect that may be exacerbated in patients previously treated with beta blockers or with ischemiarelated conduction disturbance. Unless specifically used for rate control of supraventricular dysrhythmia in a patient who cannot tolerate beta blockade, calcium channel blocker agents have no role in the ED management of ACS.

Antiplatelet Therapy In non-AMI ACS patients (ie, unstable angina), dramatic reductions in the progression to acute infarction are noted with appropriate antiplatelet therapy. The administration of antiplatelet therapy, particularly aspirin, is indicated in the ED for most ACS patients. For AMI, the administration of aspirin and other antiplatelet agents is associated with significant reductions in mortality, ranging from 25% to 50%.

Aspirin.  Aspirin, the prototypical antiplatelet agent, is the most cost-effective treatment in ACS care. It irreversibly acetylates platelet cyclooxygenase, thereby removing all activity for the life span of the platelet (8–10 days). Thus, aspirin stops the production of proaggregatory thromboxane A2 and is an indirect antithrombotic agent. Aspirin also has important nonplatelet effects because it inactivates cyclooxygenase in the vascular endothelium, thereby diminishing the formation of antiaggregatory prostacyclin. It is well established and accepted that aspirin independently reduces the mortality of patients with AMI without fibrinolytic therapy (overall 23% reduction) and is synergistic when used with fibrinolytic therapy (42% reduction in mortality). The usual dose is 324 mg of non–enteric-coated aspirin, chewed and swallowed. Enteric-coated aspirin should be avoided in the acute setting of ACS due to delays in the onset of antiplatelet activity.48 The administration of aspirin in the ED is strongly recommended immediately on identification of any patient with suspected ACS, either UA or AMI. It should be administered to all such patients unless significant allergy, hemorrhage, or other issues, such as a potential aortic dissection, contraindicates its use. More recent studies have established that lower dose aspirin (162 mg) at preventing adverse cardiac events, with fewer bleeding risks. These findings were consistent when given alone or with other antiplatelet agents (eg, clopidogrel). Glycoprotein IIb/IIIa Receptor Inhibitors.  Glycoprotein IIb/IIIa receptor inhibitors (GPIs) are potent antiplatelet agents; they include abciximab, eptifibatide, and tirofiban. GPIs, however, demonstrate clinical usefulness in only a subset of ACS patients, those undergoing PCI as a reperfusion strategy. Therefore, the primary indication regarding GPI administration is planned mechanical coronary intervention. Furthermore, the largest studies on GPI administration timing have not shown outcome benefit to upstream use in the ED when compared to catheterization laboratory administration. Currently, there is no clear indication for the ED administration of GPIs unless other antiplatelet agents are not tolerated or unavailable. This class of medications is not standardly given in the ED setting, and other antiplatelet agents (PSY12 receptor inhibitors) are preferred for upstream administration in the care of ACS.5 Numerous trials have demonstrated the effectiveness of these agents in the subset of ACS patients who are managed with PCI, with or without an intracoronary stent. These trials have consistently shown reduced mortality, need for subsequent revascularization, and recurrent ischemia, although at the cost of an increase in hemorrhagic complications. Multiple studies evaluating GPI use in ACS patients have concluded that patients who undergo PCI benefit markedly from GPI administration. In ACS patients managed medically, without mechanical revascularization, consistent benefit with GPI therapy is not found with the use of direct outcome measures or secondary markers of successful reperfusion, and hemorrhagic complications are increased. The benefits of GPI therapy were established mainly before the development of contemporary invasive strategies, raising questions about the timing (ie, upstream initiation in the ED) when combined with other antiplatelet therapies. Although initially small preliminary studies have shown promise for upstream GPI administration, larger trials have not supported their routine use in the ED. Evidence supports a highly selective strategy for the use of GPIs that balances ACS risk in the treatment of a patient with dual-agent platelet inhibition and planned PCI versus the potential bleeding risk. GPIs consistently demonstrate benefit in ACS patients treated with urgent mechanical revascularization; in other groups of ACS patients, such as medically managed patients,

CHAPTER 68  Acute Coronary Syndrome

patients receiving a combination fibrinolytic agent, or transferred patients, an invariable positive effect has not been established. PSY12 Receptor Inhibitor Agents.  The thienopyridines ticlopidine, clopidogrel, and prasugrel are more potent platelet inhibitors than aspirin. They inhibit the transformation of the PSY12 receptor into its high-affinity ligand-binding state, irreversibly inhibiting platelet aggregation for the duration of the life of the platelet. Ticlopidine has nonlinear kinetics and, with repeated administration, reaches a maximal effect after 8 to 11 days of use. Clopidogrel, a ticlopidine analogue, and prasugrel have the advantage of a rapid onset of action. Clopidogrel has traditionally been the preferred ED agent of this class due to its relatively rapid onset of action, improved safety profile, and proven efficacy when given upstream and in association with thrombolytic therapy. Prasugrel incurs a higher bleeding risk than clopidogrel, in patients older than 75 years, those who weigh more than 60 kg, those who have had a previous transient ischemic attack (TIA) or stroke, and those at high risk for bleeding. The ACCOAST trial showed no improvement in outcomes for patients treated with prasugrel in the ED versus dosing at the time of PCI. Because of this and other similar studies, prasugrel is not recommended for upstream use in the ED in ACS patients.49 Ticlopidine is associated with a risk of neutropenia, thrombotic thrombocytopenic purpura, and agranulocytosis; furthermore, it demonstrates a much slower onset of platelet inhibition. With clopidogrel, maximal platelet inhibition occurs after 3 to 5 days of clopidogrel therapy with 75 mg daily; an earlier onset of platelet inhibition is seen when a higher loading dose is used (300–600 mg). For example, there is clear benefit to clopidogrel administration (300 mg loading dose) at least 6 hours before PCI in patients with STEMI; higher doses (eg, 600 mg) demonstrate a trend toward improvement at slightly earlier time periods (ie, 3–4 hours). Ticagrelor, a nucleoside analogue, also acts as a PSY12 receptor inhibitor, however, via a different mechanism not requiring hepatic activation. It is rapidly absorbed, reaching peak serum concentration at 2.5 hours. Clinical data have demonstrated that ACS patients given ticagrelor were less likely to die from cardiovascular causes, but these improved outcomes are tempered by higher rates of nonprocedure-related bleeding, including more frequent fatal intercranial hemorrhage when compared with clopidogrel administration. Further analysis of the PLATO study has assessed the increased cost of ticagrelor versus clopidogrel when combined with aspirin and determined that with the increased life expectancy, ticagrelor plus aspirin is a “good value for the money.”50 Cangrelor, an IV PSY12 receptor inhibitor, has potential for significant therapeutic advantages over the other drugs in this class due to its immediate onset of antiplatelet activity and very short half-life. It is administered IV in its active form (unlike clopidogrel), not as a prodrug requiring metabolism prior to its onset of action. Unlike the oral drugs in this class, which that require 2 to 6 hours to reach active levels, cangrelor is active immediately on injection. This has potential benefits in patients who are undergoing rapid PCI—specifically, the STEMI population with an invasive management plan. Cangrelor also has a very short half-life (4–6 minutes), which makes the treatment of potential CABG patients with a PSY12 receptor inhibitor possible up until the time of surgery. Initial studies have shown the ability to maintain low levels of platelet activity in the presurgery time period on cangrelor, compared to the recommended 5 days off of medication with the oral PSY12 receptor inhibitors, without an increase in major bleeding in CABG patients.51 Cangrelor also appears to have the potential for improved outcomes in patients undergoing PCI when compared to current antiplatelet therapy.52 The drug is currently seeking US Food and Drug Administration (FDA) approval, after rejection in 2014 due to mixed results in

previous clinical trials. Cangrelor received a favorable vote for limited indications from the FDA in April 2015 and may be available for clinical use in the near future. In accordance with the 2013 AHA Guidelines for STEMI management, patients should receive a loading dose of clopidogrel or ticagrelor in addition to standard ACS care (ASA, anticoagulants, and reperfusion therapy), assuming there are no contraindications to its use, prior to PCI (upstream).6 For patients with definite or likely NSTEMI, in accordance with the 2014 AHA guidelines for NSTEMI management, the administration of a PSY12 receptor inhibitor should also be initiated upstream in the ED prior to PCI.5 Another indication for the ED administration of clopidogrel is the patient with a high-risk ACS presentation who is truly allergic to ASA (ACC/AHA class I indication).5 This high-risk presentation would be characterized by objective clinical abnormality, including a significantly abnormal serum marker or 12-lead ECG. Considerations include the ultimate treatment strategy chosen (ie, medical vs. invasive) and the time to angiography if an invasive plan is selected. ACS patients managed medically (ie, noninvasively) or invasively with coronary angiography deferred to a later time are the most appropriate potential candidates for clopidogrel. In the patient selected for invasive management, the time to the procedure is a primary issue in considering clopidogrel; patients undergoing early angiography, within 6 hours, are less likely to derive significant benefit, whereas deferred catheterization likely will gain advantage. In the patient with UA or NSTEMI, clinical benefit is confirmed in UA patients when treated with clopidogrel in a noninvasive strategy scenario, with an increase in the incidence of major hemorrhage. As noted, invasively managed patients receiving the drug with less time to procedure performance do not benefit from such treatment. The NSTEMI patient demonstrates improved outcome with clopidogrel therapy when a conservative treatment scenario is initially followed. Of note, a large portion of these patients will undergo PCI within the first 24 hours after admission; however, this so-called delayed PCI allows for benefit to occur from clopidogrel administered earlier in the course of management. The STEMI patient who is managed medically (ie, with a fibrinolytic agent) will also benefit from clopidogrel use. Clopidogrel therapy in conjunction with fibrinolysis, followed by deferred cardiac catheterization occurring at least 2 days after AMI—clearly beyond the 6-hour window—decreases the rates of death, recurrent ACS, and urgent coronary revascularization. This improvement occurs without a significant increase in hemorrhage. The potential need for urgent CABG should also be strongly considered. The higher risk ACS patient will more likely benefit from PSY12 receptor inhibitor therapy, but that same patient is also more likely to need urgent CABG. It is not possible, however, to identify ACS patients requiring urgent CABG reliably. Previous registries have shown that as many as 14% of ACS patients will undergo CABG, a reasonably frequent rate of surgical intervention; most centers, however, report a 2% to 5% incidence of coronary surgery. Reviews of ED ACS patients have been unable to demonstrate one or a combination of clinical features apparent in the ED that reliably identify patients not requiring CABG. It is interesting and important to note that although these CABG patients had a greater incidence of bleeding perioperatively, outcomes were not statistically different in clopidogrel versus placebo groups in this surgical subset. It is likely that as the cardiovascular surgeon gains more experience with PSY12 receptor inhibitor administration, and as other alternatives such as cangrelor become available for perioperative therapy in the CABG patient, this concern will continue to decrease.53 The ACC and AHA have suggested, in the form of a class I recommendation, that clopidogrel or ticagrelor should be

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withheld for at least 24 hours before urgent on-pump CABG, if possible.5 If CABG is performed within 5 days of clopidogrel use, patients have increases in the following: incidence of operative and postoperative hemorrhage; need for transfusions; need for reoperation for hemostasis; and postoperative mortality. Nevertheless, the recommendation suggests that early PSY12 receptor inhibitor therapy be considered in patients who likely will not require CABG.5 In that it does not appear possible for the emergency clinician to predict reliably which patients will require urgent CABG, collaborative multidisciplinary pathways should be developed, with emergency clinicians,, cardiologists, and cardiovascular surgeons providing input.54

Antithrombins As with antiplatelet therapies in ACS patients, significant reductions in the progression to acute, recurrent, or extensive infarction and death are noted in individuals treated with aggressive antithrombin therapy. There are currently four options for antithrombin therapy in the setting of ACS, including unfractionated heparin (UFH), LMWH, direct thrombin inhibitors (bivalirudin), and factor Xa inhibitors (fondaparinux). Antithrombotic therapy is indicated for ACS patients with recurrent anginal pain, AMI (NSTEMI and STEMI), a significantly positive serum marker, and a dynamic 12-lead ECG. Heparins.  The term heparin refers not to a single structure but to a family of mucopolysaccharide chains of varying lengths and composition—hence, unfractionated—with pronounced antithrombotic properties. At standard doses, UFH binds to antithrombin III, forming a complex that is able to inactivate factor II (thrombin) and activate factor X. This prevents the conversion of fibrinogen to fibrin, thus preventing clot formation. Heparin by itself has no anticoagulant property. This indirect effect on thrombin inhibits clot propagation; it prevents heparin, however, from having any effect on bound thrombin in a thrombus. UFH also assists in the inactivation of factors XIa and IXa through antithrombin and interacts with platelets. UFH has a profound synergistic effect with aspirin in preventing death, AMI, and refractory angina in ACS patients, particularly those with AMI and, to a lesser extent, high-risk UA. UFH should be administered early in patients with the following ACS features: recurrent or persistent chest pain, AMI, positive serum marker, and a dynamic ECG. In patients receiving thrombolytic therapy and UFH, it has been shown that bleeding and mortality were higher in patients receiving an 80-unit/kg bolus and 18-unit/kg infusion compared with patients with a lower bolus amount and infusion rate. Therefore, the weight-adjusted regimen recommended for UFH in the setting of a STEMI receiving thrombolytic therapy or non-ST elevation ACS patients is an initial bolus of 60 units/kg (maximum, 4000 units) and an initial infusion of 12 units/kg/hr with an activated partial thromboplastin time goal of 1.5 to 2.5 times the control value.5,6 The weight-adjusted regimen UFH in STEMI patients receiving PCI is dependent on the planned use of a GPI during PCI. If GPI use is planned during PCI, the bolus dose should be 50 to 70 units/kg (no maximum dose) and, if no GPI use is planned, the bolus dose should be 70 to 100 units/ kg (no maximum dose).5,6 LMWHs constitute approximately one-third of the molecular weight of heparin and are less heterogeneous in size. LMWHs inhibit the coagulation system in a fashion similar to that of UFH. Approximately one-third of the heparin molecules bind to antithrombin III and thrombin. The remaining molecules bind only to factor Xa. The variable efficacy found among the LMWHs is attributed to different ratios of antifactor Xa to antifactor IIa. High-ratio preparations have a clear advantage over standard heparin; enoxaparin has the highest ratio of available LMWHs. LMWH was designed on the basis of

the hypothesis that the inhibition of earlier steps in the blood coagulation system would be associated with a more potent antithrombotic effect than inhibition of subsequent steps. This results from the amplification process inherent in the coagulation cascade—that is, a single factor Xa molecule can lead to the generation of multiple thrombin molecules. Potential advantages of LMWH over UFH include easier administration, greater bioavailability, more consistent therapeutic response among patients, and longer serum half-life, producing a more manageable administration schedule, albeit at a higher cost. The combination of aspirin, beta blocker, and LMWH significantly decreases the rate of nonfatal AMI or death at 1 in the first several weeks after treatment but has much less pronounced impact out to multiple months. Studies comparing outcomes between LMWH and UFH have shown mixed results; some show better outcomes with LMWH, but others do not. In summary, the LMWH enoxaparin demonstrates some degree of benefit compared with UFH in patients at higher risk for non–ST segment elevation ACS who are treated conservatively without immediate PCI (ie, beyond 24 hours). For STEMI patients managed aggressively with rapid PCI, UHF is preferred over enoxaparin.5 Enoxaparin is administered in a twice-daily regimen subcutaneously at a dose of 1 mg/kg for all ACS patients. If patients have renal dysfunction, with an estimated glomerular filtration rate of less than 30 mL/min, the dose should be reduced to 1 mg/kg in a single daily administration. Few safety data are available for enoxaparin in ACS patients with renal insufficiency, and UFH may be preferable. Contraindications to heparin therapy include known allergy, active ongoing hemorrhage, and predisposition to such hemorrhage. Furthermore, patients who have their heparin therapy changed (UFH to LMWH and vice versa) during the active treatment phase of their ACS care experience higher rates of bleeding. Most patients with AMI require therapy with heparin, whether it is fractionated or unfractionated. Non-AMI ACS, however, is an entirely different issue because UA is a heterogeneous condition. Only high-risk UA patients (recurrent or continued pain, or new ischemic electrocardiographic changes) should be considered for heparin therapy. For example, the stable patient with a classic description of new-onset angina, who is sensation-free with a negative serum marker and normal ECG, is still correctly diagnosed with UA. In contrast, an individual with ongoing pain, intermittent or constant, with a dynamic ECG clearly is experiencing an active, unstable coronary event. The latter patient, who is at higher risk, can benefit from heparin therapy more than the former. Heparin therapy, however, can be a major contributor to morbidity and mortality among hospitalized patients. Major bleeding develops in 1 of every 90 patients treated, and heparininduced thrombocytopenia in 1 of 34 patients. LMWH is as effective as UFH in patients with non–ST segment elevation ACS and does not greatly increase the bleeding risk while decreasing the risk of thrombocytopenia. Other Antithrombins: Bivalirudin, Fondaparinux, and Hirudin.  The direct thrombin inhibitor bivalirudin is a potent antithrombin anticoagulant providing significant theoretical advantages compared with heparin. Bivalirudin is a bifunctional 20–amino acid peptide designed on the basis of the structure of hirudin. It has properties similar to those of hirudin but also interacts with the catalytic site of thrombin. Bivalirudin, however, is more effective than heparin in reducing death or reinfarction in patients with ACS, particularly those patients undergoing very early PCI. Bivalirudin, compared with heparin, produces similar rates of ischemia and major bleeding at 1 month. Bivalirudin when used with clopidogrel is comparable to the combination of

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heparin and GPI before coronary angiography or PCI. When used alone, it is inferior to the combination of heparin and GPI. Bivalirudin should be considered an acceptable alternative anticoagulant agent compared with the UFH in the STEMI patient undergoing PCI.5 Fondaparinux is a synthetic oligosaccharide with a structure similar to the heparins. It is the first widely used selective factor Xa inhibitor. With the increased emphasis on the reduction of hemorrhagic complications in ACS care, this drug may be considered as a reasonable alternative to UFH in the care of NSTEMI patient receiving non-invasive management; however, the increased risk of catheter-associated thrombi during PCI prevents its use without additional UFH administration when an invasive strategy is chosen. In previous comparison studies, fondaparinux was found to be similar to enoxaparin in the short-term reduction of ischemic events, yet substantially reduced major bleeding and improved long-term outcome. When the use of fondaparinux was reviewed in STEMI patients managed medically with streptokinase, it was found that fondaparinux significantly reduced hemorrhage as well as death and MI when compared to UFH and LMWH. As a result, fondaparinux has a class 1 AHA recommendation as an alternative to UFH and LMWH in NSTEMI and STEMI patients that are not undergoing PCI.5,6 Hirudin is a peptide derived from the leech salivary gland but was also synthesized as recombinant hirudin. It binds directly with high affinity to thrombin and can inactivate thrombin already bound to fibrin (clot-bound thrombin) more effectively than UFH. Hirudin does not require endogenous cofactors, such as antithrombin III, for its activity. Also, unlike heparin, hirudin can inhibit thrombin-induced platelet aggregation. Hirudin has demonstrated little significant benefit over other anticoagulants in ACS, with a possibly increased rate of hemorrhage; thus, its pharmaceutical production was discontinued in 2012.

Reperfusion Therapies Rapidly reestablishing perfusion in the infarct-related coronary artery with the use of fibrinolytic therapy or PCI increases the opportunity for myocardial salvage, with resultant reductions in mortality and improvements in quality of life post-MI. Pharmacologic and mechanical methods of reperfusion are both effective under specific clinical conditions. More than 2 decades ago, the importance of early coronary artery patency was recognized, and it was demonstrated that 90-minute patency predicts improved rates of survival and preserves left ventricular function. Fibrinolytic therapy unequivocally improves survival in patients with STEMI and is an ACC/AHA class I recommendation.5-7 Although fibrinolysis has widespread availability and proven ability to improve coronary flow, limit infarct size, and improve survival in STEMI patients, many individuals with acute infarction are not suitable candidates. Patients with absolute contraindications to fibrinolytic therapy, certain relative contraindications, cardiogenic shock, and UA, and most NSTEMI cases, may not be eligible. The limitations of fibrinolytic therapy, as well as the benefits of percutaneous coronary intervention, suggest that rapidly performed PCI is often the treatment of choice in the STEMI patient. To provide the most significant benefit, PCI must be performed as soon as possible after the initial presentation. In certain other settings, PCI that is delayed is inferior to rapidly administered fibrinolytic agents, assuming that the patient has no contraindications to this therapy. Fibrinolytic Therapy Fibrinolytic

Agent Selection.  Options for fibrinolytic therapy include streptokinase (the original fibrinolytic agent) and three types of plasminogen activator: tissue-type plasminogen

activator (t-PA) and two recombinant tissue-type plasminogen activators, r-PA (reteplase) and tenecteplase (TNK). Initial studies comparing streptokinase with slower administration of t-PA have shown no difference in outcomes in the setting of AMI. Subsequent studies, however, have shown improved outcomes with the use of t-PA compared to streptokinase in the setting of AMI, due to so-called accelerated administration of the former agent. Due to more effective options for fibrinolytic therapy, and easier to administer alternatives, streptokinase is no longer marketed in the United States. It is still used in many areas of the world due to of its low cost when compared to the other fibrinolytic options. Fibrinolytic practice remains highly affected by early studies testing the hypothesis that early and sustained infarct vessel patency is associated with better survival rates in patients with AMI. Investigators have studied multiple different fibrinolytic strategies and found that accelerated t-PA given over 90 minutes, plus IV heparin, shows improved results when compared to streptokinase in combination with multiple forms of anticoagulation. Unlike in previous trials, t-PA was given in a more aggressive, front-loaded, 90-minute infusion (referred to as accelerated t-PA). In addition to mortality, coronary artery patency and degree of normalization of flow were found to be directly affected by this accelerated t-PA administration. This was the first proven association of the relationship between early coronary artery patency and improved clinical outcome. The accelerated t-PA patients showed significant mortality benefit following treatment (15%), and the benefit out to 1-year follow-up was highly consistent across virtually all subgroups, including older patients, AMI location, and time since symptom onset. Also, the angiographic evaluation demonstrated a strong relationship between TIMI flow and outcome. Patients with strong forward flow (ie, TIMI grade 3 flow) at 90 minutes had significantly lower mortality rates than patients with little to no flow. The mechanism for this benefit was found to be earlier, more complete infarct vessel patency with accelerated t-PA; this early t-PA patency advantage over other agents was lost by 180 minutes after symptom onset. As would be expected, patients with the higher risk derived the most substantial benefit with accelerated t-PA compared with streptokinase in this large study. Accelerated t-PA is associated with increased risk of hemorrhagic strokes compared to streptokinase, but the combined endpoint of death and disabling stroke still favors the accelerated t-PA regimen. Other large studies have compared accelerated t-PA with r-PA; r-PA can be administered in a fixed, double-bolus dose with no adjustment required for weight, which simplifies administration. r-PA has been found to be equivalent to accelerated t-PA, and results have been nearly identical for the two drugs. The one exception was the patient with presentation more than 4 hours after onset of symptoms, a significant number of patients in many institutions. In this group, accelerated t-PA may be superior to r-PA because of its greater fibrin specificity. In the setting of STEMI, TNK has been found to have several potential benefits: (1) its longer half-life allows it to be administered as a single bolus; (2) it is 14 times more fibrin-specific than t-PA and even more so than r-PA; and (3) it is 80 times more resistant to plasminogen activator inhibitor type 1 than t-PA. In comparisons of single-bolus TNK (30–50 mg on the basis of body weight) or accelerated t-PA (100 mg total infusion) in the setting of AMI, there were no differences in mortality or intracranial hemorrhage. However, there may be benefit in 30-day mortality among patients with presentation more than 4 hours after onset of symptoms in those treated with TNK, as well as fewer nonintracranial major bleeding episodes in this group. On the basis of these results, it is concluded that TNK is equally or minimally more effective, particularly in late presenters. Concerning adverse reactions, TNK also appears modestly safer than accelerated t-PA. Finally, because of its single-bolus administration, TNK is

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markedly easier to use in prehospital environments and the ED. At present, it appears that TNK is marginally more effective, minimally safer, and easier to administer than t-PA, and thus is recommended. Furthermore, cost differences are minimal and likely will not affect medical decision making in the ED. Eligibility Criteria for Fibrinolytic Agent Therapy.  In the absence of contraindications, fibrinolytic therapy should be considered in patients with STEMI and the onset of ischemic symptoms within the previous 12 hours when it has been anticipated that primary PCI cannot be performed within 120 minutes of first medical contact.5-7 The following section discusses the specific issues regarding fibrinolytic agent eligibility. 12-Lead Electrocardiogram.  Combined with the patient’s history and physical examination, the 12-lead ECG is the key determinant of eligibility for fibrinolysis. The electrocardiographic findings should be consistent with STEMI based on the European Society of Cardiology (ESC)/American College of Cardiology Foundation (ACCF)/AHA/World Heart Federation Task Force for the Universal Definition of Myocardial Infarction. These findings include diagnostic ST elevation in the absence of LVH or LBBB, including ST elevation at the J point in at least two contiguous leads more than 2 mm in men or more than 1.5 mm in women in leads V2 and V3 and/or more than 1 mm in other contiguous chest or limb leads.4 Other electrocardiographic findings that should be considered for fibrinolytic therapy include the following: (1) ST elevation in aVR with coexistent multilead ST depression, concerning for proximal LAD or left main coronary artery occlusion; and (2) evidence of posterior transmural injury (posterior STEMI) indicated by ST segment depression in two or more precordial leads (V1–V4).6 Patients with new LBBB and AMI are at increased risk for a poor outcome and benefit significantly from the administration of rapid reperfusion therapy if they are experiencing an AMI. Tthe new development of LBBB in the setting of AMI suggests proximal occlusion of the LAD artery, placing a significant portion of the left ventricle in ischemic jeopardy. However, new or presumably new LBBB at presentation should not be considered diagnostic of AMI in isolation.55 The finding of a new or presumably new LBBB at presentation of AMI occurs infrequently and, because of this poor diagnostic accuracy, an isolated new LBBB is no longer considered a STEMI equivalent. Rather, one of the more specific electrocardiographic findings to identify STEMI in the setting of LBBB, as defined by Sgarbossa, should be present before an LBBB is considered for STEMI treatment.6 A new or presumably new LBBB in a patient with a classic presentation of AMI who is very ill from an ACS perspective should be expeditiously evaluated with prompt cardiology consultation, if possible, to expedite cardiac-focused care. Patients with STEMI in anterior, inferior, or lateral anatomic locations benefit from fibrinolytic therapy. Acute, isolated posterior wall MI, diagnosed by posterior leads, may be another electrocardiographic indication for fibrinolysis. Although unproven in large fibrinolytic agent trials, patients with isolated posterior AMI may be considered for reperfusion therapy; the emergency clinician at the bedside is in most appropriate position to make these treatment decisions. Fibrinolytic therapy should not be used routinely in patients with only ST segment depression on the 12-lead ECG; in fact, the mortality rate may actually be increased. Multiple studies have demonstrated a significant increase in mortality in fibrinolytictreated patients who presented only with ST segment depression. Acute posterior wall AMI presenting with anterior ST segment depression, as noted, can be considered an exception to this general statement. Patient Age.  Past trials do not provide evidence to support withholding fibrinolytic therapy or choosing one particular agent over another on the basis of the patient’s age. It is general consen-

sus at this point that age alone should no longer be considered a contraindication to fibrinolytic therapy. It must be noted, however, that patients older than 75 years do have a higher incidence of hemorrhagic stroke than younger patients. Time From Symptom Onset.  The generally accepted therapeutic time window for administration of a fibrinolytic agent after the onset of STEMI is 12 hours. Patients treated within the first 6 hours of STEMI have the best outcome. Later administrations, from 6 to 12 hours after STEMI onset, also confer benefit, although of a lesser magnitude. The Late Assessment of Fibrinolytic Efficiency (LATE) trial, which compared fibrinolytic therapy with placebo, found a significant 26% decrease in 35-day mortality in patients treated with t-PA, heparin, and aspirin 6 to 12 hours after the onset of symptoms. There was no significant decrease in mortality among patients treated 12 to 24 hours after symptom onset. Blood Pressure Extremes.  Patients with a history of chronic hypertension should not be excluded from fibrinolytic therapy if their blood pressure is adequately controlled or can be lowered to acceptable levels with standard therapy for ischemic chest pain. The admission blood pressure is also an important indicator of risk of intracerebral hemorrhage. It has been shown that the risk of cerebral hemorrhage increases with systolic blood pressure higher than 150 mm Hg on admission and further increases when systolic blood pressure is 175 mm Hg or higher. Despite an increased mortality rate during the acute setting, fibrinolytic therapy in the setting of hypertension has shown an overall longterm benefit for patients with systolic blood pressure higher than 150 to 175 mm Hg. Although the literature appears to indicate an acceptable risk-benefit ratio for patients with substantially increased systolic blood pressure, a persistently elevated blood pressure—during the ED presentation—that is higher than 200/120 mm Hg is generally considered to be an absolute contraindication to fibrinolytic therapy. The benefit of fibrinolytic therapy in patients with hypotension is unclear. Multiple trials have shown no apparent reduction in mortality rate with fibrinolytic therapy among patients classified as Killip class III or IV. However, reviews of data on STEMI patients have demonstrated that patients with an initial systolic blood pressure below 100 mm Hg who were not treated with fibrinolytic therapy had a very high risk of death (35.1%), and those who were treated with fibrinolytic therapy had the largest absolute benefit (60 lives saved/1000 patients). Although cardiogenic shock and CHF are not contraindications to fibrinolysis, PCI is the preferred method of reperfusion if it can be accomplished on site. Retinopathy.  Active diabetic hemorrhagic retinopathy is a strong relative contraindication to fibrinolytic therapy because of the potential for permanent blindness caused by intraocular bleeding. There is no reason, however, to withhold the use of a fibrinolytic agent in a diabetic patient with evidence of simple background retinopathy. Patients with diabetes mellitus who sustain a STEMI have an almost doubled incidence of mortality. It is impossible to determine the presence or absence of active retinal hemorrhage in the ED during the care of STEMI; thus, the emergency clinician should consider the risk-benefit analysis with respect to the presentation and involve the patient in the decision making. Cardiac Arrest Requiring Cardiopulmonary Resuscitation.  CPR is not a contraindication to fibrinolytic therapy unless CPR is prolonged—more than about 10 minutes—or extensive chest trauma from manual compression is evident. Although the in-hospital mortality rate is higher in AMI patients who experience cardiac arrest and then receive fibrinolytic agents in the ED, no difference has been found in the rates of bleeding complications. Specifically, hemothorax and cardiac tamponade were not diagnosed in cardiac arrest patients receiving CPR and

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fibrinolytics who survived to admission. Even CPR prolonged beyond 10 minutes does not appear to be associated with higher rates of complication. Again, the emergency clinician should consider the risk-benefit analysis with respect to the presentation in this high-acuity, complex medical situation. Previous Stroke or Transient Ischemic Attack.  A history of a previous stroke or TIA is a major risk factor for hemorrhagic stroke after treatment with fibrinolytic therapy. A history of previous ischemic stroke should remain a strong relative contraindication to fibrinolytic therapy, and previous hemorrhagic stroke is an absolute contraindication. Previous Myocardial Infarction or Coronary Artery Bypass Graft.  In the setting of STEMI, a previous MI should not preclude consideration for treatment with fibrinolytic agents. Without treatment, there is a potential for greater loss of function in the newly infarcting region of the myocardium. In patients with a previous MI, studies of fibrinolysis have demonstrated a 26% relative mortality rate reduction, and patients with a history of past MI who received fibrinolytic therapy for recurrent acute infarction have a decreased mortality rate compared to control patients without fibrinolytic therapy. Many studies have reported successful fibrinolysis in STEMI patients with a prior CABG, but these patients should be preferentially considered for direct angioplasty, if immediately available, or combined fibrinolysis and rescue angioplasty. Complete thrombotic occlusion of the bypass graft is the cause of AMI in approximately 75% of cases as opposed to native vessel occlusion. Because of the large mass of thrombus and absent flow in the graft, conventional fibrinolytic therapy may be inadequate to restore flow. Recent Surgery or Trauma.  Recent surgery or trauma is considered a relative contraindication to fibrinolytic therapy. The term recent has been subject to variable interpretation in fibrinolytic trials. The ACCF/AHA guidelines list significant head or facial trauma in the past 3 months and intracranial or intraspinal surgery within the past 2 months as absolute contraindications to fibrinolytic therapy in STEMI. Major surgery within the past 3 weeks and recent internal bleeding (2–4 weeks) are also listed as relative contraindications to fibrinolytic therapy in the setting of STEMI.5,6 Menstruation.  Because natural estrogen is partially cardioprotective, there is very little clinical experience with fibrinolysis in premenopausal women. Gynecologists have indicated that any excessive vaginal bleeding that may occur after undergoing fibrinolytic therapy should be readily controllable by vaginal packing and therefore can be considered as a compressible site of bleeding. Percutaneous Coronary Intervention.  Although fibrinolysis has widespread availability and a proven ability to improve coronary flow, limit infarct size, and improve survival in STEMI patients, many individuals with acute infarction are not suitable candidates. PCI has many theoretic advantages over fibrinolysis, including an increased number of eligible patients, lower risk of intracranial bleeding, significantly higher initial reperfusion rate, earlier definition of coronary anatomy with rapid triage to surgical intervention, and risk stratification allowing safe, early hospital discharge. Potential disadvantages include lack of operator expertise and numerous catheterization laboratory logistic issues, including limited geographic availability and delays to therapy application. However, it must be stated that PCI is superior when applied early and rapidly in the STEMI patient, yet it loses its treatment advantage over fibrinolysis if time to procedure is prolonged. Several trials of varying sizes comparing primary PCI with fibrinolysis have been reported. Interventions in the early trials were performed before the widespread adoption of coronary stents with GPI. Despite a clear and consistent benefit of PCI in

restoring patency of the infarct-related artery, differences in mortality in the individual trials were difficult to evaluate because of the smaller sample sizes. It has been shown that compared with standard-dose t-PA, PCI reduces the combined occurrence of nonfatal reinfarction or death, is associated with a lower rate of intracranial hemorrhage, and results in similar left ventricular function. Other studies have indicated that primary angioplasty is associated with a higher rate of patency of the infarct-related artery, less severe residual stenotic lesion, better left ventricular function, and less recurrent myocardial ischemia and infarction than in patients receiving streptokinase. Multiple studies comparing PCI versus t-PA have now shown a decrease in death, reinfarction, and nonfatal disabling stroke in patients with STEMI when treated with PCI. These results even held true in the setting of accelerated t-PA administration and patients requiring transfer for PCI when the transfer can occur within 3 hours. Multiple studies continue to support the findings that PCI is superior to fibrinolytic therapy in the setting of STEMI, even where rapid transfer for PCI is necessary. The combination of dual-antiplatelet therapy in addition to PCI with stenting has been shown to reduce the risk of death, recurrent MI, stroke, or need for urgent revascularization by about 50% compared to PCI with angioplasty alone. This dramatic reduction in death and cardiovascular events has led to PCI with stenting to replace simple angioplasty as the treatment of choice for STEMI. The longer term results with PCI, however, are less well established. Much of the earlier literature comparing acute reperfusion therapies in STEMI did not include the use of coronary stenting during PCI or contemporary dual-agent platelet therapy. Previous large studies showed no overall mortality advantage of PCI at 6 months. The issue of long-term outcome in PCI-managed STEMI patients is further complicated by drug-eluting stents (DESs). Early studies used bare metal stents, which, in the setting of an acute thrombotic event such as STEMI, raised concern regarding stent thrombosis with obstruction and recurrent AMI. PCI with stenting is superior to standard angioplasty. The addition of DESs to the equation has produced less favorable results, however, with similar rates of MI and death coupled with a lower rate of revascularization in the DES patients at several years postintervention. Rescue Percutaneous Coronary Intervention.  Historically, rescue PCI was considered advantageous in patients whose infarct-related arteries failed to reperfuse after fibrinolytic therapy. These patients are profoundly ill, with a markedly worse outcome. Some centers routinely catheterize patients after fibrinolytic therapy to determine whether successful reperfusion has occurred and to perform PCI if feasible. Other centers catheterize patients after fibrinolytic therapy only if there is clinical evidence that the infarct-related artery fails to open, as suggested by continued chest pain or persistent ST segment elevation. Large trials have compared outcomes after rescue PCI with a conservative management strategy in STEMI patients in whom fibrinolysis has failed. Rescue PCI has not been associated with improved short-term or long-term survival; furthermore, increased rates of stroke and transfusion were noted in this group. In a meta-analysis of STEMI patients who did not achieve satisfactory reperfusion after fibrinolysis, rescue PCI was not associated with mortality reductions. In this very ill group, however, the incidence of heart failure and recurrent infarction was reduced. Repeat fibrinolysis was not associated with significant improvements in mortality or recurrent infarction. Although the decision to offer rescue PCI to the patient in whom fibrinolytic therapy has failed remains controversial, evidence favors rescue PCI (class IIa recommendation)5,6 and does not support the use of repeat fibrinolysis. Facilitated Percutaneous Coronary Intervention.  Facilitated percutaneous coronary intervention refers to combination

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therapy involving fibrinolysis coupled with emergent PCI. This concept originally was developed to maximize therapy in STEMI patients who would be transferred urgently for PCI. The patient would receive the additive benefit of medical therapy (a fibrinolytic agent) before transfer, optimizing perfusion in the culprit artery before arrival at the PCI-capable institution. Unfortunately, outcomes from this facilitated approach are less optimal than fibrinolysis or standard PCI alone.56 In light of these results, the continued use of a facilitated PCI approach should not be used at this time outside of a scientific investigation. Choice of Reperfusion Therapy.  As noted, the two primary choices for reperfusion therapy in the STEMI patient include fibrinolysis and PCI. Important issues to consider in this treatment choice include the selected form of reperfusion therapy, total elapsed time of infarction, patient’s candidacy for fibrinolysis (ie, presence or absence of contraindications), type of hospital facility (ie, PCI-capable), and anticipated time to transfer to the PCI-capable facility. Regardless of the strategy selected, the system’s reperfusion goal should be a first medical contact to therapy time that is within 120 minutes—a 30-minute goal for the initiation of fibrinolysis and 120-minute goal for PCI performance. These time periods include transfer for PCI; in other words, if a transfer from one hospital to another is part of an individual patient’s care plan, the first medical contact is the initial hospital.5-7 With respect to treatment benefit, there are important timebased differences when one considers PCI and fibrinolysis. First, PCI is the preferred strategy for STEMI reperfusion therapy, assuming that it can be performed in timely fashion. Second, the changing impact on mortality, as total infarction time increases, is much more pronounced with fibrinolysis as compared to PCI. The success of PCI in reestablishing perfusion in the early hours after STEMI does not change significantly with time; conversely, the ability of fibrinolytic therapy to restore coronary perfusion decreases significantly with increasing time of infarction, reaching a significant reduction at approximately 6 hours of total STEMI time. The following discussion considers the preferred reperfusion strategy for the STEMI patient arriving at non–PCI-capable hospital. The patient should be considered for immediate transfer without fibrinolysis to a PCI-capable facility within an appropriate time period (AHA class I recommendation).5-7 If the patient is a candidate for fibrinolysis and cannot be transferred to a PCIcapable hospital within an appropriate time period, immediate fibrinolytic therapy should be administered, with consideration of subsequent transfer for cardiac catheterization within the next 24 hours; at this time, PCI can be performed, if indicated. If the patient is not a fibrinolytic candidate, transfer should be arranged as soon as possible.5-7 In this series of recommendations, “appropriate time period” is a key phrase and must be considered from the perspective of two important variables—the total time duration of acute infarction at the time of presentation and anticipated time to performance of PCI. From these two perspectives, the following general statements regarding reperfusion management of the STEMI patient who arrives at a non–PCI-capable hospital can be made: • If presentation is within 2 hours or less of symptom onset, consider immediate fibrinolysis unless transfer time for PCI is anticipated to be no more than 60 minutes (AHA class IIB recommendation). • If presentation is within 2 to 3 hours of symptom onset, consider immediate fibrinolysis or PCI if time to transfer time for PCI is anticipated to be no more than 60 to 120 minutes (AHA class IIB recommendation). • If presentation is within 3 to 12 hours of symptom onset, consider PCI as opposed to initial fibrinolysis if time to

transfer time for PCI is anticipated to be no more than 120 minutes (AHA class IIB recommendation). As the total STEMI time increases, the overall effectiveness of fibrinolysis decreases significantly; at 6 hours of STEMI time, a longer delay allowing for transfer for PCI is a reasonable management option.7 If the STEMI patient arrives at a PCI-capable hospital, PCI remains the reperfusion therapy of choice, with the same time constraints as noted above. The STEMI patient should arrive in the catheterization laboratory with initiation of procedure within 120 minutes of initial medical contact.5-7 If PCI is not possible at the PCI-capable hospital and the patient is a fibrinolytic candidate, fibrinolytic therapy should be administered if a delay beyond 120 minutes is anticipated. Other candidates for PCI include high-risk STEMI patients, so-called late presenters (ie, >3 hours since the onset of STEMI symptoms), patients in cardiogenic shock, and individuals with contraindication to fibrinolysis. Furthermore, when the diagnosis of STEMI is in doubt, PCI is the most appropriate diagnostic and therapeutic strategy. Hospitals should have a fibrinolytic therapy plan in place for the treatment of STEMI patients in the event of PCI delay or unavailability. If the time required to mobilize staff and arrange for PCI is prolonged, or if delays in transfer are anticipated, fibrinolysis is preferred within the first several hours of STEMI occurrence. Prior agreement between the ED and cardiovascular physicians at institutions with invasive capability must be obtained and a transfer pathway should be in place so that PCI consideration does not introduce further delays in fibrinolytic drug administration. Consensus clinical pathways limit additional delays in the administration of fibrinolytic agents for patients who are considered for PCI in STEMI. It has been well established that delays to reperfusion therapy have negative consequences. Delays in reperfusion are associated with increased mortality for PCI and fibrinolysis treatment strategies and appear to be more pronounced in patients undergoing fibrinolysis. A cooperative effort among all providers and units can markedly reduce the door to therapy time in STEMI patients.42 A so-called STEMI alert system, analogous to the trauma alert approach, mobilizes hospital-based resources, optimizing the approach to the AMI patient. This system, whether activated by data gathered in the ED or in the field, has the potential to offer time-sensitive therapies in a rapid fashion. Emergency clinician activation of the catheterization laboratory has demonstrated very high rates of accurate STEMI diagnosis while markedly reducing the time to definitive therapy, with very low rates of inappropriate activation (ie, the STEMI mimicker). The ACC and AHA recognize the numerous challenges and potential difficulties in achieving these reperfusion therapy time goals.6 Reperfusion Therapy in Cardiogenic Shock.  Patients with STEMI experiencing cardiogenic shock, which occurs in up to 10% of cases, demand special consideration because of a mortality rate approaching 80%. Fibrinolysis is not effective in these patients, likely owing to a significantly lower coronary perfusion pressure. In circulatory shock states, the occlusive thrombus is not exposed to the fibrinolytic agent, resulting in clinical failure of the drug. In large fibrinolytic trials, STEMI patients in cardiogenic shock were not found to benefit from fibrinolysis. Conversely, primary PCI has been investigated in more than 600 patients in several small studies. A cumulative analysis has revealed a significantly lower mortality rate (45%) compared with placebo or historical controls. In previous studies that compared the outcomes of STEMI patients in cardiogenic shock, patients were randomly assigned to emergency revascularization (PCI or emergent CABG) or initial medical stabilization, including fibrinolysis. Overall mortality at

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30 days did not differ significantly between the revascularization and medical therapy groups, but the 6-month mortality was lower in the revascularization group. This finding—of reduced mortality in PCI compared to fibrinolytic therapy for patients with cardiogenic shock in the setting of STEMI—has been repeated in multiple studies. Thus, emergency revascularization with PCI or CABG is preferred for patients with STEMI complicated by cardiogenic shock, irrespective of the delay to treatment.6 Fibrinolytic therapy should be considered in eligible patients who are otherwise unsuitable candidates for PCI or CABG.6

Resuscitated Cardiac Arrest With Suspected Acute Coronary Syndrome In the patient who has been resuscitated from out-of-hospital cardiac arrest (OHCA), postresuscitation care in the ED includes many important areas of management. Beyond the basic critical care interventions, urgent coronary reperfusion should be considered in the resuscitated OHCA patient who has experienced a cardiogenic cardiac arrest. More than 50% of these resuscitated, cardiogenic, OHCA patients who have undergone urgent coronary reperfusion survive to hospital discharge, a survival rate higher than the approximate 10% survival rate of all patients experiencing OHCA cardiac arrest in the out-of-hospital arena. Most of these patients have satisfactory neurologic function at the time of hospital discharge.57 The literature base considering this issue is heterogeneous, addressing a broad range of resuscitated patient types, including important differences in the various initial cardiac arrest rhythms, range of subsequent mental status after the return of spontaneous circulation (ROSC), and cardiopulmonary status in the ED. Thus, the most appropriate candidate types for urgent coronary reperfusion have not been conclusively identified.58-63 Most OHCA patients have a cardiogenic cause responsible for the cardiac arrest. ACS is considered to be the most frequent cause, including STEMI and NSTEMI; not surprisingly, the ECG demonstrates ST segment deviation in many of these patients. For example, the alert patient with ventricular tachycardia or ventricular fibrillation who has been resuscitated and demonstrates STEMI on the ECG likely will benefit significantly from emergent PCI.7 Although STEMI patients are the most likely group to achieve benefit from emergent cardiac catheterization with PCI, if indicated, electrocardiographic findings should not be considered as strict selection criteria for performing urgent PCI. It has been noted that patients with electrocardiographic presentations other than STEMI derive benefit from this intervention.58,63 Importantly, a clinical presentation of coma after cardiac arrest should not be considered a contraindication to reperfusion therapy because this finding is commonly present. Multiple investigations have followed patients with resuscitated cardiac arrest complicated by STEMI. Among those patients who were conscious at the time of PCI, invasive therapy restored coronary perfusion in more than 90%of cases, and all these patients survived without neurologic deficit. The outcome in the comatose patient subgroup was less favorable, with approximately a 50% survival rate and good neurologic outcome, yet still markedly better than the average OHCA victim who has achieved ROSC.1 Therapeutic hypothermia used in the resuscitated, unresponsive OHCA patient with presumed cardiogenic cause and, when combined with PCI, demonstrates an impressive rate of survival, with good neurologic outcome. Based on previous case series therapeutic hypothermia coupled with PCI demonstrates a significantly improved rate of survival. The AHA, in their 2015 guidelines, have suggested that urgent cardiac catheterization with PCI, if indicated, should be considered in the resuscitated OHCA patient, regardless of the presence or absence of ST segment elevation.7 These guidelines noted that “…coronary angiography with PCI, if indicated, should be per-

formed emergently in those resuscitated patients with suspected cardiogenic cardiac arrest who demonstrate electrocardiographic ST segment elevation…”7; this recommendation is a class I indication. Furthermore, addressing two specific presentation types, emergent coronary angiography “…is a reasonable intervention in the resuscitated cardiogenic cardiac arrest …[in patients who are comatose and do not demonstrate ST segment elevation on the ECG]”7 (class IIA indication). It is reasonable to consider including PCI as part of a standard postresuscitation care program because almost 50% of cardiogenic cardiac arrest survivors have an acute occlusion or culprit lesion amenable to intervention.58 For a range of issues, PCI is the preferred reperfusion strategy in the post-ROSC patient; in this patient presentation with STEMI, in which PCI is not available in timely fashion, fibrinolysis can be considered, assuming that there are no contraindications. Cardiac catheterization with the possibility of PCI, if warranted, can offer survival and functional benefits to selected patients. Patient selection for emergent PCI after resuscitation from OHCA, however, is a challenging, difficult to answer question. What is clear in this situation is that a subset of these patients, with and without ST segment elevation, alert or comatose, do benefit significantly from emergent reperfusion therapy, delivered along with other appropriate postresuscitation management. With the significant benefit derived by some individuals, emergent reperfusion should be considered in the OHCA patient who has achieved ROSC. In this consideration, the most appropriate discussion should include the emergency clinician and cardiologist. It must be noted that the emergency clinician can suggest and advocate for such and intervention but the invasive cardiologist ultimately makes this decision, as is appropriate in the turnover of care that is occurring.

Management Summary: Potential Pharmacologic Management Approach The patient with stable or resolved chest pain, with a normal to minimally abnormal ECG and a negative serum marker, is best managed initially with NTG sublingually or topically in combination with aspirin. Resolution of the discomfort with continued stability probably does not warrant further ED pharmacologic management. Continued or recurrent pain in the ED may be treated with parenteral morphine sulfate. Continued pain may ultimately require IV NTG, heparinization with UFH or LMWH, and additional antiplatelet therapy with a thienopyridine (eg, clopidogrel, ticagrelor). The patient with stable UA (ie, new-onset or altered pattern but now symptom-free and lacking abnormal serum markers and an abnormal ECG) does not require heparin or other more aggressive platelet inhibition therapy in most cases. The ACS patient with an abnormal ECG, particularly ST segment and T wave abnormalities, or elevated serum marker levels may warrant numerous therapies, including ASA, heparin, and other antiplatelet agents (typically a thienopyridine). NTG may be administered by the topical or IV route. The patient with recurrent angina may also benefit from such an approach. Heparin therapy is generally indicated in this case. The AMI patient without ST segment elevation—the NSTEMI patient—requires aspirin, NTG, heparin, a thienopyridine, or an alternative second antiplatelet agent, and morphine sulfate. The patient with STEMI is treated with the preceding medications noted and should be considered for urgent revascularization, achieved by fibrinolytic agents, PCI, or, in the rare case, CABG.

DISPOSITION Just as coronary artery disease and ACS represent a spectrum of disease, there is a similar spectrum of disposition options for

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patients presenting to the ED with chest pain or other complaints concerning for ACS. These options include rapid transport to the cardiac CCL within minutes of arrival for emergent intervention, ICU admission, acute care admission with cardiac monitoring, observation unit admission (actual or virtual), and discharge to home after evaluation. Patients with evidence of an acute or ongoing ACS event will require admission to the hospital. The final location of these admissions will depend on the patient’s clinical presentation, electrocardiographic findings, results of the troponin assay, and cardiorespiratory status. If the patient’s presentation and ECG are consistent with STEMI, the disposition is determined by the reperfusion options available at the facility. In a facility where interventional cardiology and PCI are available, the patient can be urgently transported to the CCL for reperfusion via PCI, as long as this can be accomplished without delay. If PCI is not available as a timely option, fibrinolytic therapy should be initiated rapidly. Regardless of the reperfusion strategy of choice, patients with STEMI will require ICU admission due to the significant risk of adverse events during the first 24 hours of hospitalization. All hospitals, regardless of their size or resources, should have a clear care pathway for STEMI patients that may include CCL activation or fibrinolysis, followed by admission to the ICU; an expedited transfer should also be considered for the appropriate patient, dependent on the initial facility’s capabilities. In patients who have evidence of ACS without STEMI, their disposition is based on the emergency clinician’s risk assessment of the patient and his or her clinical presentation. Patients with high-risk presentations, including dynamic electrocardiographic changes, uncontrolled ischemic pain, or rising troponin levels (consistent with NSTEMI or unstable angina) will likely benefit from ICU-level care and monitoring due to their significant risk of adverse events. If the patient has no evidence of active ischemia, most risk stratification tools recommend separating patients into categories based on the risk of ACS and adverse events. High-risk patients without dynamic electrocardiographic changes or elevated troponin levels often benefit from hospitalization in a monitored bed, with further diagnostic testing and management. Intermediaterisk patients often benefit from abbreviated stays in an observation unit (structural or virtual unit) for repeat troponin level tests and possible provocative testing or anatomic imaging, if indicated. Patients at low risk of ACS can often receive evaluation in the ED setting, followed by discharge with primary care follow-up and possible outpatient testing, as indicated.

Transfer of a Patient With Acute Coronary Syndrome There are several indications for the transfer of a patient with ACS to a facility with PCI capability. These include rapid access to PCI, persistent hemodynamic instability or ventricular dysrhythmias, and postinfarction or postreperfusion ischemia. Hospital transfer for PCI is also suggested for patients with fibrinolytic contraindications who may benefit from PCI or CABG. The urgent transfer of a fibrinolytic-eligible STEMI patient to another institution for PCI is not recommended until fibrinolytic therapy has been initiated if a delay in PCI application is anticipated. The ACC/AHA guidelines have noted that in hospitals without PCI capability, immediate transfer for primary PCI is a treatment option when it can be accomplished within 60 to 120 minutes of first medical contact, depending on the duration of STEMI at the time of presentation.7 If delays in PCI performance are anticipated, and the patient is an acceptable candidate for fibrinolysis, the fibrinolytic should be started before or during transport to the receiving hospital. This decision is made in conjunction with the receiving cardiologist. Many institutions are not PCI-capable. Thus, the decision for the emergency clinician involves not only the relatively simple fibrinolysis versus PCI issue but also the potential need for urgent transfer to a larger center. Previous studies have explored the potential benefit of PCI over fibrinolysis and the all-important impact of transfer of the STEMI patient in a noninterventional hospital, These studies revealed about a 25% reduction in the composite endpoints of death, recurrent infarction, stroke, and/ or revascularization in fibrinolytic patients compared to those in the PCI group. The conclusion was that the early benefit from a transfer-related invasive strategy was sustained over long-term follow-up, but the benefit was largely a result of a lower event rate in the PCI patients in the first 30 days after presentation. The potential need to transfer the STEMI patient over long distances can also affect reperfusion therapy decisions. This is usually seen in rural areas with long transport times to the nearest PCI facility. In this setting, organized processes for rapid transfer should be in place to address the expected delays, including a rapid initiation of transfer by the emergency clinician, an agreed-on expedited transfer process to the PCI center, and rapid access to a transport vehicle (ground or air) that will be needed for safe transport. Multiple investigations have suggested that rapid transfer for PCI in the STEMI patient can occur in the rural setting with acceptable time to therapy.

KEY CONCEPTS • Angina-equivalent symptoms that are not characteristically associated with ACS vary widely and often distract from the diagnosis. The patient’s age, diabetes status, ethnicity, and gender are considered with an atypical history. • Limitations of the 12-lead ECG in ACS include initial nondiagnostic findings, evolving fluctuations with ongoing symptoms, anatomic myocardial blind spots, and confounding or obscuring patterns, such as LBBB. • Patients with proximal left anterior descending artery stenosis (Wellens syndrome) may have deeply inverted or biphasic T waves in the anterior precordial leads. • ST segment elevation in lead aVR more than 0.5 mV suggests left main coronary artery disease. • Functional testing strategies for ACS include graded exercise testing, echocardiography, and myocardial scintigraphy. Graded exercise testing, with or without nuclear scintigraphy, can be used in the

patient with low to moderate likelihood of CAD who is able to exercise. Myocardial scintigraphy with pharmacologic stress can be used in the debilitated or older patient (ie, unable to exercise). Echocardiography with pharmacologic stress is appropriate for the woman older than 45 years, the patient with diabetes mellitus, and the patient with other forms of organic heart disease (eg, valvular dysfunction, low cardiac output states). • The use of coronary CT angiography is most appropriate in the younger patient; excessive coronary calcification can reduce the ability of CCTA to evaluate the patient for significant CAD reliably. • Fibrinolysis is not effective in patients with STEMI who are in cardiogenic shock. • Unless used for rate control of supraventricular dysrhythmia in a patient who cannot tolerate beta blockade, calcium channel blockade is not recommended for those with ACS.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 68  Acute Coronary Syndrome

REFERENCES 1. Go AS, et al: Heart disease and stroke statistics—2014 update. A report from the American Heart Association. Circulation 129:e28–e292, 2013. 2. Mackay J, Mensah G, editors: The atlas of heart disease and stroke, Geneva, 2004, World Health Organization. 3. Hunink MG, et al: The recent decline in mortality from coronary heart disease, 1980-1990: the effect of secular trends in risk factors and treatment. JAMA 227: 535–542, 1997. 4. Thygesen K, et al: Third universal definition of myocardial infarction. J Am Coll Cardiol 60:1581–1598, 2012. 5. Amsterdam EA, et al: 2014 AHA/ACC guideline for the management of patients with non–st-elevation acute coronary syndromes. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation 130:e344–e426, 2014. 6. O’Gara PT, et al: 2013 ACCF/AHA Guideline for the management of ST-elevation myocardial infarction: executive summary. Circulation 127:529–555, 2013. 7. O’Connor RE, et al: Part 9: acute coronary syndromes; 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 132:S483–S500, 2015. 8. Holly J, et al: Prospective evaluation of the use of the thrombolysis in myocardial infarction score as a risk stratification tool for chest pain patients admitted to an ED observation unit. Am J Emerg Med 31:185–189, 2013. 9. Davis M, et al: A prospective evaluation of the utility of the prehospital 12-lead electrocardiogram to change patient management in the emergency department. Prehosp Emerg Care 18:9–14, 2014. 10. Nam J, et al: Systematic review and meta-analysis of the benefits of out-of-hospital 12-lead ECG and advance notification in ST-segment elevation myocardial infarction patients. Ann Emerg Med 64:176–186, 2014. 11. Mahler SA, et al: Identifying patients for early discharge: performance of decision rules among patients with acute chest pain. Int J Cardiol 168:795–802, 2013. 12. Weisenthal BM, et al: Relation between thrombolysis in myocardial infarction risk score and one-year outcomes for patients presenting at the emergency department with potential acute coronary syndrome. Am J Cardiol 105:441–444, 2010. 13. Hess EP, et al: Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis. Canadian Med Assoc J 182:1039–1044, 2010. 14. Body R, et al: The value of symptoms and signs in the emergent diagnosis of acute coronary syndromes. Resuscitation 81:281–286, 2010. 15. Smith SW, et al: Electrocardiographic differentiation of early repolarization from subtle anterior ST-segment elevation myocardial infarction. Ann Emerg Med 60:45–52, 2012. 16. Goebel M, et al: A new STEMI equivalent pattern? Prominent T wave and J point depression in the precordial leads associated with ST segment elevation in lead aVr. Am J Emerg Med 32:e5–e8, 2014. 17. Kelly AM, Kim S: Does undetectable troponin I at presentation using a contemporary sensitive assay rule out myocardial infarction? A cohort study. Emerg Med J 32:760–763, 2014. 18. Body R, et al: Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay. Ann Clin Biochem 52:543–549, 2015. 18a.  Zhelev Z, et al: Diagnostic accuracy of a single baseline measurement of Elecsys troponin T high-sensitivity assay for diagnosis of acute myocardial infarction in emergency department: systematic review and meta-analysis. BMJ 350:h15, 2015. 19. Kelly AM, Klim S: Prospective external validation of an accelerated (2-h) acute coronary syndrome rule-out process using a contemporary troponin assay. Int J Emerg Med 7:42, 2014. 20. Mahler S, et al: The HEART pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 8:195–203, 2015. 21. Reichlin T, et al: Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation 124:136–145, 2011. 22. Bonaca MP, et al: Evaluation of the diagnostic performance of current and nextgeneration assays for cardiac troponin I in the BWH-TIMI ED Chest Pain Study. Eur Heart J Acute Cardiovasc Care 2:195–202, 2013. 23. de Lemos JA, et al: Association of troponin t detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 304:2503– 2512, 2010. 24. Aldous SJ, et al: Early dynamic change in high-sensitivity cardiac troponin T in the investigation of acute myocardial infarction. Clin Chem 57:1154–1160, 2011. 25. Parsonage WA, et al: Validation of an accelerated high-sensitivity troponin T assay protocol in an Australian cohort with chest pain. Med J Aust 200:161–165, 2014. 26. Agewall S, et al: Troponin elevation in coronary vs. non-coronary disease. Eur Heart J 32:404–411, 2011. 27. Yukihito, et al: High-sensitivity cardiac troponin T in essential hypertension. J Cardiol 58:226–231, 2011. 28. Volz KA, et al: Creatine kinase-MB does not add additional benefit to a negative troponin in the evaluation of chest pain. Am J Emerg Med 30:188–190, 2012. 29. Kontos MC, et al: Troponin-positive, MB-negative patients with non-ST-elevation myocardial infarction: an undertreated but high-risk patient group: results from the National Cardiovascular Data Registry acute Coronary Treatment and Intervention Outcomes Network-Get With The Guidelines (NCDR ACTION-GWTG) registry. Am Heart J 1608:19–25, 2010. 30. Larochelle MR, et al: Reducing excess cardiac biomarker testing. J Gen Intern Med 29:1468–1474, 2014.

31. Wolk MJ, et al; American College of Cardiology Foundation Appropriate Use Criteria Task Force: ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol 63:380–406, 2014. 32. Stefanini GG, Windecker S: Can coronary computed tomography angiography replace invasive angiography? Coronary computed tomography angiography cannot replace invasive angiography. Circulation 131:418–426, 2015. 33. Achenbach S: Can coronary computed tomography angiography replace invasive angiography? Yes: it is all about finding the right test for the right person at the right time. Circulation 131:410–417, 2015. 34. Taylor AJ, et al: ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation 122:e525–e555, 2010. 35. den Dekker MA, et al: Diagnostic performance of coronary CT angiography for stenosis detection according to calcium score: systematic review and meta-analysis. Eur Radiol 22:2688–2698, 2012. 36. Hoffmann U, et al: Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med 367:299–308, 2012. 37. Hulten E, et al: Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials. J Am Coll Cardiol 61:880–892, 2013. 38. Mahler S, et al: The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes 8:195–203, 2015. 39. O’Connor RE, et al: Part 10: Acute coronary syndromes: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 122:S787–S817, 2010. 40. O’Connor RE, et al: Emergency medical services management of ST-segment elevation myocardial infarction in the United States— report from the American Heart Association Mission: Lifeline Program. Am J Emerg Med 32:856–863, 2014. 41. Camp-Rogers T, et al: Hospital-based strategies contributing to PCI time reduction in the STEMI patient: a review of the “systems of care” approach. Am J Emerg Med 30:491–498, 2012. 42. Lubovich A, et al: Bypassing the emergency room to reduce door-to-balloon time and improve outcomes of ST elevation myocardial infarction patients: analysis of data from 2004-2010 ACSIS Registry. J Interv Cardiol 28:141–146, 2015. 43. Squire BT, et al: Effect of prehospital cardiac catheterization lab activation on doorto-balloon time, mortality, and false-positive activation. Prehosp Emerg Care 18:1–8, 2014. 44. Lee CH, et al: Early cardiac catheterization laboratory activation by paramedics for patients with ST-segment elevation myocardial infarction on prehospital 12-lead electrocardiograms. Prehosp Emerg Care 14:153–158, 2010. 45. Ranchord AM, et al: High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial. Am Heart J 163:168–175, 2012. 46. Stub D, et al: Air versus oxygen in ST-segment elevation myocardial infarction. Circulation 131:2143–2150, 2015. 47. Grosser T, et al: Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 127:377–385, 2013. 48. Montalescot G, et al: Pretreatment with prasugrel in non-ST segment elevation acute coronary syndromes. N Engl J Med 369:999–1010, 2013. 49. Cowper PA, et al: Economic analysis of ticagrelor therapy from a U.S. perspective: results from the PLATO study. J Am Coll Cardiol 65:465–476, 2015. 50. Angiolillo D, et al: Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA 307:265–274, 2012. 51. Bhatt DL, et al: Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 368:1303–1313, 2013. 52. Angiolillo DJ, et al: Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA 307:265–274, 2012. 53. Ferraris VA, et al: 2012 Update to the Society of Thoracic Surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations. Ann Thorac Surg 94:1761–1781, 2012. 54. Jain S, et al: Utility of left bundle branch block as a diagnostic criterion for acute myocardial infarction. Am J Cardiol 107:1111–1116, 2011. 55. Itoh T, et al: Comparison of long-term prognostic evaluation between preintervention thrombolysis and primary coronary intervention: a prospective randomized trial: five-year results of the IMPORTANT study. Circ J 74:1625–1634, 2010. 56. Kern KB: Optimal treatment of patients surviving out-of-hospital cardiac arrest. J Am Coll Cardiol Intv 5:597–605, 2012. 57. Hollenbeck RD, et al: Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI. Resuscitation 85:88–95, 2014. 58. Cronier P, et al: Impact of routine percutaneous coronary intervention after out-ofhospital cardiac arrest due to ventricular fibrillation. Crit Care 15:R122, 2011.

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59. Nanjayya VB, Nayyar V: Immediate coronary angiogram in comatose survivors of out-of-hospital cardiac arrest—an Australian study. Resuscitation 83:699–704, 2012. 60. Strote JA, et al: Comparison of role of early (less than six hours) to later (more than six hours) or no cardiac catheterization after resuscitation from out-of-hospital cardiac arrest. Am J Cardiol 109:451–454, 2012.

61. Waldo SW, et al: Comparison of clinical characteristics and outcomes of cardiac arrest survivors having versus not having coronary angiography. Am J Cardiol 111:1253–1258, 2013. 62. Zanuttini D, et al: Impact of emergency coronary angiography on in-hospital outcome of unconscious survivors after out-of-hospital cardiac arrest. Am J Cardiol 110:1723–1728, 2012.

CHAPTER 68: QUESTIONS & ANSWERS 68.1. A 40-year-old man presents with a 3-hour history of left-sided chest pain, slightly worse in the supine position, associated with mild dyspnea and diaphoresis. He is 2 weeks status post–left anterior/lateral subendocardial myocardial infection (MI), with acute stenting of the left anterior descending and circumflex arteries. He is unable to discern if this pain is the same as his original cardiac pain. His current medications are aspirin, 81 mg/day,

lovastatin, 80 mg/day, amlodipine 10 mg/day, and clopidogrel 75 mg/day. His electrocardiogram (ECG) is shown here. Cardiac troponin I is within normal limits. Vital signs are temperature, 38° C oral, heart rate (HR), 110 beats/min, blood pressure (BP), 153/96 mm Hg, respiratory rate (RR), 22 breaths/min, and O2 saturation, 96%. What is the most likely diagnosis?

I

aVR

V1

V4

II

aVL

V2

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aVF

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A. Coronary ischemia B. Dressler’s syndrome C. Infarct pericarditis D. Pleuritic chest wall pain E. Ventricular aneurysm formation Answer: B. Dressler’s syndrome is a late sequela of typically nontransmural MI. It may occur 1 week to several months post MI. It is an immune-mediated process sometimes associated with pleural or pericardial effusion. Infarct pericarditis is usually seen within the first week after a transmural infarct, and the classic pericarditis electrocardiographic finding may be overshadowed by the MI changes. PR segment depression is seen in both entities. The characteristic ECG, presence of fever, and pain with recumbency argue for this diagnosis. A ventricular aneurysm would be expected after transmural MI; the ECG will demonstrate ST

segment elevation, usually with prominent Q waves and T waves of diminished amplitude. Myocardial ischemia is a possibility, but troponin is negative and ECG is noncontributory. 68.2. A 37-year-old male renal dialysis patient presents with a 6-hour history of intermittent left-sided chest pain. He missed his last dialysis session due to feeling ill. His past history is significant for hypertension with secondary renal failure, tobacco use, and hypercholesterolemia. His current medications are amlodipine, 10 mg/day, a statin, and his renal failure medications. Vital signs are temperature, 36.7° C oral, HR, 92 beats/min, BP, 170/110 mm Hg, RR, 22 breaths/min, and O2 saturation, 95%. His ECG is shown below. The serum potassium level is 5.8 mEq/L. What is the most important intervention?

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A. Calcium gluconate, 1 g IV, followed by dextrose, 100 g, and regular insulin, 10 units IV B. Emergent dialysis C. IV enoxaparin D. IV metoprolol E. Nitroglycerin, aspirin, 325 mg orally, and cardiology consultation Answer: E. The ECG shows asymmetric hyperacute T waves, possibly consistent with coronary ischemia. This is clinically the early electrocardiographic manifestation of AMI. The differential diagnosis of hyperacute T waves is ischemia, hyperkalemia, benign early repolarization, left ventricular hypertrophy, left bundle branch block, and pericarditis. The asymmetry of the T waves argues for ischemia, as does the relatively modest rise in the serum potassium. Enoxaparin might be indicated, but only as part of an acute coronary regimen with appropriate renal dosing. Beta blockers would worsen his hyperkalemia and would have to be carefully considered before administration. 68.3. A 63-year-old woman with a past medical history of diabetes presents with altered mental status, diaphoresis, and substernal chest pain for 4 hours. Vital signs are HR, 96 beats/min, BP, 80/50 mm Hg, RR, 26 breaths/min, temperature, 37° C, and O2 saturation, 94%. The ECG clearly demonstrates a large, anterior, ST segment elevation MI. Your institution does not have a cardiac catheterization laboratory. The closest hospital with a cardiac catheterization laboratory is 2 hours by ground, and no aircraft is available due to weather. After normal saline boluses, what is the most appropriate treatment? A. Administer aspirin, PSY12 inhibitor, intravenous (IV) unfractionated heparin (UFH), vasopressor therapy as needed, and admit to your institution. B. Administer aspirin, PSY12 inhibitor, IV UFH, and immediate transfer to primary percutaneous coronary intervention (PCI) center by ground emergency medical services (EMS). C. Administer aspirin, PSY12 inhibitor, IV UFH, IV fibrinolysis, and immediate transfer to the PCI center. D. Administer aspirin, PSY12 inhibitor, IV UFH, and transfer to the primary PCI center when helicopter becomes available in 4 hours. Answer: B. Patients who present with ST segment elevation myocardial infarction (STEMI) and cardiogenic shock should be preferentially treated with percutaneous coronary intervention (PCI) if there are no contraindications to mechanical reperfusion. Because PCI is the preferred therapy, a delay of beyond the usual threshold of 60 to 120 minutes from first medical contact to PCI for the administration of fibrinolytics is tolerated. Although a delay beyond 120 minutes is tolerable, it should be as small as possible. 68.4. A 48-year-old man with history of hypertension and hypercholesteremia presents with chest pain and hyperacute T waves in an anterior distribution on the initial ECG. During your initial history and physical examination. the patient experiences ventricular fibrillation that responds to cardiopulmonary resuscitation (CPR) and defibrillation after being pulseless for a period of 3 minutes. Following cardiac arrest, the patient is comatose, with the following vital signs: HR, 110 beats/ min, BP, 160/98 mm Hg, RR, 12 breaths/min (intubated), temperature, 36.5° C, and O2 saturation, 96%. A repeat ECG demonstrates a large, evolving anterior STEMI.

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Which of the following treatment plans is most appropriate? A. Administer aspirin, PSY12 inhibitor, IV UFH, IV fibrinolysis, and admission to intensive care unit (ICU) B. Administer aspirin, PSY12 inhibitor, IV UFH, IV fibrinolysis, initiation of therapeutic hypothermia, and admission to ICU C. Neurologic examination for brain death and admission to palliative care because outcome almost universally fatal D. Rapid revascularization with percutaneous coronary intervention (PCI), initiation of therapeutic hypothermia, and admission to ICU for comprehensive postresuscitation care E. Supportive care, and admission to ICU Answer: D. A neurologic examination immediately following cardiac arrest is poorly prognostic of a favorable neurologic outcome with modern postresuscitation care. The sharp increase in survival with a favorable neurologic outcome has elevated rapid revascularization with percutaneous coronary intervention (PCI) and immediate application of therapeutic hypothermia as part of comprehensive postresuscitation care as a class I ACC/AHA recommendation. Although not contraindicated, fibrinolysis is inferior to PCI following cardiac arrest and should only be used when a patient is not a candidate for PCI. 68.5. Which of the following is an absolute contraindication to fibrinolytic therapy? A. Age older than 75 years B. Appendectomy performed 2 months ago C. Previous coronary artery bypass grafting (CABG) D. Previous hemorrhagic stroke E. Systolic blood pressure of 175/90 mm Hg following administration of vasoactive agents Answer: D. Although patients older than 75 years have a higher risk of intercerebral hemorrhage, age should not be considered a contraindication to fibrinolysis. Although prior CABG patients should be preferentially considered for PCI, there is no contraindication to fibrinolytic use in these patients if PCI is not available. Systolic blood pressure above 150 mm Hg is a risk factor for intracerebral hemorrhage. Only hypertension persistently above 200/120 mm Hg, despite reasonable efforts, should be considered an absolute contraindication. Recent major surgery or trauma is a relative contraindication for fibrinolysis; however, the term recent is variably defined in the fibrinolytic literature and never as more than 6 weeks. 68.6. Which of the following drugs provides mortality benefit in the setting of AMI? A. Aspirin B. Intravenous beta blocker C. Intravenous morphine D. Nitroglycerin E. Oxygen Answer: A. The ISIS-2 trial has demonstrated that aspirin independently reduces mortality by 23% in the setting of AMI. Intravenous morphine has not been shown to improve mortality and has been associated with mortality. Although nitroglycerin does improve symptoms and cause vasodilation, it has never been proven to improve mortality. Oxygen beyond that needed to maintain an oxygen saturation of 94% has been associated with additional mortality. The use of intravenous beta blockers does not offer significant benefit and is associated with an increased rate of adverse events.

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68.7. A 42-year-old male patient presents with 45 minutes of chest pain. The ECG is depicted below. You are working at a noninvasive (ie, no PCI capability) hospital; transfer time to the closest major medical center with PCI

capability is 4.5 hours considering weather and logistics. The patient has no contraindications for fibrinolysis. Which of the following statements is most appropriate?

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

A. The patient must be transferred rapidly to the closest PCI center, with initiation of appropriate β-adrenergic blocking agents and antiplatelet and anticoagulant therapies before transfer. B. The patient should receive a fibrinolytic agent followed by appropriate antiplatelet and anticoagulant therapies with admission to your hospital’s ICU. C. The patient should receive a fibrinolytic agent followed by appropriate antiplatelet and anticoagulant therapies, with transfer to the closest PCI center for immediate PCI. D. The patient should receive a fibrinolytic agent followed by appropriate antiplatelet and anticoagulant therapies, with transfer to the closest PCI center within 24 hours for reevaluation and consideration of immediate PCI.

Answer: D. The ECG demonstrates an extensive anterolateral STEMI. The patient is young and has presented early in the STEMI evolution. This patient is at extreme risk due to the extensive nature of the STEMI and yet can benefit significantly from early reperfusion therapies. A delay of more than 60 to 120 minutes in this patient is not appropriate for the initiation of reperfusion therapies; furthermore, he is a candidate for a fibrinolytic agent. The early initiation of reperfusion therapy (fibrinolysis or PCI) is vital to reduce morbidity and mortality. Such a significant delay in this case for PCI is not justified, so a fibrinolytic agent is preferred. On arrival at the closest PCI center, the patient can be evaluated for PCI if he has not demonstrated successful reperfusion with resolution of chest discomfort and normalization of the ST segment elevation.

C H A P T E R 69 

Dysrhythmias Donald M. Yealy  |  Joshua M. Kosowsky

PRINCIPLES The term dysrhythmia denotes any abnormality in cardiac rhythm. In this chapter we review the electrophysiology of normal and abnormal cardiac impulse formation and conduction and then provide a general approach to dysrhythmia recognition and management, along with an overview of antidysrhythmic agents. Finally, we discuss the evaluation and treatment of specific dysrhythmias in the prehospital and emergency department (ED) settings.

Cardiac Cellular Electrophysiology The electrophysiologic function of cardiac cells depend on an intact resting membrane potential. Membrane potential is largely the result of differential concentrations of Na+ and K+ on either side of the cell membrane, measuring approximately −90 mV in normal resting nonpacemaker cells. This gradient exists because of the Na+-K+ exchange pump and concentration-dependent flow of K+ out of the cell. The influx of Ca2+ through passive exchange with Na2+ also allows for conduction and myofibril contraction (Fig. 69.1). In normal nonpacemaker cells, an electrical stimulus causes the membrane potential to become less negative, termed depolarization. When the membrane potential reaches −70 mV, specialized Na2+ channels open, causing a rapid influx of positive charge into the cell. This so-called fast channel activity further decreases the membrane potential and is augmented at 30 to 40 mV by a second slow channel that allows Ca2+ influx. When these channels close, resting potential is restored by the sodium-potassium pump, an event termed repolarization (Fig. 69.2). In nonpacemaker cells, depolarization from a second electrical stimulus is not possible when the membrane potential remains more positive than −60 mV, called the effective refractory period (Fig. 69.3). When the membrane potential reaches −60 to −70 mV, some fast channels are capable of responding but impulse propagation is not normal; this is known as the relative refractory period. At a membrane potential of −70 mV or less, fast channels are ready for activity (see Fig. 69.3). Pacemaker cells differ from non–impulse-generating cells in that they can spontaneously depolarize via slow Na+ influx. Dominant pacemaker cells are present in the sinoatrial (SA) node, but other pacemaker cells exist in the atrioventricular (AV) node, within the His-Purkinje system, and elsewhere. With a failure of normal pacemaking cells, or other pathologic conditions such as metabolic derangement or myocardial ischemia, nonpacemaker cells undergo spontaneous depolarization.

Anatomy and Conduction The SA node is an area of specialized impulse-generating tissue at the junction of the right atrium and the superior vena cava. Its blood supply is from the right coronary artery (RCA) in 55% of patients and left circumflex artery (LCA) in 45%. The normal SA

node produces spontaneous depolarization at a faster rate than other pacemakers and is usually the dominant pacemaker. In healthy adults, the SA node normally maintains a rate of 60 to 90 beats/min. Hypothermia and vagal stimulation slow the sinus rate, whereas hyperthermia and sympathetic stimulation increase the rate. Low or absent parasympathetic tone—for example, with certain drugs or after heart transplantation—creates a faster sinus rate. In the absence of normal SA node impulses, other myocardial tissues may assume the role of pacemaker. The AV node has an intrinsic impulse-generating rate of 45 to 60 beats/min. Infranodal pacemakers within the His bundle, Purkinje system, and bundle branches maintain intrinsic rates ranging from 30 to 45 beats/ min. Under pathologic conditions, other atrial and ventricular tissues may pace the heart at varying rates. Impulses from the SA node are propagated through the atrial tissue to the AV node. Atrial depolarization is characterized by the P wave on the surface electrocardiogram (ECG; Fig. 69.4). The AV node is an area of conduction tissue separating the atria and the ventricles, located in the posterior-inferior region of the interatrial septum. Its blood supply is from a branch of the RCA in 90% of patients (right dominant) and from the LCA in the remaining 10% (left dominant). Transmission of impulses within the AV node is slower than in other parts of the conducting system (Table 69.1) because of a dependence on slow-channel ion influx for membrane depolarization. An accessory pathway refers to conduction tissue outside the AV node that forms an alternative, or bypass, tract between the atria and ventricles. The term preexcitation refers to early ventricular depolarization via an accessory pathway. On the surface ECG, the time it takes for conduction of an impulse through the atria to the ventricles is represented by the PR interval, normally ranging from 0.10 to 0.20 second (see Fig. 69.4). Impulses originating in lower atrial tissues or accessory pathways often have a shortened PR interval. PR prolongation is usually a result of nodal or supranodal conduction system disease. After passing through the AV node, impulses propagate to the His bundle onto the three main bundle branch fascicles—the right bundle branch (RBB), left anterior-superior bundle (LASB), and left posterior-inferior bundle (LPIB). The RBB and LASB are typically supplied by the left anterior descending (LAD) artery, whereas the LPIB may be supplied by the RCA or LCA. After conduction down the three main bundle branches, impulses are delivered to the Purkinje fibers, which propagate impulses to myocardial tissues in a swift and orderly fashion, allowing for coordinated ventricular contraction. If an impulse arrives prematurely, it may be conducted abnormally (termed aberrant, associated with bundles that are relatively refractory) or blocked (if the bundles are completely refractory). On the surface ECG, the QRS complex represents ventricular depolarization (see Fig. 69.4), normally 0.09 second or less; a duration of 0.12 second or longer is abnormal. The T wave corresponds to ventricular repolarization and its duration depends, among other things, on the length of the cardiac cycle. The QT 929

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Na+-Ca2+ exchange Ca2+

Na+ Na+ K+ Na+, K+-ATPase exchange pump K+ Na+

ization is acquired torsades de pointes, which typically arises in the setting of a prolonged QT interval and a new metabolic or drug trigger. Delayed afterdepolarizations classically arise in the setting of rapid heart rates and intracellular Ca2+ overload, as seen with digitalis toxicity or reperfusion therapy for acute myocardial infarction. Reentry dysrhythmias arise from repetitive conduction of impulses through a self-sustaining circuit (Fig. 69.6). To maintain a reentry circuit, one conduction pathway must have a longer refractory period than the other, so that when an impulse exits one limb of the circuit, it may then reenter the other in retrograde fashion. The cycle is then repeated, creating a self-sustaining dysrhythmia. Reentry mechanisms are responsible for most narrow-complex tachycardias and many ventricular tachycardias (VTs). Treatment is predicated on altering conduction in one or both limbs of the circuit.

CLASSIFICATION OF ANTIDYSRHYTHMIC DRUGS

K Flow of K+ down its concentration gradient Fig. 69.1.  Flow of various ions across the myocardial cell membrane. The Na+-K+ pump exchanges three Na+ ions for each two K2+ ions, generating a net negative flow of 10 mV. The flow of K down the concentration gradient (dark arrow) generates another 80 mV of current. The Na+-Ca2+ exchange adds little to the resting potential. ATPase, Adenosine triphosphatase. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2, St. Louis, 1989, Mosby.)

TABLE 69.1 

Conduction Velocities in Various Heart Tissues TISSUE

VELOCITY (M/S)

Atrium

1000

Atrioventricular node

200

His-Purkinje system

4000

Ventricles

400

interval represents the total time of ventricular depolarization and repolarization and is altered by inherent physiologic abnormalities, metabolic changes, drugs, or structural changes. This interval is key to assess for QT prolongation in any patient with syncope or ventricular dysrhythmia, given the link to ventricular dysrhythmia recurrence.1

Mechanisms of Dysrhythmia Formation Enhanced automaticity refers to spontaneous depolarization in nonpacemaker cells or depolarization at an abnormally low threshold in pacemaker cells (Fig. 69.5). Classic examples of enhanced automaticity include the idioventricular rhythms of severe hyperkalemia or myocardial ischemia and the atrial and junctional tachycardias (JTs) associated with digitalis toxicity. Triggered activity refers to abnormal impulse(s) resulting from afterdepolarizations. Afterdepolarizations are fluctuations in membrane potential that occur as the resting potential is restored. These fluctuations may precipitate another depolarization just before full resting potential is reached (early afterdepolarizations) or after full resting potential is reached (delayed afterdepolarizations). The classic dysrhythmia associated with early afterdepolar-

The four classes of antidysrhythmic medications are categorized according to their electrophysiologic effects (Box 69.1). Class I agents exert their major effects on the fast Na+ channels, resulting in membrane stabilization. The subclasses IA, IB, and IC have differing effects on depolarization, repolarization, and conduction. Class II agents are the β-adrenergic antagonists, which depress SA node automaticity, slow AV node conduction, and suppress conduction in ischemic myocardial tissue. Class III agents prolong repolarization and refractory period duration, predominantly via their effects on K+ channels. Class IV agents are the Ca2+ channel blockers, which slow conduction through the AV node and suppress other calcium-dependent dysrhythmias. Other agents important in the emergency treatment of dysrhythmias include magnesium sulfate, digitalis, and adenosine.

Class IA Agents Class IA agents slow conduction through the atria, AV node, and His-Purkinje system and suppress conduction in accessory pathways. Class IA agents also exhibit anticholinergic and mild negative inotropic effects.

Procainamide Procainamide is the most commonly used class IA agent in the emergency treatment of ventricular and supraventricular dysrhythmias, and it can alter normal and accessory pathway conduction. In stable patients, the recommended administration is a rate of 20 to 30 mg/min until the dysrhythmia is terminated, hypotension occurs, or the QRS complex widens (to 50% of the pretreatment width), up to a total dose of 18 to 20 mg/kg (12 mg/kg if congestive heart failure is present). Procainamide triggers hypotension from vasodilatory effects in 5% to 10% of patients. Other class IA agents are not currently in use for acute care.

Class IB Agents Class IB agents slow conduction and depolarization less than other class I agents, and they shorten repolarization rather than prolonging it. Class IB agents have little effect on accessory pathway conduction.

Lidocaine Lidocaine is the sole class IB agent used in emergency rhythm management. Lidocaine can suppress dysrhythmias from enhanced automaticity, such as VT. Lidocaine also suppresses SA and AV node function and is associated with asystole in the setting

CHAPTER 69  Dysrhythmias

Overshoot

Repolarization

Plateau phase

+ 20

Time

–20 –40 Membrane resting potential

–80 –90

2

0 3 Restoration of ionic balance

4 Intracellular fluid space

4 K+

K+ ATP ADP +

Sarcolemma

a N

+

Ca2+

Na+

Extracellular fluid space

A

K+

–60

1

Depolarization

Millivolts

0

SA node

Atria

AV node

AN

SA

N NH

1 2 3 0

4

0

4

1 2 3 1

NH 0

His bundle H

2 3

4

Purkinje fiber

1

B

2

100 mV

Ventricles

200 msec

0 3

4

BB

C

Fig. 69.2.  A, Action potential of a myocardial cell and its relation to ion flow. B, Action potentials of various myocardial tissues. C, Action potentials of various pacemaker cells. Note that phase 4 becomes flatter as its location becomes more distal. AN, Atrial-nodal; AV, atrioventricular; BB, bundle branch fascicles; H, His bundle; N, nodal; NH, nodal-His; SA, sinoatrial. (A, B, from Calcium in cardiac metabolism, Whippany, NJ, 1980, Knoll Pharmaceutical; and C, from Conover M: Understanding electrocardiography, ed 5, St Louis, 1988, Mosby.)

Class IC Agents

Supernormal refractory period Relative refractory period + 20 Time

Millivolts

0

1

–20 –40 –60 –65 –80 –90

0

4

2 Effective (absolute) refractory period

3 Threshold potential 4

Fig. 69.3.  Action potential showing various refractory periods. (From Calcium in cardiac metabolism, Whippany, NJ, 1980, Knoll Pharmaceutical.)

of acute myocardial ischemia. Currently, lidocaine is a second-line agent in ventricular tachycardia due to lower conversion rates compared to other agents. It also may have a role in prophylaxis from recurrent dysrhythmias in those surviving out-of-hospital ventricular fibrillation,2 although experimental data are limited.

The class IC agents profoundly slow depolarization and conduction. More than any other class, these agents are associated with prodysrhythmia, the creation of a new ventricular dysrhythmia3; this potential exists with class IA agents albeit much less. Class IC agents are approved only for oral use in the United States.

Flecainide Flecainide is a class 1C antidysrhythmic agent used for paroxysmal supraventricular tachycardia and certain forms of VT. Flecainide has high oral bioavailability, variable half-life, and narrow therapeutic index, all hampering its use. Flecainide is not recommended for patients with ischemic or structural heart disease.

Propafenone Propafenone shares electrophysiologic properties with classes IA and IC agents and possesses some β-adrenergic and calcium channel–blocking properties. Oral propafenone is used to prevent

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atrial fibrillation and ventricular dysrhythmias. Like flecainide, this is used with caution in patients who have ischemic and/or structural heart disease.

Class II Agents Class II agents—β-adrenergic blockers—suppress SA node automaticity and slow conduction through the AV node. Because of their effect on AV node conduction, class II agents are well suited to control the ventricular rate in patients with atrial tachydysrhythmias and can be useful to terminate AV nodal reentrant tachycardias (AVNRTs). In the setting of acute myocardial

ischemia, beta blockers play a role in preventing ventricular dysrhythmias. All beta blockers are active at β1 and β2 receptors (Table 69.2) to varying degrees. Those with more prominent β1 effects are called cardioselective. Relative contraindications to the use of beta blockers include asthma or chronic obstructive lung disease, advanced congestive heart failure, and third-trimester pregnancy. Beta blockers should not be used in patients with preexisting bradycardia or heart block beyond first-degree. Acute side effects of beta blockers include bronchospasm, heart failure, excessive bradycardia, and hypotension. Intravenous (IV) beta blockers can trigger additive side effects when used in conjunction with calcium channel blockers, notably hypotension or bradycardia.

Esmolol

SA node

Esmolol is a β1-selective agent useful in the emergency setting because of its rapid onset of action and short elimination half-life (minutes). Common dosing of esmolol is an IV bolus of 500 µg/ kg followed by a continuous infusion beginning at 50 µg/kg/min and titrating to need and effect.

Metoprolol Metoprolol is available in oral and IV preparations. Although not approved for dysrhythmia treatment in the United States, metoprolol (5–10 mg IV every 10–15 minutes in an adult, titrated to response) will slow atrial and nodal tachycardias.

Class III Agents Normal values SP = 34.9 ± 2.1 msec PA = 37 ± 7 AH = 77 ± 16 HV = 40 ± 3

ECG

All class III agents prolong the refractory period primarily by blocking K+ channels, with variable effects on the QT interval. In

TABLE 69.2 

Cardiac and Respiratory β-Adrenergic Receptors and Responses to Pharmacologic Manipulation

HBE H

A

RESPONSE TO RECEPTORS

LOCATION

STIMULATION

ANTAGONISM

β1-Adrenergic

Heart

Increased heart rate and ectopy Increased contractility

Decreased heart rate and ectopy Decreased contractility

β2-Adrenergic

Airway (smooth muscle) Peripheral vasculature

Decreased tone (relaxation) Decreased tone (relaxation)

Increased tone (contraction) Increased tone (contraction)

V

Fig. 69.4.  Electrical events in the heart related to surface electrocardiogram (ECG) and His bundle electrogram (HBE). The approximate relationship of sinus node discharge is also related to the surface ECG. AH, Atrioventricular nodal conduction time; HV, His-Purkinje conduction; PA, intraatrial conduction time; SA, sinoatrial; SP, SA conduction time. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2,  St. Louis, 1989, Mosby.)

0 mV

0 mV

TP

A

–90 mV

B

–90 mV

Fig. 69.5.  A, Enhanced normal automaticity (dashed line). B, Abnormal automaticity. TP, Threshold point. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2, St. Louis, 1989, Mosby.)

CHAPTER 69  Dysrhythmias

general, class III agents are alternatives to class I agents for the treatment of many ventricular and atrial dysrhythmias.

Bretylium Bretylium was once the most commonly used class III agent. Due to its frequent hemodynamic side effects and limited effectiveness, bretylium is no longer available in the United States.

Amiodarone Amiodarone is approved for the treatment of ventricular and supraventricular dysrhythmias and is the preferred choice for drug treatment of acute ventricular tachycardia. In addition to features in common with all class III agents, amiodarone has other effects, including actions that are similar to those of class IA, II, and IV agents.

A

B

Ibutilide Ibutilide has a unique mechanism of action characterized by the induction of a slow inward Na2+ current, thereby prolonging the refractory period. IV ibutilide is approved for cardioversion of atrial fibrillation and atrial flutter. Because of QT prolongation and the risk of polymorphic VT, most health care providers choose to start ibutilide only in a monitored setting.

Sotalol

A

X

The serum half-life of amiodarone is 25 hours after a single IV dose and up to 50 days during long-term oral use. Because of its unusual pharmacokinetics, oral regimens vary widely. The acute side effects of amiodarone include hypotension, bradycardia, and heart failure (Box 69.2). There is an additive risk of bradycardia and hypotension when amiodarone is used in conjunction with calcium channel or β-adrenergic blockers. Rates of prodysrhythmia are relatively low. Long-term amiodarone use is associated with extracardiac side effects, including irreversible lung and thyroid disease. Amiodarone alters the pharmacokinetics of numerous other drugs, including digoxin and warfarin.

Sotalol is a β-adrenergic receptor blocker with type III antidysrhythmic properties. It is used orally for the suppression of supraventricular and ventricular dysrhythmias. Like ibutilide, start sotalol should be started in a monitored setting, watching for QT prolongation; it has a very limited role in emergency care.

X

Dofetilide A

B

C

B

Fig. 69.6.  Mechanism of reentry.

Dofetilide is a powerful class III agent approved for chemical cardioversion and maintenance of sinus rhythm in patients with

BOX 69.1 

Classification of Antidysrhythmic Drugs CLASS I

Sodium (fast) channel blockers—slow depolarization with varying effects on repolarization. These drugs have membrane-stabilizing effects. Class IA Moderate slowing of depolarization and conduction; prolong repolarization and action potential duration. Procainamide Quinidine Disopyramide Class IB Minimally slow depolarization and conduction; shorten repolarization and action potential duration. Lidocaine Phenytoin Tocainide Mexiletine Class IC Markedly slow depolarization and conduction; prolong repolarization and action potential duration. Flecainide Encainide Lorcainide Propafenone (shares properties with class IA agents) Vernakalant (atrial-specific, investigational) a

Shares activity with class I agents. Shares activity with class II agents.

b

CLASS II

β-Adrenergic blockers Propranolol Esmolol Metoprolol Atenolol

CLASS III

Antifibrillatory agents—prolong action potential duration and refractory period duration with antifibrillatory properties. Bretylium (historical significance) Amiodarone Dofetilide Ibutilidea Sotalolb Dronedarone Azimilide

CLASS IV

Calcium (slow) channel blockers Verapamil Diltiazem

MISCELLANEOUS Digitalis Magnesium sulfate Adenosine

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BOX 69.2 

BOX 69.3 

Adverse Effects of Amiodarone

Adverse Effects of Digitalis

ACUTE EFFECTS

COMMON EFFECTS

Hypotension Slowing of heart rate Decreased contractility

LONG-TERM EFFECTS

Common Effects Corneal deposits Photosensitivity Gastrointestinal intolerance Less Common Effects Hyperthyroidism Heart failure Pulmonary toxicity, fibrosis Hypothyroidism Bradycardia Prodysrhythmic effect

DRUG INTERACTIONS Increased Levels Phenytoin Procainamide Warfarin Digoxin Flecainide

atrial fibrillation or flutter. However, because of its high risk for prodysrhythmia, it can only be prescribed by physicians with specialized training.1 It has no current role in emergency care.

Dronedarone Structurally related to amiodarone, dronedarone displays class III properties in addition to those of other antidysrhythmic classes. Dronedarone is approved for oral use to maintain sinus rhythm in patients with atrial fibrillation or flutter but is contraindicated in patients with severe or recent heart failure. It has no current role in emergency care.

Class IV Agents Class IV agents block slow Ca2+ channels, slowing conduction within the AV node and suppressing the SA node to a lesser degree. Like beta blockers, these are used in patients with supraventricular tachycardia. All class IV agents are associated with peripheral vasodilation. Verapamil has the least effect on peripheral vascular tone, and diltiazem has an effect between that of verapamil and purely peripherally acting calcium channel blockers (eg, nifedipine). In the acute setting, IV calcium salts (1 g, slow IV delivery) attenuate these peripheral vasodilatory effects. Class IV drugs should not be administered to patients with second- or third-degree AV block unless a functional pacemaker is in place and should be avoided in patients with first-degree block.

Diltiazem IV diltiazem dosing is a 0.25- to 0.35-mg/kg bolus over 2 minutes. For longer term rate control, a continuous infusion (5–15 mg/hr initially, then titrated to need) or an oral dose (60–90 mg immediate-release formulation initially) will sustain the response.

Gastrointestinal intolerance (eg, nausea, vomiting, abdominal pain, diarrhea, anorexia) Fatigue Drowsiness Visual color disturbances Headache Depression Apathy

LESS COMMON EFFECTS

Psychosis Cardiac symptoms Heart block Increased ectopy Combined block and ectopy (multifocal atrial tachycardia with block or complete atrioventricular block with accelerated junctional rhythm, usually in overdose setting) Ventricular tachycardia

Verapamil IV verapamil is rarely used today given the advent of diltiazem, although still effective. If used, start at a dose of 0.1 mg/kg over 1 to 2 minutes; for the average healthy adult, this translates to a dose of 5 to 10 mg, which can be repeated or increased by 50% if unsuccessful and there is no hypotension 10 minutes after administration. In older adults or those with borderline hypotension (systolic blood pressure of 90–110 mm Hg), use a smaller dose (0.05 mg/kg or 2.5-mg increments).

Miscellaneous Agents Digoxin Digitalis compounds have a variety of effects on myocardial cells. Digoxin inhibits the adenosine triphosphate (ATP)–dependent Na+-K+ exchange pump, increasing intracellular Na+ concentrations and decreasing intracellular K+ concentrations. The resultant increase in intracellular Ca2+ concentration accounts for the positive inotropic effects of digitalis. The prodysrhythmic effects of digoxin are enhanced automaticity and triggered activity, particularly at high therapeutic or toxic doses. At the same time, digoxin slows AV node conduction via lengthening of the refractory period. Digoxin (0.25–0.5 mg IV) can control the ventricular rate in patients with supraventricular tachycardia, notably atrial fibrillation and atrial flutter. Because of its delayed onset of action (often not therapeutic for 30 minutes or longer and peaking at 6 hours) and narrow therapeutic window, digitalis is not a first-line agent for emergency therapy. Side effects of digoxin are listed in Box 69.3 and are aggravated by hypokalemia, hypercalcemia, hypomagnesemia, increased catecholamine levels, and acid-base disturbances. Digoxin toxicity is discussed in Chapter 147.

Magnesium Magnesium can abort ventricular dysrhythmias via its membranestabilizing properties. Magnesium (1–2 g IV) may terminate torsades de pointes and is an adjunct in VT therapy.

CHAPTER 69  Dysrhythmias

Adenosine Adenosine is a naturally occurring purine nucleoside that is the best choice for the termination of regular, nonatrial, narrowcomplex tachydysrhythmias, notably junctional reentry. Administered as an IV bolus, adenosine causes an abrupt slowing of AV conduction in anterograde and retrograde pathways. Adenosine has an onset of action of 5 to 20 seconds and a duration of effect of 30 to 40 seconds. Except in rare cases, adenosine has little or no effect on infranodal conduction pathways. For this reason, adenosine is an option as a diagnostic (and sometimes therapeutic) agent in patients with wide-complex tachydysrhythmia when the cause is unclear. Start adenosine by using a 6-mg rapid IV bolus (large, non– distal vein followed by a rapid flush) in for adults (≥50 kg body mass); key is the rapid bolus technique, with higher success noted after training to adhere to that tenet of delivery.4 If no response is seen within 1 to 2 minutes, increase the dose to a 12-mg IV bolus. If no effect is seen after a second 12-mg dose, then reassess the rhythm and use another therapy. There is no benefit to repeating adenosine when transient lowering is seen after a dose is given, followed by a return to the previous rhythm. Pediatric doses are 0.05 mg/kg initially, with doubling at similar intervals, up to a total dose of 0.25 mg/kg. Side effects occur in up to one-third of patients given adenosine and are usually minor and self-limited. These include flushing, dyspnea, chest pressure, nausea, headache, dizziness, transient bradycardia or heart block, and hypotension. Asystole is possible but generally transient. Because of its short duration of action, adenosine is not an effective rate control agent for atrial fibrillation or flutter, although it can help unmask these rhythms when not apparent on the initial surface ECG.

APPROACH TO DYSRHYTHMIA: RECOGNITION AND MANAGEMENT Clinical Features Dysrhythmias are classified according to their electrophysiologic origin, appearance on the ECG, and underlying ventricular rate. Although overlap exists, the following categorization is useful: • Bradycardias • Extrasystoles • Narrow-complex (QRS < 0.12 second) tachycardias (regular and irregular) • Wide-complex (QRS ≥ 0.12 second) tachycardias (regular and irregular) Classically, the approach to any specific dysrhythmias is broadly defined based on clinical stability, which is driven by the effect on perfusion. Clearly unstable patients have severe or multiple end-organ features of hypoperfusion, such as altered sensorium, respiratory distress, hypotension, syncope, and/or chest pain suggestive of myocardial ischemia. Stable patients may be asymptomatic or have mild symptoms, such as lightheadedness, dyspnea on exertion, palpitations, and/or mild anxiety. In practice, clinical stability is a continuum; in the absence of profound altered sensorium or hypotension, a clear line distinguishing stable and unstable patients is often not present. One simple axiom is important: • Clearly unstable patients with a primary dysrhythmia outside of a clear external trigger (eg, bradycardia for hypothermia or tachycardia for hypovolemic or distributive shock) need prompt electrical therapy—a countershock if there is a fast rate with a pulse and cutaneous pacing if there is a slow rate with a pulse.

Care of patients with cardiac arrest (those with no pulse) is covered elsewhere in this text (see Chapter 8). A key consideration is whether a dysrhythmia is the cause or effect of a clinical presentation; for example, rapid atrial fibrillation may cause hypotension or may be a response to volume depletion or ischemia. Failure to consider the clinical situation can lead to an inappropriate treating of the rhythm to the detriment of the patient (eg, giving a rate-slowing agent when the tachycardia is a response to volume depletion). Recognizing this potential, treatment of patients who are clearly unstable and with a dysrhythmia is best done assuming that the rhythm is the cause. In a stable patient, a more systematic approach should be used to identify the cause and choose the most appropriate therapy.

Initial Assessment of Stable Patients The approach begins with gathering evidence from the history, physical examination, and 12-lead ECG with a rhythm strip. The nature of any symptom is important, including the timing, velocity of onset (gradual vs. abrupt, with the latter often re-entrant based), and duration. For the patient with palpitations, questions about the rate and regularity of the heartbeat are often asked, and having the patient tap out the rhythm with a finger can aid. Other important questions are about precipitating events and associated symptoms, such as dizziness, chest pain, dyspnea, and/or syncope. The past history—notably of rhythm disturbances, ischemic or structural heart disease—and a medication history may raise a concern for specific rhythms. For example, a new and symptomatic wide-complex tachycardia in a patient with known ischemic heart disease is much more often VT than a supraventricular dysrhythmia. Occasionally, the family history helps, particularly if there are first-degree relatives with a history of dysrhythmia, unexplained syncope, or sudden death—all of which suggest an inherited disorder, such as an accessory pathway or Brugada’s syndrome. Aside from palpating the pulse and listening to the heart sounds, the physical examination should be focused on detecting evidence of end-organ hypoperfusion (eg, agitation or confusion) or clues to an underlying cause of the dysrhythmia (eg, left ventricular failure). Observing the patient’s rhythm on a continuous cardiac monitor while he or she reports symptoms can add valuable information.

DIAGNOSTIC CONSIDERATIONS Differential Diagnosis Loose leads, muscle contraction, shivering, tremors, and other patient movement can produce artifactual findings on a monitor, rhythm strip, or 12-lead ECG (Fig. 69.7). Such pseudodysrhythmias mimic and are often mistaken for serious dysrhythmias, including ventricular fibrillation. The important point is avoiding decisions based solely on the ECG without incorporating the clinical context.

Diagnostic Testing The 12-lead ECG is essential to evaluating any patient with a suspected dysrhythmia. Use of a single ECG lead is often adequate for diagnosis, especially in unstable patients; multiple leads are optimal in stable patients. The latter helps detect as the presence or absence of P waves (often best seen in inferior leads or V1-2; Fig. 69.8), the relationship between P waves and QRS complexes, prolongation of the QRS and QT interval, and evidence of ischemia or prior myocardial infarction (Box 69.4). For certain conditions, such as Brugada’s syndrome, the 12-lead ECG, together with a history of syncope, is diagnostic. Because useful information

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II

V1

V5 Fig. 69.7.  Pseudodysrhythmia. In this case, atrial flutter waves appear to be present but are recognized as an artifact when the patient and right side of the electrocardiogram are examined.

I

aVR

V

II

aVL

V

III

aVF

V

Fig. 69.8.  Note the P waves before the QRS complexes in lead aVF.

BOX 69.4 

Basic Electrocardiographic Observations During Dysrhythmia Analysis 1. Ventricular rate—fast (>100 complexes/min), slow (0.12 s), borderline (0.09–0.12 s), or normal. If determined without electrocardiogram being physically present (eg, prehospital radio medical command), ask for QRS duration in “number of small boxes” from printed rhythm strip (each box = 0.04 s) to ensure accuracy. 4. P wave presence and relationship to QRS complexes—May require mapping of P waves with calipers to detect those falling within QRS complex or T wave. 5. Rhythm changes—examine these areas closely for clues. 6. Multiple leads, especially chest leads or esophageal lead if difficulties with P wave visualization are experienced. 7. Comparison with previous tracings (if available) is often valuable.

about paroxysmal dysrhythmias is at the onset or termination of the rhythm, inspect those areas carefully and save the strip(s) for future reference. Maneuvers that alter autonomic tone target relative increases in parasympathetic tone through the vagus nerve to help expose certain dysrhythmias and terminate others. In the ED, these maneuvers often fail, likely from a selection bias (easy responders terminate before arrival) or poor clinical technique. Vagal maneuvers, such as carotid sinus massage and the Valsalva maneuver, transiently slow AV conduction, which may help terminate or uncover a supraventricular rhythm disturbance. The key to using physical methods of enhancing parasympathetic tone is to optimize technique—have the patient lie flat, lift the legs, and ask for a Valsalva effort, with or without massage, to enhance success.5,6 A nodal reentrant tachycardia may terminate abruptly with vagal maneuvers, whereas it often temporarily slows the ventricular rate in those with atrial fibrillation or atrial flutter; VT patients rarely have any change after vagal maneuvers. Auscultate the neck for bruits before carotid sinus massage, particularly in older patients, and avoid the maneuver if any are found or previous carotid disease is likely. Vagal maneuvers are frequently unsuccessful in the ED, but will rarely result in clinical deterioration. Poor technique often impairs massage-based maneuvers—for example, not

CHAPTER 69  Dysrhythmias

having the patient supine or incorrect massage of the carotid artery instead of the carotid body. Other vagotonic maneuvers, such as rectal or ocular massage and ice water head dunking, are impractical and less effective.

MANAGEMENT Sinus Bradycardia and Sinoatrial and Atrioventricular Block Bradycardia is defined as a ventricular rate of less than 60 beats/ min, although in practice rates above 50 beats/min are not usually a concern. Bradycardia occurs because of depression of the sinus node or because of a conduction system block; when the rate falls below a particular threshold, a subsidiary pacemaker elsewhere in the atrium, AV junction, or ventricle may assume the dominant role, resulting in an escape rhythm.

letes or young adults with a high resting vagal tone. Sinus bradycardia occurs in a variety of pathologic conditions associated with vagal stimulation, ranging from autonomic-mediated syncope to hemoperitoneum or acute inferior wall myocardial infarction. Other pathologic causes of sinus bradycardia include hypothermia, hypoxia, drug effects (especially β-adrenergic blockers and calcium channel blockers), and intrinsic sinus node disease (ie, sick sinus syndrome; see later). When sinus bradycardia drops below 40 beats/min, a junctional escape rhythm often emerges. Sinus bradycardia is often asymptomatic and requires no specific treatment. If needed, first-line treatment for symptomatic sinus bradycardia in adults is atropine, a 0.5-mg IV bolus, repeated as needed every 3 to 5 minutes, to a total dose of 3 mg. Occasionally, a second-line agent such as dopamine or epinephrine infusion is needed. Emergency cutaneous pacing for sinus bradycardia is rarely indicated.

Sinus Dysrhythmia

Sinus Bradycardia Sinus bradycardia is characterized by a P wave with normal morphology, a fixed P-P interval equal to the R-R interval, and a ventricular rate below 60 beats/min (Fig. 69.9). This pattern may be found in healthy individuals, particularly well-conditioned ath-

Sinus dysrhythmia is a manifestation of the natural variation in heart rate that occurs during the respiratory cycle, manifested on the surface ECG as normally conducted P waves with a variable P-P interval (Fig. 69.10). It is a normal variant and is seen frequently in children and young adults.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Fig. 69.9.  Sinus bradycardia.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Fig. 69.10.  Sinus dysrhythmia (note slight irregularity).

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Sinus Arrest and Sinoatrial Exit Block

Atrioventricular Block

A lack of atrial depolarization can occur because of failure of the sinus node to generate an impulse (sinus arrest) or failure of impulse conduction out of the SA node (SA exit block; Fig. 69.11). With SA exit block, it is not uncommon to see dropped P waves in regularly occurring patterns, representing 2 : 1, 3 : 1, or 4 : 1 block. Sinus arrest and SA exit block may be manifestations of intrinsic SA node disease, but can also be seen under conditions of increased vagal tone, whether benign or pathologic. When symptomatic, the approach to treatment is similar to that for sinus bradycardia.

AV block results from impaired conduction through the atria, AV node, or proximal His-Purkinje system. First- and second-degree AV blocks represent partial impairment of conduction, whereas third-degree block indicates complete interruption. Advanced or high-grade AV block refers to AV block resulting in a ventricular rate that is pathologically slow.

Sick Sinus Syndrome Sick sinus syndrome (SSS) is a group of dysrhythmias caused by disease of the sinus node and its surrounding tissues, creating sinus bradycardia, sinus arrest, or SA exit block. A variant of SSS known as bradycardia-tachycardia syndrome is characterized by one or more of these bradydysrhythmias alternating with a tachydysrhythmia, typically atrial fibrillation. SSS is most common in older adults, a result of fibrotic degeneration. It is also associated with cardiomyopathies, connective tissue diseases, and certain drugs. In the acute setting, treat the specific rhythm, although be wary about a profound subsequent bradycardia that could require temporary pacing following the use of a nodal blocking agent (especially a calcium channel blocker) for the tachycardic presentation. Long-term management requires permanent pacemaker placement for symptomatic bradycardia to allow for pharmacologic therapy for atrial fibrillation.

First-Degree Atrioventricular Block First-degree AV block is from prolonged conduction at the level of the atria, AV node (most common), or His-Purkinje system. On the ECG, first-degree AV block shows a prolonged PR interval (>0.20 second), typically with a narrow QRS complex (Fig. 69.12). First-degree AV block is a normal variant in up to 2% of healthy young adults. First-degree AV block requires no specific treatment other than avoiding any prolonged nodal blocking agents.

Second-Degree Atrioventricular Block Second-degree AV block is when one or more (but not all) atrial impulses fail to reach the ventricles. The conduction ratio is the number of P waves to the number of QRS complexes over a period of time (eg, 3 : 2, 2 : 1). In circumstance in which the atrial rate is unusually fast—atrial flutter, for example—a conduction ratio of 2 : 1 may be physiologic, reflecting the normal refractory period of the AV node. However, in most other cases, a conduction ratio more than 1 : 1 is pathologic. Second-degree AV block is classified

A

B

V1 Fig. 69.11.  A, Incomplete sinus block. B, Complete sinus block (sinus arrest) with ventricular escape rhythm.

Fig. 69.12.  First-degree atrioventricular block.

CHAPTER 69  Dysrhythmias

into two types on the basis of the underlying pathophysiology and appearance of the ECG (Table 69.3). Type I Second-Degree Atrioventricular Block.  Type I second-degree AV block, also called Wenckebach or Mobitz I AV block, is associated with progressive impairment of conduction within the AV node. The surface ECG shows a lengthening of the PR interval from beat to beat until a P wave is entirely blocked (so-called dropped beat). This pattern gives the appearance of successive P waves retreating into the preceding QRS complexes (Fig. 69.13). Grouped beating (eg, pairs, trios) occurs and is not unique to type I second-degree AV block (Box 69.5). Type I second-degree AV block occur in a variety of conditions, benign and pathologic; often, these are associated with increased vagal tone and do not require specific treatment. In the setting of an acute myocardial infarction, type I second-degree AV block is generally transient and associated with a good outcome.

TABLE 69.3 

Features of Types I and II Second-Degree Atrioventricular Block FEATURE

TYPE I

TYPE II

Clinical

Usually acute Inferior myocardial infarction Rheumatic fever

Often chronic Anteroseptal

Digitalis or beta blockers

a

Lenègre disease (Lev disease) Cardiomyopathy

Anatomic

Usually AV node

Infranodal

Electrophysiology

Increased relative refractory period Decremental conduction

No relative refractory period All or none conduction

Electrocardiographic features

RP/PR reciprocity Prolonged PR interval QRS duration normal

PR interval stable PR interval usually normal QRS duration prolonged

Response to atropine and exercise

Improves

Worsens

Response to carotid massage

Worsens

Improvesa

Primarily refers to conduction ratio. AV, Atrioventricular.

Type II Second-Degree Atrioventricular Block.  Type II second-degree AV block, or Mobitz II block, is a conduction block just below the level of the AV node. On the surface ECG, conduction of atrial impulses is sporadic and typically periodic, but the PR interval does not widen from beat to beat (Fig. 69.14). The QRS complex is usually narrow, but concomitant infranodal conduction disturbances (ie, bundle branch blocks) can be seen in those with type II second-degree AV block. Type II second-degree AV block can occur at conduction ratios similar to those seen with type I second-degree block but can also occur at higher conduction ratios (eg, 3 : 1, 4 : 1, or higher). When the conduction ratio is exactly 2 : 1, it is hard to distinguish type I from type II second-degree AV block on the surface ECG. In general, the presence of a prolonged PR interval makes type I block more likely, whereas the presence of wide QRS complexes makes type II block more likely. Type II second-degree AV block arises as a result of senescent degeneration, drug toxicity, ischemia, or other pathologic conditions; it generally carries a worse prognosis than type I seconddegree AV block. In acute myocardial infarction, type II second-degree AV block is associated with anterior wall injury and is often a precursor to complete AV block. No specific therapy is needed, aside from ensuring that pacemaking capability is immediately available.

Third-Degree Atrioventricular Block Third-degree AV block, also known as complete heart block, is absent conduction of any atrial impulses (Fig. 69.15). Complete heart block is typically accompanied by a slow escape rhythm, with the width and frequency of QRS complexes depending on the site of the escape rhythm pacemaker. Pacemakers above the His bundle are associated with a narrow-complex QRS at a rate of 45 to 60 beats/min, whereas pacemakers at or below the His bundle produce a wide-complex QRS at a rate of 30 to 45 beats/min. BOX 69.5 

Causes of Grouped Impulses Wenckebach mechanism (usually at atrioventricular node, but can occur elsewhere) Sinoatrial exit block Atrial tachycardia or flutter with alternating conduction Frequent extrasystoles Nonconducted atrial trigemini Concealed or interpolated extrasystoles

Fig. 69.13.  Second-degree atrioventricular block, type I (Wenckebach). Note the prolongation of the PR interval between the second and third beats, followed by a nonconducted atrial impulse.

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Mobitz type II second-degree AV block

P

P

P

P

P

P

P

P

P

A

B Fig. 69.14.  A, Second-degree atrioventricular (AV) block, type II. In this example, 3 : 1 conduction is shown. B, Second-degree AV block with 2 : 1 conduction. From the rhythm strip alone, it is difficult to categorize this as a type I or II block. (A from Goldberger AL, Goldberger E: Clinical electrocardiography, ed 2, St Louis, 1981, Mosby.)

6 sec

Fig. 69.15.  Complete (third-degree) atrioventricular block. Note that there is no constant relationship of P waves to QRS complexes, even though some are noted in close proximity.

The hallmark of complete heart block is AV dissociation (ie, no electrocardiographic relationship between P waves and QRS complexes), with an R-R interval longer than the P-P interval. Conversely, the presence of AV dissociation with an R-R interval shorter than the P-P interval (eg, as occurs with accelerated junctional rhythms and VTs) does not imply third-degree heart block. When the atrial rate and the escape rates are similar (termed isorhythmic), detecting AV dissociation may require a long rhythm strip to track the P waves and QRS complexes. When complete heart block occurs in the presence of atrial fibrillation, the fibrillatory atrial waves are accompanied by a slow and regular ventricular response (so-called regularized atrial fibrillation). This specific dysrhythmia is classically associated with digitalis toxicity. Third-degree AV block can be congenital but is usually acquired because of senescent degeneration of the electrical conduction system or as a result of acute ischemia, drug therapy, or other pathologic conditions (eg, Lyme or Chagas’ disease). In the ED setting, management of type II second-degree or complete AV block depends on the cause and presence of symptoms. Patients with newly acquired or symptomatic advanced AV block should be admitted to the hospital; in those who are

markedly symptomatic (ie, signs of hypoperfusion at rest), temporary transcutaneous or transvenous pacing should be started until the reversible cause can be treated (eg, ST elevation myocardial infarction, beta blocker overdose) or a permanent pacemaker is placed. Atropine is usually ineffective.

Extrasystoles An extrasystole is an electrical impulse originating from an ectopic atrial or ventricular focus. Depending on the site of origin and timing of the impulse, there may not be an associated mechanical contraction. The terms premature atrial contraction and premature ventricular contraction are widely used but are misleading, because contraction may not occur with the extra electrical activity seen on the ECG. The extrasystole and its preceding impulse are the couplet, and the coupling interval is the period between these two beats. Bigeminy (Fig. 69.16) occurs when there is an extrasystole after every native beat, so that every other impulse is extrasystolic; trigeminy (every third beat) and quadrigeminy (every fourth beat) are similar. Most extrasystoles are the result of enhanced automaticity from the atria, AV node, His-Purkinje system, or ventricles.

CHAPTER 69  Dysrhythmias

Fig. 69.16.  Ventricular bigeminy.

Fig. 69.17.  Premature atrial contractions.

1220 msec

1240 msec

1360 msec

Fig. 69.18.  Premature atrial contractions (PACs) with noncompensatory pauses and one aberrantly conducted impulse (upper strip). Note that conducted and nonconducted PACs reset the sinus node, with the latter creating a pause.

Premature Atrial Contractions Premature atrial contractions (PACs; Fig. 69.17) are common and usually have little clinical significance. PACs on the ECG are an abnormal P wave early within a cardiac cycle, although sometimes the P wave may be difficult to detect if it is buried within the preceding T wave. Most PACs will depolarize the sinus node, resetting its refractory period. Because of this, the P-P interval between two sinus beats surrounding a PAC will be less than twice the intrinsic P-P cycle length (see Fig. 69.17). If a PAC reaches the AV node or infranodal conducting system during its absolute refractory

period, there will be no ventricular depolarization. A nonconducted (or blocked) PAC typically results in a noncompensatory pause (ie, R-R interval less than twice the intrinsic R-R cycle; Fig. 69.18) because the sinus node is reset. Blocked PACs are a common cause of electrocardiographic pauses and can be easily overlooked. On occasion, a PAC can be the precipitant of a more important dysrhythmia, such as atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia (PSVT). If a PAC reaches the infranodal conducting system during its relative refractory period, the QRS complex is widened (or aberrant), typically with an RBBB pattern. Because the refractory period depends on the previous cycle length, an early arriving PAC

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TABLE 69.4 

Features Distinguishing Premature Atrial Contractions With Abnormal Conduction From Premature Ventricular Contractions PREMATURE ATRIAL CONTRACTIONS

PREMATURE VENTRICULAR CONTRACTIONS

No compensatory pause

Fully compensatory pause (unless interpolated)

Preceding P wave (different from sinus P wave; occasionally buried in T wave)

No preceding P waves (although retrograde atrial conduction can cause inverted P wave after QRS)

Usually classic right bundle branch block pattern (especially if long-short cycle sequence appears) identical to sinus QRS

Left bundle branch block, right bundle branch block, or hybrid pattern

QRS axis normal or near-normal

Frequently bizarre QRS axis

QRS rarely > 0.14 s

QRS often > 0.14 s

A

B

Fig. 69.19.  Premature ventricular contractions with compensatory pause. Note that a sinus P wave can be seen in the T wave of the extrasystolic beat. Also note the secondary T wave changes in beats 1 and 4 (the T wave is opposite the main deflection of the QRS complex).

II Fig. 69.20.  Interpolated premature ventricular contraction.

that follows a long cardiac cycle is more likely to be aberrantly conducted. PACs are benign and require no specific treatment, but they may accompany catecholamine excess, myocardial ischemia, heart failure, hyperthyroidism, or a metabolic abnormality.

Premature Ventricular Contractions Premature ventricular contractions (PVCs) occur in a wide variety of states. Occasional PVCs are common in healthy adults or conditions associated with catecholamine excess, such as pain, anxiety, and use of stimulants (eg, caffeine, nicotine, cocaine, amphetamines). Pathologic conditions associated with frequent PVCs include myocardial infarction, potassium or magnesium disturbances, and medication toxicity (notably any with sodium channel–blocking or sympathetic enhancing activity). Although usually not requiring intervention, frequent PVCs may herald the onset of VT, especially in the setting of ST elevation myocardial infarction or in patients with a prolonged QT interval. A PVC appears as a wide–QRS complex extrasystole without a preceding P wave (Fig. 69.19). Because retrograde conduction of

a PVC rarely extends far enough to capture and reset the SA node, atrial impulses continue to arrive at the AV node at the intrinsic sinus rate. As a result, the R-R interval surrounding a PVC ends up being equal to exactly twice the intrinsic R-R interval length (see Fig. 69.19), a phenomenon termed a compensatory pause. Rarely, a PVC will capture the SA node, resulting in a noncompensatory pause, or will fail to capture the AV node, leaving the underlying rhythm completely unaffected (a so-called interpolated PVC; Fig. 69.20). The morphology of a PVC depends on the origin of the impulse, with a left bundle branch block (LBBB) appearance resulting from an extrasystolic focus in the right ventricle, and vice versa. Multiform (or multifocal) PVCs come from more than one source and have variable morphologies. When a PVC occurs at or around the time that a supraventricular impulse is set to depolarize the ventricle, the result is a fusion QRS complex (Fig. 69.21). Table 69.4 lists common features of PACs and PVCs. Direct therapy for PVCs toward correcting any precipitating condition whether it is catecholamine excess, drug effect, electrolyte imbalance, or cardiac ischemia (Box 69.6). Often, PVCs do not require treatment in the ED. When occurring in isolation, treat symptomatic PVCs with a beta blocker (metoprolol, 5–10 mg IV or 25–50 mg PO), although this is rarely an emergent need. Although lidocaine suppresses PVCs, do not use it routinely in the absence of VT because of limited clinical benefit and the risk of asystole.

Narrow-Complex Tachycardia Narrow-complex tachycardias have a QRS complex duration of 0.12 second or less on the surface ECG and a ventricular rate more than 100 beats//min. The term supraventricular tachycardia may

CHAPTER 69  Dysrhythmias

F

F

V4

V4 Fig. 69.21.  Sinus rhythm with premature ventricular contraction and run of accelerated idioventricular rhythm. Note fusion beats (F) displaying a hybrid appearance of both morphologies.

BOX 69.6 

Causes of Premature Ventricular Contractions and Ventricular Tachycardia Acute or previous myocardial infarction or ischemia Hypokalemia Hypoxemia Ischemic heart disease Valvular disease Catecholamine excessa Other drug intoxications (especially cyclic antidepressants) Idiopathic causesb Digitalis toxicity Hypomagnesemia Hypercapnia Class I antidysrhythmic agents Ethanol Myocardial contusion Cardiomyopathy Acidosis Alkalosis Methylxanthine toxicity a

Relative increase in sympathetic tone from drugs (direct or indirect) or conditions that augment catecholamine release or decrease parasympathetic tone. Isolated premature ventricular contractions (PVCs) can occur in up to 50% of young subjects without obvious cardiac or noncardiac disease; however, multiform and repetitive PVCs and ventricular tachycardia are rarely seen in this population. b

be confusing; sometimes it is used specifically to note AV reentry tachycardia, but it can denote any tachycardia originating at or above the AV node. ECG features that help distinguish between different narrowcomplex tachycardias include the appearance of P waves and the regularity or irregularity of the R-R interval. For example, a narrow-complex tachycardia, an irregular R-R interval, and no clear P waves is almost certainly atrial fibrillation. With rapid tachycardias, evidence of atrial depolarization is often obscured by ventricular repolarization; for example, with a regular, narrowcomplex tachycardia at a rate of 150 beats/min, it can be difficult to distinguish sinus tachycardia from atrial flutter or a JT. Vagal maneuvers or adenosine may transiently slow AV nodal conduction and expose evidence of atrial depolarization and aid diagnosis.

Alternatively, the patient may convert to sinus rhythm, in which case AVNRT can be diagnosed and treated.

Sinus Tachycardia Sinus tachycardia displays a regular, usually narrow-complex tachycardia, with normal P waves preceding each QRS complex (Fig. 69.22) on the ECG. In adults, sinus tachycardia rarely exceeds a rate of 170 beats/min; in infants and young children, it is not unusual to see rates above 200 to 225 beats/min. Sinus tachycardia tends to speed up or slow down in a graded and continuous manner over time, relayed by history or observed under care. Sinus tachycardia is often a response to physiologic stress or is a compensation for a relative lack of perfusion or oxygen delivery (to increase cardiac output). Usually, the effect is salutary, as seen with hypovolemia, anemia, or hypoxemia; efforts to slow the heart rate without addressing the underlying pathophysiology are likely to make things worse. At other times, sinus tachycardia is a counterproductive response, as in acute decompensated heart failure or aortic stenosis, in which a decrease in filling time further compromises cardiac output. Even in these settings, therapy is aimed first at the underlying problem rather than the tachycardia. Sinus tachycardia can be seen with any sympathetic excess, whether endogenous (eg, pain, anxiety, fever, hyperthyroidism) or exogenous (eg, stimulants, other drugs). The approach to the patient with sinus tachycardia centers on identifying and addressing the cause(s).

Atrial Tachycardia Atrial tachycardia (AT) is an atrial rhythm with more than 100 QRS complexes/min arising from a non–sinus node site(s) within the left or right atrium. The electrocardiographic hallmark of AT is morphologically abnormal P waves on the surface ECG, all or mostly related to each QRS wave (Fig. 69.23). If the site of origin is close to the sinus node, atrial depolarization waves may look like a normal P wave. Depending on the atrial rate, the AV conduction ratio may be 1 : 1, 2 : 1, or higher. AT is common in children and young adults with structural heart disease, often precipitated by the occurrence of a PAC. The rhythm is usually transient and does not require specific therapy. AT can occur in patients with structural heart disease, hypoxemia, metabolic disturbances, and/or drug toxicity. In patients taking

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I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

V1

II

V5 Fig. 69.22.  Sinus tachycardia.

I

R

II

L

III

F

Fig. 69.23.  Atrial tachycardia (with 2 : 1 conduction) in a patient with digitalis toxicity. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2, St. Louis, 1989, Mosby.)

digitalis, suspect toxicity if AT exists, particularly in the presence of 2 : 1 or higher grade AV block. Multifocal atrial tachycardia (MAT) is a form of AT with three or more distinct P wave morphologies, and varying PR and P-P intervals from the multiple ectopic atrial foci (Fig. 69.24). MAT is associated with pulmonary disease (usually chronic obstructive pulmonary disease [COPD]) in up to 60% of cases, but can also be seen in the presence of primary cardiac pathology. On the surface ECG, MAT is often mistaken for atrial fibrillation because of the nonuniform atrial activity and irregular R-R intervals. The approach to patients with AT is to identify and treat any precipitating factors, such as hypoxia or hypoxemia, electrolyte abnormalities, and drug toxicity. In patients with suspected

hypomagnesemia, give supplemental magnesium (2 g IV over 5 minutes). Vagal maneuvers and adenosine are unlikely to be effective in AT or MAT, although these may help unmask the atrial activity. Pharmacologic therapy to slow AV conduction with a beta blocker or calcium channel blocker aids in the symptomatic but stable patient. Because AT and MAT are often precipitated by underlying illnesses, electrical cardioversion often fails or the rhythm recurs.

Atrial Fibrillation Atrial fibrillation is identified by electrical chaos; it starts from unpatterned depolarization of atrial tissues caused by multiple

CHAPTER 69  Dysrhythmias

Fig. 69.24.  Multifocal atrial tachycardia. Note that although the rhythm is irregular, at least three distinct P wave morphologies are present.

Fig. 69.25.  Atrial fibrillation with rapid ventricular response. Note that the irregularity could be easily overlooked.

microreentry circuits, generating 300 to 600 atrial impulses/min. This chaotic activity reduces cardiac output from a loss of coordinated atrial contractions and from a rapid ventricular rate, both of which may limit the diastolic filling and stroke volume of the ventricles. Atrial fibrillation is the most common sustained dysrhythmia, increasing with age; it affects 1% of the population older than 60 years and 5% of those 69 years old or more. Patients with atrial fibrillation can develop left atrial thrombi, especially in the left atrial appendage, and consequent embolic events. The risk of stroke is three to five times greater than in those without atrial fibrillation. Appendageal sequestration through transcatheter approaches may alter the need for long-term, clot-directed therapy to mitigate embolic risks, but empirical long-term data are absent. Also, ablation therapies may restore sinus rhythm without the need for ongoing drug therapy. Atrial fibrillation may be paroxysmal (spontaneously converts), persistent (requires cardioversion to convert), or permanent (when no further efforts to restore sinus rhythm are planned). Long-term approaches to management depend on many factors, including chronicity, symptomatology, underlying heart disease, and other comorbidities. The electrocardiographic hallmark of atrial fibrillation is a so-called irregularly irregular QRS pattern (Fig. 69.25). Although atrial fibrillation is not the sole cause of an irregular ventricular rhythm, it is the most common (Box 69.7). Atrial fibrillatory waves appear coarse or fine on the basis of their amplitude and are often best appreciated in the inferior leads or lead V1. Typically, the ventricular rate in adults with atrial fibrillation does not exceed 150 to 170 beats/min and often is slower, particularly in the presence of nodal blocking agents. Atrial fibrillation in an adult with a ventricular rate exceeding 200 beats/min strongly suggests the presence of an accessory conduction pathway

BOX 69.7 

Causes of Completely Irregular   (Chaotic) Rhythms Atrial fibrillation Atrial tachycardia or flutter with varying conduction Multifocal atrial tachycardia Multiple extrasystoles Wandering pacemaker (usually atrial) Parasystole

and has important implications for management (see later). Frequently, rapid atrial fibrillation with an accessory path will have a wide QRS complex, but not always; if the irregularity of ventricular depolarization is not sought by the careful use of a caliper or similar measurement, it is easy to mistake this wide but chaotic rhythm for VT. When a wide QRS complex is seen at rates below 200 beats/min but with ventricular chaos, an existing or acquired bundle branch block with atrial fibrillation is likely present. The Ashman phenomenon refers to aberrant ventricular conduction of an early-arriving atrial impulse following a relatively long R-R interval, the result of a partially refractory His bundle. Such aberrantly conducted impulses are commonly seen in atrial fibrillation but can occur in any irregular rhythm in which longshort cycle sequences occur; they typically assume an RBBB pattern (Fig. 69.26). Ashman beats can be mistaken for PVCs or paroxysmal VT, if sustained. Atrial fibrillation is usually associated with underlying heart disease (myopathic or valvular) or hypertension (Box 69.8), but can also occur in isolation (so-called lone atrial fibrillation) or as

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MCL1

Fig. 69.26.  Atrial fibrillation with classic Ashman phenomenon series of beats. Note the long-short cycle before aberrantly conducted impulses are sustained for four beats. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2, St. Louis, 1989, Mosby.)

BOX 69.8 

Causes of Atrial Fibrillation Hypertensive heart disease Cardiomyopathy Ischemic heart disease Valvular disease (especially mitral) Congestive heart failure Pericarditis Hyperthyroidism Sick sinus syndrome Myocardial contusion Acute ethanol intoxication (holiday heart syndrome) Idiopathic Cardiac surgery Catecholamine excess Pulmonary embolism Accessory pathway (Wolff-Parkinson-White) syndrome

a manifestation of hyperthyroidism. As many as one-third of patients with congestive heart failure also have atrial fibrillation. The presentation of patients with atrial fibrillation is variable. For example, patients without underlying cardiopulmonary disease may tolerate atrial fibrillation with ventricular rates of 150 to 170 beats/min, noting only palpitations or exercise intolerance. Conversely, a patient with left ventricular dysfunction and new or worsened rate control may experience dyspnea at rest. In a stable patient with preexisting atrial fibrillation and a new rapid ventricular rate, direct the initial evaluation at determining if the tachycardia is a response to some other hemodynamic stress, such as decompensated heart failure, sepsis, hypovolemia, massive pulmonary embolism, or cardiac tamponade. Failure to recognize the underlying cause of a new tachycardia may result in counterproductive attempts at rate control or cardioversion. Measuring the thyroid-stimulating hormone level is prudent in those with new or recurrent atrial fibrillation, because this can trigger the condition and be easily treated. For stable patients with persistent or recurrent rapid atrial fibrillation, administration of a nodal blocking agent with a goal of achieving a target ventricular rate of 120 beats/min or less is a first step.7,8 IV calcium channel blockers (eg, diltiazem, verapamil) or beta blockers (eg, metoprolol) are easily titrated and can be followed by an oral agent. Nodal agents should not be used for rate control in the setting of accessory pathway conduction

because AV conduction—with retrograde conduction into the accessory pathway—may be the only thing preventing the ventricular rate from accelerating and degenerating into ventricular fibrillation. The debate as to whether asymptomatic patients with persistent atrial fibrillation benefit additionally from rhythm control via cardioversion or by other means (eg, ablation) is ongoing without a definitive answer. In older adults, those with recurrence despite rhythm-directed therapy, or with valvular disease, rate control is a wise choice; 40% to 60% of all patients placed on antidysrhythmics to sustain sinus rhythm fail. For patients younger than 50 years and without valve disease, attempts to maintain sinus rhythm to avoid cardiomyopathy or stroke are reasonable. In choosing rate control for the long term, the ideal target rate is unclear, with some advocating less than 80 beats/min at rest instead of the common goal of 110 beats/min or less; there is as yet no clear evidence of either target being superior. For stable patients with new-onset or newly recurrent atrial fibrillation—defined as having a duration of 48 hours or less—or in those with therapeutic anticoagulation, ED cardioversion is an option unless valve disease, hypokalemia, or digitalis toxicity exist; the latter two conditions increase the risk of ventricular fibrillation with any type of conversion therapy.7-11 If atrial fibrillation has been present longer than 2 days or for an uncertain interval in the absence of ongoing anticoagulation, do not attempt cardioversion to avoid the increased risk of systemic embolization (1%–4% at 30 days). The choice of electrical versus pharmacologic cardioversion is dependent on institutional factors and patient preference, although success rates are higher with electrical conversion (80%–95%).9,10 Among patients with new or recurrent atrial fibrillation of less than 48 to 72 hours duration, up to 50% will convert spontaneously to sinus rhythm within 24 hours. Patients with valvular disease fail cardioversion or recur frequently, limiting the ED options to rate control. Various agents are available for the pharmacologic cardioversion of patients with stable atrial fibrillation in the ED, including the class IA, IC, and III antidysrhythmics (Box 69.9). In practice, IV procainamide, amiodarone, and ibutilide are the agents most commonly used in the ED setting. Amiodarone is commonly used because it initially slows the ventricular response without the need for an antecedent rate-controlling agent. Although there are differences in success rates among various agents, the overall response is 40% to 65% for drug-based ED cardioversion, although it may require up to 6 hours to occur. Do not use class IC antidysrhythmics in patients with structural or ischemic heart disease. For atrial fibrillation with accessory pathway conduction, use

CHAPTER 69  Dysrhythmias

BOX 69.9 

BOX 69.10 

Pharmacologic Approach to Atrial Fibrillation and Flutter Conversion

CHA2DS2VASC Scoring for Guiding ClotDirected Therapy in Atrial Fibrillation

IV procainamide, 30–50 mg/min, up to a total dose of 18–20 mg/kg (12 mg/kg in patients with congestive heart failure) or until conversion or side effects occur or Amiodarone, 3–5 mg/kg IV, over 15–20 min or Ibutilide, 0.015–0.02 mg/kg IV, over 10–15 min (conversion usually occurs within 20 min if successful) or Oral propafenone, 600 mg (contraindicated in setting of structural heart disease or ischemia) or Oral flecainide, 300 mg (contraindicated in setting of structural heart disease or ischemia)

CLINICAL FEATURE Congestive heart failure Hypertension Age ≥ 75 yr Diabetes mellitus Any previous stroke, transient ischemic attack, embolism Gender—female Age, 65–74 yr

NOTE: If needed, a calcium channel blocker can be given before the type IA agent (if no contraindications are present) to lower the ventricular response rate to below 120 beats/min and to attenuate further tachycardia from the vagolytic effects of these agents.

procainamide as a first-line agent because it has no effect on AV conduction. If choosing electrical cardioversion, obtain consent for the procedure and systemic sedation or analgesia needed. Ratecontrolling agents before countershock are not required and may impair success.12 While closely monitoring the airway and cardiac responses, place the pads on the front and back of the chest and use 100 J, biphasic and unsynchronized preferred; occasionally, a second attempt at 100 to 200 J is required. Many patients with atrial fibrillation, whether paroxysmal or permanent, benefit from long-term anticoagulation as prophylaxis against stroke. The American Heart Association (AHA) and European Society of Cardiology recommend using the CHA2DS2VAS2 score to guide clot prevention therapy in those with atrial fibrillation (Box 69.10).7,8 The choices include no therapy for the lowest risk strata (by definition those 0.14 s Extreme LAD artery (30 degrees) No response to vagal maneuvers

None Preceding P waves with QRS complexes QRS usually S; Q wave 0.07 second to nadir of S

QS RS

QR Notched or slurred S

A

B Fig. 69.33.  Morphology associated with the fourth criterion in the Brugada system. A, In patients with a right bundle branch–appearing complex. B, In patients with a left bundle branch–appearing complex.

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II P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

P

V1

V5

A

II

V1

V5

B

II

P

P

P

P

P

P

P

P

P

P

V1

C

V5

Fig. 69.34.  A, B, Ventricular tachycardia. Note atrioventricular dissociation. C, Intermittent, nonsustained ventricular tachycardia. Atrioventricular dissociation is evident. (Courtesy Dr. Edward Curtis.)

CHAPTER 69  Dysrhythmias

Is there an initial R wave in lead aVR?

Yes

Diagnose VT

Classification and Causes of Prolonged QT Syndromes That Produce Torsades de Pointes

No Is there an initial R or Q wave in aVR that is >40 msec?

Yes

Diagnose VT

No Is there a negative directed notch and a mostly negative QRS in aVR?

Yes

Diagnose VT

No Is the initial aVR ventricular activation velocity (vi) divided by the terminal velocity (v2) 17 or less?

Yes

BOX 69.12 

Diagnose VT

No Diagnose SVT Fig. 69.35.  Vereckei criteria for differentiation of ventricular tachycardia (VT) from supraventricular tachycardia (SVT).

Torsades de Pointes Torsades de pointes is literally translated as “twisting of the points” and is a paroxysmal form of polymorphic VT that meets the following clinical criteria (see Fig. 69.38): 1. Ventricular rate greater than 200 beats/min 2. Undulating QRS axis, with the polarity of the complexes appearing to shift about the baseline 3. Paroxysms of less than 90 seconds Torsades de pointes occurs in the setting of a prolonged QT interval, a reflection of abnormal ventricular repolarization. A prolonged QT interval can be congenital or acquired. Women are at a greater risk for Torsades de pointes. Acquired Torsades de pointes is much more common than congenital and is pausedependent, triggered by a slow heart rate. Acquired QT prolongation is the most common form seen outside a specialized pediatric setting and usually has multifactorial causes (Box 69.12). Common triggers include electrolyte disturbances (eg, hypokalemia, hypomagnesemia) and many different drugs (notably class IA and IC agents but also many others; see Box 69.12), especially when used in combination. Treatment of torsades de pointes in stable adult patients involves correcting any underlying metabolic or electrolyte abnormalities and increasing the heart rate to shorten ventricular repolarization. In patients with torsades de pointes, do not use class IA and IC antidysrhythmics. Empirical IV magnesium sulfate is effective in treating torsades de pointes, even in the absence of hypomagnesemia, and may prevent recurrence if electrical cardioversion succeeds. A baseline ventricular rate of 100 to 120 beats/min is usually enough to prevent acquired torsades de pointes, achieved by overdrive pacing (ie, external pacing at a rate greater than the patient’s intrinsic rate) or via β-adrenergic infusion. Use electrical cardioversion for unstable patients, as outlined in the discussion of VT with sustained torsades de pointes, without any attempt to synchronize. Congenital torsades de pointes is rare and is triggered by sympathetic excess or tachycardia; it is usually seen in children and young adults. Patients often have syncope during exertion and

PAUSE-DEPENDENT (ACQUIRED)

Drug-induced—class IA and IC antidysrhythmics; many phenothiazines and butyrophenones (notably haloperidol and droperidol), cyclic antidepressants, antibiotics (especially macrolides), organophosphates, antihistamines, antifungals, antiseizure and antiemetic agents Electrolyte abnormalities—hypokalemia, hypomagnesemia, hypocalcemia (rarely) Diet-related—starvation, low protein Severe bradycardia or atrioventricular block Hypothyroidism Contrast injection Cerebrovascular accident (especially intraparenchymal) Myocardial ischemia

ADRENERGIC-DEPENDENT (TACHYCARDIA-PROMPTED)

Congenital Jervell and Lange-Nielsen syndrome (deafness, autosomal recessive) Romano-Ward syndrome (normal hearing, autosomal dominant) Sporadic (normal hearing, no familial tendency) Mitral valve prolapse Acquired (Rare) Cerebrovascular disease (especially subarachnoid hemorrhage) Autonomic surgery: radical neck dissection, carotid endarterectomy, truncal vagotomy

a prolonged QT interval on the ECG. In contrast to acquired forms, treat congenital torsades de pointes with beta blockers.

Brugada’s Syndrome Brugada’s syndrome is characterized by ventricular dysrhythmias triggering syncope or sudden cardiac death in the absence of structural heart disease. This syndrome is caused by an inherited disorder of sodium channels and is commonly diagnosed in men during young adulthood. The Brugada electrocardiographic pattern shows a downward coved or humped (saddleback) ST segment elevation in leads V1 to V3 (Fig. 69.39), sometimes simulating an RBBB appearance. The ST segment findings may be transient or elicited only with pharmacologic stimulation. Any patient with unexplained syncope and a Brugada pattern ECG requires admission for consideration of an implanted defibrillator. For patients in whom a Brugada pattern ECG is noted incidentally, there is no consensus on treatment, but we recommend referral to a cardiologist.

DISPOSITION Patients with dysrhythmias that are markedly symptomatic and nonresponsive to ED therapy require admission; in those without symptoms or only palpitations, and who resolve, with no evidence of structural heart disease, outpatient ambulatory monitoring and close contact with a cardiologist is an option.24 When evaluating anyone with symptomatic rhythm changes, we recommend a cardiology consultation. Those with VT or torsades de pointes, and most symptomatic patients with type II second-degree or complete heart block, require admission.

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A

B

C

P

P

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

II

II

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

II

Fig. 69.36.  Ventricular tachycardia. A, RS complexes are present in chest leads, but RS duration is greater than 100 ms. Although the Brugada criteria indicate that no further analysis is necessary, atrioventricular dissociation is also evident, and QRS morphology in lead V6 is consistent with ventricular tachycardia. B, Some RS complexes are present, RS duration is no longer than 100 msec, and atrioventricular dissociation is difficult to appreciate. The morphologic criteria for ventricular tachycardia are fulfilled because S is notched in V1 and QR is present in V6. C, Diagnosis is based on morphologic criteria because S is notched in V1 and V2 and QS is present in V6. (Courtesy Dr. Edward Curtis.)

CHAPTER 69  Dysrhythmias

L

V2

V6

Fig. 69.37.  Bidirectional ventricular tachycardia in a patient with digitalis toxicity. (From Marriott HJL, Conover MB: Advanced concepts in dysrhythmias, ed 2, St. Louis, 1989, Mosby.)

Fig. 69.38.  Torsades de pointes with classic spiraling of QRS complexes around the baseline.

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I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

V1

10 mm/mV 25 mm/s Average I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

B Fig. 69.39.  Brugada’s syndrome, with ST elevation in V1S. The ST elevation is coved (upper, A) or saddleback (lower, B) and may be transient.

KEY CONCEPTS • Electrical therapy is used for any unstable patient in whom a dysrhythmia is the cause of symptoms—pacing if the heart rate is slow, countershock with sedation if fast. • Assume that any regular, new-onset, symptomatic, wide-complex tachycardia is VT until proven otherwise. • Type II second-degree AV block is never a normal variant and implies a conduction block below the AV node. When the conduction ratio is 2 : 1, assume that type II block exists until proven otherwise and have pacing readily accessible.

• Consider an accessory pathway syndrome in anyone with tachycardia exceeding a rate of 225 to 250 beats/min, regardless of the QRS complex morphology, and avoid nodal blocking agents. • Look closely for irregularity in tachycardia over 200 beats/min; this and underlying atrial fibrillation can be missed if R-R intervals at fast rates are not carefully tracked.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 69  Dysrhythmias

REFERENCES 1. Moskovitz JB, Hayes BD, Martinez JP, et al: Electrocardiographic implications of the prolonged QT interval. Amer J Emerg Med 31:866–871, 2013. 2. Kudenchuk PJ, Newell C, White L, et al: Prophylactic lidocaine for post resuscitation care of patients with out-of- hospital ventricular fibrillation. Resuscitation 84:1512– 1518, 2013. 3. Pfizer: Risk evaluation and mitigation strategy (REMS) document—NDA 20-931 Tikosyn (dofetilide). . 4. Hwang CM, Kim JY, Choi SH, et al: Effect of adenosine after instruction of injection in patients with paroxysmal supraventricular tachycardia presented to the emergency department. J Korean Soc Emerg Med 26:571–576, 2015. 5. Smith GD, Fry MM, Taylor D, et al: Effectiveness of the Valsalva manoeuvre for reversion of supraventricular tachycardia. Cochrane Database Syst Rev (2):CD009502, 2015. 6. Than M, Peacock WF: Supraventricular tachycardia: back to basics. Lancet 386:1712, 2015. 7. Camm AJ, Lip GY, De CR, et al: 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33:2719–2747, 2012. 8. January CT, Wann LS, Alpert JS, et al: 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. JACC 64:e1–e76, 2014. 9. Cohn BG, Keim SM, Yealy DM: Is emergency department cardioversion of recentonset atrial fibrillation safe and effective? J Emerg Med 45:117–127, 2013. 10. Stiell IG, Clement CM, Brison RJ, et al: Variation in management of recent-onset atrial fibrillation and flutter among academic hospital emergency departments. Ann Emerg Med 57:13–21, 2011. 11. Stiell IG, Clement CM, Perry JJ, et al: Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with recent-onset atrial fibrillation or flutter. CJEM 12:181–191, 2010. 12. Blecher GE, Stiell IG, Rowe BH, et al: Use of rate control medication before cardioversion of recent-onset atrial fibrillation or flutter in the emergency department is associated with reduced success rates. CJEM 14:169–177, 2012.

13. Patel MR, Mahaffey KW, Garg J, et al: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891, 2011. 14. Ruff CT, Giugliano RP, Braunwald E, et al: Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a metaanalysis of randomised trials. Lancet 383:955–962, 2014. 15. Scheuermeyer FX, Grafstein E, Heilbron B, et al: Emergency department management and 1-year outcomes of patients with atrial flutter. Ann Emerg Med 57:564–571, 2011. 16. Holdgate A, Foo A: Adenosine versus intravenous calcium channel antagonists for the treatment of supraventricular tachycardia in adults. Cochrane Database Syst Rev (4):CD005154, 2006. 17. Gebril A, Hawes S: Is intravenous adenosine effective and safe in patients presenting with unstable paroxysmal supraventricular tachycardia? Emerg Med J 29:251–254, 2012. 18. Schmitz G, Rezaie S: Do elevated troponins during supraventricular tachycardia (SVT) predict the presence of coronary artery disease? . 19. Minhas R, Vogelaar G, Wang D, et al: A prehospital treat-and-release protocol for supraventricular tachycardia. CJEM 17:395–402, 2015. 20. Baxi RP, Hart KW, Vereckei A, et al: Vereckei criteria as a diagnostic tool amongst emergency medicine residents to distinguish between ventricular tachycardia and supraventricular tachycardia. J Card 59:307–312, 2012. 21. Martin-Sanchez FJ, Bueno H: Are available electrocardiographic methods accurate enough to diagnose ventricular tachycardia in the emergency department? Acad Emerg Med 21:217–219, 2014. 22. Szelenyi Z, Duray G, Katona G, et al: Comparison of the “real-life” diagnostic value of two recently published electrocardiographic methods for the differential diagnosis of wide QRS complex tachycardia. Acad Emerg Med 20:1121–1130, 2013. 23. deSouza IS, Martindale JL, Sinert R: Antidysrhythmic drug therapy for the termination of stable, monomorphic ventricular tachycardia: a systematic review. Emerg Med J 32:161–167, 2015.

CHAPTER 69: QUESTIONS & ANSWERS 69.1. What is the primary electrochemical difference between pacemaker and nonpacemaker cells? A. Lack of a plateau phase 3 in nonpacemaker cells B. Rapid phase 0 upstroke in nonpacemaker cells after stimulus C. Slow calcium ion influx during phase 2 for pacemaker cells D. Slow phase 4 spontaneous depolarization in pacemaker cells E. Transient membrane repolarization by potassium channel closure during phase 1 for pacemaker cells Answer: D. The spontaneous return to a depolarization threshold during phase 4 (diastole) characterizes pacemaker cells. Both cell types then exhibit a rapid phase 0 upstroke resulting from sodium ion (Na+) influx, brief repolarization resulting from potassium ion (K+) efflux (phase 1), plateau phase resulting from balanced calcium ion (Ca2+) entry and K+ efflux (phase 2), and then repolarization resulting from Ca2+ channel closure and K+ efflux (phase 3). 69.2. For a reentrant tachydysrhythmia to occur, what three conditions exist? A. Electrolyte disturbance, ischemia, and altered conduction in an endogenous atrioventricular pathway B. Electrolyte disturbance, two conduction pathways, with one of the pathways being slower C. Ischemia, two conduction pathways, with one of the pathways being slower D. Two conduction pathways, one path being slower, and differing responsiveness E. Two conduction pathways with equal responsiveness Answer: D. Remember that a conducting pathway is bidirectional. In a typical scenario, the alpha pathway of the atrioventricular

(AV) node is the anterograde conducting limb, and the beta pathway is the retrograde conducting limb. Reentrant dysrhythmias are almost always AV nodal and narrow complexes that start and end abruptly. 69.3. Classic antifibrillatory effects are seen with which class of antidysrhythmic? A. IA B. IB C. IC D. II E. III Answer: E. Class III agents, of which amiodarone is the prototype, prolong the action potential and refractory period duration. Class I agents have variable effects on depolarization rate and repolarization duration. 69.4. The most frequent proarrhythmic effects are seen with which class of antidysrhythmic? A. IA B. IB C. IC D. II E. III Answer: C. Class IC agents, such as flecainide, encainide, and propafenone, markedly slow depolarization and conduction and prolong repolarization and action potential duration. Class IB agents generally have the least proarrhythmic effect. 69.5. A 49-year-old woman presents with a sudden onset of palpitations and shortness of breath. This has happened once before. She has no past history and takes no medications. Vital signs are temperature, 36.0° C (96.8° F)

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oral, blood pressure, 115/69 mm Hg, heart rate 156 beats/min, respiratory rate 24 breaths/min, and oxygen (O2) saturation, 98%. Her electrocardiogram (ECG) is shown in Fig. 69.28. What is the most appropriate intervention? A. Adenosine, 6 mg IV B. Digitalis, 0.25 mg IV C. Diltiazem, 0.4 mg/kg IV D. Propranolol, 1 mg IV E. Synchronized electrical cardioversion after IV sedation with midazolam

Answer: A. Adenosine causes slowing of conduction in the anterograde and retrograde pathways, with no effect on ventricular contractility. It converts a high percentage of narrow-complex tachycardias to sinus rhythm, but with a 25% recurrence rate. Diltiazem would not be unreasonable, but the quoted dose is too high. Calcium channel blockers also exert their effects only on the anterograde pathway, with little direct effect on accessory pathways. Contractility may be diminished. Digitalis use has been largely supplanted by adenosine and class IV agents. Its onset of action after IV use is 1.5 to 2 hours. Cardioversion would not be indicated unless the patient exhibited hemodynamic instability.

C H A P T E R 70 

Implantable Cardiac Devices Benjamin Squire  |  James T. Niemann PRINCIPLES Electrical cardiac pacing for the management of bradyarrhythmias was first described in 1952, and permanent transvenous pacing devices were introduced into clinical practice in the early 1960s.1 The first devices for endocardial defibrillation were implanted in surviving victims of sudden cardiac death in 1980.2 Implanted electrical devices for the management of cardiac dysrhythmias have changed rapidly over the years, with both increasing complexity and miniaturization. Between 1993 and 2009, 2.9 million new permanent pacemakers were implanted in the United States.3 Indications for the use of permanent pacemakers in the management of congenital and acquired heart disease has expanded beyond treatment of dysrhythmias to include cardiac resynchronization therapy for heart failure.4-6 A number of large clinical trials comparing implantable cardioverter-defibrillators (ICDs) with antiarrhythmic drugs for the prevention of sudden cardiac death resulting from ventricular dysrhythmias have indicated that ICDs significantly improve survival.7,8 Such studies have led to a dramatic increase in ICD implantations, and it is estimated that there are more than 125,000 new ICD implants annually in the United States.9 The widespread use of these devices assures that emergency clinicians will encounter patients, often with symptoms that may be related to the normal function or malfunction of the pacemaker or ICD.

CLINICAL FEATURES Guidelines for the implantation of these devices have been developed by a joint task force of the American Heart Association (AHA) and the American College of Cardiology (ACC) and are periodically updated.10,11 Similar to categorization of evidence for other recommendations or guidelines, recommendations are categorized as class I, II, or III. Class I includes conditions for which there is general agreement that a device should be implanted. A class II recommendation includes conditions for which these devices are frequently used but for which there is disagreement about their need or benefit. Class III is reserved for conditions for which there is general agreement that a device is not needed. Class I indications for a permanent pacemaker or ICD are listed in Boxes 70.1 and 70.2. In general, pacing is recommended for patients with symptomatic heart block, symptomatic sinus bradycardia, and atrial fibrillation with a symptomatic bradycardia (low ventricular response rate) in the absence of medications that affect atrioventricular (AV) conduction. Biventricular pacing (cardiac resynchronization therapy) is indicated for systolic heart failure patients with left ventricular ejection fracture under 35% and left bundle branch block.5,11-13

Pacemaker Terminology A letter code, initially established in 1974 and revised as technology advances, standardizes nomenclature for pacemakers. Table 70.1 includes an explanation of the five-letter code scheme and the standard abbreviations in each category. The first three code

letters are used most commonly. Using this table, one should be able to understand the features of any pacing mode. For example, a VDD (Ventricle, Dual, Dual) pacemaker is capable of pacing only the ventricle, sensing both atrial and ventricular intrinsic depolarization, and responding by dual inhibition of both atrial and ventricular pacing if intrinsic ventricular depolarization occurs; a paced ventricular beat is triggered in response to a sensed intrinsic atrial depolarization. The codes of a permanent pacemaker that are used most frequently and the indications, advantages, and disadvantages of each are listed in Table 70.2. Detailed algorithms for matching a patient with the appropriate pacemaker exist.10 The majority of permanent pacemakers are dual chamber and most often rate adaptive.

Pacemaker Components All pacemaker systems have three basic components: the pulse generator, which houses the power source (battery); the electronic circuitry; and the lead system, which connects the pulse generator to the endocardium. Nearly all implanted pacemakers are lithium powered. Lithium-powered pulse generators function normally for 4 to 10 or more years, depending on the pacemaker features, such as single versus dual chamber, pacing threshold, and rate adaptiveness. This long “battery life” and the fact that the output voltage of the lithium-iodine cell decreases gradually rather than abruptly, as occurred with the early mercury-zinc cell, make sudden pulse generator failure an unlikely cause of pacemaker malfunction. Permanent pacemakers have endocardial leads that are positioned in contact with the endocardium of the right ventricle and, in the case of a dual-chamber device, the right atrium, with a subclavian or cephalic vein approach used for insertion. Occasionally, an epicardial lead may be implanted during open-heart surgery performed for another indication, such as prosthetic valve insertion or correction of a congenital cardiac defect. Pacemaker leads may be either bipolar or unipolar in configuration. A bipolar endocardial lead has both the negative (distal) and the positive (proximal) electrodes, separated by approximately 1 cm, within the heart. A unipolar lead has the negative electrode in contact with the endocardial surface, and the positive pole is the metallic casing of the pulse generator. Each lead system has potential advantages and disadvantages.1 The unipolar configuration is not compatible with ICD systems and is prone to oversensing of myopotentials and electromagnetic interference but is of smaller diameter and less susceptible to fracture. The bipolar configuration is compatible with ICD systems but is larger and more prone to lead fractures. Oversensing, however, is rarely a problem. The selection of lead configuration usually depends on patient characteristics, as well as the experience and preference of the operator.

History The patient should be asked for the pacemaker identification card. The information on the card explains why a pacemaker was placed 959

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TABLE 70.1 

Five-Letter Pacemaker Code LETTER 1: CHAMBER PACED

LETTER 2: CHAMBER SENSED

LETTER 3: SENSING RESPONSE

LETTER 4: PROGRAMMABILITY

LETTER 5: ANTITACHYCARDIA FUNCTIONS

A = Atrium

A = Atrium

T = Triggered*

P = Simple

P = Pacing

V = Ventricle

V = Ventricle

I = Inhibited

M = Multiprogrammable

S = Shock

D = Dual

D = Dual

D = Dual (A and V inhibited)

R = Rate adaptive

D = Dual (shock pace)

0 = None

0 = None

0 = None

C = Communicating 0 = None

*In the triggered response mode, the pacemaker discharges or fires when it recognizes an intrinsic depolarization. As a result, pacemaker spikes occur during inscription of the QRS complex. Because this mode results in high energy consumption and a shortened battery life and because the sensing response can be misinterpreted as pacemaker malfunction, this sensing mode is not used with modern pacemakers.

TABLE 70.2 

Common Permanent Pacemakers CODE

INDICATION

ADVANTAGES

DISADVANTAGES

VVI

Intermittent backup pacing; inactive patient

Simplicity; low cost

Fixed rate; risk of pacemaker syndrome

VVIR

Atrial fibrillation

Rate responsive

Requires advanced programming

DDD

Complete heart block

Atrial tracking restores normal physiology

No rate responsiveness; requires two leads and advanced programming

DDDR

Sinus node dysfunction; for rate responsiveness atrioventricular (AV) block and need

Universal pacer; all options available by programming

Complexity, cost, programming, and follow-up evaluation

BOX 70.1 

BOX 70.2 

Class I Indications for Permanent Pacing in Adults

Class I Indications for Implantable Cardioverter-Defibrillator Therapy

1. Third-degree and advanced second-degree AV block at any anatomic level associated with any of the following: • Symptomatic bradycardia (including heart failure) or ventricular dysrhythmia presumed to be a result of AV block • Symptomatic bradycardia secondary to drugs required for dysrhythmia management or other medical condition • Documented periods of asystole lasting more than 3 seconds or an escape rate of less than 40 beats/min or an escape rhythm originating below the AV node in an awake, asymptomatic patient in sinus rhythm • Awake, asymptomatic patients with atrial fibrillation and bradycardia a documented pause of 5 seconds or longer • After catheter ablation of the AV node • Postoperative AV block that is not expected to resolve • Neuromuscular disease with AV block (eg, the muscular dystrophies) 2. Symptomatic bradycardia resulting from second-degree AV block regardless of type or site of block 3. Asymptomatic, persistent third-degree AV block with awake ventricular rate over 40 beats/min with cardiomegaly or left ventricular dysfunction or if block is below AV node 4. Chronic bifascicular or trifascicular block with intermittent third-degree AV block or type II second-degree AV block 5. Second or third-degree AV block with exercise in the absence of myocardial ischemia

1. Cardiac arrest resulting from VF or VT not caused by a transient or reversible event 2. Spontaneous sustained VT 3. Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at electrophysiologic study when drug therapy is ineffective, not tolerated, or not preferred 4. Nonsustained VT with coronary artery disease, prior myocardial infarction, left ventricular dysfunction, and inducible VF or sustained VT at electrophysiologic study that is not suppressible by a class I antiarrhythmic drug

AV, Atrioventricular.

VF, Ventricular fibrillation; VT, ventricular tachycardia.

and the pacing modality used. If the card is not available, information may be obtained by calling the device manufacturer. If the manufacturer is unknown, calls can be made to the most common manufacturers until the patient is found in one of the registries. All manufacturers provide support including representatives on call to respond to the hospital to interrogate a device. Most patients with pacemaker malfunction have symptoms reminiscent of those that prompted pacemaker therapy: syncope, near-syncope, orthostatic dizziness, lightheadedness, dyspnea, or palpitations.

CHAPTER 70  Implantable Cardiac Devices

The majority of pacemaker complications and most instances of pacemaker malfunction occur within the first few weeks or months of pacemaker implantation. After wound healing, palpation of the pulse generator site should not elicit tenderness. A wound infection or pocket infection typically arises with localized pain. Bacteremia secondary to infection of the pacing catheter, however, may arise only with fever and without other manifestations of the systemic inflammatory response syndrome. Pain in the arm ipsilateral to the site of insertion should suggest acute thrombophlebitis. Patients who develop the pacemaker syndrome secondary to the loss of AV synchrony may have nonspecific complaints of easy fatigability, generalized weakness, dyspnea, or an uncomfortable fluttering or “pounding” sensation in the neck or abdomen. Syncope or near-syncope may also occur, but these complaints should prompt an evaluation for true pacemaker malfunction. The pacemaker syndrome should be a diagnosis of exclusion.

insulation surrounding the pulse generator or the portion of the pacemaker lead that lies within the pacemaker pocket. When a local infection or bacteremia is suspected, blood cultures should be obtained and intravenous antibiotic therapy initiated. Staphylococcus aureus and Staphylococcus epidermidis are isolated in approximately 60% to 70% of cases. Gram negative infection is rare.15 Empirical antibiotic therapy should include vancomycin pending culture and sensitivity data. If blood cultures are positive, the pulse generator and pacemaker leads are usually removed, temporary transvenous pacing is performed, and intravenous antibiotic therapy is continued for 4 to 6 weeks. The permanent pacemaker and lead are subsequently reimplanted.14

Thrombophlebitis

A pacemaker infection should be suspected in the presence of fever, even if another potential source of infection can be identified. Extremely low (100 beats/min in the resting patient) pulse rates are suggestive of altered pacing parameters (battery depletion or pacemaker-mediated tachycardias). Hypotension may be present in either instance. Cannon “A” waves on inspection of the jugular venous pulse wave indicate AV asynchrony. Auscultation of lungs may reveal bibasilar rales if congestive heart failure is present. During pacing, the first heart sound may vary in intensity as a result of AV dissociation (VVI mode), and the second heart sound may be paradoxically split when ventricular pacing occurs (the right ventricle is activated first). A pericardial friction rub may also be heard if the tip of the pacing catheter has perforated the wall of the right ventricle. Perforation, however, usually occurs at the time of pacemaker implantation and is usually recognized at that time. Although the pacing catheter traverses the tricuspid valve, tricuspid regurgitation is rarely heard unless there is myocardial disease such as right ventricular dilation, which is common in the cardiomyopathies. Pedal edema may be present and is important if it is a new symptom or if chronic edema has recently worsened.

The incidence of venous obstruction associated with permanent transvenous pacemakers ranges from 30% to 50%, with approximately one-third of patients having complete venous occlusion.16 Thrombosis of varying degrees can involve the axillary, subclavian, and innominate veins or the superior vena cava (SVC). The site of insertion does not appear to affect the incidence of this complication. Chronic thrombosis of the veins of the upper arm is common and usually asymptomatic owing to extensive venous collateral circulation. Because of extensive collateralization, approximately 0.5% to 3.5% of patients develop symptoms indicative of acute thrombosis. These patients will commonly have edema, pain, and venous engorgement of the arm ipsilateral to the site of lead insertion. Although rare, SVC syndrome resulting from pacemaker leadinduced thrombosis occurs. The signs and symptoms of leadinduced SVC syndrome are identical to those described in patients with SVC syndrome and malignancy. Although symptoms might suggest thrombosis, definitive diagnosis of acute thrombosis usually requires duplex sonography of the jugular venous system or contrast-enhanced computed tomography. The symptoms usually respond to systemic anticoagulation therapy followed by long-term anticoagulation. Treatment of these clots is controversial as they are rarely associated with pulmonary embolism. There are no studies comparing treatments for deep vein thrombus (DVT) related to pacemakers. Most commonly, anticoagulation is achieved using low–molecularweight heparin followed by warfarin for 3 to 6 months.

DIFFERENTIAL DIAGNOSIS

The “Pacemaker Syndrome”

Complications of Implantation

After pacemaker implantation, a patient may develop new complaints or report a worsening of the symptoms that prompted evaluation and eventual pacemaker therapy. Such complaints often include syncope or near-syncope, orthostatic dizziness, fatigue, exercise intolerance, weakness, lethargy, chest fullness or pain, cough, uncomfortable pulsations in the neck or abdomen, right upper quadrant pain, and other nonspecific symptoms. These symptoms, termed the pacemaker syndrome, are caused by loss of AV synchrony and by the presence of ventriculoatrial conduction. This syndrome is most commonly encountered in the setting of VVI pacing but is also described with the DDI mode. With VVI pacing, the ventricle is electrically stimulated and depolarized, resulting in ventricular systole. If sinus node function is intact, the atria can be depolarized by a sinus impulse and contract when the tricuspid and mitral valves are closed. This contractile asynchrony results in an increase in jugular and pulmonary venous pressures and may produce symptoms of congestive heart failure. Atrial distention can result in reflex vasodepressor effects mediated by the central nervous system. Elevated levels of B-type natriuretic peptide (BNP) and diuresis are considered markers for the syndrome in its more severe form. If the contribution of atrial

Physical Examination

Infection Pacemaker implantation is a surgical procedure and, like all surgery, carries a risk of infection; the presence of a foreign body enhances this risk. The incidence of infection is small— approximately 2% for wound and subcutaneous pacemaker “pocket” infection and approximately 1% for bacteremia with sepsis. The presence of a foreign body complicates management, and few cases of bacteremia that develop after implantation can be managed with antibiotics alone. In most instances, reimplantation and replacement of the lead system is necessary.14 Pain and local inflammation at the site of the pacemaker are the first manifestations of a wound infection, cellulitis, or pocket infection. Approximately 20% to 25% of patients with a local infection have positive blood cultures. Bacteremia may occur in the absence of a focal infection and may arise with the typical manifestations of the systemic inflammatory response syndrome or sepsis. A hematoma of the pacemaker pocket may mimic a wound or pocket infection. Needle aspiration of the pocket should be done only under fluoroscopy, because the needle may cut the

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contraction to late diastolic ventricular filling is important in maintaining an adequate cardiac output, basal and orthostatic hypotension may occur. DDI pacing in a patient with AV block may result in this syndrome if the sinus node discharge rate exceeds the programmed rate of the pacemaker. Approximately 20% of patients report symptoms suggesting the pacemaker syndrome after pacemaker insertion. In most instances, symptoms are mild and patients adapt to them. In approximately one-third of these patients, symptoms are severe. Treatment usually requires replacing a VVI pacemaker with a dual-chamber pacemaker or lowering the pacing rate of the VVI unit. If symptoms occur in a patient paced in the DDI mode, optimizing the timing of atrial and ventricular pacing is usually required. Patients appear to prefer dual-chamber pacing to the VVI modality.17

Pacemaker Malfunction The term pacemaker malfunction refers specifically to problems with the circuitry or power source of the pulse generator, the pacemaker lead (most commonly displacement or fracture), or the interface between the pacing electrode and the myocardium (pacing or sensing threshold). In addition, environmental factors, such as extracardiac or extracorporeal electrical signals, may interfere with normal pacemaker function.18,19 With use of the standard electrocardiogram (ECG), pacemaker malfunction can be separated into three broad categories: (1) failure to capture (no pacemaker spikes or spikes not followed by an atrial or ventricular complex), (2) inappropriate sensing (oversensing or undersensing spikes occur prematurely or do not occur even though the programmed interval is exceeded), or (3) inappropriate pacemaker rate. Symptomatic pacemaker malfunction after implantation occurs in less than 5% of patients and is rarely immediately lifethreatening. Malfunction is most commonly a result of inappropriate sensing, followed by failure to capture. Typical presentations and causes of pacemaker malfunction are listed in Box 70.3. In the context of suspected pacemaker malfunction, knowledge of the pacing modalities (see Table 70.1) and what is normal for a given pacing modality are critical when the ECG is reviewed. Fortunately, patients are provided with important identifying information, usually in the form of a wallet card, after pacemaker implantation. The most important information is provided in the five-letter code. Many patients will carry a card with the specifics of their pacemaker. If that is not available and the pacer type is not described in the medical records, a standard posteroanterior chest radiograph can provide clues based on number and placement of leads. A single lead in the apex of the right ventricle indicates a VVI pacemaker. With VVI pacing, only one stimulus artifact or spike is seen with each stimulated ventricular depolarization (Fig. 70.1). If sinus node activity is present, the paced QRS

complex is dissociated from the intrinsic P waves. If separate leads are identified in the right atrium and right ventricle, the pacing modality is most often DDD or DVI, and paced P waves and QRS complexes (two spikes for each QRS complex) are seen (Fig. 70.2). Although DDD and DVI units are capable of pacing both the right atrium and the right ventricle, only one spike may be seen (Fig. 70.3). Failure to identify two spikes with a DDD or DVI unit can represent normal pacemaker function. A magnet placed externally over the pulse generator is occasionally used in the assessment of pacemaker function. Magnet application causes closure of a reed switch, turning off sensing function, thus converting the pacemaker to fixed-rate pacing. The technique is most commonly used when the patient’s intrinsic heart rate exceeds the pacemaker’s set rate and pacemaker function is inhibited. Magnet application then allows pacing to occur, despite the patient’s native cardiac activity, and pacing rate and the presence of capture can be determined. Magnets are made by each manufacturer, but any cardiac pacemaker magnet will typically activate the reed switch in any device.

Failure to Capture Failure to capture may range from the complete absence of pacemaker spikes to spikes not followed by a stimulus-induced

BOX 70.3 

Causes of Pacemaker Malfunction FAILURE TO CAPTURE

• Lead disconnection, break, or displacement • Exit block • Battery depletion

UNDERSENSING • • • •

Lead displacement Inadequate endocardial lead contact Low-voltage intracardiac P waves and QRS complexes Lead fracture

OVERSENSING

• Sensing extracardiac signals: myopotentials • T wave sensing

INAPPROPRIATE RATE

• Battery depletion • Ventriculoatrial conduction with pacemaker-mediated tachycardia • 1:1 response to atrial dysrhythmias

2

Fig. 70.1.  Normal VVI pacemaker (rhythm strip). This rhythm strip was recorded in a patient with a VVI pacemaker implanted for the treatment of symptomatic complete heart block. The pacing rate is approximately 75 beats/min (determined by measuring the time between consecutive pacemaker spikes). Each pacemaker spike is followed by a paced QRS complex. The third QRS from the left has a slightly different morphology than the paced QRS complexes. It is an intrinsic QRS complex that is sensed by the pacemaker, and a paced beat does not occur again until the programmed rate of the pacemaker is exceeded. The time interval between the spontaneous QRS and the next paced beat is approximately the same as the interval between consecutive pacemaker spikes. This sequence is subsequently repeated twice on this strip.

CHAPTER 70  Implantable Cardiac Devices

1

aVR

V1

V4

2

aVL

V2

V5

3

aVF

V3

V6

Fig. 70.2.  Normal DDD pacemaker (12-lead electrocardiogram [ECG]). Each QRS complex is preceded by two pacemaker spikes. The first spike results in atrial depolarization, and the second produces a wide QRS complex. The QRS complex is conducted with a left bundle branch morphology, which is expected with endocardial pacing at the right ventricular apex.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

SYSTEM OUTPUT = TRACEBACK LOC 11101–3000

16 JULY 1992 10:37:14

364751 F

04066

Fig. 70.3.  Normal DDD pacemaker (half-standard 12-lead electrocardiogram [ECG]). Three paced QRS complexes preceded by a stimulus artifact or spike are evident in leads I, II, and III. Paced QRS complexes occur after spontaneous or intrinsic P waves are sensed and atrioventricular (AV) conduction delay exceeds the pacemaker’s programmed AV interval. The first QRS complex in the augmented leads, best seen in lead aVF, demonstrates both a paced P wave and a paced QRS complex. Although the pacemaker is a dual-chamber device, two spikes may not always be seen preceding every QRS complex, and the presence of only one spike, or no spikes, should not be interpreted as evidence of pacemaker malfunction. Also evident on this ECG are the different amplitudes of the pacemaker spikes from lead to lead. When a single-lead rhythm strip is recorded, the selected lead should be the one in which the pacemaker spikes are most easily identified.

complex (Fig. 70.4). A complete absence of pacemaker spikes may result from battery depletion, fracture of the pacemaker lead, or disconnection of the lead from the pulse generator unit. Current lithium-iodine batteries are not subject to sudden power failure, and they display typical end-of-life functional

changes over a period of months to a year before complete depletion.1 Usually the first sign of voltage depletion is a decrease in the programmed pacing rate. This change is gradual and should be detected during the regular follow-up evaluations that pacemaker patients receive. When voltage output falls to a critical level,

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I

Fig. 70.4.  Intermittent failure to capture and slow pacing rate (lead I). This lead I rhythm strip demonstrates intermittent failure to capture of a VVI pacemaker. The first and second pacemaker spikes are followed by wide-paced QRS complexes; the third and fourth spikes are not. The pacemaker spikes occur at a rate of approximately 50 beats/min. The device was programmed to pace at a rate of 75 beats/min. This is a typical example of “end-of-life” pacing characteristics of a depleted battery.

2 Fig. 70.5.  Failure to sense or undersensing (lead II). Pacemaker spikes are evident during inscription of the ST segment on this rhythm strip. These spikes do not produce QRS complexes because they occur during the ventricular refractory period of the preceding spontaneous QRS complex. The third QRS complex on the strip is a paced QRS complex. The device is capable of capture but is undersensing the spontaneous rhythm.

stimulus strength falls below the required threshold, and failure to capture or intermittent failure to capture may be observed late in battery life. As a result, urgent or emergent battery replacement is rare. Failure to capture, which may be complete or intermittent, is most commonly a lead problem. Lead displacement is the most common cause and is most likely to occur within the first month of pacemaker insertion. The chest radiograph may demonstrate the tip of the pacing catheter displaced from the right ventricular apex. The catheter tip is commonly found in the pulmonary outflow tract, where it may have intermittent contact with endocardium, resulting in intermittent failure to pace and sense. The atrial leads of dual-chamber devices are commonly displaced into the body of the right atrium, resulting in loss of contact between the pacing lead and the atrial endocardium. Lead fracture, which is uncommon with the current polyurethane lead coating,1 produces an insulation break, resulting in failure to capture as a result of current leakage. It can be detected as a change in pacing threshold during pacemaker interrogation. Lead fractures occur at predictable locations, usually at the site of attachment to the pulse generator or at abrupt angulations that serve as stress points. Inadequate contact of the lead with the pulse generator can mimic a lead fracture. Occasionally, when a lead fracture is complete or nearly complete, a break in the catheter or its insulation can be detected on an over-penetrated posteroanterior chest radiograph. Loss of lead-pulse generator contact can be detected on the chest radiograph with close inspection of the pulse generator. Exit block (the failure of an adequate stimulus to depolarize the paced chamber) can also result in failure to pace. Exit block should be considered when the preprogrammed pacing stimulus output fails to result in capture in the presence of a normally functioning pulse generator and an intact lead system. Most commonly this problem is a result of changes in the endocardium in contact with the pacing system. Causes include ischemia or infarction of the endocardium in contact with the electrodes, systemic

hyperkalemia, and the use of class III antiarrhythmic drugs (such as, amiodarone), which affect ventricular depolarization. Although other drugs alter pacemaker threshold, the effect is small and is rarely clinically important.

Inappropriate Sensing For a pacemaker to function in a noncompetitive mode, it must be capable of sensing the intrinsic or “native” electrical activity of the heart. The electrical activity that is sensed is determined by the pacing modality (see Table 70.1). Sensing parameters are determined at the time of pacemaker insertion on the basis of the signal size of the intracardiac ECG and can be changed or finetuned externally at a later time if needed.

Undersensing Failure to sense may be complete or intermittent. It may result from a change in the sensing parameters selected at the time of insertion. This is most commonly encountered after acute right ventricular infarction or during the progressive fibrosis that accompanies many cardiomyopathies, causing intracardiac signals to decrease in amplitude. Lead displacement, fracture, and poor contact with the endocardium may also cause undersensing. Undersensing is typically recognized electrocardiographically as the appearance of pacemaker spikes occurring earlier than the programmed rate. The spike may or may not be followed by a paced complex, depending on when it occurs during the cardiac refractory period (Fig. 70.5). Failure of a stimulus spike to produce a complex when it occurs during the atrial or ventricular refractory period should not be interpreted as failure to pace.

Oversensing In rare instances, the pacemaker may detect electrical activity that is not of cardiac origin. The result may be intermittent, irregular

CHAPTER 70  Implantable Cardiac Devices

Fig. 70.6.  Oversensing (lead II). This VVI unipolar lead pacemaker is oversensing myopotentials produced by contraction of the pectoralis major. Myopotentials result in the undulating and irregular baseline seen in the middle of the strip. After muscular contraction ceases, normal pacing resumes (last four complexes on the strip).

pacing or an apparent complete absence of pacemaker function. Myopotentials produced by the pectoralis muscle (Fig. 70.6) and extracorporeal electrical signals are frequently oversensed when a unipolar lead system is used. T waves that follow an intrinsic ventricular depolarization are the most common oversensed cardiac signals. Common medical sources of electrical interference include electrocautery, which can cause temporary pacemaker inhibition, and magnetic resonance imaging (MRI), which can alter pacemaker circuitry and result in fixed-rate or asynchronous pacing. Electromagnetic interference resulting from close proximity to a microwave oven should not cause problems with currently implanted pacemaker units. The current generation of digital cellular phones do not interfere with implanted pacemakers.18

Inappropriate Pacemaker Rate A pacing rate below the programmed rate is a typical finding in pulse generator depletion and does not occur abruptly with lithium-iodine batteries. An extreme increase in pacing rate, the so-called “runaway pacemaker,” is rarely, if ever, encountered with current pacemaker technology and circuitry in which upper rate limits are set (typically 140 beats/min). An “endless loop” tachycardia may develop during dual-chamber pacing when ventriculoatrial conduction occurs, and the resulting retrograde atrial depolarization results in a stimulated or paced ventricular depolarization.19 If atrial flutter develops during dual-chamber pacing, flutter waves may be sensed and tracked, resulting in a rapid, paced ventricular rate. In both instances, the ventricular rate does not exceed its set upper limit. Patients with such rhythms may complain only of palpitations or symptoms of hemodynamic compromise. When such rhythms are detected, magnet application converts the pacemaker to a fixed rate and terminates the tachyarrhythmia.

DIAGNOSTIC TESTING Chest Radiograph A chest radiograph should be obtained to define pacing catheter tip position and to determine the number of pacing leads, unless this information is available from another source. A ventricular pacing catheter tip in the right ventricular outflow tract or an atrial catheter tip in the SVC or right ventricle is abnormal. The pulse generator site should also be examined on the radiograph.

12-Lead Electrocardiogram A standard ECG and a long rhythm strip should be obtained in all patients. With bipolar pacing systems, the stimulus artifact may be extremely small and difficult to recognize in some leads (see Fig. 70.3). Inspection of the rhythm strip may reveal failure to sense or pace, a low pacing rate, or an abnormally rapid rhythm, suggesting a pacemaker-mediated tachycardia.

The modern pacemaker has two basic functions: (1) to stimulate the heart electrically and (2) to sense intrinsic cardiac electrical activity. Additional functions are available and are noted in the pacemaker code system (see Table 70.1, letters 4 and 5). The pacemaker delivers an electrical stimulus to either the atrium or the ventricle if it does not recognize (sense) any intrinsic electrical activity from that chamber after a selected time interval. This interval is usually programmed at the time of implantation and can be changed noninvasively at a later time, if necessary, with use of a programming and an “interrogating” device provided by the pacemaker manufacturer. If the pacemaker recognizes or senses an intrinsic atrial depolarization (P wave) or ventricular depolarization (QRS complex), it inhibits or resets its output to prevent competition with the underlying intrinsic rhythm. The stimulus intensity and sensing threshold (amplitude of electrical activity that is detected as being intrinsic) are typically set at the time of implantation but can also be reprogrammed later. The two basic functions of a pacemaker can be easily recognized and confirmed on a standard 12-lead ECG or rhythm strip. The normal function of a single-chamber VVI pacemaker is most easily recognized (see Fig. 70.1). After a programmed interval is surpassed during which intrinsic ventricular activity does not occur, a pacer “spike” or stimulus artifact appears. The pacer spike is a narrow deflection that is usually less than 5 mm in amplitude with a bipolar lead configuration and usually 20 mm or more in amplitude with a unipolar lead. A wide QRS complex appears immediately after the stimulus artifact. Depolarization begins in the right ventricular apex, and the spread of excitation does not follow normal conduction pathways. Characteristically, a left bundle branch block conduction pattern is seen. A right bundle branch pattern is abnormal and may represent lead displacement through a patent foramen ovale, placement of the lead in the coronary sinus, septal perforation, or may be seen with safe right ventricular apical position. In VVI pacing the paced QRS complexes are independent of intrinsic atrial depolarization if present (AV dissociation). The recognition of normal dual-chamber pacing is more complex owing to the interactive sensing and pacing of the right atrium and ventricle (see Fig. 70.2). Dual-chamber devices are typically used in patients with non-fibrillating atria coupled with intact AV conduction. A normal-appearing QRS complex may follow an intrinsic P wave as a result of normal sinoatrial node discharge if the intrinsic atrial depolarization is conducted to the ventricles. The intrinsic P wave and QRS complex inhibit the atrial and ventricular circuitry. A normal QRS complex follows a paced P wave if the paced atrial beat is conducted through the AV node and the programmed AV delay period is not exceeded. If it is not conducted to the ventricles (AV delay period exceeded), the pacemaker stimulates the ventricle, resulting in a paced P wave and a wide, paced QRS complex with left bundle branch block configuration. Recognition of the interactivity of the paced chambers is important. A paced P wave may be mistaken for failure to sense

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Fig. 70.7.  VVI pacemaker with fusion beats (pseudomalfunction). This VVI pacemaker was implanted in a patient with atrial fibrillation and intermittent symptomatic complete heart block. In the lead II rhythm strip, the first five QRS complexes are normal in morphology and irregular, as would be expected in atrial fibrillation. The next two QRS complexes are wide and preceded by a pacemaker spike. This represents normal sensing and pacing. The eighth QRS complex is narrow but preceded by a pacemaker spike. The spikes occur at a fixed and regular interval. In this instance, spontaneous ventricular depolarization had begun at approximately the time the pacemaker discharged. The 12th QRS complex in the sequence represents a fusion beat. Within the QRS complex of the 13th beat, a pacemaker spike is visible. Again, this represents nearly simultaneous conduction of a supraventricular beat and pacemaker electrical discharge. At first glance, this may appear to be failure to sense; however, the pacemaker is functioning normally and competing with the underlying rhythm.

or pace, and malfunction may be diagnosed when it is not present (pseudomalfunction). In addition, if the programmed rate of the pacemaker approximates the patient’s intrinsic heart rate, fusion of paced and native beats may occur and represents another common type of pseudomalfunction (Fig. 70.7).

MANAGEMENT Advanced Cardiac Life Support Interventions Electrical defibrillation at recommended shock strengths (200, 300, and 360 J) can be safely performed in the patient with a pacemaker. If the sternal defibrillation pad is placed adjacent to the sternum, it is at a safe distance (>10 cm) from the pulse generator. Alternatively, defibrillation electrodes can be placed in an anteroposterior configuration. All pacemakers should be interrogated after successful resuscitation, as well as placement. A chest radiograph should also be obtained to ensure that the pacing catheter was not displaced during chest compression. Immediate return of pacing (capture) may not occur after defibrillation; this is commonly the result of global myocardial ischemia and increased pacing threshold and is not an indication of pacemaker malfunction. Temporary transcutaneous pacing may be needed if the pacemaker cannot be reprogrammed or normal pacing does not resume spontaneously. Transcutaneous pacing can also be safely used because the anterior and posterior pacing electrodes, if properly positioned, are distant from the pulse generator. Attempting temporary transvenous pacing is usually not necessary and is unlikely to be successful without fluoroscopic guidance and may also dislodge the permanent catheter. Chronic venous thrombosis, which is common and most often asymptomatic after pacemaker insertion, may preclude temporary catheter insertion through the neck veins. Insertion through the femoral vein is also difficult because the permanently implanted catheter may prevent entry into the right ventricle.

DISPOSITION As a result of the current design of modern pacemakers and the frequent follow-up evaluation of patients with pacemakers, lifethreatening emergencies resulting from pacemaker malfunction requiring emergent intervention are rare. Most instances of malfunction are subtle and difficult to recognize without interrogation of the pacemaker with manufacturer-specific devices by an individual trained in pacer interrogation. In all instances of suspected pacemaker malfunction, the patient’s cardiologist should be consulted.

IMPLANTABLE CARDIOVERTERDEFIBRILLATORS PRINCIPLES The ICD was first used clinically in 1980. Technical refinements to this modality for treating ventricular dysrhythmias have progressed even more rapidly than refinements to the less complex standard pacemaker. A surge in the use of ICDs is reflective of improved survival with ICDs versus antiarrhythmic therapy in patients at risk for sudden cardiac death. Generally accepted indications for ICD implantation are noted in Box 70.2. Many patients still require drug therapy after ICD implantation to suppress ventricular dysrhythmias, minimize the frequency of ICD shocks, improve patients’ tolerance, and decrease energy use, which prolongs ICD life.

CLINICAL FEATURES Terminology and Components The majority of ICDs are now placed percutaneously in a manner similar to that of the standard pacemaker. A transvenous electrode system has largely replaced epicardial lead placement, which required thoracotomy. An epicardial defibrillation lead may occasionally be placed during coronary artery bypass surgery or in a few patients who cannot be defibrillated with use of existing transvenous electrode systems. The typical modern ICD consists of components similar to those in the standard permanent pacemaker, namely, a power source, electronic circuitry, and lead system. In addition, the standard ICD has a high-voltage capacitor and complex microprocessor memory.20 The power source is lithium chemistry based with a battery life of 5 to 10 years. The longevity is largely determined by the frequency of shocks. All ICDs are also ventricular pacemakers. The right ventricular lead is used for sensing and pacing, and shocks are typically delivered between a coil in the right ventricular lead and the pulse generator. If dual-chamber pacing is required, a second lead is placed in contact with the endocardium of the right atrium. A biphasic waveform is currently the preferred waveform for internal defibrillation. The biphasic waveform is more effective at lower energies than earlier monophasic waveforms and allows a smaller capacitor to be used, thereby reducing the size and increasing the comfort of the ICD unit. The diagnostic and treatment functions of the ICD are determined at the time of implantation. In most instances, the cardioversion and defibrillation thresholds are determined at the time

CHAPTER 70  Implantable Cardiac Devices

of ICD insertion by inducing ventricular tachycardia (VT) and ventricular fibrillation (VF) and adjusting the shock strength at a level above the minimum required to terminate the induced rhythm. Optimally, the required shock strength for defibrillation is less than half the maximum output (approximately 30 J) of the device. VT is typically managed with use of either low-energy shocks or antitachycardia pacing that interrupts the VT reentrant circuit. Antitachycardia pacing is less likely to have proarrhythmic effects and requires less energy, thereby extending battery life. In the setting of VF, ICDs are capable of delivering up to five additional shocks if the first shock fails.

tained VT, or (3) intracardiac T waves detected by the ICD system are sensed as QRS complexes and the ICD interprets this as an increased heart rate. Temporary ICD deactivation with magnet application may be necessary if oversensing is the problem. Syncope, near-syncope, dizziness, or lightheadedness in the patient with an ICD may indicate undersensing of sustained VT or inappropriately low shock strength to terminate the rhythm. An approach to the evaluation of ICD malfunction is shown in Fig. 70.8.

DIFFERENTIAL DIAGNOSIS

Diagnostic testing depends on presenting symptoms. As with pacemakers, chest radiograph can identify lead placement. ECG is indicated to evaluate for arrhythmias. Patients who present with history of more than one ICD shock should have the ICD interrogated while in the ED.

Complications of Implantation Complications of ICD implantation are nearly identical in type and frequency to those of permanent pacemaker implantation and management as well.

DIAGNOSTIC TESTING

MANAGEMENT

Malfunction

Advanced Cardiac Life Support Interventions

Patients with ICD malfunction usually come to the emergency department (ED) with a limited number of specific symptoms (Box 70.4). In contrast to patients with a permanent pacemaker, ICD patients are usually aware of when the ICD delivers a discharge or shock. The most common complaint of ICD patients is the occurrence of frequent shocks.20 An increasing shock rate may be appropriate and not indicative of ICD malfunction if the patient is experiencing an increase in the frequency of VT or VF episodes. An increase in the frequency of episodes may occur in the setting of hypokalemia, hypomagnesemia, ischemia (with or without infarction) related to underlying coronary artery disease, or the proarrhythmic effect of drugs administered to decrease the frequency of ventricular tachyarrhythmias. Many ICD patients, particularly those with newly implanted devices, report that their device has discharged, but subsequent device interrogation reveals that no discharge occurred. An increase in the shock frequency is a manifestation of ICD sensing malfunction if (1) a supraventricular tachyarrhythmia is inappropriately sensed as VT, (2) shocks are delivered for nonsus-

An ICD does not prevent sudden death in all patients at risk, and a patient with an ICD may arrive in cardiac arrest (2% annual incidence in patients with implanted devices). Cardiac arrest is not necessarily an indication of ICD malfunction. Appropriate repeated shocks may have been delivered but were ineffective. Alternatively, the ICD may not have sensed VF or the ventricular ectopic activity that typically precedes VF. Resuscitation efforts in the patient with an ICD should be undertaken in accordance with current recommendations. Transthoracic defibrillation can be performed in the standard manner with a monophasic or biphasic

BOX 70.4 

Causes of Implantable CardioverterDefibrillator Malfunction Increase or abrupt change in shock frequency • Increased frequency of VF or VT (consider ischemia, electrolyte disorder, or drug effect) • Displacement or break in ventricular lead • Recurrent nonsustained VT • Sensing and shock of supraventricular tachyarrhythmias • Oversensing of T waves • Sensing noncardiac signals Syncope, near-syncope, dizziness • Recurrent VT with low shock strength (lead problem, change in defibrillation threshold) • Hemodynamically significant supraventricular tachyarrhythmias • Inadequate backup pacing for bradyarrhythmias (spontaneous or drug induced) Cardiac arrest • Assume malfunction, but probably caused by VF that failed to respond to programmed shock parameters VF, Ventricular fibrillation; VT, ventricular tachycardia.

Analyze stored and clinical data

No tachyarrhythmia (oversensing)

Tachyarrhythmia

SVT (inappropriate detection)

VT/VF (appropriate detection)

Intracardiac signals

Extracardiac signals

Repetitive VT/VF (“VT storm”) First shock success

Frequent or repetitive shocks

Single VT/VF ICD-classified shock failure

Shock failure to terminate VT/VF

Successful shock misclassified by ICD

Fig. 70.8.  Approach to the patient with shocks. Top, Flow diagram for one or infrequent shocks. Bottom, Diagram for multiple or repetitive shocks. ICD, Implantable cardioverter-defibrillator; SVT, supraventricular tachycardia; VT/VF, ventricular tachycardia/ventricular fibrillation. (Redrawn from Swerdlow CD, Zhang J: Implantable cardioverter defibrillator shocks: a troubleshooting guide. Rev Cardiovasc Med 2:61, 2001.)

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defibrillator if VF is the arrest rhythm. The sternal electrode or paddle should be placed in a parasternal location approximately 10 cm from the ICD subcutaneous pouch if the device has been implanted in the right deltopectoral area. If it has been implanted in the left deltopectoral region, this recommended safety distance is usually exceeded. ICD discharge during manual chest compressions poses no risk to providers, although the rescuer may feel a weak shock. Although generally not indicated, the device can be deactivated with magnet application during resuscitation. Deactivation is probably more important in the immediate post-resuscitation period. Ventricular dysrhythmias are common at this time due to prolonged global myocardial ischemia during the arrest period, reperfusion, and the hyperadrenergic state, which is worsened by the use of intravenous epinephrine during resuscitation. ICD malfunction should be assumed, and these post-resuscitation rhythms treated with standard pharmacologic agents (lidocaine and amiodarone). Although class 1 antidysrhythmic agents may raise the defibrillation threshold of the ICD, their impact on the defibrillation threshold during transthoracic countershock, due to the high energy, is clinically inconsequential.

DISPOSITION As a result of the difficulty in documenting or excluding ICD function or malfunction in the patient with transient symptoms, the device should be interrogated to guide further evaluation and therapy. In cases in which the patient reports a single ICD shock, an assessment for acute cardiac ischemia, worsening of chronic congestive heart failure, symptoms of new-onset heart failure, and electrolyte abnormalities should be performed. In the absence of a change in clinical status, such patients can be discharged in consultation with the managing or consulting cardiologist after timely follow-up is ensured. For patients reporting multiple shocks, interrogation is essential, because in many of these cases the defibrillator has not discharged and the patient is experiencing hiccoughs, diaphragmatic twitching, or other nonelectrical phenomena. In such cases, discharge home is the rule. When multiple defibrillator discharges are confirmed by interrogation, emergent consultation is required along with admission to a monitored setting for extended telemetric observation. If frequent ventricular ectopy is noted, intravenous amiodarone is indicated.20 ICD interrogation allows assessment of ICD function and preceding dysrhythmia episodes.20 Based on the findings, reprogramming may be necessary; and if a lead problem is detected, reimplantation is required. Similar to a pacemaker, a magnet can be placed over the ICD to inactivate the defibrillator. This should be done only if the emergency clinician is confident that the ICD is delivering inappropriate shocks, such as a supraventricular tachycardia.

BIVENTRICULAR PACING PRINCIPLES Biventricular pacing, also known as cardiac resynchronization therapy, is a therapy for patients with left-sided heart failure and ventricular dyssynchrony. Indications for biventricular pacing have expanded to include patients with New York Heart Association (NYHA) class II, III or IV heart failure, left ventricular dysfunction, and left bundle branch block, or patients with AV block and ventricular systolic dysfunction with NYHA class I, II, or III heart failure.5,11-13

CLINICAL FEATURES Left bundle branch block causes an altered sequence of depolarization of the left ventricle such that the interventricular septum

contracts before the left ventricular free wall, leading to inefficient mechanical pumping. Biventricular pacing “resynchronizes” the ventricles by simultaneously pacing the left and right ventricles, eliminating the delay in left ventricular free wall contraction and improving systolic function. Right atrial and right ventricular leads are positioned as for conventional atrial and univentricular pacing. The left ventricular lead is positioned in a left ventricular epicardial location via the coronary sinus and veins, preferably in a posterolateral or lateral location. The QRS duration of paced ventricular complexes is often but not always less than the QRS duration measured before resynchronization therapy.5 Cardiac resynchronization therapy has not been shown to be beneficial in heart failure with narrow QRS.21

DIFFERENTIAL DIAGNOSIS The complications and malfunctions inherent with conventional cardiac pacing are also observed with biventricular pacing. In addition, biventricular pacing has unique complications related to placement of the left ventricular pacing lead through the coronary sinus. In large clinical trials, coronary sinus dissection occurred in 0.3% to 4.0% of patients and coronary vein or coronary sinus perforation in 0.8% to 2.0% of patients. Cardiac tamponade caused by perforation of the coronary venous system is seen in less than 1% of patients. Dislodgement of the left ventricular electrode with resultant loss of pacing occurs as an early complication in approximately 10% of patients. Patients with malfunction of a biventricular pacing system frequently report palpations or acute decompensation of chronic heart failure.

DIAGNOSTIC TESTING Biventricular pacing can usually be recognized on the standard ECG (Fig. 70.9). Two stimulus artifacts or “spikes” may be seen preceding a paced QRS complex. With biventricular pacing, a predominantly negative QRS complex is seen in lead I, in contrast to the typical upright complex seen with right ventricular pacing (see Fig. 70.2). A predominantly positive QRS complex is seen in lead V1 with biventricular pacing.5

MANAGEMENT Patients with biventricular pacemakers have advanced heart failure and may be treated using all current heart failure treatments (see Chapter 71). As with standard pacemakers, transvenous pacing is rarely needed and may be difficult due to preexisting leads blocking passage of the transvenous pacing wire. Cardiac tamponade due to pacemaker placement is treated using usual technique. Treatment of lead misplacement or dislodgement requires cardiology consultation.

DISPOSITION Disposition of patients with biventricular pacemakers will depend on presenting symptoms and or complications.

CARDIAC ASSIST DEVICES PRINCIPLES Mechanical ventricular assistance devices have been used as a “bridge” to transplantation since the 1960s.22 Newer devices, such as the Jarvik 2000 and HeartMate II, are continuous flow pumps that are portable and powered with long lasting, wearable battery packs allowing patients to live in their community. With advancing technology, infectious complications and postoperative mortality have decreased, significantly with 2 year survival in over half

CHAPTER 70  Implantable Cardiac Devices

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Fig. 70.9.  Biventricular pacemaker. This 12-lead electrocardiogram (ECG) demonstrates an atrial sensed, biventricular pacemaker in a patient with cardiac synchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) system (CRT-D). The PR interval is 350 msec and represents the programmed atrioventricular (AV) delay for this patient. The paced QRS complexes have an S wave in lead I and an R wave in lead V1 that are distinctly different from the morphology and axes seen with right ventricular apical pacing. The second beat from the left is a premature ventricular contraction (PVC). There is a pacemaker “spike” superimposed on this complex, likely representing safety pacing in CRT-D.

of patients.23 The greatest mortality is noted within the first 30 days after implantation and during hospitalization. These mechanical assist devices may be used as a bridge to cardiac transplant or as “destination” therapy in patients who do not qualify for cardiac transplantation.22,24 Three types of implanted heart assist devices now exist. These include the left ventricular assist device (LVAD), the biventricular assist device (BiVAD) and the total artificial heart (TAH). Mechanical options for patients with biventricular heart failure include the BiVAD and the TAH. The BiVAD is similar to the LVAD, but it consists of two pumps—one assisting the right ventricle, one assisting the left ventricle. The failing heart is left in place while the pumps are attached to it. The mechanism, as well as complications and precautions for the BiVAD are similar to those for the LVAD.

CLINICAL FEATURES The LVAD supports the patients cardiac output via a mechanical pump that draws blood from an inflow cannula in the left ventricle and pumps it into the ascending aorta via an outflow cannula. The pump at the left apex is connected via a driveline exiting the patient at the epigastrium to the external controller box. The controller box and batteries are worn by the patient on a belt and shoulder harness, allowing freedom of movement. The controller displays battery life and alarms. Patients with LVADs require lifelong anticoagulation to prevent the graft from clotting. Most patients also have a pacemaker or automatic implanted cardiac defibrillator (AICD) placed. The most common LVADs produce a non-pulsative flow, therefore patients are essentially pulseless making traditional hemodynamic vital sign interpretation impossible. Adequate perfusion can be assessed by evaluating mental status and alertness, oxygenation, and renal function. Blood pressure may be measured using a manual cuff with a Doppler probe over the radial or brachial artery. The cuff pressure is reduced until a constant sound is heard. The pressure at this point represents the mean arterial pressure. Blood pressure can also be measured invasively using an arterial catheter. Assessing the LVAD for device malfunction can be challenging, but assistance is available by calling the patient’s LVAD coordina-

tor by phone, as well as enlisting the help of the patient’s family members who receive extensive training when the device is implanted. The screen on the control panel can help determine if the problem may be due to battery level, flow, or other malfunction. Listening to the epicardium should reveal a continuous noise if the pump is operating.

DIFFERENTIAL DIAGNOSIS Like any other patient with indwelling catheters, the driveline can become a conduit for infection and patients with LVADs are prone to infections that may be localized around the LVAD device, as well as systemic including bacteremia. These infections are treated with broad-spectrum antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA) coverage with device removal rarely necessary. Most LVAD patients are anticoagulated and are at increased risk for bleeding. This most frequently presents as intracranial or gastrointestinal hemorrhage. In addition to pharmacologic anticoagulation, patients with LVAD can develop acquired von Willebrand’s factor (vWF) platelet dysfunction. Reversal of anticoagulation should be approached with caution due to risk of graft failure due to obstructing thrombus, and patients who are inadequately anticoagulated are at risk for pump failure due to thrombus. A patient with hemodynamic collapse due to clot on inflow or outflow cannulas can be treated with intravenous heparin or in extreme cases, thrombolysis. Patients with an LVAD experiencing signs of shock or poor perfusion may be due to right ventricular failure, because the device does not support the right ventricle. This can be evaluated with a bedside echocardiogram showing a small right ventricle with poor contraction. In these cases, preload augmentation with titrated fluid boluses may improve hemodynamics. Inotropes such as dopamine, dobutamine, or a combination of these drugs have also proven beneficial in these situations. Dysrhythmias are frequent with LVAD patients. Because the pump can maintain forward flow despite dysrhythmias, the patient may remain awake and conscious despite persistent VF. Most patients have an AICD place, which should respond to tachydysrhythmias. If there is no AICD or the AICD is not functioning, LVAD patients may be cardioverted using standard

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TABLE 70.3 

Comparison of Common Ventricular Assist Devices THORATEC VAD

HEARTMATE II

HEARTMATE I OR XVE

Flow type

Pulsatile: Patient will have a pulse and BP

Axial: Patient will not have a pulse or BP Use Doppler to confirm flow

Pulsatile: Patient will have a pulse and BP

Backup method

Hand pump

No external method

Hand pump

Battery life

Up to 3 hours

Up to 10 hours

Up to 10 hours

Defibrillation or cardioversion

No precautions

No precautions

Use hand pump during procedure

Cardiac arrest

Use hand pump

No external method

Use hand pump

BP, Blood pressure.

external pads, taking care not to place pads directly over mechanical parts. Patients may also be treated with any antidysrhythmic medication.

DIAGNOSTIC TESTING ECG is useful in LVAD patients to identify arrhythmias. Ultrasound or echocardiogram may be used for LVAD patients to confirm blood flow. Electrocardiography and echocardiography are not useful in patients with the TAH, because there is no native heart and no electrical activity.

MANAGEMENT Chest compressions risk dislodging the device, resulting in massive hemorrhage, although a recent case series of eight patients with LVAD who received chest compressions showed no cannula dislodgements with four patients surviving the initial arrest.25 Prior to considering chest compressions, multiple methods should be used to confirm absence of circulation, and attempts should be made to correct mechanical pump malfunction. In some devices, the hand pump can be used to provide backup circulation, and

early transition to cardiopulmonary bypass should be considered (Table 70.3). In contrast to the BiVAD, with the TAH, the failing heart is removed and the TAH implanted. The currently available TAH (SynCardia) produces pulsatile flow. Because the native heart has been removed, patients with a TAH have no cardiac electrical activity (asystole); therefore defibrillation and pacing are never indicated. Chest compressions are not effective with the TAH and could be harmful due to traumatic disruption of the heart or drive lines. Epinephrine and vasopressin are generally not recommended for TAH patients, because there is no native heart to respond.

DISPOSITION Although patients with an LVAD or TAH typically require care at cardiac transplant centers, they often present to their local community or closest ED. In such cases, telephone consultation with an expert at a transplant center can assist in management and help facilitate transfer. Emergency clinicians need to be familiar with management of LVAD and TAH complications and be able to stabilize these patients to the extent possible prior to transfer.

KEY CONCEPTS • Pacemaker malfunction soon after implantation (within 6 to 8 weeks) is usually a result of a lead problem, such as a lead displacement, or a pacemaker programming failure, such as a pacing rate too slow for the patient’s needs. • Pacemaker malfunction arises in a limited number of ways: failure to pace, oversensing, undersensing, and pacing at an inappropriate rate (too fast or too slow). • With lithium-iodine batteries, abrupt failure is an unlikely cause of pacemaker malfunction. • If a patient with a pacemaker has a fever of unclear cause, pacemaker lead infection and endocarditis should be considered. • Because paced ventricular complexes are conducted with a left bundle branch block pattern, a paced rhythm obscures the electrocardiographic diagnosis of acute myocardial infarction. A right bundle branch pattern is abnormal and suggests lead displacement. • Magnet application does not turn off a pacemaker, it turns off the sensing or inhibition function. Fixed-rate pacing that is independent

of or in competition with the underlying native rhythm will ensue. Removal of the magnet restores the inhibitory activity of the pacemaker and returns it to demand pacing mode. • Defibrillation is safe in patients with a pacemaker or implantable cardioverter-defibrillator (ICD). Paddles should be placed at least 10 cm from the subcutaneous implant site of the device. Alternatively, anteroposterior defibrillation with adhesive defibrillation electrodes can be performed. There are no reports of injury to rescuers from ICD discharges during manual chest compressions. • Most left ventricular assist device (LVADs) do not produce pulsatile flow; therefore, these patients will not have a palpable pulse. Because chest compressions may be harmful, multiple methods should be used to confirm absence of circulation and attempts should be made to correct mechanical pump malfunction. • Patients with a total artificial heart (TAH) have no native heart and no cardiac electrical activity. Electrocardiogram (ECG) for the TAH will read asystole. Defibrillation and pacing will not be effective. Chest compressions will not be effective and may be harmful.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 70  Implantable Cardiac Devices

REFERENCES 1. Beck H, Boden WE, Patibandla S, et al: 50th anniversary of the first successful permanent pacemaker implantation in the United States: historical review and future directions. Am J Cardiol 106(6):810–818, 2010. 2. van Welsenes GH, Borleffs CJ, van Rees JB, et al: Improvements in 25 years of implantable cardioverter defibrillator therapy. Neth Heart J 19(1):24–30, 2011. 3. Greenspon AJ, Patel JD, Lau E, et al: Trends in permanent pacemaker implantation in the United States From 1993 to 2009. J Am Coll Cardiol 60(16):1540–1545, 2012. 4. Ramani GV, Uber PA, Mehra MR: Chronic heart failure: contemporary diagnosis and treatment. Mayo Clin Proc 85(2):180–195, 2010. 5. Tang AS, Wells GA, Talajic M, et al: Cardiac-resynchronization therapy for mild-tomoderate heart failure. N Engl J Med 363(25):2385–2395, 2010. 6. Al-Majed NS, McAlister FA, Bakal JA, et al: Meta-analysis: cardiac resynchronization therapy for patients with less symptomatic heart failure. Ann Intern Med 154:401–412, 2011. 7. Zipes DP, Camm AJ, Borggrefe M, et al: ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114(10):e385–e484, 2006. 8. Packer DL, Gillis AM, Calkins H, et al: ICDs: evidence, guidelines, and glitches. Heart Rhythm 8(5):800–803, 2011. 9. Mond HG, Proclemer A: The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009—a World Society of Arrythmia’s project. Pacing Clin Electrophysiol 34(8):1013–1027, 2011. 10. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51(21):e1–e62, 2008. 11. Tracy CM, Epstein AE, Darbar D, et al: ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task

12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

25.

Force on Practice Guidelines and the Heart Rhythm Society. Circulation 126(14): 1784–1800, 2012. Curtis AB, Worley SJ, Adamson PB, et al: Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 368(17):1585–1593, 2013. Goldenberg I, Kutyifa V, Klein HU, et al: Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370(18):1694–1701, 2014. Baddour LM, Epstein AE, Erickson CC, et al: Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 121(3):458–477, 2010. Tischer TS, Hollstein A, Voss W, et al: A historical perspective of pacemaker infections: 40-years single-centre experience. Europace 16(2):235–240, 2014. Kucher N: Deep-vein thrombosis of the upper extremities. N Engl J Med 364:861, 2011. Modi S, Krahn A, Yee R: Current concepts in pacing 2010-2011: the right and wrong way to pace. Curr Treat Options Cardiovasc Med 13(5):370–384, 2011. Ismail MM, et al: Third-generation mobile phones (UMTS) do not interfere with permanent implanted pacemakers. Pacing Clin Electorphysiol 33(7):860–864, 2010. Richter S, Muessigbrodt A, Salmas J, et al: Ventriculoatrial conduction and related pacemaker-mediated arrhythmias in patients implanted for atrioventricular block: an old problem revisited. Int J Cardiol 168(4):3300–3308, 2013. Borne RT, Varosy PD, Masoudi FA: Implantable cardioverter-defibrillator shocks: epidemiology, outcomes, and therapeutic approaches. JAMA Intern Med 173(10): 859–865, 2013. Ruschitzka F, Abraham WT, Singh JP, et al: Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 369(15):1395–1405, 2013. Boilson BA, Raichlin E, Park SJ, et al: Device therapy and cardiac transplantation for end-stage heart failure. Curr Probl Cardiol 35:8, 2010. Slaughter MS, Rogers JG, Milano CA, et al: Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 361(23):2241–2251, 2009. Starling RC, Naka Y, Boyle AJ, et al: Results of the post–U.S. Food and Drug Administration–approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: A prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 57(19):1890–1898, 2011. Shinar Z, Bellezzo J, Stahovich M, et al: Chest compressions may be safe in arresting patients with left ventricular assist devices (LVADs). Resuscitation 85(5):702–704, 2014.

CHAPTER 70: QUESTIONS & ANSWERS 70.1. Which of the following conditions is an indication for permanent pacemaker placement after acute myocardial infarction? A. Asymptomatic persistent third-degree atrioventricular (AV) block B. New-onset left bundle branch block C. Symptomatic persistent second-degree infranodal AV block D. Transient symptomatic third-degree AV block Answer: C. Symptomatic persistent symptomatic second- or third-degree AV block and bilateral bundle branch block with persistent second-degree AV block at the His-Purkinje level are also indications. 70.2. Which of the following technical characteristics is applicable for most permanent pacemakers? A. A unipolar pacemaker configuration is less prone to oversensing of myopotentials. B. Bipolar systems are implantable cardioverterdefibrillator (ICD) compatible. C. Lithium battery life is 10 to 20 years. D. Most leads are implanted within the myocardium. E. Optimal ventricular lead placement is at the right ventricular outflow tract. Answer: B. Bipolar systems have the proximal (positive) and distal (negative) leads in close proximity to each other on the surface of the endocardium. Bipolar leads are more fracture prone but less likely to oversense myopotentials and are also ICD compatible. In unipolar systems, the proximal lead is enclosed in the pulse generator. Typical lithium battery life is 4 to 10 years. Unipolar lead amplitude is approximately four times longer than typical bipolar

spikes (20 mm vs. 5 mm). Lead placement should not be in the outflow tract. 70.3. A 72-year-old man presents with dyspnea. He has a history of symptomatic bradycardia that required pacemaker placement and a history of hypertension and peripheral vascular disease. In the course of your evaluation, an electrocardiogram (ECG) is obtained showing a ventricular-paced rhythm with a right bundle branch morphology, rate 72. Vital signs are normal. This likely indicates which of the following? A. A nonfunctioning atrioventricular (AV) sequential system B. A ventricular demand pacemaker C. Electrolyte disturbance D. Lead displacement E. Right ventricular apex depolarization by a unipolar endocardial lead Answer: D. The typical depolarization begins in the right ventricular apex, and a left bundle branch pattern is the norm. The presence of a right bundle branch block (RBBB) pattern should raise suspicion of lead displacement. Electrolyte disturbance does not typically cause a morphology change. 70.4. A 60-year-old man presents with swelling and tenderness around his left subclavian pacemaker. It was implanted 2 years previously for heart block. It was last interrogated 8 weeks prior by his cardiologist, with good function documented. Physical examination is unremarkable except for mild tenderness with minimal swelling and erythema at the pulse generation site. Vital signs are unremarkable.

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Which of the following interventions should be performed next? A. A course of oral antibiotics with Staphylococcus aureus coverage should be initiated. B. Blood cultures should be sent. C. Local aspiration should be considered to rule out hematoma. D. Serial examinations would be acceptable management. Answer: B. The incidence of wound/pocket infection is 1% or 2%. With infection, however, the incidence of bacteremia is 20% to 25%. Local signs may be minimal. If pacemaker site infection is suspected, blood cultures, admission for intravenous (IV) antibiotics, and cardiology consultation with the potential need for pacemaker explantation should be undertaken. 70.5. What is the incidence of venous obstruction after permanent transvenous pacemaker placement? A. 38° C (100.4° F) Vascular phenomena—arterial emboli, septic pulmonary infarcts, mycotic aneurysm, conjunctival hemorrhages, or Janeway lesions Immunologic phenomena—Osler’s nodes, Roth’s spots, and rheumatoid factor Microbiologic evidence—single positive blood culture (except for coagulase-negative Staphylococcus or an organism that does not cause endocarditis) Echocardiographic findings—consistent with endocarditis but do not meet major criteria

radiograph may show signs of heart failure or embolic disease, and an electrocardiogram (ECG) may display conduction abnormalities if an abscess has formed in the myocardium. Although not always practical, three blood cultures from three separate venipuncture sites are recommended for patients with a presumptive diagnosis of possible endocarditis, with the first and last cultures preferably drawn 1 hour apart. If the patient appears septic, cultures may be obtained more rapidly to permit initiation of early empirical therapy. Cultures need not be timed to the presence of chills or fever because patients with IE typically have a continuous bacteremia. Echocardiography should be performed in all patients for whom the suspicion of endocarditis is moderate to high. Although transthoracic echocardiography (TTE) is highly specific for vegetations in IE, it may be nondiagnostic because of obesity, chronic obstructive pulmonary disease, and chest wall deformities. Overall

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sensitivity of TTE is at most 60%.Transesophageal echocardiography (TEE), on the other hand, although more invasive and time-consuming, is far superior to TTE in its sensitivity and specificity. Explicit criteria for the diagnosis of IE are important because underdiagnosis can lead to serious morbidity and death, whereas overdiagnosis can result in weeks of unnecessary antimicrobial therapy. The modified Duke criteria are the most widely accepted and validated, stratifying patients with suspected bacterial endocarditis into three distinct categories—definite, possible, and rejected (Box 73.1).6

The American Heart Association guidelines limit prophylaxis to conditions with the highest risk of adverse outcome from IE (Box 73.3).9 Virtually all the procedures that are routinely performed in the ED, including suturing of lacerations, endotracheal intubation, placement of central venous catheters, vaginal deliveries, and placement of Foley catheters (in the absence of infection), do not require prophylactic antibiotics.

MANAGEMENT

PRINCIPLES

Once the diagnosis of IE is established, whether by clinical, echocardiographic, or microbiologic methods, antimicrobial therapy should be administered. The choice of antibiotics depends on the likely (or known) causative organism but is usually empirical. In the ED, however, usually without results of an echocardiogram (TTE or TEE), the diagnosis of endocarditis is not confirmed. In addition, there is increasing concern regarding communityacquired, methicillin-resistant S. aureus (MRSA), even in native valve endocarditis. Thus, a combination of 15 mg/kg of vancomycin and 2 g of ceftriaxone is a reasonable empirical antibiotic choice in someone with undifferentiated sepsis and suspected endocarditis. Endocarditis is a heterogeneous disease. Although initial treatment is medical, early consultation with a cardiac surgeon is advisable when mechanical complications are observed or expected (eg, in patients with acute heart failure or those with infections involving prosthetic valves; Box 73.2). Consultation with an infectious diseases specialist or cardiologist is also useful. Early valve replacement for more severe disease may decrease the risk of embolic events.7 If possible, most patients with left-sided endocarditis should be initially managed in facilities with access to cardiac surgery. With appropriate antibiotic therapy, most patients with IE will defervesce within 1 week. The duration of antibiotic therapy needs to be sufficient to eradicate microorganisms present within the valvular vegetations. This may require 6 weeks, or more, depending on the organism and type of vegetation.8

Background and Importance

DISPOSITION

CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS

Historically, most patients with IE received the entire course of antimicrobial therapy while in the hospital. The development of home health care, however, allows selected patients with endocarditis to be treated as outpatients during much or all of their therapy. Patients selected for outpatient therapy should be hemodynamically stable, compliant, and capable of managing the technical aspects of IV therapy.

PROPHYLAXIS

RHEUMATIC FEVER

From 1920 to 1950, acute rheumatic fever (ARF) was the leading cause of death in US children and the most common cause of heart disease in individuals younger than age 40 years. During the 1960s and 1970s, the incidence of ARF in the United States and other developed countries declined dramatically because of widespread antibiotic treatment of streptococcal infections, declining prevalence of the more virulent strains of group A streptococci, and improved living conditions. Children 4 to 9 years of age remain at greatest risk, with an incidence of ARF of 2 to 14 cases/100,000. In many developing nations, however, ARF continues to be a leading cause of childhood mortality. RHD peaks in adults between the ages of 25 and 34 years and continues to be a leading cause of morbidity and mortality in impoverished areas.10

Pathophysiology ARF is a delayed nonsuppurative complication of streptococcal pharyngitis. Although the pathogenesis remains obscure, ARF results from an exaggerated immunologic response to group A beta-hemolytic streptococci that results in antibodies crossreacting with tissues in the heart, joints, skin, and central nervous system. Patients with a history of ARF are predisposed to recurrent infections, and repeated infections lead to progressive heart damage.

Acute rheumatic fever occurs approximately 3 weeks after the initial bout of pharyngitis (ranging from 1–5 weeks). Up to onethird of patients with documented ARF do not remember having had pharyngitis in the preceding month. Fever is generally present during the acute phase of rheumatic fever, rarely lasting more

BOX 73.3  BOX 73.2 

Conditions Requiring Surgical Therapy for Infective Endocarditis Infective endocarditis with acute heart failure Fungal endocarditis Periannular extension of infection Recurrent emboli Large mobile vegetations Persistent bacteremia

High-Risk Conditions for Bacterial Endocarditis Prosthetic heart valve History of endocarditis Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits Completely repaired congenital heart defects with prosthesis during the first 6 mo after the procedure Repaired congenital heart disease with residual defect at or adjacent to the site of the prosthetic device Cardiac valvulopathy in a transplanted heart

CHAPTER 73  Infective Endocarditis, Rheumatic Fever, and Valvular Heart Disease

than 2 weeks without a characteristic pattern. Along with fever, manifestations of ARF may include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. Migratory polyarthritis is the most common manifestation of ARF. Arthritis tends to occur early in the course of ARF and often coincides with a rising titer of streptococcal antibodies. The polyarthritis classically affects larger joints, such as the knees, ankles, elbows, and wrists, and the pain can be more severe than physical findings suggest. Analysis of the synovial fluid generally reveals a sterile inflammatory fluid. Cardiac manifestations of ARF may be subtle and can include symptoms and signs of pericarditis, myocarditis, and endocarditis. The mitral valve is the most common valve affected in ARF, causing mitral regurgitation. Inflammation of the valvular endocardium can result in permanent deformity and impairment of one or more cardiac valves over the course of decades. Stenotic lesions of the mitral or aortic valves are unusual at presentation, but are common late manifestations of RHD (Fig. 73.1). Chorea is manifested by random, rapid, purposeless movements, usually of the upper extremities and face. Chorea is relatively rare in ARF and tends to emerge after a longer latency period than some of the other manifestations. Erythema marginatum and subcutaneous nodules are found in fewer than 10% of cases of ARF. Their presence, however, should suggest the diagnosis. Erythema marginatum is a nonpruritic, painless, evanescent

so-called smoke ring of erythema that commonly appears on the trunk and proximal extremities (Fig. 73.2). Subcutaneous nodules are pea-sized and nontender. They typically appear over the extensor surfaces of the wrists, elbows, knees and, occasionally, the spine.

DIAGNOSTIC TESTING In 1944, Jones formulated major and minor criteria for the diagnosis of ARF. After multiple revisions, the Jones criteria remain the diagnostic basis for this disease (Box 73.4).11 The diagnosis of ARF necessitates evidence of an antecedent streptococcal infection plus at least two major, or one major and two minor, manifestations from the Jones criteria. Although throat cultures are usually negative at the time of clinical onset of ARF, antistreptolysin

BOX 73.4 

Jones Criteria (Revised) for the Diagnosis of Acute Rheumatic Fever MAJOR MANIFESTATIONS Carditis Polyarthritis Chorea Erythema marginatum Subcutaneous nodules

MINOR MANIFESTATIONS

Arthralgias Fever Increased erythrocyte sedimentation rate or C-reactive protein level Prolonged PR interval

EVIDENCE OF PRECEDING STREPTOCOCCAL INFECTION

Positive throat culture for group A beta-hemolytic streptococci or positive rapid streptococcal antigen test Elevated or rising streptococcal antibody titer, usually antistreptolysin O

A

B Fig. 73.1.  Transthoracic echocardiography of symptomatic rheumatic mitral stenosis (* represents a thickened anterior mitral leaflet). Ao, Aorta; LA, left atrium; LV, left ventricle; RV, right ventricle. (From Marijon E, et al: Rheumatic heart disease. Lancet 379:953–964, 2012.)

Fig. 73.2.  Erythema marginatum. This is one form of annular erythema seen in 10% of cases of children with acute rheumatic fever but is rare in adults with the disease. (From Cohen J, Powderly WG: Infectious diseases, ed 2, New York, 2004,Mosby.)

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antibody titers remain positive for 4 to 6 weeks from the time of infection. The erythrocyte sedimentation rate and C-reactive protein levels are typically elevated, and a prolonged PR interval is common and suggestive in ARF.

MANAGEMENT AND DISPOSITION All patients with ARF should receive antibiotic therapy, regardless of the clinical history of pharyngitis. Penicillin can be administered orally (250 mg for children, 500 mg for adults, bid or tid for 10 days) or intramuscularly (600,000 units of benzathine penicillin in patients weighing 27 kg as a one-time dose). Treatment for arthritis consists of antiinflammatory agents, usually aspirin, administered until symptoms are absent and the erythrocyte sedimentation rate and C-reactive protein concentration normalize. Patients with severe carditis are often treated with corticosteroids, but no evidence supports this treatment.10,12 Patients with congestive heart failure should be managed accordingly. Treatment of patients with ARF involves only symptom relief and does not decrease the likelihood of progression to RHD. Primary prevention involves treating those with group A streptococcal pharyngitis within 9 days of the onset of symptoms because this greatly decreases the risk of ARF. Patients with a history of ARF should receive ongoing prophylactic antibiotics (generally, penicillin) to prevent recurrences. The recommended duration of secondary prophylaxis varies, depending on the presence and severity of cardiac involvement.

VALVULAR HEART DISEASE PRINCIPLES Anatomy and Physiology Of the four heart valves, three (tricuspid, pulmonic, and aortic) are composed of three cusps, whereas the mitral valve has only two cusps. Each cusp is a double layer of endocardium attached at its base to the fibrous skeleton of the heart. The margins of the cusps are attached to muscular projections from the ventricles (papillary muscles) via tendinous cords (chordae tendineae). Contraction of the ventricle, and consequently the papillary muscle, results in the opening or closing of the valve, depending on its location.

Mitral Stenosis The most common cause of mitral stenosis is RHD. Symptoms of valvular dysfunction typically develop after a latency period of 1 to 3 decades. Many patients will not recall a history of ARF. Less common causes of mitral stenosis include congenital mitral stenosis and mitral annular calcification.

Pathophysiology The normal cross-sectional area of the mitral valve orifice is 4 to 6 cm2. Stenosis becomes clinically significant when the area decreases to below 2 cm2. Impeded flow from the left atrium to the left ventricle results in left atrial hypertension, restricted cardiac output and, ultimately, pulmonary congestion. As the disease progresses, patients may develop pulmonary hypertension and right ventricular failure. The most common complication of mitral stenosis is atrial fibrillation, which, in the absence of rate control, is not well tolerated. Patients with underlying mitral stenosis will decompensate under other conditions associated with increased cardiac demand and reduced ventricular filling, such as pregnancy, anemia, infection, and hyperthyroidism.

Clinical Features Early symptoms of mitral stenosis include reduced exercise tolerance and dyspnea on exertion. Patients with more advanced disease may have orthopnea and, if right ventricular failure is present, peripheral edema. Hemoptysis, caused by the rupture of a bronchial vein, and hoarseness, caused by compression of the recurrent laryngeal nerve, are classic but uncommon presentations. Aside from the typical signs of heart failure, findings that suggest the presence of mitral stenosis include a loud S1 and an opening snap in early diastole, accompanied by a low-pitched, rumbling diastolic apical murmur. Although the chest radiograph may be normal, left atrial enlargement may be suggested by straightening of the left heart border in more advanced cases. Common electrocardiographic abnormalities, in addition to atrial fibrillation, include left atrial enlargement and, ultimately, right ventricular hypertrophy. Echocardiography confirms the diagnosis and assesses the severity of disease.

Management Medical treatment for patients with mitral stenosis is comprised of diuresis for symptoms of vascular congestion and anticoagulation for atrial fibrillation. Once symptoms have developed, however, median survival without intervention is 7 years.13 Several surgical options exist, ranging from balloon valvulotomy or open commissurotomy to valve reconstruction or replacement. Management of the patient with mitral stenosis in the ED centers on identification and treatment of underlying precipitants, such as atrial fibrillation or anemia, diuresis, and referral for definitive intervention.

Mitral Regurgitation Acute and chronic mitral regurgitation are two distinct disease entities. Acute mitral regurgitation is a true emergency. It can result from idiopathic rupture of the chordae tendineae, papillary muscle dysfunction in the setting of acute ischemia, papillary muscle rupture 2 to 7 days postinfarction, or perforation of a valve leaflet in the setting of infectious endocarditis or trauma. Chronic mitral regurgitation, on the other hand, usually occurs in the setting of dilated cardiomyopathy (due to enlargement of the mitral annular ring) or RHD, often coexisting with mitral stenosis. Other causes of chronic mitral regurgitation include MVP and connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome.

Pathophysiology Acute mitral regurgitation is associated with low left atrial compliance and thus sharply elevated left atrial pressure, which results in acute pulmonary congestion. In contrast, chronic mitral regurgitation is characterized by high left atrial compliance and nearnormal left atrial pressures, with reduced forward output. Patients with chronic mitral regurgitation typically decompensate in the setting of volume overload.

Clinical Features The characteristic presentation of acute mitral regurgitation is one of fulminant pulmonary edema. This is accompanied by a unique, harsh, midsystolic murmur that radiates to the base rather than the axilla. Patients typically have no prior history of heart failure. The ECG may display signs of ischemia or infarction. The presentation of chronic mitral regurgitation is similar to that of chronic systolic heart failure, with clinical symptoms and

CHAPTER 73  Infective Endocarditis, Rheumatic Fever, and Valvular Heart Disease

signs of decompensated congestion. The murmur is classically described as holosystolic, heard best at the apex and radiating to the axilla. The ECG often reflects left atrial and ventricular hypertrophy. Atrial fibrillation is common, and left atrial enlargement may be suggested by the chest radiograph. Echocardiography may demonstrate a normal or above-normal ejection fraction, but some portion of systolic flow is retrograde.

Management When the diagnosis of acute mitral regurgitation is suspected, emergency echocardiography and cardiac catheterization will assess the degree of regurgitation and urgency for surgery. Initial stabilization should include treatment of pulmonary edema with nitrates and diuretics. In a hypotensive patient, a counterpulsation intraaortic balloon pump may provide temporary stabilization as a bridge to surgery. The natural history of chronic mitral regurgitation is generally a very slow progression, with 15-year survival approaching 70% with medical therapy, including diuretics and afterload-reducing agents. However, once the ejection fraction falls below 60%, valve repair or replacement is recommended to avoid irreversible left ventricular dysfunction.13

Aortic Stenosis The most common cause of aortic stenosis is calcific degeneration, which is prevalent in older adults with coronary artery disease. This also occurs in younger individuals with a bicuspid aortic valve. Aortic stenosis can also coexist with mitral stenosis in patients with RHD.

Pathophysiology The normal aortic valve area is larger than 3 cm2. Significant obstruction occurs when the valve area is reduced by more than 50%. Critical aortic stenosis is defined by a valve area of less than 0.8 cm2 or a pressure gradient across the valve that exceeds 50 mm Hg. Compensatory left ventricular hypertrophy can maintain cardiac output until the stenosis becomes severe. Further progression of disease is associated with left ventricular dysfunction, left atrial enlargement, and atrial fibrillation. Individuals with severe or critical aortic stenosis are preload-dependent and have very little cardiovascular reserve. Any disruption of the delicate balance between myocardial oxygen supply and demand (eg, rapid atrial fibrillation, dehydration, acute blood loss) can result in precipitous decompensation.

Clinical Features Classic symptoms of aortic stenosis progress from angina (increased demand resulting from wall stress and decreased supply resulting from reduction in perfusion pressure) to exertional syncope (fixed cardiac output and vasodepressor response), to congestive heart failure (diastolic and ultimately systolic dysfunction). In an older patient with chest pain, particularly if seemingly preload-dependent, the possibility of aortic stenosis, with or without coronary artery disease, should be considered. The classic auscultatory finding in aortic stenosis is a crescendodecrescendo systolic murmur heard best at the base (right second intercostal space) that radiates into the carotids and is associated with the presence of an S4 gallop and a soft aortic component of S2. Although counterintuitive, as the severity of disease increases, the murmur peaks later and becomes less apparent. Carotid pulses may be delayed (tardus) and diminished in intensity (parvus). The ECG typically reveals left ventricular hypertrophy. Echocardiography is required for the assessment of the severity of stenosis and presence of left ventricular dysfunction.

Management The natural history of aortic stenosis is one of slow progression, without symptoms for years. Once symptoms develop, medical management has a limited role, and survival is markedly reduced unless the valve is replaced. In high-risk patients, balloon valvuloplasty is feasible and safe as a bridge to percutaneous or surgical valve replacement, but long-term survival is poor with valvuloplasty alone.14 In the acute setting, management of decompensated aortic stenosis centers on judicious fluid resuscitation, blood transfusion, restoration of sinus rhythm, and avoidance of vasodilators and diuretics and inotropic agents, if possible. When there is no response to medical therapy and the patient is a candidate for valve replacement, an intraaortic balloon pump may provide a bridge to surgery.

Aortic Insufficiency Aortic insufficiency can occur as a consequence of RHD, infectious endocarditis, or the presence of a bicuspid valve. Aortic root abnormalities, such as ectasia, aneurysm, or dissection, can also lead to aortic insufficiency.

Pathophysiology In acute aortic insufficiency, left ventricular compliance is low, and left ventricular pressure increases rapidly during diastole, leading to acute pulmonary congestion. In chronic aortic insufficiency, the left ventricle dilates, allowing the heart to maintain normal or near-normal cardiac output, despite significant regurgitation. The enhanced stroke volume results in a wide pulse pressure and the clinical signs that are commonly associated with aortic insufficiency. Pulmonary congestion, when present, is generally a consequence of volume overload.

Clinical Features Patients with acute aortic insufficiency can present with severe respiratory distress and/or frank cardiogenic shock. At the same time, the physical findings specific to acute aortic insufficiency can be quite subtle. The pulse pressure will be widened only slightly, if at all, and the short, soft, diastolic murmur may be difficult to detect. Emergent echocardiography is required to confirm the diagnosis. In contrast, chronic aortic insufficiency is characterized by a widened pulse pressure, which may be accompanied by a number of classic physical findings, such as a rapidly rising and falling carotid pulse (water hammer,or Corrigan’s, pulse), spontaneous nail bed pulsations (Quincke’s sign), or a to and fro murmur over the femoral artery (Duroziez’s sign). A high-pitched, blowing, diastolic murmur at the left sternal border is characteristic of chronic aortic insufficiency. An Austin-Flint murmur—the soft diastolic rumble caused by a regurgitant stream against the mitral valve—may also be present.

Management In contrast to chronic aortic insufficiency, acute aortic insufficiency is a surgical emergency necessitating urgent valve replacement, along with repair of any underlying aortic root pathology. Medical stabilization entails the cautious use of vasodilators and diuretics. For obvious reasons, intraaortic balloon counterpulsation is contraindicated in the presence of an incompetent aortic valve. Chronic aortic insufficiency is managed like other types of decompensated heart failure, with emphasis on diuresis, as well as preload and afterload reduction. Ideally, however, valve repair or replacement should be performed before the development of left ventricular systolic dysfunction.13

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MVP is associated with a wide variety of clinical symptoms, including chest pain, palpitations, dyspnea, lightheadedness, and fatigue. Appropriately controlled clinical studies, however, such as the Framingham Heart Study, have suggested that patients with MVP and control subjects may be equally symptomatic. The classic auscultatory feature of MVP is a midsystolic click caused by snapping of the chordae tendineae with prolapse of the valve. Occasionally a mid to late systolic murmur can be appreciated over the mitral area. Confirmation of the diagnosis is made by echocardiography.

regurgitant murmur, or louder than expected stenotic murmur. Echocardiography may demonstrate the thrombus or restricted leaflet motion. Treatment options include fibrinolytic therapy and surgery. The incidence of systemic embolization from a prosthetic valve is approximately 1%/year. Compared with aortic valve prostheses, mitral valve prostheses are associated with twice the risk of systemic embolization, with rates roughly equal for a biologic mitral valve or appropriately anticoagulated mechanical mitral valve. The vast majority of diagnosed embolic events (85%) involve the central nervous system, and roughly 50% of these result in permanent impairment.16 A mild hemolytic anemia resulting from sheer forces through the prosthetic valve aperture is common but usually subclinical. In more severe case, presenting features can include dyspnea, fatigue, and even jaundice. Iron replacement is effective therapy for most patients but transfusion may be required in severe cases. If hemolysis is the result of a periprosthetic leak or other structural failure, scheduled reoperation is commonly required. The incidence of PVE is highest during the initial months after surgery and is similar for mechanical and bioprosthetic valves. Early PVE, within 60 days of surgery, is presumed to be caused by a pathogen acquired perioperatively and is associated with higher morbidity and mortality, whereas late PVE is more likely related to transient bacteremia and is generally associated with a more benign course. As with other forms of endocarditis, fever is the most common presenting symptom, whereas other manifestations are variable. Echocardiography can identify vegetations, but a normal study does not rule out endocarditis. In the ED, the diagnosis of PVE is generally presumptive because definitive diagnosis requires blood cultures or biopsy.

Management

Disposition

Cardioselective beta blockers may control symptoms such as palpitations, chest pain, and anxiety. Lifestyle modifications, such as exercise, relaxation techniques, and avoidance of ethanol or caffeine and other stimulants, may also be helpful. Often, simple reassurance about the generally benign nature of the disease will suffice.

Patients with acute symptoms related to valvular heart disease should be admitted to the hospital until their condition has stabilized and the cause for their decompensation has been addressed. For patients with stable valvular disease, outpatient cardiology follow-up is recommended.

Mitral Valve Prolapse MVP is defined pathophysiologically as an abnormal movement of one or both of the mitral valve leaflets during systole. Although generally a benign condition, it is infrequently associated with more serious cardiac pathology such as mitral regurgitation, endocarditis, and arrhythmias. Echocardiographic studies report a true prevalence of less than 1% in h men and women versus the previously reported 5%, with a female predominance.15

Pathophysiology Structurally, MVP is characterized by myxomatous proliferation of the spongiosa layer within the mitral valve that results in abnormal billowing of the leaflet during systole. MVP usually occurs in isolation but, like other valvular diseases, may be associated with other connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome.

Clinical Features

Complications of Prosthetic Valves Prosthetic heart valves are classified as mechanical or biologic. The latter category includes whole valve transplants (human or porcine) as well as bioprosthetic valves, which are typically manufactured from bovine pericardium. All prosthetic heart valves are associated with complications, ranging from structural failure and thrombosis to systemic embolization, hemolysis, and endocarditis. In the acute setting, the diagnosis of a prosthetic valve complication can be challenging because symptoms and signs are often subtle. Primary structural failure is extremely uncommon with modern mechanical valves. When it does occur, the presentation is one of acute severe regurgitation and shock, and emergent valve replacement is required. With biologic valves, in contrast, structural failure is relatively more common, but less dramatic. At 10 years, 20% to 30% of bioprosthetic valves exhibit some evidence of structural failure, and most are replaced electively. Symptoms are characteristically insidious in onset and are similar to those of native valvular disease. Prosthetic valve thrombosis occurs with mechanical and biologic valves. When adequately anticoagulated, mechanical valves have thrombotic complications at a similar rate (≈2%/year) as biologic valves.16 Symptoms of prosthetic valve thrombosis are generally subacute and may have characteristics of stenotic disease, regurgitant disease, or both. On physical examination, the diagnosis is suggested by a decreased or absent valve click, new

KEY CONCEPTS • Many patients seen early in the bacteremic phase of IE lack a murmur and are indistinguishable from those with viremia. • Patients for whom suspicion of endocarditis is moderate to high require blood cultures, echocardiography, and admission for definitive diagnosis and initiation of empirical therapy. • Prophylaxis for IE is rarely, if ever, indicated for procedures performed in the ED. • Acute rheumatic fever is a delayed nonsuppurative complication of streptococcal pharyngitis characterized by arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. • In a patient with severe mitral stenosis, hypovolemia and tachycardia are poorly tolerated. Slow and full are appropriate goals. • In patients with critical aortic stenosis, excessive preload reduction with vasodilators and diuretics is to be avoided. • In patients with acute aortic insufficiency, classic physical findings may be absent. Medical stabilization entails the cautious use of vasodilators and diuretics. Intraaortic balloon counterpulsation is contraindicated. • Complications of prosthetic heart valves range from structural failure and thrombosis to systemic embolization, hemolysis, and endocarditis.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 73  Infective Endocarditis, Rheumatic Fever, and Valvular Heart Disease

1006.e1

REFERENCES 1. Hoen B, Duval X: Infective endocarditis. N Engl J Med 369:785, 2013. 2. Cahill TJ, Prendergast BD: Infective endocarditis. Lancet 387:882–893, 2016. 3. Bor D, et al: Infective endocarditis in the US, 1998–2009: a nationwide study. PLoS ONE 8:e60033, 2013. 4. Thuny F, et al: Management of infective endocarditis: challenges and perspectives. Lancet 379:965–975, 2012. 5. Lalani T, et al: In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Intern Med 173:1495–1504, 2013. 6. Topan A: Assessment of the Duke criteria for the diagnosis of infective endocarditis after twenty-years. An analysis of 241 cases. Clujul Med 88:321–326, 2015. 7. Kang D, et al: Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 366:2466–2473, 2012. 8. Baddour LM, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council: Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 132:1435–1486, 2015. 9. Wilson W, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group: Prevention of infective endocarditis: guidelines from the American Heart Association: a

10. 11. 12. 13.

14. 15. 16.

guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 116:1736–1754, 2007. Marijon E, et al: Rheumatic heart disease. Lancet 379:953–964, 2012. Gewitz MH, et al: Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation 131:1806–1818, 2015. Cilliers A, et al: Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev (6):CD003176, 2012. Nishimura RA, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines: AHA/ACC 2014 guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63(22):e57–e185, 2014. Ben-Dor I, et al: Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. J Am Coll Cardiol Intv 3:1150–1156, 2010. Delling FN, Vasan RS: Epidemiology and pathophysiology of mitral valve prolapse new insights into disease progression, genetics, and molecular basis. Circulation 129:2158–2170, 2014. Whitlock RP, et al; American College of Chest Physicians: Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl):e576S–600S, 2012.

CHAPTER 73: QUESTIONS & ANSWERS 73.1. What is the most common manifestation of acute rheumatic fever (ARF)? A. Carditis B. Chorea C. Erythema marginatum D. Polyarthritis E. Subcutaneous nodules Answer: D. Arthritis occurs early in the course of ARF. The knees, ankles, elbows, and wrists are commonly affected, and pain can be out of proportion to physical findings. Cardiac manifestations are subtle and may reflect endocarditis, myocarditis, or pericarditis. Chorea, nodules, and erythema marginatum are rare. Chorea is typically a late finding. 73.2. A 49-year-old woman presents with progressive dyspnea on exertion and orthopnea. Vital signs are temperature 36.7° C (98.1° F; oral), heart rate, 110 beats/min, blood pressure, 135/80 mm Hg, respiratory rate, 22 breaths/min, and oxygen (O2) saturation, 97% on room air. The physical examination is remarkable for clear lung fields and an irregularly irregular rhythm with a 4/6 diastolic



murmur in the left anterior axillary line. She has no peripheral edema. Which of the following would be appropriate hemodynamic management of her cardiac pathophysiology? A. Aggressive diuresis B. β1-Agonist to increase chronotropy C. Beta blockade D. Selective arterial vasodilator E. Selective venodilator

Answer: C. This patient has a picture consistent with atrial fibrillation and mitral stenosis. The apical diastolic murmur and left atrial enlargement, along with progressive dyspnea, all support the diagnosis. Tachycardia is poorly tolerated because of the need for higher left atrial pressures and a longer time during diastole to perfuse across the stenotic valve. Slow and full would be appropriate guidelines. Both diuresis and a venodilator might decrease venous return. Any agent producing tachycardia would decrease diastole time and left ventricular preload. An arterial vasodilator would have little effect, given the normal blood pressure and the fact that systemic vascular dilation would not be seen at the mitral valve level as long as the aortic valve was competent.

SECTION FOUR

Vascular System C H A P T E R 74 

Hypertension Phillip D. Levy  |  Aaron Brody PRINCIPLES Background Hypertension (HTN) is an important but largely treatable risk factor for cardiovascular disease that affects almost one-third of Americans and approximately 1 billion people worldwide.1,2 Although more than 80% of those with HTN are aware of their condition and most (~75%) are receiving at least some form of antihypertensive therapy, blood pressure (BP) remains uncontrolled in nearly 50% of patients.3,4 The implications of this on the practice of emergency medicine are clear. According to data from a nationwide emergency department (ED) sample between 2006 and 2010, one of every five ED visits included HTN as a diagnosis.5 Moreover, as shown in the most recent analysis of the National Hospital Ambulatory Medical Care Survey,6 moderate (ie, >140–159/90–99 mm Hg) to severely elevated (ie, ≥160/ 100 mm Hg) BP is present in over 40% of ED patients.7 Despite this understanding, there is a critical divide between what constitutes emergency and medicine when it comes to elevated BP in the ED. When associated with acute target organ damage (TOD), HTN represents a true emergency that warrants emergent intervention. However, this is relatively rare and, for the vast majority, acute TOD will be not be present, even in the setting of markedly elevated BP. Although such patients have a low likelihood of near-term adverse events and are thus not emergencies per se, they would undoubtedly benefit from measures to decrease their overall cardiovascular risk through better BP control. This distinction is thus a key aspect of the approach to HTN in the ED and a core feature of emergency medicine practice.

Importance Hypertension is a major modifiable risk factor for the development of cardiovascular, cerebrovascular, and renovascular disease. Uncontrolled BP is strongly associated with heart failure, myocardial infarction, stroke, vascular dementia, and chronic kidney disease. The risk of developing these conditions increases with the degree of BP elevation, and it has been estimated that the risk of cardiovascular disease doubles for each elevation of 20 mm Hg systolic and 10 mm Hg diastolic BP, starting at 115/75 mm Hg. Conversely, BP treatment can lower the risk for stroke by 40%, myocardial infarction by 25%, and heart failure by 50%. The distribution of HTN is not uniform. African Americans have higher rates of disease (40.4% vs. 27.1% for whites) and poorer BP control, leading to an increased risk of adverse outcome,8-10 whereas people of Hispanic ethnicity have lower rates (26%). This disparity, in combination with other economic, social, and lifestyle determinants, leads to dramatically increased

morbidity of cardiovascular disease in the African American population.11 HTN is the single most important contributor to racial differences in life-years lost from cardiovascular disease, accounting for 50% of the excess risk within the African American community.12

Definition of Hypertension and Relevant Terminology Although BP below 120/80 mm Hg is considered normal, an understanding of what constitutes HTN has been evolving. Present definitions are based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), which set a BP level of 120 to 139/80 to 89 mm Hg as pre-HTN, 140 to 159/90 to 99 mm Hg as stage I HTN, and 160/100 mm Hg or higher as stage II HTN.13 In the JNC 8, a much anticipated update to this pivotal guideline, no changes to these categorical definitions were proposed.14 However, greater emphasis was placed on age-based treatment thresholds, with antihypertensive therapy recommended when the systolic BP exceeds 140 mm Hg for those younger than 60 years and 150 mm Hg for those 60 years of age or older. As with other guidelines, a diastolic BP of 90 mm Hg or higher remains an indication for treatment, regardless of age.15 Historically, the approach to BP measurement has been officebased, with a diagnosis of HTN considered to be present when BP of 140/90 mm Hg or higher is detected on properly measured, seated readings on two or more occasions. Recent data have suggested that 24-hour ambulatory BP measurement may be a better method for establishing a diagnosis of HTN.16 Ambulatory BP measurement enables the evaluation of BP over a range of conditions, minimizing the potential for so-called white coat effects while increasing the likelihood of detecting masked HTN. The increased reliability of the ambulatory BP measurement has prompted recent guidelines to recommend that the threshold for HTN be set at 135/85 mm Hg when the BP is determined via this approach.17,18 How ED-measured BPs fit into this paradigm is not clear. Many ED patients with elevated BP will have an established history of HTN, but a sizeable proportion will not, presenting an opportunity to establish the diagnosis. Although this should be approached with caution on the basis of a single ED measurement, demonstration of persistently elevated BP over several prior ED visits may be a reasonable indicator of true underlying HTN. Prior studies have shown that as many as 70% of patients with elevated BP in the ED will also have an abnormal BP at primary care follow-up, and this proportion increases with the ED BP value. Newer automated BP devices that perform serial measurements, discarding the first reading and averaging subsequent 1007

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Acute target organ damage

Elevated BP

Vascular System

Hypertensive emergency

Evaluate and treat (usually IV antihypertensive)

Elevated blood pressure without history of HTN

Reassess BP, reassure patient, consider referral for measurement in primary care setting

Poorly controlled chronic HTN

Refer to primary care, consider initiation/titration of chronic antihypertensive therapy

No acute target organ damage

Fig. 74.1.  Schematic for the approach to elevated blood pressure (BP) in the emergency department. HTN, Hypertension.

values, have been shown to improve the accuracy of office-based methods and may be a useful adjunct in the ED for such patients.19 Perhaps more important in the ED setting than making the diagnosis of chronic HTN is understanding the need for acute intervention among patients who have marked BP elevations (ie, ≥180/100 mm Hg). Although terms such as hypertensive crisis, hypertensive urgency, and accelerated or malignant HTN, are liberally applied to such patients, they are poorly defined and are often used interchangeably and incorrectly by emergency clinicians. A better approach focuses on the presence (or absence) of signs or symptoms attributable to acute TOD within the context of established or potentially new-onset HTN, thus distinguishing patients with active vasculopathy from those without. Based on this conceptual model, there are three distinct subgroups of patients with elevated BP that are relevant to emergency medicine practice: 1. Hypertensive emergency—a disease state defined by acute TOD, manifest by newly developed clinical sequelae or diagnostic test abnormalities. A hypertensive emergency can exist in patients with or without underlying chronic HTN. Although it has been estimated that 1% to 2% of patients with chronic HTN will experience a hypertensive emergency in their lifetime, hospitalization for this condition is relatively rare, occurring in only 110 of every 100,000 admissions in the United States.20 2. Poorly controlled chronic HTN—a presentation in which patients with established HTN are found to have elevated BP without specific attributable symptoms or evidence of acute TOD. Such presentations often result from nonadherence to treatment regimens or inadequate medical management, but may also reflect refractory disease. Concurrent use of seemingly innocuous medications, including nonsteroidal antiinflammatory drugs (NSAIDs), steroids, decongestants, appetite suppressants, over-the-counter stimulants, oral contraceptives, and tricyclic antidepressants or rebound from short-acting antihypertensives, such as clonidine, may be contributory. 3. Elevated BP without prior history of HTN—a relatively frequent occurrence in which routine ED vital signs identify an elevated BP. Such individuals also may visit the ED after an outpatient physical examination, community health screening event, or self-performed, automated BP measurement identifies elevated BP. Whether or not this truly represents HTN can be difficult to determine in the ED, and all such patients should have repeat measurement of BP, ideally 1 hour or more after arrival, and after analgesic treatment for those with acute pain. Depending on the circumstance, an evaluation for potential TOD may be warranted, along with referral for subsequent follow-up in an outpatient setting.

An approach to elevated BP in the ED based on this understanding is presented in Fig. 74.1.

Physiology of Hypertension Whereas BP is known to rise with increasing age, onset of HTN in the non–older adults represents a complex interplay of multiple inciting factors, including neurohormonal dysregulation, vascular modulation, sodium intake, psychosocial stress, and obesity. Alterations in cardiac and renal function are also important, serving as contributors to and consequences of ongoing BP elevation. Despite an advanced understanding of the pathophysiology of HTN, the definitive cause of elevated BP remains unknown in more than 90% of patients. These individuals are labeled as having primary or essential HTN, and the cause is considered idiopathic. In the subset of patients for whom an identifiable cause can be ascertained, the term secondary HTN applies (Table 74.1). Although it may not be possible to diagnose and treat such causes of secondary HTN in the ED, when suspected, early referral for outpatient evaluation or, in some cases, hospital admission to expedite evaluation, may be warranted.

Neurohormonal Dysregulation The sympathetic nervous system (SNS) has a pivotal role in the development of HTN.21 Norepinephrine, the principal sympathetic neurotransmitter, is a potent stimulator of vasoconstriction. This effect is mediated through peripheral α1-adrenergic receptor activation in vascular smooth muscle cells and occurs predominantly in small-diameter arterioles. Although individually these vessels contribute a miniscule amount to BP, in aggregate they serve as the primary driver of systemic vascular resistance (SVR) and constitute the main force that amplifies afterload in HTN.22 The SNS also stimulates β1-adrenergic receptors in the heart, leading to an increase in cardiac output (CO) through augmentation of stroke volume and heart rate, but these are considered lesser contributors to the pathologic process of high BP. Sympathoactivation exerts additional direct effects on the kidney that promote sodium reabsorption, leading to an increase in circulating blood volume, and trigger renin release, resulting in angiotensin II production and further vasoconstriction.23 In addition to activation by the SNS, the renin-angiotensinaldosterone system exerts critical independent effects on BP.24,25 Renin is an enzyme produced by juxtaglomerular cells in the kidney in response to several factors beyond adrenergic stimulation, including sodium load in the distal tubule and renal perfusion status. Renin cleaves angiotensin I from its plasma globulin precursor, angiotensinogen. Angiotensin I is then converted to

CHAPTER 74  Hypertension

TABLE 74.1 

Secondary Causes of Hypertension CAUSE

DIAGNOSTIC TEST

CLINICAL CLUES

Cushing’s syndrome and other glucocorticoid excess states

History; dexamethasone suppression test

Glucose intolerance; purple striae

Hyperaldosteronism and other mineralocorticoid excess states

24-hr urinary aldosterone level or other mineralocorticoids

Unexplained hypokalemia

Oral contraceptive use

History

Pheochromocytoma

24-hr urinary metanephrine and normetanephrine

Labile or paroxysmal HTN with palpitations, pallor, perspiration

Thyroid disease Parathyroid disease

Serum TSH Serum PTH

Temperature intolerance, weight loss, tachycardia; hypercalcemia

Sleep study with O2 saturation

Obesity; narcolepsy

ENDOCRINE

PULMONARY Obstructive sleep apnea RENAL Chronic pyelonephritis

History; urinalysis, urine culture

Diabetic nephropathy and other chronic kidney disease

Estimated GFR; urine albumin/ creatinine ratio

Nephritic and nephrotic syndromes

Urinalysis; renal biopsy

Polycystic kidney disease

Renal ultrasound

Renovascular conditions (eg, renal artery stenosis)

Doppler flow study; magnetic resonance angiography

HTN onset before the age of 30 yr or after 55 yr; abdominal bruit; refractory HTN control; recurrent pulmonary edema; unexplained renal failure

TOXIC OR METABOLIC Chronic alcohol abuse

History; ETOH level

Sympathomimetic drug use

History; drug screen

Tyramine-containing foods

History

Paroxysms of HTN, especially in those taking monoamine oxidase inhibitors

CT angiography

Decreased lower extremity pulses

VASCULAR Atherosclerosis Coarctation of the aorta

CT, Computed tomography; ETOH, ethyl alcohol; GFR, glomerular filtration rate; HTN, hypertension; O2, oxygen; PTH, parathyroid hormone; TSH, thyroid-stimulating hormone.

angiotensin II by circulating and tissue-bound (especially in the lung), angiotensin-converting enzyme (ACE). Angiotensin II exerts systemic and renal effects by binding to angiotensin II type I (AT1) receptors, which results in arterial vasoconstriction, sodium reabsorption, and modulation of the glomerular filtration rate (GFR). Through AT1 receptor binding in the adrenal gland, angiotensin II also serves as a potent stimulator of aldosterone release, which promotes further sodium reabsorption and potassium excretion.

Vascular Modulation Continued vascular stimulation by the SNS and renin-angiotensinaldosterone system, coupled with an increase in wall tension caused by HTN itself, leads to ongoing remodeling throughout the arterial tree.26,27 In large vessels such as the aorta or carotid arteries, this results in increasing intima-media thickness, with minimal luminal narrowing—unless there is unrelated plaque buildup. In contrast, small-vessel and arteriolar remodeling reduce the lumen diameter.28 Although both forms of remodeling work to normalize wall stress associated with HTN, they reduce vasodilatory capacity and enhance the vasoconstrictor response when faced with a hypertensive stimulus.

Sodium Intake The average American has a daily sodium intake of close to 3500 mg (150 mEq)—more than double the recommended level of 1500 mg (≈65 mEq) recommended by the American Heart Association (AHA) in its 2011 guidelines.29 Randomized trials have demonstrated a reduction in systolic BP with diminished daily sodium intake (up to 7 mm Hg/1200 mg, or a 52-mEq decrease in hypertensive individuals)30; however, the impact of this intervention on long-term cardiovascular outcomes is unclear.31 Salt sensitivity is defined by an increase in BP with intake of a high-sodium diet. It is linked to obesity but may be more directly related to defects in renal ion transport mechanisms that lead to ongoing sodium retention and potassium depletion.32 Although not fully defined, the latter plays a critical role, because the entire effect of salt sensitivity on BP can be mitigated with high-dose (≈4000 mg, or 100 mEq/day) potassium supplementation.33-35

Psychosocial Stress Life stressors, especially socioeconomic status, are known to affect health and wellness adversely. Through its effects on SNS function and the hypothalamic-pituitary axis, stress modulates BP and is a

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specific contributor to disparities in HTN.36,37 Although episodic stress reactions can lead to transient sympathetic surges, sustained stimulation related to ongoing concern over life circumstances (eg, financial security, crime and safety, racism) triggers a chronic adaptive response and has been emerging as an important consideration in patients with seemingly idiopathic HTN.38,39

Obesity Obesity is a known risk factor for the development of HTN. For every increase of body mass index by 5 kg/m2, the risk of hypertension increases by 1.4 (95% confidence interval [CI], 1.38–1.49).4 Elevated BP in obese individuals correlates with high circulating aldosterone and cortisol levels, which in turn may be related to salt sensitivity.40 Obesity, especially truncal, is also strongly associated with diabetes and obstructive sleep apnea, both of which contribute to poor BP control.41

Pathophysiology of Target-Organ Damage Uninterrupted by treatment, continued vasoconstriction in chronic HTN leads to a number of deleterious consequences that culminate in TOD. On a macrocirculatory level, the central components of the cardiovascular system (ie, heart, large blood vessels) are most affected. Sustained elevations in SVR cause significant augmentation of the pressure wave reflected from the periphery back to the central circulation (termed the augmentation index), thus driving up left ventricular (LV) afterload; the increase manifests with a rise in the central aortic pressure and change in the morphology of its waveform.22,42 This results in increasing impedance to forward flow from the heart, which in turn necessitates greater contractile force to maintain aortic valve opening and the duration of ventricular ejection.43 Active contraction against this resistance also increases intraventricular wall tension, which, together with ongoing stimulation from, among other things, the SNS and renin-angiotensin-aldosterone system, triggers cardiomyocyte hypertrophy and myocardial fibrosis. Initially, this leads to an increase in LV mass, which enhances the heart’s pumping against excessive afterload. However, when progressive, the net result is LV stiffening and impaired diastolic function, with an increase in LV filling pressure and diminished flow from the left atrium to the left ventricle. If the increase in afterload is sudden, an abrupt decrease in stroke volume occurs, precipitating backflow of fluid into the lungs and rapid onset of so-called flash pulmonary edema. If excess afterload is more gradual or even chronic, a subacute rise in LV end-diastolic pressure may cause increased wall tension, with compression of the subendocardial microvasculature and myocardial ischemia. Over time, this contributes to LV wall thinning, chamber dilation, and eventually systolic dysfunction. On a microcirculatory level, the initial beneficial effect of vascular remodeling gradually gives way to critical luminal narrowing and the potential for regional ischemia from occlusion or loss of vessel wall integrity with leakage or rupture. Autoregulation, the intrinsic capacity of resistance vessels to dilate or constrict rapidly in response to dynamic perfusion pressure changes, works to maintain relatively constant blood flow and is protective with moderate fluctuations. Small-vessel ischemic episodes, many of which are silent, are the primary cause of chronic TOD, including progressive white matter (ie, multi-infarct) disease in the brain and hypertensive nephropathy.44,45 Cerebral microbleeds, which are identified by imaging of hemosiderin deposits on brain magnetic resonance imaging (MRI) scans, are a relatively new class of subclinical brain injury associated with chronic HTN and portend more rapid cognitive decline in older adults.46-48 Unlike the pattern of TOD that occurs with poorly controlled chronic HTN, a hypertensive emergency results from acute

endothelial injury triggered by an abrupt rise in vascular pressure that overwhelms autoregulatory mechanisms. A subsequent drop in nitric oxide (NO)–mediated vascular smooth muscle relaxation and excess release of endothelin further increase SVR, which functionally maintains BP at severely elevated levels. Unchecked wall tension ensues, and terminal arterioles dilate and eventually rupture, leading to a proinflammatory hypercoagulable state, with fibrin deposition and diffuse ischemia.49 Rising pressure in the proximal capillary beds causes fluid leakage and tissue edema, which, combined with the process of fibrinoid necrosis, produces acute TOD along with microangiopathic hemolytic anemia and other signs of small vessel injury.

CLINICAL FEATURES Although BP elevation alone does not define any particular clinical syndrome, acute TOD does not occur in the absence of moderate to severe HTN (ie, ≥180/110 mm Hg). Conversely, in the absence of symptoms, the mere presence of an excessively high BP in the ED (regardless of the level) does not herald imminent development of TOD.

Hypertensive Emergency Most hypertensive emergencies occur in patients with chronic HTN.50 Organ system involvement is relatively consistent and is dominated by injury to the heart, brain, or kidneys (Table 74.2). True hypertensive emergencies are defined by the target organ acutely involved. Focal neurologic deficit or altered mentation point to brain injury, whereas chest pain or shortness of breath may be indicative of cardiac or vascular involvement. Although frequently accompanied by an elevated BP, symptoms such as headache, epistaxis, and dizziness are not, in and of themselves, evidence of acute TOD and, in isolation, do not constitute a hypertensive emergency nor do they indicate the need for acute BP reduction.

TABLE 74.2 

Hypertensive Emergencies by Organ System INJURY PATTERN BY TARGET ORGAN Heart (cumulative) • Acute heart failure • Acute coronary syndrome

27–49 14–37 11–12

Brain (cumulative) • Acute ischemic stroke • Spontaneous intracranial hemorrhage • Hypertensive encephalopathy

37–45 6–25 5–23 8–16

Kidney • Acute renal risk • Acute kidney injury

15 8

Vascular • Aortic dissection

1–2

Other • Eclampsia • Acute hypertensive retinopathy a

APPROXIMATE INCIDENCEa (%)

2 1

Adapted from Levy P: Hypertensive emergencies: on the cutting edge. Advancing the standard of care: cardiovascular and neurovascular emergencies. www.emcreg.org.

CHAPTER 74  Hypertension

Hypertensive Encephalopathy Hypertensive encephalopathy is the essential factor in hypertensive emergencies. Resulting from diffuse, vasogenic cerebral edema, it is caused by a failure of autoregulation in the brain, with vasospasm, ischemia, increased vascular permeability, punctate hemorrhages, and interstitial edema. Severe headache, vomiting, and altered mental status are common features, which may progress to seizures or coma. Retinal involvement may cause blurred vision progressing to complete blindness. When present, focal neurologic deficits do not follow a singular anatomic pattern and may occur on opposite sides of the body, indicating diffuse cerebral dysfunction rather than an anatomically localized stroke syndrome or spaceoccupying lesions. Papilledema, although difficult to recognize, is often present, along with significant hypertensive retinopathy. Computed tomography (CT) may not show acute hemorrhage or other acute pathology. Diffuse or regional cerebral edema and small hemorrhages have been reported. The combination of diffuse cerebral dysfunction on clinical examination, normal or nonspecific CT scan, and markedly elevated systemic BP, particularly if supported by objective findings such as papilledema or retinal hemorrhage, is sufficient to make a presumptive diagnosis of hypertensive emergency and necessitates the initiation of acute antihypertensive therapy. Hypertensive encephalopathy is fully reversible with early, prompt BP reduction (30%–40% decrease); recently published data from the Nationwide Inpatient Sample have suggested that the overall in-hospital mortality rate is less than 1%.51 First defined in 1996, posterior reversible encephalopathy syndrome (PRES) has a neurologic presentation similar to that of hypertensive encephalopathy, albeit with less global and more region-specific features. Also caused by increased vascular permeability secondary to endothelial damage with vasogenic edema, PRES is characterized by a constellation of symptoms related to posterior cerebral impairment, including visual changes, headache, altered mental status, and seizures.52 It is diagnosed by the visualization of white matter edema in the posterior parietaltemporal-occipital regions on MRI. As the name suggests, PRES is reversible by treating the underlying cause. HTN is the most common condition associated with PRES, although it may also be seen with kidney disease, malignancies, cytotoxic therapy, and autoimmune disease.

Other Hypertension-Related Emergencies The clinical features of other hypertension-related emergencies cross over with nonhypertensive manifestations, and they are described in greater detail elsewhere in this text. Moreover, these conditions are defined by more than just HTN and, in many cases, their onset is incidental to, not caused by, elevated BP. However, long-standing HTN is often a contributor to the underlying problem and, when elevated BP is causal, effective treatment can have a dramatic impact on the clinical course. Elevated BP frequently accompanies acute intracranial hemorrhage, and the rapid initiation of antihypertensive therapy is a routine component of ED care (see Chapter 91). HTN is the primary populationattributable risk factor for the development of chronic cardiac dysfunction, and more than 50% of ED patients with acute heart failure have elevated BP on presentation (see Chapter 71). Patients with acute heart failure and HTN respond well to vasodilatory agents and afterload reduction. Nitroglycerin has long been used in the setting of acute coronary syndrome and demand ischemia (see Chapter 68), and antihypertensive therapy is a key component of ED management for acute aortic dissection (see Chapter 75). Acute kidney injury in the setting of elevated BP may be a consequence of associated TOD, especially acute heart failure, particularly when these patients are on baseline diuretic or calcium channel blocker therapy. Recent or chronic NSAID or newly

initiated ACE inhibitor therapy may also contribute, but the effect of these agents are usually transient (see Chapter 87).44 Preeclampsia and eclampsia are discussed in Chapter 178.

Blood Pressure Elevation Acute Target Organ Damage in the Context   of Systemic Illness Any medical condition that leads to a hypermetabolic state can impair electrolyte homeostasis and trigger an intrinsic vasomotor response, causing BP to rise acutely. Depending on the circumstance, this may also be associated with clinical or diagnostic evidence of acute TOD. Distinguishing this from a true hypertensive emergency necessitates demonstration that the elevated BP does not contribute directly to the pathologic condition. Treatment of the underlying disorder will often resolve the BP elevation, although BP reduction may play a role in supportive management.

Absence of Target Organ Dysfunction Most patients who are found to have significant HTN on intake vital signs measurement or who come to the ED because BP was found to be elevated in an outpatient setting or by self-measurement do not have an acute hypertensive emergency. For such patients, acute reduction of BP is not indicated and offers no tangible outcome benefit. Although many patients who fall into this group have poorly controlled chronic HTN, some will lack such a history. To connote an absence of acute TOD, these patients are often described by the term asymptomatic, but this is potentially misleading because nonspecific symptoms (eg, low-grade or recurrent headache, atypical chest pain, dyspnea, dizziness, generalized weakness, focal but anatomically uncorrelated weakness or numbness, vague visual disturbances) are frequently present. However, with the exception of dyspnea, the occurrence of these symptoms appears to be unrelated to the degree of BP elevation. In addition, despite widespread belief among the lay community and some members of the health care profession that acute severe HTN contributes to epistaxis, there is no evidence to support a causal relationship.53 As a general rule, acute BP reduction is not indicated in patients with elevated BP who lack acute TOD, even when vague symptoms are present. In many cases, BP will spontaneously improve with time, and there is no need to hasten this with antihypertensive therapy. If chronic oral medications have been missed, as is often the case, these should be restarted, perhaps with the first dose administered in the ED to reinforce the importance of future compliance, although this is in no way required and will not change any outcome. However, there are no data supporting a threshold BP that warrants such treatment or a target BP to be achieved before discharge. Importantly, the administration of a short-acting, potent antihypertensive agent such as clonidine or hydralazine simply to improve BP values lacks rationale or evidence of benefit and, according to a retrospective cohort study, may be associated with an increased likelihood of subsequent ED visit for issues related to HTN.54 As previous experience with sublingual nifedipine has shown, BP reduction in the absence of acute TOD is also potentially dangerous, inducing relative cerebral hypoperfusion and increasing the likelihood of related morbidity and mortality, and should not be administered in the ED.

DIAGNOSTIC CONSIDERATIONS Differential Diagnoses Differential considerations are based on patient subtype. For those with a suspected hypertensive emergency, the decision point

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centers on the potential causal relationship between patient presentation and acutely elevated BP. Clinical entities within this broader heading, such as stroke syndromes and acute heart failure, carry their own differentials, but a full discussion of each is beyond the scope of this chapter. Depending on the clinical scenario, ancillary testing may be needed to rule out alternatives to a hypertensive cause, particularly in patients with systemic illness. For those with poorly controlled chronic HTN, a consideration of cause (ie, primary vs. secondary) may be warranted. A related diagnostic evaluation (see Table 74.1) can usually be pursued on an outpatient basis, but for some (ie, individuals with multiple episodes of flash pulmonary edema, symptomatic paroxysmal episodes of labile BP, or suspected poor follow-up), initiation of treatment from the ED or admission to the hospital is needed. The final factor to consider is whether a newly detected BP elevation is caused by true HTN. Although the diagnostic accuracy of BP can be enhanced by a second repeat measurement in the ED, the ideal approach may be to average several measurements taken over a brief period of observation. For those without a previous history of HTN, definitive diagnosis will typically require reassessment in an outpatient setting.

Diagnostic Testing The diagnostic evaluation of hypertensive emergency is guided by symptoms and signs identified on clinical examination but will often involve a number of tests. In nearly all cases, laboratory testing to look for acute or worsening renal dysfunction (ie, basic metabolic panel, urinalysis) and microangiopathic hemolytic anemia (ie, complete blood count with manual differential, peripheral smear) may be needed. Individuals with chest pain or shortness of breath may require a chest radiograph, electrocardiogram, and cardiac biomarker (ie, troponin, natriuretic peptide [NP]) measurement. Advanced cardiovascular imaging by CT, transesophageal echocardiography, or MRI should be considered if there is clinical suspicion for aortic dissection. When focal neurologic deficits or altered mentation is present, nonenhanced brain imaging by CT and, in many cases, MRI, will be needed, along with laboratory tests to evaluate for potential toxic, metabolic, or infectious causes. Hypertensive retinopathy identified on funduscopy signifies underlying TOD and, when present, is strongly associated with an enhanced risk of stroke in patients with HTN.55 Findings of acute hypertensive retinopathy include focal intraretinal periarteriolar transudates (whitish ovoid lesions deep in the retina), focal retinal pigment epithelial lesions (evidence of choroidal injury), macular and optic disk edema, and cotton wool spots (fluffy white lesions that consist of swollen ischemic axons caused by small vessel occlusion). Hard exudates, which consist of lipid deposits located deep in the retina, are also a common but late occurrence. When identified, such funduscopic abnormalities are considered diagnostic; however, they may be absent in more than 30% of patients with a clinically evident hypertensive emergency.56 Lesions of acute retinopathy are distinct from more chronic changes, which include arterial narrowing, copper or silver wiring of the arterioles, arteriovenous nicking, and retinal hemorrhages. The spectrum of retinal findings in HTN can be graded on a five-point scale (Box 74.1). Despite such value, funduscopy is infrequently performed in the evaluation of severely elevated BP in ED patients. Technical challenges and a lack of experience likely contribute to this. Nonmydriatic digital fundus photography can help overcome these issues and has shown promise as an adjunct to detect chronic and acute changes associated with hypertensive retinopathy in the ED setting.57 Although funduscopy provides useful information, whether this or any other form of diagnostic evaluation is needed in the ED for those without overt TOD is a matter of debate. Although

BOX 74.1 

Funduscopic Grading of Suspected Hypertensive Retinopathy Grade 0—normal Grade 1—minimal arterial narrowing Grade 2—obvious arterial narrowing with focal irregularities Grade 3—arterial narrowing with retinal hemorrhages and/or exudate Grade 4—grade 3 plus disk swelling

the JNC 7 has provided recommendations on routine testing in the primary care setting, there is no specific guidance for the ED.13 In the only prospective multicenter study of JNC 7–recommended routine tests (ie, basic metabolic panel, urinalysis, electrocardiography, chest x-ray) performed in the ED, clinically meaningful abnormalities were detected in only 6% of patients, none of which were definitively attributable to HTN. However, in settings where HTN-related kidney disease is prevalent (eg, predominantly African American communities),58 evaluation of renal function by a basic metabolic panel may be a reasonable consideration. Although such information is highly unlikely to affect emergent management, there is value in knowing baseline renal function and electrolyte levels, particularly if the initiation of chronic antihypertensive therapy is planned. Urine testing, especially spot measurement of the urine albumin-to-creatinine (Cr) ratio, is a reasonable alternative to detect subclinical kidney disease, although it does not provide information on electrolyte levels.59 Newer markers of renal dysfunction, including cystatin C, neutrophil gelatinase-associated lipocalin, and kidney injury molecule–1, may also be considered, but their availability in most medical centers is limited,60 and they are not indicated for an emergent evaluation. Unlike renal function, there is no simple, efficient test for detecting subclinical cardiac disease in the ED, and evaluation in this setting is guided by symptoms. Although chest x-ray and electrocardiography are often used, they have poor sensitivity for TOD (especially LV hypertrophy), and abnormalities, when identified, are unlikely to alter clinical management.61 Serum NP levels (ie, B-type NP [BNP] and N-terminal pro-BNP [NT-proBNP]) have yielded conflicting results and are not optimal screening tests, nor are they indicated for the emergent evaluation of HTN unless there is suspected cardiac TOD. Based on findings from a recent study, in which echocardiography was used as the criterion standard, the prevalence of subclinical hypertensive heart disease in select populations appears to be substantial (≈90%), suggesting the need for development of a more effective screening strategy.62 Bedside cardiac ultrasound in the ED focused on the identification of LV hypertrophy and perhaps diastolic dysfunction has shown potential for this purpose63-65; however, validation of such an approach in large prospective trials will be needed before widespread adoption can be endorsed.

MANAGEMENT Acute Blood Pressure Control Antihypertensive Therapy Antihypertensive therapy is indicated in treatment of acute hypertensive encephalopathy and in the presence of specific target organ injury (see earlier). The goal of acute antihypertensive therapy is to lower BP safely and effectively in a relatively rapid fashion while maintaining peripheral perfusion. Although some oral (ie, clonidine) or sublingual (ie, captopril, nitroglycerin)

CHAPTER 74  Hypertension

medications are capable of this, patients who truly require acute lowering of BP benefit from the predictable controlled effects of a parenteral agent by titrated intravenous (IV) boluses or by adjustable infusion. Mean arterial pressure (MAP), a summary measure that represents the average arterial pressure during one cardiac cycle, is a composite of circulatory inputs. The relationship is defined by the following equation: MAP = (CO × SVR) + CVP

where SVR reflects vasogenic tone in the arterioles (ie, afterload), CO reflects the pumping force of the heart, and central venous pressure (CVP) represents intravascular volume (ie, preload) and the effective hydrostatic force in the circulatory system. The hemodynamic response to a specific medication or class of medications is a function of how they interact with this equation and, as shown in Table 74.3, effects can differ substantially. Existing IV antihypertensive agents exert their effects directly through receptor-mediated actions (largely agonist or antagonist properties) or indirectly through a decrease in the production or release of endogenous vasoconstrictors. The magnitude of BP reduction reflects the mechanism of action as well as the pharmacokinetic and pharmacodynamic activity, with some variability in the latter based on aging. According to the STAT (Studying the Treatment of Acute hyperTension) registry, labetalol and nitroglycerin are the most common IV antihypertensive medications used in the ED,66 but outcome data related to different agents are lacking. Thus, although studies such as CLUE (Evaluation of IV Nicardipine and Labetalol Use in the Emergency Department)67 have suggested more favorable effects on BP reduction with nicardipine, a dihydropyridine calcium channel blocker, clear superiority of one drug over another has yet to be demonstrated. A general guide to IV antihypertensive therapy is provided in Table 74.4. However, depending on the desired response profile, certain agents may be more appealing than others for a specific indication.

Blood Pressure Goals Optimal treatment of a true hypertensive emergency involves therapy that is directed toward the precipitant of specific TOD and the acute consequences of elevated BP rather than the BP itself. Based on recommendations in JNC 7, the long-standing approach to acute antihypertensive therapy has been to target a maximal reduction in MAP of 20% to 25% within the first hour and a goal BP of 160/100 mm Hg by 2 to 6 hours.13 This arises from an understanding of the cerebral autoregulation curve, which maintains stable blood flow within a range of pressures (MAP of 60–160 mm Hg) under normal circumstances, but resets in chronic HTN with a shift of the lower limit toward the right. This shift tends to settle at a point approximately 25% below baseline MAP, resulting in concern for a decrease cerebral blood flow with BP reduction beyond this. Although such a consideration is relevant for patients who have poorly controlled chronic HTN, BP is often markedly elevated compared with baseline and well above the lower limit of the individual patient’s autoregulation curve in the setting of a hypertensive emergency. Consequently, a margin of safety exists in this case, with antihypertensive therapy serving to bring BP down to (rather than along) the perfusion plateau from the ascending portion of the autoregulation curve (Fig. 74.2). Use of a single BP goal for all hypertensive emergencies fails to account for this and may preclude the ability to interrupt the pathophysiology causing acute TOD effectively. Therefore, the best approach is to focus on condition-specific targets. An overview of respective treatment goals and relevant caveats for differing indications is found in Table 74.5.

Acute Coronary Syndrome and Acute Heart Failure In acute coronary syndrome complicated by HTN, the primary goal (beyond expeditious reperfusion) is a decrease in cardiac work and improved coronary artery perfusion, each of which can be dramatically affected by changes in afterload. Similarly, in

TABLE 74.3 

Hemodynamic Effect Profile of Common Intravenous Antihypertensive Medications HEMODYNAMIC EFFECT CLASSIFICATION

AGENT(S)

SYSTEMIC VASCULAR CENTRAL VENOUS CARDIAC OUTPUT RESISTANCE PRESSURE

Adrenergic inhibitors • α1-Blockers • β1-Blockers • Mixed α1–β1 blockers

Phentolamine, urapidila Esmolol, metoprolol Labetalol

↑ ↓ ↓

↓ ↑↓ ↓

↑ ↑↓ ↑↓

↑↓



↑↓

Angiotensin-converting enzyme inhibitors Enalaprilat Calcium channel blockers

a

Dihydropyridine

Clevidipine, nicardipine





↑↓

Nondihydropyridine

Diltiazem, verapamil





↑↓

Direct-acting vasodilators

Hydralazine





↑↓

Dopamine-1 receptor agonists

Fenoldopam

↑↓



↑↓

Loop diuretics

Furosemide, bumetanide, torsemide ↑↓





Natriuretic peptide receptor agonists

Nesiritide







Nitric oxide donors

Sodium nitroprusside, nitroglycerin, isosorbide dinitrate







Also has serotonin-1A (5-HT1A) agonist properties. Adapted from Levy P: Hypertensive emergencies: on the cutting edge. Advancing the standard of care: cardiovascular and neurovascular emergencies. www.emcreg.org.

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TABLE 74.4 

Guide to Intravenous Antihypertensive Therapy MEDICATION BY CLASS

BOLUS OR LOADING DOSE

INFUSION RATE

TIME TO ONSET

DURATION OF ACTION COMMENTS

ADRENERGIC INHIBITORS Phentolamine

5–15 mg q5min

0.2–0.5 mg/min

1–2 min

10–30 min

Avoid with coronary artery disease

Urapidil

12.5–50 mg q5min

9–30 mg/hr

1–2 min

2.5 hr

Not FDA approved

Esmolol

0.5–1 mg/kg × 1

50–300 µg/kg/min

1–2 min

20 min

Metoprolol

5 mg q5min

None

10–30 min 5–8 hr

Labetalol

20–80 mg q10min

1–2 mg/min

2–5 min

0.625–1.25 mg q15min

1–2 mg/hr

15–30 min 6–12 hr

3–6 hr

Beta blocker effects predominate (1:7)

ACE INHIBITOR Enalaprilat

May produce prolonged hypotension; avoid in pregnancy

CALCIUM CHANNEL BLOCKERS Clevidipine

None

2–32 µg/hr

1–2 min

1–5 min

Nicardipine

None

5–15 mg/hr

5–15 min

4–6 hr

Avoid with aortic stenosis and liver failure (hepatic metabolism)

Diltiazem

0.25–0.35 mg/kg q15min

5–15 mg/hr

5–15 min

6 hr

Will decrease blood pressure but not often used for this indication

Verapamil

2.5–5 mg IV q15min

None

5–15 min

6 hr

1.5–5 µg/kg/min

10–20 min 2–4 hr

Causes reflex activation of the sympathetic nervous system

None

0.1–0.3 µg/kg/min; titrate by 0.1 µg/kg

130 mm Hg), lower targets are indicated (BP, 160/90 mm Hg, or MAP, 110 mm Hg). Although reasonably informative, these guidelines were developed based on incomplete efficacy data that included limited

information on the ideal time to achieve BP targets. Results from the recent Second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2; N = 2829) augment the AHA/ASA guidelines and indicated the following: (1) an association between intensive antihypertensive therapy targeting a systolic BP of 140 mm Hg within 1 hour; and (2) improved functional outcome at 90 days for patients with a baseline systolic BP between 150 and 220 mm Hg, although no difference in mortality or major disability was found.84 However, in a recent post hoc analysis of INTERACT2, patients who achieved a reduction in systolic BP of 20 mm Hg or more within the first hour of treatment (N = 1092) were 35% less likely to experience a poor outcome, suggesting that optimal recovery from acute ICH requires early, intensive antihypertensive therapy.85 Data from the Antihypertensive Treatment of Cerebral Hemorrhage (ATACH II) study (NCT01176565), which has enrolled 1280 patients and has included an intervention arm of target systolic BP lower than 140 mm Hg within 4.5 hours

CHAPTER 74  Hypertension

A

B

C

Fig. 74.3.  Serial electrocardiograms demonstrating resolution of relative myocardial ischemia in a profoundly hypertensive patient with acute heart failure after treatment with high-dose intravenous nitroglycerin. A, BP, 241/122 mm Hg. Anterior leads (V1–3) show ST segment elevation and lateral leads (V5–6) show ST depression. B, BP, 192/103 mm Hg. Anterior lead ST elevation has resolved, but lateral lead ST depressions persist. C, BP, 150/92 mm Hg. ST segment deviations have largely resolved.

of ICH onset, will have provided much needed additional insight into the timing and intensity of BP control in this patient population.86 As with ischemic stroke, labetalol and nicardipine are the preferred agents for acute BP reduction. However, in INTERACT2, the choice of antihypertensive therapy was at emergency clinician

discretion and urapidil, an α-adrenergic antagonist, was the most commonly used agent (32.5%) in the intensive treatment arm, followed by nitroglycerin or nitroprusside (27.0%), nicardipine (16.2%), and labetalol (14.4%). Whether such heterogeneity in antihypertensive therapy may have influenced outcomes is not known, making the pending ATACH-II study, in which nicardipine

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is being used exclusively, all the more important. Nimodipine, an oral dihydropyridine calcium channel blocker, is specifically indicated for patients with subarachnoid hemorrhage, although its benefit appears to be related more to a reduction in intracranial arterial vasospasm than to an effect on SVR.

below 1%—or for those on chronic diuretic therapy, a fractional excretion of urea (FEurea); calculated as

Hypertensive Encephalopathy

below 35%—serve as indictors of a prerenal cause. When antihypertensive therapy is indicated, fenoldopam, a potent dopamine 1A receptor agonist, is preferred because it leads to improved perfusion of the corticomedullary region and has been associated with a reduction in need for subsequent dialysis and rate of in-hospital death. Enalaprilat should be avoided because it produces differential effects on the precapillary and postcapillary glomerular vascular bed (ie, greater vasodilation in efferent than afferent arterioles), which increases the risk of further deterioration in estimated GFR. Peripheral-acting calcium channel blockers, such as clevidipine and nicardipine, have no adverse effect on glomerular autoregulation and are acceptable first-line alternatives to fenoldopam. Other agents, including labetalol and sodium nitroprusside, may also be used.

Unlike acute stroke syndromes, in which HTN may be reactive rather than causative, a direct association exists between the degree of BP elevation and neurologic symptoms in patients with hypertensive encephalopathy. Once alternative causes of altered mentation have been ruled out, therapy should be directed toward the initiation of rapid BP reduction. The goal is to return BP to a point at which autoregulation can regain control of cerebral blood flow and the process leading to cerebral edema can be reversed—a circumstance that necessitates MAP to be brought back down to the pressure curve plateau. To achieve this, reductions in MAP of 30% to 40% may be needed. Whereas MAP targets should still be kept in mind, symptom resolution is the best gauge of therapeutic effectiveness, with treatment directed specifically toward improvement of encephalopathy. The agents of choice for BP reduction in hypertensive encephalopathy are labetalol and nicardipine because they produce an even decrease in resistance across vascular beds in different organ systems. In contrast, NO donors (nitroglycerin and nitroprusside), although widely used for this indication, have a differential effect on the cerebral and systemic circulations, resulting in a relative increase in cerebral BP and a shunt effect to the peripheral circulation. This serves to decrease cerebral blood flow and may produce a greater than anticipated reduction in cerebral perfusion, thereby increasing the risk of ischemia in watershed areas of the brain. This may be worsened by the relative increase in intracranial pressure known to occur with sodium nitroprusside therapy. Several case reports have described neurologic deterioration with administration of nitroglycerin in posterior reversible encephalopathy syndrome (PRES), a subtype of hypertensive encephalopathy, supporting this as an actual rather than theoretical concern.87 Similar differential circulatory effects may also occur with hydralazine (a direct-acting vasodilator that inhibits calcium release from the sarcoplasmic reticulum) and, unless BP is completely refractory to other therapy, it is best to avoid use of these agents.

Acute Kidney Injury Defined by an increase in serum creatinine level of 0.3 mg/dL or more in 48 hours, 1.5 or more times baseline in 7 days, or a urine volume of less than 0.5 ml/kg/hr over 6 hours,88 acute kidney injury (AKI) represents an abrupt worsening of renal function. Although often a manifestation of ongoing glomerular injury from chronic poor BP control, deterioration of kidney function in the setting of severe HTN may be precipitated by prerenal causes, including volume depletion (often related to concurrent diuretic therapy), extrinsic alterations in the GFR (often triggered by drug-mediated, afferent arteriolar vasoconstriction and ACE inhibitor–induced autoregulatory modulation) or intrinsic nephron destruction caused by acute pressure overload. Consequently, some patients require fluid administration to augment volume, whereas others need antihypertensive therapy to mitigate pressure-mediated nephrogenic damage. Laboratory testing is useful to differentiate which approach should be initiated. A blood urea nitrogen (BUN)/Cr ratio higher than 20 and a fractional excretion of sodium (FENa); calculated as Urine Na × Serum Cr ×100 Serum Na × Urine Cr

Serum Cr × Urine urea ×100 Serum urea × Urine Cr

Preeclampsia and Eclampsia Although delivery is the definitive treatment, BP control is a critical part of early management.89 Similar to hypertensive encephalopathy, preeclampsia and, to a greater degree, eclampsia, represent an overwhelming of cerebral autoregulation, and rapid BP reduction is essential. Because they are acute (rather than chronic) complications in a relatively healthy young population, there is generally no resetting of the autoregulation curve in preeclampsia or eclampsia, and adverse consequences can develop at seemingly “low” (but relatively high) pressures. The threshold for intervention, therefore, is set lower than with other hypertensive emergencies (ie, systolic BP exceeding 160 mm Hg).90 Magnesium sulfate is considered first-line therapy for all cases of preeclampsia and eclampsia.91 It relaxes smooth muscle (partly through calcium antagonism), which leads to some decrease in peripheral and cerebral vascular resistance, limits cerebral edema formation by protecting the blood-brain barrier, and has central anticonvulsant activity. However, its antihypertensive effects are modest, and additional treatment is typically needed to control BP. Hydralazine and labetalol by IV bolus are equally effective for this purpose and have a limited impact on placental blood flow.92 Nicardipine is a reasonable alternative and may produce a more profound decrease in BP than labetalol.

Sympathetic Crises Hyperadrenergic states can result from endogenous sources of catecholamine excess (ie, pheochromocytoma) but, more commonly, they are triggered by the intake of exogenous substances that interfere with norepinephrine—and to a lesser degree, epinephrine—metabolism, such as cocaine, amphetamines, and tyramine-containing foods, especially in patients on monoamine oxidase inhibitors. The net result is a cardiostimulatory and vasopressor response that manifests clinically as tachycardia and marked HTN. In patients with cocaine or amphetamine intoxication, such peripheral effects are compounded by central sympathetic activation, and the hemodynamic derangements can often be improved by the administration of benzodiazepines and other sedative medications. When BP is persistently elevated and target organ compromise is present, antihypertensive treatment will be needed. Phentolamine, a reversible pure alpha blocker, is considered first-line therapy, producing a reliable decrease in peripheral and coronary vasoconstriction, with few adverse effects. Nitroglycerin can also be used and is specifically indicated for patients with associated

CHAPTER 74  Hypertension

Untreated chronic hypertension or a new diagnosis? • Start thiazide diuretic. • Hydrochlorothizide 25 mg qd • Chlorthalidone 25 mg qd

Uncontrolled chronic hypertension on monotherapy? • Start dual therapy, adding a new class of medication. • Calcium channel blocker • Amlodipine 5 mg qd • Angiotensin-converting enzyme inhibitor • Lisinopril 10–20 mg qd • Angiotensin receptor blocker • Losartan 50 mg qd • Thiazide diuretic (if not already on one)

Uncontrolled chronic hypertension on dual therapy? • Double medication dose up to maximum. • Add on third class of medication.

Fig. 74.4.  Modified approach to initiation and escalation of antihypertensive therapy for use in ED patients Note that the proposed medications are representative of listed classes and may be substituted with equally dosed alternatives agents in the same class, as needed.

chest pain and suspected coronary artery vasospasm. Other agents, including fenoldopam, clevidipine, nicardipine, and sodium nitroprusside, are acceptable alternatives. Heart rate control may also be needed, especially in patients with pheochromocytoma, in whom adrenal release of epinephrine may be particularly high, and a short-acting beta blocker such as esmolol is ideal for this purpose. However, to avoid precipitation of unopposed alpha receptor activity and a worsening of HTN, beta blocker therapy should be paired with a vasodilator. Although labetalol has combined alpha and beta blocker properties, beta receptor effects strongly predominate when the drug is administered in IV form (alpha/beta ratio of 1:7). Consequently, IV labetalol is susceptible to a similar differential response and should be used with caution in the setting of catecholamine excess.

Chronic Antihypertensive Therapy Poorly controlled chronic HTN on a single visit or a clear trend toward persistently elevated BP over time requires referral for timely follow-up, with reinforcement of goal BP recommendations and emphasis on the need for lifelong dietary and medication compliance. Initiation of oral antihypertensive therapy for new-onset HTN and re-initiation or uptitration for patients with chronic HTN is appropriate from the ED if follow-up cannot be ensured.93 Although it is unclear whether this practice will have any impact on long-term outcomes, it is associated with a substantial reduction in BP at follow-up and appears to be safe.94 Although there are multiple medication options, a relatively simple algorithm for prescribing chronic antihypertensive therapy has been proposed by the AHA, starting with a thiazide diuretic for most patients.95 Calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers (ARBs) are included as acceptable first-line alternatives and recommended as add-ons for patients with persistent, poorly controlled BP. Because most patients with stage II HTN will ultimately require multiple agents to control their BP, initiation of two-drug therapy when the systolic BP is higher than 160 mm Hg or diastolic BP higher than 100 mm Hg is recommended.13 There is increasing evidence that improved compliance with reduced side effects and outcome benefit can be achieved using low-dose combination tablets, especially combined ACE inhibitors and thiazide-like diuretics.96-99 The general approach proposed by the JNC 8 is similar but includes specific recommendations about the use of thiazide diuretics or calcium channel blockers as first-line therapy in blacks and ACE inhibitors or ARBs in patients with chronic kidney disease.14 However, unlike the JNC 7, preferential use

of ACE inhibitors or ARBs in diabetic patients is no longer recommended in JNC 8, and lower BP targets (ie, 100 beats/min

+++

  , ventilation−perfusion ratio. DVT, Deep vein thrombosis; PE, pulmonary embolism; V/Q

thrombophilia has no value in the ED setting, or any other setting.28

Clinical Features Symptoms vary widely during this process, ranging from no symptom to cardiovascular collapse. The patient can feel focal, sharp, pleuritic pain and exhibit a splinting response to breathing. Over several days, the infarcted segment becomes consolidated on chest radiography and exudes a pleural effusion, manifesting an intense underlying inflammatory process. Chest pain from noninfarcting PE can be highly variable and vague, with as many as 30% of patients with definite PE having no perception of chest pain.29 In contrast, if asked in a detailed and structured way, approximately 80% of patients with PE admit to having some sensation of dyspnea.29 The dyspnea may be constant and oppressive or may be intermittent and perceived only with exertion, possibly due to an exercise-induced increase in pulmonary vascular resistance.

Pulmonary embolism can produce hypoxemia (pulse oximetry reading 4 or sRGS >4

Moderate (15-40%) or Wells ≤4 or sRGS ≤4

PERC rule

Consider LMWH if no contraindication –

+ Order imaging

No PE

Quant Ddimer*

4, sRGS > 4, or presence of other high risk factors (eg, unexplained hypoxemia, third trimester) +

PERC rule

Option 1

Option 2



Abnormal

CXR

Shared decisionmaking: Quant Ddimer*

Q or VQ scan

Normal 1st 2-hour delay to catheter directed thrombolysis anticipated: Large clot burden on CTPA1 and Yes episodic hypotension (SBP 1.0 or SaO2 left ventricle (LV) on CT scan; reflux of contrast into inferior vena cava (IVC) and liver. Abnormal echographic findings include dilated or hypokinetic RV and estimated RV systolic pressure > 40 mm Hg.84,85 Elevated biomarkers include brain natriuretic peptide (BNP) level > 90 pg/mL pro-BNP level > 900 pg/mL, or any troponin concentration > 99th percentile for normal, with 1.7); 9, surgery that required opening of the chest cavity, peritoneum, skull, or spinal canal within the previous 14 days; 10, subacute bacterial endocarditis under treatment; 11, pregnancy; 12, large pericardial effusion. Relative contraindications: age > 75 years; dementia; surgery more than 30 days but less than 60 days prior; any prior stroke; symptoms suggesting transient ischemic attack in the past 30 days; any prior gastrointestinal bleeding; concurrent use of a thienopyridine (eg., clopidogrel); INR > 1.7 from warfarin use; any metastatic cancer, tongue bites, recent fracture, recent fall with head strike, history of hematuria, nosebleeds, recent dental extraction, or orthopedic surgery. HR, Heart rate; SBP, systolic blood pressure.

CHAPTER 78  Pulmonary Embolism and Deep Vein Thrombosis

Standard Anticoagulation Patients with a high PTP, no contraindication to anticoagulation, and evidence of hemodynamic instability, including recent syncope, any hypotension, hypoxemia, or clinical evidence of right heart strain (criteria defined in Table 78.4 as more severe moderate PE or high-risk PE) should receive empirical heparin prior to waiting for the results of pulmonary vascular imaging. Patients with a positive imaging for DVT or PE should receive anticoagulation using one of the agents in Table 78.3, administered in the ED as soon as the diagnosis is confirmed.66 Low-molecular-weight (LMW) heparin is advantageous when compared to unfractionated heparin based on robust meta-analyses that have clearly demonstrated lower rates of major hemorrhage, heparin-induced thrombocytopenia, and VTE, with similar cost.67 Patients can now be anticoagulated in the ED with apixaban (Eliquis) or rivaroxaban (Xarelto), which are orally available agents that specifically inhibit one enzyme in the clotting pathway. These drugs can be started without prior or concomitant use of heparin, and they provide therapeutic anticoagulation effect as rapidly as subcutaneous LMW heparin (see Table 78.3). By obviating the need for twice-daily subcutaneous injections and blood monitoring, these drugs can facilitate outpatient treatment of DVT and PE. Patients with a history of heparin-induced thrombocytopenia should receive fondaparinux, argatroban, apixaban, or rivaroxaban. Most hematologists, internists, and obstetricians prefer that pregnant patients with VTE receive twice-daily LMW heparin.68 The anticoagulant effect of unfractionated heparin can be almost completely and rapidly reversed with protamine, whereas LMW heparin can only be 50% neutralized with protamine. Protamine has no effect on fondaparinux, rivaroxaban, or apixaban. At present, based on data in healthy volunteers, the best agent to correct coagulopathy from apixaban or rivaroxaban is four-factor activated prothrombin complex (Beriplex P/N or K-Centra, 50 U/ kg, IV).69,70 No clinical trials have been published to test the effect of these agents on bleeding in people with apixaban or rivaroxaban coagulopathy. Regarding isolated subsegmental PE, if the patient has no evidence of DVT on bilateral lower extremity ultrasonography, no signs of cardiopulmonary stress (eg, normal biomarkers, normal ECG), and no ongoing major risk for thrombosis (eg, active malignancy, atrial fibrillation), it is reasonable and prudent to withhold anticoagulation for patients with isolated subsegmental filling defects on CTPA.71 If a patient with a negative CTPA scan has ongoing dyspnea and signs of pulmonary hypertension— enlarged right ventricle,72 enlarged pulmonary artery, or reflux of contrast into the liver, the mosaic pattern, acute pulmonary hypertension on the ECG73—or hypoxemia without an apparent alternative cause, at minimum, the patient should have transthoracic echocardiography performed. If this demonstrates pulmonary hypertension or right ventricular overload, the patient should be referred or admitted to a pulmonary specialist to guide further testing.40,41 Recent evidence has indicated that up to 50% of outpatients diagnosed with PE may be stable enough to be treated as outpatients (low-risk criteria; see Table 78.4).74,75 In settings where good follow-up can be obtained, and the patient can be taught to selfadminister LMW heparin and can access an anticoagulation clinic within 48 hours, a low-risk patient with PE can be discharged from the ED. My choice, however, is to implement a protocol that includes the Hestia criteria to select low-risk patients (see Box 78.1), together with monotherapy with apixaban or rivaroxaban; this has been associated with low rates of complications and economic advantages.26,76 For a patient diagnosed with PE in the presence of a major contraindication to anticoagulation, such as a recent cerebral hemorrhage or large cerebral infarction, or brain metastases, the

appropriate consultant should be contacted for urgent placement of an inferior vena cava filter. If vena caval interruption cannot be performed within 12 hours, one option is to perform a baseline head CT scan, start an unfractionated heparin infusion at 18 U/ kg/hr (without a bolus), and admit the patient to the intensive care unit for close neurologic monitoring and frequent partial thromboplastin time (PTT) determinations. The rationale for using unfractionated heparin is that it can be reversed more reliably by discontinuing the heparin drip and administering protamine, 1 mg/kg IV, than fractionated heparin. Case reports and series have suggested that inhaled nitric oxide might be helpful for patients with severe PE and an absolute contraindication to anticoagulation, but this treatment has not yet been subjected to rigorous study.77 Most patients with PE state that they feel better the day after starting heparin anticoagulation, and more than half go on to nearly a full recovery of pre-PE health status. The in-hospital mortality rate of patients diagnosed with PE who remain hemodynamically stable while in the ED was thought to be 10%, but a recent large, multicenter, US-based registry of 1880 patients diagnosed with PE in the ED found the in-hospital mortality rate directly attributable to PE as 1.1% and an all-cause mortality rate of 5.4%.29 Approximately 10% to 20% of PE survivors complain of persistent dyspnea and exercise intolerance that permanently degrades their quality of life.78

Fibrinolytic (Thrombolytic) Therapy Fibrinolytic therapy in PE remains a controversial treatment option. Recent meta-analyses of randomized trials that compared fibrinolysis plus heparin to heparin alone have reached different conclusions about mortality benefit, with one study finding significant improvement79 and another no difference80 in mortality. Most experts, even those generally opposed to fibrinolysis, believe that patients with arterial hypotension (systolic blood pressure < 90 mm Hg or >40-mm Hg drop from baseline) should receive full-dose systemic fibrinolysis (100 mg of alteplase over 2 hours or tiered-dose tenecteplase, per the TNKase label). No one doubts that the bleeding risk increases with systemic fibrinolysis, but the risk of intracranial hemorrhage appears to be mostly confined to patients older than 65 years.79 The “to lyse or not to lyse PE” controversy has been made more complex by recent studies suggesting a possible lower risk of significant hemorrhage associated with the lower, half-dose alteplase (50 mg over 2 hours), administered by peripheral vein.81 Moreover, many large treatment centers have adopted the use of catheter-directed thrombolysis, which administers the fibrinolytic directly into the thrombus, with or without adjunctive ultrasonic energy.82 The potential advantage of this approach is a lower risk of hemorrhage due to the lower dose of fibrinolytic agent (eg, 20–25 mg of alteplase infused intrathrombus over 24 hours.) No evidence has yet demonstrated a survival advantage or any patient-oriented advantage of catheter-directed therapy. However, one small randomized trial has demonstrated improved quality of life end points with bolus administration of tenecteplase for severe submassive PE.83 The clinical course of patients with obstructive PE can be unpredictable. Many patients with massive PE remain stable in the ED. Other patients are stable on arrival, but progressively deteriorate over hours as right ventricular function declines. Of ED patients without hypotension, 3% experience cardiac arrest while in the ED and die within 24 hours.33 A patient can be stable and then hypotensive within minutes because of the highly variable effect of the clot on right ventricular outflow obstruction, especially when it straddles the main pulmonary artery (Fig. 78.12). Additional mechanisms of rapid instability include new embolization of clot material, release of mediators of pulmonary vasospasm, sudden bradyasystolic arrhythmias, and respiratory

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Vascular System

A

narrow-complex tachycardia to an incomplete right bundle branch block to a complete right bundle branch block (Fig. 78.13) is evidence of life-threatening pulmonary hypertension and impending cardiac arrest. Clinical evidence of impending or actual respiratory failure indicates the need for prompt endotracheal intubation using a standard rapid sequence intubation technique, preferably with ketamine or etomidate for induction of anesthesia with neuromuscular blockade. Other induction agents that depress cardiac function or reduce preload may precipitate severe hypotension and should be avoided or their dosage reduced. The effect of biphasic, positive pressure–assisted noninvasive ventilation (BiPAP) on hemodynamics with massive PE has not been studied. For patients with PE and persistent hypotension, the role of volume loading to resuscitate massive PE remains uncertain. Most experts use norepinephrine as the vasopressor of choice to attempt to increase blood pressure. In the case of impending respiratory or cardiac arrest, fibrinolytic therapy should be strongly considered.

Surgical Embolectomy

B Fig. 78.12.  CT evidence suggesting more severe PE. A, Proximal pulmonary embolism on a contrast-enhanced CT scan of the chest. This CT scan is at the level of the bifurcation of the main pulmonary artery. The left main branch of the pulmonary artery shows a massive filling defect (arrows). B, Evidence of right ventricular strain, shown by the larger size of the right ventricle compared with the left ventricle.

For patients with known floating thrombi in the right heart or patients with severe refractory hypotension, surgery is the most likely intervention to save the patient’s life. Surgical embolectomy commonly includes extracorporeal cardiopulmonary bypass and an experienced cardiothoracic surgeon. Surgical embolectomy may be the best option for patients who have severe PE with a contraindication to fibrinolysis; however, extracorporeal perfusion requires intensive heparin anticoagulation, and the patient’s mental status cannot be monitored during surgery—a key concern in patients with a high risk of intracranial hemorrhage. Numerous case reports have suggested heroic results from the bolus administration of thrombolytic therapy to patients with cardiac arrest from PE. The administration of fibrinolytic therapy does not absolutely preclude surgical intervention. Patients who have been treated with a fibrinolytic agent can undergo sternotomy or thoracotomy for embolectomy and survive without fatal hemorrhage. The decision to perform embolectomy ultimately resides with the cardiac surgeon.

Disposition failure. Clues to oncoming cardiopulmonary decompensation include worsening respiratory distress and worsening hypoxemia, rising shock index (the heart rate divided by the systolic blood pressure), systolic arterial blood pressure less than 90 mm Hg, and syncope or a sharp change in mental status, including seizurelike convulsive episodes. Deterioration in the ECG from a

Table 78.5 summarizes the criteria that can be used to risk-stratify patients with PE into four groups. This stratification may help guide the decision to place the patient in an intensive care unit versus an intermediate or regular inpatient bed and whether to administer heparin only or consider escalated therapy (see Fig. 78.11).

CHAPTER 78  Pulmonary Embolism and Deep Vein Thrombosis

A

B

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Fig. 78.13.  Serial electrocardiograms obtained 2 minutes apart show the progression from a narrow complex rhythm (A) to a right bundle branch block pattern (B) in a patient with massive bilateral pulmonary emboli. Shortly after the second tracing was obtained, the patient developed cardiovascular collapse refractory to vigorous resuscitation efforts.

TABLE 78.5 

Risk Stratification and Associated Treatment Recommendations for Acute PE CATEGORY

CRITERIA

ACTION

89

Low-risk PE

• Begin anticoagulant treatment sPESI of 0 (see Table 78.3) Hestia criteria negative (see Box 78.1)90 • Optional admission to unmonitored SBP > 90 mm Hg at all times and all of the following: no proximal clot or RV regular bed dilation on CTPA, shock index < 1, SaO2 > 94%, no pulmonary hypertension • Consider outpatient treatment if adequate on ECG (Daniel score < 3), normal troponin, BNP, or pro-BNP level • Compliance and follow-up can be assured

Moderate-risk PE

SBP > 90 mm Hg at all times and any one of the following: Proximal clot and RV > LV on CTPA scan (see Fig. 78.12)72,84,85,88 Elevated troponin or BNP level (>90 pg/mL) or pro-BNP level (>900 pg/mL) Echocardiogram with any degree of right ventricular hypokinesis

More severe Any moderate risk criteria and appearance of at respiratory distress (submassive); Shock index > 1 and severe right ventricular hypokinesis on echocardiography moderate-risk PE Worsening Daniel score, particularly a new incomplete right bundle branch block (RBBB) or progression of incomplete RBBB to complete RBBB SaO2 < 90% and serum troponin level clearly elevated New altered mental status High-risk (major) PE

Any SBP 25 mg/dL, or serum sodium level < 130 mmol/L). If a high-risk patient with ascites is identified in the ED and contraindications are absent, prophylactic therapy should be initiated. Finally, in patients with ascites secondary to cirrhosis, the prevention of SBP should also include consideration of discontinuation of proton pump inhibitors, which adversely alter acid secretion and gut flora, and beta blockers, which may increase risk secondary to their resultant systemic hypotension. Patients with diagnosed SBP require hospitalization and will ultimately need a referral to a primary care physician or gastroenterologist for close outpatient follow-up. Most patients with SBP will not require repeat abdominal paracentesis. In those with inconsistent symptoms, abnormal treatment response, atypical organisms, or recent β-lactam exposure, repeat paracentesis may help differentiate secondary bacterial peritonitis requiring surgical interventions.

HEPATIC ABSCESSES

Fig. 80.9.  Contrast CT scan of liver showing large cystic masses (black arrow, white arrow) with irregular, contrast-enhancing borders in a patient with pyogenic liver abscess caused by Streptococcus milleri.

Hepatic abscesses fall into two broad categories, pyogenic and amebic. Although there may be similarities in clinical presentation, the pathophysiology and treatment differ significantly.

Pyogenic Abscess Principles Liver abscesses are usually associated with biliary tract obstruction or cholangitis but may be related to diverticulitis, pancreatic abscess, omphalitis, appendicitis, inflammatory bowel disease, pneumonia, or bacteremia. Often, no underlying cause for hepatic abscess is identified. Solitary and multiple abscesses occur with approximately equal frequency, usually in the right lobe of the liver. Patients with multiple lesions tend to be more severely ill, with less favorable outcomes. Causative organisms may be anaerobic and aerobic; E. coli, Klebsiella, Pseudomonas, and Enterococcus spp., anaerobic streptococci, and various Bacteroides spp. are usually isolated.

Fig. 80.10.  Contrast CT scan of liver showing pyogenic liver abscess. This complex cystic mass with air-fluid level (arrow) was caused by gasproducing Klebsiella pneumoniae.

Clinical Features The clinical presentation is characterized by the onset of high fever, chills, right upper quadrant (RUQ) pain, nausea, and vomiting. Patients generally have an acute presentation and appear quite ill, particularly if there is underlying cholangitis. Physical findings include elevated temperature, RUQ tenderness, hepatomegaly, and occasionally dullness to percussion and decreased breath sounds over the right lower chest. Jaundice may be apparent, especially if coexistent biliary tract obstruction is present.

Differential Diagnosis The differential diagnosis of pyogenic hepatic abscess includes amebic liver abscess, hepatitis, cholangitis, and pancreatic and subphrenic abscesses.

Diagnostic Testing Laboratory findings include leukocytosis in 70% to 80% of cases, elevated alkaline phosphatase levels in up to 90%, and bilirubin level in excess of 2 mg/dL in 50% of patients. Although blood culture sensitivities are approximately 30% in patients with pyogenic abscesses, they should be determined in advance of treatment and while awaiting definitive drainage and testing from the abscess site. Serum aminotransferase levels commonly are elevated 2 to 4 times normal. Chest radiographs may reveal a

right pleural effusion, basilar atelectasis, and/or an elevated right hemidiaphragm. The most useful, sensitive, and expeditious imaging modalities include ultrasonography and CT (Figs. 80.9 and 80.10).

Management The initial treatment of a pyogenic hepatic abscess is hemodynamic stabilization, IV antibiotics, and pain control. Pending definitive microbial identification, broad-spectrum antibiotic coverage should be initiated and continued for 2 to 6 weeks, depending on the size of the abscess and patient response. Although there has been no consensus on treatment regimens, IV antibiotic coverage targeting gram-negative bacteria and anaerobes is recommended. This may include cefotaxime (2 g tid) plus metronidazole (500 mg tid) or ampicillin (2 g qid) in conjunction with gentamycin (1.7 mg/kg tid) and metronidazole or monotherapy with piperacillin-tazobactam (3.375 IV qid), imipenem, or meropenem. The addition of vancomycin is indicated for an acutely ill or unstable patient, as well as any patient with grampositive cocci on staining or when suspicion for enterococcal or staphylococcal organisms is high. Fluoroquinolones, although often combined with metronidazole for continuation of treatment as an outpatient, should be avoided in areas with E. coli resistance greater than 10%.25

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Gastrointestinal System

Definitive treatment for abscesses larger than 3 cm requires drainage. This usually is done percutaneously under image guidance, reserving open surgical drainage only for complex cases associated with intraperitoneal soiling, intestinal perforation, or biliary obstruction. Complications include rupture of the abscess into the peritoneal cavity or an adjacent anatomic structure (eg, thoracic cavity, lung, pericardium).

Disposition Patients with pyogenic hepatic abscess require hospitalization. Consultation with a general surgeon, gastroenterologist, or interventional radiologist will be necessary.

Amebic Abscess Principles Amebiasis is one of the most common protozoal infections worldwide. Transmission generally occurs by the fecal-oral route, often as a consequence of ingesting contaminated water or foodstuffs. Although intestinal disease is by far the most common manifestation of infection, extraintestinal disease can occur, with the liver most commonly affected. Entamoeba histolytica is the only ameba responsible for invasive disease, and only certain varieties of E. histolytica are pathogenic after invasion of the intestinal mucosa and transit through the portal vein. As with a pyogenic abscess, involvement of the right liver lobe is more common.

Clinical Features The clinical presentation generally is acute with fever, chills, nausea, vomiting, and abdominal pain. Diarrhea is common in children but is present in less than one-third of adults. Careful questioning of patients without diarrhea often yields a history of intestinal illness several weeks prior to presentation. Many patients complain of cough, which may direct attention away from the liver. A chronic illness of several months’ duration, although less common than the acute presentation, can occur. Physical findings include an elevated temperature, RUQ tenderness, hepatomegaly, and dullness, with decreased breath sounds over the right lower chest.

Differential Diagnosis In order of their frequency of occurrence, the differential diagnosis includes pyogenic abscess, biliary tract disease, hepatitis, pneumonia, appendicitis, and pancreatitis. Respiratory symptoms and abnormalities on the chest radiograph may cause confusion with pulmonary illnesses. Hepatic imaging is helpful in establishing the diagnosis; however, differentiation from pyogenic illness is difficult and requires additional laboratory testing.

Diagnostic Testing Laboratory findings in patients with an amebic abscess are not specific. Neutrophilic leukocytosis is common. The alkaline phosphatase level is elevated in 75% of cases and aminotransferase levels in 50%. Hyperbilirubinemia is uncommon and, when present, is indicative of biliary obstruction. The chest radiograph may reveal a right pleural effusion, basilar atelectasis, or elevated right hemidiaphragm. Ultrasound of the liver may reveal specific findings unique to amebic abscess, specifically a peripherally based, round or oval mass, with a well-circumscribed border and homogeneous hypoechoic center (Fig. 80.11). CT and magnetic resonance imaging (MRI) are alternative abdominal imaging modalities if ultrasonography is inconclusive. The diagnosis is

Fig. 80.11.  Ultrasound of the liver demonstrating amebic abscess showing a peripherally located abscess with a homogeneous, hypoechoic center (arrow).

supported by identification of a pathogenic protozoan in the stool. Even in cases of invasive intestinal disease, the yield may be low. An enzyme-linked immunosorbent assay (ELISA) and counterimmune electrophoresis are the recommended diagnostic tests. The indirect hemagglutination test remains positive for an extended period and is therefore not helpful in establishing the presence of acute infection.

Management Management of an amebic abscess consists of supportive therapy and initiation of amebicidal therapy. Metronidazole, 750 mg PO or IV tid for 7 to 10 days, is the therapeutic agent of choice. Most patients will respond to this regimen with percutaneous catheter drainage required only in refractory or complicated cases. The most serious complication of amebic liver disease is rupture into adjacent anatomic structures. Involvement of the lung occurs in 20% to 35% of cases of extrahepatic disease, often manifesting as a massive pleural effusion or consolidative pneumonia. With rupture into a bronchus, the patient can have cough productive of an anchovy paste–like substance or necrotic debris or frank hemoptysis. Abdominal pain with peritonitis can result from rupture into the abdominal cavity. Involvement of the pericardium occasionally is seen with lesions in the left lobe of the liver and can be catastrophic, either acutely as a consequence of pericardial tamponade or chronically from constrictive pericarditis.

Disposition Select patients with amebic liver abscess can be managed as outpatients. This approach is best suited for those with mild clinical disease, stable living circumstances, and adequate access to medications and follow-up care. In patients with more severe disease, evidence of complications, or questionable social circumstances, hospitalization is advised.

MISCELLANEOUS DISORDERS AND CONDITIONS OF THE LIVER Liver Disease in Pregnancy The two primary hepatic disorders associated with pregnancy are benign cholestasis and acute fatty liver.

CHAPTER 80  Disorders of the Liver and Biliary Tract

Benign Cholestasis Benign cholestasis during pregnancy is common and has a familial linkage. Onset is in the third trimester and is heralded by the development of progressive pruritus. The bilirubin level may be elevated but not dramatically, so jaundice is uncommon. Laboratory tests reveal elevated alkaline phosphatase, 5′-nucleotidase, and bilirubin levels. Although the chief concern to the mother is discomfort from pruritus, the illness can bode poorly for the fetus, with an increased incidence of prematurity, stillbirth, and fetal distress. Malabsorption of vitamin K can result in serious coagulopathy in the fetus, predisposing to spontaneous intracranial hemorrhage. Treatment is supportive and should include subcutaneous vitamin K for the mother antepartum and for the newborn after delivery. Cholestasis resolves without incident after delivery.

Acute Fatty Liver Acute fatty liver of pregnancy is a malignant disorder that if unrecognized, can progress rapidly to maternal and fetal demise. The illness occurs in the latter part of the third trimester and is more common in primigravidas and twin pregnancies. The initial clinical features include fatigue, anorexia, nausea, and vomiting. Physical findings include mild jaundice and abdominal tenderness, most prominently in the midepigastrium and right upper quadrant. The liver may not be palpable because of the enlarged uterus. Abnormal laboratory findings include moderate elevation of aminotransferase levels (5 to 10 times normal) hyperbilirubinemia, hypoglycemia, and evidence of disseminated intravascular coagulation—prolonged PT and partial thromboplastin time, hypofibrinogenemia, elevated fibrin split products, and thrombocytopenia. Treatment involves aggressive fluid and electrolyte support, glucose administration, and immediate delivery. Liver disease in pregnancy generally resolves without permanent sequelae after delivery.

Budd-Chiari Syndrome Budd-Chiari syndrome is caused by hepatic venous outflow obstruction located anywhere above the level of hepatic venules. The disorder is associated with hypercoagulable states, such as factor V Leiden, protein S and C deficiency, thrombophilia, antithrombin III deficiency, myeloproliferative disorder, Behçet’s disease, paroxysmal nocturnal hemoglobinuria, and oral contraceptive use. The clinical presentation varies from fulminant hepatic failure in acute high-grade obstruction to the insidious onset of jaundice to ascites in more subacute forms. Clinical symptoms correlate with the degree of venous obstruction and rate of venous occlusion. Fulminant disease is clinically indistinguishable from acute hepatic necrosis and hepatocellular disease secondary to viral infection. It is important to make the distinction between these two causes of hepatic failure early because treatment options differ. Prompt intervention in patients with Budd-Chiari syndrome offers the possibility of effective relief of signs and symptoms, with a potentially favorable outcome. Doppler ultrasound imaging of the hepatic vein has been reported to have a sensitivity of 85% to 95% for the diagnosis of Budd-Chiari syndrome and emerges as the diagnostic modality of choice in the ED setting. The management of Budd-Chiari syndrome relates to the severity and acuity of disease. Newly diagnosed Budd-Chiari syndrome with acute decompensation will require immediate consultation and consideration for transjugular intrahepatic portosystemic shunt placement, percutaneous angioplasty, or thrombolytic therapy. Previously diagnosed disease with worsening

ascites can be managed with modification of diuretics and therapeutic paracentesis, followed by referral to a primary care physician or gastroenterologist. Portacaval shunting and liver transplantation are options for disease refractory to medical or other less invasive percutaneous interventions.

Liver Transplantation Human orthotopic liver transplantation offers a 5-year survival rate of approximately 80%, but complications are common. Early complications include bleeding, acute rejection, vascular and biliary tract problems, and infection. Delayed complications include malignancy, recurrence of underlying disease, infection, chronic rejection, medication toxicity, and renal failure. Many early complications will manifest during the immediate postoperative period. Delayed complications may occur 1 year or more after transplantation. Liver transplant recipients are at increased risk for opportunistic infections as a consequence of their immunosuppressive therapy. Presenting signs and symptoms may be subtle. Chronic rejection manifests with low-grade temperature elevation, fatigue, and jaundice. Expected laboratory abnormalities include elevated bilirubin and transaminase levels, prolonged PT or INR, and low serum albumin level. Renal failure may not be clinically apparent until the glomerular filtration rate has declined significantly. Routine serum creatinine level measurement is the best means of identifying this disorder early, when successful intervention is still possible. The most common combination of immunosuppressive agents used after liver transplantation includes a corticosteroid (eg, prednisone) along with a calcineurin inhibitor (eg, cyclosporine or tacrolimus) and sirolimus, mycophenolate, or azathioprine. Corticosteroid toxicity may produce glucose intolerance, osteoporosis, gastric ulceration, and muscle wasting. Cyclosporine and tacrolimus can cause renal impairment, which is the most common dose-limiting effect of these agents. Azathioprine can be hepatotoxic but is more often associated with bone marrow suppression, placing the patient at increased risk for infectious complications and bleeding diathesis. Management of patients with complications related to their liver transplant is directed by the nature of the problem. Accordingly, assessment may include a complete blood count (CBC) and determination of glucose, BUN, creatinine, serum electrolyte, transaminase, bilirubin, and albumin levels, as well as coagulation studies. Hepatobiliary imaging is indicated if tumor, vascular occlusion, or biliary tract obstruction is suspected. Ultrasound studies with Doppler interrogation can be particularly useful in the ED setting. Consultation with a transplantation specialist is recommended for any patient with a problem potentially related to the organ transplant or immune-modulating medications.

BILIARY TRACT DISORDERS CHOLELITHIASIS Principles The principal cause of biliary tract disease is related to the development of gallstones. There are two categories of gallstones, cholesterol stones and pigmented stones. Cholesterol stones usually occur as a consequence of an elevated concentration of cholesterol in bile relative to the other principal constituents, bile acids and phospholipids. Bile acids and lecithin, the primary bile phospholipid, act in concert to solubilize cholesterol. As cholesterol levels rise or bile acid and lecithin levels decline, cholesterol has an increasing tendency to form crystals. These crystals, particularly in an incompletely

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emptying gallbladder, serve as a nidus for stone formation. Factors associated with an increased risk of cholesterol stone formation include increased age, female gender, massive obesity, rapid weight loss, cystic fibrosis, parity, drugs (eg, clofibrate, oral contraceptive agents), and familial tendency. Pigmented stones are of two varieties, black and brown. Black stones occur exclusively in the gallbladder, contain a high concentration of calcium bilirubinate, and are usually encountered in older adults and those with intravascular hemolytic diseases (eg, sickle cell anemia, hereditary spherocytosis). Brown stones are associated with infection and can form in the gallbladder and intrahepatic and extrahepatic bile duct systems. Although bacterial infections are usually incriminated, parasites (eg, Ascaris lumbricoides, Clonorchis sinensis) have also been linked to brown stone formation. Both types of pigmented stones contain calcium bilirubinate and therefore may be visible on plain abdominal radiographs. For a stone to be radiopaque, it must contain at least 4% calcium by weight.

Clinical Features The most common clinical manifestation of cholelithiasis is biliary colic. The pathophysiology is related to the passage of small stones from the gallbladder through the cystic duct into the common bile duct. The term colic is often misleading; affected patients commonly report steady pain, rather than intermittent or cramping discomfort. The pain most often is perceived in the RUQ but may be localized over a wide region of the upper abdomen. Radiation of pain, if it occurs, generally is to the base of the right scapula or shoulder. Associated signs and symptoms include nausea and vomiting, which may be severe enough to lead to fluid and electrolyte imbalances. Patients with biliary colic commonly report similar self-limited occurrences in the past and may offer an association between symptom onset and eating. Physical findings include mild tenderness to palpation, without guarding or rebound in the RUQ or epigastric region.

Differential Diagnosis Considerations in the differential diagnosis of biliary colic include cholecystitis, peptic ulcer disease of the stomach or duodenum, pancreatitis, and hepatitis. Patients with cholelithiasis may occasionally have chest pain, so cardiopulmonary syndromes must be considered as well. A compatible clinical history in conjunction with normal laboratory test values (ALT, AST, lipase, and alkaline phosphatase levels), gallstones on ultrasound, and minimal or no tenderness in the RUQ favor the diagnosis of cholelithiasis. If abnormalities are not visualized, a chest radiograph or electrocardiogram may help differentiate between cardiopulmonary and biliary pathology.

Diagnostic Testing No pathognomonic clinical laboratory findings are recognized; results of commonly performed tests typically are within normal limits. Important tests to perform include ALT and AST level measurements to evaluate for the presence of hepatitis, bilirubin and alkaline phosphatase level determinations to look for evidence of common duct obstruction, and lipase level measurement to assess for the presence of pancreatitis. The diagnosis of biliary colic is made clinically in conjunction with the demonstration of stones in the gallbladder. Ultrasonography is the procedure of choice for investigating the gallbladder because it can be performed rapidly, is highly sensitive, and provides the added value of permitting the evaluation of surrounding structures (Fig. 80.12). Oral cholecystography with the use of iopanoic acid is an alternative (when ultrasonography is not

LONG GB

FF

GBW Stones

Fig. 80.12.  Gallbladder with gallstones (Stones), thickened gallbladder wall (GBW), and pericholecystic fluid (FF). Together these findings constitute the sonographic signs of cholecystitis.

available or cannot be performed successfully) and can identify gallstones in 95% of patients with cholelithiasis in whom the gallbladder can be visualized.

Management The initial management of biliary colic is correction of fluid and electrolyte disturbances and relief of symptoms. Vomiting is managed with antiemetics and, if necessary, nasogastric suction. Pain often can be controlled with antispasmodics (eg, glycopyrrolate), nonsteroidal antiinflammatory drugs (NSAIDs), and opiate analgesic agents, as needed. The definitive management of cholelithiasis usually involves surgical removal of the gallbladder; however, other options are available. Oral administration of bile acid (eg, chenodeoxycholate, ursodeoxycholate) over a period of months to years can result in dissolution of small to medium-sized stones. Extracorporeal shock wave lithotripsy may be successful in a select, technically suitable set of patients who have functioning gallbladders and, ideally, have a small number of stones. The most common complication of biliary colic is fluid and electrolyte imbalances secondary to vomiting. Other adverse consequences include Mallory-Weiss tears from uncontrolled emesis and cholangitis from unrecognized and persistent common bile duct obstruction.

Special Considerations Biliary colic is an uncommon symptom in children and is usually associated with an underlying hemolytic disorder (eg, sickle cell anemia, spherocytosis). Acute management of biliary colic is the same for children and adults. Cholelithiasis may be encountered in pregnant women. Diagnosis in this population is made more difficult by the common occurrence of nausea and vomiting, particularly in the first trimester, and the presence of an enlarged uterus in later pregnancy, which alters anatomic relationships and interferes with an abdominal examination. Ultrasound imaging is of considerable diagnostic use in this setting. ED management is the same for pregnant and nonpregnant patients; however, definitive therapy generally is delayed until after parturition.

Disposition Hospitalization should be considered for unremitting pain, intolerance of oral intake, significant electrolyte abnormalities, or

CHAPTER 80  Disorders of the Liver and Biliary Tract

laboratory tests indicating obstruction or possible cholecystitis. In other patients, symptom control can often be achieved and electrolyte and volume depletion corrected such that the patient can be discharged home with antiemetics and agents for pain control after demonstrating tolerance for oral intake. Referral to a general surgeon as an outpatient for further evaluation and consideration of cholecystectomy should be included in discharge planning.

CHOLECYSTITIS Principles Acute cholecystitis is defined as sudden inflammation of the gallbladder. The risk factors for cholecystitis are similar to those for cholelithiasis—female gender, increasing age and parity, and obesity. Although gallstones play a prominent role in the pathogenesis of cholecystitis, a minority of cases are categorized as acalculous. Obstruction of the cystic duct appears to be the critical factor in the development of gallbladder inflammation. Gallstones are identified in 95% of patients with cholecystitis and may be located in the common bile duct in many patients with acalculous cholecystitis. Causes of cystic duct obstruction unrelated to stone disease include tumor, lymphadenopathy, fibrosis, parasites, and kinking of the duct, which leads to filling and distention of the gallbladder. The ensuing inflammatory reaction may be related to mucosal ischemia from increased hydrostatic pressure or to the action of cytotoxic products of bile metabolism (eg, lysophosphatidylcholine). Although bacteria are isolated from the bile of inflamed gallbladders in most cases, the role of infection is not completely understood. Coliforms (eg, E. coli) represent the most common isolates, but anaerobes have been identified in as many as 40% of cases.

Clinical Features The most common presenting symptom of cholecystitis is pain, usually in the right upper quadrant. Although the pain initially may be colicky, it will become constant in virtually all cases. A previous history of similar but less severe and self-limited symptoms is a valuable diagnostic clue, as is documentation of previous gallstones. Nausea and vomiting are typical features, and the patient may exhibit fever or describe radiation of pain, generally to the tip of the right scapula.

Physical findings include tenderness in the RUQ or epigastric region, often with guarding or rebound. Murphy’s sign (tenderness and an inspiratory pause elicited by palpation of the RUQ during a deep breath) is compatible with, but not specific for, gallbladder inflammation. Fever and tachycardia are commonly absent, so cholecystitis remains a diagnostic consideration in the absence of these findings in patients with abdominal pain and RUQ pain and tenderness to palpation.

Differential Diagnosis Diagnostic considerations in addition to cholecystitis include hepatitis, hepatic abscess, pyelonephritis, right lower lobe pneumonia or pleurisy, pancreatitis, peptic ulcer disease of the duodenum with perforation or penetration, and appendicitis. Accurate diagnosis often requires the use of sonographic or, less commonly, scintigraphy or CT.

Diagnostic Testing A polymorphonuclear leukocytosis with left shift is common, but a WBC count in the normal range has been seen in up to 40% of patients. Serum aminotransferase, bilirubin, and alkaline phosphatase levels may be mildly elevated but more often are within normal limits. An elevated lipase level should suggest the diagnosis of pancreatitis, instead of or in addition to cholecystitis. Plain abdominal radiographs may reveal calcified stones, gas in the gallbladder, or an upper quadrant sentinel loop, but are uncommon and nonspecific. Ultrasound imaging is the most useful test in the ED. Visualization of the gallbladder without identification of stones has an extremely high negative predictive value for cholecystitis, whereas the presence of stones, thickened gallbladder wall, and pericholecystic fluid has a positive predictive value, in excess of 90% (Fig. 80.13). Nuclear scintigraphy with technetium-99m–labeled iminodiacetic acid (IDA) generally is considered the most sensitive and specific imaging test for cholecystitis. IDA administered IV is taken up by hepatocytes and secreted into the bile canaliculi. Failure to obtain an outline of the gallbladder within 1 hour of administration of IDA in the presence of hepatic and common duct visualization proves cystic duct obstruction. In the appropriate clinical setting, this finding is diagnostic of cholecystitis. Conversely, visualization of the gallbladder and common duct within

RT LIV TRANS

A

B Fig. 80.13.  Abdominal ultrasound images from a patient with common bile duct obstruction. A, Multiple dilated intrahepatic ducts (arrows). B, Significant dilated common bile duct (arrows). The duct measures 2 cm in diameter.

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1 hour of administration has a high negative predictive value. Scintigraphy with IDA loses its sensitivity as the serum bilirubin level rises above 5 to 8 mg/dL; however, scintigraphy with diisopropyl IDA (diisopropyl iminodiacetic acid, or mebrofenin) allows visualization of the biliary tree in patients with total serum bilirubin in the range of 20 to 30 mg. Although not the preferred imaging modality, CT can identify cholecystitis with a sensitivity of 92% and specificity of 99%. It is of particular value in cases of emphysematous and hemorrhagic cholecystitis.

Management Supportive measures provide the foundation for initial management of acute cholecystitis—IV crystalloid administration to optimize volume status and antiemetics to manage emesis. Pain control can be addressed with NSAIDs or narcotic analgesics and possibly nasogastric suctioning, which may have the added benefit of diminishing the stimulus for biliary secretion and excretion, thereby adding to pain relief. Despite the questionable role of microbial infection in the pathogenesis of cholecystitis, antibiotics are recommended and should be continued until 1 day after the gallbladder is removed. Unless clinical evidence of sepsis exists, coverage with a single broad-spectrum antibiotic, such as IV piperacillin-tazobactam (3.375 g qid) is recommended. The most serious complication of cholecystitis is gangrene of the gallbladder, with necrosis and perforation. Localized perforation may lead to pericholecystic abscess or fistula formation, with the latter predisposing to gallstone ileus at a later date. Patients with diabetes mellitus are at increased risk for bacterial invasion of the gallbladder wall and emphysematous cholecystitis (Fig. 80.14).

Special Considerations Cholecystitis is uncommon in children; however, when it occurs, it should be managed as for adults. Cholecystitis in the pregnant woman poses challenges in diagnosis and therapy. Initial therapy is identical to that for the nonpregnant patient, but the issue of surgical intervention requires an individualized consultation between a surgeon and obstetrician. Acalculous Cholecystitis.  This is more common in older adults and most often is found in patients who are recovering from non–biliary tract surgery. Over the past decade, acalculous

A

disease has been increasingly encountered as a complication of advanced acquired immunodeficiency syndrome (AIDS), usually secondary to infection with cytomegalovirus (CMV) or Cryptosporidium. In comparison with calculous disease, acalculous cholecystitis tends to have a more acute and malignant course, with a high mortality rate. The same techniques are used to diagnose acalculous disease as for other forms of cholecystitis but are less sensitive and specific for this entity. Sonographic findings include thickening of the gallbladder wall, pericholecystic fluid, and lack of response to cholecystokinin. Scintigraphic findings are the same as for calculous disease. Emphysematous Cholecystitis.  This is an uncommon variant of cholecystitis, occurring in approximately 1% of cases. It is characterized by the presence of gas in the gallbladder wall, presumably consequent to the invasion of the mucosa by gasproducing organisms (eg, E. coli, Klebsiella spp., Clostridium perfringens). It is more common in diabetic patients, has a male predominance, and is acalculous in up to 50% of cases. Clinical presentation and physical findings are similar to those for cholecystitis. Plain radiographs or CT scans of the abdomen will reveal gas in the gallbladder wall. Because of a high incidence of gangrene and perforation, emergency cholecystectomy is recommended. Antibiotic coverage should include ceftriaxone, 1–2 g every 24 hours, plus metronidazole (500 mg IV tid) or monotherapy with a β-lactamase inhibitor or carbapenem. The mortality rate for emphysematous cholecystitis is approximately 15%.

Disposition Hospitalization for antibiotic therapy and pain management is required. Surgery is recommended for patients with cholecystitis; however, the optimal timing for surgery is not certain. Surgery usually is performed after symptoms have subsided but while the patient is still hospitalized.26 Immediate cholecystectomy or cholecystotomy is reserved for the complicated case in which the patient has gangrene or perforation.

CHOLANGITIS Principles Acute obstructive cholangitis is usually the consequence of common duct blockage by a gallstone but may be associated with malignancy or a benign stricture. The key factors contributing to

B Fig. 80.14.  A, X-ray demonstrating air around the wall of the gallbladder and CT scan (B) demonstrating a luminal air-liquid level and air within the wall of the gallbladder.

CHAPTER 80  Disorders of the Liver and Biliary Tract

cholangitis are obstruction, elevated intraluminal pressure, and bacterial infection. Incomplete obstruction occurs more commonly than complete blockage. Bacteria may gain access to the obstructed common duct in a retrograde manner from the duodenum, by way of the lymphatics, or from portal vein blood. The most commonly encountered organisms are similar to those encountered in other varieties of biliary tract disease—E. coli, Klebsiella, Enterococcus, and Bacteroides.

TABLE 80.4 

Ampicillin-sulbactam

3 g IV qid

Clinical Features

Piperacillin-tazobactam

3.375 g IV qid

Patients most often experience fever, chills, nausea, vomiting, and abdominal pain. The classic triad of physical findings first described by Charcot consists of RUQ pain, fever, and jaundice. These findings are compatible not only with cholangitis, but also with cholecystitis and hepatitis. Sepsis is a common complication and is evidenced by tachycardia, tachypnea, and frank hypotension. The presence of Charcot’s triad along with the clinical signs of sepsis—hypotension and altered sensorium—is referred to as Reynolds’ pentad.

Differential Diagnosis Although patients with cholangitis generally have a higher fever and appear more ill than those with cholecystitis, considerable variability and overlap are possible. The presence of jaundice is the clinical sign most helpful in differentiating between these two disorders. An elevated bilirubin level is characteristic of cholangitis and uncommon in cholecystitis. Ultrasonographic evidence of dilated common and intrahepatic ducts usually is required to distinguish cholangitis from cholecystitis.

Diagnostic Testing Common laboratory abnormalities include polymorphonuclear leukocytosis, hyperbilirubinemia, elevated alkaline phosphatase level, and moderately increased aminotransferase levels. Arterial blood gas measurements are useful to identify base deficit as an early sign of sepsis. Sonography can be helpful if it demonstrates common and intrahepatic ductal dilation, whereas identification of stones in the gallbladder or common duct suggests the underlying cause of obstruction (see Fig. 80.12). Although nuclear scintigraphy cannot determine the cause, it is a more sensitive means to diagnose early obstruction. There is a high incidence of nonvisualization of the biliary tree with cholescintigraphy in patients with common duct obstruction when sonography fails to identify dilation. Alternative imaging techniques include CT, percutaneous transhepatic cholangiography (THC), and endoscopic retrograde cholangiopancreatography (ERCP). Although these techniques may be more expensive and time-consuming, the latter two have the added benefit of offering potential therapeutic benefit. Endoscopic cholangioscopy can permit culture of bile, direct removal of obstructing stones, or decompression of the biliary tree by sphincterotomy or stent placement.

Management Treatment of cholangitis includes hemodynamic stabilization with crystalloid fluid and, if necessary, vasopressors. Broadspectrum antibiotic coverage should be initiated immediately after blood culture specimens have been obtained. The choice of antibiotics should be guided by local sensitivities and must provide coverage for enteric microbes. Table 80.4 lists antimicrobial therapies for cholangitis. The key to successful treatment is early biliary tract decompression, which may be achieved with THC, ERCP, or surgery.

Antimicrobial Treatment for Cholangitis Targeting Gram-Negative and Anaerobic Pathogens DRUG REGIMEN

DOSAGE

FIRST-LINE SINGLE-DRUG REGIMEN

FIRST-LINE MULTIDRUG REGIMEN Ceftriaxone + Metronidazole

1 g IV every 24 h + 500 mg IV tid

ALTERNATIVE TREATMENT REGIMENS Ciprofloxacin + metronidazole

400 mg IV every 12 h + 500 mg IV tid

Levofloxacin + metronidazole

750 mg IV every 24 h + 500 mg IV tid

Imipenem

500 mg IV qid

Meropenem

1 g IV tid

Doripenem

500 mg IV tid

Ertapenem

1 g IV every 24 h

Disposition Patients with cholangitis require hospitalization, preferably in a monitored setting. Prompt consultation with a service that can provide for biliary tract decompression—surgery, interventional radiology, or gastroenterology—is necessary.

SCLEROSING CHOLANGITIS Sclerosing cholangitis is an idiopathic inflammatory disorder affecting the biliary tree characterized by diffuse fibrosis and narrowing of the intrahepatic and extrahepatic bile ducts. It is commonly associated with inflammatory bowel disease, particularly ulcerative colitis; however, in 25% of cases, it appears as an isolated disorder. Patients usually report weight loss, lethargy, jaundice, and pruritus. Rarely, infective cholangitis may develop. Prompt diagnosis may be challenging because of the sclerotic nature of the bile ducts and absence of duct dilation on ultrasound imaging. Surgical exploration or ERCP often is required for diagnosis. The management of uninfected cases is primarily symptomatic. Cholestyramine, a bile acid sequestrant, may diminish pruritus.

AIDS CHOLANGIOPATHY Manifestations of advanced HIV disease, generally associated with CD4+ counts less than 200/mm3 , may include any one of a group of disorders collectively referred to as AIDS cholangiopathy. These disorders include bile duct stricture, papillary stenosis, and sclerosing cholangitis. The precise pathophysiology is not completely understood but is related to infection with CMV, Cryptosporidium, microsporidia, or Mycobacterium avium complex. The clinical presentation is similar to that for other causes of cholangitis, with fever and RUQ pain. Laboratory test results include increased levels of alkaline phosphatase and minor elevation of transaminase levels. The bilirubin level is less commonly elevated than in other disorders that cause cholangitis. Ultrasonography generally is helpful in identifying bile duct stricture, thickening, or dilations, as are IDA scans. Management involves endoscopic sphincterotomy or stent placement in conjunction with treatment of the underlying infection.

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KEY CONCEPTS Hepatitis Viral Hepatitis

The clinical presentation of viral hepatitis is highly variable, and many cases, particularly in children, are asymptomatic. • Incubation times vary—hepatitis A, 15–45 days; hepatitis B, 60–90 days; hepatitis C, 30–90 days. • Highly effective immunizations exist against hepatitis A and B viruses. • Postexposure, passive immunization exists for hepatitis A and B viruses but its use is mainly limited to nonimmunized, hepatitis B–exposed individuals. • Direct-acting antiviral regimens using nucleoside inhibitors have revolutionized hepatitis treatment. A sustained virologic response with negative HCV RNA testing is achieved in over 90% of individuals. • Viral hepatitis is a reportable disease. Additional care in the ED and patient education should be provided to prevent disease spread. • The process of identifying the causative agent or source should be initiated because it affects disease prognosis and public health.

Alcoholic Hepatitis

• Liver disease caused by alcohol use progresses from steatosis to fibrosis to cirrhosis, and finally to hepatocellular carcinoma. Hepatitis may accompany the cirrhosis. • With cessation of alcohol intake, steatosis may reverse within 2 weeks. • Alcoholic hepatitis, although generally a mild disease with minor clinical manifestations, can be a cause of fulminant hepatitis. • Laboratory tests may help distinguish alcoholic hepatitis from viral hepatitis in that the former is associated with milder enzyme level elevations and a relative predominance of AST to ALT levels. • Management of patients with alcoholic hepatitis should include fluid and electrolyte repletion, a high-calorie and vitamin-supplemented diet, and referral for alcohol dependence treatment. • Variceal bleeding is treated with octreotide (50-µg bolus followed by 50 µg/h), somatostatin (250-µg bolus and 250-µg/hour infusion), or vasopressin (0.4-unit bolus followed by 0.4–1 unit/min continuous infusion) is important. • Oral prednisone, 40 mg daily, or IV methylprednisolone, 32 mg daily, should be used for patients with alcoholic hepatitis and mDF more than 32.

Cirrhosis

Patients with cirrhosis most often present to the ED with complications of their disease—ascites, variceal bleeding, hepatorenal syndrome, or hepatic encephalopathy. • Impaired hepatic synthetic and metabolic function in patients with cirrhosis may necessitate correction of coagulopathy before invasive procedures and modification of medication dosage. • Prior to performing procedures, the targeted platelet count should be more than 50,000/mm3. • When volumes more than 5 L are removed during paracentesis to treat ascites, albumin, (8 g/L of ascitic fluid removed) should be given. • Cryoprecipitate, 1 unit/10 kg body weight, is preferred over fresh-frozen plasma when treating liver-associated coagulopathies in a patient with active bleeding. • Angiotensin-converting enzyme inhibiting drugs and angiotensin receptor blocking drugs should be avoided in patients with cirrhosis. Both lower mean arterial blood pressure and may increase mortality. • Hepatorenal syndrome is heralded by an increasing creatinine level in the setting of liver failure. It is associated with a high rate of mortality and should be managed with norepinephrine, 0.5–3 mg/h in combination with albumin 1 g/kg (maximum, 100 g).

Hepatic Encephalopathy

• Hepatic encephalopathy is a state of cerebral and neuromuscular dysfunction secondary to increased ammonia levels and their effects on cerebral metabolism.

• The severity of hepatic encephalopathy does not directly correlate with the serum ammonia level. • Consideration and evaluation for underlying exacerbating conditions, such as GI bleeding, hypokalemia, infection and dehydration, should be undertaken during the evaluation and treatment of hepatic encephalopathy. • The differential diagnosis for hepatic encephalopathy should consider all causes of altered sensorium. The broad scope of the differential diagnosis may necessitate additional testing, including serum chemistry, CSF studies, toxicology studies, and head CT scanning. • Management of hepatic encephalopathy includes correction of underlying electrolyte abnormalities, dietary guidance, administration of lactulose (30–60 g/day) and rifaximin (400 mg tid). • L-Ornithine–L-arginine may be added to the regimen and has demonstrated ability to lower serum ammonia levels. • Probiotics, acarbose, flumazenil, and polyethylene glycol require further investigation in the treatment of hepatic encephalopathy.

Spontaneous Bacterial Peritonitis

• SBP should be considered in any patient with ascites with abdominal pain, fever, or unexplained clinical deterioration. • E coli and Klebsiella remain the two most commonly identified organisms in SBP. • The diagnosis of SBP is dependent on obtaining ascitic fluid for cell count and culture. • Use of leukocyte esterase reagent strips may provide a convenient means of bedside screening of ascitic fluid for SBP. • An ascitic fluid granulocyte count greater than 250 cells/mm3 (100 cells/mm3 in peritoneal dialysis patients) is an indication for antibiotic treatment. • Treatment of SBP includes cefotaxime, 2 g tid, for 5 days. • Additional testing and imaging may assist in differentiating SBP from peritonitis secondary to other abdominal or lung pathologies.

Hepatic Abscesses

• Pyogenic abscesses often occur in the right lobe of the liver from anaerobic or aerobic microbes. • Abdominal ultrasound and CT are the imaging modalities of choice. • Imaging does not distinguish pyogenic from amebic abscesses. • Treatment should be initiated prior to abscess drainage. • Treatment regimens for pyogenic abscess include: • Cefotaxime + metronidazole • Ampicillin + gentamycin + metronidazole • Ciprofloxacin or levofloxacin or moxifloxacin + metronidazole • Piperacillin-tazobactam • Impinem or meropenem, or doripenem or ertapenem • Definitive treatment for abscesses larger than 3 cm includes image-guided percutaneous drainage. • Surgical drainage is reserved for complex cases.

Amebic Abscess

• Although similar in many ways to pyogenic abscess, diagnosis is made via stool analysis or ELISA testing. • Most patients will have elevation in alkaline phosphatase and aminotransferase levels. • Ultrasound may reveal specific findings unique to an amebic abscess, including a peripherally located abscess with a well-circumscribed boarder and a homogeneous, hypoechoic center. • Coupled with imaging, laboratory data including ELISA or counterimmune electrophoresis may aide in differentiating amebic from pyogenic abscesses. • Definitive treatment of amebic abscess is amebicidal therapy with IV or oral metronidazole (750 mg tid for 7–10 days).

Cholelithiasis

• Biliary colic should be considered in patients with nausea, vomiting, and RUQ pain.

CHAPTER 80  Disorders of the Liver and Biliary Tract

KEY CONCEPTS—cont’d • Diagnosis with ultrasound of the biliary system and possibly laboratory abnormalities suggests obstruction of the biliary tree. • Initial management is supportive, with the goal of treating pain and correcting fluid and electrolyte abnormalities. • Patients without findings of infection who are tolerating oral intake may be managed in the outpatient setting. • Definitive care requires outpatient surgical referral for cholecystectomy.

Cholecystitis

• The vast majority of patients with cholecystitis have gallstones; however, approximately 8% have acalculous disease. The latter group of patients tend to have more severe disease and are at increased risk for complications. • Despite an unclear relationship between bacterial infection and pathophysiology, antibiotic therapy is recommended.

• Combination therapy with a third-generation cephalosporin and metronidazole or monotherapy with a carbapenem or β-lactamase inhibitor is recommended. • Patients with acalculous and emphysematous cholecystitis are at increased risk for gangrene and perforation and require emergency cholecystectomy.

Cholangitis

• Cholangitis is an emergency condition resulting from extrahepatic bile duct obstruction and bacterial infection. • The classically seen triad consists of RUQ pain, fever, and jaundice • Effective management requires prompt fluid resuscitation and administration of broad-spectrum antibiotics. • Definitive management includes hospitalization and early biliary tract decompression, which can be achieved surgically, transhepatically, or by ERCP.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Centers for Disease Control and Prevention: Viral hepatitis. . 2. Chou HH, Chien WH, Wu LL, et al: Age-related immune clearance of hepatitis b virus infection requires the establishment of gut microbiota. Proc Natl Acad Sci U S A 112:2175–2180, 2015. 3. Selvarajah S, Busch MP: Transfusion transmission of HCV, a long but successful road map to safety. Antivir Ther 17:1423–1429, 2012. 4. Soriano V, Vispo E, Labarga P, et al: Viral hepatitis and HIV co-infection. Antiviral Res 85:303–315, 2010. 4a.  Villano SA, Vlahov D, Nelson KE, et al: Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 29(3):908–914, 1999. 5. Galbraith JW, Franco RA, Donnelly JP, et al: Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department. Hepatology 61:776– 782, 2015. 6. Denniston MM, Klevens RM, McQuillan GM, et al: Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008. Hepatology 55:1652–1661, 2012. 7. Yurdaydın C, Idilman R, Bozkaya H, et al: Natural history and treatment of chronic delta hepatitis. J Viral Hepat 17:749–756, 2010. 8. Bruno R, Aghemo A: Hepatitis C virus post-exposure prophylaxis: a reasonable option in the era of pangenotypic direct-acting antivirals. J Hepatol 63:1294, 2015. 9. Jacobson IM, Dore GJ, Foster GR: Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 384:403–413, 2014. 10. Lawitz E, Sulkowski MS, Ghalib R: Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naïve patients: the COSMOS randomised study. Lancet 384:1756–1765, 2014. 11. Afdhal N, Reddy KR, Nelson DR: Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 370:1483–1493, 2014.

12. Afdhal N, Zeuzem S, Kwo P: Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370:1889–1898, 2014. 13. Rhem J, Samokhvalov AV, Shield KD: Global burden of alcoholic liver diseases. J Hepatol 59:160–168, 2013. 14. Gao B, Bataller R: Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141:1572–1585, 2011. 15. Dugum M, McCullough A: Diagnosis and management of alcoholic liver disease. J Clin Transl Hepatol 3:109–116, 2015. 16. DiNubile MJ: Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 373:281–282, 2015. 17. Alessandria C, Elia C, Mezzabotta L: Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: standard vs half-albumin doses. a prospective, randomized unblinded pilot study. Dig Liver Dis 43:881–886, 2011. 18. Runyon BA: Introduction to the Revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 57:1651–1653, 2013. 19. Roberts JA, Pea F, Lipman J: The clinical relevance of plasma protein binding changes. Clin Pharmacokinet 52:1–8, 2013. 20. Bass NM, et al: Rifaximin treatment in hepatic encephalopathy. N Engl J Med 362:1071–1081, 2010. 21. Rockey DC, Vierling JM, Mantry P: Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology 59:1073–1083, 2014. 22. Bai M, He M, Yin Z: Randomised clinical trial: l-ornithine-l-aspartate reduces significantly the increase of venous ammonia concentration after TIPSS. Aliment Pharmacol Ther 40:63–71, 2014. 23. Tsipotis E, Shuja A, Jaber BL: Albumin dialysis for liver failure: a systematic review. Adv Chronic Kidney Dis 22:382–390, 2015. 24. Li PK, Szeto CC, Piraino B: Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int 30:393–423, 2010. 25. Carpenter C, Gilpin N: Hepatic abscess. . 26. Polo M, Polazzi S, Payet C, et al: Acute cholecystitis-optimal timing for early cholecystectomy: A French nationwide study. J Gastrointest Surg 11:2003–2010, 2015.

CHAPTER 80: QUESTIONS & ANSWERS 80.1. Which of the following statements regarding hepatitis A is true? A. Fecal shedding and highest infectivity coincide with symptomatic disease. B. In the United States, approximately 20% of urbandwelling adults are seropositive. C. Occult disease is more common in children than in adults. D. The incidence of it is fairly consistent across ethnic groups. E. The most common risk factor for children is travel. Answer: C. Children are more likely to have occult disease (up to 70%). Adult seropositive rates approach 50% among urbandwelling adults. The incidence varies widely across ethnic groups. In areas of pediatric vaccinations, increasing adult cases are seen among intravenous drug users (IVDUs) and homosexual males. The stage of highest infectivity precedes symptoms. 80.2. Which of the following statements concerning hepatitis D infection is true? A. Hepatitis D is spread primarily via the fecal-oral route. B. Infection with hepatitis D is an independent event with a course nearly identical to that of hepatitis A. C. It is common to see aspartate aminotransferase (AST) level elevations far in excess of alanine aminotransferase (ALT) level elevations. D. Many cases are misdiagnosed as acute or reactivated hepatitis B. E. Unconjugated bilirubin levels are 2 or 3 times higher than conjugated levels. Answer: D. Hepatitis D virus infection can only occur with (coinfection) or after (superinfection) hepatitis B infection. It is spread via the parenteral route, such as by IV drug use. Many cases are misdiagnosed as acute or reactivation hepatitis B because B

markers will be positive. There are no unique biochemical or laboratory patterns for any of the viral hepatitis infections. Hepatitis D does seem to have a direct cytotoxic potential as opposed to other viral causes, where the host immunologic response causes much of the hepatitis. 80.3. A 26-year-old man presents with complaints of pruritus and a raised rash for 7 days. The rash has been associated with nausea and painful symmetrical swelling of both wrists and metacarpophalangeal joints. He has no past medical history and takes no medications. He works in a retail store. Vital signs are normal, and the physical examination is remarkable for right upper quadrant tenderness, bilateral mild wrist effusion with minimal warmth and no erythema, and diffuse skin urticaria. The remainder of the examination is negative. Blood count, chemistries, and liver studies are remarkable for WBC, 11,800 cells/mm3, AST, 212 IU/L, ALT, 395 IU/L, normal alkaline phosphatase level, and total bilirubin of 2.3 mg/ dL. Which of the following tests would be most likely to yield the diagnosis? A. CMV titers B. Hepatitis A antigen C. Hepatitis B surface antigen D. Herpes simplex I titers E. Monospot test Answer: C. A small number of patients with hepatitis B develop a prodrome of arthralgias and arthritis (symmetric small joints) and dermatitis. The dermatitis is typically urticarial but may be macular, popular, or petechial. 80.4. Scleral icterus becomes clinically apparent at approximately which serum bilirubin level? A. 2 mg/dL B. 2.5 mg/dL

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C. 3 mg/dL D. 3.5 mg/dL E. 4 mg/dL Answer: B. Icterus is often first noted in the sublingual or subungual areas. 80.5. Which of the following statements regarding the typical laboratory profile for a patient with acute viral hepatitis is true? A. AST is generally elevated in excess of ALT. B. Direct and indirect bilirubin are elevated in almost equal proportions. C. Lactate dehydrogenase (LDH) levels are almost always normal. D. The alkaline phosphatase level is generally elevated 5 to 10 times normal. E. The WBC generally shows a marked polymorphonuclear leukocytosis. Answer: B. The alkaline phosphatase level is rarely elevated more than 2 or 3 times normal, and LDH levels are modestly elevated. The WBC count may range from low, with lymphocytic predominance, to a polymorphonuclear (PMN)-predominant leukocytosis. ALT is almost always elevated in excess of AST. 80.6. A 26-year-old woman returns for follow-up after initial evaluation for possible acute hepatitis. Her hepatitis panel has returned with the following results: Hepatitis A IgM Negative Hepatitis A IgG Negative Hepatitis B surface antigen Positive Hepatitis B surface antigen IgG Negative Hepatitis B core antigen IgM Positive Hepatitis B core antigen IgG Negative Hepatitis C antigen Negative Which of the following is the most appropriate diagnosis? A. Acute hepatitis A B. Acute hepatitis B C. Immunity to hepatitis B D. Previous hepatitis A E. Previous hepatitis B Answer: B. Acute hepatitis A is characterized by IgM to hepatitis A. Prior infection is determined by IgG antibody. Acute hepatitis B is characterized by the presence of surface antigen and IgM antibody to core antigen. Surface antigen alone may be absent late in the course of the disease or may present chronically unrelated to the current episode. IgG to the core antigen indicates previous infection. IgG to the surface antigen is the best marker for immunity. 80.7. A 39-year-old man presents with a 4-day history of abdominal pain and nausea. He has no significant past history and takes no medications. Vital signs are temperature, 37.7° C (99.9° F) oral, heart rate (HR), 98 beats/min, respiratory rate (RR), 20 breaths/min, and blood pressure, 119/68 mm Hg. The physical examination reveals scleral icterus, a normal cardiopulmonary examination, moderate right upper quadrant tenderness without rebound, and guaiacnegative stool. Laboratory assessment reveals the following: Total bilirubin 9.8 mg/dL Conjugated bilirubin 4.6 mg/dL Unconjugated bilirubin 5.2 mg/dL AST 5300 IU/L

ALT 8400 IU/L Alkaline phosphatase 750 IU/L Albumin 3.9 mg/dL INR 1.2 Hematocrit 42% Platelet count 396,000/mm3 WBC 9900/mm3 Blood urea nitrogen (BUN) 53 mg/dL Creatinine 0.9 mg/dL Which of the following courses of action is most appropriate? A. Admission for observation and GI consultation B. CT scan of the abdomen with contrast C. Gastrointestinal (GI) referral for interferon therapy D. Reassurance E. Tapering course of corticosteroids Answer: A. Altered sensorium and prolongation of the PT beyond 5 seconds or INR beyond 1.5 suggest fulminant hepatic failure. Similarly, an unexplained elevation of the BUN or creatinine level may portend hepatorenal syndrome, which can be fatal. The BUN level elevation in this hepatitis patient warrants admission for hydration, close observation, and GI consultation. Interferon has had some success in symptomatic hepatitis B patients but does not affect the early course. There is no role for corticosteroids. 80.8. The risk of liver injury in men increases as daily consumption of alcohol exceeds which of the following? A. 10 g B. 20 g C. 40 g D. 60 g E. 80 g Answer: E. This is equivalent to a six-pack of beer, four to six glasses of wine, or three or four mixed drinks daily. For women, the risk increases with a daily consumption of more than 20 g of alcohol. 80.9. A 63-year-old alcoholic man presents with altered mental status. His family reports 3 days of decreasing ambulation and increasingly nonsensical conversation. He has no other known past medical history and takes no medications. Vital signs are unremarkable. The physical examination reveals a thin, unkempt man who is oriented to person only but is cooperative and follows commands. He falls asleep easily. There is no scleral icterus, and cardiopulmonary, abdominal, stool guaiac, and neurologic examinations are negative. A noncontrast CT scan of the head is negative. Pertinent laboratory findings are as follows: Hematocrit (HCT) 34% Hemoglobin 11.4 g/dL Platelet count 108,000/mm3 WBC 9300/mm3 AST 148 IU/L ALT 86 IU/L Total bilirubin 2 mg/dL Albumin 2.2 mg/dL Alkaline phosphatase 158 IU/L INR 1.8 38 mg/dL BUN Creatinine 2.1 mg/dL Ethanol 0 mg/dL Bicarbonate 30 mmol/L Sodium 133 mEq/L Potassium 3.6 mEq/L Chloride 95 mEq/L

CHAPTER 80  Disorders of the Liver and Biliary Tract

What is the most appropriate intervention? A. Admission for lactulose, 30 to 60 g daily, titrated to modest diarrhea B. Determination of further therapy, admission, and treatment based on serum ammonia levels C. Discharge with the family; neomycin, 500 mg every 4 to 6 hours D. Oral metronidazole, 250 mg qid E. Oral vitamin K for 2 weeks Answer: A. Ammonia accumulates in severe liver disease and crosses the blood-brain barrier to eventually form glutamine. Ammonia levels correlate poorly with encephalopathy. Lactulose is an osmotic cathartic that acidifies colonic contents, causing ammonia trapping. Neomycin is a poorly absorbed aminoglycoside that reduces colonic bacteria but is relatively contraindicated in cases of renal insufficiency. Therapies for hepatic encephalopathy that have been under clinical investigation include metronidazole, zinc, flumazenil, and eradication of Helicobacter pylori. Vitamin K would have modest benefit due to loss of hepatic synthetic abilities. Plasma would not be indicated unless active bleeding occurred. 80.10. A 23-year-old G2P1 woman at 35 weeks of gestation presents with 3 days of fatigue, anorexia, nausea, and vomiting. She reports moderate epigastric and right upper quadrant pain. The physical examination is remarkable for icteric sclerae, slightly dry mucous membranes, and moderate tenderness in the right upper quadrant. She is afebrile and her uterus is not tender. Urgent ultrasound shows a viable moving fetus at 34 weeks’ estimated gestational size, with good cardiac activity, and liver and gallbladder ultrasound reveals no obvious gallstones or ductal dilations but moderate hepatomegaly. Laboratory analysis is remarkable for the following: AST 1050 IU/L ALT 1265 IU/L Total bilirubin 9.9 mg/dL

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Conjugated bilirubin 4.6 mg/dL Unconjugated bilirubin 5.2 mg/dL Alkaline phosphatase 328 mg/dL Glucose 62 mg/dL Hemoglobin 9.3 g/dL Platelet count 105,000/mm3 Normal electrolytes 0.6 mg/dL Creatinine Prothrombin time 14.8 sec Albumin 3.1 g/dL What is the most appropriate treatment? A. Clear liquids, antiemetics, and follow-up outpatient ultrasound in 48 hours B. Contrast CT scan of the abdomen C. Hydration, antiemetics, and discharge after symptom resolution D. Intensive care unit admission for monitoring for DIC E. Stabilization and urgent delivery Answer: E. Acute failing liver of pregnancy typically presents in the latter third trimester. Treatment involves aggressive fluid and electrolyte support, glucose administration, and immediate delivery. Liver disease generally resolves without sequelae. The illness is more common in primigravidas and twin pregnancies. 80.11. What is the most sensitive and specific imaging test for acute cholecystitis? A. Contrast CT scan B. Nuclear scintigraphy with iminodiacetic acid (IDA) C. Serum alkaline phosphatase level D. Serum bilirubin level E. Ultrasonography Answer: B. IDA administered IV is taken up by hepatocytes and secreted into bile canaliculi. Visualization of the gallbladder and common duct within 1 hour has a negative predictive value of 98%. Scintigraphy with IDA loses its sensitivity at bilirubin levels of 5 to 8 mg/dL.

C H A P T E R 81 

Pancreas Rachel Berkowitz  |  Gabriel Rose

ACUTE PANCREATITIS

Pathophysiology

Background Acute pancreatitis is an inflammatory condition that occurs when enzymatic autodigestion and an inflammatory cascade result in destruction of pancreatic tissue. Its presentation may range widely from mild, self-limited disease to sepsis and multiorgan failure. Recurrent intermittent bouts of acute pancreatitis may result in morphologic and functional changes of the gland, known as chronic pancreatitis. The overall mortality due to acute pancreatitis is 4% to 10%, although in severe cases mortality may be as high as 30%.1 Although mortality from acute pancreatitis has decreased with improvements in recognition, understanding, and therapy, the annual incidence of the disease and number of hospital admissions attributed to it have been trending upward.2

Acute pancreatitis begins with an initial inciting event, such as exposure to a toxin or pharmacologic agent, or duct obstruction by gallstones. Cellular injury disrupts normal membrane trafficking and triggers the inappropriate activation of trypsinogen and other digestive enzymes. This in turn leads to autodigestion of pancreatic tissue and stimulation of an inflammatory cascade, which further damages the pancreas. Locally, cytokines cause increased vascular permeability, which can result in complications such as edema, hemorrhage, and/or necrosis. Systemically, inflammatory mediators may lead to a systemic inflammatory response syndrome (SIRS) response and potentially sepsis and shock. Bacteremia may occur due to translocation of intestinal flora. Distant organ dysfunction manifested, for example, by pleural effusions, acute respiratory distress syndrome, and renal failure, may also ensue.

Causes

Disease Classification

There are numerous causes of acute pancreatitis (Box 81.1); however, the most common causes in the United States are gallstones (40%–70%) and chronic alcohol consumption (25%– 35%).3 In women, the diagnosis is usually related to gallstones, whereas in men it is usually alcohol-related.4 Endoscopic retrograde cholangiopancreatography (ERCP) is the third leading cause of acute pancreatitis, followed by drugs and trauma. Less common causes include infection, hypertriglyceridemia (serum triglyceride levels > 1000 mg/dL), hypercalcemia, tumors, genetic enzymatic defects, and gland architectural anomalies.5 In 10% to 30% of cases, the cause remains unknown, although it is thought that many of these idiopathic cases are due to occult microlithiasis. The risk of biliary pancreatitis is actually correlated with the decreasing size of gallstones. Smoking and diabetes are independent risk factors for the development of pancreatitis.

Acute pancreatitis can be classified by type—interstitial edematous versus necrotizing pancreatitis—and by local complications. Most patients have the interstitial edematous type, which usually resolves within the first week of illness. About 5% to 10% of patients develop necrotizing pancreatitis, which can involve the pancreatic parenchyma and surrounding tissue. Local complications involving the pancreas, as defined by the revised 2012 Atlanta Classification, are categorized based on whether they occur in the setting of interstitial or necrotizing pancreatitis and whether they are encapsulated (Box 81.2).6 Necrotic tissue may remain sterile, liquefy, or become infected. Infected lesions are associated with increased morbidity. Local complications usually occur after the first week and should be suspected in patients with prolonged or recurrent symptoms, secondary elevation of pancreatic serum markers, or signs of sepsis, such as fever and leukocytosis.

Anatomy and Physiology

Clinical Features

The pancreas is a retroperitoneal organ with endocrine and exocrine functions (Fig. 81.1). It contains three segments—head, body, and tail—that span across the upper abdomen. The pancreatic head sits within the concave C loop of the duodenum, located in the epigastrium. The body of the pancreas traverses posteriorly to the stomach, and the pancreatic tail abuts the hilum of the spleen in the left upper quadrant. A large main pancreatic duct (duct of Wirsung) courses within the pancreas from the tail to the head, where it meets the common bile duct to form the ampulla of Vater, which drains its contents into the duodenum via the sphincter of Oddi. The exocrine function of the pancreas is carried out by the excretion of various digestive enzymes, such as trypsinogen. The endocrine function of the pancreas includes secretion of the regulatory hormones insulin, glucagon, and somatostatin.

Patients with acute pancreatitis typically complain of the rapid onset of constant epigastric or left upper quadrant pain. Pain is usually of moderate to severe intensity, with intensity having no correlation with disease severity. The pain may radiate to the mid back or flanks, sometimes in a bandlike distribution, and may be accompanied by nausea and vomiting. Patients often relate previous episodes of similar pain, relating to biliary colic or mild bouts of pancreatitis. The general appearance is often notable for a patient who is restless and in moderate distress, searching for a position of comfort, such as bending forward. Vital signs commonly reflect patient discomfort or an existing inflammatory process, with rises in temperature, heart rate, or respiratory rate. Blood pressure may be slightly elevated secondary to pain, although in severe or complicated cases hypotension and signs of shock may be present.

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Jaundice can be caused by an obstructing gallstone. Respirations may be shallow due to splinting from pain. Pulmonary examination may reveal decreased breath sounds or basilar crackles in the setting of pulmonary complications. The abdomen can appear normal or distended. Classic descriptions of Cullen’s sign (bluish periumbilical discoloration due to hemoperitoneum) and Grey Turner’s sign (reddish-brown discoloration around the flanks due to retroperitoneal bleeding) are rarely seen but, in cases of hemorrhagic necrotizing pancreatitis, can carry a poor prognosis. Auscultation of the abdomen may reveal normal, diminished, or absent bowel sounds if the patient has concomitant ileus. Palpation of the abdomen often reveals epigastric tenderness with guarding, with rebound tenderness being a less common finding. Right upper quadrant tenderness and the presence of Murphy’s sign may be seen in cases of gallstone pancreatitis.

BOX 81.1 

Causes of Acute Pancreatitis TOXIC—METABOLIC Alcohol Drugs Hyperlipidemia Hypercalcemia Uremia Scorpion venom

MECHANICAL—OBSTRUCTIVE

Biliary stones Congenital—pancreas divisum, annular pancreas Tumors—ampullary, neuroendocrine, pancreatic carcinoma Post-ERCP Ampullary dysfunction or stenosis Duodenal diverticulum Trauma

BOX 81.2 

INFECTIOUS

Local Complications of Acute Pancreatitis

Viral—mumps, coxsackie, HIV, CMV, EBV, varicella Bacterial—TB, Salmonella, Campylobacter, Legionella, Mycoplasma Parasitic—Ascaris

INTERSTITIAL EDEMATOUS PANCREATITIS

• Acute peripancreatic fluid collection—homogeneous fluid collection adjacent to pancreas; seen within 4 wk of symptom onset • Pancreatic pseudocyst—homogeneous fluid collection with well-defined wall; seen >4 wk from symptom onset

VASCULAR

Vasculitis Embolism Hypoperfusion, ischemia Hypercoagulability

NECROTIZING PANCREATITIS

OTHER

• Acute necrotic collection—heterogeneous collection of fluid and necrosis; intrapancreatic and/or extrapancreatic • Walled-off necrosis—heterogeneous collection of fluid and necrosis with well-defined wall; intrapancreatic and/or extrapancreatic; seen >4 wk from symptom onset

Idiopathic Hereditary Diabetes mellitus, DKA Autoimmune CMV, Cytomegalovirus; DKA, diabetic ketoacidosis; EBV, Epstein-Barr virus; ERCP, endoscopic retrograde pancreatography; HIV, human immunodeficiency virus; TB, tuberculosis.

Adapted from Banks PA, Bollen TL, Dervenis C, et al: Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62:102–111, 2013. Spleen

Portal vein Bile duct

Hepatic artery Splenic artery

Superior pancreaticoduodenal artery Tail of pancreas

Superior mesenteric vein Head of pancreas Inferior pancreaticoduodenal artery

Uncinate process Superior mesenteric artery

Fig. 81.1.  Diagrammatic representation of the pancreas, anterior view. (Redrawn from Feldman M, Friedman LS, Sleisenger MH, editors: Sleisenger & Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management, ed 7, Philadelphia, 2002, Saunders.)

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In addition to the direct injury to the pancreas, patients may have local complications involving surrounding structures—for example, bowel necrosis, splenic or portal vein thrombosis, gastrointestinal bleeding, or gastric outlet obstruction. Most of these tend to be late findings. Systemic complications are related to the progression of local inflammation and may result in SIRS. Although in most cases these conditions resolve within days, if persistent there may be progression to fulminant sepsis, shock, and organ failure, especially if there is underlying chronic disease. The pulmonary, cardiovascular, and renal systems are the most important determinants when assessing for organ failure. Increased microvascular permeability is the primary cause of pulmonary sequelae, although enzymatic degradation of surfactant may also play a role. Patients may develop acute respiratory distress syndrome, atelectasis, or pleural effusion, manifested as hypoxemia or respiratory distress. Pleural effusions are present in up to 50% of patients and tend to develop more frequently on the left side. Cardiovascular collapse, as evidenced by decreased mean arterial pressure or the need for inotropic support, may develop as shock results from fluid shifts and volume loss. Renal failure, demonstrated by an elevated creatinine level, may arise from a combination of hypoperfusion and the effects of inflammatory mediators. In addition, coagulopathy occurs from cytokine-mediated activation of the coagulation cascade, potentially leading to thrombocytopenia or disseminated intravascular coagulation. Metabolic abnormalities are also common. Hyperglycemia results from decreased insulin production and hypocalcemia from low albumin and magnesium levels.

Diagnostic Testing The diagnosis of acute pancreatitis is based on the presence of at least two of three criteria—clinical features, laboratory results, and imaging. Clinical features refer to classic historical and exam findings as discussed above, for example, constant upper abdominal pain, possibly with radiation to the back, and tenderness to palpation. The other two criteria rely on diagnostic testing.

Laboratory Results

Differential Diagnosis for Acute Pancreatitis

Laboratory diagnosis of pancreatitis is based on serum amylase and lipase levels. Amylase is an enzyme that functions in carbohydrate digestion that is produced by the pancreas and salivary glands, as well as several other organs to a smaller extent. Amylase levels rise in pancreatitis, but elevations can also be seen in many other conditions, such as malignancy, trauma, burns, salivary and liver disease, cholecystitis, renal failure, HIV, and pregnancy. In acute pancreatitis, the amylase level typically rises within 3 to 6 hours and remains elevated for about 3 to 5 days. Lipase plays a major role in fat metabolism and is produced predominantly by the pancreas. Elevated lipase levels can also be seen in certain extrapancreatic disease processes, but it is more specific for pancreatitis than amylase. Although the lipase level begins to rise in the same time frame as the amylase level, it peaks more rapidly; due to renal reabsorption, rather than excretion, it remains elevated for 1 to 2 weeks. We recommend use of the lipase level in the diagnosis of acute pancreatitis. The amylase level was once preferred because it was cheaper and more widely available, but this is no longer the case, and it is now recognized that the lipase level has greater specificity and sensitivity.8 The difference in sensitivity is particularly notable in patients with delayed presentations and with pancreatitis due to alcohol and hypertriglyceridemia.2 Testing for both enzymes does not improve diagnostic sensitivity or specificity. For both enzymes, three times the upper limit of normal is the most commonly used cutoff value because studies have demonstrated high sensitivity at this level. The degree of amylase or lipase level elevation does not correlate with disease severity or prognosis. Serum transaminase, bilirubin, calcium, and triglyceride levels may be useful in determining the cause of pancreatitis. The alanine aminotransferase level has been shown to be particularly specific for biliary pancreatitis, with a positive predictive value of 95%.

ABDOMINAL DISORDERS

Imaging

Differential Diagnoses A number of disease processes have the ability to mimic the presentation of acute pancreatitis and should be considered in the differential diagnosis (Box 81.3). Inflammation of nearby intraabdominal organs, such as the gallbladder, stomach, and duodenum, are often characterized by a similar pattern of epigastric or upper quadrant abdominal pain. Myocardial infarction, pneumonia, and aortic pathology may also present as lower thoracic or upper abdominal pain, with radiation to the back. BOX 81.3 

Peptic ulcer disease Gastritis, gastroenteritis Biliary colic, cholecystitis Cholangitis Ureteral stone Bowel obstruction Mesenteric ischemia Abdominal aortic aneurysm (AAA) Ectopic pregnancy Perforated viscus

CARDIOPULMONARY DISORDERS Myocardial infarction Pneumonia Pericarditis Pleural effusion

SYSTEMIC DISORDERS Sickle cell crisis Diabetic ketoacidosis

Confirmation of pancreatitis with abdominal imaging is done by computed tomography (CT) or, less commonly, magnetic resonance imaging (MRI) or ultrasound. Although CT is very sensitive and specific for acute pancreatitis, it is not routinely needed for the diagnosis or indicated in the emergency department (ED). CT is only recommended in the following circumstances: (1) in cases of diagnostic uncertainty—for example atypical abdominal pain—or normal pancreatic enzyme levels in the setting of high clinical suspicion; (2) to rule out other suspected intra-abdominal pathology—for example, bowel obstruction or aortic aneurysm; and (3) to assess for complications in patients who fail to respond to appropriate therapy after at least 48 hours.9 The evaluation of complications by CT is best done at least 3 to 7 days after presentation. During the first few days, CT does not accurately identify the degree of pancreatic necrosis, typically underestimating its extent. Complications such as abscess and pseudocyst do not generally develop until several weeks after the onset of symptoms. Studies of patients undergoing early CT have found no benefit compared to delayed imaging.10

CHAPTER 81  Pancreas

If CT is performed, it should be done with intravenous (IV) contrast. The CT scan is normal in 15% to 30% of patients with mild cases of pancreatitis. Abnormal findings include enlargement of the gland and loss of its typical texture and borders. As disease worsens, CT shows decreased or heterogeneous enhancement and increased inflammatory signs, such as surrounding fluid and fat stranding (Fig. 81.2). Pancreatic necrosis is suggested by areas demonstrating no enhancement (Fig. 81.3). In cases for which contrast is contraindicated, CT without contrast may still be useful: alternatively, MRI can be performed. MRI findings of pancreatitis are similar to those of CT. MRI provides superior imaging of the gallbladder and biliary tract, but

is more costly and has limited availability. Ultrasound may show an edematous swollen pancreas, but the study image is often obscured by bowel gas. Although it has limited value in the diagnosis of pancreatitis, ultrasound is sensitive for imaging biliary disease and should be performed early following the diagnosis of pancreatitis to help determine the cause. Abdominal radiographs show primarily nonspecific findings and do not contribute to the diagnosis of pancreatitis. Chest radiography should be performed when pulmonary complications are suspected.

Predicting Disease Severity Although the diagnosis of pancreatitis is relatively straightforward, predicting the disease course is difficult. A number of classification schemes and severity scoring systems have been developed, but none are particularly helpful in the ED at the time of initial patient presentation. The 2012 Atlanta Classification, developed by international consensus to provide a universally applicable system for categorizing pancreatitis severity, is widely recognized (Box 81.4). Based on

A Fig. 81.3.  CT scan showing necrotizing pancreatitis. There is decreased enhancement of the pancreas where the parenchyma has been replaced by necrotic fluid (arrow). (Courtesy Dr. Cash Horn.)

BOX 81.4 

Revised Atlanta Classification of   Acute Pancreatitis MILD

No organ failure No local or systemic complications

MODERATE

Transient organ failure (48 h)a

B Fig. 81.2.  CT scan showing acute interstitial pancreatitis with mild peripancreatic fluid and fat stranding (arrows). A, Axial view. B, Coronal view. (Courtesy Dr. David T. Schwartz.)

a

Organ failure defined as a modified Marshall score of 2 or more for the respiratory, cardiovascular, or renal system. Adapted from Banks PA, Bollen TL, Dervenis C, et al: Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62:102–111, 2013.

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this classification, a patient cannot be diagnosed with severe pancreatitis until 48 hours following presentation, further underlining the dynamic nature of pancreatitis and difficulty in predicting severity at the time of ED evaluation.6 Scoring systems for assessing the severity of pancreatitis are based on using combinations of a variety of clinical features, vital signs, and serum markers. One of the oldest and most well-known is Ranson’s criteria (Box 81.5). This system uses five criteria evaluated at presentation and six criteria evaluated 48 hours later. The total number of criteria present determine a score that can be used to predict the associated mortality rate. Another commonly used scoring system is the Acute Physiology and Chronic Health Evaluation II (APACHE II), which was designed as an intensive care unit (ICU) instrument and consists of 15 variables. A Ranson’s score more than 3 or APACHE II score more than 8 is considered high risk for severe disease. There is also a classification system based on imaging for patients who undergo CT. The modified CT severity index (CTSI) allots points for various CT findings, such as pancreatic inflammation, pancreatic necrosis, fluid collections, and extrapancreatic complications. The score has been shown to correlate with hospital length of stay and development of organ failure, but is no more accurate then clinical scoring systems in predicting outcomes (Table 81.1).11 These systems have been criticized for their complexity, inadequate sensitivity or specificity, reliance on data that may not be immediately available, and inability to calculate a score at presentation. As a result, newer and less cumbersome schemas have been proposed. The bedside index for severity in acute pancreatitis,

BOX 81.5 

Ranson’s Criteriaa AT ADMISSION

Age > 55 yr WBC > 16,000/mm3 Glucose > 200 mg/dL AST > 250 IU/L LDH > 350 IU/L

AT ADMISSION (if biliary cause) Age > 70 yr WBC > 18,000/mm3 Glucose > 220 mg/dL AST > 250 IU/L LDH > 400 IU/L

AT 48 HOURS

Management The treatment of acute pancreatitis is mainly supportive. Volume replacement is important because patients with pancreatitis are often volume-depleted from decreased oral intake, emesis, diaphoresis, or third-spacing of fluids. Early fluid resuscitation reduces the incidence of SIRS and organ failure at 72 hours.15 IV fluid resuscitation within the first 24 hours appears to be more important than the total volume received at 48 hours.16 Fluid resuscitation should be targeted toward reversing hypotension and hemoconcentration and preserving urine output. Hematocrit, blood urea nitrogen, and creatinine can be used as surrogate markers for these goals. Both normal saline (NS) and lactated Ringer’s (LR) solutions are good fluid choices. If available, we prefer LR because it appears to result in better outcomes.17 In large volumes, NS use can lead to the development of a hyperchloremic metabolic acidosis. Acidosis is known to be detrimental in shock states, contributing to the systemic inflammatory cascade. Furthermore, a low pH activates trypsinogen, which makes the pancreatic acinar cells more prone to injury, thereby worsening the severity of pancreatitis. As fluid status is being corrected, electrolyte levels may also need to be addressed. Hypocalcemia is frequently due to hypoalbuminemia, so calcium replacement is not necessary unless the ionized calcium level is low or the neuromuscular effects of hypocalcemia, such as Chvostek’s or Trousseau’s signs, are present. If there is concurrent hypomagnesemia, repletion with magnesium may correct the hypocalcemia. Hyperglycemia results from impaired insulin release, increased gluconeogenesis, and alterations in glucose uptake. Some patients will require exogenous

TABLE 81.1 

Hematocrit drop > 10% BUN rise > 5 mg/dL Calcium < 8 mg/dL PO2 < 60 mm Hg Base deficit > 4 mEq/L Fluid sequestration > 6 L

Test Characteristics for Scoring Systems in Prediction of Outcomes30

AT 48 HOURS (if biliary cause)

Ranson’s

Hematocrit drop > 10% BUN rise > 2 mg/dL Calcium < 8 mg/dL Base deficit > 5 mEq/L Fluid sequestration > 4 L a

BISAP, is a newer scoring system based on five factors: blood urea nitrogen level, impaired mental status, SIRS, age, and pleural effusions.12 Compared to other scoring systems, it has lower sensitivity and similar specificity.13 According to the Harmless Acute Pancreatitis Score (HAPS), in patients with no peritonitis (no rebound or guarding) and normal hematocrit and creatinine levels, there is a very low risk of mortality, necrosis, or need for hemodialysis or ventilatory support. HAPS has been shown to be 97% specific for mild disease, although not sensitive.14 Several isolated serum markers have also been proposed as indicators of severity. C-reactive protein is the most helpful due to its high sensitivity and wide availability; however, its level does not peak until 72 hours following the onset of symptoms. Interleukin-6 and procalcitonin have also shown promise as single markers.

One point given per criterion: 0–2 points, mortality rate, 1%; 3–4 points, mortality rate, 15%; 5–6 points, mortality rate, 40%; ≥7 points, mortality rate, 100%. AST, Aspartate transaminase; BUN, blood urea nitrogen; LDH, lactate dehydrogenase; WBC, white blood cells.

SCORING SYSTEM

PREDICTION OF SEVERE PANCREATITIS

PREDICTION OF MORTALITY

Sensitivity

Specificity

Sensitivity

Specificity

84%

90%

100%

77%

APACHE II

70%

72%

100%

66%

CTSI

86%

71%

100%

59%

BISAP

38%

92%

57%

88%

APACHE, acute physiology and chronic evaluation; CTSI, computed tomography severity index; BISAP, bedside index of severity in acute pancreatitis Data from Papachristou GI, Muddana V, Yadav D, et al: Comparison of BISAP, Ranson’s, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am J Gastroenterol 105:435–441, 2010.

CHAPTER 81  Pancreas

insulin because untreated hyperglycemia may contribute to worsening pancreatitis and immune function. Pain control is another important aspect of management. Opioids are often required because the pain associated with pancreatitis is typically severe. When available, we prefer to use patient-controlled analgesia. Although there is a theoretical risk of morphine causing sphincter of Oddi spasm, there are no clinical studies showing that the administration of morphine causes or worsens pancreatitis or cholecystitis. There are also very little data comparing the efficacy of different opioids for the relief of pain in pancreatitis.18 Antiemetics may also be needed for symptomatic relief. It was once thought that oral or enteral nutrition would worsen pancreatitis by stimulating the secretions of the exocrine pancreas and thereby autodigestion; however, we now know that this does not occur and withholding enteral feeding actually has detriments. It leads to increased gastrointestinal mucosal atrophy and permeability and amplifies bacterial overgrowth and translocation of gut bacteria. It has also been established that total parenteral nutrition is associated with many complications.19 Therefore, oral or enteral nutrition is the preferred method of feeding and may actually be therapeutic. In moderate to severe cases of pancreatitis, early enteral feeding by nasogastric or nasojejunal tube is safe and effective. In mild cases, early oral feeding is safe and may lead to less days of hospitalization.20 A low-fat, solid diet is as safe as clear liquids and can be given as tolerated.21 Antibiotics are not indicated for the prevention of infectious sequelae. Even in severe cases of pancreatitis, antibiotic prophylaxis has not been shown to improve mortality or the need for surgical intervention.22 Their use should be limited to infected necrotizing pancreatitis or extrapancreatic infections such as cholangitis and bacteremia. SIRS features such as tachycardia and tachypnea are common in acute pancreatitis but are nonspecific and do not necessarily portend sepsis or organ failure. However, during the initial ED presentation, it may be difficult to rule out sepsis as the cause. Therefore antibiotics should be initiated if there is suspicion of an infectious source, but not based on SIRS criteria alone. In cases of known infected pancreatic necrosis, the chosen antibiotic regimen should cover gram-negative and grampositive bacteria as well as anaerobes. A quinolone plus metronidazole (ciprofloxacin, 400 mg, and metronidazole, 500 mg bid) or a carbapenem (meropenem, 1 g, or imipenem-cilastatin, 500 mg to 1 g tid) are suitable regimens due to bacterial coverage and pancreatic tissue penetration. Protease inhibitors and histamine 2 (H2) blockers have been proposed as treatment options for acute pancreatitis in the past, but are no longer recommended because studies have shown no effect on clinical outcomes.23 Early ERCP is indicated for patients with cholangitis or biliary obstruction and is recommended within 24 hours of admission. Studies have shown no benefit for other patients with pancreatitis, regardless of predicted severity.24 Because of the potential complications associated with ERCP, it should not be performed unless there is evidence of cholangitis or biliary obstruction, such as jaundice, elevated bilirubin level, and signs of sepsis. Suspicion of choledocholithiasis based on a dilated biliary tree on CT does not itself warrant ERCP. Magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) is recommended for further evaluation in this case. Surgical intervention is rarely indicated at the time of presentation. It is recommended that patients with mild biliary pancreatitis undergo cholecystectomy during the index admission, but not emergently. Asymptomatic pancreatic necrosis and pseudocysts do not need treatment. Infected or symptomatic necrotizing pancreatitis often requires surgical, endoscopic, or radiologic intervention, but not until approximately 4 weeks later, when the collection becomes walled off.

Disposition It is possible to discharge patients with mild presentations whose symptoms are adequately controlled, are tolerating oral intake, and have no signs of complications. However, due to the unpredictable course of pancreatitis, hospital admission for further observation and management is typically warranted. Most patients with acute pancreatitis have mild cases. They are easily managed on a general medical floor and usually discharged within 1 week. About 20% will suffer complications and require a longer hospital stay or higher level of care. The following features should prompt consideration of ICU admission—moderately severe pancreatitis (according to the revised Atlanta classification), continued need for volume resuscitation, persistent SIRS, significant electrolyte abnormalities, older age, or other factors that render a patient high risk for deterioration. Patients who may need endoscopic, surgical, or interventional radiology procedures should be managed in or referred to a specialist center, defined as a high-volume center with daily access to these services. A nationwide analysis has shown that admission to a hospital with an annual volume of acute pancreatitis cases in the highest third is associated with shorter lengths of stay and lower mortality.25

CHRONIC PANCREATITIS Chronic pancreatitis is a progressive inflammatory disorder of the pancreas in which the parenchyma of the gland is gradually replaced by fibrous tissue. It is most commonly diagnosed in middle age, with a mean age at diagnosis of 62 years. The risk is at least twice as high for men compared to women and for African Americans compared to whites.26 Pancreatitis exists as a spectrum, with acute pancreatitis leading to recurrent acute pancreatitis, which in turn leads to chronic pancreatitis. Only a minority of patients progress across this spectrum, with evolution dependent on a number of environmental and hereditary factors. Chronic pancreatitis can be classified as toxic-metabolic, obstructive, genetic, autoimmune, related to recurrent and postnecrotic acute pancreatitis, or idiopathic. Alcohol abuse is the most common cause. Increased risk is associated with alcohol consumption more than five drinks/day. Smoking is also a well-established independent risk factor. The exact mechanisms whereby the various risk factors ultimately result in disease are not entirely understood; however, there is a common pathophysiologic pathway involving progressive inflammation and fibrosis, leading to acinar cell dysfunction and morphologic changes that impair endocrine and exocrine functions. Patients may subsequently develop malnutrition and diabetes and, in some cases, pancreatic cancer.

Clinical Features Patients with chronic pancreatitis may present with prolonged or recurrent abdominal pain, findings relating to local complications and structural changes (eg, bowel obstruction, vascular thrombosis), or signs of pancreatic endocrine and exocrine dysfunction (eg, glucose intolerance, malabsorption, steatorrhea). The nature of the abdominal pain will often be similar to that of acute pancreatitis, described as severe, constant epigastric pain radiating to the mid back, often associated with nausea and vomiting. Food and alcohol intake tend to exacerbate the pain, and weight loss is common. It has been proposed that as the disease process continues, pain may diminish due to progressive loss of functional acinar cells, but evidence has been conflicting.27 On physical examination, patients may appear jaundiced due to alcoholic cirrhosis or biliary obstruction or ill from prolonged malnutrition and malabsorption. The abdomen is usually tender,

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and a palpable mass representing a pancreatic pseudocyst or tumor may be appreciated.

avoidance of alcohol and cigarettes, are also important in the long-term treatment of chronic pancreatitis.

Differential Diagnoses

Disposition

The diagnosis of chronic pancreatitis may be relatively clear-cut in a patient with a history of recurrent pancreatitis or frequent pain that is typical in the presence of risk factors for pancreatitis. However, other diagnoses should always be considered because these patients may also have pathology unrelated to the pancreas or complications of pancreatitis. The list of alternative diagnoses is similar to that for acute pancreatitis (see Box 81.3); however, chronic abdominal processes, such as peptic ulcer disease, gastritis, biliary colic, and irritable bowel syndrome are more consistent with recurrent episodes of upper abdominal pain. In addition, patients with chronic pancreatitis who are opioid-dependent may have withdrawal symptoms that mimic an exacerbation of pancreatitis.

Patients with chronic pancreatitis typically present to the ED with acute exacerbations of pain or complications of their disease. The prognostic indices used for acute pancreatitis can be applied to these patients. Most patients will require admission, with over 90% of hospitalizations related to presentations for abdominal pain.31

Diagnostic Testing The initial diagnosis of chronic pancreatitis is made by one of several imaging modalities, including CT, MRCP, or EUS. CT findings include dilated pancreatic ducts, atrophy, microcalcifications, and complications such as pseudocyst. MRCP and EUS are accurate methods for visualizing pancreatic parenchymal and ductal changes. EUS is the most sensitive imaging test for chronic pancreatitis and is best able to detect subtle and early changes.28 ERCP has mostly been replaced by MRCP because ERCP is invasive and carries a 4% risk of precipitating pancreatitis. These imaging techniques can also rule out pancreatic cancer, which is important because 5% of patients with pancreatic cancer are initially misdiagnosed with chronic pancreatitis.29 For acute exacerbations of chronic pancreatitis, the same diagnostic principles apply as for acute pancreatitis—clinical features, laboratory analysis, and imaging. However, laboratory tests are less helpful in chronic pancreatitis because serum lipase and amylase levels do not rise to the same degree and may be normal. Liver function test results (eg, transaminase, alkaline phosphatase, bilirubin levels) may be elevated in patients with concurrent alcoholic liver disease or biliary duct obstruction. Hypocalcemia and hypoalbuminemia are common, and impaired pancreatic endocrine function may be reflected by hyperglycemia. Although an abdominal radiograph is not necessary, up to 30% of patients have a characteristic finding of pancreatic calcification, which is pathognomonic for the disease.27

Management The treatment of chronic pancreatitis is supportive and largely focused on pain relief and correction of fluid and electrolyte imbalances. Acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) are the preferred initial agents, although escalation to tramadol or a more potent opioid analgesic is often necessary.30 In patients who fail traditional medical management, other pain control options with varying supportive evidence include oral enzyme replacement, octreotide, antioxidants, and celiac plexus block. Referral to a pain management specialist may be beneficial because pain can be difficult to control and the risk of addiction is significant. Beyond ED care, endoscopy may be indicated for the drainage of symptomatic pseudocysts and ductal leaks that result in ascites or for stenting obstructed bile ducts. Surgery is aimed at the restoration of gastrointestinal function and pain relief by decompression of ductal obstruction, which is usually reserved for patients for whom conservative medical treatments have failed. Nutrition replacement, along with lifestyle modifications such as

PANCREATIC CANCER Pancreatic cancer is a particularly lethal form of cancer because it often goes undetected until the later stages. The survival rate is less than 10%, with only about 5% of patients surviving 5 years from the time of diagnosis. Most deaths are related to metastatic disease. Metastasis usually occurs within the abdomen, especially to the liver, but also to the lungs. Ampullary masses, which make up a small percentage of cases, are associated with a better prognosis (up to 50% may be successfully resected) because they tend to cause biliary obstruction, leading to earlier presentation and diagnosis. Pancreatic cancer typically affects people older than 40 years, with a mean age of 71 years at diagnosis. Approximately 85% of cases are adenocarcinoma. About 10% are neuroendocrine tumors such as gastrinomas (Zollinger-Ellison syndrome), insulinomas, and glucagonomas. About two-thirds of pancreatic cancers occur in the head of the pancreas. Smoking is the most clearly linked risk factor for pancreatic cancer; other associations include alcohol abuse, obesity, diabetes, and chronic pancreatitis.32

Clinical Features Typical presenting symptoms include abdominal pain, back pain, anorexia, nausea, weight loss, and weakness. Tumors may cause obstruction, leading to cholestasis, jaundice, pancreatitis, or gastric outlet obstruction. Diabetes is also common. Late-onset diabetes in the setting of these symptoms is suggestive of pancreatic cancer.33 The presentation of neuroendocrine tumors is related to the hormone secreted by the tumor. For example, insulinomas are associated with hypoglycemia, gastrinomas with peptic ulcers, gastroesophageal reflux disease, and diarrhea, and glucagonomas with glucose intolerance, weight loss, and dermatitis.

Diagnostic Testing Abdominal CT with IV contrast is the recommended imaging modality for confirming the diagnosis and for guiding initial management. On CT, pancreatic carcinoma appears as an area of hypoattenuation. CT may also show secondary signs such as pancreatic duct cutoff, dilation of the pancreatic or common bile duct, atrophy, or border irregularities. Although abdominal ultrasound is sensitive for detecting ductal dilatation, it is not sensitive enough for the diagnosis of pancreatic masses. EUS, on the other hand, may be of value in the diagnosis of pancreatic cancer. It is the most sensitive test in early disease and for masses smaller than 2 cm.33

Management Surgical resection can be curative, but is only possible in a very small subset of patients with no direct tumor extension. In patients with locally and systemically advanced disease, treatment is palliative. Chemotherapy and radiation may prolong survival to a small extent.33

CHAPTER 81  Pancreas

Treatment in the ED generally involves pain control and management of complications such as gastrointestinal bleeding, bowel obstruction, acute cholangitis, and venous thrombosis. In situations where the diagnosis of pancreatic cancer is made

in the ED, the disease process may be advanced, and patients may benefit from the emergency clinician expediting their evaluation and facilitating multidisciplinary involvement in the patient’s case.

KEY CONCEPTS • Acute pancreatitis represents a wide spectrum of disease, ranging from mild, short-lived disease to severe life-threatening disease with a mortality rate as high as 30%. • Most cases of acute pancreatitis are caused by gallstones, followed closely by alcohol abuse. • Diagnosis of acute pancreatitis relies on the presence of at least two of these three criteria—typical clinical features, serum amylase or lipase level 3 times the upper limit of normal, confirmatory imaging. • Determining the serum lipase level is preferred over the amylase level because of its greater sensitivity and specificity. • CT does not need to be performed routinely, but only for cases of diagnostic uncertainty or in the later phases to rule out complications. • Following the diagnosis of pancreatitis, abdominal ultrasound should be performed early to determine if the cause is biliary.

• Treatment of acute pancreatitis is mainly supportive, with fluid resuscitation and pain control paramount. Lactated Ringer’s solution is more physiologic than normal saline and may confer better outcomes in patients receiving large volumes of fluids. There is no evidence to support one analgesic agent over another. • Antibiotics are not indicated for prophylaxis and are not purely based on SIRS criteria, but should be given in cases of infected pancreatic necrosis or other clear evidence suggesting infection. • ERCP is only indicated in cases of cholangitis or biliary obstruction. • Most patients require hospitalization for symptomatic control, monitoring of hydration and nutrition status, and management of complications. • There is no perfect scoring system to help predict severity and outcomes in pancreatitis. The most widely accepted systems include Ranson’s, APACHE-II, CTSI, and BISAP. Each has different strengths and weaknesses.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Roberts SE, Thorne K, Evans PA, et al: Mortality following acute pancreatitis: social deprivation, hospital size and time of admission: record linkage study. BMC Gastroenterol 14:153, 2014. 2. Tenner S, Baillie J, DeWitt J, et al: American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 108:1400–1416, 2013. 3. Lankisch PG, Apte M, Banks PA: Acute pancreatitis. Lancet 386:85–96, 2015. 4. Yadav D, Lowenfels AB: The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 144:1252–1261, 2013. 5. Mitchell RM, Byrne MF, Baillie J: Pancreatitis. Lancet 361:1447–1455, 2003. 6. Banks PA, Bollen TL, Dervenis C, et al: Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62:102–111, 2013. 7. Working Group IAP/APA Acute Pancreatitis Guidelines: IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 13:e1–e15, 2013. 8. Smith RC, Southwell-Keely J, Chesher D: Should serum pancreatic lipase replace serum amylase as a biomarker of acute pancreatitis? ANZ J Surg 75:399–404, 2005. 9. Baker ME, Nelson RC, Rosen MP, et al: ACR Appropriateness Criteria® acute pancreatitis. Ultrasound Q 30:267–273, 2014. 10. Shinagare AB, Ip IK, Raja AS, et al: Use of CT and MRI in emergency department patients with acute pancreatitis. Abdom Imaging 40:272–277, 2015. 11. Khanna AK, Meher S, Prakash S, et al: Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI scores, IL-6, CRP, and procalcitonin in predicting severity, organ failure, pancreatic necrosis, and mortality in acute pancreatitis. HPB Surg 2013:367581, 2013. 12. Wu BU, Johannes RS, Sun X, et al: The early prediction of mortality in acute pancreatitis: a large population-based study. Gut 57:1698–1703, 2008. 13. Papachristou GI, Muddana V, Yadav D, et al: Comparison of BISAP, Ranson’s, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am J Gastroenterol 105:435–441, 2010. 14. Lankisch PG, Weber-Dany B, Hebel K, et al: The harmless acute pancreatitis score: a clinical algorithm for rapid initial stratification of nonsevere disease. Clin Gastroenterol Hepatol 7:702–705, 2009. 15. Warndorf MG, Kurtzman JT, Bartel MJ, et al: Early fluid resuscitation reduces morbidity among patients with acute pancreatitis. Clin Gastroenterol Hepatol 9:705–709, 2011. 16. Gardner TB, Vege SS, Chari ST, et al: Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 9:770–776, 2009. 17. Wu BU, Hwang JQ, Gardner TH, et al: Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 9:710–717 e711, 2011.

18. Meng W, Yuan J, Zhang C, et al: Parenteral analgesics for pain relief in acute pancreatitis: a systematic review. Pancreatology 13:201–206, 2013. 19. Marik PE: What is the best way to feed patients with pancreatitis? Curr Opin Crit Care 15:131–138, 2009. 20. Eckerwall GE, Tingstedt BB, Bergenzaun PE, et al: Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery—a randomized clinical study. Clin Nutr 26:758–763, 2007. 21. Moraes JM, Felga GE, Chebli LA, et al: A full solid diet as the initial meal in mild acute pancreatitis is safe and results in a shorter length of hospitalization: results from a prospective, randomized, controlled, double-blind clinical trial. J Clin Gastroenterol 44:517–522, 2010. 22. Jafri NS, Mahid SS, Idstein SR, et al: Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis. Am J Surg 197:806–813, 2009. 23. Seta T, Noguchi Y, Shikata S, et al: Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis. BMC Gastroenterol 14:102, 2014. 24. Tse F, Yuan Y: Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev (5):CD009779, 2012. 25. Singla A, Simons J, Li Y, et al: Admission volume determines outcome for patients with acute pancreatitis. Gastroenterology 137:1995–2001, 2009. 26. Levy P, Dominguez-Munoz E, Imrie C, et al: Epidemiology of chronic pancreatitis: burden of the disease and consequences. United European Gastroenterol J 2:345–354, 2014. 27. Braganza JM, Lee SH, McCloy RF, et al: Chronic pancreatitis. Lancet 377:1184–1197, 2011. 28. Rana SS, Vilmann P: Endoscopic ultrasound features of chronic pancreatitis: a pictorial review. Endosc Ultrasound 4:10–14, 2015. 29. Munigala S, Kanwal F, Xian H, et al: New diagnosis of chronic pancreatitis: risk of missing an underlying pancreatic cancer. Am J Gastroenterol 109:1824–1830, 2014. 30. Chauhan S, Forsmark CE: Pain management in chronic pancreatitis: a treatment algorithm. Best practice and research. Clin Gastroenterol 24:323–335, 2010. 31. Mullady DK, Yadav D, Amann ST, et al: Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut 60:77–84, 2011. 32. Ryan DP, Hong TS, Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med 371:1039– 1049, 2014. 33. Hidalgo M: Pancreatic cancer. N Engl J Med 362:1605–1617, 2010.

CHAPTER 81: QUESTIONS & ANSWERS 81.1. A 28-year-old woman presents with recurrent pancreatitis. She is otherwise healthy and takes no medications. This episode of pain was preceded by several similar episodes of intermittent epigastric pain that lasted several hours at a time. A previous ultrasound examination of the liver, gallbladder, and pancreas was normal. She does not smoke, drink, or use over-the-counter medications. The physical examination is remarkable for moderate epigastric tenderness without rebound. Vital signs are normal. Laboratory evaluation reveals an elevated lipase level and moderate leukocytosis. Urinalysis and urine pregnancy test results are normal. What would be the most appropriate intervention? A. After stabilization, referral to a gastroenterologist for endoscopic retrograde cholangiopancreatography (ERCP) B. After stabilization, referral to a gastroenterologist for upper endoscopy C. Computed tomography (CT) scan of the abdomen to rule out pancreatic pseudocyst D. Repeated ultrasound examination of the liver, gallbladder, and pancreas E. Symptomatic treatment only unless her clinical picture worsens Answer: A. Many cases of presumed idiopathic pancreatitis may be due to small stones or sludge that cannot be seen by ultrasound examination but may be seen by ERCP. Pancreatic pseudocyst is more likely in alcoholic pancreatitis and typically occurs gradually, several months after a severe episode.

81.2. Which of the following statements regarding acute pancreatitis is true? A. Acute pancreatitis may develop in 20% to 30% of ERCP cases. B. The most common adult cause is alcohol abuse. C. The most common geriatric cause is infection. D. The most common pediatric causes are trauma and infection. E. The most common viral cause is HIV infection. Answer: D. The most common viral causes are mumps and coxsackievirus B. The most common adult and geriatric cause is gallstones. Acute pancreatitis is seen in 1% to 10% of ERCP cases. 81.3. Which of the following statements about the serum amylase level is true? A. Elevations may be seen after muscle trauma. B. In acute pancreatitis, levels rise in 1 or 2 hours and normalize in 2 days. C. Increasing the cutoff value decreases the sensitivity for detection of pancreatitis. D. It is a less sensitive test than the serum lipase level for the diagnosis of pancreatitis. E. It is not renally cleared. Answer: A. Although amylase is produced primarily in the pancreas and salivary glands, other sources are muscle, testes, ovaries, small intestine, and fallopian tubes. Levels rise within 6 to 24 hours and normalize in 3 to 7 days. Amylase is renally excreted. Levels may be normal in up to 25% of pancreatitis cases and

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elevated in normal individuals. It is likely to be as sensitive as the serum lipase level but is less specific. Increasing the cutoff value decreases the sensitivity but increases the specificity. 81.4. Which of the following statements regarding the use of radiographic studies for the evaluation of pancreatitis is true? A. CT is indicated in pancreatitis if there is acute deterioration. B. Oral administration of a contrast agent for abdominal CT may aggravate pancreatitis. C. The study of choice in suspected gallstone pancreatitis is ultrasonography. D. Ultrasonography and CT of the abdomen are equally accurate for visualizing the biliary tract.

E. Ultrasonography may help differentiate pancreatitis from pancreatic pseudocyst. Answer: A. There is no perfect test. Ultrasonography has a sensitivity of 94% for gallstones but far less for common bile duct stones or biliary dilation, for which ERCP is the test of choice because of its sensitivity for detecting small duct stones or strictures. CT is excellent for ruling out other causes of abdominal pain (eg, pseudocyst, abscess, necrosis, vascular abnormalities, hemorrhage) and is indicated if the diagnosis is uncertain, if fever and leukocytosis are present, and with acute deterioration. Oral contrast material does not aggravate pancreatitis. A non–contrastenhanced helical scan may also be helpful if an oral contrast agent cannot be tolerated.

C H A P T E R 82 

Disorders of the Small Intestine* Chad E. Roline  |  Robert F. Reardon SMALL BOWEL OBSTRUCTION Background Small bowel obstruction (SBO) is a common problem encountered in the emergency department (ED). Advances in imaging as well as operative techniques have greatly improved the prognosis for patients with this condition and have decreased the mortality rate from nearly 60% in 1900 to less than 8% today.

Anatomy and Physiology There are several different types of SBO. The term mechanical obstruction implies the presence of a physical barrier to the movement of the intestinal contents. Obstructions of this type can be further subclassified according to the cause of the obstruction relative to the intestinal wall (Box 82.1). Lesions external to the intestinal tract cause obstruction by compressing from outside the gut. This is usually a result of postoperative adhesions, but hernias and intraperitoneal neoplasms are other causes. Lesions intrinsic to the intestinal tuberculosis itself can cause mechanical obstruction, such as primary intestinal neoplasms, localized infection (eg, intestinal wall tuberculosis), and trauma-related conditions (eg, a hematoma of the intestinal wall). Lesions within the intestinal lumen itself can lead to obstruction, such as bezoars, ingested foreign bodies, and gallstone ileus. Another important distinction of SBO is whether the obstruction is a simple or closed loop obstruction. A simple obstruction occurs at a single point. A closed loop–type obstruction involves obstruction at two locations, thus creating a segment of bowel with compromised blood flow proximally and distally. Closed loop obstructions are seen when a twist develops in the mesentery or, in the case of an internal hernia, when a loop of bowel becomes entrapped in a defect in the mesentery (Fig. 82.1). If not promptly recognized and relieved, a closed loop obstruction can quickly lead to intestinal infarction and necrosis, which has twice the mortality rate of simple obstructions. In contrast to a mechanical obstruction, a neurogenic or functional obstruction occurs as a result of disruption of the normal coordinated peristaltic activity of the gastrointestinal (GI) tract in the absence of a physical blockage within the intestinal lumen. This is also commonly referred to as an adynamic ileus. The causes of adynamic ileus are listed in Box 82.2. It often occurs in patients who have undergone abdominal surgery and is transient in nature. Some degree of functional obstruction is considered normal after surgery and results from multiple factors, including an inflammatory response to intestinal manipulation, effects of analgesics, and release of hormones and neurotransmitters. In addition to surgery, a number of medical conditions can lead to a functional SBO, including infection, medications, and metabolic abnormalities. The term pseudo-obstruction refers to a poorly understood and complex syndrome in which the signs and symptoms of mechanical obstruction, including the appearance of dilated bowel on *The contributors would like to thank Dr. Susan P. Torrey and Dr. Philip Henneman for their work in earlier editions. 1112

radiography, are present in the absence of a mechanical lesion. This is thought to involve disruption of intestinal pacemaker activity controlled by a specialized group of cells found in the GI tract called the interstitial cells of Cajal (ICCs). These cells regulate the contractility of the intestinal smooth muscle and are under the influence of the enteric nervous and autonomic systems. Pathology at any one of these sites can lead to pseudo-obstruction. Causes include degenerative neuropathies, autoimmune and paraneoplastic disease, and hereditary conditions. The symptoms of pseudo-obstruction are often chronic and respond poorly to treatment.

Pathophysiology Interruption of normal flow through the intestinal lumen triggers a cascade of physiologic changes that correlate with the progressive development of symptoms. In the presence of a mechanical obstruction, the bowel proximal to the blockage first becomes mildly dilated by the accumulation of partially digested food and normal intestinal secretions. These secretions are referred to as succus entericus and are secreted by cells lining the intestinal wall in response to mechanical stimulation. Increased intestinal dilation causes an increase in peristalsis throughout the intestines, which can trigger frequent and loose bowel movements early in the progression of the obstruction as well as episodes of nausea and vomiting. As the process continues, the bowel wall becomes edematous and the normal absorptive function of the intestinal wall decreases, leading to further accumulation of contents in the intestinal lumen proximal to the obstruction. Owing to the loss of normal intestinal motility, bacterial overgrowth begins to occur in the proximal small bowel. It is this overgrowth in a location of the intestines that is normally relatively sterile that explains the feculent nature of the emesis frequently observed in patients with SBO. As the obstruction continues, there is a transudative fluid loss into the peritoneal cavity, leading to worsening hypovolemia and dehydration. In addition, if the obstruction is proximal in location, continued bouts of emesis can lead to electrolyte abnormalities, metabolic alkalosis, severe hypovolemia, and shock. In a closed loop obstruction, the increase in intraluminal pressure occurs much more rapidly because the intestinal contents cannot flow retrograde. Intestinal venous congestion and then arterial obstruction can also progress quickly to intestinal ischemia and infarction, referred to as a strangulation obstruction. If not promptly relieved, necrosis and intestinal perforation can occur. The resulting leakage of the intestinal contents into the peritoneum can lead to peritonitis and sepsis. In the developed world, the most common cause of SBO is postoperative adhesions, which account for approximately 60% of cases.1 These adhesions develop as a result of a process involving the interaction among numerous types of cells, cytokines, and coagulation factors caused by damage to peritoneal surfaces, with a subsequent increase in fibrin formation.2 It has been estimated that 93% to 100% of patients who undergo transperitoneal surgery will develop postoperative adhesions, and up to 25% of them will develop a SBO. In cases of emergent laparotomy for trauma, GI tract perforation is a major independent risk factor

CHAPTER 82  Disorders of the Small Intestine

BOX 82.1 

Lesions Causing Small Bowel Obstruction Relative to the Intestinal Wall EXTERNAL TO INTESTINAL WALL

Postoperative adhesions Hernias Volvulus Compressing masses (tumors, abscesses, hematomas)

INTRINSIC TO INTESTINAL WALL

Primary neoplasms Inflammatory (eg, Crohn’s disease, radiation enteritis) Infectious causes (eg, intestinal tuberculosis) Intussusception Traumatic (intestinal wall hematoma) Intraluminal Bezoars Foreign bodies Gallstones Ascaris infestation

BOX 82.2 

Causes of Adynamic Ileus Metabolic disease (especially hypokalemia) Medications (eg, narcotics) Infection (retroperitoneal, pelvic, intrathoracic) Abdominal trauma Laparotomy

Fig. 82.1.  Diagram of internal hernia. Note the formation of a closed loop, which creates a high risk for strangulation (arrows). (From Martin LC, Merkle EM, Thompson WM: Review of internal hernias: radiographic and clinical findings. AJR Am J Roentgenol 186:703–717, 2006. Reprinted with permission from the American Journal of Roentgenology.)

for the development of SBO while the patient is still in the hospital. Over the last several years, numerous physical bioabsorbable barriers and pharmacologic agents have been evaluated as potentially useful in decreasing the formation of postoperative adhesions.3 The second most common cause of SBO is tumors, which are responsible for roughly 20% of cases. This includes malignancies, such as adenocarcinomas, carcinoid tumors, lymphomas, and sarcomas, and benign conditions, including adenomas, leiomyomas, and lipomas. In addition to these primary GI tumors, gynecologic cancers, especially ovarian cancer, are a very common cause of SBO. Metastatic disease is yet another tumor-related cause of SBO (eg, metastatic breast, skin, and testicular cancers). Hernias are the third most common cause of SBO, found in approximately 10% of cases. Similar to their relative frequency in general, ventral and inguinal hernias are usually encountered, but femoral, parastomal, lateral ventral (also called spigelian hernia), and internal hernias may also lead to SBO. Although rare in the general population, internal hernias are a recognized complication of bariatric surgery, especially when a Roux-en-Y type procedure has been performed. In this group, internal hernias have been described in up to 5% of patients and usually develop at the mesocolic window. Another rare type of hernia is the obturator hernia. This hernia develops into the obturator foramen and is especially common in older women who have recently lost a significant amount of weight. The female pelvis is wider and the obturator canal is more oblique in women than in men. This, in combination with a loss of preperitoneal fat in older, often emaciated patients, predisposes to the development of an obturator hernia. Because an external mass is absent, the diagnosis can be especially challenging, which explains why it carries the highest mortality of any abdominal hernia, nearly 70% when it is incarcerated. Gallstone ileus is a rare but important cause of mechanical SBO (Fig. 82.2). It is responsible for 1% to 4% of all cases of mechanical obstruction and is most frequently seen in older adults with underlying medical problems. The pathogenesis involves the entry of a gallstone into the intestinal tract through a biliary-enteric fistula. This results from the localized inflammation of cholecystitis and, in most cases, entry occurs via a cholecystoduodenal fistula, although cholecystocolonic and cholecystogastric fistulae can also be involved. After entering the intestinal lumen, the gallstone migrates distally. As a stone moves through the intestinal lumen, it often increases in size as bowel content sedimentation becomes attached. Eventually, the gallstone becomes lodged, usually in the ileum, which is the narrowest segment of the small bowel, and the patient then develops symptoms of obstruction.

Fig. 82.2.  Gallstone ileus of the small intestine at laparotomy. (Courtesy J.C. Campbell, Plymouth, England; www.surgical-tutor.org.uk.)

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Small bowel volvulus occurs infrequently but is a potentially catastrophic cause of SBO. This condition results from the abnormal twisting of a loop of small bowel around the axis of its own mesentery. Although it accounts for only 3% to 6% of SBO cases in the West, it is much more common in Africa, India, and the Middle East, where it is responsible for up to 20% of cases. Primary small bowel volvulus occurs in an otherwise normal abdominal cavity; secondary small bowel volvulus occurs when a congenital or acquired abnormality leads to the development of the volvulus, as in the case of intestinal malrotation or as a result of postoperative adhesions. A reported increase in small bowel volvulus during Ramadan has been attributed to eating a large amount of food bulk after prolonged fasting, causing the proximal jejunum to descend into the pelvis, displacing empty small bowel loops upward and initiating malrotation. Alterations in gut motility and increased small bowel length have also been suggested as possible predisposing factors. Secondary causes of small bowel volvulus include intestinal malrotation caused by the arrest of normal rotation of the embryonic gut or because of postoperative adhesions. In the case of malrotation, more than 50% of affected children present for evaluation before 1 month of age with small bowel volvulus. Because a small bowel volvulus is a classic closed loop obstruction, prompt recognition and surgical treatment are imperative because the risk of strangulation is high. The term intussusception describes the invagination or “telescoping” of a part of the small intestine into itself. This results in the development of venous and lymphatic congestion, with consequent intestinal edema, which can lead to intestinal ischemia and perforation. Intussusception occurs in patients of all ages but is most frequently seen in children younger than 2 years. It is the most common cause of intestinal obstruction in infants 6 to 36 months of age. Unlike ileocolic intussusception, which can often be treated nonoperatively by enema reduction, surgery is more often required in cases of intussusception limited only to the small bowel. In children, the cause is usually idiopathic, but several studies have shown an association with adenovirus infection. It has been postulated that enteric adenovirus infection may trigger stimulation of the lymphatic tissue in the intestinal tract, which may create a lead point for the intestine to be dragged into itself by the normal peristaltic activity of the intestines. In contrast to the idiopathic nature of intussusception in children, a mechanical cause is found in more than 90% of adult cases. Tumors, benign or malignant, are discovered as the initiating cause in more than 65% of adult cases. Adult intussusception has been reported in association with acquired immunodeficiency syndrome (AIDS) as a result of lymphoma or unusual infections, such as atypical mycobacterial infections.

Clinical Features History Patients with SBO commonly report crampy abdominal pain, abdominal distention, nausea, vomiting, constipation, and/or the inability to pass flatus. The pain is often described as periumbilical in location and typically has a crescendo-decrescendo pattern. The recurrent waves of discomfort can last from seconds to minutes. In more proximal obstruction, symptoms of nausea and vomiting can be much more severe, and the onset of symptoms is often more abrupt. Distal obstructions typically cause symptoms over a slower period of 1 to 2 days and are frequently accompanied by greater abdominal distention. The colon requires up to 24 hours to empty after the formation of an SBO, and the associated small bowel distention stimulates peristalsis; consequently, flatus and the passage of stool may continue, even in the

presence of a complete obstruction. A history of previous obstructions as well as a thorough past surgical history should be obtained, and any history of malignancy or inflammatory bowel disease should be elicited. The use of medications (especially narcotics) that may affect bowel function should be reviewed.

Physical Examination The physical examination starts with a careful evaluation of the patient’s hemodynamic status, degree of distress, and general condition. Thus, patients requiring resuscitation can be quickly identified, and the appropriate interventions, including intravenous (IV) fluids, can be initiated early. Inspection of the patient includes a careful search for abdominal distention and hernias and should include a genital examination. Although bowel sounds in SBO are frequently described as high-pitched and tinkling in nature, studies have shown that they are also frequently decreased or absent. One study has shown that physicians listening to recordings of bowel sounds were able to identify SBO correctly in only 42% of affected patients.4 The presence of peritoneal signs usually indicates late obstruction with complications, including strangulation. However, abdominal palpation in the setting of bowel dilation can give the false impression of peritonitis, because quick compressiondecompression of dilated bowel may elicit a pain response. For this reason, it may be helpful to determine the presence of pain with cough or gentle shaking of the patient’s pelvis to investigate for true peritonitis better.

Differential Diagnosis The diagnosis of SBO should be considered in any patient with abdominal pain and vomiting, especially if there is a history of prior abdominal surgery. It may be difficult to differentiate SBO from nonobstructive intestinal motility disorders, such as adynamic ileus or intestinal pseudo-obstruction, by history and physical examination alone. Other conditions to consider in the differential diagnosis include gastroenteritis, mesenteric adenitis, constipation, cholelithiasis or nephrolithiasis, ectopic pregnancy, pancreatitis, peptic ulcer disease, atypical myocardial infarction, leaking abdominal aortic aneurysm (AAA), and mesenteric ischemia. These pathologies have typical signs, symptoms, and diagnostic findings that can help differentiate them from one another and from SBO, but this may be challenging, especially early in the course of the particular disorder.

Diagnostic Testing Laboratory Although laboratory tests are not helpful in diagnosing the presence of SBO, they can be useful in assessing the degree of dehydration and metabolic disruption resulting from the obstruction. Studies have evaluated the use of lactate and creatinine phosphokinase to identify strangulation complicating SBO. Intestinal fatty acid binding protein, which is released by necrotic enterocytes, has also been studied in an attempt to identify strangulation. Unfortunately, all the biomarkers studied to date may be normal until very late in the process of intestinal strangulation. While recognizing this, an elevated lactate level should increase the clinical suspicion for strangulation.

Imaging Traditionally, plain film radiographs have been the initial imaging test of choice in the diagnosis of SBO. Abdominal plain film

A

Supine

Upright

CHAPTER 82  Disorders of the Small Intestine

B

Fig. 82.3.  A, Supine plain film radiograph showing dilated loops of small bowel in a patient with small bowel obstruction. B, Upright abdominal plain radiograph revealing multiple air-fluid levels and small bowel dilation, consistent with a diagnosis of small bowel obstruction.

radiographs should include supine and upright or decubitus views. An upright chest radiograph may also be obtained to evaluate for subdiaphragmatic free air resulting from a bowel perforation. Characteristic plain radiographic findings of SBO include distended loops of bowel, normally greater than 3 cm in diameter, seen centrally in the radiograph (Fig. 82.3). In addition, unlike the haustra of the large intestine, which do not cross the full diameter of the bowel, the valvulae conniventes (or plicae circulares) of the small bowel cross the entire lumen of the small intestine, thus helping differentiate SBO from large bowel obstruction. In general, the greater the number of distended loops, the more distal the obstruction. No gas should be seen in the large bowel unless the films are obtained early in the course of the obstruction or in the presence of a partial SBO. An adynamic ileus, on the other hand, tends to show extensive air-filled loops throughout the entire GI system and no small bowel dilation. Unfortunately, plain radiographic findings are diagnostic in only 50% to 60% of cases of SBO, equivocal in 20% to 30%, and normal, nonspecific, or misleading in 10% to 20%. Computed tomography (CT) has become an increasingly popular imaging modality for the evaluation of SBO and has become the gold standard for imaging in suspected SBO. CT detects SBO with a high degree of sensitivity and specificity. In addition, unlike plain films, CT scans provides more information about the cause of obstruction, such as a tumor. More important acutely, unlike plain radiographs, CT scans are very sensitive for detecting strangulation, with a specificity of 96% and likelihood ratio of 9.3.5 According to the American College of Radiology Appropriateness Criteria, the CT scan of choice for the evaluation of a suspected high-grade bowel obstruction is a scan of the abdomen and pelvis with IV contrast and without oral contrast. This guideline states that “oral contrast will not reach the site of obstruction, wastes time, adds expense, can induce further patient discomfort, will not add to diagnostic accuracy, and can lead to complications, particularly vomiting and aspiration.”6 Historically ultrasound had limited value for evaluating SBO due to the significant artifact caused by gas within the GI tract.

Fig. 82.4.  Ultrasound image of fluid-filled dilated small bowel in small bowel obstruction. (Courtesy Masaaki Ogata, Kobe, Japan.)

However, the improved resolution of newer scanning devices has made this modality more attractive and an exciting area of exploration in the diagnosis of SBO. Typical ultrasound findings in SBO include fluid-filled bowel with dilated loops greater than 2.5 cm in diameter with decreased or absent peristalsis with proximally collapsed bowel (Fig. 82.4). Abdominal free fluid between loops of dilated bowel (the tanga sign) is suggestive of a high-grade obstruction.7 In summary, although the benefits of plain radiographs include rapid acquisition and lower radiation, they are diagnostic in only 50% of SBOs. Ultrasound is quickly emerging as a potentially very useful tool in the diagnosis of SBO, but further research is needed

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to clarify its role. Abdominal and pelvis CT scanning with IV contrast currently remains the preferred imaging test of choice because it is the most sensitive and specific test for detecting SBO and is the most likely to identify both the cause and complications of the obstruction (specifically strangulation) with a high degree of sensitivity.

Management Hemodynamically unstable patients should be resuscitated with crystalloid solution via a large-bore catheter. Findings suggestive of bowel strangulation should prompt rapid surgical consultation. Although many emergency clinicians and surgeons consider the use of nasogastric decompression to be dogma, its effect in decreasing the duration of SBO has scant support in the medical literature. In the era of modern antiemetics, in the setting of a simple SBO due to adhesions, if the patient’s symptoms of nausea and vomiting can be controlled with medication (eg, ondansetron 4 mg IV every 6 to 8 hours or metoclopramide, 10 mg IV every 6 to 8 hours), it may be reasonable to delay nasogastric tube insertion. However, if symptoms persist or if the patient has an altered level of consciousness placing him or her at risk for aspiration, a nasogastric tube should be promptly inserted and attached to wall suction. There is no benefit to the use of long intestinal tubes instead of a traditional nasogastric tube. Placement of a nasogastric tube is a noxious procedure, and attempts should be made to anesthetize the patient’s nasopharynx with topical anesthetic before insertion. There are numerous serious complications associated with SBO. Persistent vomiting can lead to hypovolemia, metabolic alkalosis, and shock. If strangulation occurs, necrosis of the bowel can lead to perforation, and leakage of contaminated bowel contents into the peritoneal space can cause peritonitis, intra-abdominal abscess formation, and sepsis. As one would expect, complications are more common in older adults and those with comorbidities. There are also several potential complications related to surgical intervention for SBO, including wound infection and short bowel syndrome. Unfortunately, in addition to these adverse effects, the rate of recurrence of SBO is high—40% for patients treated nonoperatively and 27% for those treated operatively. For patients with SBO secondary to adhesions, the relative risk of recurrence increases with the number of prior episodes of obstruction. For those with four or more episodes of adhesional SBO, the recurrence rate is more than 80%. There is no convincing evidence to recommend the empirical use of antibiotics for the nonoperative management of a simple SBO. In patients in whom surgical exploration is planned or perforation is suspected, antibiotics are recommended and should provide coverage against the gram-negative and anaerobic organisms that colonize the intestinal tract (eg, a second-generation cephalosporin such as cefuroxime, 1000 mg IV tid, or a broadspectrum carbapenem such as meropenem, 1000 mg IV tid). SBO in the presence of known malignancy is very common, occurring in up to 30% of patients with colon cancer and in 50% of patients with ovarian cancer at some time in the course of their disease. Patients who do not qualify for surgical intervention because of intra-abdominal carcinomatosis, massive ascites, or poor overall health status can be treated with self-expanding metal stents and the use of octreotide, 0.3 mg/day, given over three doses or as a continuous infusion to reduce GI secretions rapidly, may provide palliative relief. A collaborative approach with the patent’s oncologist and consulting surgeon can provide the ideal individualized treatment for the patient in this situation. In the setting of terminal metastatic disease, although surgery may provide temporary symptomatic improvement, it often comes at the cost of a significant proportion of the patient’s remaining days being spent in the hospital.8

Disposition Patients with SBO merit admission to the hospital. Many simple SBOs related to adhesions will resolve with conservative treatment in the next 48 to 72 hours. In case of a partial SBO, in which initial imaging suggests that some colonic contents can pass the obstruction, some surgical guidelines suggest administration of a watersoluble contrast medium at admission or after 48 hours of failed conservative treatment. Appearance of contrast in the colon within 24 hours of administration predicts nonoperative resolution of the obstruction.9,10 One study has found that patients with SBO admitted to a surgical service for inpatient management had a shorter length of stay, lower hospital charges, and lower mortality than those admitted to a medical service.11 This was attributed largely to the fact that patients for whom conservative management was failing and needed surgical intervention were identified earlier when being managed primarily by the surgical team. Regardless of admitting service, patients with SBO need frequent reassessment to determine disease progression or resolution. Finally, although laparoscopic surgery was once considered inappropriate for the management of SBO, there has been a growing experience with its successful use in patients with SBO, particularly those with obstructions caused by adhesions.12

ACUTE MESENTERIC ISCHEMIA Background Acute mesenteric ischemia involves the sudden reduction or loss of blood flow to the small bowel and may also involve the right colon. The left colon has a much higher degree of collateral blood flow and is less prone to mesenteric ischemia. When acute mesenteric ischemia occurs, rapid intestinal injury results. This condition should be clearly differentiated from chronic mesenteric ischemia (CMI), also referred to as intestinal angina, which often manifests as recurrent episodes of abdominal pain resulting from insufficient intestinal blood flow during periods of increased postprandial metabolic demand. CMI does not usually require emergent therapy; however, it is also possible for acute mesenteric ischemia to develop in these patients. Overall, acute mesenteric ischemia is a rare clinical problem. There are four specific clinical categories that make up the overwhelming majority of causes, each with distinct epidemiologic risk factors—mesenteric arterial embolus, mesenteric arterial thrombosis, nonocclusive mesenteric ischemia, and mesenteric venous thrombosis. Despite significant advances in the understanding of the pathophysiology, the mortality rate has remained as high as 60 to 80%, and the diagnosis and treatment of this vascular catastrophe have remained difficult.

Anatomy and Physiology The mesenteric vessels arise from the primitive ventral segmental arteries. Although there is considerable individual variability, these vessels typically regress as embryologic development proceeds, with the exception of the 10th, 13th, and 21st segmental arteries. These become the celiac trunk, superior mesenteric artery (SMA), and inferior mesenteric artery (IMA), respectively. The celiac trunk arises from the anterior aspect of the abdominal aorta and branches into the common hepatic, splenic, and left gastric arteries. These vessels supply the distal esophagus to the duodenum at the entrance of the bile duct. The SMA normally arises 1 cm below the celiac trunk and runs toward the cecum, terminating as the ileocolic artery. The SMA supplies the distal half of the duodenum to the proximal two-thirds of the transverse colon. The IMA originates approximately 6 to 7 cm below the SMA and gives rise to the left colic artery, sigmoid arteries, and

CHAPTER 82  Disorders of the Small Intestine

hemorrhoidal arteries. Anatomically, this vessel provides blood flow to the distal third of the transverse colon to the rectum. The gut receives 20% of cardiac output at rest and up to 35% after eating. Of this, up to 70% supplies the mucosa due to the high metabolic demands required for the absorptive function of this intestinal layer. Intestinal blood flow is regulated by a complex combination of intrinsic and extrinsic mechanisms to match intestinal demands with blood supply. Intrinsic factors provide the moment to moment control of the intestinal circulation; they function independently from neural control. This intrinsic modulation has been proposed to involve the release of local metabolites produced as a result of mucosal ischemia. These metabolites then diffuse to the local arterioles, triggering relaxation in the smooth muscle and increased blood flow, thereby allowing for efficient adjustments to the intestinal blood supply. Smooth muscle relaxation can also be brought about directly by a decrease in the perfusion pressure in the arterioles themselves. These two mechanisms are referred to as the metabolic and myogenic pathways. Intestinal blood flow is also controlled extrinsically through neural and hormonal mechanisms. Increased sympathetic tone to the paired celiac ganglia located adjacent to the celiac trunk results in mesenteric and arteriolar vasoconstriction. Hormonal influences include the direct action of angiotensin II released as a result of decreased extracellular volume, as well as vasopressin, which causes mesenteric vasoconstriction.

Pathophysiology Although these mechanisms allow for the mesenteric circulation to adapt to wide variations in the metabolic needs of the gut and systemic perfusion, the bowel is very quickly injured in the setting of acute compromise. Because of the high metabolic demands of the intestinal mucosa, structural damage to the intestinal villi can be observed histologically within 15 minutes of absolute ischemia. If not corrected, mucosal sloughing occurs within 3 hours. By 6 hours, transmural necrosis is complete (Fig. 82.5). Complicating the situation even further, reestablishment of blood flow at this point results in the systemic release of several proinflammatory cytokines and toxic oxygen radicals caused by reperfusion, which can lead to multiorgan failure and rapid death.

and two-thirds are women. Emboli are usually cardiac in origin and arise from left atrial or ventricular mural thrombi or valvular lesions. Risk factors for the development of such thrombi include myocardial ischemia or infarction, cardiomyopathies, ventricular aneurysms, endocarditis, and atrial dysrhythmias, specifically atrial fibrillation. Compared with the estimated annual risk of stroke of 2.3%, the annual risk of AMI caused by thromboembolism secondary to atrial fibrillation is 0.14%.13 The SMA is most frequently affected because of the large caliber of the vessel and its narrow takeoff angle from the aorta. The embolus typically lodges 3 to 10 cm distal to the origin of the SMA (Fig. 82.6). The jejunum is most often involved, as it is distant from the collateral flow provided from the celiac and inferior mesenteric arteries.

Mesenteric Arterial Thrombosis Mesenteric arterial thrombosis results from the progression of atherosclerotic disease of the mesenteric vasculature. Risk factors for development include advanced age, hypertension, diabetes, and tobacco use. Affected patients frequently have a history suggestive of CMI of several months’ or years’ duration. Unlike embolic occlusions, thrombosis usually occurs in the proximal SMA at the origin of the vessel.

Nonocclusive Mesenteric Ischemia Nonocclusive mesenteric ischemia occurs as a result of mesenteric vasospasm in the absence of a physical obstruction. This vasospasm is triggered by mesenteric hypoperfusion or excessive sympathetic nervous system activity. Mesenteric hypoperfusion can result from a wide variety of conditions, including sepsis, severe dehydration, pancreatitis, or hemorrhagic shock. Excessive sympathetic activity can result from congestive heart failure, or the use of medications and drugs such as vasopressors, cocaine, or digoxin. Once initiated, this vasospasm often persists even after correction of the underlying condition, and repeated episodes of ischemia and reperfusion occur. Studies suggest that this recurrent pattern of ischemia and reperfusion may result in more severe histologic injury than a single episode of prolonged ischemia.

Mesenteric Arterial Embolism Arterial emboli, the most common cause of acute mesenteric ischemia, are responsible for approximately 50% of cases. The median age of patients with mesenteric arterial emboli is 70 years,

Fig. 82.5.  Gross pathologic image of intestinal ischemia and infarction. Note mucosal hyperemia and hemorrhage. (From Gore RM, et al: Imaging in intestinal ischemic disorders. Radiol Clin North Am 46:845–875, 2008.)

Fig. 82.6.  Coronal abdominal CT angiogram with large superior mesenteric artery embolism (arrow). (From Gore RM, et al: Imaging in intestinal ischemic disorders. Radiol Clin North Am 46:845–875, 2008.)

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Factors Associated With Mesenteric Venous Thrombosis HYPERCOAGULABLE STATES

Polycythemia vera Sickle cell disease Antithrombin III deficiency Protein C or S deficiency Malignancy Myeloproliferative disorders Estrogen therapy, oral contraceptive pills Pregnancy

INFLAMMATORY CONDITIONS

Fig. 82.7.  Superior mesenteric venous thrombus (red arrow) in a patient with nondescript abdominal pain. Hematologic evaluation revealed factor V Leiden thrombophilia. (From Gore RM, et al: Imaging in intestinal ischemic disorders. Radiol Clin North Am 46:845–875, 2008.)

Mesenteric Venous Thrombosis

Pancreatitis Diverticulitis Appendicitis Cholangitis

TRAUMA

Operative venous injury Postsplenectomy Blunt or abdominal trauma

MISCELLANEOUS

Congestive heart failure Renal failure Decompression sickness Portal hypertension

Mesenteric venous thrombosis is the least common cause of acute mesenteric ischemia (AMI), accounting for only 5% to 15% of all mesenteric ischemic events. It usually involves the superior mesenteric vein and its branches (Fig. 82.7). In the vast majority of cases (>75%), an underlying inherited thrombotic disorder or inherited or acquired hypercoagulable state can be identified. The most common cause is factor V Leiden mutation, which is thought to account for 20% to 40% of cases. Other inherited prothrombotic states implicated in the development of mesenteric venous thrombosis include deficiency in antithrombin III, protein C, or protein S. Hematologic conditions predisposing to this condition include polycythemia vera and essential thrombocythemia. Oral contraceptive use accounts for 9% to 18% of the episodes of mesenteric venous thrombosis in young women. Local intraabdominal inflammation secondary to pancreatitis, malignancy, or inflammatory bowel disorders also increases the risk of mesenteric venous thrombosis. Finally, the venous stasis caused by portal hypertension is a recognized risk factor. Box 82.3 summarizes causes of mesenteric venous thrombosis.

(vomiting or diarrhea) in a patient with cardiac disease. This is especially true in cases of SMA embolism or thrombosis, in which symptoms and clinical deterioration can rapidly occur. In cases of mesenteric venous thrombosis, the symptoms are slower in onset and often have been present for several days by the time the patient seeks medical attention. Approximately one-third of patients with acute embolic mesenteric ischemia and 50% of patients with acute mesenteric venous thrombosis have a personal history of an embolic event, such as a pulmonary embolism, deep vein thrombosis, or ischemic stroke. Patients with nonocclusive mesenteric ischemia are often already critically ill and in the hospital, making it difficult or impossible for them to provide historical details to the treating physician.

Unusual Causes of Mesenteric Ischemia

Physical Examination

In addition to the conditions already described, there are numerous case reports of unusual causes of mesenteric ischemia. These include SMA dissection leading to occlusion, tumor emboli, retroperitoneal fibrosis, and various types of vasculitis, including Buerger’s disease, polyarteritis nodosa, and Takayasu’s arteritis. Because these conditions involve a rare cause of an already rare condition, they frequently go unrecognized until patients develop major adverse effects.

Clinical Features

The pain in acute mesenteric ischemia is typically described as being out of proportion to the physical examination findings. The patient may be writhing in pain but have a soft abdomen without guarding, especially early in the course of the event, when only the visceral structures are ischemic. As the parietal peritoneum becomes ischemic, the abdominal physical findings progress. If the ischemia progresses to infarction, peritonitis may be present. Heme-positive stools may also be noted. Hypotension, tachycardia, and tachypnea are all signs of severe ischemia and suggest a poor prognosis.

History

Differential Diagnosis

The history at presentation of mesenteric ischemia is largely dependent on the nature of the underlying cause. The traditional historical triad of acute mesenteric ischemia is the sudden onset of poorly localized abdominal pain and gastric emptying

Other potentially devastating conditions to consider in the differential diagnosis of acute-onset severe abdominal pain include leaking AAA, perforated viscus, bowel obstruction, biliary disease, and atypical myocardial infarction.

CHAPTER 82  Disorders of the Small Intestine

Diagnostic Testing Laboratory Tests Initial laboratory results in patients with acute mesenteric ischemia are often nonspecific and may include leukocytosis, an elevated hematocrit secondary to hemoconcentration, and metabolic acidosis. Several serum biomarkers have been investigated as early indicators including lactate, D-dimer, interleukin (IL)-6, and serum ischemia-modified albumin levels. A meta-analysis has shown a pooled sensitivity of 86% and pooled specificity of 42% for l-lactate, and a pooled sensitivity of 96% and a pooled specificity of 40% for D-dimer.14 To date, no biomarkers have been found that are sufficiently sensitive and specific to diagnose or eliminate mesenteric ischemia based on laboratory results alone. Recognizing these limitations, when considering this diagnosis, the serum lactic acid level is currently the most useful laboratory test available. In addition to its wide availability and rapid turnaround time, the short half-life of serum lactic acid (≈20 minutes) may be useful for the emergency clinician to allow for serial measurements, especially early in the course of suspected acute mesenteric ischemia.

Imaging Plain abdominal radiographs in mesenteric ischemia are usually nonspecific. Later in the disease course, plain radiographic findings may show so-called thumbprinting, in which multiple, round, smooth soft tissue densities project into the intestinal lumen because of mucosal and submucosal edema and hemorrhage. More specific but very late plain radiographic findings indicating infarction include pneumatosis intestinalis and portal venous gas. Mesenteric angiography remains the gold standard in the radiographic evaluation for mesenteric ischemia and offers the benefit that diagnosis and initial treatment can occur concurrently. However, angiographic services are often not readily available on a routine basis. As a result, CT angiography has largely replaced conventional angiography as the initial imaging study of choice for the evaluation of mesenteric ischemia. Several studies have shown that with the emergence of multidetector scanners, the sensitivity and specificity for mesenteric ischemia are high, approximately 94% and 96%, respectively.15 Duplex sonography has been found to be very specific (92%– 100%) for the detection of AMI, but its sensitivity is decreased (70%–89%) by limited evaluation beyond the proximal main vessel. It is also unable to provide much information about complications of acute mesenteric ischemia, including bowel infarction.

Management Once AMI has been diagnosed, the goals of treatment are to restore mesenteric blood flow as rapidly as possible, manage underlying conditions, treat persistent mesenteric vasospasm if present, and mitigate the risk of further clot propagation. Initial interventions should focus on fluid resuscitation and hemodynamic stabilization. Because these patients are often older adults

with cardiac comorbidities, invasive monitoring may be indicated. If vasopressors are required, dobutamine, low-dose dopamine, or milrinone are recommended, because these have been shown to have less of a vasoconstrictive effect on the mesenteric vasculature than other agents. With evidence of infarction, perforation, or peritonitis, antibiotics suitable for enteric coverage, such as ceftriaxone, 1g IV qd, or ciprofloxacin 500 mg qd, with either in combination with metronidazole, 500 mg IV tid, are recommended, and a surgeon should be promptly consulted. Further management depends on the cause of ischemia, and controversies exist about the optimal management of these critically ill patients. Regardless of cause, if signs of intestinal infarction or perforation with peritonitis are present, prompt emergent laparotomy is warranted. Preoperative conventional angiography may be beneficial to attempt rapid revascularization, and studies have suggested that initial endovascular revascularization may significantly improve patient outcomes and dramatically alter the future treatment of AMI.16,17 Numerous reports have detailed the use of thrombolytic agents, angioplasty, embolectomy, or vascular stenting to restore mesenteric blood flow. In addition, the phosphodiesterase inhibitor papaverine may be continuously infused directly into the compromised vessel. This agent results in elevated levels of cyclic adenosine monophosphate (cAMP), which results in profound smooth muscle relaxation. Because cAMP undergoes over 90% first-pass hepatic metabolism, few systemic effects are noted when it is infused directly into the mesenteric circulation. Primary treatment of nonocclusive mesenteric ischemia involves interventions to reverse the underlying cause and consideration for papaverine infusion via angiographic catheter, as well as IV heparin to prevent thrombosis in the vasospastic vessel. Papaverine infusion is often maintained for 24 hours, at which time angiography may be repeated to evaluate for the resolution of vasospasm. If peritoneal signs develop, laparotomy is indicated. If the underlying medical condition persists, the mortality of nonocclusive mesenteric ischemia remains high. The treatment of mesenteric venous thrombosis is unique in that in the absence of peritoneal findings, initial treatment with heparin infusion alone may be adequate. However, if peritoneal findings are present or develop later in the patient’s hospital course, bowel necrosis is likely, and prompt laparotomy is indicated. If the patient recovers, long-term anticoagulation with warfarin usually is provided to prevent recurrence. An appropriate evaluation for hypercoagulable conditions should be undertaken. Even with prompt recognition and treatment of acute mesenteric ischemia, a complicated course is expected. Secondary reperfusion injury is common, and bowel initially identified as viable may progress to necrosis. Other complications include wound infections, sepsis, and pneumonia. Given the population in which AMI tends to occur, the physiologic stress of this disease process also places patients at high risk for myocardial infarction, renal failure, and pulmonary embolism while in the hospital.

Disposition All patients with acute mesenteric ischemia require admission to the intensive care unit.

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KEY CONCEPTS Small Bowel Obstruction

• The most common cause of SBO is postoperative adhesions. Other common causes include neoplasm and hernias. • Abdominal CT with IV contrast is the gold standard for imaging in cases of suspected SBO. It is sensitive and specific and provides information about the cause of the obstruction and potential complication of strangulation. • Bedside ultrasound for SBO may be a potentially useful imaging modality, but more research is needed. • Many patients with SBO will improve with nonoperative conservative treatment; however, prompt surgical exploration is recommended when there is suspected bowel strangulation. • Antibiotics are not indicated in cases of simple SBO. • The recurrence rate for SBO is high, regardless whether treatment is operative or nonoperative.





• •

Acute Mesenteric Ischemia

• Acute mesenteric ischemia (AMI) is a rare vascular catastrophe, with a very high mortality. • AMI should be considered in patients older than 50 years with a history of cardiac disease who have acute abdominal pain, which



may initially appear severe and out of proportion to physical examination findings. Within the diagnosis of AMI are four distinct clinical entities with specific associated risk factors, clinical presentations, and treatments—mesenteric arterial embolism, mesenteric arterial thrombosis, nonocclusive mesenteric ischemia, and mesenteric venous thrombosis. Although no current laboratory test has sufficient sensitivity or specificity to diagnose acute mesenteric ischemia alone, determination of the serum L-lactate level is currently the most useful. CT angiography is the initial imaging test of choice for the evaluation of suspected AMI. Successful management of acute mesenteric arterial embolism and thrombosis frequently requires multispecialty, care including general or vascular surgery, interventional radiology, and critical care, with the goal of restoring mesenteric blood flow as quickly as possible. Unlike cases of arterial embolism or thrombosis, in the absence of peritonitis, mesenteric venous thrombosis is often successfully managed with heparin alone.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 82  Disorders of the Small Intestine

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REFERENCES 1. ten Broek RP, Issa Y, van Santbrink EJ, et al: Burden of adhesions in abdominal and pelvic surgery: systematic review and meta-analysis. BMJ 347:f5588, 2013. 2. Hellebrekers BW, Kooistra T: Pathogenesis of postoperative adhesion formation. Br J Surg 98:1503–1516, 2011. 3. Schnüriger B, Barmparas G, Branco BC, et al: Prevention of postoperative peritoneal adhesions: a review of the literature. Am J Surg 201:111–121, 2011. 4. Gu Y, Lim HJ, Moser MA: How useful are bowel sounds in assessing the abdomen? Dig Surg 27:422–426, 2010. 5. Jancelewicz T, Vu LT, Shawo AE, et al: Predicting strangulated small bowel obstruction: an old problem revisited. J Gastrointest Surg 13:93–99, 2009. 6. American College of Radiology (ACR): ACR Appropriateness Criteria: suspected small-bowel obstruction. . 7. Jang TB, Schindler D, Kaji AH: Bedside ultrasonography for the detection of small bowel obstruction in the emergency department. Emerg Med J 28:676–678, 2011. 8. Paul Olson TJ, Pinkerton C, Brasel KJ, et al: Palliative surgery for malignant bowel obstruction from carcinomatosis: a systematic review. JAMA Surg 149:383–392, 2014. 9. Maung A, et al: Evaluation and management of small-bowel obstruction: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg 73(Suppl):S362–S369, 2013.

10. Catena F, Di Saverio S, Kelly MD, et al: Bologna Guidelines for Diagnosis and Management of Adhesive Small Bowel Obstruction (ABSO): 2010 Evidence-Based Guidelines of the World Society of Emergency Surgery. World J Emerg Surg 6:5, 2011. 11. Oyasiji T, Angelo S, Kyriakides TC, et al: Small bowel obstruction: outcome and cost implications of admitting service. Am Surg 76:687–691, 2010. 12. Tierris I, Mavrantonis C, Stratoulias C, et al: Laparoscopy for acute small bowel obstruction: indication or contraindication? Surg Endosc 25:531–535, 2011. 13. Menke J, Lüthje L, Kastrup A, et al: Thromboembolism in atrial fibrillation. Am J Cardiol 105:502–510, 2010. 14. Cudnik MT, Darbha S, Jones J, et al: The diagnosis of acute mesenteric ishemia: a systematic review and meta-analysis. Acad Emerg Med 20:1087–1100, 2013. 15. Meke J: Diagnostic accuracy of multidetector CT in cute mesenteric ischemia: systematic review and meta-analysis. Radiology 256:93–101, 2010. 16. Arthurs ZM, Titus J, Bannazadeh M, et al: A comparison of endovascular revascularization with traditional therapy for the treatment of acute mesenteric ischemia. J Vasc Surg 53:698–705, 2011. 17. Resch TA, Acosta S, Sonesson B: Endovascular techniques in acute arterial mesenteric ischemia. Semin Vasc Surg 23:29–35, 2010.

CHAPTER 82: QUESTIONS & ANSWERS 82.1. What is the most common cause of small bowel obstruction in the developed world? A. Gallstone ileus B. Hernias C. Intussusception D. Postoperative adhesions E. Tumors Answer: D. In the developed world, postoperative adhesions account for approximately 60% of cases of small bowel obstruction. Patients with a history of intestinal or pelvic surgery are at the highest risk. 82.2. Which of the following patients are at the highest risk of developing an obturator hernia? A. 2-year-old boy with no known medical problems B. 45-year-old woman with a 1-year history of hysterectomy C. 67-year-old man with a history of metastatic prostate cancer D. 80-year-old woman with a 3-month history of rapid weight loss Answer: D. This type of hernia is especially common in older women who have recently lost a significant amount of weight. The female pelvis is wider, and the obturator canal is more oblique in women. This, in combination with a loss of preperitoneal fat, predisposes to its development. Because an external mass is absent, diagnosis is especially challenging and explains why it carries the highest mortality of any abdominal hernia, at nearly 70% when incarcerated. 82.3. A 55-year-old woman with a history of Roux-en-Y gastric bypass surgery presents with a 1-day history of worsening colicky abdominal pain and vomiting. A CT scan reveals an internal hernia. What is the most appropriate disposition? A. Administer broad-spectrum antibiotics and admit to the medicine floor. B. Arrange for barium swallow with small bowel follow-through C. Insert nasogastric tube and admit to the medicine floor. D. Prompt surgical consultation and preparation for surgery should occur.

Answer: D. Although rare in the general population, internal hernias are a recognized complication of bariatric surgery, especially when a Roux-en-Y type procedure has been performed. Because of the closed loop nature of an internal hernia, they are not suitable for conservative management and require surgical intervention. 82.4. What is the length of time from acute absolute ischemia of the intestines to completion of transmural necrosis? A. 15 minutes B. 60 minutes C. 2 hours D. 6 hours E. 24 hours Answer: D. Although the mesenteric circulation is able to adapt to variations in circulation, the small bowel is quickly injured after acute ischemia. Within 15 minutes, structural damage to the intestinal villi can be seen histologically. If blood flow is not restored, mucosal sloughing can start to occur within 3 hours and, by 6 hours, transmural necrosis is complete. 82.5. A 35-year-old woman who currently smokes while taking oral contraceptive pills presents with 2 days of progressively worsening diffuse abdominal pain without peritoneal findings on examination. A CT scan reveals mesenteric venous thrombosis. What is the next most appropriate step? A. Arrange for formal mesenteric venous angiography to confirm and treat. B. Arrange for immediate exploratory laparotomy regardless of current clinical status, given the high risk of severe complications. C. Discharge home because this will resolve without intervention. D. Institute pain control and admit to the floor. E. Start anticoagulation with therapeutic dosing of heparin. Answer: E. The treatment of mesenteric venous thrombosis is unique in that in the absence of peritoneal findings, initial treatment with heparin alone may be adequate. In the vast majority of cases (>75%) an underlying inherited or acquired hypercoagulable state can be identified. Oral contraceptive use accounts for 9% to 18% of cases in young women.

C H A P T E R 83 

Acute Appendicitis Michael Alan Cole  |  Robert David Huang PRINCIPLES Background The appendix was once considered a vestigial organ; however, it is currently theorized that it serves as a repository for commensal bacteria that assist in normal digestive processes and may allow for recolonization of intestinal flora in times of enteric bacterial destruction. Phylogenetic studies have supported the appendix as likely having a so-called positive fitness value during mammalian evolution, whereas recent clinical research studies have demonstrated a possible increased risk of clostridial infections in patients who have had prior appendectomies.1-3 Appendicitis is the most common cause of acute abdominal pain requiring operative intervention in patients younger than 50 years. It is the most common nonobstetric abdominal emergency in pregnant females, usually occurring in the second trimester. Risk factors for appendicitis include white ethnicity, male gender, and young age (69% of cases occur in patients 38.3°C (101°F) Percussion tenderness Psoas sign

Rectal examination Increased skin temperature

RLQ, Right lower quadrant. Adapted from Laurell H, Hansson L-E, Gunnarsson U. Manifestations of acute appendicitis: a prospective study on acute abdominal pain. Dig Surg 30:198–206, 2013.

CHAPTER 83  Acute Appendicitis

Develop pretest probability for appendicitis based on history, physical examination, and laboratory data Treat symptomatically

Moderate risk*

Low risk

Pregnant No

• Consider/treat alternative diagnoses • Discharge with precautionary instructions

High risk

Yes

Consider graded compression ultrasound** Negative/ nondiagnostic Positive

Consult OB & Gen. Surgery Graded compression ultrasound

Positive

CT with IV contrast (no enteric contrast)

Negative/ nondiagnostic

MRI with no IV contrast (+/- enteric contrast) Positive

Positive

Negative

Negative

Is the patient still symptomatic

No

Diagnosis of appendicitis is made

Is the patient still symptomatic?

Yes

Administer IV antibiotics

Yes

No

Admit for observation and symptomatic therapy

Surgical consultation

Admit for observation and symptomatic therapy

• Consider/treat alternative diagnoses • Discharge with precautionary instructions

Is the patient a candidate for conservative management

No

Yes

Operative appendix removal within 12 hours of diagnosis

Admit for continued IV antibiotics, serial examinations and observation

*In moderate pre-test probability patients, the provider may consider admission for serial examinations or discharge in select cases.

**In pediatric patients, graded compression ultrasound should always be the first imaging test performed.

Fig. 83.2.  Suggested clinical management pathway for emergency department patients with possible appendicitis. Gen., General; OB, obstetrician.

patients presenting with abdominal pain, not just those with right lower quadrant pain. Table 83.3 lists the most common differential diagnoses for appendicitis.

DIAGNOSTIC TESTING Laboratory Data Laboratory data should not be viewed as diagnostic for appendicitis. Rather, it should be used in association with the patient’s clinical history and physical examination to formulate a more

comprehensive assessment of the patient’s condition and further risk-stratify the patient for treatment and disposition purposes.

White Blood Cell Count A patient’s white blood cell (WBC) count does not by itself have the sensitivity, specificity, or predictive value necessary to be clinically useful in diagnosing or excluding appendicitis. An elevated WBC count (>10,000–12,000/mm3) has a sensitivity of 62% to 85%, specificity of 32% to 82%, positive LR of 1.59 to 2.7, and negative LR of 0.25 to 0.46. Even in a subgroup analysis of

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TABLE 83.2 

Common Maneuvers and Physical Findings Associated With Appendicitis and Their Predictive Valuesa MANEUVER

DESCRIPTION

SENSITIVITY AND SPECIFICITY (%)

Iliopsoas (psoas) sign

Increased abdominal pain with patient lying on left side while provider passively extends the patient’s right leg at the hip with both knees extended

Sensitivity: 13–42 Specificity: 79–95

Rovsing’s sign

Abdominal pain in the RLQ while palpating the left lower quadrant

Sensitivity: 7–68 Specificity: 58–96

Obturator sign

Increased abdominal pain in the supine patient as the provider internally and externally rotates the right leg as it is flexed at the hip

Sensitivity: 8 Specificity: 94

a

Overall poor sensitivity decreases the value of these findings. However, if found, these signs moderately increase the likelihood of having appendicitis. RLQ, Right lower quadrant.

TABLE 83.3 

Urinalysis

Differential Diagnosis in Appendicitis

Urinalysis demonstrates pyuria, hematuria, and/or bacteria in up to 48% of patients with appendicitis. These abnormalities are due to the inflamed appendix abutting the ureter, with resultant ureteral inflammation. Nevertheless, findings on urinalysis of more than 30 red blood cells (RBCs)/high-power field or more than 20 WBCs/high-power field are more consistent with urinary tract infections than appendicitis.

ALL PATIENTS Nonspecific abdominal pain Gastroenteritis Epiploic appendigitis Ureterolithiasis, nephrolithiasis Inflammatory bowel disease Ileus or bowel obstruction Intestinal perforation Testicular torsion (males)

FEMALE PATIENTS

PEDIATRIC PATIENTS

Ectopic pregnancy Henoch-Schönlein Ovarian torsion purpura Pelvic inflammatory Mesenteric disease lymphadenitis Ovarian cyst Meckel’s diverticulum

increasingly high cutoff values for the WBC count (eg, >15,000 or 20,000/mm3), it is still not significant enough to be used in clinical practice to diagnose or exclude acute appendicitis.7,8

C-Reactive Protein The C-reactive protein (CRP) level is a nonspecific, systemic inflammatory marker synthesized by the liver. It has a poor predictive value in diagnosing or excluding acute appendicitis.8 An elevated CRP (>8–10 mg/L) has a sensitivity of 65% to 85%, specificity of 32% to 87%, positive LR of 1.59 to 4.2, and negative LR of 0.11 to 3.2.8,9 Some studies have suggested that CRP may be useful for predicting the severity of appendicitis and likelihood of complications; however, its value in diagnosing appendicitis lies in combining CRP with the WBC (see below).10

Combined Inflammatory Markers The American College of Emergency Physicians clinical policy on patients with suspected appendicitis states that the combination of a WBC more than 10,000/mm3 and CRP more than 8 mg/L has a positive likelihood ratio of 23 and a negative likelihood ratio of 0.03. These combined laboratory findings offer the greatest impact when excluding appendicitis in patients with a low pretest probability of the disease. Although more research is needed, based on the best available evidence, we recommend using the combination of low WBC (8 mm without such changes) Appendiceal circumferential wall thickening >2 mm with mural enhancement (sign of inflammation)

Not all criteria listed need to be fulfilled but the combination and severity of these findings contribute to a diagnosis: Appendiceal diameter > 7 mm

Fat stranding (hyperechoic signals associated with periappendiceal inflammation) (secondary finding) and peritoneal fluid

Calcified appendicolith

Signs of inflammation adjacent to the appendix, such as fat stranding or phlegmon formation

Peritoneal fluid surrounding the appendix (secondary finding)

Signs of periappendiceal inflammation (eg, fat stranding, clouding of the adjacent mesentery)

Presence of an abscess or a fluid filled appendix

• Appendiceal diameter > 6–7 mma • Noncompressible appendix

Appendiceal circumferential wall thickening > 2 mm

a

It is important to note that the diameter of a normal nondiseased appendix may be up to 11 mm, so the other findings of appendicitis must be factored in when making the diagnosis of appendicitis on CT or MRI. Due to the graded compression technique used in ultrasound, there is more certainty regarding diagnostic criteria for appendiceal diameter.

abdominal radiographs. Therefore, care must be taken to make the final diagnosis based on radiographic findings, although intraperitoneal air often expedites the patient’s disposition to the operating room.

Graded-Compression Ultrasound Within the medical community, there is a growing awareness of the risks associated with ionizing radiation, and efforts are being made to use methods of diagnosis that reduce or eliminate these risks.12 Graded compression ultrasound (US) is an imaging tool commonly used in evaluating patients for appendicitis. It is a diagnostic technique in which steady pressure is applied with the US probe to the abdomen to reduce bowel gas and collapse normal bowel to promote visualization of the appendix. Studies involving graded compression US for the diagnosis of appendicitis have reported sensitivities of 75% to 90%, specificities of 83% to 95%, positive LRs of 4.5 to 5.8, and negative LRs of 0.19 to 0.27, with an average positive predictive value of 90%.13 Table 83.4 lists US criteria for the diagnosis of appendicitis. The benefits in using US for the diagnosis of appendicitis include decreased cost relative to other imaging modalities, lack of ionizing radiation exposure, and decreased time to diagnosis. Limitations of US use include decreased specificity and increased pain due to the transducer pressure needed for the graded compression process. Most importantly, a number of US examinations cannot visualize the appendix (ie, nondiagnostic) for a number of reasons, including lack of operator experience, patient factors (eg, obesity), superimposed bowel gas, or atypically located appendix.14 In cases with nondiagnostic US findings, the patient typically requires further imaging with CT (or magnetic resonance imaging [MRI] in pregnancy) or admission for observation and serial examinations. Ultrasound is most useful in children, for whom the risks of ionizing radiation are greatest, and rates of overweight and obese individuals are lower than adults and pregnant females (Figs. 83.3 and 83.4). A distinction must be made between radiology-based US and bedside (point of care) US examination performed by an emergency clinician. Recent studies have demonstrated that bedside US is not as effective at diagnosing appendicitis, with a sensitivity for diagnosis of 60% to 70%, with specificities of 94% to 98%.15,16 Finally, in women with CMT, masses found on pelvic examination, or concern for a gynecologic cause of the patient’s symptoms,

Fig. 83.3.  Ultrasound image of appendicitis in an 8-year-girl. Note the dilated noncompressible appendix (thin arrows) and the presence of a fecalith, with posterior acoustic shadowing (thick arrow). (Courtesy Dr. Michael Cole, with permission.)

pelvic US is an important study to help determine ovarian pathology or tuboovarian abscesses. This should be performed before CT imaging in an attempt to elucidate an alternative diagnosis and may be completed simultaneously with a graded compression US to assess for appendicitis.

Computed Tomography CT of the abdomen and pelvis is considered the test of choice for definitive assessment of possible appendicitis in nonpregnant patients. It demonstrates an overall sensitivity of 94% to 100% and specificity of 91% to 99%, with a positive LR of 9.29 to 13.3, negative LR of 0.1 to 0.09, and positive predictive value of 95% to 97%.13 CT is accurate and consistent in diagnosing appendicitis and decreases the negative appendectomy rate. CT is readily available in most hospitals, can be performed in a rapid fashion, is not operator-dependent, can be interpreted by most radiologists and surgeons, and has a greater likelihood of finding an alternative diagnosis (vs. US; Figs. 83.5 and 83.6).

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Fat stranding

Discrete abscess from perforated appendix

Fig. 83.4.  Graded compression ultrasound scan demonstrating a dilated noncompressible appendix (thin arrow) representing appendicitis.

Fig. 83.5.  CT scan with typical findings of acute appendicitis. thick arrow, thin arrows, dashed line arrow.

The greatest disadvantage of CT is the ionizing radiation. A CT scan of the abdomen exposes the patient to an average dose of ionizing radiation equivalent to 8 examination 10 mSv. To put this in perspective, the average ionizing radiation dose associated with an abdominal x-ray is 0.7 mSv, and the average dose associated with coronary angioplasty is 15 mSv. An abdominal CT carries an excess risk of fatal cancer of 1 in 2000, a value that is even greater in children. However, this value must be tempered by the fact that the general population has a lifetime risk of being diagnosed with cancer of 1 in 3. The risk of radiation increases conversely with age, with children and fetuses having the greatest risk of adverse outcomes of radiation due to their smaller body habitus, more rapidly developing cells, and increased incubation time for genetic mutations to manifest.

Fig. 83.6.  Oral contrast CT scan showing discrete abscess from appendiceal perforation, with periappendiceal fat streaking. (Courtesy Jefferson Radiology, Avon, CT.)

To this end, there have been recent studies of low-dose CT protocols for the diagnosis of appendicitis. These low-dose protocols decrease the average dose to approximately 2 mSv, with no detriment in the negative appendectomy rate. However, there is less diagnostic certainty by radiologists about the diagnosis of appendicitis with these studies. These are relatively new protocols that show promise but require more studies before they can be universally adopted.17,18 Table 83.4 lists CT findings diagnostic of appendicitis. In some cases, the appendix cannot be visualized. In these cases, if CT demonstrates no findings of inflammation in the RLQ, it has been found that appendicitis is unlikely. However, patients with low amounts of intra-abdominal body fat may not display secondary signs of inflammation; consequently, these patients may lack this important marker of appendicitis on CT imaging, leading to falsenegative study results. The term tip appendicitis refers to obstruction and inflammation limited to the distal tip of the appendix and is a subtle finding on CT that is a common cause of falsenegative interpretation.19 To assess for appendicitis, CT should be performed with IV contrast only. Enteric contrast of any type, oral or rectal, contributes little to the assessment of appendicitis. In addition, studies have demonstrated that non–contrast-enhanced CT has acceptable accuracy in diagnosing appendicitis. Furthermore, according to the American College of Radiology’s appropriateness criteria for imaging suspected appendicitis, CT imaging with or without IV contrast are acceptable imaging modalities, with the use of enteric contrast being deferred to institutional preference. Therefore, if there are contraindications to IV contrast, there should be little hesitation to move forward with non–contrast-enhanced CT for the evaluation of appendicitis.17

Magnetic Resonance Imaging When considering the evaluation for appendicitis, current evidence supports the use of MRI for assessment in pregnant females if US is nondiagnostic. MRI has the advantage of not using ionizing radiation and is not operator-dependent. However, its use is limited by its increased cost, increased time required to acquire images, limited availability, and need for the radiologist or surgeon

CHAPTER 83  Acute Appendicitis

to be skilled in MRI scan interpretation. MRI demonstrates a sensitivity of 85% to 100%, specificity of 95% to 99.2, average positive predictive value of 92.4, and average negative predictive value of 99.7.20 Table 83.4 lists MRI criteria for the diagnosis of appendicitis. In pregnant patients, IV gadolinium contrast should not be used when evaluating for appendicitis due to potentially harmful effects on the fetus.21 Enteric contrast may be used at the discretion of the interpreting radiologist or per institutional protocol.

Combined Imaging Pathways An imaging pathways that combine US and CT, in which abdominopelvic CT is performed if the graded compression US is nondiagnostic or negative, have demonstrated combined sensitivities of 94% to 99%, specificities of 91% to 97.5%, and significant reductions in CT utilization.22,23 It has been projected that this pathway would save $547/patient in imaging costs and $25 million/year in aggregate by reducing imaging costs, unnecessary surgeries, and unnecessary hospitalizations, not to mention decreased radiation exposure.24 As institutions increase their experience with the use of US to diagnose appendicitis, we think that a combined US-CT pathway will gain acceptance and improve health care delivery. Interestingly, a so-called radiation-free imaging pathway that combines US and MRI, in which abdominopelvic MRI is performed if the US is nondiagnostic or negative, has been recently studied in the emergency pediatric population, with outcomes similar to those of the combined US-CT pathway. However, at this time, there is a paucity of sufficient data and lack of institutional resources to suggest the routine use of this approach.25

Summary of Imaging Methods Fig. 83.2 illustrates a suggested pathway regarding imaging. For nonpregnant patients, graded compression US may be first considered. In nonpregnant females, a pelvic US may also be considered to assess for pelvic pathology. The ability to visualize the appendix on US is institution-dependent, and the provider’s decision to use US initially may depend on the institution’s level of experience with this modality. If the US studies are negative or nondiagnostic (ie, no appendix is visualized and no alternative pathology is noted), the patient may undergo CT imaging of the abdomen and pelvis with IV contrast (no PO contrast). An alternative to CT imaging in low-risk cases with nondiagnostic US is admission for observation and serial examinations. If the patient is pregnant, graded compression and pelvic US should always be the initial studies of choice, followed by MRI of the abdomen without IV contrast in cases of nondiagnostic or negative US findings. If MRI is not available, and transfer to a facility with MRI capabilities is not feasible, then, after consultation with a radiologist, general surgeon, and obstetrician, abdominal CT scanning with IV contrast may be considered. However, in low-risk cases, admission for observation and serial examinations is an acceptable alternative.

MANAGEMENT Supportive Care Decisions surrounding supportive care will depend on the patient’s condition and needs. Supportive care should be initiated prior to a definitive diagnosis and should continue until the patient leaves the ED. Patients should remain NPO. IV fluids (normal saline or lactated Ringer’s) may be administered to maintain hydration and support hypotensive patients. Systemic signs of infection are more common in perforated appendicitis and should be supported by

IV fluids, antipyretics, and antibiotics (see below). The patient’s pain and nausea should be treated with parenteral opiate analgesia and antiemetics, respectively. There have been a number of goodquality studies that support the concept that opiate analgesia does not negatively affect a patient’s abdominal examination when the patient has an abdominal condition that requires surgery.26,27 Therefore, parenteral opiate analgesia should not be withheld from the patient unless there are contraindications to its use (eg, severe hypotension, allergies). In rare cases, acute appendicitis can cause severe sepsis or septic shock.

Antibiotic Therapy Antibiotic therapy should be promptly administered on making the diagnosis of appendicitis or in patients with suspected appendicitis and severe sepsis or septic shock. The choice of antibiotics should include broad-spectrum gram-negative and anaerobic coverage. For nonperforated appendicitis, we recommend ciprofloxacin, 400 mg IV, and metronidazole (Flagyl), 500 mg IV; or ceftriaxone, 1g IV, and metronidazole, 500 mg IV; or ampicillinsulbactam, 3g IV monotherapy. For perforated appendicitis, we recommend broader spectrum antibiotics, such as piperacillintazobactam, 3.375 to 4.5g IV, cefepime, 2 g IV, or imipenemcilastatin, 500 mg IV. Methicillin-resistant Staphylococcus aureus (MRSA) coverage is not typically needed to treat appendicitis but may be considered if the patient has previously known MRSA colonization.28

Definitive Treatment Definitive treatment of acute appendicitis will depend on whether there are associated complications, and all decisions should be made in consultation with the surgical service. Nonperforated appendicitis with a well-circumscribed abscess should be treated with IV antibiotics and percutaneous drainage. Perforated appendicitis with or without abscess is treated with IV antibiotics and urgent operative intervention.28 Nonperforated appendicitis without abscess (ie, uncomplicated appendicitis) is traditionally treated with IV antibiotics and surgical removal of the inflamed appendix. However, recent and historical data have demonstrated that conservative treatment of appendicitis with antibiotic therapy and a period of inpatient observation may be a viable treatment option for certain patients. There is historical precedence for nonoperative management of appendicitis, and recent studies have found that there may be value in risk-stratifying patients with appendicitis based on their CT findings. In appendicitis with low-risk features, antibiotic therapy with a period of inpatient observation is a feasible option.29,30 Features associated with failed conservative management include the presence of a fecalith, abscess, tumor, or fluid collection or appendiceal diameter of more than 1.1 cm.31 In patients with any of these features, operative intervention is preferred. A minority of patients treated conservatively may fail the inpatient observation period and still require surgery; a minority of those discharged after conservative treatment carry the risk of recurrence of appendicitis. However, with a negative appendectomy rate of 3.6% to 10% and a complication rate as high as 18%—including small bowel obstruction, adhesions, surgical site infection, and abscess formation—nonoperative care is an option worth considering.32 The decision regarding definitive treatment of acute appendicitis should be made in consultation with the surgical service and the risks and benefits of conservative treatment versus surgical intervention should be frankly discussed with the patient, surgeon, and emergency clinician. When the decision is made to proceed with surgical removal of the appendix, in uncomplicated appendicitis, delaying surgery up to 12 hours after diagnosis is made (eg, “waiting until the

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morning”) is acceptable and does not lead to worse clinical outcomes; one recent study has demonstrated that inpatient delay of appendectomy by up to 24 hours does not result in worse outcomes.33 Although limited in-hospital delay of operative care has not been shown to increase perforation risk or morbidity, delay by patients initially seeking care does increase the risk of perforation and associated morbidity. Lack of insurance, male gender, and a greater number of comorbid conditions are factors associated with increased perforation risk. The choice of laparoscopic versus open appendectomy is made by the surgeon; however, laparoscopic appendectomy has become the current method of choice.

DISPOSITION There are three possible disposition pathways when a diagnosis of appendicitis is considered. A diagnosis of appendicitis is made

based on imaging or, rarely, clinical assessment alone. In this case, antibiotics should be initiated, surgical consultation should be obtained, and the patient should be admitted for operative intervention or, in select cases, IV antibiotics and observation. Based on clinical and laboratory assessment, the risk of appendicitis is low, and no imaging study was performed. In this case, the patient may be discharged home if he or she is reliable, has improved clinical status (ie, feels better), and understands the provider’s thought process and precautionary instructions. Alternatively, if these criteria are not met, the patient may be transferred to an observation unit or hospitalized for serial examinations. If the patient’s imaging results are inconclusive, or if they are negative but the patient is still symptomatic, the patient may be admitted for observation, symptomatic treatment, serial examinations, and kept NPO, although select patients in this category may still be discharged at the provider’s discretion.

KEY CONCEPTS • Appendicitis is a progressive illness caused by appendiceal luminal distention followed by appendiceal wall ischemia, transmural inflammation, and eventual perforation, with resultant peritonitis. • Clinical history, physical examination, and laboratory findings need to be combined to formulate a comprehensive assessment. No one finding can definitively diagnose or exclude appendicitis. • The most useful historical features in evaluating appendicitis are RLQ pain, pain preceding vomiting, and migration of pain to the RLQ. • The most useful physical findings in evaluating appendicitis are RLQ tenderness and rigidity. • Cervical motion tenderness is not specific for pelvic pathology and is found in up to 28% of females with appendicitis. • A rectal examination contributes little and should not be routinely performed in the evaluation of appendicitis. • The white blood cell count alone is neither sensitive nor specific for appendicitis and offers little in the evaluation of appendicitis.

• When clinicians have a low pretest possibility for appendicitis, the combination of a WBC count below 10,000/mm3 and CRP level below 8 mg/L support the exclusion of appendicitis as a likely diagnosis. • Nonoperative management of acute appendicitis (IV antibiotics, admission) is gaining support. The patient should not have high-risk features (eg, presence of a fecalith, abscess, tumor, or fluid collection or appendiceal diameter >1.1 cm) and should be made aware of the risk of failed observation as an inpatient or recurrent appendicitis once discharged, both of which would then require surgical removal of the appendix. • Once the diagnosis of appendicitis is made, in-hospital delay of appendectomy of up to 12 hours has not demonstrated negative outcomes when compared to emergent operative care.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 83  Acute Appendicitis

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REFERENCES 1. Smith HF, Parker W, Kotzé SH, et al: Multiple independent appearances of the cecal appendix in mammalian evolution and an investigation of related ecological and anatomical factors. Comptes Rendus Palevol 12:339–354, 2013. 2. Im GY, Modayil RJ, Lin CT, et al: The appendix may protect against Clostridium difficile recurrence. Clin Gastroenterol Hepatol 9:1072–1077, 2011. 3. Clanton J, Subichin M, Drolshagen K, et al: Fulminant Clostridium difficile infection: an association with prior appendectomy? World J Gastrointest Surg 5:233–238, 2013. 4. Hendahewa R, Shekhar A, Ratnayake S: The dilemma of stump appendicitis—a case report and literature review. Int J Surg Case Rep 14:101–103, 2015. 4a.  Laméris W, van Randen A, Go PM, et al: Single and combined diagnostic value of clinical features and laboratory tests in acute appendicitis. Acad Emerg Med 16(9): 835–842, 2009. 5. Brown TW, McCarthy ML, Kelen GD, et al: An epidemiologic study of closed emergency department malpractice claims in a national database of physician malpractice insurers. Acad Emerg Med 17:553–560, 2010. 6. Takada T, Nishiwaki H, Yamamoto Y, et al: The role of digital rectal examination for diagnosis of acute appendicitis: a systematic review and meta-analysis. PLoS ONE 10:e0136996, 2015. 7. Howell JM, Eddy OL, Lukens TW, et al: Clinical policy: critical issues in the evaluation and management of emergency department patients with suspected appendicitis. Ann Emerg Med 55:71–116, 2010. 8. Yu C-W, Juan L-I, Wu M-H, et al: Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg 100:322–329, 2013. 9. Farooqui W, Pommergaard H-C, Burcharth J, et al: The diagnostic value of a panel of serological markers in acute appendicitis. Scand J Surg 104:72–78, 2015. 10. Shindoh J, Niwa H, Kawai K, et al: Diagnostic power of inflammatory markers in predicting severity of appendicitis. Hepatogastroenterology 58:2003–2006, 2011. 11. Bachur RG, Hennelly K, Callahan MJ, et al: Diagnostic imaging and negative appendectomy rates in children: effects of age and gender. Pediatrics 129:877–884, 2012. 12. Miglioretti DL, Johnson E, Williams A, et al: The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr 167:700–707, 2013. 13. van Randen A, Laméris W, van Es HW, et al: A comparison of the accuracy of ultrasound and computed tomography in common diagnoses causing acute abdominal pain. Eur Radiol 21:1535–1545, 2011. 14. Abo A, Shannon M, Taylor G, et al: The influence of body mass index on the accuracy of ultrasound and computed tomography in diagnosing appendicitis in children. Pediatr Emerg Care 27:731–736, 2011. 15. Mallin M, Craven P, Ockerse P, et al: Diagnosis of appendicitis by bedside ultrasound in the ED. Am J Emerg Med 33:430–432, 2015. 16. Elikashvili I, Tay ET, Tsung JW: The effect of point-of-care ultrasonography on emergency department length of stay and computed tomography utilization in children with suspected appendicitis. Acad Emerg Med 21:163–170, 2014. 17. Smith MP, Katz DS, Lalani T, et al: ACR Appropriateness Criteria® right lower quadrant pain—suspected appendicitis. Ultrasound Q 31:85–91, 2015.

18. Kim K, Kim YH, Kim SY, et al: Low-dose abdominal CT for evaluating suspected appendicitis. N Engl J Med 366:1596–1605, 2012. 19. Gaetke-Udager K, Maturen KE, Hammer SG: Beyond acute appendicitis: imaging and pathologic spectrum of appendiceal pathology. Emerg Radiol 21:535–542, 2014. 20. Burke LMB, Bashir MR, Miller FH, et al: Magnetic resonance imaging of acute appendicitis in pregnancy: a 5-year multiinstitutional study. Am J Obstet Gynecol 213:693.e1–693.e6, 2015. 21. Expert Panel on MR Safety, Kanal E, Barkovich AJ, et al: ACR guidance document on MR safe practices: 2013. J Magn Reson Imaging 37:501–530, 2013. 22. Thirumoorthi AS, Fefferman NR, Ginsburg HB, et al: Managing radiation exposure in children—reexamining the role of ultrasound in the diagnosis of appendicitis. J Pediatr Surg 47:2268–2272, 2012. 23. Polites SF, Mohamed MI, Habermann EB, et al: A simple algorithm reduces computed tomography use in the diagnosis of appendicitis in children. Surgery 156:448– 454, 2014. 24. Bachur RG, Levy JA, Callahan MJ, et al: Effect of reduction in the use of computed tomography on clinical outcomes of appendicitis. JAMA Pediatr 169:755–760, 2015. 25. Aspelund G, Fingeret A, Gross E, et al: Ultrasonography/MRI versus CT for diagnosing appendicitis. Pediatrics 133:586–593, 2014. 26. Manterola C, Vial M, Moraga J, et al: Analgesia in patients with acute abdominal pain. Cochrane Database Syst Rev (1):CD005660, 2011. 27. Poonai N, Paskar D, Konrad S-L, et al: Opioid analgesia for acute abdominal pain in children: A systematic review and meta-analysis. Acad Emerg Med 21:1183–1192, 2014. 28. Solomkin JS, Mazuski JE, Bradley JS, et al: Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 50:133–164, 2010. 29. Salminen P, Paajanen H, Rautio T, et al: Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA 313:2340–2348, 2015. 30. Vons C, Barry C, Maitre S, et al: Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, noninferiority, randomised controlled trial. Lancet 377:1573–1579, 2011. 31. Shindoh J, Niwa H, Kawai K, et al: Predictive factors for negative outcomes in initial non-operative management of suspected appendicitis. J Gastrointest Surg 14:309– 314, 2010. 32. Seetahal SA, Bolorunduro OB, Sookdeo TC, et al: Negative appendectomy: a 10-year review of a nationally representative sample. Am J Surg 201:433–437, 2011. 33. Drake FT, Mottey NE, Farrokhi ET, et al: Time to appendectomy and risk of perforation in acute appendicitis. JAMA Surg 149:837–844, 2014. 34. Ashdown HF, D’Souza N, Karim D, et al: Pain over speed bumps in diagnosis of acute appendicitis: diagnostic accuracy study. BMJ 345:e8012, 2012. 35. Laurell H, Hansson L-E, Gunnarsson U: Manifestations of acute appendicitis: a prospective study on acute abdominal pain. Dig Surg 30:198–206, 2013.

CHAPTER 83: QUESTIONS & ANSWERS 83.1. What percentage of women with acute appendicitis have accompanying cervical motion tenderness (CMT)? A. 10% B. 15% C. 20% D. 25% E. 30% Answer: D. Prior to the advent of routine imaging of the appendix, as many as 25% of women with acute appendicitis were initially misdiagnosed because of the presence of CMT. 83.2. Which of the following statements regarding ultrasonographic visualization of the appendix is true? A. A compressible appendix is a positive finding. B. An appendiceal diameter greater than 6 or 7 mm is a positive finding. C. The sensitivity of ultrasound for appendicitis is 94% to 98%. D. Ultrasonography has good reliability for detecting a retrocecal appendix. E. Ultrasonography compares favorably with computed tomography (CT) scanning for the detection of appendicitis. Answer: B. A noncompressible appendix with a diameter greater than 6 or 7 mm in a setting of clinical appendicitis is considered

a positive finding. Ultrasound sensitivities are 75% to 90%. It is a less useful modality in the obese, those with peritoneal adhesions, and those with a retrocecal appendix. The sensitivity of helical CT scanning with rectal contrast approaches 98%, much higher than ultrasonography. 83.3. A 27-year-old G3P2 woman at 22 weeks of gestation presents with 2 days of right lower quadrant (RLQ) abdominal pain. It began midline and later became more pronounced in the RLQ. The physical examination was remarkable for RLQ tenderness without rebound. The gynecologic examination was negative except for a nontender gravid uterus, with good fetal movement by transabdominal ultrasound. Urinalysis showed 8 to 10 white blood cells (WBCs)/high-power field (HPF) and occasional bacteria. Complete blood count (CBC) showed a WBC count of 12,700/mm3 with 77% neutrophils. Hemoglobin level was 11 g/dL. RLQ ultrasound was limited, with no visualization of a normal or abnormal appendix, and transvaginal ultrasound did not show an obvious gynecologic or obstetric problem. Repeat examination showed continued RLQ tenderness. What is the most appropriate intervention? A. Administer cephalexin for urinary tract infection and schedule a 48-hour clinic recheck B. Admit for observation and serial examination

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C. Obtain surgical consultation for laparotomy D. Order a CT scan of the abdomen. E. Order a magnetic resonance imaging (MRI) scan Answer: E. MRI scanning for appendicitis may be helpful in pregnant women, in whom the avoidance of radiation exposure is a significant consideration, and exploratory surgery carries additional risks. 83.4. In men and children with classic symptoms and signs of appendicitis, what is the most appropriate initial intervention? A. Antibiotics and serial abdominal examinations B. CT scan of the abdomen C. MRI scan of the abdomen

D. Surgery E. Ultrasonography Answer: E. In men and children with classic appendicitis, imaging adds little to the evaluation and only exposes patients to unnecessary radiation. However, it has become less and less common for a patient with a history and examination concerning for appendicitis to undergo surgery without further imaging. Ultrasound is the most appropriate initial intervention because it uses no radiation and can often visualize and diagnose appendicitis without significant delay. Graded compression ultrasound for appendicitis is specific but lacks the sensitivity of CT scan so, if the appendix is not visualized, a discussion can be had with the general surgeon to determine if it is necessary to obtain further information (via CT or MRI).

C H A P T E R 84 

Gastroenteritis Thomas Nguyen  |  Saadia Akhtar OVERVIEW Background Gastroenteritis is an inflammation of the stomach and small and large bowel intestines. Most cases present as a self-limited illness, and most patients have nausea, vomiting, and diarrhea, often with diarrhea being the predominant symptom. Diarrhea is defined as the passage of three or more unformed liquid stools a day, stools of more than 250 g/day, or stool that takes the form of the container into which it is placed.1 Dysentery refers to an inflammation of the intestine, particularly the colon, causing diarrheas associated with blood and mucus; it is generally associated with fever, abdominal pain, and rectal tenesmus (sense of incomplete defecation). Gastroenteritis is one of the leading causes of morbidity and mortality worldwide, especially in children. Approximately 180 million cases of acute diarrhea occur each year in the United States, most of which are self-limited and without consequence. The incidence has been increasing due to increased international travel and the increased consumption of raw produce, such as spinach and fresh fruits. Viruses account for most of the infectious causes.2 Diarrhea-related deaths in developed countries occur most often in older adults or debilitated patients; Clostridium difficile and noroviruses are most frequently implicated. Patients with C. difficile, HIV infection, or immunocompromised-related enteritis or those with fever and bloody stools require early diagnosis and treatment to maximize good outcomes. Diagnostic testing should be reserved for cases due to specific pathogens that cause a more severe clinical illness or cases due to an outbreak. Clinicians can play an important role in surveillance and mitigating the spread of infection. Gastroenteritis is classified as being acute or chronic. Acute gastroenteritis is associated with symptoms that last for less than 2 weeks, usually from viral or bacterial causes. Chronic gastroenteritis consists of symptoms lasting for more than 2 weeks that is often caused by parasites or noninfectious conditions.

Pathophysiology The pathophysiology of an infection related to gastroenteritis involves one of four mechanisms—ingestion of preformed toxins, adherence of the infectious pathogens to the intestinal cell walls, invasion of mucosal cell walls, and production of enterotoxins and cytotoxins. All these mechanisms lead to an increase in fluid secretion and/or a decrease in fluid absorption in the gastrointestinal (GI) tract.1

Clinical Features History The history should take into account epidemiologic factors that may help identify the likely organism (Table 84.1). For example,

travel outside of the United States raises suspicion for traveler’s diarrhea, contact with persons on a cruise ship with a GI outbreak is suspicious for norovirus, a recent camping trip and exposure to river water suggests giardiasis, and recent hospitalization or antibiotic use and patients in long-term care facilities are risk factors for C. difficile infection. Associated factors are helpful in narrowing the list of possible causative organisms and in initiating treatments. For example, GI symptoms after a short exposure period (1–6 hours) may imply preformed toxins from staphylococcal or Bacillus organisms. Diarrhea lasting more than 2 weeks may indicate the presence of Giardia or other protozoa, although noninfectious causes should be considered, such as inflammatory bowel disease. Norovirus classically causes a sudden onset of severe vomiting and only moderate diarrhea. Large-volume diarrhea usually indicates small bowel involvement, such as viral gastroenteritis or illness due to Vibrio cholerae. Colonic involvement causes smaller volume loss and more likely will be bloody or have fecal leukocytes from invasive organisms. Vomiting without diarrhea generally should not be referred to as gastroenteritis. Other causes should be sought out, such as a small bowel obstruction. A history of fever, abdominal pain, tenesmus, and bloody stools are signs of dysentery and may imply invasive organisms such as Campylobacter or Shigella. Yersinia enterocolitica GI infection often mimics acute appendicitis or regional enterocolitis due to its invasion of the local mesenteric lymph nodes. Patients with lightheadedness and hypotension are likely to be dehydrated from diarrhea and vomiting. Muscle cramping may imply hypokalemia or hyponatremia from lack of oral intake or loss of electrolytes in the diarrhea.

Physical Examination The physical examination focuses on the patient’s general hydration status and assesses for life-threatening conditions. The emergency clinician should first assess the vital signs. In the clinical setting of gastroenteritis, hypotension and tachycardia likely indicate that the patient is dehydrated. Fever, altered mental status, and a toxic appearance may signify that the patient has severe illness and possibly sepsis. Other disease states may mimic gastroenteritis, and a thorough examination is warranted. For example, a low-grade fever in a patient with tachycardia, tremors, and diarrhea in the presence of a goiter may represent hyperthyroidism. Evaluation of the skin for the presence of petechiae or purpura, especially in the extremities, can suggest possible sepsis or disseminated intravascular coagulation (DIC). Dry mucous membranes, decreased skin turgor, and decreased urine output may also help gauge dehydration. In infants, an accurate measure of weight loss, lack of tears, decrease in urine output, or depressed fontanelle are all good predictors of dehydration. The abdominal examination focuses on conditions that may mimic gastroenteritis, such as small bowel obstruction, bowel ischemia, appendicitis, and colitis. The examiner should listen carefully for bowel sounds. Generally, bowel sounds are hyperactive in acute gastroenteritis. Abdominal findings such as focal tenderness, rebound, guarding, distention, and rigidity may indicate a surgical abdomen. If the 1129

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TABLE 84.1 

Diagnostic Testing

Epidemiologic Factors

Diagnostic testing for patients with apparent gastroenteritis is guided by the clinical assessment. Routine laboratory tests, including a complete blood count and serum metabolic profile, are not needed in every case. Further evaluation may be required for patients presenting with severe illness or severe dehydration. Laboratory tests should be done for patients with high fevers, severe abdominal pain, bloody stools or persistent diarrhea. Special attention should be given to older adults with abdominal pain and immunocompromised patients. For most cases of gastroenteritis, if the patient appears well and is likely to have a selflimited illness, stool cultures are not required. Stool cultures should be sent for patients with severe illness, fever of 38.5° C (101°F) or higher, dysentery, persistent diarrhea for 14 days or longer and for patients who are immunocompromised or who have been recently hospitalized or placed on antibiotics. If diarrhea is persistent, stools for ova and parasite should be sent. Stools sent for fecal leukocytes, lactoferrin, or hemoccult testing may help identify colonic inflammation with an invasive organism. Stool studies and culture should be performed when certain bacterial and parasitic infections are suspected, such as C. difficile, Campylobacter, Shiga toxin–producing Escherichia coli (STEC), or giardiasis because targeted antibacterial treatment may be initiated to prevent the spread (eg, in an outbreak of daycare workers) and decrease the duration of symptoms. Tables 84.2, 84.3, and 84.4 summarize specific diagnostic testing for bacterial, viral, and parasitic infections, respectively.

FACTOR

IMPLICATIONS

Foreign travel

Traveler’s diarrhea—enterotoxigenic Escherichia coli Southeast Asia—Vibrio species Rotavirus—South America, Asia, Africa

Recent camping

Giardia, Aeromonas, Cryptosporidium

Recent antibiotics

Increase in C. difficile infection

Daycare exposure

Rotavirus

Exposure to raw seafood

Noncholera Vibrio

Anal-receptive sex—men Shigella, Campylobacter, Salmonella who have sex with men HIV-positive status

Mycobacterium avium-intracellulare complex, microsporidia. cytomegalovirus, Giardia

Outbreaks

Cruise ships—norovirus Contaminated local water, food, products, restaurants; organism usually identified by local health department (eg, Campylobacter, Salmonella, E. coli)

patient reports blood or mucus in the stool or complains of rectal pain, a rectal examination should be performed to assess for gross blood, mucus, or rectal lesions.

Differential Diagnosis Other diagnoses to consider include small bowel obstruction (SBO), diverticulitis, inflammatory bowel disease (IBD), ischemic bowel disease, appendicitis, malabsorption, celiac disease, and irritable bowel syndrome. A patient with a history of abdominal surgery who presents with crampy abdominal pain and vomiting, distended tender abdomen, and is not passing any gas or stools is likely to have an SBO. In diverticulitis, pain is generally localized to the left lower abdomen. IBD usually first presents in the young adult as recurrent diarrhea, with cramping. The stool may contain mucus and blood. Risk factors are obesity, smoking, and a family history of IBD, with the highest risk in females and Jewish persons of European ancestry. There may be extraintestinal manifestations, such as uveitis and erythema nodosum. Patients with ischemic bowel may present with abdominal pain. ranging from mild to severe tenderness with peritoneal signs. Risk factors include older age, low-flow states such as dehydration, recent congestive heart failure exacerbation, sepsis, smoking, and atherosclerotic disease and those at risk for thromboembolic events such as atrial fibrillation. Patients with gastroenteritis are generally not critically ill and deterioration is not as rapid as seen in those with ischemic bowel disease. Viruses account for up to 70% of cases of infectious gastroenteritis, bacteria, 15% to 20%, and parasites, about 10% to 15%. It is difficult to identify the exact organism causing the GI illness on initial presentation. The predominance of vomiting along with upper respiratory symptoms is more likely associated with a viral cause. A rapid onset of vomiting as the predominant symptom may suggest the presence of preformed bacterial toxins. The presence of high fever, fecal blood, abdominal pain, or colitis likely indicates an invasive bacterial organism.3

Management Patients who are severely dehydrated should receive an intravenous (IV) fluid bolus of isotonic solution, such as normal saline (NS) or lactated Ringer’s (LR). Electrolytes should be repleted, with special attention to the sodium and potassium levels. Antiemetics prevent ongoing loss of fluids and help with the initiation of oral rehydration therapy (ORT). The exact cause of vomiting in gastroenteritis is not known, although it is thought to be due to peripheral stimuli arising from the GI tract primarily via the vagus nerve or by serotonin stimulation of the 5-hydroxytryptamine 3 (5-HT3) receptors in the intestinal tract. These signals are transmitted to the emetic center in the brainstem that stimulates the muscles in the diaphragm, abdominal wall, and intestinal tract to produce vomiting. All the areas involved in the pathogenesis of vomiting are rich in serotoninergic, dopaminergic, histaminic, and muscarinic receptors, thus providing the basis for using serotonin inhibitors, dopamine inhibitors, and antihistamines. Odansetron, 4 mg IV, or metoclopramide, 10 mg IV, are safe and cost-effective and can be easily converted to an oral dose. Side effects of odansetron include headache and diarrhea. The American Academy of Pediatrics (AAP), Centers for Disease Control and Prevention (CDC), European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN), and World Health Organization (WHO) all strongly support the use of oral rehydration therapy (ORT) as first-line treatment for acute gastroenteritis, except in cases of severe dehydration. Although ORT has been extensively studied in children, the results can generally be applied to adults. It is known to be safe and effective as the treatment of choice for mild and moderate dehydration. Morbidity and mortality can be greatly reduced with the use of ORT. It is also associated with fewer major adverse events and results in shorter hospital stays. Fluids containing glucose and electrolytes provide optimal rehydration due to the cotransport of the water across the intestinal lumen. Some choices of oral rehydration solution (ORS) are the standard WHO ORS (331 mOsm/kg), reduced osmolarity

CHAPTER 84  Gastroenteritis

TABLE 84.2 

Bacteria: Diagnosis and Treatment ORGANISM

DIAGNOSIS

TREATMENT

Shigella

Stool culture (conventional)

Ciprofloxacin, 750 mg daily for 3 days; or azithromycin, 500 mg daily for 3 days

Salmonella   Nontyphoid

Stool culture (conventional)

  Typhoid

Stool culture (conventional)

No treatment in nonsevere cases. For severe cases (fever, bloody diarrhea, bacteremia)—levofloxacin (Levaquin), 500 mg daily for 7–10 days Fluoroquinolone daily for 7 days; IV ceftriaxone, 1–2 g for 7 days

Campylobacter jejuni

Stool culture (conventional)

Azithromycin, 500 mg daily for 3 days

Vibrio cholerae

Stool culture with salt- containing media (TCBS)

Doxycycline, 7 mg/kg up to 300 mg once

Vibrio—noncholera (Vibrio parahaemolyticus)

Stool culture with TCBS

Ciprofloxacin, 750 mg daily for 3 days; or azithromycin, 500 mg daily for 3 days

Enterotoxigenic Escherichia coli

Stool culture; assay for toxin

Ciprofloxacin, 750 mg daily for 3 days, rifaximin 200 mg tid for 3 days; azithromycin, 1 g once

Shiga toxin–producing E. coli; E. coli O157:H7

Sorbitol MacConkey and serotyping for O157

No treatment, supportive care only; antibiotics increase risk for HUS

Yersinia enterocolitica

Cefsulodin-irgasan-novobiocin (CIN) agar

Supportive care; in severe cases, TMP-SMX (Bactrim), fluoroquinolones

Clostridium difficile

Stool for C. difficile toxin

Metronidazole, 500 mg tid for 10 days; vancomycin, 125 mg PO qid for 10 days

Staphylococcus aureus

Food may be cultured for Staphylococcus

Supportive care

Clostridium perfringens

Detection of spores in stool

Supportive care

Bacillus cereus

Food may be cultured

Supportive care; for severe cases—vancomycin, 125 mg qid; or clindamycin, 500 mg tid for 7–10 days

HUS, Hemolytic uremic syndrome; TMP-SMX, trimethoprim-sulfamethoxazole.

TABLE 84.3 

Virus: Diagnosis and Treatment ORGANISM

DIAGNOSIS

TREATMENT

Norovirus

Stool sample—real-time reverse transcription–polymerase chain reaction (RT-PCR) assay

Supportive care

Sapovirus

PCR assay, immunoassay

Supportive care

Rotavirus

Rotavirus antigen in stool sample

Supportive care; vaccine and natural infection do not provide immunity; RotaTeq (RV5), given in three doses at ages 2, 4, and 6 mo; or Rotarix (RV1), given in two doses at ages 2 and 4 mo

Adenovirus

Antigen detection, PCR assay, virus isolation, serology

Supportive care

Astrovirus

PCR assay, electron microscopy, immunoassay

Supportive care

WHO ORS (245 mOsm/kg), and Pedialyte (oral electrolyte solution for children; 250 mOsm/kg). One systematic review of 15 randomized controlled trials, including 2397 children, has shown that reduced osmolarity rehydration solution is associated with a reduced need for unscheduled IV infusions, lower stool volume, and less vomiting compared with a standard WHO rehydration solution.4 Simple home remedies such as diluted fruit drinks and chicken broth or commercial solutions such as Gatorade will also suffice. The official recommendation by ESPGHAN is to hydrate orally with reduced osmolarity or hypotonic fluids. Oral intake of food, if tolerated, should be continued during the illness, because fasting may actually worsen the capacity of the bowel to absorb fluid. The

presence of the food in the bowel lumen promotes mucosal recovery and improves fluid absorption.5 Antimotility drugs such as loperamide and diphenoxylate hydrochloride can help limit the number of watery stools and prevent dehydration. The initial dose of loperamide is 4 mg orally, followed by 2 mg after each unformed stool, up to a maximum of 16 mg/day for 48 hours. However, in patients with suspected bacterial dysentery, it is recommended that antimotility agents be administered in conjunction with antibiotics because antimotility agents may increase the contact time with the toxins or invasive organisms. In general, antibiotics are not indicated for the treatment of the vast majority of cases of acute gastroenteritis. However,

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TABLE 84.4 

Parasitic Infections: Diagnosis and Treatment ORGANISM

DIAGNOSIS

TREATMENT

Giardia lamblia

Stool microscopy for ova and parasite; immunoassay

Tinidazole—2 g PO single dose Metronidazole—500 mg PO bid or 250 mg tid for 5–7 days Nitazoxanide—500 mg bid for 3 days Alternative agents Albendazole—400 mg once daily for 5 days Mebendazole—200 mg PO tid for 5 days Quinacrine—100 mg PO tid for 5 days Paromomycin—10 mg/kg PO tid day for 5–10 days

Entamoeba histolytica

Stool microscopy, culture, immunoassay

Metronidazole—500–750 mg PO tid for 7–10 days; Tinidazole—2 g PO once a day for 3 days; Nitazoxanide—500 mg PO bid for 3 days Intraluminal infection Paromomycin—25–30 mg/kg PO tid for 7 days Diiodohydroxyquin—650 mg PO tid for 20 days for adults Diloxanide furoate—500 mg PO tid for 10 days for adults

Cryptosporidium

Stool microscopy, culture, immunoassay

Nitazoxanide—500 mg PO bid for 3 days

Cyclospora cayetanensis

Stool microscopy, stool culture, acid-fast stain, fluorescence microscopy

Trimethoprim—trimethoprim-sulfamethoxazole (TMP-SMX), one double-strength 160/800 mg tablet PO bid for 7–10 days

empirical antibiotic therapy can be considered in the following circumstances—patients who appear toxic or have fever or dysentery (see discussion below), patients with severe traveler’s diarrhea, patients with suspected C. difficile colitis, patients who are immunocompromised, or when a known organism is isolated from a community outbreak. Tables 84.2 and 84.4 summarize recommended antibiotics for treating various bacterial and parasitic infections, respectively.

Disposition Most patients with gastroenteritis can be managed as outpatients. Written instructions should be given with recommendations for oral fluid intake, diet, and follow-up care. Hospitalization should be considered for patients with a toxic appearance, severe or persistent symptoms, inability to tolerate oral liquids, significant electrolyte abnormalities, and severe dehydration. Special consideration should be given to patients at the extremes of age or who are immunocompromised. These patients likely will require a more extensive evaluation and further care.

gastric acid. Antibiotic use reduces normal intestinal flora and therefore increases the colonization of pathogens such as C. difficile. Immunosuppressed patients such as those with HIV infection or patients on chemotherapy are predisposed to nontyphoid Salmonella. Poor sanitation and overcrowded conditions also enhance the spread of infected organisms. Bacteria organisms are broadly categorized as invasive or noninvasive. Invasive gastroenteritis is a clinical diagnosis made in the presence of signs or symptoms of intestinal mucosal invasion, such as fever, gross or occult blood in the stool, tenesmus (feeling of constantly needing to pass stool), or severe abdominal pain (Table 84.5). Patients with noninvasive gastroenteritis generally do not exhibit fever, produce bloody stools, or experience significant abdominal pain. Noninvasive gastroenteritis likely suggests the presence of a viral pathogen or toxin-producing bacteria. This illness typically is brief and self-limited, and diagnostic testing is not likely to be of benefit (Table 84.6).

INVASIVE BACTERIA

BACTERIAL GASTROENTERITIS

Campylobacter Enteritis

In the United States, foodborne diarrheal illness caused by bacteria has increased over the past decades. The four most commonly reported bacterial pathogens are Campylobacter, nontyphoid Salmonella, STEC, and Shigella. The causes of most diarrheal illnesses are never discovered. Most laboratories are equipped to culture only the common pathogens, and routine stool cultures for diagnostic testing often miss organisms such as enterotoxigenic E. coli, enteroaggregative E. coli, enteroinvasive E. coli, and noncholera Vibrio spp.6 There are several risk factors that influence the development of bacterial gastroenteritis. Very young patients have low immunity, and maternal passive immunity is lost after weaning from breast-feeding. Older adults are at risk due to the age-related intestinal mucosal alteration of mucosa production, gut flora, and cell surface receptor affinity for toxins. The use of antacids such as proton pump inhibitors decreases the bactericidal effect of

Epidemiology Campylobacter is the most commonly diagnosed cause of bacterial enteritis in developed countries. It is more common during the summer months. Campylobacter spp. are a common cause of so-called backpacker’s diarrhea, along with Giardia, both of which are frequently acquired by drinking water from wilderness sources.

Pathophysiology Campylobacter organisms are small, spiral-shaped, gram-negative bacteria. The most common species isolated are Campylobacter jejuni (94%), Campylobacter coli (1%), and Campylobacter fetus. Campylobacter spp. produce disease primarily by direct invasion of the colonic epithelium. Most infections are acquired by handling or eating raw or undercooked poultry meat. The primary

CHAPTER 84  Gastroenteritis

TABLE 84.5 

Invasive Bacteria and Clinical Features ORGANISM

CLINICAL FEATURES

INCUBATION PERIOD, DURATION, SOURCE

Campylobacter jejuni

Most common bacteria; organism identified in stool cultures; acute watery diarrhea, fevers, dysenteric characteristics

I, 2–5 days D, 5–14 days S, food, water, chickens

Nontyphoid

Usually foodborne (eg, poultry); acute watery diarrhea, often with fever; common in sickle cell and immunocompromised patients

I, 12– 24 h D, 2–7 days S, eggs, poultry, unpasteurized milk, pets

Typhoid

Fever, abdominal pain, ileus, systemic effects; most infections acquired during international travel

I, 12–24 h D, 2–7 days

Shigella

Most common bacterial organism identified in stool cultures; acute watery diarrhea, fever, dysenteric characteristics; Toxigenic

I, 1–2 days D,2–7 days S, water, person to person

Yersinia enterocolitica

Acute diarrhea, dehydrating; rare in United States but common with travel to Asia; can mimic appendicitis

I, 12–48 h D, 5–14 days S, food, water, milk, cats, dogs, pigs

Vibrio, noncholera (V. parahaemolyticus)

Associated with seafood, shellfish watery diarrhea, dysentery

I, 8–24 h D, 5–14 days S, raw, undercooked seafood

Escherichia coli Shiga toxin-producing; E. coli O157:H7

Watery, bloody diarrhea; foodborne—contaminated beef and produce; toxigenic; associated with HUS and TTP

I, 3–8 days D, 5–10 days S, uncooked beef, water, person to person, raw milk

SALMONELLA

D, Duration; HUS, hemolytic uremic syndrome; I, incubation; S, source; TTP, thrombotic thrombocytopenic purpura.

TABLE 84.6 

Noninvasive Toxigenic Bacteria and Clinical Features ORGANISM

CLINICAL FEATURES

INCUBATION PERIOD AND DURATION AND SOURCE

Staphylococcus aureus

Short incubation period, 2–7 h; preformed toxin; vomiting; lasts 65 years and children < 5 years) are at greatest risk of complications and death.12

Pathophysiology Transmission of norovirus occurs via the fecal-oral route (eg, ingestion of contaminated food and water and exposure to airborne droplets of vomitus-containing viral particles and fomites.

It has an incubation period of 1 to 2 days, with symptoms typically lasting for 48 to 72 hours. Norovirus is highly infectious for all age groups, and a small amount of inoculum (≈100 virions) is needed for virus transmission. Shedding of the virus in the stool can occur up to 2 to 3 weeks after onset of symptoms.

Clinical Features The onset of symptoms is commonly abrupt and associated with a rapid recovery. Vomiting is a prominent feature. Patients develop diarrhea that is usually moderate in amount, defined as four to eight stools over a 24-hour period. The diarrhea is characterized as nonbloody stool with a loose to watery consistency that lacks mucus. Associated symptoms include generalized malaise, myalgias, headache. and fever, which occur in approximately 50% of cases. Infection may be protracted and symptoms may be present for a longer period due to prolonged viral shedding, especially in the immunocompromised patient.13 Postinfectious complications of the condition include dyspepsia, reflux, and constipation. In rare circumstances, patients may present with central nervous system (CNS) complications, such as seizures and encephalopathy.

Diagnostic Testing The diagnosis of viral gastroenteritis is commonly based on clinical features of the condition. A norovirus outbreak in the community is suspected when these criteria are met: mean incubation period of 24 to 48 hours; mean duration of illness of 12 to 60 hours; presence of vomiting in more than 50% of cases, and absence of bacterial pathogens on stool cultures. These criteria have a 99% specificity and 68% sensitivity for the diagnosis.14 Identification of the exact causative viral agent is not necessary in most cases. However, in the setting of an outbreak, it is very important to isolate the causative organism so that successful mechanisms that disrupt viral transmission can be recognized. The main laboratory tools to diagnose norovirus infection are genomic amplification via the reverse transcriptase polymerase chain reaction (RT-PCR), immunoassays, and electron microscopy. RT-PCR can detect a stool viral load as low as less than 100 particles/g. PCR testing can also be performed on food and environmental samples. In comparison to RT-PCR, immunoassays have a lower sensitivity and specificity and hence have limited use in the diagnosis of sporadic cases of gastroenteritis. Electron microscopy is best used for the diagnosis of viral gastroenteritis due to rotavirus and astrovirus because large viral loads are shed in these conditions.

TABLE 84.7 

Viral Causes and Clinical Features ORGANISM

MODE OF TRANSMISSION

CLINICAL FEATURES

Norovirus

Ingestion of contaminated food and water; touching contaminated surfaces; extremely contagious

Most common cause of gastroenteritis in United States and most common cause of US foodborne-disease outbreaks; fever, headache, myalgias, nausea, vomiting, abdominal pain, diarrhea; incubation period, 12–48 h

Sapovirus

Ingestion of contaminated food and water; fecal-oral route Fever, nausea, vomiting, diarrhea; usually causes mild illness

Rotavirus

Ingestion of contaminated food and water; touching contaminated surfaces

Fever, nausea, vomiting, abdominal pain and watery diarrhea; incubation period ≅ 2 days

Adenovirus

Close personal contact; touching contaminated surfaces

Rare cause of serious illness; fever, diarrhea; can cause non-GI illness (eg, bronchitis, pneumonia, conjunctivitis)

Astrovirus

Fecal-oral route

Malaise, headache, abdominal pain, diarrhea; vomiting less common

CHAPTER 84  Gastroenteritis

Management Viral gastroenteritis due to norovirus has no specific treatment. Management is based on the clinical condition of the patient. Supportive care, including oral hydration or IV fluid replacement, may be required. Implementation of proper hand hygiene is key to prevent the disease from occurring. During norovirus gastroenteritis outbreaks, patients should be placed on contact precautions in a cohort setting. Routine disinfection and cleaning of environmental surfaces and equipment should also take place.15

Rotavirus Epidemiology The name rotavirus originated from the Latin word rota, meaning wheel, based on the classic appearance of the virus under electron microscopy. The virus predominantly infects infants and young children, with a milder disease occurring in adults. Prior to the development of the rotavirus vaccine, rotavirus was the leading cause of diarrhea in the United States among infants and children. Rotavirus is a stable virus and primarily transmitted via the fecaloral route and direct contact with contaminated surfaces. In the United States, epidemics occur typically in the winter and spring, from December to June.

Pathophysiology Pathogenesis of the illness is associated with diarrhea, which occurs as a result of three main mechanisms—the direct effect of the rotavirus enterotoxin NSP4, loss of brush border enzymes, and activation of the enteric nervous system.

Clinical Features Clinical features of rotavirus infection in children include fever, nausea, vomiting and nonbloody watery diarrhea. The virus has an incubation period of approximately 2 days. Symptoms can last from 3 to 8 days. Patients may also present with loss of appetite and signs of dehydration, including dry mucous membranes and decreased urinary output. Children with rotavirus can also have concurrent respiratory symptoms; 2% to 3% have CNS complications, including seizures, encephalopathy, and encephalitis. A milder form of rotavirus infection occurs in adults, especially in household members of infected children. Older adults and immunocompromised patients are at increased risk for more severe disease with protracted illness. This is important to help determine the duration of isolation and repeat testing to ensure

eradication of the virus. Rotavirus has been anecdotally implicated in cases of necrotizing enterocolitis, intussusception, and biliary atresia.16

Diagnostic Testing Rotavirus infection is diagnosed using antigen detection in stool samples. Large viral loads are shed, making electron microscopy a useful diagnostic test. Additional methods include immunoassays such as the enzyme-linked immunosorbent assay (ELISA) and latex agglutination. ELISA will detect virus from the onset of clinical symptoms. Nucleic acid testing, such as via the PCR assay, is the most sensitive test.17

Management Rotavirus is a self-limited illness that lasts for a few days in healthy individuals. Treatment involves supportive care and managing fluid status. Hospitalization is required in approximately 1 of 70 children infected with the virus. Prevention of rotavirus infection occurs with the use of two, live, attenuated oral vaccines—the pentavalent human bovine rotavirus reassortant vaccine (RV5, PRV, RotaTeq) and attenuated human rotavirus vaccine (RV1, HRV, Rotarix). The two vaccines have similar efficacy and safety profiles. Studies have shown that the vaccines are very effective in preventing the viral illness and hospitalization due to rotavirus gastroenteritis. The CDC recommends the following vaccination schedule: RotaTeq (RV5), to be given in three doses at ages 2, 4, and 6 months and Rotarix (RV1), to be given in two doses at ages 2 and 4 months. Rotavirus vaccines are contraindicated in certain infants. Children who have a latex allergy should not receive the RV1 vaccine because the applicator contains latex. Additional rotavirus vaccine contraindications include an allergy to any of the ingredients in the vaccines, anaphylaxis to a previous vaccine dose, history of intussusception, and severe combined immunodeficiency (SCID).18 Neither natural infection nor vaccine ensures protection from future infections, so vaccinated and unvaccinated children may develop multiple episodes of rotavirus gastroenteritis. The rotavirus vaccinations have been estimated to reduce rotavirus gastroenteritis by more than 90% among infants in all care settings and more than 70% for children aged 1 to 4 years.19

PARASITES Table 84.8 lists the clinical features of common parasites causing gastroenteritis; Table 84.4 summarizes appropriate diagnostic tests and treatment.

TABLE 84.8 

Parasites and Clinical Features ORGANISM

MODE OF TRANSMISSION

CLINICAL FEATURES

Giardia lamblia

Ingestion of contaminated food and water; fecal-oral route

Nausea, vomiting, abdominal cramps, flatulence, greasy stool that can float

Entamoeba histolytica

Ingestion of contaminated food and water; touching contaminated surfaces; fecal-oral route

Fever, anorexia, abdominal cramping, watery or bloody diarrhea; illness ranges from asymptomatic infection, fulminant colitis, peritonitis to extraintestinal amebiasis

Cryptosporidium

One of the most frequent causes of waterborne disease in US population

Abdominal cramping, diarrhea

Cyclospora cayetanensis

Ingestion of contaminated food and water; fecal-oral route

Nausea, vomiting, loss of appetite, weight, bloating, abdominal cramping, diarrhea

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Giardia Epidemiology Giardia lamblia is a well-known protozoan parasite that causes sporadic or epidemic gastroenteritis worldwide. The illness occurs more commonly in developing countries that have poor sanitary conditions. Approximately 20,000 cases occur in the United States on an annual basis, with the peak being in the summer to fall months. Infants, young children, travelers, immunocompromised individuals, and patients with cystic fibrosis or hypochlorhydria are at greatest risk for developing the disease.

but still has a positive stool culture. Asymptomatic carriers, especially children and food handlers, may need to be treated to reduce the risk of spread and decrease the risk of developing chronic intermittent diarrhea. In endemic areas, the reinfection rate is high; therefore, treatment may not be cost-effective. Prevention of the disease is promoted by the use of strict handwashing and the avoidance of ingesting contaminated water. To avoid spread of illness in hospitals, patients diagnosed with giardiasis and who are incontinent or wearing diapers should be placed on contact precautions.

Amebiasis

Pathophysiology

Epidemiology

G. lamblia exists in two forms, trophozoite (active form) and cyst (inactive form). Trophozoites attach to the mucosal lining of the small intestine and cause symptoms. This active form of the parasite is unable to survive outside the body for an extended period of time and hence cannot spread infection to others. The cystic form, however, is viable outside of the body for prolonged periods and, once ingested, changes into the trophozoite form. Trophozoites generate the cysts that exit the body via the feces. Giardia infection is transmitted via cysts through several routes, including ingestion of contaminated food and water and fecal-oral route transmission. Infection can result from the ingestion of as few as 10 cysts. Giardiasis is a common cause of diarrhea that occurs in hikers exposed to contaminated water. Person to person transmission can also occur in settings with poor hygiene— for example, child care settings with children who are not toilettrained. Infection can also be transmitted via anal intercourse.

Amebiasis is caused by the protozoan Entamoeba histolytica, which is found worldwide. The genus Entamoeba is comprised of many species, but E. histolytica is the only one linked to disease pathology. Amebiasis is more common in developing countries with poor sanitary conditions. Most E. histolytica infections are asymptomatic, with only 10% of carriers presenting with symptoms. Approximately 50 million cases of invasive E. histolytica disease occur worldwide each year. Specific groups of individuals are more predisposed to amebic colitis, such as those at the extremes of age, pregnant females, and malnourished individuals. Travelers to endemic areas are also at risk for infection.

Clinical Features Clinical features of acute giardiasis consist of sudden onset of diarrhea associated with malaise, weight loss, nausea, abdominal cramping, and bloating. Stools are characterized as being foulsmelling and fatty.

Diagnostic Testing Immunoassays have higher diagnostic sensitivities than stool microscopy and are the preferred diagnostic modality, when available. Several immunoassay tests are available, including direct immunofluorescent assays, immunochromatographic assays, and ELISAs. Stool microscopy can identify ova and parasites, especially in the acute phase, when cysts and trophozoites appear in the stool. In subacute, chronic, and asymptomatic cases, trophozoites may be present in the stool in small numbers or on an intermittent basis. Collection of multiple stool samples (eg, three stool samples collected on separate days) can increase sensitivity of the test. Biopsy of duodenal-jejunal tissue or aspiration of the duodenaljejunal area by endoscopy may be required to make the diagnosis when repeated stool samples tested for ova and parasites do not yield any organisms.

Management Treatment of symptomatic cases consists of metronidazole, 500 mg PO bid, or 250 mg PO tid daily for 5 to 7 days. A single PO dose of tinidazole, 2 g, or nitazoxanide, 500 mg PO bid for 3 days, can also be given. Alternative agents include albendazole, mebendazole, and quinacrine. Treatment of asymptomatic giardiasis is controversial. An asymptomatic carrier can be someone who was initially diagnosed and treated for giardiasis and who now has no clinical symptoms

Pathophysiology E. histolytica exists in two forms, the trophozoite and cystic forms. The parasite is transmitted by the ingestion of the cystic form, which is the infective stage of the disease. Cysts can survive in the environment for weeks to months and can be found on the contaminated hands of food handlers or in fecally contaminated food and water. The infection can also spread through ingestion of cysts via anal-oral sexual practices. Trophozoites are formed when excystation occurs in the terminal ileum or colon, resulting in the invasive stage of the disease. Trophozoites can cause tissue destruction by penetrating into the colonic mucosal barrier, leading to secretory bloody diarrhea and colitis. Extraintestinal disease can also occur by the hematogenous spread of trophozoites via the portal circulation to the liver and other organs.

Clinical Features Acute amebic dysentery has an incubation period that ranges from 1 week to 1 year. Patients present with acute onset of severe abdominal cramps associated with fever, profuse, bloody diarrhea, and tenesmus. Gradual onset of symptoms can result in chronic amebic colitis. Individuals present with intermittent diarrhea, with two to four foul-smelling stools daily, usually containing blood-streaked mucus. Associated symptoms of fever, weight loss, abdominal cramping, and flatulence can be present. The clinical condition may have alternating symptomatic and asymptomatic periods, which last over months to years. The most common serious complication of amebic colitis is amebic liver abscess.

Diagnostic Testing Diagnosis of amebic colitis in the past was based on microscopic identification of cysts and trophozoites in stool samples. Trophozoites can also be identified in biopsy samples that can be obtained during colonoscopy. The development of stool antigen assays has enhanced the diagnostic process for amebic colitis. EIA kits for E. histolytica antibody and antigen detection are available. Molecular

CHAPTER 84  Gastroenteritis

analysis by PCR-based assays can also be used to distinguish E. histolytica from the nonpathogenic Entamoeba dispar species.

Management Treatment of benign cyst passers consists of paromomycin, 500 mg PO tid for 7 days. Oral iodoquinol, 650 mg tid for 20 days, or diloxanide furoate, 500 mg PO tid for 10 days, can also be given. For mild to moderate disease, metronidazole, 750 mg tid for 10 days, can be prescribed, followed by paromomycin treatment as above. Paromomycin can cause diarrhea as a side effect, thus making it difficult to assess the patient’s response to the metronidazole if both drugs are given together. Preventive measures using standard precautions to prevent fecal-oral spread should be followed.

FOOD POISONING Principles Foodborne gastroenteritis is an illness caused by the ingestion of food contaminated by viruses, bacteria, or bacteria toxins. Food poisoning is the term typically used for gastroenteritis caused by the ingestion of preformed toxins, such as staphylococcal toxins, B. cereus toxins, histamine-like substances from scombroid fish poisoning, ciguatoxins from ciguatera fish poisoning, or Clostridium botulinum toxins. The enterotoxins can also be produced in vivo after the ingestion of the bacterium and subsequent production of the enterotoxin in the intestinal lumen. Examples are C. perfringens, B. cereus, C. botulinum, enterotoxigenic E. coli, Vibrio cholerae, non-cholera Vibrio spp. such as V. enterocolitica, and Shiga toxinproducing E. coli. See the earlier section (“Noninvasive ToxinForming Bacteria”) for detailed background, clinical presentations, diagnosis, and treatment for each of these organisms. Scombroid and ciguatera fish poisoning are discussed in this section.

Clinical Features Food poisoning usually manifests 1 to 6 hours after the ingestion of preformed toxins from Staphylococus, B. cereus (short incubation form), and scombroid fish or ciguatera fish poisoning. Moderate incubation periods of 8 to 16 hours are seen after the ingestion of toxin-forming bacteria such as C. perfringens or B. cereus (long incubation form). Longer incubation periods of more than 16 hours are associated with ETEC, STEC, and Shigella and Vibrio spp. The clinical presentation usually involves an abrupt onset of nausea, vomiting, and abdominal cramping followed by watery diarrhea. Fever is usually absent, and symptoms should resolve within 24 hours. In some cases, B. cereus predominantly causes diarrhea and cramping. Often, there is a clear food exposure, such as at a picnic with many people in attendance who have the same illness at the same time.

Diagnostic Testing Diagnostic testing is usually not indicated in cases of food poisoning, and most individuals will recover within 24 hours. A detailed history of the timing, types, and places of recent sources of food ingestion should be obtained. Similar patterns of GI illness involving others who may have ingested the same foods will probably identify the causes. If identification for outbreak surveillance is needed, stool samples can be sent to test for for specific organisms. Most state health departments encourage consumers to report food poisoning incidents to their local health department. Physi-

cians and laboratories must report each singular diagnosed infection that is included in a notifiable disease list maintained by local, state, and/or federal agencies (www.cdc.gov/foodsafety). Foodborne illnesses are included in the notifiable disease lists. Examples include: salmonellosis, shigellosis, cholera, Shiga toxin– producing E. coli (STEC), norovirus, and hepatitis A.20 Physicians should suspect an outbreak when they are seen by a larger than normal number of people exhibiting the same symptoms.

Management In general, oral hydration is the mainstay of treatment. Antiemetics such as odansetron, 4 mg PO, or metoclopramide, 10 mg PO, may be prescribed to enhance oral hydration. Antibiotic therapy is rarely required because most patients will have a self-limited illness.

Scombroid Fish Poisoning Epidemiology Scombroid fish poisoning remains one of the most common forms of fish poisoning in the United States. The disease takes its name from the family Scombridae (eg, tuna, mackerel, skipjack, bonito, and related species) but results from the ingestion of a wide variety of dark meat fish, including nonscombroid species such as herring, bluefish, anchovy, sardine, amberjack, black marlin, and mahi mahi. The fish species most commonly implicated are mahi mahi, tuna, and bluefish. Most US cases occur in Hawaii and Florida, followed in frequency by California, New York, Washington, and Connecticut. However, scombroid poisoning can occur in any location where so-called fresh fish are flown in.

Pathophysiology The meat of implicated species naturally contains unusually high levels of histidine. Scombroid fish poisoning results from the ingestion of heat-stable toxins produced by bacterial action on the histidine present in the dark meat of the fish. The bacteria responsible are normal constituents of the surface marine flora, rather than contaminants. The histidine decarboxylase activity of these organisms produces histamine and histamine-like substances, which cause the symptoms of scombroid fish poisoning. High levels of histamine in the fish correlate directly with the occurrence of the illness. Formation of the scombrotoxins is directly related to improper preservation and refrigeration of the fish from the time they are caught until when they are cooked. In general, the problem is caused by improper refrigeration by the supplier rather than being the fault of the restaurant serving the fish. Other foods, notably Swiss cheese, contain sufficient amounts of histidine and have also been implicated.

Clinical Features The symptoms of scombroid fish poisoning resemble those of histamine intoxication. While eating the fish, the patient may note a metallic, bitter, or peppery taste, although many affected fish do not have an abnormal odor or taste. Symptoms usually develop abruptly within 20 to 30 minutes and consist of facial flushing, diarrhea, severe and throbbing headache, palpitations, and abdominal cramps. Other manifestations may include dizziness, dry mouth, nausea and vomiting, and urticaria. The facial flushing resembles a sunburn and can extend over the entire skin surface. The conjunctivae usually are infected. The duration of the major symptom complex generally is less than 6 hours and,

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although weakness and fatigue persist longer, the clinical course usually is benign. The attack rate is very high; most persons sharing the same toxic fish will become ill.

Management Parenteral antihistamine therapy, such as diphenhydramine, 50 mg IM or IV, or cimetidine, 300 mg IM or IV, usually relieve all symptoms promptly. This is not an allergic reaction, so patients should not be told that they are allergic to these fish, nor should they be prohibited from eating them again in the future. Suspected cases of scombroid should be immediately reported to the health department.

Ciguatera Fish Poisoning Epidemiology Ciguatera fish poisoning is a common public health problem, with appreciable economic significance. It is endemic in tropical regions but is found worldwide. Fish caught around Hawaii and Florida cause most US cases but, because the responsible ocean fish are now commonly transported inland, cases can be seen virtually anywhere. More than 400 fish species that frequent coral reefs have been implicated as ciguatoxin carriers, but fewer than 50 are commercially important; these include amberjack, barracuda, grouper, king mackerel, parrotfish, sea bass, snapper, sturgeon, surgeonfish, and ulua.

Pathophysiology Ciguatera fish poisoning results from the ingestion of the ciguatoxin neurotoxin. Ciguatoxin is produced by the marine dinoflagellate Gambierdiscus toxicus, which attaches itself to marine algae and is passed up the food chain. The lipid-soluble toxin accumulates in the tissues of the larger predacious coral reef fish, with the highest concentrations in the liver, intestines, head, and roe. It does not affect the fish in any way. Only humans suffer its ill effects when the toxin is ingested. Ciguatoxin is heat- and acid-stable, odorless, and tasteless. It is not deactivated by cooking or freezing, nor is the toxin eliminated by drying, salting, smoking, marinating, or pickling. It is not possible to predict whether a fish contains sufficient amounts of the toxin to produce illness. Ciguatoxin has anticholinesterase and cholinergic properties, but its neurotoxicity is mediated by its effect on sodium channels. Ciguatoxins cause a hyperpolarizing shift of the voltage dependence of channel activation so that sodium channels are open at the resting membrane potential. Spontaneous firing of neurons occurs as tetrodotoxin-sensitive sodium channels are activated, giving rise to the typical neurologic signs and symptoms.

Clinical Features Ciguatera fish poisoning is usually seen in the spring and summer months. The incubation period is approximately 2 to 6 hours, but a delay of 12 to 24 hours is not unusual. Attack rates are very high—80% to 90% of persons exposed become ill. Symptoms tend to be related to the amount of toxin ingested and vary considerably in their severity. If not fully recovered from an initial ingestion of ciguatoxin, affected persons are likely to have much more serious symptoms from a second ingestion. Classically, patients exhibit GI and neurologic symptoms. The GI symptoms (eg, nausea, vomiting, profuse watery diarrhea, crampy abdominal pain, diaphoresis) tend to appear first and resolve over the first 24 hours. The constellation of neurologic symptoms consists largely of dysesthesias and paresthesias around

the throat and the perioral area—burning feet, which may resemble alcoholic peripheral neuropathy, loose painful teeth, and sometimes CNS changes, such as ataxia, weakness, vertigo, visual hallucinations, and even confusion and coma. Distortion of temperature perception is vividly described by patients with ciguatera poisoning. Cold allodynia, defined as dysesthesia experienced on contact with cold water or cold objects, is almost pathognomonic of ciguatera poisoning and often is incorrectly referred to as cold-hot temperature reversal. Another classic feature is a return or a worsening of all the symptoms after ingestion of alcohol. Ciguatera poisoning lasts an average of 1 to 2 weeks, but at least 50% of victims are still symptomatic at 8 weeks. The neurologic symptoms, particularly the paresthesias and dysesthesias, tend to persist longer than the GI symptoms and have been reported up to years later.

Management Treatment is primarily supportive. IV fluids are given to replace volume losses from vomiting and diarrhea, and analgesics are given as needed. In severe cases, the toxin may exhibit some anticholinesterase activity, manifested as bradycardia and hypotension, which can be treated with atropine, 0.5 mg IV, and dopamine, 5 to 20 µg/kg/min via IV drip. Patients should be told to abstain from alcohol in any amount until symptoms have completely resolved. Pruritus may be managed with a histamine H1 receptor antagonist, such as diphenhydramine 25 mg PO qid, or cetirizine, 10 mg once daily. Amitriptyline, 25 mg bid, can bring about a dramatic reduction in the pruritus and dysesthesias, two of the most disturbing and protracted symptoms. The naturally occurring compound brevenal was shown to inhibit ciguatoxin-induced neurosecretion in laboratory studies. This compound may prove beneficial in treating the neurologic sequelae of ciguatera fish poisoning.

SPECIFIC GROUPS WITH GASTROENTERITIS Traveler’s Diarrhea Epidemiology Traveler’s diarrhea is the most common illness afflicting people traveling from resource-rich regions to the developing world. Approximately 10 million international travelers develop diarrhea annually, usually within the first week of travel. The traveler’s destination is the most important factor in assessing the risk of developing disease. Ingestion of contaminated food and water is the primary mode of transmission of traveler’s diarrhea.

Pathophysiology A variety of viruses, bacteria, and parasites cause traveler’s diarrhea. Bacterial and viral pathogens have an incubation period ranging from 6 to 48 hours. Parasitic causes have a longer incubation period, up to 2 weeks in duration. Bacterial pathogens cause approximately 80% of cases. ETEC is the most common bacterial cause for traveler’s diarrhea (see earlier, “Enterotoxigenic Escherichia coli”). Other causative agents are listed in Table 84.9.

Clinical Features Classically, traveler’s diarrhea presents with passage of three or more unformed stools in a 24-hour period, with at least one of these symptoms: fever, nausea, vomiting, abdominal pain or cramps, or blood in the stools. Patients with a moderately severe

CHAPTER 84  Gastroenteritis

TABLE 84.9 

TABLE 84.10 

Causative Organisms and Treatment of Traveler’s Diarrhea

Preventive Medications and Treatment for Traveler’s Diarrhea in Adults

ORGANISM

TREATMENT

Enterotoxigenic Escherichia coli (ETEC)

Ciprofloxacin, 500 mg bid or 750 mg PO once daily for 1–3 days

PHARMACOLOGIC AGENT

Enteroaggregate E. coli

Ciprofloxacin, 500 mg bid or 750 mg PO once daily for 1–3 days

Campylobacter

Azithromycin, 500 mg PO daily for 3 days

Salmonella

Levaquin, 500 mg PO daily for 7 days

Shigella

Ciprofloxacin, 750 mg PO daily for 3 days

Norovirus

Supportive care

Rotavirus

Supportive care

Giardia

Metronidazole, 500 mg PO bid or 250 mg tid for 5–7 days

case have one or two unformed stools in 24 hours, with at least one of these symptoms or the passage of more than two unformed stools in 24 hours without any other symptoms. Mild disease relates to the passage of one or two unformed stools in 24 hours without the presence of other symptoms. Patients commonly present with low-grade fever, abdominal cramping, and watery diarrhea. Traveler’s diarrhea is typically a self-limited illness.

Diagnostic Testing Diagnostic testing should be reserved for patients with severe or persistent symptoms. Stool cultures are rarely necessary. Cultures are mainly sent to confirm outbreaks. If stool cultures are sent, testing should specifically look for enterotoxigenic E. coli, Shigella, Campylobacter, and norovirus. If the enteritis is chronic (>2 weeks in duration), associated with foul-smelling and excessive flatulence, the stool should be examined for Giardia.21

Management The best strategy regarding traveler’s diarrhea is prevention. Travelers should avoid eating dairy products, raw fruits and vegetables, or undercooked meat and seafood. Peeled fruits are generally safe. Individuals should use water that has been boiled, which is the most reliable method to make the water safe for consumption. Travelers should also avoid ice and food served at room temperature. Table 84.10 lists preventive medications and treatment of traveler’s diarrhea. The risk of traveler’s diarrhea can be reduced by more than 90% with the use of prophylactic antibiotics. However, due to the development of adverse side effects and resistance, prophylaxis is recommended only for individuals with comorbidities that place them at high risk for complications of diarrhea (eg, renal failure patients, patients with inflammatory bowel disease, or patients with ileostomies or colostomies). Prophylactic antibiotics should not be given for more than 2 to 3 weeks.22 The risk of developing traveler’s diarrhea is also reduced by the use of alcohol-based hand sanitizers (containing >60% alcohol) and meticulous hand hygiene. The antacid bismuth subsalicylate decreases the incidence of traveler’s diarrhea by 65% due to its antibacterial and antisecretory effects. The recommended dose is two tablets qid or 1 fluid ounce qid. Bismuth subsalicylate should be avoided in those who are allergic to aspirin because it contains

RECOMMENDED DOSE

ADVERSE EFFECTS

PREVENTION Bismuth subsalicylate

524 mg PO qid

Contains hydrogen sulfide, which turns stool and tongue black in color

Ciprofloxacin

500 mg once or twice daily

Achilles tendon damage; Clostridium difficile infection

Rifaximin

200 mg once or twice daily

Considered safe because it is not absorbed

TREATMENT Bismuth subsalicylate

524 mg PO qid (1 oz Contains hydrogen liquid or two tablets) sulfide, which turns stool and tongue black in color

Loperamide

4 mg initially, then 2 mg after each unformed stool; not to exceed 8 mg/day.

Lowest effective dose should be taken to prevent post–traveler’s diarrhea constipation

Ciprofloxacin

500 or 750 mg once daily for 1–3 days

Achilles tendon damage; C. difficile infection

Rifaximin

200 mg tid for 3 days

Considered safe because it is not absorbed

Azithromycin

500 mg daily for 3 days or 1000 mg in single dose

Nausea is common adverse effect

salicylate. Potential side effects include blackening of the tongue and stool. It should not be taken for more than 3 weeks.23 Loperamide, an opioid antimotility drug, can decrease the frequency of loose stools. In patients with fever or bloody stools, an antimotility agent should be given in combination with an antibiotic because it may increase the contact time of the toxin or invasive infectious agents with the intestinal mucosa. Children younger than 2 years should not receive loperamide because it is linked with rare reports of paralytic ileus associated with abdominal distention. The mainstay of treatment for traveler’s diarrhea is hydration. Antibiotics such as quinolones, azithromycin, and rifaximin and antimotility agents can be prescribed, when indicated (see Table 84.8). The decision to initiate treatment for traveler’s diarrhea is based on the initial amount of diarrhea, severity of associated signs and symptoms, and need for resolution of the diarrhea in regard to the patients’ travel plans. Commercially available oral rehydration packets can be used by travelers to maintain their fluid status. In patients with mild symptoms, described as having one to three loose stools/24 hours, with or without mild enteric symptoms, loperamide can be used to decrease the number of loose stools. Bismuth subsalicylate can also be taken to control nausea. Promethazine, an antihistamine, can be given in oral or suppository form for severe nausea and vomiting. In patients with moderate to severe traveler’s diarrhea, antibiotics can shorten the duration of disease by 1.5 days. The choice of antibiotic is based on the location of the traveler. A fluoroquinolone such as ciprofloxacin is the antibiotic of choice

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for most geographic locations. It can be given as 750-mg oral single-dose therapy or as a 3-day course. Azithromycin, 500 mg PO daily for 3 days, is the drug of choice to treat Campylobacter, which is a common cause in Southeast Asia. Rifaximin, 200 mg PO tid for 3 days is an alternate antibiotic that can be prescribed for patients with noninvasive illness. It is not effective against invasive pathogens such as Campylobacter, Salmonella, and Shigella spp.24

Gastroenteritis in the Immunocompromised Host With HIV/AIDS The evaluation of gastroenteritis in HIV-positive patients deserves special attention because these patients are at risk for opportunistic enteric infections and are more likely to develop chronic gastroenteritis. In addition to the regular enteropathic bacterial pathogens, HIV-positive patients, particularly those with a CD4+ count less than 200/mm3, are more susceptible to certain viruses and parasites, such cytomegalovirus (CMV), Cyclospora, Cryptosporidium, Isospora, Mycobacterium avium-intracellulare complex (MAI), and Giardia. HIV itself may also cause diarrheal illness. Although not precisely clear, it is thought that HIV may cause a direct infection of the enterocytes and invasion of the lymphoid tissues of the GI tract. Patients with an extremely low CD4+ count, less than 100/mm3, typically tend to have opportunistic infections that are chronic in nature.25

Clinical Features The history should ascertain treatment with highly active antiretroviral therapy (HAART), the CD4+ count and viral load. A history of previous enteric pathogen-related diarrheal illness is important because recurrence rates are common. Anal receptive intercourse may predispose the patient to colonic pathogens, such as Giardia, Entamoeba, CMV, Shigella, and Campylobacter. Antiviral therapy–induced diarrhea has been also known to be the cause of watery diarrhea in HIV-positive patients. In HAART-naïve populations, Cryptosporidium and CMV infections are the two most common causes. Chronic high-volume watery diarrhea often is indicative of small bowel disease from one of the coccidia, Cryptosporidium and Cystoisospora belli. Although selflimited in the healthy host, coccidial disease often is persistent in patients with CD4+ counts less than 200/mm3. CMV and MAI also produce a chronic illness in those with CD4+ counts less than 100/mm3. Fever, weight loss, and abdominal pain are prominent; diarrhea is mild to moderate and sometimes bloody, typical of colonic disease. Microsporidia have emerged as a common cause of diarrhea in patients with AIDS in whom the CD4+ count is less than 100/mm3. Salmonella infections, especially with S. typhimurium, are common in immunocompromised hosts. Patients with AIDS who acquire Salmonella enteritis are at increased risk for bacteremia and metastatic focal infection compared with normal hosts. C. difficile enteritis occurs more commonly in patients with AIDS owing to the common use of prophylactic antibiotic therapy and frequent hospitalizations. It is the most common bacterial enteritis in the AIDS population.

Diagnostic Testing In patients with AIDS, the presenting signs and symptoms generally do not allow consistent classification of diarrheal illness, as is done for the immunocompetent host, because many patients with AIDS have multiple, concomitant enteric pathogens. However, some clinical pictures are typical. Patients with a fulminating clinical course usually have a disseminated infection, such as infection with CMV or MAI complex. Massive weight loss is also associated with diarrhea caused by infection with those two organisms and the coccidia Cryptosporidium and Cystoisospora. Voluminous watery diarrhea usually is a result of one of the coccidial organisms, including Cyclospora and Isospora. Patients with a proctocolitis-like picture most often have herpes simplex virus or CMV infection. Laboratory testing should initially focus on testing stool samples for C. difficile toxins and other bacteria, specifically Salmonella. If the stool is bloody and the CD4+ count is less than 200/mm3, stool should be sent for CMV and MAI testing. If the diarrhea is present for more than 14 days, three stool samples for stool ova and parasites should also be sent. An acid-fast smear should be requested to look for Cryptosporidium, Cystoisospora, Isospora, and Cyclospora if suspected as described. If the patient has suspected infectious colitis but recent stool analyses have been negative for any organism, an inpatient flexible sigmoidoscopy may be performed to enhance the yield of a pathogen. Small bowel biopsy and duodenal aspiration may be indicated when stool examination, cultures, and sigmoidoscopy fail to yield a definitive diagnosis. Small bowel studies are most helpful for detecting infection with Cryptosporidium, CMV, MAI, Giardia, or C. belli. Small bowel enterocolitis generally presents with watery diarrhea without fever or fecal leukocytes.26

Management Treatment should be directed toward the presumptive causative organism. As for immunocompetent patients, a cautious approach to initiating any antibiotic is suggested. Empirical antibiotic treatment should be started if the patient has fever, bloody stool, appears ill, or has a low CD4+ count. Ciprofloxacin, 500 mg PO, may be empirically initiated while the evaluation is in progress. If Giardia or C. difficile is suspected, metronidazole, 500 mg PO, should be added. If CMV colitis is suspected, foscarnet, 90 mg/kg IV, should be given. See Tables 84.3, 84.4, and 84.5 for treatment of specific organisms. Treatment failure is common and is often due to incorrect initial therapy. For example, CMV colitis can also mimic invasive bacterial pathogens because it can also cause severe colitis with bloody stool, fever, and abdominal cramps. Treatment failures are also due to the propensity for infections to recur or become chronic. Parasitic infections in immunocompromised patients may be difficult to eradicate, even with correct treatment. Gastroenteritis in the HIV-positive patient is often complex, prolonged in duration, and difficult to treat. It is recommended that an infectious disease specialist be involved in the care of these patients. Patients who have AIDS or are immunocompromised should generally be admitted for further management.

KEY CONCEPTS • Gastroenteritis is usually self-limited and requires supportive care only. • Routine laboratory testing or stool cultures are not indicated for most patients. • Caution should be used in the care of the very old and young. They have the highest morbidity and mortality in gastroenteritis.

• Hand hygiene with soap and water or hand sanitizers will contain the spread of most infectious agents in gastroenteritis. • Patients with fever, dysentery, bloody stools, severe dehydration, a suspicion for C. difficile, or immunocompromised state should have a complete blood count, electrolytes, and stool cultures sent.

CHAPTER 84  Gastroenteritis

KEY CONCEPTS—cont’d • Use of oral rehydration therapy (ORT) for dehydration is a preferred management strategy. • Hypotonic oral rehydration solution is preferred (eg, WHO-modified ORT solution). • The use of antiemetic medications may help with ORT. Odansetron, 4 mg IV or IM, is safe and cost-effective. • Early realimentation with normal feeding is advised and continuation of breast-feeding is suggested, if possible. • Campylobacter is the most common cause of bacterial enteritis in developed countries. • The norovirus, previously referred to as the Norwalk-like virus, is the most common cause of acute gastroenteritis in children and adults and usually occurs in the winter months. • Bacterial pathogens cause approximately 80% of cases for traveler’s diarrhea; enterotoxigenic Escherichia coli (ETEC) is the most common cause. • In patients with fever or bloody stools, an antimotility agent should be given in combination with an antibiotic because it may increase the contact time of the toxin or invasive infectious agents with the intestinal mucosa. • Classic food poisoning manifests usually 1 to 6 hours after the ingestion of preformed toxins from bacterial organisms such Staphylococcus, B. cereus, or C. perfringens. • Food poisoning is generally short-lived (24 hours), and its treatment is generally supportive care only.

• Risk factors for C. difficile colitis include recent antibiotic use (1–4 weeks), recent hospitalization, living in a long-term care facility, and use of antacids. • Evaluation (colonoscopy) for toxic megacolon and pseudomembranous colitis is recommended for patients with C. difficile colitis who are older, have a high leukocytosis finding, appear septic, and have a tender distended abdomen. Consider empirical antibiotic treatment for suspected C. difficile (metronidazole, 500 mg tid for 10 days) or traveler’s diarrhea (ciprofloxacin, 500 mg twice daily for 1–3 days). • Scombroid poisoning results from eating spoiled dark meat fish; it is not an allergic reaction but results from an ingestion of histamine. • In addition to the regular enteropathic bacterial pathogens, HIV-positive patients, particularly those with a CD4+ count 50% or positive Gram stain, is considered confirmatory. Treatment is typically with intraperitoneal antibiotics given for a 10- to 14-day course.

C H A P T E R 88 

Sexually Transmitted Diseases Jeffry McKinzie PRINCIPLES Sexually transmitted diseases (STDs) are a diverse group of conditions caused by more than 30 viral, bacterial, and parasitic organisms that are transmitted through sexual contact.1 Approximately 20 million newly acquired STDs occur in the United States each year, with an estimated $16 billion in associated health care costs.2,3 STDs are seen across all demographic, cultural, and socioeconomic strata; and all sexually active persons are at risk for acquiring them. Factors associated with higher risk for STDs reflect the importance of individual sexual practices and risktaking behaviors (ie, multiple sex partners, substance abuse, commercial sex workers, men who have sex with men, and unsafe sex practices), as well as various demographic and social determinants that influence health status (ie, adolescents and young adults, minorities, and low socioeconomic status). STDs are among the most common urogenital conditions encountered in the emergency department (ED). The management of patients with STDs is particularly challenging for multiple reasons: (1) the clinical presentation is highly variable; (2) available diagnostic tests have limited sensitivity and results are usually delayed; (3) compliance with treatment, follow-up, and partner notification is often poor; and (4) misdiagnosis and suboptimal treatment can result in serious sequelae. In addition to the morbidity associated with individual STDs, many of these infections also increase the risk of human immunodeficiency virus (HIV) transmission and acquisition in both the infected person and their sexual partners. Thus, STDs have a significant impact on individual and public health. Patients with STDs frequently present with complaints related to the genitalia but may also present with a variety of nonspecific dermatologic, gastrointestinal, musculoskeletal, and systemic complaints. Because the signs and symptoms of many common STDs are often nonspecific, one must maintain a high level of awareness for these conditions and their associated complications. A thorough history, including sexual history, and focused physical examination facilitate appropriate diagnosis and treatment. The sexual history should include number and gender of sexual partners, types of sexual practices, use of barrier contraception (condoms), and past history of STDs. Obtaining an accurate sexual history may be difficult due to the sensitive nature of the subject, lack of established physician-patient rapport, and other constraints of the ED setting. Evaluation is facilitated by the use of a nonjudgmental approach, maintenance of patient privacy, and assurance of confidentiality. The differential diagnosis for STDs is extensive, including many other infectious and noninfectious conditions (Table 88.1). Most STDs can be broadly categorized as conditions characterized by one of the following manifestations: genital ulcers, genital discharge, epithelial cell infections, and infestation by ectoparasites. Some STDs, such as syphilis, frequently have associated systemic symptoms in addition to their genitourinary manifestations. Other STDs, such as HIV, may have systemic manifestations in the absence of genitourinary signs and symptoms. STDs frequently coexist. Diagnosis of one STD should prompt consideration of other coexisting infections, which may not be

clinically apparent. Screening for other STDs, including HIV, should be considered, because early diagnosis and treatment benefits both the individual patient and the public health. Despite current recommendations from the Centers for Disease Control and Prevention (CDC) for routine HIV screening among patients age 13 to 64 years in all health care settings, systematic HIV testing is not routinely performed in most EDs.4 When available, rapid HIV testing should be considered. Patients should be counseled regarding the need for HIV testing if it is not performed in the ED. Empirical antibiotic treatment designed to cover the most likely infecting organisms is recommended for patients with suspected STDs to maximize eradication of disease in the individual patient and reduce the spread of infection to other susceptible persons. Empirical therapy is particularly important when there are concerns about the patient’s ability to obtain appropriate follow-up care. Confirmatory diagnostic studies should still be considered, even when empirical therapy is provided. Microbiologic diagnosis confirms the appropriate choice of empirical therapy, provides guidance for potential changes in treatment, and facilitates reporting of specific STDs to public health authorities. The diagnosis of an STD provides the physician with a “teachable moment” to educate the patient regarding important factors, including (1) nature of the infection and how it is transmitted; (2) compliance with prescribed therapy and recommended follow-up; (3) importance of preventive measures, including condom use and other safe sex practices; and (4) partner notification and treatment. Patients diagnosed with STDs should be counseled to abstain from sexual intercourse for at least 7 days after the patient and partner(s) complete treatment. Proper counseling helps to ensure the success of initial treatment and reduce the incidence of reinfection. When the diagnosis of an STD is suspected but not confirmed, the patient should be informed of the uncertainty of the diagnosis and the rationale for empirical treatment. The physician should be sensitive to the stress and anxiety that may ensue when discussing the diagnosis of an STD, particularly with a patient who assumes he or she is in a monogamous relationship. A respectful, nonjudgmental, and compassionate manner should be maintained. The CDC supports the use of expedited partner therapy (EPT) to ensure treatment in sexual partners of selected patients diagnosed with gonorrhea or chlamydia.5 With EPT, the clinician provides patient-delivered treatment for sexual partners without personally evaluating them. Although EPT may be suitable in some practice settings, its use in the ED is potentially problematic due to lack of knowledge regarding the partner’s medical history, allergies, pregnancy status, and other factors. In addition, some states prohibit the prescribing or dispensing of medications to patients who have not been seen and are unknown to the provider. Updated information regarding the use of EPT and applicable state regulations is available online from the CDC website.6 All patients diagnosed with an STD in the ED should be advised to notify their sexual partners to seek prompt evaluation and treatment. An organized mechanism for follow-up of positive diagnostic test results is recommended when these results are not available 1197

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TABLE 88.1 

Differential Diagnosis of Common Sexually Transmitted Disease Syndromes GENITAL ULCERS

GENITAL DISCHARGE

EPITHELIAL CELL LESIONS

ECTOPARASITES

Genital herpes

Gonorrhea

Genital warts

Pubic lice

Primary syphilis

Chlamydia

Secondary syphilis

Scabies

Chancroid

Nongonococcal urethritis (NGU)

Molluscum contagiosum

Other lice (body, head)

Lymphogranuloma venereum

Pelvic inflammatory disease

Neoplasm

Other mites (chiggers)

Granuloma inguinale

Trichomoniasis

Nevi

Ticks

Skin tags

Trauma

Bacterial vaginosis

Neoplasm

Candida vaginitis

Behçet’s disease

Foreign body

Abscess (draining)

Irritants/allergens

until after the patient and physician have left the ED. Obtaining accurate contact information at the time of the initial ED visit is important in ensuring timely patient notification. Reporting requirements vary by state, but the following STDs must be reported in all 50 states: gonorrhea, chlamydia, syphilis, chancroid, and HIV. Reporting may be laboratory-based or provider-based, or both. The clinician should be familiar with applicable state reporting requirements and the reporting mechanism used at their hospital. This chapter reviews the clinical features, diagnosis, and treatment of selected common STDs encountered in the ED setting. Readers are referred to the “Sexually Transmitted Diseases Treatment Guidelines” published by the Centers for Disease Control for additional information regarding the diagnosis and treatment of these conditions, as well as other less common STDs.7 Updates regarding changes in treatment guidelines are provided by the CDC in the Morbidity and Mortality Weekly Report, available at www.cdc.gov/mmwr.

DISORDERS CHARACTERIZED BY GENITAL ULCERS Genital ulcers may be caused by several different STDs, as well as various other infectious and noninfectious conditions. Genital herpes is the most common ulcerating STD seen in the United States, followed by syphilis. Chancroid is an uncommon cause of genital ulcers in the United States, and other STDs that may be manifested by genital ulcers (lymphogranuloma venereum, granuloma inguinale) are rare. Although the history, clinical appearance of the ulcers, and other associated findings provide helpful clues in differentiating the various causes of genital ulcers, these features are not specific enough to provide a definitive diagnosis. Diagnostic studies such as dark field microscopy, serology for syphilis, polymerase chain reaction (PCR), and viral culture should be considered to discriminate between the various etiologies and facilitate a definitive diagnosis, even when empirical therapy is initiated. Diagnostic testing is particularly important in patients that are unresponsive to previous empirical antibiotic therapy. Ulcerating STDs play an important role in facilitating the transmission and acquisition of HIV.

Herpes Principles Genital herpes is a lifelong viral infection caused by one of two types of herpes simplex virus (HSV): HSV-1 or HSV-2. Sexual transmission occurs more commonly with HSV-2, with an esti-

mated 50 million people infected in the United States alone.8 Many cases are undiagnosed. HSV is often transmitted by persons who are unaware that they are infected, or who are asymptomatic at the time of transmission. HSV transmission occurs through viral contact with a break in the skin or intact mucous membranes. The average incubation period is 4 days but may range from 2 to 12 days. The virus ascends via sensory nerves to the dorsal root ganglia, where it becomes latent but may reactivate periodically. Herpes, like other ulcerating STDs, facilitates the transmission and acquisition of HIV. Herpes infection in pregnant women may result in transmission to the infant at the time of delivery, with devastating associated neonatal morbidity and mortality.

Clinical Features Typical herpetic lesions begin as a cluster of small erythematous painful vesicles, which quickly ulcerate (Fig. 88.1). Lesions may occur anywhere the organism is inoculated, but they are typically seen on the skin of the external genitalia, perineum, and buttocks and on the mucous membranes of the vagina, rectum, and oropharynx. Primary infection occurs when a patient is infected with HSV-1 or HSV-2 with no preexisting antibodies to either type. The primary infection is usually more painful and symptomatic, with associated tender regional lymphadenopathy, fever, malaise, headache, and other systemic symptoms. Dysuria is common due to the proximity of the lesions to the urethra. The symptoms of untreated primary infection typically last from 2 to 4 weeks before resolving spontaneously. Nonprimary infection occurs when a patient is infected with HSV-1 or HSV-2 and has preexisting antibodies to the other viral type (ie, a patient with preexisting antibodies to HSV-1 due to orolabial herpes becomes infected with HSV-2 causing genital herpes). Patients with a nonprimary infection typically have fewer skin lesions and less systemic symptoms than those with primary infections. Recurrent episodes tend to be less symptomatic and shorter in duration, with lesions occurring in the same distribution due to reactivation of latent infection in the affected nerve roots. Recurrences are more frequent with infection caused by HSV-2 than with HSV-1. Recurrent outbreaks are often heralded by prodromal symptoms of itching, burning, and paresthesias prior to the development of skin or mucous membrane lesions. Reactivation of latent HSV may occur in response to a variety of stressors, including acute illness or injury, immunosuppression, psychological stress, and menses. Recurrences typically become less frequent and less severe over time. Extragenital complications of HSV infection include meningoencephalitis, transverse myelitis, hepatitis, pneumonitis, transverse myelitis, and disseminated

CHAPTER 88  Sexually Transmitted Diseases

TABLE 88.2 

Treatment of Common Ulcerating Sexually Transmitted Diseasesa DISEASE Herpes simplex   Primary episode

  Recurrent episodes

Syphilisb   Primary, secondary, and early latent syphilis   Neurosyphilis

Fig. 88.1.  Genital herpes lesions on the penile shaft.

infection. Asymptomatic viral shedding and transmission occurs even in the absence of visible lesions on the skin or mucous membranes.

Diagnostic Testing The diagnosis of genital herpes is frequently made based upon clinical findings. Although the presence of typical skin or mucous membrane lesions is suggestive of herpes, the clinical diagnosis is both insensitive and nonspecific. A history of similar lesions in the same anatomic distribution supports the clinical diagnosis. PCR is the diagnostic test of choice, with the highest sensitivity and specificity in the presence of active lesions. Viral culture is also specific but less sensitive than PCR. Dark-field microscopy and serologic testing for syphilis should be considered to help differentiate cases of syphilis. The utility of these diagnostic studies is limited in the ED because test results are delayed, but results may be helpful at the time of follow-up. Direct fluorescent antibody (DFA) and serology for HSV are available, but less commonly used in the ED setting. Cytologic testing (Tzanck preparation) is nonspecific and insensitive and should not be relied upon to make the diagnosis of HSV.

Management Genital herpes is treated with the antiviral medications acyclovir, famciclovir, or valacyclovir. Antiviral therapy is not curative but has been shown to decrease the duration and severity of symptoms and the development of complicated HSV infection, particularly when started early during the primary infection. Prompt initiation of antiviral treatment is key to obtaining optimal clinical benefit. Although most studies have evaluated drug initiation within 72 hours of symptom onset, antiviral therapy may still be offered after this time frame in the presence of ongoing symptoms and the development of new lesions. Multiple regimens are available for treatment of primary and recurrent episodes of genital herpes with oral antiviral medications (Table 88.2). Oral antiviral therapy is generally well tolerated with few side effects. Suppressive therapy

Chancroid

RECOMMENDED TREATMENTS Acyclovir 400 mg PO tid for 7 to 10 days or Acyclovir 200 mg PO five times a day for 7 to 10 days or Valacyclovir 1000 mg PO bid for 7 to 10 days or Famciclovir 250 mg PO tid for 7 to 10 days Acyclovir 400 mg PO tid for 5 days or Acyclovir 800 mg PO bid for 5 days or Acyclovir 800 mg PO tid for 2 days or Valacyclovir 500 mg PO bid for 3 days or Valacyclovir 1000 mg PO daily for 5 days or Famciclovir 125 mg PO bid for 5 days or Famciclovir 1000 mg PO bid for 1 day or Famciclovir 500 mg PO once, then 250 mg bid for 2 days Benzathine penicillin G 2.4 million units IM single dose Aqueous penicillin G 3 to 4 million units IV every 4 hours for 10 to 14 days Ceftriaxone 250 mg IM single dose or Azithromycin 1000 mg PO single dose or Ciprofloxacin 500 mg PO bid for 3 days

a

Alternative treatment regimens for selected patients (including pregnancy, drug allergies) can be found at www.cdc.gov/std/treatment. Pregnant women with syphilis who are allergic to penicillin should be admitted for desensitization and treatment with penicillin. IM, Intramuscular; PO, per os (by mouth). b

with daily antiviral use has been shown to decrease the frequency of recurrences while the medication is being taken, but it does not affect the frequency or severity of recurrences after the drug is discontinued. Topical antiviral therapy provides minimal clinical benefit and is not recommended.

Disposition Most patients with genital herpes are managed as outpatients. Hospitalization for parenteral therapy with acyclovir is indicated for systemic complications of HSV infection, including meningoencephalitis, hepatitis, pneumonitis, and disseminated infection. Patients with genital herpes should be counseled that transmission may occur even in the absence of clinical symptoms. Condom use has been shown to reduce but not eliminate the incidence of HSV transmission. Discordant couples (ie, those in which one partner is HIV+) should be advised to avoid sexual contact during active outbreaks, which is when viral transmission is highest. Condoms should be used during asymptomatic periods. Patients with genital herpes should also be counseled regarding the increased risk of acquisition and transmission of HIV in the presence of genital ulcers.

Syphilis Principles Humans are the only known host for Treponema pallidum, the spirochete that causes syphilis. The incidence of syphilis has

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declined significantly since penicillin became widely available in 1945, but outbreaks still occur intermittently. After a progressive decline in the incidence of syphilis from 1990 to 2000, there has been an increase in recent years. More than 17,000 cases of primary and secondary syphilis were reported to the CDC in 2013.9 The rates of primary and secondary syphilis are higher among those between 20 to 29 years old, minority groups, and men who have sex with men. It is more common in the southeastern United States compared to other regions of the country.

Clinical Features Syphilis has been called “the great imitator,” because its clinical manifestations are protean. Syphilis is divided into primary, secondary, latent, and tertiary stages based upon clinical and serologic findings. The primary and secondary stages of syphilis are most commonly seen in the ED setting. Transmission occurs when the spirochetes gain access through disrupted epithelium of the skin or mucous membranes. The average incubation period is approximately 21 days but may range from 3 to 90 days. Primary syphilis is initially manifested by the development of a painless papule at the site of inoculation. The lesion ulcerates, forming the chancre of primary syphilis (Fig. 88.2). The chancre is classically described as a relatively painless clean-based ulcer with well demarcated indurated edges, measuring approximately 1 to 2 cm in size. Nontender regional lymphadenopathy may be seen. Although the chancre often occurs in the genital or perianal area, it may occur at any site of inoculation, including the oropharynx, breasts, hands, and other sites. The chancre will heal spontaneously over the course of 3 to 6 weeks. Because the chancre is relatively painless, it may go unnoticed by the patient. Secondary syphilis will develop in approximately 25% of patients with primary syphilis over a period of several weeks to months. Manifestations of secondary syphilis include rash, generalized lymphadenopathy, mucous membrane lesions, and systemic symptoms. The rash is diffuse, involving the face, trunk, and extremities, including the palms and soles. The appearance of the rash is highly variable. Lesions may be macular, papular, scaly, or pustular in appearance (Fig. 88.3). Mucous patches are multiple shallow erosions of the oropharyngeal mucosa that are usually accompanied by other dermatologic and systemic manifestations of secondary syphilis. Condyloma lata, which resemble genital warts, are broad-based papular lesions that occur on the genitalia

and perineum and typically have a moist surface appearance (Fig. 88.4). Lymphadenopathy is typically diffuse, rubbery, and nontender. Epitrochlear adenopathy is particularly suggestive of secondary syphilis. A nonspecific “moth-eaten” alopecia may be seen. Systemic manifestations include low-grade fever, anorexia, headache, malaise, myalgias, and weight loss. Symptoms of secondary syphilis will resolve without treatment, with subsequent progression to latent syphilis. Latent syphilis is present when there is serologic evidence of syphilis infection in the absence of any clinical signs or symptoms. Latent infection acquired within the past 12 months is defined as early latent syphilis, whereas late latent syphilis includes cases of latent infection of greater than 12 months or unknown duration. Patients with early latent syphilis are considered to be infectious. Those with late latent syphilis are generally not infectious, with an important exception—pregnant women with late latent syphilis can transmit the infection to the fetus. Latent syphilis can persist indefinitely before progressing to tertiary syphilis. Tertiary syphilis, which includes cardiovascular manifestations and gummatous disease, is uncommon in the United States. Aortitis, aortic aneurysm, and gummatous lesions of the skin, bones, and other organs may be seen. In patients with untreated syphilis, the estimated risk of eventual progression to tertiary

Fig. 88.3.  Rash of secondary syphilis on palms and soles. (From Morse S, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 4, London, 2010, Saunders/Elsevier, Fig. 7.24,  p 188.)

Fig. 88.2.  Chancre of primary syphilis. (From Morse S, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 4, London, 2010, Saunders/Elsevier, Fig. 7.9, p 185.)

Fig. 88.4.  Condyloma lata of secondary syphilis.

CHAPTER 88  Sexually Transmitted Diseases

syphilis ranges from 25% to 40%. Neurosyphilis refers to infection involving the central nervous system (CNS) and may be seen in any stage of syphilis. Manifestations of neurosyphilis include altered mental status, meningitis, cranial nerve abnormalities, stroke, peripheral neuropathy, and auditory and ophthalmic abnormalities. Congenital syphilis, which is transmitted perinatally to the fetus, is relatively uncommon in recent years in the United States but has significant associated morbidity in infected children.

Diagnostic Testing T. pallidum is fastidious and cannot be cultured in the laboratory. The diagnosis of syphilis can be confirmed with darkfield microscopy or by serologic testing. Visualization of the spirochete on darkfield examination of specimens obtained from a chancre or from the moist lesions of secondary syphilis provides an immediate diagnosis. Dark-field microscopy is particularly useful in primary syphilis when false negative serology is common. The sensitivity and specificity of dark field microscopy vary depending upon the experience of the microscopist and the use of proper specimen collection techniques. The utility of darkfield microscopy is limited by the need for specialized laboratory equipment and appropriately trained personnel, which are lacking at many hospitals. Serologic tests for syphilis include nonspecific nontreponemal tests and specific treponemal tests. Both types of serologic testing are necessary for the proper diagnosis of syphilis. Nontreponemal tests include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR). The VDRL and RPR provide quantitative measurements of nonspecific antibodies that are produced in response to T. pallidum infection. The titers correlate with disease activity, typically rising with active syphilis infection and declining after successful treatment. The sensitivity of nontreponemal tests is approximately 70% to 80% in primary syphilis but rises to nearly 100% in secondary syphilis. False positive nontreponemal tests may be seen in a variety of conditions, including pregnancy, endocarditis, autoimmune disease, and other acute or chronic illnesses. A positive nontreponemal test should always be confirmed with a specific treponemal test. Specific treponemal tests include the fluorescent treponemal antibody absorption (FTA-ABS) and the microhemagglutination test for antibodies to T. pallidum (MHA-TP). These treponemal tests provide qualitative measurements of specific antitreponemal antibodies. Although these treponemal tests are highly specific for syphilis, they may remain positive for life even after successful treatment and cure. A nontreponemal test is used for screening purposes and serves as a better marker for acute infection, with the specific treponemal test used to confirm the diagnosis.

penicillin and the absence of proven alternative therapies. Patients with these conditions should be admitted for desensitization and treatment with penicillin. The Jarisch-Herxheimer reaction is an acute worsening of symptoms that may develop after antibiotic therapy is initiated for syphilis. The patient typically reports worsening malaise, myalgias, and fever within 24 hours of antibiotic treatment. The condition has traditionally been thought to be caused by the sudden lysis of spirochetes, but the mechanism is poorly understood. Treatment is supportive, including rest, hydration, and antipyretics. The symptoms resolve spontaneously. Anticipatory guidance regarding the appropriate management of this common self-limited reaction may prevent a return visit to the ED.

Disposition Most cases of syphilis are treated on an outpatient basis. Hospitalization is recommended for patients with penicillin allergy who require desensitization prior to penicillin therapy, including pregnant women with syphilis and patients with neurosyphilis or congenital syphilis.

Chancroid Principles Chancroid is an ulcerating STD caused by the gram-negative organism Haemophilus ducreyi. Chancroid is common in parts of the developing world but is rare in the United States, with only 10 cases reported in 2013. Like other ulcerating STDs, chancroid is a cofactor for the transmission and acquisition of HIV.

Clinical Features After an incubation period of less than 1 week, a tender erythematous papule develops at the site of inoculation. The initial lesion rapidly ulcerates, and multiple painful ulcers subsequently develop (Fig. 88.5). The ulcers typically have an irregular, inflamed, and “dirty” appearance compared to the well circumscribed cleanbased chancre of syphilis, and the smaller punched-out appearance of herpetic ulcers. Painful inguinal lymphadenopathy is common and may progress to bubo formation. A bubo is a large, painful, fluctuant unilateral inguinal lymph node, which may spontaneously rupture and drain purulent material.

Management Penicillin is the cornerstone of treatment for syphilis, with T. pallidum remaining highly sensitive to penicillin. The dosage and preparation of penicillin and the length of treatment vary depending upon the stage of the disease and the associated clinical manifestations (see Table 88.2). A single dose of long-acting benzathine penicillin G (2.4 million units intramuscularly) is curative in the majority of cases of primary, secondary, and early latent syphilis. Patients with significant penicillin allergy can be treated with doxycycline or tetracycline for 2 weeks if no contraindication to these drugs exists. Ceftriaxone has antitreponemal activity, but the optimal dosage and duration of therapy have not been established. Azithromycin has some efficacy but is not recommended as a first line therapy due to documented resistance and treatment failures. Penicillin remains the drug of choice for patients with neurosyphilis, congenital syphilis, and syphilis during pregnancy even in the presence of penicillin allergy, due to the known efficacy of

Fig. 88.5.  Multiple vulvar ulcers due to chancroid. (From Morse S, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 4, London, 2010, Saunders/Elsevier, Fig. 8.14, p 219.)

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Diagnostic Testing

Gonorrhea

Differential diagnosis of genital ulcers includes herpes and syphilis, both of which are more common than chancroid in the United States. Although the appearance of the ulcers may suggest the diagnosis of chancroid, the clinical diagnosis may be inaccurate. Dark-field microscopy and serologic testing are useful in identifying syphilis, whereas PCR and viral culture can confirm HSV infection. Chancroid is usually a clinical diagnosis based upon the presence of typical painful genital ulcers and associated tender adenopathy. Culture provides definitive diagnosis but is difficult due to the fastidious nature of H. ducreyi, which requires special culture media.

Principles

Management

Clinical Features

Patients with chancroid are treated as outpatients. Single-dose therapy with azithromycin or ceftriaxone is recommended for suspected chancroid (see Table 88.2). Alternative treatment regimens include oral ciprofloxacin or erythromycin.

The signs and symptoms of gonorrhea vary depending upon the sex of the patient, the site of inoculation, and the local or systemic spread of the infection. The incubation period for gonorrhea typically ranges from 3 to 7 days. Most men with gonococcal urethritis become symptomatic within 1 to 2 weeks, prompting them to seek curative treatment. Patients complain of urethral discharge and dysuria. The discharge is usually copious and purulent, although the clinical appearance alone cannot differentiate gonococcal urethritis from NGU (Fig. 88.6). Women with gonococcal cervicitis are often asymptomatic until ascending infection develops. Because many women remain asymptomatic for prolonged periods, a larger reservoir of untreated women exists. When present, symptoms of gonococcal cervicitis may include abnormal vaginal discharge, dyspareunia, and intermenstrual bleeding. Women with gonococcal cervicitis may also complain of dysuria due to associated urethritis. Gonococcal proctitis may occur in men and women who engage in receptive anal intercourse and in women who are inoculated by infected vaginal secretions. Patients with gonococcal proctitis are often asymptomatic but may complain of rectal pain, tenesmus, rectal discharge, or bleeding. Anoscopy may reveal abnormal discharge and inflamed friable rectal mucosa.

DISORDERS CHARACTERIZED BY GENITAL DISCHARGE Some STDs, including gonorrhea, chlamydia, trichomoniasis, and pelvic inflammatory disease (PID), are frequently characterized by the presence of genital discharge in absence of genital ulcers and lymphadenopathy. The differential diagnosis of genital discharge is broad, including infections that are not sexually transmitted and noninfectious conditions (see Table 88.1). For example, bacterial vaginosis and candidiasis are common conditions that are not considered to be sexually transmitted but are frequently found during the evaluation of a woman with vaginal discharge. Urethritis, cervicitis, and vaginitis caused by various organisms can present with associated genital discharge. Infectious causes of urethritis are generally divided into two categories: gonococcal urethritis and nongonococcal urethritis (NGU). Urethritis occurs in men and women and may be asymptomatic, particularly in persons with NGU. When present, symptoms include dysuria, urethral pruritus, and urethral discharge. The absence of visible discharge does not exclude the diagnosis. A clinical diagnosis of urethritis can be made on the basis of any of the following findings in the setting of compatible symptoms: (1) mucoid, mucopurulent or purulent urethral discharge, (2) Gram stain of urethral discharge containing two or more white blood cells (WBCs) per oil immersion field, (3) firstvoid urine sediment containing 10 or more WBCs per high-power field, and (4) positive leukocyte esterase test on first-void urine. Diagnosis and management of specific causes of urethritis are discussed later. Cervicitis is characterized by the presence of purulent or mucopurulent discharge from the endocervix and the presence of cervical friability. Many women with cervicitis are asymptomatic. The discharge may be visible in the endocervical canal or noted on an endocervical swab specimen. Cervical friability is demonstrated when endocervical bleeding is easily induced with gentle passage of a swab through the cervical os. Gonorrhea and chlamydia are common causes, but trichomonas and HSV may also cause cervicitis. Frequently, no organism is isolated despite the presence of clinical findings consistent with cervicitis. Women with cervicitis may complain of abnormal vaginal discharge, dyspareunia, and postcoital vaginal bleeding. Pelvic examination may demonstrate endocervical discharge and friability as described earlier. These findings are insensitive, and the absence of these findings on history and examination do not exclude the diagnosis of cervicitis. Specific causes of cervicitis and their management are discussed later.

Gonorrhea is the second most commonly reported STD in the United States, with more than 300,000 cases reported to the CDC annually. Humans are the only reservoir for the causative organism Neisseria gonorrhoeae, a gram-negative intracellular diplococcus. The prevalence of gonorrhea varies widely, with higher rates of gonorrhea seen among adolescents and young adults, minorities, people with low socioeconomic status, those with a history of substance abuse, and those who engage in high risk sexual behaviors.

Fig. 88.6.  Purulent urethral discharge due to gonococcal urethritis.

CHAPTER 88  Sexually Transmitted Diseases

Gonococcal pharyngitis is usually acquired from oral sexual exposure. Patients with pharyngitis are usually asymptomatic but may complain of sore throat. Tonsillar erythema and cervical lymphadenopathy may be present. Gonococcal conjunctivitis was historically seen most often in infants born to infected mothers. Because infants are now routinely prophylaxed at birth, gonococcal conjunctivitis is now more common in adults who self-inoculate by rubbing the eye with contaminated fingers. Severe conjunctival injection with copious purulent discharge is typically seen. The infection can progress rapidly to corneal ulceration, perforation, and blindness if untreated. Disseminated gonococcal infection (DGI) results from hematogenous spread of N. gonorrhoeae. DGI may occur in the absence of any signs or symptoms of the initial local infection. Characteristic clinical findings include rash, polyarthralgias, tenosynovitis, and septic arthritis. The rash usually consists of petechial or pustular lesions in an acral distribution on the distal extremities. The rash is sparse, with 2 to 10 skin lesions being typical and more than 40 lesions uncommon. Septic arthritis presents as a swollen, red, warm, and painful joint. One or more joints may be involved. The knees, wrists, and ankles are the most common sites. Rarer complications of DGI include hepatitis, meningitis, and myocarditis.

Diagnostic Testing In symptomatic men, a Gram stain of urethral discharge that reveals gram-negative intracellular diplococci has a sensitivity and specificity approaching 100% for the diagnosis of gonorrhea. Gram stain results are available rapidly. A positive Gram stain does not exclude coinfection with chlamydia or other organisms. Culture and nucleic acid amplification tests (NAATs) are both useful to confirm the diagnosis. NAATs are widely available and have replaced culture as the diagnostic gold standard. The sensitivity of NAATs for the detection of N. gonorrhoeae is higher than that of culture. A wider variety of specimens can be used for NAATs, including first-void urine and swabs from the urethra, cervix, and vagina. Suitable specimens can be obtained by the examining clinician or provided by the patient. Although NAATs is not yet FDA-approved for use with specimens obtained from the oropharynx, rectum, or conjunctivae, some laboratories have established performance specifications and met Clinical Laboratory Improvement Amendment (CLIA) guidelines for use of NAATs with oropharyngeal and rectal specimens. Culture with selective Thayer Martin media is still useful in selected patients and has the advantage of allowing antimicrobial susceptibility testing. Isolation of N. gonorrhoeae from the blood, synovial fluid, or skin lesions establishes a definitive diagnosis of DGI, but sensitivity of these cultures is poor. The organism may be more readily identified from other sites (urethra, cervix, rectum, or pharynx) even in the absence of localized symptoms at these sites. When accompanied by the appropriate clinical presentation, identification of gonorrhea by NAATs or culture from any site is sufficient for a presumptive diagnosis of DGI.

Treatment Recommended treatment options for gonorrhea have changed in recent years due to the increasing antimicrobial resistance of N. gonorrhoeae. Ceftriaxone remains the drug of choice for the treatment of gonorrhea. Single-dose therapy with an intramuscular injection of ceftriaxone 250 mg is recommended for most cases of gonococcal urethritis, cervicitis, proctitis, and pharyngitis (see Table 88.2). Concomitant therapy with a single dose of azithromycin 1 g per os (by mouth) (PO) is recommended to provide synergistic coverage with ceftriaxone against N. gonorrhoeae and

coverage of possible coexisting chlamydia infection. Directly observed therapy with both ceftriaxone and azithromycin can be administered in the ED to ensure compliance. The use of oral cephalosporins or fluoroquinolones is no longer recommended for the treatment of gonorrhea due to increasing antimicrobial resistance.10,11 DGI and gonococcal arthritis are treated with parenteral ceftriaxone 1 g daily. Several parenteral antibiotic regimens are available for treatment of severe or complicated PID (discussed later in this chapter).

Disposition Uncomplicated gonococcal infections are treated on an outpatient basis. Hospitalization may be warranted for more severe cases of upper tract infection, such as PID or epididymo-orchitis. Admission and treatment with parenteral ceftriaxone is recommended for DGI, septic arthritis, and conjunctivitis.

Chlamydia Principles Chlamydia is the most commonly reported STD in the United States, with more than 1.4 million cases reported to the CDC in 2013. Chlamydia trachomatis, an obligate intracellular organism, is the causative pathogen. Approximately 50% of men and 70% of women who are infected with chlamydia are asymptomatic. Adolescents and young adults 15 to 24 years old have the highest rate of chlamydia infection. The reported rate of chlamydia is twice as high among women compared to men, reflecting the higher number of women screened for this infection.

Clinical Features Chlamydia infection is a common cause of NGU. When present, the urethral discharge associated with chlamydia is typically scant, mucoid, and less purulent than the discharge seen with gonorrhea. Dysuria is less pronounced and presentation is often delayed. Chlamydia cervicitis may present with mucopurulent cervical discharge or postcoital bleeding but is often asymptomatic. When untreated, chlamydia can progress to upper tract infection, including epididymitis and orchitis in men and PID in women. Patients with epididymitis and orchitis complain of unilateral scrotal pain and swelling, and they may also report symptoms of urethritis. Swelling and tenderness of the epididymis and testicle are usually present. Epididymitis is more common with chlamydia infection alone or combined gonorrhea and chlamydia infections, rather than with gonorrhea alone. Chlamydia frequently contributes to the development of PID, which may be indolent or clinically silent, but results in significant chronic sequelae.

Diagnostic Testing Differentiation between chlamydial and gonococcal infection based solely upon history and physical examination is unreliable, and these infections frequently coexist. NAATs are the diagnostic test of choice, with sensitivity greater than 90% and specificity of 99% for the diagnosis of chlamydia. NAATs assays are approved for use with specimens obtained from the urethra, cervix, vagina, or first-void urine specimens. Some laboratories meet CLIA guidelines to perform NAATs on specimens from the oropharynx and rectum.

Management Recommended treatment regimens for chlamydia urethritis or cervicitis include single-dose azithromycin 1 g PO or a 7-day

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TABLE 88.3 

TABLE 88.4 

Treatment of Sexually Transmitted Diseases Associated With Genital Dischargea

Treatment of Complicated or Upper Genitourinary Tract Sexually Transmitted Diseasesa

DISEASE

DISEASE

RECOMMENDED TREATMENTS

Disseminated gonorrhea

Ceftriaxone 1 g IV or IM every 24 hours plus Azithromycin 1 g PO single dose Hospitalization and identification consult recommended

RECOMMENDED TREATMENTS

Gonorrhea   Urethritis, cervicitis, proctitis, pharyngitis

Ceftriaxone 250 mg IM single dose plus Azithromycin 1 g PO single dose

Chlamydia   Urethritis, cervicitis, proctitis, pharyngitis

Azithromycin 1 g PO single dose or Doxycycline 100 mg PO bid for 7 days

Gonococcal conjunctivitis

Nongonococcal urethritis (NGU)

Azithromycin 1 g PO single dose or Doxycycline 100 mg PO bid for 7 days

Ceftriaxone 1 g IV or IM single dose plus Azithromycin 1 g PO single dose Consider hospitalization & ID consult

Epididymitis/orchitis

Trichomoniasis

Metronidazole 2 g PO single dose or Tinidazole 2 g PO single dose

Ceftriaxone 250 mg IM single dose plus Doxycycline 100 mg PO bid for 10 daysb or Ceftriaxone 250 mg IM single dose plus Levofloxacin 500 mg PO every day for 10 daysc or Levofloxacin 500 mg PO every day for 10 daysd

a

Alternative treatment regimens for selected patients (including pregnancy, drug allergies) can be found at www.cdc.gov/std/treatment. IM, Intramuscular; PO, per os (by mouth).

course of doxycycline 100 mg PO bid (Table 88.3). Both regimens are equally efficacious when taken as directed, but single-dose azithromycin is preferable if there is concern for possible noncompliance with doxycycline. Azithromycin is the drug of choice in pregnancy. Alternative regimens for the treatment of lower tract chlamydia infection include a 7-day course of erythromycin, levofloxacin, or ofloxacin. Suspected upper genitourinary tract infection with chlamydia (ie, epididymitis, PID) requires a longer course of antibiotic therapy ranging from 10 to 14 days (Table 88.4). Empirical treatment for both gonorrhea and chlamydia is recommended when confirmatory test results are unavailable, because history and physical examination cannot reliably differentiate these conditions and coinfections often occur. Single-dose ceftriaxone 250 mg IM plus single-dose azithromycin 1 g PO treats uncomplicated gonorrhea in addition to lower tract chlamydia infection.

Disposition Most chlamydia infections are treated on an outpatient basis. Patients with severe upper tract infection and associated complications (tubo-ovarian abscess, severe PID) may require hospitalization for parenteral antibiotics, pain control, antiemetics, hydration, and other measures.

Nongonococcal Urethritis NGU is most often caused by Chlamydia trachomatis, but may also be caused by Trichomonas vaginalis, Mycoplasma genitalium, other Mycoplasma species, Ureaplasma species, and other organisms. Patients with NGU are often asymptomatic. Symptoms, when present, are usually less prominent than those seen with gonococcal urethritis. Clinical features are not sufficiently specific to distinguish between gonococcal urethritis and NGU, and coinfection is common. NAATs have high sensitivity and specificity for chlamydia and gonorrhea. Wet mount microscopy can identify cases of trichomoniasis. Diagnostic testing is not routinely performed for other causes of NGU. Fortunately, most causative organisms respond to single-dose therapy with azithromycin 1 g PO. Azithromycin is more effective than doxycycline for M. genitalium. Additional empirical treatment with single-dose ceftriaxone 250 mg IM is recommended when gonorrhea has not been ruled out with negative NAATs. Single-dose metronidazole 2 g PO is recommended for cases of trichomoniasis.

Pelvic inflammatory disease (PID)   Inpatient

  Outpatient

Cefotetan 2 g IV every 12 hours plus Doxycycline 100 mg PO or IV every 12 hours or Cefoxitin 2 g IV every 6 hours plus Doxycycline 100 mg PO or IV every 12 hours or Clindamycin 900 mg IV every 8 hours plus Gentamicin 2 mg/kg IV loading dose, then 1.5 mg/kg every 8 hours Ceftriaxone 250 mg IM single dose plus Doxycycline 100 mg PO bid for 14 days ± Metronidazole 500 mg PO bid for 14 days

a

Alternative treatment regimens for selected patients (including pregnancy, drug allergies) can be found at www.cdc.gov/std/treatment. For suspected gonorrhea and/or chlamydia. c For suspected gonorrhea and/or chlamydia and enteric organisms (ie, men who practice insertive anal intercourse). d For suspected enteric organisms. IM, Intramuscular; IV, intravenous; PO, per os (by mouth). b

Trichomoniasis Principles Trichomonas vaginalis is the flagellated protozoan organism responsible for trichomoniasis, the most common curable STD worldwide. Women are typically more symptomatic than men, but asymptomatic infection occurs in both sexes. Trichomoniasis usually causes mild disease, but significant morbidity can occur. Trichomoniasis has been associated with PID, preterm birth among pregnant women, prostatitis, epididymitis, and increased susceptibility to HIV acquisition.

Clinical Features Trichomoniasis causes vaginitis in women. Common symptoms include vaginal discharge, pruritus, dysuria, urinary frequency, dyspareunia, and postcoital bleeding. The discharge is classically described as malodorous, frothy, and greenish yellow in color (Fig. 88.7). Pelvic examination may reveal erythema of the vaginal mucosa and vulva, in addition to the discharge. Punctate hemorrhages of the cervix (“strawberry cervix”) are seen in up to 10% of cases. Trichomoniasis is often asymptomatic in men but may cause urethritis with associated dysuria and urethral discharge.

CHAPTER 88  Sexually Transmitted Diseases

occurrence of birth defects.12 Current CDC guidelines advise that single-dose therapy with metronidazole may be used during any stage of pregnancy. The treatment of asymptomatic pregnant women with trichomoniasis is controversial, because there is conflicting data regarding the possible increased incidence of preterm labor in pregnant women treated with metronidazole.

Disposition Trichomoniasis is treated on an outpatient basis. Patients should be counseled to avoid alcohol use for at least 24 hours after completion of metronidazole therapy and 72 hours after completion of tinidazole therapy, due to the occurrence of a disulfiram-like reaction following alcohol use.

Pelvic Inflammatory Disease Fig. 88.7.  Frothy vaginal discharge due to trichomoniasis. (From Morse S, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 4, London, 2010, Saunders/Elsevier, Fig. 5.23,  p 140.)

Principles PID is an ascending infection that begins at the level of the endocervix but progresses to the upper reproductive tract, causing endometritis, salpingitis, and peritonitis. N. gonorrhoeae and Chlamydia trachomatis have traditionally been implicated in the development of PID, but many women diagnosed with PID do not test positive for either of these organisms.13 Negative testing for gonorrhea and chlamydia from endocervical specimens does not reliably exclude them as a cause for upper tract infection. Polymicrobial involvement is common, with anaerobes, enteric organisms, vaginal flora, and other STDs often implicated in PID. An estimated 10% to 20% of women with gonorrhea or chlamydia may develop PID if they do not receive proper treatment. Among women with PID, 18% experience chronic pelvic pain, 9% develop ectopic pregnancy, and 8% develop infertility.14

Clinical Features

Fig. 88.8.  T. vaginalis on a wet mount slide prep. (From Centers for Disease Control and Prevention [CDC]: Public Health Image Library [PHIL]. Image #14500. Available at phil.cdc.gov/phil/.)

Diagnostic Testing The diagnosis of trichomoniasis is usually confirmed with microscopic examination of a saline wet mount slide, which reveals motile flagellated trichomonads and leukocytes (Fig. 88.8). The sensitivity of the wet mount slide is approximately 50% to 65%. Trichomonas may be seen incidentally on microscopic analysis of the urine sediment. NAATs are superior to microscopic examination, with reported sensitivity and specificity greater than 95% for some assays. A point-of-care antigen detection test for trichomonas is now available. Culture is also confirmatory, but seldom used in the ED.

Management Treatment of trichomoniasis is indicated in both symptomatic and asymptomatic men and nonpregnant women. Single-dose metronidazole 2 g PO or single-dose tinidazole 2 g PO are both highly effective, with reported cure rates ranging from 90% to 95% (see Table 88.3). Alternatively, metronidazole 500 mg twice daily for 7 days can be used. Metronidazole is the recommended treatment for symptomatic trichomoniasis during pregnancy. A meta-analysis failed to reveal any relationship between metronidazole exposure during the first trimester of pregnancy and the

PID causes a spectrum of illness ranging from asymptomatic infection to severe illness with associated peritonitis and systemic toxicity. Lower abdominal pain is the most common presenting complaint. Other symptoms include dyspareunia, abnormal vaginal discharge or bleeding, dysuria, and fever. Nausea, vomiting, diarrhea, and anorexia may be present, mimicking gastrointestinal conditions. Physical findings may include lower abdominal tenderness, cervical friability, mucopurulent discharge, cervical motion tenderness, and adnexal tenderness. Vital sign abnormalities, such as fever and tachycardia, may be seen.

Diagnostic Testing PID is a clinical diagnosis. No single historical, physical, or laboratory finding or combination of findings is sufficiently sensitive or specific to make a definitive diagnosis of PID. Because PID causes significant morbidity, the CDC recommends a low threshold for the diagnosis and empirical treatment of PID. The diagnosis of PID should be considered and presumptive treatment initiated in any sexually active woman at risk for STDs who presents with lower abdominal or pelvic pain if no alternative diagnosis is identified and if one or more of the following findings are present on pelvic examination: (1) cervical motion tenderness, or (2) uterine tenderness, or (3) adnexal tenderness. These criteria have high sensitivity but low specificity for the diagnosis of PID. Because the use of these criteria will result in the over-diagnosis of PID, one should consider other possible diagnoses. The use of the additional criteria improves the specificity of the diagnosis of PID but decreases the diagnostic sensitivity (Table 88.5). NAATs for gonorrhea and chlamydia are recommended. A pregnancy test should always be obtained, because ectopic

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TABLE 88.5 

Diagnosis of Pelvic Inflammatory Diseasea MINIMUM CRITERIA

ADDITIONAL CRITERIAb

Cervical motion tenderness or

Mucopurulent cervical discharge

Adnexal tenderness or

Cervical friability

Uterine tenderness

Oral temperature >101° F Elevated erythrocyte sedimentation rate Elevated C-reactive protein White blood cells (WBCs) on microscopy of vaginal secretions Laboratory confirmation of endocervical gonorrhea or chlamydia

a

In a sexually active woman at risk for sexually transmitted diseases (STDs) who presents with abdominal pain and no alternative diagnosis is identified, a presumptive diagnosis of pelvic inflammatory disease (PID) may be based upon the criteria listed in this table. b Additional criteria increase specificity but decrease sensitivity for the diagnosis of PID.

abscess or pyosalpinx may be identified on pelvic ultrasound or CT. Perihepatitis, known as Fitz-Hugh-Curtis syndrome, is occasionally seen and may result in associated right upper quadrant abdominal pain.

Bacterial Vaginosis Principles Bacterial vaginosis is the most common cause of abnormal vaginal discharge in the United States. Although bacterial vaginosis is not considered to be an STD, it is often encountered during the evaluation of patients with an abnormal vaginal discharge. Bacterial vaginosis is due to an alteration in the vaginal flora with replacement of normal Lactobacillus species by a polymicrobial group of organisms, including Gardnerella vaginalis, anaerobes, and others.

Clinical Features and Diagnostic Testing

pregnancy and other pregnancy-related conditions may mimic PID. Computed tomography (CT) and pelvic ultrasonography may reveal findings supporting the diagnosis of PID, including evidence of swelling and inflammation within the endometrial cavity and fallopian tubes. Imaging studies are also helpful in ruling out other diagnoses, such as appendicitis, and for identifying complications of PID, such as tubo-ovarian abscess. Laparoscopy can confirm the diagnosis but is of limited utility due to its invasive nature, limited availability, and expense. In addition, laparoscopy may not identify mild cases of PID.

Many women with bacterial vaginosis are asymptomatic. Symptomatic women complain of a malodorous thin whitish vaginal discharge. A fishy odor is often reported and can be accentuated with the addition of 10% potassium hydroxide (KOH) solution to a wet mount slide at the time of pelvic examination (the “whiff test”). The pH of vaginal fluid is greater than 4.5. Microscopic examination of the wet mount slide reveals clue cells, which are vaginal epithelial cells with indistinct borders due to a coating of bacteria. Bacterial vaginosis is associated with an increased risk of PID and complications of pregnancy (premature rupture of membranes and preterm delivery). Bacterial vaginosis may also be a cofactor in the acquisition and transmission of other STDs, including HIV.

Management

Management

Treatment should be initiated as soon as possible after the diagnosis is made and should not await the results of microbiologic testing or other delayed diagnostic studies. Delays in the initiation of antibiotic therapy contribute to the development of complications of PID. Multiple inpatient and outpatient antibiotic regimens are available for the treatment of PID (see Table 88.4). The total duration of antibiotic therapy is 14 days. The addition of anaerobic coverage with metronidazole should be considered. The clinician must weigh the potential benefit of providing broader spectrum antibiotic coverage against the potential risks of antibiotic side effects, greater expense, and patient noncompliance with a more complicated treatment regimen. Supportive care measures include analgesics, antipyretics, and hydration. Sexual intercourse should be deferred until symptoms have resolved and antibiotic therapy has been completed by the patient and her partner.

Treatment is recommended for all symptomatic women with bacterial vaginosis, regardless of pregnancy status. The established benefit of therapy is the relief of vaginal symptoms. There is conflicting data regarding the efficacy of treatment in reducing the incidence of associated illnesses in pregnant and nonpregnant women. Treatment of bacterial vaginosis in asymptomatic women is not recommended. Treatment of male sexual partners is of no benefit. Recommended treatment regimens for bacterial vaginosis include: (1) metronidazole 500 mg PO twice a day for 7 days, (2) metronidazole gel 0.75% 5 g intravaginally once a day for 5 days, and (3) clindamycin cream 2% 5 g intravaginally at bedtime for 7 days. Symptomatic pregnant women can be treated with the same oral or topical regimens recommended for nonpregnant women. The use of intravaginal Lactobacillus preparations and other probiotics are of no proven benefit in the restoration of normal vaginal flora or in the treatment of bacterial vaginosis.

Disposition Most women with PID are treated as outpatients. Current recommendations no longer mandate hospitalization for adolescents or for HIV-positive patients with PID.7 Follow-up within 72 hours is recommended to ensure appropriate response to initial treatment. Women who meet any of the following criteria should be considered for inpatient treatment of PID: • Surgical emergencies cannot be excluded (ie, appendicitis) • Pregnancy • Tubo-ovarian abscess • Severe illness, nausea and vomiting, or high fever • Inability to follow or tolerate outpatient oral regimens • Failure to respond to oral antibiotic therapy In addition to chronic pelvic pain, ectopic pregnancy, and infertility, other complications of PID are common. Tubo-ovarian

Vulvovaginal Candidiasis Principles Vulvovaginal candidiasis is usually caused by the yeast species Candida albicans. An estimated 75% of women will have at least one episode of candidiasis during their lifetime, and recurrent episodes are common. Like bacterial vaginosis, candidiasis is not considered to be an STD but is frequently encountered in the evaluation of patients with abnormal vaginal discharge.

Clinical Features and Diagnostic Testing Common nonspecific symptoms include pruritus, abnormal discharge, dyspareunia, and external dysuria. Pelvic examination

CHAPTER 88  Sexually Transmitted Diseases

may reveal the vulvar erythema and edema with satellite lesions, erythema of the vaginal mucosa, and a thick curdy whitish vaginal discharge. Microscopic examination of a wet mount slide may reveal the presence of budding yeast or pseudohyphae. Diagnosis is facilitated with the use of 10% KOH, which disrupts other cellular structures and facilitates visualization of fungal elements. Fungal culture is the diagnostic gold standard but is rarely performed.

Management Multiple topical antifungal azole drugs are recommended for the treatment of vulvovaginal candidiasis, including clotrimazole, miconazole, butoconazole, terconazole, and tioconazole. Several topical agents are available over-the-counter. Fluconazole is the only oral antifungal agent approved by the FDA for treatment of candidiasis. A single dose of fluconazole 150 mg PO is highly effective in nonpregnant women but is contraindicated during pregnancy. A 7-day course of topical azoles is recommended during pregnancy. Single-dose and short-course therapy with azoles is associated with a cure rate of 80% to 90% in uncomplicated Candida vulvovaginitis. Male sexual partners may develop Candida balanitis, which typically responds to topical antifungal therapy. Treatment of asymptomatic sexual partners is of no proven benefit.

Fig. 88.9.  Perianal condyloma acuminata. (From Morse S, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 4, London, 2010, Saunders/Elsevier, Fig. 11.10, p 294.)

EPITHELIAL CELL INFECTIONS Condyloma Acuminata (Genital Warts) Principles Genital warts are caused by human papillomavirus (HPV). More than 40 types of HPV can infect humans, with the majority of HPV infections remaining asymptomatic or unrecognized. Clinically apparent warts occur in approximately 1% of cases. HPV types 6 and 11 cause most cases of visible genital warts and are considered non-oncogenic. HPV types 16 and 18 are responsible for most cases of cervical cancer and are also associated with vaginal, vulvar, anal, penile, and oropharyngeal cancers. Bivalent and quadrivalent HPV vaccines are approved for use in the United States in children, adolescents, and young adults.

Clinical Findings Genital warts are typically manifested by small painless fleshy papular lesions on the skin or mucous membranes (Fig. 88.9). The slow-growing lesions gradually become more lobulated, pedunculated, or verrucous in appearance. Lesions may become friable and painful due to local irritation or secondary infection. Warts are typically found on the external genitalia, buttocks, and perineum, but they may occur anywhere the organism is inoculated.

Diagnostic Testing A clinical diagnosis of genital warts is usually made by visual inspection. Differential diagnosis includes molluscum contagiosum, skin tags, nevi, neoplasm, and condyloma lata. Genital warts may have a moist appearance in intertriginous areas, but they do not usually have the denuded surface typically seen with condyloma lata in secondary syphilis. The duration of lesions and presence of associated symptoms are helpful features, because genital warts are often present for months or years but have no associated systemic symptoms. Dark-field microscopy and serology are useful in excluding a diagnosis of syphilis. Although not generally performed in the ED, biopsy can confirm the diagnosis

and exclude neoplasm. The application of topical acetic acid to mucosal lesions to screen for HPV is nonspecific and is not recommended.

Management All available treatments for HPV have significant failure rates. Treatment options include patient-applied regimens and provideradministered regimens. Patient-applied regimens include topical application of imiquimod cream, podofilox solution or gel, or sinecatechins ointment. The patient must be able to adequately visualize and reach the lesions to use of these patient-applied agents. These modalities are preferable to some patients, because they can administer the treatment in the privacy of their own home. Provider-administered treatments include surgical excision, cryotherapy, or topical therapy with trichloroacetic acid (TCA) or bichloracetic acid (BCA). Podophyllin-based therapy is contraindicated during pregnancy due to possible teratogenic effects. The emergency clinician may elect to defer initiation of treatment for genital warts and refer the patient to a primary care provider or STD clinic, because the condition is not emergent and a prolonged course of treatment is usually required.

Molluscum Contagiosum Molluscum contagiosum is a localized skin infection caused by a member of the pox virus family. The condition is common in childhood when it is usually acquired via nonsexual contact. It may be sexually acquired in adolescents and adults. Clinical appearance consists of one or more small 2 to 5 mm papules. The lesions have a waxy appearance, and central umbilication is common. Spontaneous resolution typically occurs within 6 to 12 months. Differential diagnosis may include genital warts, skin cancers, nevi, skin tags, and other benign skin lesions. Clinical diagnosis is made based upon the typical appearance of the lesions. No specific diagnostic testing or treatment is necessary in the ED. The patient can be referred to a primary care provider or dermatologist for curettage, cryotherapy, or treatment with topical agents for lesions that persist.

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ECTOPARASITES Pediculosis Pubis Pediculosis pubis is a parasitic infestation caused by Phthirus pubis, the pubic louse. Although pubic lice are usually sexually transmitted, they can be transmitted via nonsexual contact with infected individuals or contact with infested fomites, such as linen or clothing. Symptoms include pruritus and mild discomfort at the site of the bites. Small erythematous maculopapular lesions with associated punctate bleeding may be seen. The lice are visible in the pubic hair or attached to the skin while feeding. The eggs (nits) are attached to the shaft of the pubic hairs. Diagnosis is confirmed by visual inspection. Treatment includes topical permethrin 1% creams and rinses which are available over-the-counter. Permethrin should be applied to the affected area and washed off after 10 minutes. Alternative topical agents include pyrethrin shampoo, malathion, and lindane. The patient should attempt to remove any visible nits, because topical treatment is not always ovicidal. Potentially infested linen and clothing should be washed in hot water with detergent. Repeat topical treatment can be applied in 1 to 2 weeks to kill any newly hatched lice. Resistance to pediculicides has been

widely reported. An alternative topical agent or oral ivermectin may be used for treatment failures.

Scabies Sarcoptes scabiei is the mite responsible for scabies. The organism is transmitted via direct person-to-person contact or exposure to infested linens and clothing. Although sexual transmission is common, many cases occur from nonsexual contact. The mite creates superficial burrows in the skin where eggs and excrement are deposited. Intense pruritus is caused by a hypersensitivity reaction to the foreign material in the skin. Careful inspection often reveals characteristic burrows in the skin. Excoriations, papules, and nodules are frequently seen. Commonly affected areas include the groin, genitalia, axilla, and interdigital web spaces of the hands. Diagnosis can be confirmed by microscopic examination of scrapings from characteristic skin lesions, which reveals the mites. The preferred treatment is permethrin 5% cream applied topically and washed off after 8 to 14 hours. Permethrin is nontoxic and can be used safely in pregnancy and in patients of all ages. Alternative agents include topical benzyl benzoate, topical lindane, or oral ivermectin. Linen and clothing should be washed in hot water with detergent.

KEY CONCEPTS • The ED diagnosis of STDs is often based on clinical findings. Empirical antibiotic treatment is warranted to cover the most likely infecting organisms based upon history and physical examination findings. Rapidly available diagnostic tests (Gram stain, darkfield microscopy, wet mount microscopy, and others) increase diagnostic sensitivity and specificity. • Confirmatory diagnostic studies (PCR, culture, serology, and others) should be considered even when results are not immediately available. A mechanism for follow-up of test results should be established and appropriate patient contact information obtained. • STDs frequently coexist. Diagnosis of one STD should prompt consideration and screening for others, including HIV. • Infection with any STD increases the risk of acquisition and transmission of HIV. • Genital herpes, the most common ulcerating STD, is often transmitted by persons who are unaware that they are infected or are asymptomatic at the time of transmission. • Nontreponemal serologic screening tests (VDRL, RPR) may yield false-positive or false-negative results in a patient with a genital ulcer and suspected syphilis.

• In a patient with a genital ulcer, visualization of spirochetes on darkfield microscopy is highly specific for the diagnosis of syphilis and provides rapid confirmatory results. • Single-dose antibiotic therapy should be used for treatment of STDs when possible. Directly observed therapy administered in the ED enhances treatment compliance. • A single dose of azithromycin 1g PO will treat chlamydia causing lower genitourinary tract infection (urethritis, cervicitis) but is inadequate for treatment of upper tract infection (PID, epididymo-orchitis). • A single dose of ceftriaxone 250 mg IM will treat gonorrhea causing both upper and lower genitourinary tract infection in men and women. • A single dose of long-acting benzathine penicillin G (2.4 million units IM) will treat primary and secondary syphilis. • A single dose of metronidazole 2 g PO is the treatment of choice for symptomatic trichomoniasis during all stages of pregnancy. • Single-dose antibiotic therapy is inadequate for the treatment of PID. • HIV, syphilis, gonorrhea, chlamydia, and chancroid are reportable diseases in all 50 of the United States.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 88  Sexually Transmitted Diseases

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REFERENCES 1. World Health Organization: Sexually transmitted infections (STIs). Available at . 2. Satterwhite CL, et al: Sexually transmitted infections among U.S. women and men: prevalence and incidence estimates, 2008. Sex Transm Dis 40(3):187–193, 2013. 3. Owusu-Edusei K, et al: The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sex Transm Dis 40(3):197–201, 2013. 4. Rothman RE, et al: 2009 US emergency department HIV testing practices. Ann Emerg Med 58:S3–S9, 2011. 5. Centers for Disease Control and Prevention (CDC): Expedited partner therapy in the management of sexually transmitted diseases, Atlanta, GA, 2006, US Department of Health and Human Services. 6. Centers for Disease Control and Prevention (CDC): Sexually transmitted diseases: expedited partner therapy. Available at . 7. Workowski KA, et al: Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 64(RR–03):1–137, 2015. 8. Bradley H, Markowitz LE, Gibson T, et al: Seroprevalence of herpes simplex virus types 1 and 2—United States, 1999-2010. J Infect Dis 209(3):325–333, 2014.

9. Centers for Disease Control and Prevention: Sexually Transmitted Disease Surveillance 2013, Atlanta, 2014, US Department of Health and Human Services. 10. Centers for Disease Control and Prevention (CDC): Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. Morb Mortal Wkly Rep 61(31): 590–594, 2012. 11. Centers for Disease Control and Prevention (CDC): Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. Morb Mortal Wkly Rep 56(14):332– 336, 2007. 12. Caro-Patón T, Carvajal A, Martin de Diego I, et al: Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol 44:179, 1997. 13. Burnett AM, et al: Laboratory-confirmed gonorrhea and/or chlamydia rates in clinically diagnosed pelvic inflammatory disease and cervicitis. Am J Emerg Med 30: 1114–1117, 2012. 14. Centers for Disease Control and Prevention: Sexually Transmitted Disease Surveillance 2013, Atlanta, 2014, US Department of Health and Human Services.

CHAPTER 88: QUESTIONS & ANSWERS 88.1. A 30-year-old pregnant female presents for evaluation of a genital ulcer. Darkfield microscopy reveals spirochetes. She is allergic to penicillin. Which of the following statements is false? A. Azithromycin is an acceptable treatment alternative for primary syphilis during pregnancy in a patient with known penicillin allergy. B. Nontreponemal serologic tests for syphilis (rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL]) may yield false negative results in primary syphilis. C. Primary syphilis facilitates the transmission and acquisition of human immunodeficiency virus (HIV) infection. D. Syphilis is a reportable disease in all 50 states. E. The chancre of primary syphilis will heal spontaneously without antibiotic therapy. Answer: A. Penicillin remains the drug of choice for treatment of syphilis during pregnancy. A pregnant patient with syphilis and known penicillin allergy should be admitted for desensitization and treatment with penicillin. Nontreponemal serologic tests may yield false negative results in primary syphilis when antibody titers have not yet risen. False positive serology may be seen with a variety of other medical conditions. Visualization of spirochetes on darkfield microscopy confirms the diagnosis of syphilis. All sexually transmitted diseases (STDs) facilitate the transmission and acquisition of HIV. Reportable STDs in all 50 states include gonorrhea, chlamydia, syphilis, HIV, and chancroid. 88.2. A 17-year-old female presents with complaints of pelvic pain. She reports multiple sexual partners and inconsistent condom use. Pelvic examination reveals yellow cervical discharge, cervical motion tenderness, and bilateral adnexal tenderness. Pregnancy test is negative. Which of the following statements regarding this scenario is correct? A. All adolescents with pelvic inflammatory disease require hospital admission for intravenous antibiotics. B. A negative nucleic acid amplification test for gonorrhea and chlamydia reliably excludes the diagnosis of pelvic inflammatory disease. C. In the absence of an identifiable alternative diagnosis, the clinical diagnosis and empirical treatment of pelvic inflammatory disease is warranted. D. The clinical diagnosis of pelvic inflammatory disease requires the presence lower abdominal tenderness and cervical motion tenderness and adnexal tenderness on physical examination.

E. Women treated as outpatients for pelvic inflammatory disease should have a follow up evaluation in 2 weeks. Answer: C. The clinical diagnosis of pelvic inflammatory disease is warranted in a sexually active woman at risk for sexually transmitted diseases (STDs) if no alternative diagnosis is identified and any one of the following findings is present on examination: (1) cervical motion tenderness, (2) uterine tenderness, and/or (3) adnexal tenderness. Additional diagnostic criteria (mucopurulent cervical discharge, fever, elevated white blood count, positive testing for gonorrhea or chlamydia, and others) improve specificity but decrease sensitivity in the diagnosis of pelvic inflammatory disease (PID). Adolescents with PID may be treated as outpatients using the same criteria as adult women. Women receiving outpatient treatment for PID should be advised to seek a follow up evaluation within 48 to 72 hours. 88.3. A previously healthy 22-year-old female is diagnosed with pelvic inflammatory disease (PID). Pregnancy test is negative. She is well-perfused and nontoxic in appearance. She is tolerating oral intake without difficulty. She has no known drug allergies. Which of the following antibiotic regimens is acceptable for outpatient treatment of pelvic inflammatory disease? A. Azithromycin 1 g per os (by mouth) (PO) (single dose) and metronidazole 500 mg bid for 14 days. B. Ceftriaxone 125 mg IM (single dose) and doxycycline 100 mg bid for 7 days. C. Ceftriaxone 250 mg IM (single dose) and azithromycin 1 g PO (single dose). D. Ceftriaxone 250 mg IM (single dose) and doxycycline 100 mg PO bid for 14 days. E. Metronidazole 2 g PO (single dose) and doxycycline 100 mg PO bid for 14 days. Answer: D. Pelvic inflammatory disease is typically a polymicrobial infection. Neisseria gonorrhoeae and/or Chlamydia trachomatis are frequently implicated organisms, but anaerobes, enteric organisms, and normal vaginal flora may also be present. Empirical treatment of PID should include adequate coverage for gonorrhea and chlamydia. A single dose of ceftriaxone 250 mg IM is adequate treatment for upper tract gonococcal infection. A 14-day course of antibiotics is recommended for adequate chlamydia coverage in PID. The addition of anaerobic coverage, such as metronidazole, should be considered. 88.4. A 24-year-old sexually active male presents with painful genital ulcers. Physical examination reveals a cluster of 2

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to 3 mm tender superficial ulcers on the penile shaft. He reports a history of similar lesions in the same location sporadically in the past. Which statement regarding this clinical scenario is false? A. Both herpes simplex virus (HSV)-1 and HSV-2 can be transmitted through sexual contact. B. Genital herpes is a lifelong viral infection. C. Prompt initiation of antiviral medication reduces the duration and severity of symptoms. D. Topical antiviral therapy is not recommended. E. Use of condoms is not necessary to prevent transmission in the absence of clinically apparent lesions. Answer: E. Genital herpes is a lifelong infection caused by herpes simplex virus. Sexual transmission is more common with HSV-2 but may also occur with HSV-1. Condom use is recommended during asymptomatic periods, because viral shedding and transmission may occur even in the absence of clinically apparent lesions. Antiviral therapy is not curative. Prompt initiation of systemic antiviral medication within 72 hours (acyclovir, famciclovir, or valacyclovir) reduces the duration and severity of symptoms, particularly at the time of primary infection. Topical antiviral therapy is not recommended. 88.5. A 24-year-old female presents to the emergency department (ED) complaining of vaginal discharge. A copious frothy whitish discharge is noted on speculum examination. Microscopic examination of a saline wet mount reveals motile flagellated organisms. Which of the following statements is correct? A. Metronidazole is the drug of choice for treatment of symptomatic trichomoniasis during all stages of pregnancy. B. Punctate hemorrhagic lesions are seen on the cervix in most cases of trichomonas vaginitis.

C. Tinidazole is a safe alternative for treatment of trichomoniasis during pregnancy. D. Trichomoniasis is always symptomatic in men and women. E. Wet mount microscopy approaches 100% sensitivity in the diagnosis of trichomonas vaginitis. Answer: A. Metronidazole is the drug of choice for treatment of symptomatic trichomoniasis during all stages of pregnancy. Tinidazole should be avoided in pregnant women due to limited data regarding safety for use in pregnancy. Visualization of flagellated protozoans on wet mount microscopy of vaginal discharge is highly specific, but only 50% to 65% sensitive for the diagnosis of trichomoniasis. Punctate hemorrhagic lesions on the cervix (so called “strawberry cervix”) is seen in up to 10% of cases. Nucleic acid amplification tests for trichomonas are highly sensitive and specific. Trichomoniasis may be asymptomatic in men and women. 88.6. Which of the following sexually transmitted diseases (STDs) can be treated with single-dose antibiotic therapy administered in the emergency department (ED)? A. Chancroid B. Primary and secondary syphilis C. Trichomoniasis D. Urethritis caused by gonorrhea or chlamydia E. All of the above Answer: E. Single-dose antibiotic therapy is efficacious for many STDs, including gonococcal urethritis and cervicitis, primary and secondary syphilis, trichomoniasis, and chancroid. Single-dose azithromycin is recommended for coverage of lower genitourinary tract infection with chlamydia. Treatment of upper genitourinary tract STDs, including pelvic inflammatory disease and epididymoorchitis, requires a longer course of antibiotic therapy. Directly observed therapy administered in the ED promotes compliance.

C H A P T E R 89 

Selected Urologic Disorders Carl A. Germann  |  Jeffrey A. Holmes

URINARY TRACT INFECTION IN ADULTS Urinary tract infection (UTI) is the most frequent bacterial infection occurring more commonly in women than in men. In the United States, the urinary tract is the most common source of infection of patients presenting in septic shock, with an associated mortality of 10% to 20%. UTI describes an inflammatory response of the urothelium to microorganisms in the urinary tract, resulting in clinical symptoms that include dysuria, frequency, urgency, hematuria, and suprapubic or costovertebral angle discomfort. The diagnosis of a UTI requires the presence of urinary-specific symptoms or signs in a patient who has bacteruria and no other identified source of infection.1 Bacteriuria is the presence of bacteria in the urine but is not considered to represent a UTI in the absence of clinical manifestations. Bacteriuria accompanied by symptoms should be treated, whereas bacteriuria in the absence of symptoms should be treated only in select patients (eg, pregnant women, immunosuppressed patients). UTIs are classified as lower (confined to the bladder) or upper (involving the ureters or kidneys) and as uncomplicated or complicated. An uncomplicated infection occurs in a nonpregnant individual with a structurally and functionally normal urinary tract. A complicated UTI is a heterogeneous term that may be associated with an underlying functional or structural abnormality, history of urinary instrumentation or organ transplantation, or systemic disease, such as renal insufficiency, diabetes, and immunodeficiency. UTIs in men are generally categorized as complicated given the higher incidence of associated urologic abnormalities. However, men can experience a UTI without an underlying structural or functional abnormality. Complicated UTIs often require a prolonged course of antibiotic therapy and a more in-depth approach to testing and anatomic evaluation. The term urethritis refers to the inflammation of the urethra secondary to an infection or trauma. Frequently, urethritis may be a manifestation of a sexually transmitted disease (STD), such as gonococcal urethritis in Neisseria gonorrhoeae infection, but may occur in other clinical scenarios as well. Cystitis generally refers to inflammation of the bladder resulting in increased urinary frequency, urgency, dysuria, and suprapubic pain. The causes of cystitis can be separated into bacterial and nonbacterial (eg, radiation) categories. Acute pyelonephritis is a UTI involving the renal parenchyma and collecting system, manifesting with the clinical syndrome of fever, chills, and flank pain. Management and disposition of patients with acute pyelonephritis depend on whether the infection is simple or complicated.

Anatomy and Physiology In women, the urethra is short and opens close to the vulvar and perirectal areas. This contributes to the much higher incidence of UTI in women. The route of infection in men is also usually ascending, from the urethra to the prostate to the bladder and then to the kidney. Risk factors for cystitis and pyelonephritis

include sexual intercourse, use of spermicides, previous UTI, new sex partner, and history of UTI in a first-degree female relative.

Pathophysiology UTIs arise when urinary pathogens from the bowel or vagina colonize the periurethral mucosa and ascend through the urethra and into the collecting system. Infrequently, bacterial infection of the urinary tract arises from hematogenous or lymphatic sources. This is frequently the pathologic mechanism in debilitated and chronically ill patients who are immunosuppressed. Numerous abnormalities of the urinary tract interfere with its innate ability to resist infection. Obstruction from any cause, with resultant stasis of urine, is the major causative factor. Urinary calculi may cause obstruction and increased susceptibility to the development of a UTI. Subgroups of patients who are more susceptible than the normal population to UTIs include diabetic patients, pregnant women, older adults, patients who are unable to empty their bladder completely, patients with indwelling urinary catheters, and those with immunodeficiency disorders. Lower UTIs are more common in aging men in the setting of prostatic enlargement or obstruction. Escherichia coli is responsible for an estimated 75% to 95% of cases of UTI and pyelonephritis in men and women.2 Other less common bacteria that may be responsible for infection include Staphylococcus saprophyticus and other members of the Enterobacteriaceae family (Klebsiella pneumonia and Proteus mirabilis). Unusual microorganisms may be found in institutionalized or hospitalized populations. Such settings and conditions predispose the patient to alterations in the normal gastrointestinal (GI) flora, leading to complex UTIs. The uropathogens in these patients include more resistant strains of Escherichia, Klebsiella, Proteus, and Enterobacter, as well as Pseudomonas, Enterococcus, Staphylococcus, Providencia, Serratia, Morganella, Citrobacter, Salmonella, Shigella, and Haemophilus spp., Mycobacterium tuberculosis, and fungi.

Clinical Features UTI is usually manifested as dysuria, with or without frequency, urgency, hematuria, or suprapubic discomfort. Symptoms of dysuria, frequency, hematuria, nocturia, and urgency all increase the probability of UTI, with likelihood ratios between 1.10 and 1.7, whereas vaginal discharge decreases the likelihood of UTI.3 The probability of cystitis is greater than 90% in women who have dysuria and frequency without vaginal discharge or irritation. Symptoms of UTI in men may also represent storage or voiding disturbances that are common in aging men (eg, prostatic enlargement). Commonly, men with lower UTIs have symptoms of urinary urgency, frequency, dysuria, hematuria, and suprapubic pain. If fever and chills are present in association with irritative symptoms and difficulty voiding, acute bacterial prostatitis should be strongly considered. A digital rectal examination of the prostate 1209

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gland with attention to size, shape, and consistency can identify prostatic enlargement, inflammation, or cancer. Clinical signs and symptoms suggestive of pyelonephritis include fever, chills, flank pain, costovertebral angle tenderness, and nausea or vomiting, with or without symptoms of cystitis. The presentation of pyelonephritis can be particularly challenging in those who are debilitated and older adults because they may not be able to verbalize their symptoms and can present without fever; these patients may present with nonspecific complaints such as altered mental status, lethargy, abdominal pain, or generalized weakness.

Differential Diagnosis Bacterial UTI is the most common cause of dysuria. Differential considerations include acute urethritis or acute vaginitis from sexually transmitted infections, as well as mechanical trauma or irritation (Table 89.1). In general, if historical information includes contact with multiple sexual partners, recent change in sexual partners, or sexual partner with dysuria or discharge, Chlamydia trachomatis and N. gonorrhoeae infection should be strongly considered. Because the diagnosis of UTI is rarer in men, a high suspicion for an STD such as gonococcal or nongonococcal urethritis should be maintained. Trauma, calculi, chemical irritation, candidal infections, psychogenic disorders, neoplasm, and malformations or space-occupying lesions compressing the distal genitourinary tract can also cause dysuria. Older men may have dysuria due to prostatic hypertrophy or prostatitis.

Diagnostic Testing Urinalysis and Urine Culture A clean-catch, midstream specimen is the preferred type of urine sample for analysis. This is particularly important in woman in whom contamination from the perineum may result in a false-positive test result. However, even when the procedure is

TABLE 89.1 

Clinical Differentiation of Major Causes of Dysuria CAUSE

CLINICAL FEATURES

Urinary tract infection

Internal dysuria Frequency, urgency, voiding small volumes Abrupt onset Suprapubic pain Often associated with diaphragm use Presence of pyuria Presence of hematuria (50% of patients)

Sexually transmitted disease Internal dysuria Occasional history of frequency, urgency, voiding small volumes Gradual onset History of new or multiple sexual partners Vaginal discharge Vaginitis

External dysuria Gradual onset Vaginal discharge Vaginal odor Pruritus

From Stamm W: Protocol for diagnosis of urinary tract: reconsidering the criterion for significant bacteriuria. Urology 32(Suppl 2):6–12, 1988.

performed correctly, a specimen may be contaminated because the surrounding areas can be difficult to clean. A predominance of epithelial cells suggests that the specimen is contaminated. Sterile catheterization is the most accurate method of obtaining a urine specimen in women and may be the best solution for achieving a reliable urinalysis if the patient is unable to provide a cleancatch specimen or is actively menstruating. In men, the specimen is not affected significantly by lack of cleansing or by the timing of specimen collection. Therefore, it is not appropriate to catheterize an adolescent or adult man simply for the purpose of collecting a urine specimen unless he is experiencing urinary retention. Urine screening tests provide a quick and inexpensive diagnostic tool, with a goal of reliably predicting specimens that will provide positive or negative cultures. The most commonly used screening tests measure urinary leukocyte esterase and nitrite. Both can be detected by a color change on dipstick testing. Leukocyte esterase is an enzyme found in neutrophils, and nitrite is produced from nitrate reductase, present in gram-negative bacteria. However, not all uropathogens, such as S. saprophyticus and Enterococcus, convert nitrate into nitrite.4 Dipstick-positive hematuria has also been shown to increase the likelihood for UTI.3 These findings often are combined to improve overall diagnostic accuracy. A urine dipstick test indicating the presence of nitrite or leukocytes and microscopic blood is moderately sensitive (75%) but less specific (66%) for predicting a UTI.5 These tests should be used with caution because they can be less sensitive than the microscopic examination of urine (urinalysis). Given the limited negative predictive value of urine dipstick testing, a UTI may be difficult to rule out, even when all features are negative.6 However, when there is a low pretest probability of UTI, a negative dipstick result for leukocyte esterase and nitrites excludes infection.6 When the history is strongly suggestive of a UTI and the dipstick is negative, we recommend that a urine culture be sent. Urine microscopy is an adjunct to the dipstick and helps reduce the number of urine cultures performed. Although no accepted level of pyuria is diagnostic of UTI, careful quantitation with a hemocytometer chamber will find pyuria in nearly all cases of acute UTI caused by coliforms. Pyuria is defined as 10 or more WBCs/mm3. Microscopic examination of urine to identify bacteria remains the most reliable test for a diagnosis of UTI, but is often not available. The diagnosis of a UTI can be made only with clinical symptoms and the determination of bacteriuria; however, the diagnosis is confirmed with urine culture. The Infectious Disease Society of America (IDSA) defines a positive culture as 105 or more colonyforming units (CFU)/mL.7 The presence of 105 CFUs/mL of bacteria in a urine culture is associated with a 95% likelihood of infection, whereas 104 CFUs/mL is associated with a 50% likelihood of infection. There is no absolute number of CFUs that is definitive for a UTI; the culture results alone are not diagnostic of infection and must be combined with symptoms suggestive of a UTI. The presence of bacteria on culture in the absence of clinical manifestations does not always indicate infection but may be due to contamination of the specimen. The decision to perform a urine culture should be assessed for its relevance to patient care. Patients with frequency, dysuria, urgency, and suprapubic pain should be treated on the basis of symptoms, and a urine culture is not required to guide therapy. Patients with relapse or recurrent infections, complicated infection, or those in whom multidrug-resistant organisms are suspected based on previous microbiology or exposure to antibiotics should have a culture performed (Box 89.1). An STD may mimic a UTI and, in sexually active patients, cultures for C. trachomatis and N. gonorrhoeae should be considered. Other causes of acute dysuria include infections with Trichomonas vaginalis and herpes simplex virus.

CHAPTER 89  Selected Urologic Disorders

BOX 89.1 

Patient Groups for Whom Urine Culture Is Indicated • • • • • • • • • • • • • • • •

Children Adult men Immunocompromised patients Patients with treatment failure (ie, with persistent urinary symptoms despite recently completed course of antibiotics) Patients with duration of symptoms more than 4 to 6 days Older patients at risk for bacteremia Ill-appearing patients with signs and symptoms suggestive of pyelonephritis or bacteremia Pregnant women Patients with known chronic or recurrent renal infection Patients with known anatomic urologic abnormalities Patients in whom urinary tract obstruction is suspected (eg, stones, benign prostatic hypertrophy) Patients with serious medical diseases, including diabetes mellitus, sickle cell anemia, cancer, and other debilitating diseases Patients with alcoholism or drug dependence Recently hospitalized patients Patients taking antibiotics Patients who recently have undergone urinary tract instrumentation (eg, cystoscopy, catheterization)

Fig. 89.2.  Ultrasound image demonstrating a normal kidney. (Courtesy Dr. Peter Croft.)

radiation exposure. A suggestion of obstruction based on clinical suspicion or lack of response to medical therapy necessitates performance of an abdominal ultrasound or noncontrast CT scan. A contrast CT scan of the abdomen is the most comprehensive initial test for assessing the kidneys, ureters, and bladder.8 It has a high sensitivity for detecting abscess, obstruction, and acute inflammation. Imaging with an abdominal CT scan is recommended for those with pyelonephritis and known functional or anatomic abnormalities, recent instrumentation, immunosuppression, or concern for obstruction. Its disadvantages include radiation exposure, cost, and potential to induce contrast reactions and acute kidney injury. Contrast-induced complications occur infrequently in patients with a serum creatinine level less than 1.5 mg/dL and can be further avoided by intravenous (IV) hydration with normal saline. CT without contrast can be performed in patients with renal insufficiency and is the preferred study in patients with a clinical concern for urolithiasis.

Management Simple Urinary Tract Infection Fig. 89.1.  Ultrasound image demonstrating hydronephrosis with a dilated collecting system. (Courtesy Dr. Peter Croft.)

Imaging Most patients with acute cystitis or pyelonephritis do not need emergency imaging of the urinary tract. Imaging is reserved for patients with a clinical suspicion for underlying structural abnormalities or complicating factors such as abscess, urolithiasis, or emphysematous pyelonephritis. Patients with pyelonephritis who have severe or worsening illness or persistent fever 48 to 72 hours after the initiation of appropriate antimicrobial treatment should undergo imaging to exclude renal stones, abscesses, or obstruction. Ultrasonography is indicated to assess for potential urinary obstruction. Although it is not as sensitive as a contrast computed tomography (CT) scan, it is a sensitive tool for detecting postvoid residual bladder volume, intrarenal and perinephric abscess, and presence of hydroureter and hydronephrosis (Figs. 89.1 and 89.2). Ultrasound can also detect the presence of pyelonephritis and congenital anomalies. Regardless of patient age, this procedure is relatively inexpensive and avoids the hazards of contrast and

In 2011, the IDSA released updated clinical practice guidelines for the treatment of uncomplicated cystitis.7 The options for treating uncomplicated lower UTI include single-dose therapy with fosfomycin, 5 days of nitrofurantoin, or 3 days of trimethoprimsulfamethoxazole (Table 89.2). Fluoroquinolones such as ciprofloxacin or levofloxacin should not be used as first-line agents for empirical treatment of uncomplicated UTIs. Instead, they should be reserved for patients who have failed first-line therapy or have contraindications. The most recent IDSA guidelines have focused on the unnecessary use of fluoroquinolones for uncomplicated UTIs because the resistance of E. coli to ciprofloxacin in the United States has increased from 3% in 2000 to 17% in 2010.7 In contrast, resistance to nitrofurantoin and fosfomycin has not meaningfully increased since their introduction.7 The IDSA guidelines acknowledge that cystitis is often a self-resolving infection, with spontaneous symptom improvement occurring in up to 50% of patients.9 However, there is limited evidence regarding antimicrobialsparing treatment for UTIs. Antibiotics should be chosen with local resistance patterns in mind. The IDSA recommends avoiding antimicrobial agents when local resistance exceeds 20%, emphasizing the need to be familiar with local outpatient resistance patterns. Although most

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TABLE 89.2 

Antibiotic Options for Acute Uncomplicated Cystitis ANTIMICROBIAL

DOSE (ORAL)

DURATION

COMMON SIDE EFFECTS

Trimethoprim-sulfamethoxazole

160/800 mg bid

3 days

Nausea, vomiting, anorexia, hypersensitivity reactions

Nitrofurantoin

100 mg bid

5 days

GI disturbance, headache, allergic reactions

Fosfomycin

3 g as a single dose

Diarrhea, nausea, headache, vaginitis, dizziness

TABLE 89.3 

Antibiotic Options for Acute Uncomplicated Pyelonephritis ANTIMICROBIAL

DOSE (ORAL)

DURATION

COMMON SIDE EFFECTS

Ciprofloxacin

500 mg bid

7 days

GI disturbance, headache, dizziness, tremors, restlessness, confusion, rash, Candida infections

Levofloxacin

750 mg once daily

5 days

Same as for ciprofloxacin

Trimethoprim-sulfamethoxazole

160/800 mg bid

10–14 days

Nausea, vomiting, anorexia, hypersensitivity reactions

TABLE 89.4 

Antibiotic Options for Complicated Pyelonephritis ANTIMICROBIAL

DOSE (IV)

COMMON SIDE EFFECTS

Cefepime

1–2 g every 12 hours

Abdominal pain, muscle cramps, nausea, vomiting

Ceftriaxone

1 g every 24 hours

Fever, cough, sore throat, fatigue

Piperacillin-tazobactam

3.375 g every 6 hours

Diarrhea, nausea, vomiting, rash

Aztreonam

1 g every 8–12 hours

Cough, abdominal pain, nausea, vomiting

Ciprofloxacin

400 mg every 12 hours

GI disturbance, headache, dizziness, tremors, restlessness, confusion, rash, Candida infections

Levofloxacin

500 mg every 24 hours

Same as for ciprofloxacin

hospitals monitor the resistance of organisms cultured in their microbiology laboratory, these data may reflect drug-exposed, hospital-acquired organisms more than community-acquired, outpatient-based illnesses. Thus, hospital antibiograms likely overestimate community resistance patterns. Nitrofurantoin is an excellent drug for the treatment of acute bacterial cystitis. It is inexpensive and maintains low serum and high urine levels. Nitrofurantoin is effective against E. coli but is inactive against other pathogens, such as Proteus and Pseudomonas aeruginosa. The rate of clearance is proportional to the creatinine clearance, and dose adjustments are necessary with renal impairment. The most common adverse effects of using nitrofurantoin are GI effects, including nausea, vomiting, and diarrhea. Fosfomycin is appealing for emergency department (ED) use because it can be given as a single dose for simple cystitis and therefore does not require that a patient go to the pharmacy. Fosfomycin is an inhibitor of cell wall synthesis, structurally unrelated to any other antibiotic, and is active against most urinary tract pathogens. Both nitrofurantoin and fosfomycin remain effective against extended-spectrum, β-lactamase–producing bacteria.10 A useful adjunctive therapy for UTIs is phenazopyridine (Pyridium). It produces topical analgesia in the urinary tract and helps relieve dysuria. Patients should be cautioned that body secretions and excretions (eg, tears, urine) will turn orange. This side effect can stain contact lenses and alarm unknowing patients. The clinical presentations of UTIs and STDs can overlap and, at times, empirical treatment must be directed at both possibilities. In these cases, levofloxacin (500 mg/day for 7 days) has

activity against common uropathogens as well as chlamydia and can be used with a single intramuscular dose of ceftriaxone (250 mg) for gonorrhea coverage.

Complex Urinary Tract Infection Patients with mild to moderate pyelonephritis without complicating factors can be safely treated on an outpatient basis as long as the patient is able to eat and drink, has achieved adequate pain control, and has appropriate social support in the home. Given the risk for systemic illness, bacteremia, and progression to severe sepsis, medications must achieve therapeutic levels not only in the urine but also in the renal tissues and bloodstream. Therefore, fluoroquinolones are the first-line choice (Table 89.3). In areas in which the prevalence of resistance of fluoroquinolones is less than 10%, we recommend a 7-day course of ciprofloxacin for empirical outpatient treatment for uncomplicated pyelonephritis. In areas in which there is more than 10% fluoroquinolone resistance, IDSA guidelines recommend giving a long-acting parenteral antibiotic, such as 1 g ceftriaxone, followed by 10 to 14 days of an oral cephalosporin.7 Trimethoprim-sulfamethoxazole (TMP-SMX) for 10 to 14 days is an alternative treatment. Nitrofurantoin and fosfomycin do not achieve adequate blood and tissue levels and therefore are not effective for pyelonephritis. A severe upper tract UTI necessitating hospitalization initially should be treated with parenteral antibiotics, such as cefepime, ceftriaxone, piperacillin-tazobactam, aztreonam, or a fluoroquinolone, with transition to oral therapy after the patient has been afebrile for 24 to 48 hours (Table 89.4).

CHAPTER 89  Selected Urologic Disorders

Oral therapy should be continued for 2 weeks. Because 20% of cultures are resistant to ampicillin, cephalothin, and sulfonamides, antibiotic therapy should be initiated with a fluoroquinolone. Follow-up urine cultures are recommended given the diverse flora and high rate of antimicrobial resistance. In men, if there are no signs of toxicity, the patient can be treated on an outpatient basis with any of the urinary antibacterial agents (eg, TMP-SMX, nitrofurantoin, fluoroquinolones) for 7 to 14 days. If concomitant prostatitis is suspected, TMP-SMX or a fluoroquinolone is recommended for 14 days. If evaluation demonstrates suspicion for prostate involvement, recurrent infection, or hematuria, the patient should be referred to a urologist for further evaluation. Patients with symptoms of prostatic enlargement can be treated with α-adrenergic receptor antagonists and/or 5-alpha-reductase inhibitor therapy (Table 89.5). Surgical treatment produces the most significant, long-term symptom improvement; it includes transurethral prostate resection, open prostatectomy, laser vaporization, transurethral microwave therapy, or needle ablation. Decisions regarding treatment options are based on the degree of obstruction and symptoms. Disposition.  Hospitalization is required in the presence of clinical toxicity (eg, fever, tachycardia, hypotension, vomiting), inability to take oral medications, an immunocompromised state, third-trimester pregnancy, failure of oral outpatient therapy, urologic abnormalities, or patients with significant comorbid conditions, including heart failure and renal insufficiency. A subgroup of patients with an upper tract UTI do not require immediate hospital admission but may benefit from IV hydration and pain and fever control, along with a first dose of an IV fluoroquinolone before discharge from the ED. Chapter e6 discusses the use of ED observation units for this type of care. If these patients do not have any contraindications, as previously discussed, improve clinically, and can tolerate food and drink, they can be safely discharged home on a 10- to 14-day course of an oral fluoroquinolone, TABLE 89.5 

Medication Options for Prostatic Enlargement ANTIMICROBIAL

DOSE

ALPHA-ADRENERGIC RECEPTOR ANTAGONIST Alfuzosin

10 mg once daily

Doxazosin

1 mg once daily

Tamsulosin

0.4 mg once daily

Terazosin

1 mg once daily or at bedtime

5-ALPHA-REDUCTASE INHIBITORS Dutasteride

0.5 mg once daily

Finasteride

5 mg once daily

with close primary physician follow-up. Urine culture with sensitivity testing and further diagnostic evaluation are not necessary in this patient population.

Complicated Urinary Tract Infection in High-Risk Populations Pregnancy.  UTI during pregnancy represents a special situation. Although the incidence of UTI in pregnancy is approximately the same as in nonpregnant women, pyelonephritis is more common during pregnancy.1 This is likely a result of the physiologic changes that occur within the urinary tract of pregnant women, which include ureteral and renal pelvis dilation. Factors associated with a higher risk of bacteriuria include a history of prior urinary tract infection, preexisting diabetes mellitus, increased parity, and low socioeconomic status. Unlike bacteriuria in nonpregnant females, bacteriuria in pregnant women, even if they are asymptomatic, should be treated. Untreated bacteriuria in pregnancy is associated with premature labor, low birth weight, perinatal mortality, maternal anemia, and maternal pyelonephritis. Like nonpregnant women, E. coli is the most common uropathogen. The symptoms of UTI and pyelonephritis are also the same as in nonpregnant patients; however, urinary frequency and urgency may be symptoms of a normal pregnancy. Specimen collection and diagnostic strategies are also similar. A urine culture specimen should be obtained, along with a follow-up culture as a test of cure. Options for empirical treatment for UTI include amoxicillinclavulanate, cefpodoxime, nitrofurantoin, fosfomycin, and TMP-SMX (Table 89.6). TMP-SMX and nitrofurantoin should be avoided during the first trimester. TMP-SMX is associated with teratogenic risk and nitrofurantoin may cause fetal malformations when used in the first trimester. Both medications should also be avoided during late pregnancy because TMP-SMX can cause kernicterus, and nitrofurantoin may precipitate hemolytic anemia when used after 37 weeks.11 Fluoroquinolones should be avoided in pregnancy. Hospital admission should be considered for patients in their last trimester, who appear ill, or who have evidence of pyelonephritis and would benefit from treatment with parenteral antibiotics and IV fluids. Parental regimens for the empirical treatment of pyelonephritis are similar to those for nonpregnant patients, except the use of fluoroquinolones, and include ceftriaxone, cefepime, aztreonam, and piperacillin-tazobactam (Table 89.7). Nitrofurantoin and fosfomycin do not achieve tissue levels adequate to treat pyelonephritis appropriately. Hospitalized pregnant patients who are afebrile for 48 hours can be discharged on oral antibiotics, directed by culture susceptibility results, to be completed in 10 to 14 days. Indwelling and Temporary Urinary Catheters.  Guidelines published by the IDSA have defined catheter-associated UTI (CAUTI) as the presence of symptoms (eg, new onset or worsening of fever, rigors, altered mental status, malaise, or lethargy with

TABLE 89.6 

Antibiotic Options for Bacteriuria in Pregnancy ANTIMICROBIAL

DOSE (ORAL)

DURATION

CONTRAINDICATIONS

Amoxicillin-clavulanate

500 mg tid

3–7 days

Cefpodoxime

100 mg bid

3–7 days

Nitrofurantoin

100 mg bid

5–7 days

First trimester and 38 weeks to delivery

Fosfomycin

3 g as a single dose

Trimethoprim-sulfamethoxazole

160/800 mg bid

3 days

First trimester and term

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TABLE 89.7 

Parental Antibiotic Options for Pyelonephritis in Pregnancy ANTIMICROBIAL

DOSE (IV)

Ceftriaxone

1 g every 24 hours

Cefepime

1 g every 12 hours

Piperacillin-tazobactam

3.375 g every 6 hours

Aztreonam

1 gram every 8–12 hours

no other identified cause; flank pain, costovertebral angle tenderness, acute hematuria; or pelvic discomfort) and more than 1000 CFU/mL of one or more bacterial species.1 Screening for or treating asymptomatic bacteriuria in patients with indwelling catheters is not indicated. Antibiotic treatment results in the development of resistant microorganisms, whereas removal of the catheter leads to the spontaneous elimination of bacteria in many patients. Treatment of patients with a UTI in whom removal of the catheter is contraindicated includes urine culture and sensitivity, antibiotic therapy, replacement of the catheter, and strong consideration for hospitalization in those who exhibit altered vital signs, systemic symptoms, or a toxic appearance. Many patients with indwelling urinary catheters who present to the ED are older and not able to verbalize their symptoms or lack clinical signs of infection. Given that a catheter-associated UTI is a common cause of subsequent bacteremia and mortality, empirical antimicrobial therapy, in addition to replacement or removal of the catheter, is often appropriate in such patients. Urine culture with antibiotic sensitivity testing will help guide antibiotic therapy in this patient population. The most important risk factor for bacteruria is the duration of catheterization. The most effective strategy for addressing CAUTIs is to prevent the infection from occurring by placing urinary catheters only when indicated and considering the use of intermittent catheterization and condom catheters, when appropriate.

PROSTATITIS More than 90% of men with febrile UTIs show involvement of the prostate.12 Prostatitis encompasses four distinct clinical processes—acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis–chronic pelvic pain syndrome, and asymptomatic inflammatory prostatitis. Acute bacterial prostatitis generally affects man between the ages of 20 and 40 years, with a second peak in men older than 60 years. Acute prostatitis is caused by a bacterial infiltration that is usually precipitated by reflux of urine infected by E. coli, Klebsiella, Enterobacter, Proteus, or Pseudomonas spp. Chronic bacterial prostatitis is a persistent bacterial infection of the prostate lasting more than 3 months. Approximately 10% of acute bacterial prostatitis cases develop into chronic bacterial prostatitis.13 This can be caused by undertreated acute bacterial prostatitis or highly virulent strains. Like acute bacterial prostatitis, gram-negative bacteria are responsible for most cases of chronic prostatitis. Of patients with chronic bacterial prostatitis, 10% will develop chronic pelvic pain syndrome (CPPS).14 CPPS is defined as urologic pain in the pelvic region associated with urinary symptoms or sexual dysfunction lasting for at least 3 of the previous 6 months. CPPS is not associated with current infection, malignancy, or structural abnormality. Symptoms of chronic bacterial prostatitis may not differ from those of CPPS. It is a heteroge-

Fig. 89.3.  Prostate abscess. B, Bladder; P, prostate; R, rectum. (From Vandover JC, Patel N, Dalawari P: Prostatic abscess. J Emerg Med 2011;40:  e83–e85, 2011.)

neous condition with broad diagnostic criteria and uncertain cause, making it difficult to determine an effective treatment regimen reliably.

Clinical Features Patients with acute prostatitis often report UTI symptoms such as fever, chills, dysuria, urinary frequency or urgency, and/or perineal and low back pain. A rectal examination will reveal an exquisitely tender and swollen prostate gland in more than 90% of patients. There is no evidence that performing a rectal examination induces clinically significant bacteremia. Clinical manifestations of chronic prostatitis vary widely, making recognition difficult. Most patients report some degree of voiding symptoms (eg, frequency, urgency, dysuria), low back and perineal pain and, occasionally, myalgias. Fever and chills are uncommon except during an acute exacerbation of the chronic infection. Findings on the physical examination, including examination of the prostate, often are unremarkable. The diagnosis is based on history, physical examination, and positive urine culture.

Diagnostic Testing Acute bacterial prostatitis is a clinical diagnosis. A urine Gram stain and culture are recommended to identify causative organisms and guide treatment. Blood cultures are recommended for patients with acute prostatitis and fever who have not yet received antibiotics.15 Although acute bacterial prostatitis is usually caused by typical urinary pathogens, an STD such as chlamydia and gonorrhea should be considered, especially in sexually active patients. Urethral swabs or first-voided urine, with subsequent culture or DNA amplification, should be obtained if a STD is suspected. The most common complications of acute prostatitis are acute urinary retention and prostatic abscess. Approximately 10% of men with acute prostatitis will have some urinary retention, which can be diagnosed using bedside ultrasound. Transrectal ultrasound or CT can detect prostatic abscess and should be considered in patients who fail to improve with antibiotics (Fig. 89.3).

CHAPTER 89  Selected Urologic Disorders

Management Outpatient therapy can be used if the patient is not systemically ill, can tolerate oral medications, and does not have urinary retention. General support measures for outpatients should include bed rest, analgesics, nonsteroidal antiinflammatory drugs (NSAIDs), hydration, and stool softeners. Alpha blocker therapy is also recommended for obstructive voiding symptoms related to prostatitis (see Table 89.5). There is no consensus regarding an optimal treatment regimen, so regional patterns of antibiotic resistance should be considered. Few antimicrobial agents are able to penetrate the prostrate and achieve sufficient concentrations to eradicate infection. Fluoroquinolones, such as ciprofloxacin or levofloxacin, achieve the highest concentrations in the prostate and are the first-line agents in the treatment of bacterial prostatitis. Empirical parenteral antibiotics such as ciprofloxacin, levofloxacin, or ceftriaxone are recommended until fever and other symptoms have subsided. After improvement, oral antibiotics are recommended for at least 4 weeks (Table 89.8). If an STD is suspected, azithromycin can treat both chlamydia and gonorrhea. If the patient appears systemically ill, cannot tolerate oral medications, or has urinary retention, hospitalization and parenteral antibiotics are warranted. Treatment options include ciprofloxacin 400 mg IV every 12 hours, levofloxacin 500 mg IV every 24 hours, or ceftriaxone 2 g IV every 24 hours, with or without gentamicin, 3 to 5 mg/kg per day. Following clinical improvement, the patient may be transitioned to an oral regimen, such as a fluoroquinolone. The duration of treatment should be a minimum of 2 weeks, although 4 to 6 weeks may be necessary. The treatment of chronic bacterial prostatitis consists of antibiotics for 4 to 12 weeks (see Table 89.8). Of the researched treatments, α-adrenergic receptor blockers and antibiotics used alone or in combination result in the greatest improvement in symptoms. Antiinflammatories may also be beneficial. Patients thought to have chronic prostatitis or CPPS should be referred to a urologist. Treatment of prostatic abscess consists of broad-spectrum intravenous antibiotics (eg, ciprofloxacin, 400 mg IV every 12 hours) and urologic consultation for perineal drainage or surgical débridement.

RENAL CALCULI Multiple pathogenic factors interact to cause the formation of renal calculi. Risk factors include older age, male gender, obesity, and family history (Box 89.2). Its incidence depends on geographic, ethnic, dietary and genetic factors. It affects up to 20% of the population worldwide, and recurrence rates are close to 50%.16 In the United States, prevalence rates for renal calculi are

TABLE 89.8 

Oral and Parental Antibiotic Options for Prostatitis (4–6 Weeks’ Duration) ANTIMICROBIAL

DOSE

Ciprofloxacin

400 mg every 12 hours (IV)

Levofloxacin

500 mg every 24 hours (IV)

Ceftriaxone

2 g every 24 hours (IV)

Ciprofloxacin

500 mg every 12 hours (PO)

Levofloxacin

500 mg once daily (PO)

Trimethoprim-sulfamethoxazole

160/800 mg bid (PO)

11% in men and 7% in women; the incidence of kidney stones has continued to rise in all age groups and genders.17 Nearly 70% of all ureteral calculi occur in individuals aged 20 to 50 years, with an increased prevalence reported in areas with hot or dry climates.

Pathophysiology Most ureteral calculi originate in the kidney and then pass into the collecting system. The chemical composition of urinary tract stones is the key factor for determining optimal management. Stone are generally composed of calcium, struvite, or uric acid. Most stones (75%) are composed of calcium oxalate, alone or in combination with calcium phosphate. The hyperexcretion of calcium is a major contributor to stone formation; its most common identified cause is hyperparathyroidism. Other medical conditions that lead to increased calcium levels include hypercalcemia of malignancy, sarcoidosis, and excessive calcium ingestion or increased absorption from the gut. The other major component of calcium stones, oxalate, is influenced by diet. Hyperoxaluria occurs in the presence of small bowel disease, bariatric surgery, Crohn’s disease, ulcerative colitis, and radiation enteritis. Magnesium ammonium phosphate (struvite) stones account for approximately 15% of all renal calculi. Struvite stones occur almost exclusively in patients with UTIs and often are referred to as infection stones. They form as a result of the presence of ureasplitting organisms, such as Proteus, Providencia, Klebsiella, Pseudomonas, and Staphylococcus. Patients with anatomic abnormalities that predispose them to recurrent UTIs are at increased risk of developing struvite stones. Most staghorn calculi—stones that fill the greater part of the collecting system—are composed of struvite. Uric acid stones account for 10% of all stones in the United States. Approximately 15% of patients with symptomatic gout have uric acid calculi, and the incidence of uric acid stones increases with the use of uricosuric agents. In addition to hyperuricosuria, aciduria is considered necessary, because the precipitation of uric acid is unlikely at a higher urine pH. A distinctive feature of uric acid stones is their radiolucency. Impaction along the genitourinary tract is a serious complication of renal calculi and can cause several physiologic changes. Once obstruction occurs, a rapid redistribution of renal blood

BOX 89.2 

Risk Factors for Urolithiasis Metabolic disease or disturbance Crohn’s disease Milk-alkali syndrome Primary hyperparathyroidism Hypernatriuria Hyperuricosuria Sarcoidosis Recurrent UTI Renal tubular acidosis (type I) Gout Laxative abuse Positive family history Hot arid climates (southeast United States) Male gender (white men affected more commonly than black men) Previous kidney stone Dehydration UTI, urinary tract infection.

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flow results in a decrease in the glomerular filtration rate (GFR). As glomerular and tubular function decrease, renal excretion shifts to the unaffected kidney. Obstruction also causes a rapid decrease in ureteral peristaltic activity. In the presence of infection, renal and ureteral function may be impaired. Complete obstruction of the ureters may lead to loss of renal function, with an increased incidence of irreversible damage after 1 to 2 weeks, including rupture of the renal calyx. Partial obstruction is associated with a lower likelihood of renal injury, but may still result in irreversible damage. Although calculus size and location are important determinants of the degree of disease, the major cause of progressive renal damage is associated infection. The stone behaves as a foreign body and leads to stasis and obstruction, decreasing host resistance and increasing the incidence of infection. Subsequent infectious complications include pyelonephritis, perinephric abscess, and gram-negative bacterial sepsis. The three primary predictors of stone passage without the need for surgical intervention are calculus size, location, and degree of patient pain. The most important factor that relates to passage of a calculus though the genitourinary tract is its size. Approximately 90% of stones smaller than 5 mm pass spontaneously within 4 weeks. This percentage decreases to 15% for stones 5 to 8 mm in size. Up to 95% of stones larger than 8 mm become impacted along the genitourinary tract, and lithotripsy or surgical removal may be required. Surgical intervention can be performed on an outpatient basis, provided the patient is able to tolerate oral intake and has adequate pain control unless the stone is infected, renal damage is considerable, there are bilateral obstructing stones, or there is obstruction of a solitary or transplanted kidney. Spontaneous passage is more frequent with stones located below the midureter than those located above the midureter. Renal calculi seldom cause complete obstruction. There are five sites along the ureter at which calculi are likely to become impacted (Fig. 89.4). First, a stone may lodge in the calyx of the kidney or pass into the renal pelvis and become lodged at the ureteropelvic junction. The relatively large renal pelvis (1 cm) narrows abruptly at its distal portion, where it is equal in diameter to its adjoining ureter (2–3 mm). The third region is near the pelvic brim, where the ureter arches over the iliac vessels posteriorly into the true pelvis. The most constricted area along the ureter, and a common location for impaction, is the ureterovesicular junction. This is the site at which the ureter enters the muscular coat of the bladder (intramural ureter). At the time of diagnosis, up to 75% of stones are located in the distal third of the ureter. Finally, calculi may become lodged in the vesical orifice.

Clinical Features The onset of pain usually is abrupt, with a crescendo of extreme pain that begins in the flank, extends laterally around the abdomen, and radiates into the groin. Pain may radiate to the testicles in men and the labia majora in women. A constant, underlying dull ache in the flank is common between episodes of colic. The cause of colicky, severe flank pain is hyperperistalsis of the smooth muscle of the calyces, pelvis, and ureter, whereas the cause of a dull ache can be acute obstruction and renal capsular tension. GI symptoms of nausea and vomiting are common. One-third of patients experience gross hematuria, with or without blood clots in the urine. Symptoms of urinary urgency and frequency often develop as the stone nears the bladder. A history of fever and chills strongly suggests superimposed infection; these cases should be regarded as true urologic emergencies. A patient with renal colic often is in severe pain and paces or writhes in pain on the stretcher, unable to find a comfortable position. Fever, if present, strongly suggests infection. The abdomen should be auscultated and palpated in search of bruits

2 mm (6 Fr)

10 mm (30 Fr)

4 mm (12 Fr)

4-6 mm (2-18 Fr)

1-5 mm (3-15 Fr)

3-4 mm (9-12 Fr)

Fig. 89.4.  Variations in caliber of the ureter. Fr, French catheter size. (Adapted from Eisendrath, Rolnick. Lich R Jr, et al: Childhood disorders and diseases. In Harrison JH, et al, editors: Campbell’s urology, vol 1, ed 4, Philadelphia, 1978, WB Saunders.)

and thrills over the abdominal aorta and iliac vessels because the clinical manifestations of aortic abdominal aneurysms may mimic those of renal colic. Patients commonly have intermittent pain that may nearly resolve between episodes of severe discomfort.

Differential Diagnosis A number of clinical diseases can produce pain similar to that of renal colic (Box 89.3). Potentially serious or life-threatening alternate diagnoses include pulmonary embolism, ectopic pregnancy, bowel obstruction, incarcerated inguinal hernia, pancreatitis, cholecystitis, renal vein thrombosis, and renal malignancies and infarction.17a One review of consecutive CT reports for patients presenting to an ED with acute flank pain has shown the most common alternate diagnoses to be biliary disease, appendicitis, pyelonephritis, ovarian cyst, renal mass, and abdominal aortic aneurysm (AAA), with and without rupture.

Diagnostic Testing Urinalysis and Culture Red blood cells (RBCs) generally are found in the urine of patients with urolithiasis. However, the absence of RBCs in the urine does not exclude the diagnosis. Up to 20% of patients with documented urolithiasis have no microscopic hematuria.3 Furthermore, there is no correlation between the degree of obstruction and absence of hematuria. Sterile pyuria can occur in the absence of infection as a result of ureteral inflammation, but the presence of a UTI should be investigated if other clinical signs of infection are present, such as

CHAPTER 89  Selected Urologic Disorders

BOX 89.3 

Differential Diagnosis for Pain Associated With Urolithiasis UROLOGIC DISEASE

Upper Urinary Tract Renal infarct Renal parenchymal tumors Urothelial tumors Papillary necrosis Pyelonephritis Hemorrhage (blood clot) Ureter Urothelial tumors Hemorrhage (blood clot) Previous surgery (eg, stricture) Metastatic tumors Lower Urinary Tract Urothelial tumors Urinary retention

NONUROLOGIC DISEASE

Intra-abdominal Peritonitis (especially appendicitis) Biliary colic Intestinal obstruction Vascular Abdominal aortic aneurysm Superior mesenteric artery occlusion Retroperitoneal Retroperitoneal lymphadenopathy Retroperitoneal fibrosis Tumor Gynecologic Cervical cancer Endometriosis Ovarian vein syndrome Musculoskeletal Muscle strain or bony injury From Lingeman J: Calculous disease of the kidney and bladder. In Harwood-Nuss A, Linden CH, Sternbach G, et al, editors: The clinical practice of emergency medicine, ed 2, Philadelphia, 1996, JB Lippincott.

fever and chills. A urinalysis with culture should be performed to look for pyuria and bacteriuria and to measure nitrite and leukocyte esterase levels when infection is suspected. The kidney does not produce urine with a pH greater than 7.5 under normal conditions, so a urinary pH higher than 7.5 should raise suspicion for the presence of urea-splitting organisms such as Proteus. Renal tubular acidosis and ingestion of absorbable alkali also may increase the urinary pH and should be considered in the differential diagnosis. A pH less than 5 often is associated with the formation of uric acid calculi.

Other Laboratory Tests Measurement of blood urea nitrogen (BUN) and serum creatinine levels is not routine but should be performed in patients who have a renal calculus with a solitary kidney, transplanted kidney, or history of renal insufficiency. On rare occasions, urolithiasis can

Fig. 89.5.  In a near-term pregnant woman with an obstructed left kidney, this intravenous pyelogram demonstrates a delayed nephrogram. The right kidney has physiologic hydronephrosis from ureteral compression by the fetal head.

present as acute renal failure resulting from obstruction of both ureters or the ureter of a solitary kidney. A slightly elevated white blood cell (WBC) count in patients with renal calculi may be the result of demargination from acute pain, but this is not a sensitive test and should be performed only in patients who are thought to be infected. A significantly elevated WBC count or left shift on the differential suggests active infection.

Imaging Imaging is not needed in all patients with renal colic but should be performed when signs and symptoms are atypical and the diagnosis is in question, the patient has a solitary or transplanted kidney, or appears toxic, or high-grade obstruction is suspected. Radiography of the Kidney, Ureter, and Bladder.  As an initial imaging study, kidney, ureter, and bladder (KUB) radiography provides only presumptive evidence of calculi (24

Time interval, h

Fig. 89.9  Testicular salvage and atrophy rates over time in testicular torsion. A, Immediate (early) surgical salvage after torsion. B, Subsequent atrophy of surgically salvaged testes after torsion at various time intervals. (From Visser AJ, Heyns CF: Testicular function after torsion of the spermatic cord. BJU Int 92:200–203, 2003.)

Epididymitis Hernia Trauma Tumor Torsion Fournier’s gangrene Ampulla of ductus deferens

Urinary bladder

Ductus deferens

Prostate gland

Seminal vesicle

Prostatic portion of urethra

Ejaculatory duct Inguinal canal

Membranous portion of urethra

Superficial inguinal ring Ductus deferens

Bulbourethral gland

Testicular artery

Spongy portion of urethra

Genital nerve

Ductus deferens

Venous plexus

Penis

Spermatic cord

Internal spermatic fascia

Head of epididymis Testis

External spermatic fascia

Body of epididymis

Cremaster muscle and fascia

Glans penis Tail of epididymis

Tunica vaginalis Dartos fascia and muscle Scrotum (skin)

Fig. 89.10.  Testes, epididymis, ductus deferens, and glands of the male reproductive system. (From Seeley RR, et al, editors: Anatomy and physiology, New York, 1989. McGraw-Hill.)

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Number of patients

200

150

TAT TT TVI EPD

100

50

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Age of patients (years) Fig. 89.11  Age distribution of boys with torsion of the appendix testis (TAT), testicular torsion (TT), tunica vaginalis inflammation (TVI), and epididymitis (EPD). (From Yang C, Song B, Liu X, et al: Acute scrotum in children: an 18-year retrospective study. Pediatr Emerg Care 27:270–274, 2011.)

Clinical Features.  Patients typically report a sudden onset of rapidly escalating pain in the scrotum, lower abdomen, or inguinal area that awakens them from sleep or develops several hours after physical activity. Although a short time from the onset of symptoms to presentation favors torsion, it cannot be reliably used to differentiate it from other causes of scrotal pain. In one large study, 72% of torsion patients presented more than 12 hours after the onset of their symptoms.28 Up to 29% of patients with testicular torsion describe similar pain in the past, caused by previous intermittent torsion in a predisposed testicle. Patients often report nausea and vomiting or abdominal pain caused by reflex stimulation of the celiac ganglion.28 Because up to 10% of torsion cases may present with abdominal pain and no scrotal pain, the scrotum should be examined in all patients presenting with abdominal pain. A history of scrotal trauma reduces a patient’s likelihood of having testicular torsion; however, approximately 10% of patients with testicular torsion report prior acute blunt trauma to the scrotum.29 In these cases, the symptoms of torsion often are misattributed to the trauma itself, delaying the diagnosis and worsening the rate of testicular salvage. The physical examination is much more reliable than the history in determining the presence of testicular torsion. The cremasteric reflex is usually absent in patients with torsion; however, its presence cannot be used to rule out torsion. Patients with torsion frequently have a tender firm testicle that can be higher than the contralateral testicle owing to shortening of the spermatic cord as it twists. Twisting also can leave the testicle in the transverse position and displace the epididymis from its usual location along the posterior aspect of the scrotum. Often, the patient’s scrotum is so swollen and tender that a complete physical examination is impossible. After 24 hours, the physical examination is not particularly helpful because many of the aforementioned findings are no longer present. Differential Diagnosis.  There is no single history or physical examination finding that accurately or reliably differentiates torsion from other causative disorders (see Table 89.9). Any patient with acute onset of scrotal pain in whom the diagnosis of torsion cannot be ruled out should undergo further diagnostic testing.

Fig. 89.12.  Doppler ultrasound image showing a testicle with no flow as a result of torsion (white box). OK? (From Blaivas M, Brannam L: Testicular ultrasound. Emerg Med Clin North Am 22:723–748, 2004.)

Diagnostic Testing  Urinalysis.  In patients in whom the history and physical findings strongly suggest torsion, emergent surgical consultation is warranted. If the diagnosis is equivocal, adjunctive tests should be performed to determine the cause of the pain. Although urinalysis results suggestive of infection are consistent with epididymitis, such findings also may be noted in patients with torsion and a concomitant UTI. Imaging.  Ultrasound imaging for testicular torsion has a sensitivity of 64% to 100% and specificity of 97% to 100%.30,31 The torsed testicle typically will be hypoechoic and enlarged (Fig. 89.12). False-negative findings occur when the testicle is examined early in the course of the disease, when blood flow is still present, and with intermittent torsion. Examination of the spermatic cord for twisting, instead of the testicle itself, has been shown to reduce the frequency of these false-negative results. Color Doppler techniques can improve the specificity of ultrasound imaging to 100% by demonstrating reduced blood flow to the affected testicle. Doppler studies can be more difficult to interpret in younger boys because blood flow is physiologically low in the testicles of prepubertal boys. As many as 50% of boys younger than 8 years do not show intratesticular flow.32 This hypovascularity can result in false-positive diagnoses, which could potentially lead to unnecessary surgical exploration. Comparison with the contralateral testicle can help avoid this misdiagnosis; as in normal patients, blood flow to the two testicles will be similar. The color Doppler appearance of the testicle depends on the degree of twisting of the spermatic cord. With 180 degrees or less of twisting of the cord, venous flow from the testicle ceases but arterial flow persists. This leads to edema of the testicle on ultrasound that can be misinterpreted as inconsistent with torsion. In contrast, with more than 180 degrees of twisting of the cord, arterial flow also ceases, leading to a lack of Doppler signal on ultrasound. Parenchymal echo texture on ultrasound may help predict the viability of the testicle. A homogenous echo texture of the parenchyma has been associated with a higher likelihood of testicular salvage. A retrospective review of 25 cases of testicular torsion has found a zero recovery rate in testes with heterogeneous echogenicity.33 In the future, the parenchymal appearance may help determine patients who are appropriate candidates for emergent surgery. Color Doppler ultrasound imaging has the advantage of being an inexpensive and rapid test, readily performed in the ED setting. It is helpful when it demonstrates torsion in patients with equivocal findings on the history and physical examination, but it does not have sufficient sensitivity to rule out a diagnosis of torsion.

CHAPTER 89  Selected Urologic Disorders

An analysis of 669 scrotal ultrasounds has revealed a 98% negative predictive value for torsion.26 A urologist should evaluate any patient in whom ultrasound findings are negative but history and physical findings are suggestive of torsion. Moreover, an ultrasound examination should never delay evaluation by a urologist in any patient with probable torsion. Magnetic resonance imaging (MRI) and radionuclide scanning of the scrotum have also been used to diagnose testicular torsion but are time-consuming. They have largely been replaced by ultrasound. Management.  The first step in the management of suspected testicular torsion is immediate consultation with a urologist. The longer the spermatic cord remains twisted, the lower the likelihood of testicular salvage. In addition, early consultation allows the urologist to accompany the patient to ultrasound—if imaging is obtained—where images can be reviewed in real time with the radiologist. After consultation, IV access is established, and analgesia is provided systemically or with a block of the spermatic cord. If the urologist is not readily available, manual detorsion should be attempted. Relief should be felt when the operator rotates the affected testicle away from the midline, as if turning the pages of a book. If this maneuver is successful, patients should report immediate improvement of symptoms. If only partial relief of pain is noticed, an attempt should be made to untwist past 360 degrees because a higher degree of rotation may be present. If pain increases or there is no relief, consider reversing the direction of reduction because up to one-third of cases can be torsed laterally. The use of ultrasound can help guide this procedure. If manual detorsion is attempted, a spermatic cord block or systemic analgesics should be administered (Fig. 89.13). In addition, evaluation by a urologist should never be delayed to perform this or any other test or maneuver. Regardless of the outcome with manual detorsion or duration of symptoms prior to presentation, patients still require surgical evaluation. A surgeon can confirm the reduction and stabilize the testes with orchiopexy. Even for symptoms lasting beyond 24 hours, testicular salvage is possible for incomplete torsion, and orchiopexy can help prevent recurrence. Removal of a necrotic testicle speeds recovery. Disposition.  Rapid diagnosis of testicular torsion is essential and should be followed by emergent surgical scrotal exploration and bilateral orchiopexy, if necessary. Loss of the testicle is usually a result of delay in seeking medical attention. However, almost 30% of cases of failed testicular salvage have been attributed to misdiagnosis, and another 13% to a delay in treatment after the proper diagnosis was established. Misdiagnosis almost universally leads to orchiectomy and represents a common source of litigation.

Torsion of Appendages of the Testis A normal scrotum has several vestigial appendages that can also twist and become ischemic, with resultant scrotal pain. This process is most common between 7 and 14 years of age, with a mean age of 10 years. In retrospective analyses, torsion of an appendage rivals epididymo-orchitis as the most common cause of the acute scrotum. The appendix testis, a remnant of the paramesonephric duct, is present in 92% of patients. It is located on the superior aspect of the testicle, between the testis and epididymis (Fig. 89.14). This appendage is prone to torsion owing to its pedunculated shape. After several days of ischemia from torsion, it will undergo necrosis, with eventual reabsorption. Its loss does not permanently affect fertility or have any impact on surrounding structures.

Clinical Features.  As with testicular torsion, patients with torsion of an appendage complain of scrotal pain but report milder symptoms, with a more gradual onset. They report nausea, vomiting, urinary symptoms, or previous episodes of similar pain less commonly than patients with testicular torsion. They usually seek medical attention later than patients with testicular torsion, generally after 48 hours of symptoms. On physical examination, twisting of the appendix testis leads to formation of a hard, tender, 2- to 3-mm nodule at the upper pole of the testicle. Unlike in testicular torsion, the entire testicle is not tender. The testicle also does not change in overall size, and the scrotum typically does not swell until late in the disease process. The cremasteric reflex typically is intact. On transillumination, the ischemic appendage may rarely be seen as a blue dot. Diagnostic Testing.  Urinalysis does not show evidence of infection. On ultrasound imaging, the appendix under torsion will appear hypoechoic. Color Doppler ultrasound can show decreased flow in normal and torsed appendages. With torsion of the appendix, a hypoechoic spherical nodule with a diameter more than 5 mm is present over the superior aspect of the testicle (Fig. 89.15). Management and Disposition.  If testicular torsion is ruled out, surgical excision of the appendix is rarely necessary. Treatment consists of scrotal support, ice, and NSAIDs. Resolution of symptoms can be expected within 7 to 10 days. Surgical excision is reserved for uncontrollable pain.

Epididymitis Epididymitis is the most common intrascrotal inflammatory disease. Most cases occur in men between 18 and 35 years of age, but the disease can affect males at any age. It is uncommon in prepubertal males. If untreated, it can lead to orchitis, testicular abscess and, rarely, sepsis. The epididymis is a tightly coiled tubular area along the posterior aspect of the testes, where sperm mature before their transit to the vas deferens. The epididymis becomes infected when organisms travel retrograde from the vas deferens. With infection, the ipsilateral testicle is also commonly involved, a condition referred to as epididymo-orchitis. The common route of infection is local extension, mainly due to infections spreading from the urethra (sexually transmitted pathogens) or bladder (urinary pathogens). The particular organisms involved in the infection depend on the sexual activity of the patient. Although the literature classically describes men younger than 35 years who are prone to C. trachomatis and N. gonorrhoeae infections, all sexually active men, regardless of age, are at risk for epididymitis from these organisms. Acute epididymitis caused by sexually transmitted enteric organisms occurs in men who are the insertive partner during anal intercourse. Other rare causes of epididymitis include M. tuberculosis, Treponema pallidum, fungal infections, amiodarone use, and systemic inflammatory conditions such as Behçet’s syndrome. In men older than 35 years, urinary tract pathogens become the predominant cause of epididymitis. Unlike younger patients, older men with epididymitis tend to have urinary tract abnormalities that predispose them to these infections. Over 50% of men older than 60 years with epididymitis have lower urinary tract obstruction. Older men also are more likely to have concomitant prostatitis, benign prostatic hypertrophy (BPH), immunosuppression, or systemic disease or have undergone recent genitourinary instrumentation or catheterization. Epididymitis in children is usually idiopathic, although children can also have congenital genitourinary anomalies that predispose them to recurrent infection. The most commonly

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MANUAL TESTICULAR DETORSION

Epididymis

Testis

Tunica vaginalis (normal)

Torsion

Bell-clapper deformity

A. Anatomy of testicular torsion. Testicular torsion occurs when the testis twists within the tunica vaginalis. Patients with the bell clapper deformity (ie, incomplete fusion of the tunica along the epididymis, which results in incomplete attachment of the testicle to the scrotum) are at higher risk.

Torsion

B. Spermatic cord block. Grasp the spermatic cord

between your thumb and index finger. Use a 30-gauge needle to infiltrate the entire cross section of the spermatic cord and its surrounding rim with anesthetic. This will cause visual ballooning of the grasped segment of the cord. Gently massage this bulge to disperse the anesthetic. Usually about 10 mL is required.

Detorsion

Lateral

C. Testicular torsion more commonly occurs in a medial direction. Initially attempt detorsion by rotating the testis outward toward the thigh. This is most successful if attempted within the first few hours of torsion, before the onset of significant scrotal swelling. Intravenous narcotics (eg, fentanyl) can be administered or a cord block performed before attempting detorsion.

Medial

D. Detorsion maneuver. Detorsion of the testicle may

require testicular rotation through two planes. To release the cremasteric muscle, rotate the testis in a caudal-tocranial direction simultaneously with medial-to-lateral rotation. The right testis is shown.

Fig. 89.13.  Manual testicular detorsion. (Adapted from Roberts J, Custalow CB, Thomsen TW, editors: Roberts and Hedges’ clinical procedures in emergency medicine, ed 6, St. Louis, 2014, Elsevier Health Sciences.)

associated abnormality is neurogenic bladder, which produces increased pressure during urination and reflux into the ejaculatory ducts. In infants, bacterial causes are more common. Clinical Features.  Patients with epididymitis experience scrotal pain of gradual onset, prompting them to present later in

the clinical course than patients with torsion. Initially, this pain may reside in the lower abdomen or flank, caused by inflammation of the vas deferens. Fever is uncommon. In the early stages of the disease, tenderness is localized to the epididymis but quickly spreads to the ipsilateral testicle. Later in the course, the scrotum can become edematous, erythematous, and extremely tender. The

CHAPTER 89  Selected Urologic Disorders

F

A

Fig. 89.14.  Ultrasound image showing the testicular appendage (A) surrounded by a hydrocele (F). (From Blaivas M, Brannam L: Testicular ultrasound. Emerg Med Clin North Am 22:723–748, 2004.) Fig. 89.16.  Ultrasound of the testicle showing an enlarged epididymis and increased blood flow on Doppler ultrasound imaging (white box). (From Blaivas M, Brannam L: Testicular ultrasound. Emerg Med Clin North Am 22:723–748, 2004.)

Fig. 89.15.  Transverse ultrasound image shows a hyperechoic mass (curved arrow) with tiny central hypoechoic areas adjacent to the left testes and epididymis with a reactive hydrocele and mild scrotal wall thickening. (From Mirochnik B, Bhargava P, Dighe MK, Kanth N: Ultrasound evaluation of scrotal pathology. Radiol Clin North Am 50:317–332, 2012.)

testis is located in the normal anatomic position, with an intact cremasteric reflex. Although Prehn’s sign—decrease in pain with elevation of the scrotum—has been touted as indicative of epididymitis, it has low sensitivity and specificity. Only 10% of patients with epididymitis from sexually transmitted organisms have symptoms of urethritis or a urethral discharge on examination. No single historical factor or physical finding has been shown to differentiate torsion from epididymitis reliably. Diagnostic Testing.  The diagnosis of epididymitis is typically made based on compatible physical examination findings and confirmed by laboratory testing. A urinalysis usually demonstrates evidence of pyuria. If patients are at risk for STD, a urethral swab or first-void urine sample should be tested for C. trachomatis and N. gonorrhoeae; a polymerase chain reaction (PCR) assay and other nucleic acid amplification tests have the greatest sensitivity

and should be used, when available. Studies have suggested that this diagnostic regimen is underused, with less than 10% of adults with epididymitis undergoing testing for STDs.34 Systemic leukocytosis may be present but is a nonspecific finding and does not differentiate epididymitis from torsion. In prepubertal children, urinalysis and urine culture rarely are positive; a retrospective review of 73 children with epididymitis has demonstrated bacteriuria in only one child.35 Nevertheless, in these patients, urine cultures should still be obtained to rule out bacterial infection because untreated bacterial infections may lead to long-term complications. Because the history and physical examination features and laboratory results cannot reliably distinguish torsion from epididymitis or other diseases, equivocal presentation for epididymitis versus testicular torsion should be assessed using testicular ultrasound with Doppler. On ultrasound, an inflamed epididymis appears enlarged and hypoechoic (Fig. 89.16). However, a minority of patients with torsion have preserved flow that can appear similar to that of epididymitis; in these cases, the presence of a spermatic cord twist, indicative of torsion, should be sought. Prepubertal children with recurrent epididymitis should undergo renal ultrasound and cystography to identify potential underlying urinary tract abnormalities. These are important to identify to reduce the risk of future inflammation. Management.  Empirical antibiotics are selected in accordance with the patient’s age, sexual history, and any previous genitourinary tract abnormalities or instrumentation (Table 89.10). Treatment focuses on curing infection, improving symptoms, preventing transmission, and reducing future complications. In patients with a suspected sexually acquired infection, ceftriaxone, 250 mg IM, should be given to treat possible N. gonorrhoeae infection. In conjunction, doxycycline, 100 mg PO bid for 10 to 14 days, should be started to treat C. trachomatis or Ureaplasma urealyticum infection.36 Treatment of sexual partners should be arranged, even if the partner’s culture demonstrates no growth. In patients with infection by enteric organisms, levofloxacin, 500 mg PO once daily, or ofloxacin, 300 mg PO every 12 hours,

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TABLE 89.10 

Treatment of Epididymitis DRUG OF CHOICE

DOSE AND ROUTE

ALTERNATIVE REGIMEN(S)

PRESUMED SEXUALLY ACQUIRED EPIDIDYMITIS Ceftriaxone followed by

250 mg IM once

Doxycycline

100 mg PO bid for 10 days

PRESUMED NONSEXUALLY ACQUIRED EPIDIDYMITISa Levofloxacin

500 mg PO daily for 10 days

Ofloxacin, 300 mg PO bid for 10 days

Prepuberty Supportive care only

Obtain urine culture; administer antibiotics only if culture is positive

a

Adjust antibacterial therapy according to results of urine culture. IM, Intramuscularly; PO, orally.

is recommended. If the patient is high risk for sexually transmitted infections and enteric organisms, treatment should include ceftriaxone and fluoroquinolones. Despite the absence of evidence to support benefit, we also recommend bed rest, scrotal elevation, analgesics, and ice packs. Most cases of pediatric epididymitis are idiopathic, and antibiotics are not routinely recommended. Urine culture specimens should be obtained for these boys, and antibiotic therapy should be initiated only if cultures reveal bacteria. Despite the absence of evidence to support benefit, we recommend that boys limit activity, elevate the scrotum with ice packs, and reduce inflammation with NSAIDs. In contrast, infants often have bacterial epididymitis and should be treated empirically with antibiotics pending urine culture results. Disposition.  Patients with systemic signs of toxicity (fever, chills, nausea, vomiting) or complications of acute epididymitis should be hospitalized and treated with parenteral antibiotics. Most well-appearing patients with uncomplicated epididymitis can be managed as outpatients. Urology follow-up should be arranged for those likely infected with enteric organisms. Signs and symptoms of epididymitis that do not subside within 3 days require reevaluation of the diagnosis and therapy.

Orchitis Orchitis is a rare acute infection of the testis. With the exception of viral diseases, genitourinary tract infections seldom primarily involve the testis. It is most common in prepubertal boys, with viral infections such as mumps causing most cases. Orchitis rarely develops in prepubertal boys with mumps but is more common in adolescent males with mumps. It tends to arise several days after the onset of parotitis. Although vaccination has significantly reduced the incidence of mumps infection, sporadic outbreaks have occurred. Infections in vaccinated individuals are increasingly common, presumably resulting from vaccine failure or antigenic differences between the infecting and vaccine strains. Owing to the testes’ relatively high threshold of resistance to infection, bacterial orchitis usually results from local bacterial spread from the epididymis, frequently referred to as epididymo-

orchitis. The most frequent bacterial pathogens are N. gonorrhoeae, C. trachomatis, E. coli, Klebsiella, and P. aeruginosa. These organisms tend to infect postpubertal males and men older than 50 years with BPH. Clinical Features.  A patient with mumps orchitis has testicular pain and swelling that commonly begins 4 to 6 days after the onset of parotitis, although it can develop in the absence of parotitis. The clinical course varies, with adults having more severe symptoms. Clinical resolution generally occurs in 4 to 5 days. Patients with bacterial orchitis typically have fever and scrotal pain. They often have constitutional signs and symptoms, including nausea, vomiting, myalgias, and malaise. The affected testicle— the disease is unilateral in 70% of patients—and the scrotum are swollen, tender, and erythematous. Diagnostic Testing.  As with all causes of scrotal pain, the first priority is to exclude testicular torsion. If the patient clearly has mumps orchitis based on the clinical presentation and a history of preceding parotitis, no other tests are necessary. For all other patients, urinalysis, urine culture, and ultrasound should be performed. On ultrasound, orchitis shows hypervascularity, commonly described as a testicular inferno. Blood tests are typically not helpful, because false-negative results are common with serologic testing, particularly in vaccinated individuals. Management.  In sexually active patients, ceftriaxone and doxycycline should be used to cover N. gonorrhoeae and C. trachomatis. In older patients, fluoroquinolones provide the best coverage of gram-negative organisms. Treatment of viral orchitis is supportive only. Although steroids may improve symptoms, they can reduce testosterone levels. All patients should receive local scrotal care as described for epididymitis. Patients with marked pain, high fever, or constitutional symptoms merit hospitalization and parenteral antibiotics.

Testicular Tumors Principles.  Tumor of the testis is the most common malignancy in young men but accounts for only 1% of all cancers in men. These tumors are more common in infertile patients and whites. They also occur with increased frequency in the nondescended and descended testicles of patients with cryptorchidism. Approximately 95% of testicular tumors are germ cell tumors, with 50% of these being seminomas and the other 50% being mixed types, including teratomas, choriocarcinomas, and yolk sac tumors. The other 5% of testicular tumors are sex cord stromal tumors. The disease course will depend on the type of tumor present, as well as the age of the patient. Clinical Features.  Testicular cancer usually presents as a painless, unilateral scrotal mass or as an incidental ultrasound finding. However, scrotal pain may be the first symptom in up to 20% of cases of patients with testicular cancer. Unlike other painless scrotal masses, such as hydroceles and varicoceles, tumors cannot be separated from the underlying testicle. Palpable tumors are more likely to be malignant compared with tumors identified only with imaging. Diagnostic Testing.  All patients with a scrotal enlargement or palpable scrotal lesions on physical examination should undergo a scrotal ultrasound examination. This study can reveal a concomitant hydrocele or homogeneous hypoechoic lesion. Intratesticular tumors are typically hypervascular, with irregular branching vessels. Leydig cell tumors are unique, because they show hypervascularity around the lesion but no internal color

CHAPTER 89  Selected Urologic Disorders

Doppler flow. Although helpful for staging purposes, CT scans of the chest and abdomen are necessary in the ED only if the patient has complaints related to these parts of the body. Most paratesticular masses are benign lesions such as epididymal cysts, epididymitis, spermatoceles, hydroceles, or hernias. Management and Disposition.  Urgent referral to a urologist is indicated for patients with intratesticular masses. The radiosensitive nature of seminomas renders the combined treatment of orchiectomy and radiation therapy highly successful for early-stage disease. Testicular cancer has become one of the most curable solid neoplasms, with an expected 5-year survival rate over 95%.37

Testicular Trauma The most concerning injury associated with trauma involves rupture of the testicle. Testicular rupture is characterized by tear of the tunica albuginea and extrusion of the seminiferous tubules. The presentation can range from a tender, large, blood-filled scrotum to minimal swelling, with mild pain of the testicle. If there is any concern for rupture, scrotal ultrasound is indicated. Disruption in the echogenic tunica albuginea is 100% sensitive and 65% specific for rupture. Early surgical intervention is associated with higher rates of testicular salvage. Hematomas can be intratesticular or extratesticular, with or without testicular rupture. Similar to rupture, rapid evacuation of an intratesticular hematoma will reduce the risk of necrosis. Extratesticular hemorrhage into the tunica vaginalis is termed a hematocele and is the most common finding after blunt scrotal injury. Surgical exploration with hematoma extraction is recommended for patients with large hematoceles to prevent testicular atrophy. Approximately 10% of patients with testicular torsion have associated trauma and require prompt identification and detorsion.

Inguinal Hernia, Acute Hydrocele, Varicocele, and Spermatocele Inguinal hernias, hydroceles, varicoceles, and spermatoceles are considerations in the differential diagnosis of an acute scrotal mass. These clinical entities are typically painless and readily identifiable on physical examination. Most children with inguinal hernias will not have a palpable mass on examination but will report a history of intermittent bulge in the groin that appears with straining or crying. Less commonly, an inguinal mass is palpable and may extend into the scrotum. If this mass becomes incarcerated, it will be tender, and often the overlying skin will be edematous and erythematous. Children typically will develop irritability, vomiting, or abdominal distention. Incarcerated hernias should be reduced promptly to prevent bowel infarction from strangulation. Reduction can be accomplished by placing the patient in a Trendelenberg position and applying gentle pressure to expel the gas and stool in the bowel from the hernia. Pressure is then applied over the distal aspect of the hernia to reduce the bowel. If this technique fails, surgery is consulted. After reduction of an incarcerated hernia, children typically require hospitalization and delayed surgical repair. Acute hydroceles typically are benign. They are caused by the accumulation of fluid between the two layers of the tunica vaginalis. They are painless, localized to the scrotum, and will transilluminate. Varicoceles are enlarged spermatic cord veins that typically are painless or cause only minimal discomfort. On examination, they are often described as feeling similar to a bag of worms, just superior to the testicle, and decrease in size when the patient is supine. In contrast, a spermatocele is a sperm-containing cyst that is

palpated as a nontender mass posterior to the testicle. Ultrasound is diagnostic of these conditions. No emergent treatment is necessary, but patients require outpatient urologic evaluation. Regardless of the cause of the scrotal swelling, concomitant pathology is always a consideration. A careful evaluation for torsion, epididymitis, and tumors should be performed.

ACUTE URINARY RETENTION Epidemiology Acute urinary retention (AUR) is the sudden inability to pass urine voluntarily from the bladder. The lifetime risk of AUR increases with age, occurring in 10% of men in their 70s and in 33% of men in their 80s. AUR is usually caused by an obstructive lesion but also can be the presenting manifestation of other pathologic processes. AUR in women is much less common than in men; common causes in women include an atonic bladder, inflammation occurring postpartum or secondary to herpes, Bartholin’s abscess, acute urethritis, or vulvovaginitis. In younger patients, it usually is caused by obstruction, cystitis, and neurologic disturbances.

Pathophysiology Holding urine requires relaxation of the bladder detrusor muscle through parasympathetic inhibition and β-adrenergic stimulation and contraction of the bladder neck and internal sphincter through α-adrenergic stimulation. Conversely, micturition requires a coordinated contraction of detrusor muscle, with the simultaneous relaxation of the urethral sphincter muscle. AUR results from a disruption of this coordinated physiology caused by an increased resistance to flow via mechanical (eg, urethral stricture, clot retention) or dynamic means (eg, increased α-adrenergic activity, prostatic inflammation) or decreased neurogenic control of the detrusor muscle (eg, drugs inhibiting bladder contractility, diabetes cystopathy). The most common cause of AUR seen in the ED is obstruction of the urinary tract distal to the bladder. In men, BPH is the most common precipitant. Enlargement of the prostate coupled with constriction of the prostatic urethra from heightened α-adrenergic tone obstructs urinary output. Strictures of the urethra after prior procedural trauma, infection, or radiation therapy can also lead to AUR. Other less common obstructive causes of AUR include prostate cancer, phimosis (inability to retract the foreskin over the glans penis) and paraphimosis (inability to reduce the foreskin over an edematous glans). In women, the most frequent obstructive causes are pelvic masses and prolapse of pelvic organs such as the bladder, rectum, or uterus. These structures cause AUR by compressing the urethra and obstructing urine flow. Finally, congenital posterior urethral valves are the most common source of AUR in children. Infectious and inflammatory conditions can also cause AUR from urethral edema and obstruction, particularly in the setting of underlying prostatic disease. The most common infectious causative disorder is acute prostatitis, followed by urethritis and vulvovaginitis. In pediatric patients. UTIs can induce sufficient dysuria that the child refuses to void, with consequent urinary retention. Pharmacologic agents associated with AUR include the anticholinergic and sympathomimetic agents. Anticholinergic agents inhibit detrusor muscle contraction, whereas sympathomimetic agents increase α-adrenergic tone in the prostate. NSAIDs and calcium channel blockers have also been known to increase the rate of AUR by inhibiting prostaglandin and calcium-mediated detrusor muscle contraction.

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Neurogenic causes of AUR result from a cortical, spinal cord, or peripheral nerve deficit in the sensory or motor nerve supply of the detrusor muscle. Most neurologic causes of AUR are chronic conditions such as multiple sclerosis, Parkinson’s disease, neoplasms, and diabetic peripheral neuropathy. Other more acute neurologic conditions that should be diagnosed emergently as causative factors in the ED include spinal trauma, stroke, epidural abscess, and intervertebral disk herniation.

Patients with an infectious cause for their symptoms may complain of dysuria, frequency, urgency, hematuria, fever, chills, and low back pain. In acute prostatitis, these symptoms can be associated with penile discharge and a tender boggy prostate. Despite the obstruction, the patient may nevertheless be able to void small amounts of urine. In vulvovaginitis and urethritis, presenting complaints also may include discharge, pruritus, and vulvar skin findings. Patients with a neurogenic cause for AUR may already have a history of neurologic disease that contributes to AUR. The examination should focus on any findings suggestive of acute neurologic deficit. Strength, sensation, and reflexes in the lower extremities should be examined because they have similar innervation to that of the bladder. The status of the bulbocavernosus reflex, anal reflex, sphincter tone, and perineal sensation should also be assessed.

Clinical Features Although the potential causes of AUR are many, the history and physical examination can considerably narrow the scope of the differential diagnosis (Table 89.11). Most patients with AUR report sudden pain and have a distended tender bladder. Patients with dementia or limited verbal ability may only present with restlessness and agitation. With lesions proximal to the bladder, patients typically note pain in the flank, whereas lesions distal to the bladder can produce pain radiating to the scrotum or labia. With acute obstruction, pain is often quite severe. Patients with slowly developing or chronic obstructions are typically older and report overflow incontinence and little to no pain. When obstruction is the cause of AUR, the patient often will recall multiple previous episodes of urinary retention. In addition to this history, patients with BPH report frequency, urgency, hesitancy, nocturia, difficulty initiating the urinary stream, decreased force of the stream, sensation of incomplete voiding, and terminal dribbling. The prostate is enlarged, firm, and nonnodular. Normal findings on the prostate examination do not exclude BPH. Patients with prostate cancer can have similar symptoms, but these are more often accompanied by weight loss, bone pain, and other constitutional signs and symptoms. These patients generally will have an enlarged nodular prostate. Examination of the penis is important to identify phimosis or paraphimosis. In women with obstruction, pelvic pain and pressure are symptoms commonly associated with AUR. A prolapsed bladder, rectum, or uterus and enlarged ovaries or uterus can be identified on pelvic examination.

Differential Diagnosis The differential diagnosis for AUR is very broad and dependent on the patient’s symptoms (Box 89.6). AUR presenting as lower abdominal pain may present similarly to small bowel obstruction, urinary tract infection, or prostatitis. Flank and back pain secondary to hydronephrosis can be confused with nephrolithiasis, pyelonephritis, and spinal pathology. Urinary symptoms of overflow incontinence and urinary hesitancy can be confused with urinary tract infection or spinal cord compression. Genital pain may present similarly to trauma, testicular torsion, or inguinal hernia.

Diagnostic Testing The only suggested diagnostic test in the ED for AUR is urinalysis. It can reveal infection or the presence of hematuria from infection, tumor, or calculi. A basic chemistry panel for the assessment of renal function should be performed only when renal damage or hydronephrosis is a concern. There is no history, physical examination, or ultrasound finding that can reliably correlate

TABLE 89.11 

Presentation and Diagnosis of Acute Urinary Retention

a

CAUSE

HISTORY

PHYSICAL EXAMINATION FINDINGS

DIAGNOSISa

Benign prostatic hypertrophy

Frequency, urgency, hesitancy Prior retention

Enlarged, firm prostate

UA

Prostate cancer

Frequency, urgency, hesitancy Previous retention Constitutional symptoms

Enlarged, firm prostate Nodular prostate

UA

Phimosis, paraphimosis

Penile pain

Nonretractable foreskin Edematous penis

Clinical only

Prostatitis

Dysuria, frequency, urgency Fever, chills

Warm, tender, boggy prostate Penile discharge

UA Urine culture

Urethritis, vulvovaginitis

Dysuria, frequency, urgency Itching

Discharge

UA Urine culture Urethral or cervical culture

Pelvic mass

Pelvic pain pressure

Prolapse of rectum, bladder, uterus

UA Ultrasound imaging, CT

Neurogenic bladder

Other neurologic complaints

Neurologic deficits

UA CT, MRI

In the emergency department setting, each of these diagnoses is made primarily by the history and findings on the physical examination. Additional tests are needed as described. CT, Computed tomography; MRI, magnetic resonance imaging; UA, urinalysis.

CHAPTER 89  Selected Urologic Disorders

BOX 89.6 

Causes of Acute Urinary Retention in Adults OBSTRUCTIVE

Benign prostatic hypertrophy Prostatitis Phimosis Paraphimosis Meatal stenosis Tumor Foreign body Calculus Stricture Hematoma Carcinoma

INFECTIOUS, INFLAMMATORY Urethritis (severe) Urinary tract infection Prostatitis Severe vulvovaginitis Genital herpes

NEUROLOGIC CAUSES

Sensory Paralytic Tabes dorsalis Diabetes Multiple sclerosis Syringomyelia Spinal cord syndromes Herpes zoster

DRUGS

Antihistamines Anticholinergic agents Antispasmodic agents Tricyclic antidepressants α-Adrenergic stimulators Cold tablets Ephedrine derivatives Amphetamines

PSYCHOGENIC PROBLEMS

Psychodynamic stressors (eg, lazy bladder syndrome)

Motor Paralytic Spinal shock Spinal cord syndromes

with an acutely elevated creatinine level. It should be considered for patients with prolonged obstruction or preexisting renal insufficiency. Additional studies are selectively indicated based on the history and physical examination to identify potentially serious or reversible causes, or when the diagnosis of AUR is unclear. With an equivocal history or physical examination, bedside ultrasound can confirm AUR. Renal and bladder ultrasound studies provide visualization of any elevated postvoid residual, obstruction, hydronephrosis, or other cause of upper urinary tract disease. Pelvic ultrasound examination and CT scan evaluate for masses or malignancy causing obstruction. MRI of the spine detects disk herniation, cord compression, and cauda equina syndrome. Cystoscopy and retrograde cystourethrography can identify problems in the lower urinary tract and usually are performed as outpatient procedures. A prostate-specific antigen assay is not helpful in diagnosing or differentiating prostate cancer from other causes of AUR and should not be routinely performed.

Management Treatment focuses on bladder decompression and identification of the underlying cause. Immediate placement of a 14 Fr to 18 Fr Foley catheter should provide decompression of the bladder. If this fails, placement of an elbowed catheter (coudé catheter) with a cephalad orientation should be attempted to assist bypassing by any obstruction. If both these techniques prove to be unsuccessful, urologic surgery should be consulted. If obstruction is believed to be caused by retained blood clots, a three-way catheter should be placed to allow for bladder irrigation. When immediate bladder decompression is required and a urologist is not available, major urethral trauma is present, or the patient has recently undergone urethral surgery, suprapubic bladder drainage should be performed. Placement of a catheter has been reported to cause postobstructive diuresis, hypotension, and hematuria. Such problems are believed to be related to rapid bladder decompression so,

historically, gradual decompression has been recommended to prevent these complications. Neither has been proven to have any clinical significance. We recommend that all patients with AUR undergo rapid and complete decompression of the bladder. Although the catheter is an inconvenience for the patient, and chronic use has been associated with UTIs, trauma, stones, and urethral strictures, early removal of the catheter is also associated with heightened risk for recurrence of AUR, which has been reported in up to 70% of cases. Leaving the catheter in place for 3 to 7 days decreases the incidence of recurrent retention. Studies have suggested that administration of an α-adrenergic blocker, such as tamsulosin, at the time of catheter insertion improves the likelihood of spontaneous voiding after catheter removal and may also improve the likelihood that a patient will not require ongoing catheter placement. These medications are associated with an increased risk of orthostatic hypotension, particularly in older adults, so initiation of treatment should be coordinated with the patient’s primary care physician. 5-Alpha-reductase inhibitors, another agent typically used for BPH, have not been shown to reduce the recurrence of AUR. Prophylactic antibiotic therapy is not recommended for patients with AUR. Although bacteriuria often develops in patients with indwelling catheters, it typically is not clinically significant, and the use of prophylactic antibiotics only promotes resistance. Definitive therapy often requires surgical correction of any underlying obstruction. This should not be performed emergently because early surgery is associated with increased morbidity.

Disposition After bladder drainage, healthy and reliable patients can be safely discharged from the ED with an indwelling catheter and urology follow-up. Patients with concomitant infection, significant comorbid illnesses, impaired renal function, neurologic deficits, or complications from catheterization require further diagnosis and treatment and probably admission.

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HEMATURIA Blood in the urine can be microscopic or gross. Although generally associated with a benign process, it can reflect serious underlying pathology, such as a urothelial malignancy. Therefore, following ED assessment, patients with hematuria require outpatient follow-up. Less commonly, patients come to the ED complaining of gross blood in their urine. Compared to microscopic hematuria, gross blood in the urine is more likely to be a presenting symptom of an underlying malignancy. Regardless of age or visibility of blood in the urine, patients with hematuria require evaluation in the ED to rule out life-threatening diagnoses, such as malignancy and AAA. Gross and microscopic hematuria can arise from anywhere along or near the urinary tract. In the upper and lower portions of the urinary tract, infection, trauma, and renal calculi are the most common causative disorders. Patients also can have more serious causes of hematuria, such as malignancy or vascular lesions (eg, AAA), and these diagnoses should be excluded. Up to 5% of patients with asymptomatic microscopic hematuria and up to 30% to 40% of patients with gross hematuria are found to have a urinary tract malignancy. The risk of urologic malignancy is increased in patients older than 35 years, male gender, and those with a history of smoking. Occasionally, hematuria also has been attributed to warfarin use, BPH, and exercise. Supratherapeutic anticoagulant therapy can lead to blood in the urine, but therapeutic anticoagulation does not typically produce spontaneous hematuria. Similarly, BPH can lead to increased vascularity of the prostate but does not increase the risk of hematuria. High-intensity exercise also can produce hematuria. This bleeding typically is transient and clinically inconsequential. Because warfarin use, BPH, and exercise do not directly cause persistent hematuria, patients with ongoing bleeding require further urologic evaluation.

Clinical Features A careful history will often identify a benign cause for hematuria, such as menstruation, recent heavy exercise, recent urologic procedure, sexual activity, and the use of agents that can produce red urine without blood (Box 89.7). Repeated episodes of bleeding during and after menstruation in women suggest endometriosis of the urinary tract. Patients may report frequency, urgency, and dysuria in the setting of infection. They may note flank pain with urolithiasis or pyelonephritis. Microscopic hematuria in the setting of a UTI should resolve after appropriate antibiotic treatment.

BOX 89.7 

Causes of Red-Colored Urine Without Hematuria Phenazopyridine Nitrofurantoin Rifampin Chloroquine Hydroxychloroquine Iodine Bromide Food coloring Beets Berries Rhubarb

The physical examination may point toward the underlying cause. For example, hypertension occurs with glomerulosclerosis and, in the setting of peripheral edema, suggests nephrotic syndrome. An abdominal bruit may be caused by an arteriovenous fistula, whereas a palpable abdominal mass may represent an AAA. Flank pain and tenderness can arise with pyelonephritis or nephrolithiasis. The external genital examination can show evidence of trauma or a tumor and may reveal a rectal or vaginal source for the bleeding. A pelvic examination should be performed in women to identify a vaginal or uterine source of bleeding.

Diagnostic Testing Microscopic hematuria is defined as the presence of three or more RBCs/high-power field (hpf) of urinary sediment. A clean-catch or catheterized urine specimen should be obtained in all patients with hematuria. Catheterization itself induces hematuria in approximately 15% of patients, but the amount of bleeding is inconsequential, rarely exceeding three RBCs/hpf. Bedside urine dipstick testing of this urine should be performed. A negative urine dipstick rules out the presence of hematuria and obviates the need for urine microscopy. If positive for blood, urine microscopy should be performed. As little as 1 mL of whole blood in 1 L of urine can produce gross hematuria, turning the urine red. A number of other substances and reactions can turn the urine red, and centrifugation of the urine and microscopic analysis differentiate these falsepositive results from true hematuria. After centrifugation, the red color persists only in the urine sediment with hematuria. By contrast, a red supernatant that contains no RBCs on microscopic analysis typically represents a benign condition (see Box 89.7). Microscopy will reveal WBCs in addition to RBCs in the presence of infection. Proteinuria, cellular casts, and dysmorphic red blood cells are seen with glomerular disease. Patients with these findings may also have cola-colored urine and should be referred to a nephrologist.

Management and Disposition The combination of a careful history, physical examination, and laboratory studies should identify benign causes of microhematuria such as infection, menstruation, vigorous exercise, and trauma. According to the AUA Guideline on Asymptomatic Microhematuria, once benign causes have been ruled out, a prompt outpatient urologic evaluation should occur.38 This evaluation generally consists of an assessment of renal function (BUN and creatinine levels, calculated GFR) and multiphasic CT urography, including sufficient phases to evaluate the renal parenchyma and urothelium of the upper tracts. CT urography identifies hydronephrosis, urinary calculi, and renal and ureteral lesions. For patients with contraindications to contrasted CT, MR urography is an acceptable alternative imaging approach. Finally, the guidelines recommend that cystoscopy be performed on all patients aged 35 years or older or those with risk factors for urinary tract malignancy, such as tobacco use, exposure to carcinogenic chemicals (eg, aniline dye, benzidine, petroleum products), or history of chronic UTIs. Risk factors for urinary tract malignancy in patients with microscopic hematuria are listed in Box 89.8. For persistent microhematuria following a negative evaluation, yearly urinalyses are recommended, with consideration for a repeat urologic examination every 3 to 5 years. By contrast, patients with gross hematuria require a thorough evaluation before discharge from the ED. Renal function should be assessed to rule out the development of renal insufficiency. The patient should also undergo appropriate imaging tests, although clear consensus is lacking on the appropriate radiographic study.

CHAPTER 89  Selected Urologic Disorders

BOX 89.8 

Risk Factors for Urinary Tract Malignancy Age > 35 yr Past or current cigarette smoking Occupational exposure (chemicals or dyes) Analgesic abuse Chronic indwelling foreign body Chronic urinary tract infection Exposure to known carcinogenic or chemotherapeutic agent Gross hematuria Irritative voiding symptoms Pelvic irradiation Urologic disorder or disease

If the initial assessment fails to identify a benign cause for the hematuria, a CT scan with contrast or renal ultrasound study should be performed. CT scanning is highly sensitive for stones, masses, and other diseases of the upper urinary tract. If contrast CT must be avoided owing to pregnancy, renal insufficiency, or history of anaphylaxis to contrast medium, ultrasound imaging is the modality of choice. Ultrasound is less sensitive than a CT scan for detecting stones, small masses, and traumatic causes of hematuria. CT is the appropriate imaging modality for traumatic hematuria because its sensitivity and specificity exceed those of ultrasound. The exact level of hematuria that should trigger imaging is unclear, but it appears that patients without gross hematuria or evidence of coexisting abdominal or pelvic injuries are unlikely to have clinically significant injuries on CT (see Chapter 40).

KEY CONCEPTS • Urinary obstruction should be ruled out in patients with a urinary tract infection (UTI) and those in septic shock. • Acute, uncomplicated urinary tract infections should be treated with fosfomycin, nitrofurantoin, or trimethoprim-sulfamethoxazole. • Fluoroquinolones are not recommended as first-line therapy for uncomplicated UTI. • The three primary predictors of stone passage without the need for surgical intervention are calculus size, location, and degree of patient pain. The most important factor that relates to passage of a calculus though the genitourinary tract is its size (stone 5.0 cm), either secondary to benign neoplasm or cysts, as seen in ovulation induction, hyperstimulation syndrome, or polycystic ovarian syndrome. In premenarchal patients, however, torsion frequently occurs despite normal ovarian size, thought to be secondary to the excessive mobility of the adnexa relative to older patients.4 Masses prone to creating adhesions, such as malignant tumors, endometriomas, or tubo-ovarian abscesses, are less likely to develop torsion than benign lesions. Torsion may be a complication of pregnancy, more likely to occur in the first and early second trimesters.5 A history of tubal ligation is a risk factor for ovarian torsion.6 A slight predominance of torsion on the right side has been noted, likely related to the stabilizing effect of the fixed sigmoid colon on the left.

Clinical Features The classic symptoms of ovarian torsion are severe, sharp, unilateral lower abdominal pain and nausea; however, some or all of these symptoms are often absent. Despite advances in imaging modalities, the preoperative diagnosis rate only approaches 40%, 1232

Diagnostic Testing Laboratory Tests No specific laboratory tests are routinely used in the diagnosis of suspected torsion. Two small studies on serum interleukin-6, a proinflammatory cytokine, have revealed a pooled sensitivity of 85% and specificity of 84% for torsion and may evolve into a useful serum marker if reproduced by larger trials.10 A negative pregnancy test may exclude ectopic pregnancy from the differential, but a positive test does not rule out adnexal torsion. Leukocytosis is not a reliable indicator of torsion.

Imaging Ultrasonography.  An ultrasound examination is the initial imaging test in the evaluation of patients with pelvic pain suggestive of ovarian torsion, but findings can vary depending on timing and duration of symptoms. Asymmetric enlargement of the ovary is the most common finding. Enlargement of an ovary with a heterogeneous stroma secondary to edema along with small, peripherally displaced follicles is the classic ultrasound appearance of torsion but is often absent, particularly with long-standing ischemia.11 Ultrasound may reveal a mass in the ovary, evidence of hemorrhage, or free pelvic fluid (Fig. 90.2). Hemorrhagic cysts and other nonneoplastic masses frequently are associated with torsion; these may appear fluid-filled, exhibit a complex pattern with debris and septations, or be visualized as a solid mass. The characteristic appearance of torsion may be difficult to appreciate if the ovary is obscured by an associated mass. In isolated tubal

CHAPTER 90  Selected Gynecologic Disorders

a

b

d

e

c

Broad ligament

Fig. 90.3.  Ovarian torsion with color Doppler image demonstrating venous and arterial flow. (From Cicchiello LA, Hamper UM, Scoutt LM. Ultrasound evaluation of gynecologic causes of pelvic pain. Obstet Gynecol Clin North Am 38:85–114, 2011.) Fig. 90.1.  Ovarian blood supply. a, Ovarian artery and vein. b, Branching arterioles supplying ovary. c, Utero-ovarian ligament. d, Utero-ovarian ligament. e, Infundibulopelvic ligament. (From Andreotti RF, Shadinger L, Fleischer A: The sonographic diagnosis of ovarian torsion: pearls and pitfalls. Ultrasound Clin 2:155, 2007.)

Fig. 90.2.  Ovarian torsion with a large pelvic mass. This transabdominal image reveals a largely homogeneous 22.8-cm pelvic mass. (From Cicchiello LA, Hamper UM, Scoutt LM: Ultrasound evaluation of gynecologic causes of pelvic pain. Obstet Gynecol Clin North Am 38:85–114, 2011.)

torsion, tubal lesions such as hydrosalpinx or a tubo-ovarian abscess may be seen. Doppler ultrasound findings are inconsistent for diagnosing ovarian torsion. Up to 60% of surgically proven torsion will have documented blood flow on Doppler examination (Fig. 90.3).3 Findings may vary depending on the time of the examination because torsion may occur intermittently, and clinical symptoms may precede arterial compromise. If a large mass is present, the examination may also be technically difficult to perform. Despite these limitations, the Doppler examination is still useful, and detection of abnormal venous flow is particularly important in early cases of torsion (Fig. 90.4). Absence of arterial flow is highly specific for torsion, with a positive predictive value of 94% to 100%.3 Visualization of the twisting of the pedicle and coiled vessels is referred to as a whirlpool sign and has a 90% positive predictive value for torsion.12

Computed Tomography.  When alternative abdominal pathologies are strong considerations in the differential diagnosis for acute pelvic pain, abdominopelvic CT may be the best initial study, particularly in patients who have a presentation atypical for torsion. In ovarian torsion, CT findings include asymmetric ovarian enlargement or asymmetric adnexal enhancement following IV contrast, fallopian tube thickening, or twisted vascular pedicle, fat stranding surrounding the affected adnexa, and uterine deviation to the twisted side.3 Pelvic free fluid in patients with a hemorrhagic infarction can be seen. A retrospective review of CT scans of patients with confirmed torsion has found that every CT scan had evidence of an ovarian abnormality, including enlargement or the presence of a mass, suggesting that torsion is unlikely if the CT visualized a normal ovary; another, more recent casecontrolled study comparing pelvic ultrasound to CT has confirmed these findings.13 Therefore, negative imaging findings should be interpreted with caution when clinical suspicion is high but, with lower suspicion, a normal-appearing ovary on the CT scan can be reassuring. Magnetic Resonance Imaging.  Magnetic resonance imaging (MRI) may demonstrate findings consistent with torsion. It is particularly helpful if the diagnosis is not clear, such as with intermittent pain over days, or for pregnant patients when the history is highly suggestive but ultrasound findings are inconclusive or equivocal. Findings on MRI suggestive of torsion are similar to those on CT (Box 90.1). Laparoscopy.  A diagnostic laparoscopy is the gold standard investigative modality in patients in whom clinical suspicion is high, despite negative imaging results. In one study of 100 nonpregnant patients with an acute abdomen, only 29 of the 66 laparoscopically proven cases of ovarian torsion were diagnosed preoperatively.14 Laparoscopy also allowed diagnosis of other unsuspected conditions, including ovarian cysts, appendicitis, and pelvic inflammatory disease.

Management and Disposition Once the diagnosis of ovarian torsion has been made, the patient should be taken to the operating room as soon as possible. The ovary often will recover, even if black or dusky in appearance at the time of surgery, because of its dual blood supply, so attempts at ovarian salvage are warranted, even if the diagnosis is made late. This is particularly true in adolescent patients. Ovarian function returns in most patients.

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A

B

C Fig. 90.4.  Arterial Doppler signal without venous signal in a patient with surgically proven torsion. The ultrasound examination also demonstrated an associated hemorrhagic cyst. (From Andreotti RF, Shadinger L, Fleischer A: The sonographic diagnosis of ovarian torsion: pearls and pitfalls. Ultrasound Clin 2:155, 2007.)

BOX 90.1 

OVARIAN CYSTS AND MASSES

Imaging Characteristics of Adnexal Torsion

Principles

ULTRASONOGRAPHY

Enlargement of the ovary Associated ovarian mass Loss of enhancement Edema Free pelvic fluid Loss of venous waveforms Loss of arterial waveforms

COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING Enlargement of the ovary Associated ovarian mass Thickening of the fallopian tube Free pelvic fluid Edema of the ovary Deviation of the uterus to the affected side Associated hemorrhage

Cysts are the most common cause of gynecologic masses. They occur at any stage of life but are most frequent in the reproductive years because of the cyclic changes of the ovary associated with menstruation (Fig. 90.5). Most ovarian cysts in premenopausal and postmenopausal women are benign and resolve with no intervention, but on occasion they may be malignant or associated with complications such as hemorrhage or torsion.15,16 Benign cysts are less common in premenarchal girls, however, with an incidence of malignancy as high as 25% when an adnexal mass is found.17 The most common type of cyst is a simple follicular, or functional cyst, developing from a follicle that fails to rupture or regress, and is defined as pathologic when the diameter exceeds 3.0 cm. Follicular cysts are typically thin-walled and filled with clear fluid, whereas a corpus luteal cyst is often filled with hemorrhagic fluid. Several other types of cystic masses can occur in the ovary, including endometriomas (chocolate cysts), nonneoplastic lesions such as benign cystic teratoma (dermoid cyst), fibroma, cystadenoma, and various types of malignant neoplasms.18

Clinical Features The most common presentation for patients with an ovarian cyst is pelvic pain. Rupture of a follicular cyst may produce transient

CHAPTER 90  Selected Gynecologic Disorders

Luteal phase Corpus luteum

Ovulation

Blood supply

Germinal epithelium Primordial follicles

Mature graafian follicle Follicular phase

Fig. 90.5.  Ovarian function during the normal menstrual cycle. (From Lambert MJ, Villa M: Gynecologic ultrasound in emergency medicine. Emerg Med Clin North Am 22:683–696, 2004.)

pelvic pain, be associated with dyspareunia, or be asymptomatic. Because of its thin fragile wall, a follicular cyst may rupture during sexual intercourse or during the pelvic examination. Follicular cysts are rarely associated with hemorrhage. Presentation of a corpus luteal cyst may range from an asymptomatic mass to dull, chronic pelvic pain to severe pain associated with rupture. Rupture of a corpus luteal cyst is frequently associated with a significant degree of hemorrhage. As with a follicular cyst, rupture may follow a pelvic examination, sexual intercourse, exercise, or trauma. Rupture of a large or complex cyst may result in severe pain and peritoneal signs. Occasionally, a large cyst may be discovered on a routine pelvic examination as an asymptomatic mass, but this is uncommon.

Differential Diagnosis Diagnostic considerations in the patient with ovarian cysts and masses include other causes of pelvic pain that require urgent intervention, such as ectopic pregnancy, pelvic inflammatory disease, urinary tract infections, nephrolithiasis, appendicitis, and diverticulitis. Tumors or abscesses of the gastrointestinal tract may also mimic adnexal masses.

Diagnostic Testing

Fig. 90.6.  Endovaginal ultrasound image of a normal ovary with a dominant follicle (arrows). (From Lambert MJ, Villa M: Gynecologic ultrasound in emergency medicine. Emerg Med Clin North Am 22: 683–696, 2004.)

Laboratory Tests The initial step in the evaluation of pelvic pain or a pelvic mass is to exclude pregnancy with a urine or serum β-human chorionic gonadotropin (β-hCG) test. A hematocrit may be valuable in the unstable patient as a marker of blood loss. The serum antigen CA-125 is elevated in 80% of women with epithelial ovarian cancer but can also be elevated by nonmalignant conditions such as endometriosis, pregnancy, and pelvic inflammatory disorder, limiting its usefulness in the emergency setting.19

Imaging Ultrasonography.  Ultrasonography is the standard initial imaging modality used to diagnose and characterize all ovarian pathologic processes and lesions, including cysts and masses. Approximately 90% of adnexal masses are adequately charac­

terized by ultrasound imaging alone.20 Transabdominal and endovaginal examinations provide useful information. The transabdominal approach should be performed with a full bladder as a sonographic window. It permits an overall view of the pelvis and will visualize large masses and pelvic free fluid. Use of the endovaginal probe, which should be performed with an empty bladder to reduce artifact, provides a detailed picture of the ovary. Follicles are part of the normal architecture of the ovary and are typically smaller than 1.0 cm in diameter, whereas the dominant follicle may measure up to 2.5 cm at the time of ovulation. Depending on the timing of the scan and degree of clot formation and lysis, hemorrhage may be seen. Fig. 90.6 demonstrates a normal ovary with a dominant follicle, Fig. 90.7 demonstrates a large cyst, and Fig. 90.8 demonstrates hemorrhage and free pelvic fluid. Ultrasound findings suggestive of malignancy include internal

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septations, solid elements within cystic structures, a thickened wall, and large amounts of ascites or free fluid. Computed Tomography.  When the differential diagnosis of unilateral pelvic pain is broad, particularly in the patient with symptoms or physical findings not solely confined to the pelvis, a CT scan may be a more appropriate initial imaging study. It is not recommended as the first-line imaging study if an adnexal mass is of primary concern due to poor soft tissue discrimination.21 Once the diagnosis of malignancy has been made, however, ultrasound is insensitive for staging or follow-up imaging, and contrastenhanced CT is indicated at that time. A CT scan can detect a cyst and associated complications, including torsion, as noted earlier. CT findings suggestive of malignancy are a cystic solid mass, necrosis in a solid lesion, complex or cystic lesion with thick, irregular walls, and the presence of ascites, peritoneal metastases, and lymphadenopathy. Magnetic Resonance Imaging.  MRI provides better soft tissue contrast as compared with CT and has been shown in multiple studies to differentiate benign from malignant adnexal

masses better as compared with ultrasound. It is limited by availability, cost, and duration of examination. MRI should be considered for pregnant patients or those with equivocal findings on ultrasound or CT.

Management and Disposition Patients with a simple cyst and improvement in symptoms may be safely discharged with referral for outpatient gynecologic follow-up to ensure resolution of the cyst. Most uncomplicated simple cysts will resolve without further intervention. Pain should be controlled with nonsteroidal antiinflammatory drugs (NSAIDs) as a first-line approach and with oral opioids reserved only for severe cases. Oral contraceptives are not recommended for the routine management of ovarian cysts; despite being theorized to accelerate the regression of ovarian cysts, multiple randomized controlled trials have shown no difference in cyst resolution when compared to expectant management.22 A complex cyst concerning for malignancy requires more urgent gynecologic intervention. Such patients may benefit from gynecologic consultation in the ED, particularly if reliable follow-up is unlikely or if the patient is particularly symptomatic.

ABNORMAL UTERINE BLEEDING IN THE NONPREGNANT PATIENT Principles

Fig. 90.7.  Endovaginal ultrasound image of a follicular cyst, with smooth wall and posterior wall enhancement. (From Cicchiello LA, Hamper UM, Scoutt LM: Ultrasound evaluation of gynecologic causes of pelvic pain. Obstet Gynecol Clin North Am. 38:85–114, 2011.)

A

An understanding of the normal menstrual cycle is needed to understand the potential causes of abnormal uterine bleeding (Fig 90.9). The menstrual cycle starts on the first day of menses. During the first part of the menstrual cycle, the endometrium thickens under the influence of estrogen, and a dominant follicle develops in the ovary, releasing an ovum at the midpoint of the cycle. After ovulation, the luteal phase begins and is characterized by the production of progesterone from the corpus luteum. Progesterone matures the lining of the uterus and, if implantation does not occur, the corpus luteum dies, accompanied by sharp drops in progesterone and estrogen levels. These changes typically are followed by menstruation. Menstrual bleeding is usually predictable, cyclic, and results from withdrawal of the effects of hormones on the endometrium, which occurs approximately 14 days after ovulation. A revised system of terminology, PALM-COEIN, regarding abnormal uterine bleeding (AUB) was created in 2011 by the International Federation of Gynecology and Obstetrics (FIGO) to

B Fig. 90.8.  Endovaginal ultrasound image of a hemorrhagic ovarian cyst with free fluid (*). (From Cicchiello LA, Hamper UM, Scoutt LM: Ultrasound evaluation of gynecologic causes of pelvic pain. Obstet Gynecol Clin North Am. 38:85–114, 2011.)

Ovarian histology

CHAPTER 90  Selected Gynecologic Disorders

BOX 90.2  Recruited follicle

Maturing follicle

Ovulation

Corpus luteum

Degenerate c. luteum

PALM—STRUCTURAL CAUSES Polyp (AUB-P)

37°C Body temperature Estradiol

Progesterone Luteinizing hormone

Follicle-stimulating hormone

Adenomyosis (AUB-A) Leiomyoma (AUB-L) Submucosal leiomyoma (AUB-LSM) Other leiomyoma (AUB-LO) Malignancy and hyperplasia (AUB-M)

COEIN—NONSTRUCTURAL CAUSES

Follicular phase

Endometrial histology

Menstruation

1

3 2

5 4

7 6

9 8

Ovulation

Hormones

36°C

PALM-COEIN Classification for Abnormal Uterine Bleeding (AUB)

Luteal phase

11 13 15 17 19 21 23 25 27 10 12 14 16 18 20 22 24 26 28 Day of menstrual cycle

(Average values. Durations and values may differ between different females or different cycles.) Fig. 90.9.  Normal menstrual cycle.

standardize language and facilitate multiinstitutional investigation (Box 90.2).23 The first four letters. PALM, represent structural causes for AUB—polyp, adenomyosis, leiomyoma, and malignancy or hyperplasia, whereas the last five letters, COEIN, represent nonstructural causes—coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified. The term dysfunctional uterine bleeding is no longer used.24 Disruption of the hypothalamic-pituitary-ovarian axis from a variety of causes can result in bleeding related to ovulatory dysfunction (AUB-O). Returning the balance of estrogen and progesterone with oral contraceptives will help many patients regulate the cycle, with reduction in or cessation of abnormal uterine bleeding.25

Clinical Features History A large number of conditions cause abnormal uterine bleeding, and a systematic history and physical examination can help narrow the possibilities. Vaginal bleeding before the age of menarche is abnormal and may be the result of infection, trauma, such as sexual abuse or a foreign body, or a structural lesion.26 In a woman of reproductive age, abnormal uterine bleeding includes a change in the frequency, duration or amount of bleeding, or bleeding between menstrual cycles. In the postmenopausal woman, any bleeding 12 months after the cessation of menses or unpredictable bleeding during hormone therapy is abnormal. The amount and frequency of bleeding and the duration of symptoms, as well as the relationship to the menstrual cycle, should be

Coagulopathy (AUB-C) Ovulatory Dysfunction (AUB-O) Endometrial (AUB-E) Iatrogenic (AUB-I) Not yet classified (AUB-N)

established. A menstrual cycle shorter than 21 days in duration or more than 35 days apart, or flow for less than 2 or more than 7 days, is classified as abnormal. A pattern of irregular bleeding between cycles or an abrupt change in the previous pattern of bleeding should also be determined. Systemic conditions, such as liver or thyroid disease, may be associated with abnormal uterine bleeding. Endometrial cancer is associated with underlying diabetes mellitus, metabolic syndrome and obesity, anovulatory cycles, nulliparity, and age older than 55 years. Cervical dysplasia or other genital tract pathology may cause postcoital or irregular bleeding, and patients should be questioned on risk factors for sexually transmitted infections. Prior history of cesarean section may contribute to iatrogenic AUB; studies have found that irregular scarring postoperatively leads to a higher prevalence of vaginal spotting.27 Disruption along the hypothalamus-pituitary-ovarian pathway leading to anovulation is frequently the cause of AUB. Disruption of this pathway may be physiologic, such as during adolescence, perimenopause, or lactation. Pathologic causes include polycystic ovary syndrome (PCOS), hypothalamic dysfunction seen in anorexia nervosa, hyperprolactinemia, and primary pituitary disease. Patients should be questioned about excessive bleeding or bruising or any family history of bleeding disorders because up to 20% of women presenting with heavy menstrual bleeding will have an underlying coagulopathy.28 Von Willebrand disease is the most common of these, seen in up to 13% of cases of AUB, and often first presents with heavy uterine bleeding since menarche.29

Physical Examination With prolonged heavy bleeding, signs of chronic anemia may be noted on the physical examination. PCOS is a common cause of abnormal uterine bleeding, and physical findings suggestive of such include obesity, acne, hirsutism, and acanthosis nigricans. Other causes of bleeding include vaginal or cervical lesions, which may be visible on the speculum examination. A leiomyoma or fibroid uterus may be palpable on the bimanual examination.

Differential Diagnosis The cause of abnormal uterine bleeding in the nonpregnant patient is extensive but may be narrowed by age. In adolescents, consider undiagnosed coagulopathy, pelvic infection, or

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hypothalamic-pituitary-ovarian axis dysregulation due to physiologic immaturity or PCOS. Patients older than adolescent age should be considered for structural lesions such as polyps or leiomyomas, endometrial hyperplasia, or anovulation secondary to PCOS or other conditions listed above. In patients older than 40 years but not yet postmenopausal, anovulatory bleeding due to perimenopause becomes more likely, as does endometrial carcinoma or hyperplasia and leiomyoma. Postmenopausal patients require an evaluation for malignancy.

Diagnostic Strategies Laboratory Studies In evaluating a woman of reproductive age with vaginal bleeding, a urine or serum pregnancy test is the most essential laboratory test. In a patient with excessive bleeding, hemodynamic instability, or clinical evidence of anemia (eg, excessive fatigue, pale conjunctiva), a hemoglobin or hematocrit test may be helpful. If coagulopathy is suspected, platelet count, prothrombin and partial thromboplastin time should be measured. Chlamydia trachomatis testing is indicated in patients at risk of infection. Thyroid dysfunction, particularly hypothyroidism, is associated with AUB, and therefore screening to determine the thyroid-stimulating hormone serum level is recommended.

Imaging The decision to perform ultrasound imaging in the ED depends on the urgency to determine the cause of bleeding and on the reliability of outpatient follow-up. Transvaginal ultrasonography (TVUS) may reveal a fibroid uterus, endometrial thickening, or a focal mass (Fig. 90.10). In postmenopausal patients with AUB, an endometrium measuring less than 4 to 5 mm thick on TVUS reliably excludes endometrial cancer. A thickened endometrium may indicate an underlying lesion or excess estrogen. For most nonpregnant patients with AUB, ultrasound findings do not immediately affect ED decision making. In patients who have access to gynecologic services, imaging may be deferred until follow-up evaluation with the gynecologist.

Fig. 90.10.  Longitudinal view of the uterus with thickened endometrium. (Courtesy Dr. Robert Reardon, Hennepin County Medical Center, Minneapolis; with permission.)

Management The likely causative disorder, as well as the amount of bleeding and stability of the patient, will guide ED management. NSAIDs are generally effective for relief of associated cramping pelvic pain.30 For anovulatory bleeding, combination oral contraceptive pills can help regulate the cycle and also counteract the long-term effects of unopposed estrogen on the endometrium. We recommend a combination oral contraceptive with 35 µg of ethinyl estradiol or 20 mg or medroxyprogesterone tid for 1 week. Contraindications must be reviewed with the patient prior to prescribing these medications, specifically to determine a history of deep vein thrombosis or pulmonary embolus, cigarette smoking, breast cancer, or liver disease. Oral tranexamic acid, a prothrombotic agent, may also be used for outpatient management of bleeding. The dose is 1.3 g orally every 8 hours for 5 days. Rarely, a patient will have uncontrolled bleeding and signs of blood loss on presentation, in which case they should receive resuscitation with blood products, as is done for other types of hemorrhagic shock. In these patients, surgical options should be considered, including urgent dilation and curettage, uterine artery embolization, or hysterectomy. Alternatively, intravenous conjugated equine estrogen may be used and was shown in one randomized controlled trial to stop bleeding in 72% of study participants in 8 hours compared to 38% treated with placebo.25 The dose is 25 mg intravenously every 4 to 6 hours for 24 hours or until the bleeding stops.

Disposition Most patients with pelvic pain from ovarian cysts or abnormal uterine bleeding without hemodynamic compromise may be managed with specific therapies to minimize symptoms and should be referred to a gynecologist for definitive management on an outpatient basis. Patients with severe, acute abnormal uterine bleeding and hemodynamic instability require urgent gynecologic consultation and hospitalization.

EMERGENCY CONTRACEPTION Emergency contraception, also commonly known as the morning after pill, consists of therapy to prevent pregnancy after unprotected or inadequately protected sexual intercourse. At present, there are three oral formulations available globally—ulipristal acetate, a progesterone receptor modulator, levonorgestrel, and combined oral contraceptives consisting of progestin and estrogen. The most commonly used regimen, and the only formulation available without a prescription in the United States, consists of a single dose of 1.5 mg or two doses of 0.75 mg levonorgestrel spaced 12 hours apart. The one-time dose is simpler to use and is at least as effective as the two-dose regimen.31 It is labeled for use for up to 72 hours from intercourse. Another regimen, a single tablet of 30 mg of ulipristal acetate, is only available with a prescription and has demonstrated effectiveness for up to 120 hours from intercourse, making it a preferred choice over levonorgestrel beyond the 72-hour window.32 Both forms of contraception are maximally effective when used within 24 hours.33 Combined oral contraceptives, also known as the Yuzpe method, has largely fallen out of favor due to the simplicity and success of levonorgestrel. Adverse effects of oral emergency contraception include nausea and headache, with combined oral contraceptives producing significantly higher rates of nausea than levonorgestrel or ulipristal alone. Irregular menstrual bleeding, which can occur within 1 week to 1 month after treatment, resolves without intervention. In addition to oral emergency contraception, the copper intrauterine device (IUD) is highly effective when placed within 5 days

CHAPTER 90  Selected Gynecologic Disorders

of intercourse and appears to be effective for as long as 10 days.34 The copper IUD carries a 1/1000 risk of uterine perforation and is associated with uterine cramping, but also provides ongoing contraceptive benefit. Both levonorgestrel and ulipristal act to delay or inhibit ovulation, whereas whereas the copper IUD prevents fertilization. As such, a common misconception is that emergency contraception is equivalent to medical abortion. None of the methods discussed involve the termination of a preexisting pregnancy, and

emergency contraception has not been shown to have any adverse effects on a developing fetus when taken during an established pregnancy. It is still possible for a patient who uses emergency contraception to get pregnant in the same menstrual cycle, so she should be advised to use an alternative form of contraception and to undergo a pregnancy test if menstruation is delayed for more than 3 weeks. Patients who receive emergency contraception should be counseled regarding birth control and have a follow-up pregnancy test should they miss their next period.

KEY CONCEPTS • Ovarian torsion is easily missed on initial presentation, and diagnosis cannot rely on radiologic findings alone. Doppler ultrasound is the optimal imaging study; absence of arterial flow, although not always present, is highly specific for torsion. Torsion should be a consideration in any patient with known risk factors, even if symptoms are subtle or atypical. • An ultrasound examination may distinguish among the various types of ovarian cysts and identify associated complications, such as torsion, hemorrhage, and malignancy. Most ovarian cysts are simple follicular cysts that resolve without pharmacologic or surgical intervention.

• Abnormal uterine bleeding has many structural, hormonal, and coagulopathic causes. Selected imaging and laboratory testing, based on a careful history and physical examination, can often lead to determination of the cause. Combined oral contraceptive pills can help regulate the cycle and alleviate AUB. • Emergency contraception is a safe effective option to prevent an undesired pregnancy. Levonorgestrel and ulipristal are both effective oral medications and are associated with fewer side effects than the traditional combined contraceptive method.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Sasaki KJ, Miller CE: Adnexal torsion: review of the literature. J Minim Invasive Gynecol 21:196–202, 2014. 2. Casey RK, Damle LF, Gomez-Lobo V: Isolated fallopian tube torsion in pediatric and adolescent females: a retrospective review of 15 cases at a single institution. J Pediatr Adolesc Gynecol 26:189–192, 2013. 3. Lourenco AP, Swenson D, Tubbs RJ, et al: Ovarian and tubal torsion: imaging findings on US, CT, and MRI. Emerg Radiol 21:179–187, 2014. 4. Tsafrir Z, Azem F, Hasson J, et al: Risk factors, symptoms, and treatment of ovarian torsion in children: the twelve-year experience of one center. J Minim Invasive Gynecol 19:29–33, 2012. 5. Hasson J, Tsafrir Z, Azem F, et al: Comparison of adnexal torsion between pregnant and nonpregnant women. Am J Obstet Gynecol 202:536.e1–536.e6,2010. 6. Asfour V, Varma R, Menon P: Clinical risk factors for ovarian torsion. J Obstet Gynaecol 35:721–725, 2015. 7. King A, Keswani S, Biesiada J, et al: The utility of a composite index for the evaluation of ovarian torsion. Eur J Pediatr Surg 24:136–140, 2014. 8. Huchon C, Staraci S, Fauconnier A: Adnexal torsion: a predictive score for preoperative diagnosis. Hum Reprod 25:2276–2280, 2010. 9. Huchon C, Panel P, Kayem G, et al: Does this woman have adnexal torsion? Hum Reprod 27:2359–2364, 2012. 10. Christopoulos G, Goubet S, Kelly T: Interleukin-6 for the diagnosis of ovarian torsion: a systematic review and meta-analysis. J Obstet Gynaecol 33:438–441, 2013. 11. Dupuis CS, Kim YH: Ultrasonography of adnexal causes of acute pelvic pain in premenopausal non-pregnant women. Ultrasonography 34:258–267, 2015. 12. Valsky DV, Esh-Broder E, Cohen SM, et al: Added value of the gray-scale whirlpool sign in the diagnosis of adnexal torsion. Ultrasound Obstet Gynecol 36:630–634, 2010. 13. Swenson DW, Lourenco AP, Beaudoin FL, et al: Ovarian torsion:case-control study comparing the sensitivity and specificity of ultrasonography and computed tomography for diagnosis in the emergency department. Eur J Radiol 83:733–738, 2014. 14. Bar-On S, Mashiach R, Stockheim D, et al: Emergency laparoscopy for suspected ovarian torsion: are we too hasty to operate? Fertil Steril 93:2012–2015, 2010. 15. Hall TR, Randall TC: Adnexal masses in the premenopausal patient. Clin Obstet Gynecol 58:47–52, 2015. 16. Rauh-Hain JA, Melamed A, Buskwofie A, et al: Adnexal mass in the postmenopausal patient. Clin Obstet Gynecol 58:53–65, 2015. 17. Oltmann SC, Garcia N, Barber R, et al: Can we preoperatively risk stratify ovarian masses for malignancy? J Pediatr Surg 45:130–134, 2010. 18. Bennett JA, Oliva E: Pathology of the adnexal mass. Clin Obstet Gynecol 58:3–27, 2015.

19. Liu JH, Zanotti KM: Management of the adnexal mass. Obstet Gynecol 117:1413– 1428, 2011. 20. Brown DL, Dudiak KM, Laing FC: Adnexal masses: US characterization and reporting. Radiology 254:342–354, 2010. 21. Perera DS, Prabhakar HB: Imaging of the adnexal mass. Clin Obstet Gynecol 58:28– 46, 2015. 22. Grimes DA, Jones LB, Lopez LM, et al: Oral contraceptives for functional ovarian cysts. Cochrane Database Syst Rev (4):CD006134, 2014. 23. Munro MG, Critchley HO, Broder MS, et al: FIGO classification system (PALMCOEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 113:3–13, 2011. 24. Committee on Practice Bulletins—Gynecology: Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 120:197– 206, 2012. 25. Committee on Practice Bulletins—Gynecology: Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol 122:176–185, 2013. 26. Borhart J: Emergency department management of vaginal bleeding in the nonpregnant patient. Emerg Med Pract 15:1–20, 2013. 27. van der Voet LF, Bij de Vaate AM, Veersema S, et al: Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding. BJOG 121:236–244, 2014. 28. Committee on Practice Bulletins—Gynecology: Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 120:197– 206, 2012. 29. Committee on Adolescent Health Care; Committee on Gynecologic Practice: Committee Opinion No. 580: von Willebrand disease in women. Obstet Gynecol 122:1368–1373, 2013. 30. Bradley LD, Gueye NA: The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol 214:31–44, 2016. 31. Practice bulletin no. 152: emergency contraception. Obstet Gynecol 126:e1–e11, 2015. 32. Glasier AF, Cameron ST, Fine PM, et al: Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 375:555–562, 2010. 33. Committee on Health Care for Underserved Women: ACOG Committee Opinion Number 542: access to emergency contraception. Obstet Gynecol 120:1250–1253, 2012. 34. Turok DK, Godfrey EM, Wojdyla D, et al: Copper T380 intrauterine device for emergency contraception: highly effective at any time in the menstrual cycle. Hum Reprod 28:2672–2676, 2013.

CHAPTER 90: QUESTIONS & ANSWERS 90.1. Which of the following statements regarding ovarian torsion is true? A. Abdominal tenderness is predictable. B. Complete arterial obstruction is common. C. Computed tomography (CT) has a higher sensitivity than ultrasound. D. Most cases are associated with an ovarian mass. E. There is a left-sided predominance. Answer: D. Most cases are associated with a benign ovarian tumor or cyst. There is a modest right-sided predominance. Due to the collateral uterine and ovarian arterial supply, complete arterial obstruction is rare. In cases of intermittent or chronic torsion particularly, abdominal tenderness may be absent. CT has a lower sensitivity than ultrasound, which is still only approximately 71%. Interpret negative studies carefully. 90.2. Which of the following patterns of menses should be considered abnormal? A. A 23-day menstrual cycle B. A 40-day menstrual cycle C. Bleeding 6 months after menopause D. Seven days of menstrual flow E. Three days of menstrual flow Answer: B. A menstrual cycle shorter than 21 days or more than 35 days apart, or flow that is less than 2 days or more than 7 days, is considered abnormal. In the postmenopausal woman, any bleeding 12 months after cessation of menses is considered abnormal.

90.3. A 33-year-old G3P3 woman presents with 7 days of heavy but painless vaginal bleeding. Her only other complaint is dizziness. Urine pregnancy test is negative. Vital signs are blood pressure, 85/40 mm Hg, and heart rate, 130 beats/ min. The pelvic examination reveals copious vaginal bleeding through a partially open cervical os. The hemoglobin level is 6.8 g/dL. Which of the following is the most appropriate intervention? A. 20 µg of ethinyl estradiol daily until the bleeding subsides B. 35 µg ethinyl estradiol bid until the bleeding subsides C. Blood transfusion and urgent gynecologic consultation for dilation and curettage D. Premarin, 25 mg IV every 6 hours E. Saline hydration followed by a 2-day recheck Answer: C. This patient is symptomatic, hypovolemic, anemic, and exhibiting ongoing bleeding. Oral estrogens are indicated in cases of modest bleeding. Parenteral estrogen may be used as an adjunct to other therapies for patients requiring admission. The degree of anemia in the face of ongoing bleeding in this case warrants gynecologic intervention. 90.4. To be most effective, the emergency contraceptive ulipristal should be given as soon as possible but is approved to be given within how many hours of intercourse? A. 12 B. 24

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C. 48 D. 72 E. 120 Answer: E. The efficacy of all emergency contraceptive pills in preventing pregnancy is greatest when a contraceptive is taken

soon after intercourse. Ulipristal is labeled for 120 hours postcoitus. Because it is not as effective as preplanned contraception, women should still be aware of the possibility of pregnancy after its use.

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Neurology C H A P T E R 91 

Stroke Todd J. Crocco  |  William J. Meurer PRINCIPLES Background Stroke is the fifth leading cause of death in the United States and a leading cause of long-term disability.1 It affects about 795,000 people per year. On average, someone has a stroke every 40 seconds, and someone dies of a stroke every 4 minutes.2 Stroke patients have an in-hospital mortality rate of 5% to 10% for ischemic stroke and 40% to 60% for intracerebral hemorrhage (ICH).3 Only 10% of stroke survivors will recover completely, making stroke a leading cause of adult disability. Stroke can be defined as any vascular injury that reduces cerebral blood flow (CBF) to a specific region of the brain, retina, or spinal cord, causing neurologic impairment. The onset of symptoms may be sudden or stuttering, often with transient or permanent loss of neurologic function. Approximately 87% of all strokes are ischemic in origin, caused by the occlusion of a cerebral vessel. Approximately 13% are hemorrhagic strokes caused by the rupture of a blood vessel into the parenchyma of the brain (ICH) or into the subarachnoid space (subarachnoid hemorrhage [SAH]). Only ischemic stroke involving the brain and ICH are discussed in this chapter. SAH is discussed in Chapter 93. Prior to the reperfusion era, treatment for stroke was not focused on reversal of damage and consisted of stabilization, observation, and rehabilitation. Current acute interventional treatment regimens are designed to reverse or minimize brain damage.4 Strategies include blood pressure (BP) management, anticoagulation, thrombolytic therapy, catheter-based interventions, and surgery.

Epidemiology Ischemic Stroke An estimated 610,000 “first-ever” ischemic strokes occur each year in the United States. These may result from either in situ thrombosis or embolic obstruction from a more proximal source, usually the heart. In more than one-third of these first-ever strokes, no clear cause is identified. Strokes of all subtypes are more common in African American and Hispanics versus nonHispanic whites. Approximately one-third of all ischemic strokes are thrombotic in nature. These can be caused by either large- or smallvessel occlusions. Common areas for large-vessel occlusions are cerebral vessel branch points, especially in the distribution of the internal carotid artery. Thrombosis usually results from clot formation in the area of an ulcerated atherosclerotic plaque that forms in the area of turbulent blood flow, such as a vessel

bifurcation. A marked reduction in flow results when the stenosis occludes more than 90% of the blood vessel diameter. With further ulceration and thrombosis, platelets adhere to the region. A clot then either embolizes or occludes the artery. Lacunae, or small-vessel strokes, involve small terminal sections of the vasculature and more commonly occur in patients with diabetes and hypertension. A history of hypertension is present in 80% to 90% of patients who experience lacunar strokes. The subcortical areas of the cerebrum and brainstem often are involved. The infarcts range in size from a few millimeters to 2 cm and are seen most commonly in the basal ganglia, thalamus, pons, and internal capsule. They may be caused by small emboli or by a process termed lipohyalinosis, which occurs in patients with hypertensive cerebral vasculopathy. One-fourth of all ischemic strokes are cardioembolic in nature. Embolization of a mural thrombus in patients with atrial fibrillation is the most common mechanism, and patients with atrial fibrillation have an approximate fivefold increased risk for development of a stroke. Noncardiac sources of emboli may include diseased portions of extracranial arteries, resulting in an arteryto-artery embolus. One common example is amaurosis fugax, in which emboli from a proximal carotid artery plaque embolizes to the ophthalmic artery, causing transient monocular blindness. Although stroke risk increases with age, approximately 3% to 4% of all strokes occur in patients 15 to 45 years old, and there have been trends observed showing the average age of first stroke is becoming younger.5 Although atherosclerosis is the most common cause in elders, causative disorders and conditions in younger patients often are uncommon and may be reversible. Pregnancy, the use of oral contraceptives, antiphospholipid antibodies (such as, lupus anticoagulant and anticardiolipin antibodies), protein S and C deficiencies, sickle cell anemia, and polycythemia all predispose patients to sludging or thrombosis, thereby increasing the risk of stroke. Fibromuscular dysplasia of the cerebral vasculature also may lead to stroke, and in rare instances prolonged vasoconstriction from a migraine syndrome causes stroke. Recreational drugs such as cocaine, phenylpropanolamine, and amphetamines are potent vasoconstrictors that have been associated with both ischemic and hemorrhagic stroke. Infectious processes, particularly varicella and recently fungal meningitis, can induce vasculopathies that lead to stroke as well or can induce longer-term inflammatory processes that ultimately cause a clinical stroke. Carotid and vertebral dissections often are associated with trauma but may follow mild events such as sneezing. Dissections are the leading determined cause of stroke in the young and are slightly less common than idiopathic strokes. Carotid and vertebral dissections also are seen more frequently in people with underlying pathology of the vessel wall, such as in fibromuscular 1241

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dysplasia and connective tissue disorders. Alteration in the vessel intima can lead to vessel stenosis, occlusion, or embolism. The patient may report a minor preceding event, such as spinal manipulation, yoga, working overhead, coughing, or vomiting. Presenting manifestations may include headache, facial pain, visual changes, cranial nerve (CN) palsies, pain over the affected vessel, Horner’s syndrome, amaurosis fugax, SAH, or an ischemic stroke. The headache frequently is unilateral and may occur days before onset of the other neurologic symptoms. Dissections are typically diagnosed by noninvasive modalities, such as ultrasonography, magnetic resonance angiography (MRA), and computed tomography angiography (CTA). Medical therapy options include early anticoagulation if SAH/intracranial dissection is not suspected. The existing data comparing antiplatelet treatment to anticoagulation is generally limited and antiplatelet treatment is generally simpler and safer.6 The use of tissue plasminogen activator (tPA) is considered as a safe and effective in extracranial carotid or vertebral dissection patients as in any other eligible patient.7

BOX 91.1 

Most Common Sites for Hypertensive Intracranial Hemorrhage AFFECTED AREA (FREQUENCY) Putamen (44%) Thalamus (13%) Cerebellum (9%) Pons (9%) Other cortical areas (25%)

COMMON CLINICAL PRESENTATION

Contralateral motor/sensory loss Limb pain, speech difficulty Uncoordinated movements of trunk and limbs Numbness, weakness, ataxia, dizziness Numbness, weakness, language disturbances

Transient Ischemic Attack A transient ischemic attack (TIA) was historically defined as a neurologic deficit with complete resolution within 24 hours; however, a portion of TIA cases have evidence of permanent brain ischemia on neuroimaging. Therefore, the American Heart Association (AHA) has adopted a tissue-based definition: A transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. About 240,000 TIAs per year occur in the United States, with an incidence rate of 8 per 1000 person years. TIAs constitute an important warning sign for the future development of cerebral infarction. Approximately 10% of the patients who experience a TIA will experience a stroke within 3 months of the sentinel event, and one-half of these occur within the first 2 days.

Hemorrhagic Stroke Spontaneous ICH causes 10% to 15% of all acute strokes, affecting approximately 65,000 patients per year. It carries a 30-day mortality rate of up to 50% with one-half of patients dying in the first 2 days. Among survivors, only one in five are living independently at 6 months. The two major underlying causes of ICH are hypertensive vasculopathy (caused by long-standing hypertension) and cerebral amyloid angiopathy (usually found in elders, which is the result of amyloid deposition in cerebral vessel walls). Hypertensive hemorrhage results from degenerative changes in the small penetrating arteries and arterioles, leading to lipohyalinosis of small, deep penetrating arteries. Such hemorrhages generally occur in the deep regions, including basal ganglia and thalamus. The most common sites for hypertensive hemorrhage are listed in Box 91.1. ICH caused by amyloid angiopathy tends to be lobar in nature and to occur more commonly in older adults. Other factors leading to ICH include underlying vascular malformations (ie, arteriovenous malformations [AVMs] and aneurysms, drug intoxication [particularly sympathomimetics, such as cocaine], malignant hypertension, saccular aneurysms, blood dyscrasias, venous sinus thrombosis, hemorrhagic transformation of an ischemic stroke, moyamoya disease, and tumors). High-risk features for such secondary forms of ICH include lobar location, presence of intraventricular blood, and younger age.

Pathophysiology The cerebral vasculature supplies the brain with a rich flow of blood that contains the critical supply of oxygen and glucose necessary for normal brain function. When a stroke occurs, there

are immediate alterations in CBF and extensive changes in cellular homeostasis. The normal CBF is approximately 40 to 60 mL/100 g of brain per minute. When CBF drops below 15 to 18 mL/100 g of brain per minute, several physiologic changes occur. The brain loses electrical activity, becoming electrically “silent,” although neuronal membrane integrity and function remain intact. Clinically, the areas of the brain maintaining electrical silence manifest a neurologic deficit, even though the brain cells are viable. When CBF is below 10 mL/100 g of brain per minute, membrane failure occurs, with a subsequent increase in the extracellular potassium and intracellular calcium and eventual cell death. The ischemic penumbra is the area of the brain surrounding the primary injury, which is preserved by a tenuous supply of blood from collateral vessels. This border zone of neuronal tissue is the area of greatest interest to investigators for possible salvage in both ischemic and hemorrhagic stroke. In ischemic stroke, the duration of occlusion plays a critical role in neuronal survival. In ICH, acute vessel rupture is most often caused by underlying small vessel disease and causes injury by several mechanisms. First, there is mass effect from the hematoma itself, followed by activation of the coagulation cascade, release of inflammatory cytokines, and blood-brain barrier (BBB) disruption. This leads to perihematomal edema formation and secondary brain injury. Finally, continued bleeding, or hematoma expansion, occurs in many patients—either continued bleeding from the primary source, or secondary bleeding at the periphery of the hemorrhage.

Anatomy and Physiology Blood is supplied to the brain by the anterior and posterior circulations. The anterior circulation originates from the carotid system and perfuses 80% of the brain, including the optic nerve, retina, and frontoparietal and anterior-temporal lobes. The first branch off the internal carotid artery is the ophthalmic artery, which supplies the optic nerve and retina. As a result, the sudden onset of painless monocular blindness (amaurosis fugax) identifies the stroke as involving the anterior circulation (specifically the ipsilateral carotid artery) at or below the level of the ophthalmic artery. The internal carotid arteries terminate by branching into the anterior and middle cerebral arteries at the circle of Willis. The anterior cerebral artery supplies the basal and medial aspects of the cerebral hemispheres and extends to the anterior two-thirds of the parietal lobe. The middle cerebral artery feeds

CHAPTER 91  Stroke

the lenticulostriate branches that supply the putamen, part of the anterior limb of the internal capsule, the lentiform nucleus, and the external capsule. Main cortical branches of the middle cerebral artery supply the lateral surfaces of the cerebral cortex from the anterior portion of the frontal lobe to the posterolateral occipital lobe. Although the posterior circulation is smaller and usually supplies only 20% of the brain, it supplies the brainstem (which is critical for normal consciousness, movement, and sensation), cerebellum, thalamus, auditory and vestibular centers of the ear, medial temporal lobe, and visual occipital cortex. The posterior circulation is derived from the two vertebral arteries that ascend through the transverse processes of the cervical vertebrae. The vertebral arteries enter the cranium through the foramen magnum and supply the cerebellum by the posterior inferior cerebellar arteries. They join to form the basilar artery, which branches to form the posterior cerebral arteries. Some variants exist, importantly, the fetal origin posterior cerebral artery, which is where the posterior cerebral artery is actually fed by the anterior circulation. The extent of injury in either an anterior or a posterior stroke depends on both the vessel involved and the presence of collateral blood flow distal to the vessel occlusion. A patient with excellent collateral blood flow from the contralateral hemisphere may have minimal clinical deficits despite a complete carotid occlusion. By contrast, a patient with poor collateral flow may have hemiplegia with the same lesion.

CLINICAL FEATURES Ischemic Stroke The signs and symptoms of an ischemic stroke may appear suddenly and without warning or may have a stuttering, insidious onset. Disruption of the flow to one of the major vascular limbs of the cerebral circulation will result in physiologic disruption to the anatomic area of the brain supplied by that blood vessel. Ischemic strokes can be classified as anterior or posterior circulation strokes, depending on the vasculature involved. The presence of neurologic deficits is highly dependent on collateral flow. In addition to the vascular supply involved, ischemic strokes can be further described by the temporal presentation of their neurologic deficits. A “stroke in evolution” is one in which focal neurologic deficits worsen over the course of minutes or hours. Approximately 20% of anterior circulation strokes and 40% of posterior circulation strokes will show evidence of progression. Anterior circulation strokes may progress within the first 24 hours, whereas posterior strokes may progress for up to 3 days. Propagation of thrombus is postulated as a likely mechanism for progression. With anterior circulation strokes (involving variously and primarily the carotid, anterior, and middle cerebral arteries), the clinical presentation rarely includes complete loss of consciousness unless the lesion occurs in the previously unaffected hemisphere of a patient who has experienced a previous contralateral stroke. Occlusions in the anterior cerebral artery mainly affect frontal lobe function. The patient has altered mentation coupled with impaired judgment and insight, as well as the presence of primitive grasp and suck reflexes on physical examination. Bowel and bladder incontinence may be features of anterior cerebral artery stroke. Paralysis and hypesthesia of the lower limb opposite the side of the lesion are characteristic. Leg weakness is more pronounced than arm weakness in anterior cerebral distribution stroke. Apraxia or clumsiness in the patient’s gait also may be noted. Marked motor and sensory disturbances are the hallmarks of occlusion of the middle cerebral artery. They occur on the side of

the body contralateral to the side of the lesion and usually are worse in the arm and face than the leg. Such disturbances may involve only part of an extremity or the face but almost always are accompanied by numbness in the same region as that of the motor loss. Hemianopsia, or blindness in one-half of the visual field, occurs ipsilateral to the lesion. Agnosia, or the inability to recognize previously known subjects, is common, and aphasia may be present if the lesion occurs in the dominant hemisphere. Patients often have a gaze preference toward the affected hemisphere because of disruption of the cortical lateral gaze centers. Aphasia, a disorder of language in which the patient articulates clearly but uses language inappropriately or understands it poorly, also is common in dominant-hemisphere stroke. Aphasia may be expressive, receptive, or a combination of both. Wernicke’s aphasia occurs when the patient is unable to process sensory input, such as speech, and thus fails to understand verbal communication (receptive aphasia). Broca’s aphasia refers to the inability to communicate verbally in an effective way, even though understanding may be intact (expressive aphasia). Aphasia should be distinguished from dysarthria, which is a motor deficit of the mouth and speech muscles; the dysarthric patient articulates poorly but understands words and word choices. Aphasia is important to recognize because it usually localizes a lesion to the dominant (usually left) cerebral cortex in the middle cerebral artery distribution. Aphasia and dysphasia are terms that are used interchangeably but must be distinguished from dysphagia, which is difficulty in swallowing. Pathology in the vertebrobasilar system (ie, posterior circulation strokes) can cause the widest variety of symptoms and as a result may be the most difficult to diagnose. The symptoms reflect CN deficits, cerebellar involvement, and involvement of neurosensory tracts. The brainstem also contains the reticular activating system, which is responsible for mediating consciousness, and the emesis centers. Unlike those with anterior circulation strokes, patients with posterior circulation stroke can have loss of consciousness and frequently have nausea and vomiting. The posterior cerebral artery supplies portions of the parietal and occipital lobes, so vision and thought processing are impaired. Visual agnosia, the inability to recognize seen objects, may be a feature, as may alexia, the inability to understand the written word. A third nerve palsy may occur, and the patient may experience homonymous hemianopsia. One of the more curious facets of this syndrome is that the patient may be unaware of any visual problem (visual neglect). Vertigo, syncope, diplopia, visual field defects, weakness, paralysis, dysarthria, dysphagia, spasticity, ataxia, or nystagmus may be associated with vertebrobasilar artery insufficiency. Posterior circulation strokes also demonstrate crossed deficits, such as motor deficits on one side of the body and sensory loss on the other. In anterior circulation strokes, by contrast, abnormalities are always limited to one side of the body. A focused neurologic examination should assess level of consciousness, speech, CN function, motor and sensory function, and cerebellar function. Level of consciousness and fluency of speech can be rapidly assessed in a dialogue with the patient to determine the presence of dysarthria or aphasia. The head should be evaluated for signs of trauma. Pupillary size and reactivity and extraocular movements provide important information about brainstem function, particularly CN III through CN VI; an abnormal third nerve function may be the first sign of tentorial herniation. Gaze preference suggests brainstem or cortical involvement. Central facial nerve weakness from a stroke should be distinguished from the peripheral causes of CN VII weakness. With a peripheral lesion, the patient is unable to wrinkle the forehead. Assessment of facial sensation, eyebrow elevation and squinting, smiling symmetry, gross auditory acuity, gag reflex, shoulder elevation, sternocleidomastoid strength, and tongue protrusion complete the CN evaluation.

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Motor and sensory testing is performed next. Muscle tone can be assessed by moving a relaxed limb. Proximal and distal muscle group strength is assessed against resistance. Pronator drift of the arm is a sensitive sign of motor weakness and can be tested simultaneously by having the patient sit with eyes closed and arms outstretched, with palms toward the ceiling, for 10 seconds. Asymmetrical sensation to pain and light touch may be subtle and difficult to detect. Double simultaneous extinction evaluation tests for sensory neglect and can be easily performed by simultaneously touching the right and left limbs. The patient may feel both the right and left sides being touched individually but may not discern touch on one side when both are touched simultaneously. Similarly, the ability to discern a number gently scratched on a forearm, graphesthesia, is another easily tested cortical parietal lobe function. These tests can help differentiate a pure motor deficit of a lacunar stroke from a sensorimotor middle cerebral artery deficit. Cerebellar testing and the assessment of reflexes and gait complete the examination. Finger-to-nose and heel-to-shin evaluations are important tests of cerebellar functions. Asymmetry of the deep tendon reflexes or unilateral Babinski’s sign may be an early finding of corticospinal tract dysfunction. Gait testing is commonly omitted yet is an informative part of the neurologic examination when it can be safely performed. Observing routine ambulation and heel-to-toe walking can assess for subtle ataxia, weakness, or focal cerebellar lesions. Several prehospital stroke scales have been created to assist emergency medical service (EMS) personnel with the rapid assessment of potential stroke patients. Many of these prehospital stroke scales have been prospectively validated for their accuracy in stroke detection. Two of the more commonly used scales include the Cincinnati Prehospital Stroke Scale (Fig. 91.1) and Los Angeles Prehospital Stroke Screen (Fig. 91.2). The National Institutes of Health Stroke Scale (NIHSS) is a useful and rapid tool for quantifying neurologic deficit in patients with stroke and can be used in determining treatment options (Table 91.1). NIHSS scores have been shown to be reproducible and valid and to correlate well with the amount of infarcted tissue on computed tomography (CT) scan. The baseline NIHSS score can identify patients who are appropriate candidates for fibrinolytic therapy, as well as those at increased risk for hemorrhage, although it is possible for patients to have disabling strokes with an NIHSS of zero (severe truncal ataxia). In addition, it has been used as a prognostic tool to predict outcome and is currently being used by some stroke centers to stratify patients for entry into treatment trials.

Cincinnati Prehospital Stroke Scale Facial Droop Normal: Both sides of face move equally Abnormal: One side of face does not move at all Arm Drift Normal: Both arms move equally or not at all Abnormal: One arm drifts compared to the other Speech Normal: Patient uses correct words with no slurring Abnormal: Slurred or inappropriate words or mute Fig. 91.1.  Cincinnati Prehospital Stroke Scale. (Adapted from Kothari RU, Pancioli A, Liu T, et al: Cincinnati Prehospital Stroke Scale: reproducibility and validity. Ann Emerg Med 33[4]:373-378, 1999.)

Hemorrhagic Stroke The classic presentation of ICH is the sudden onset of headache, vomiting, severely elevated BP, and focal neurologic deficits that progress over minutes. Similar to ischemic stroke, ICH is often associated with a motor and sensory deficit contralateral to the brain lesion. Almost 40% of patients will demonstrate significant growth in hemorrhage volume within the first few hours. Although headache, vomiting, and coma are common, many patients do not have these findings, and the clinical presentation can be identical to that of patients with ischemic stroke; the two cannot be reliably differentiated in the absence of neuroimaging. Ongoing assessment of airway and mental status is of paramount importance in patients with ICH because precipitous deterioration is always a possibility. Emergency airway management requires careful judgment: On the one hand, airway control can prevent aspiration, hypoxia, and hypercarbia; on the other, sedation and paralysis can make it difficult to follow the neurologic examination, which can help monitor for hemorrhage expansion, elevated intracranial pressure (ICP), seizure activity, and brainstem herniation. As with ischemic stroke, a careful neurologic examination is important in localizing the region and extent of injury. Baseline NIHSS and Glasgow Coma Scale scores can be used to assess stroke severity, although the Glasgow Coma Score (GCS) may be more practical to follow for neurologic deterioration (Table 91.2). In addition, serial examinations can detect early changes that may suggest ongoing bleeding during the acute phase. The ICH score can predict mortality (Table 91.3). Poor prognostic indicators for patients with ICH include a decreased level of consciousness on arrival, intraventricular hemorrhage, and large ICH volume, all of which can be assessed in the emergency department (ED) (Fig. 91.3).

DIFFERENTIAL DIAGNOSIS Ischemic Stroke Extra-axial collections of blood secondary to trauma can mimic stroke. An epidural or subdural hematoma can cause an altered mental status, focal neurologic signs, and rapid progression to coma. Elders, who represent the age group at highest risk for stroke, can be victims of recurrent falls that lead to chronic subdural hematomas. Carotid dissection may occur after neck trauma or sudden hyperextension and may be associated with focal neurologic signs and symptoms, as with an aortic dissection that extends into the carotid arteries. Other structural lesions that may cause focal neurologic signs include brain tumors and abscesses. Air embolism should be suspected in the setting of marked atmospheric pressure changes, such as in scuba diving or during medical procedures or injuries that may allow air into the vascular system. Seizures, altered mental status, and focal neurologic findings also may be manifestations of air embolism. Metabolic abnormalities also can mimic stroke syndromes. Hypoglycemia often is responsible for an altered mental status and is a well-known cause of sustained focal neurologic symptoms that can persist for several days. Wernicke’s encephalopathy causes ophthalmoplegia, ataxia, and confusion that can be mistaken for signs of cerebellar infarction. Migraine may present with focal neurologic findings, with or without headache. A seizure followed by Todd’s postictal paralysis may mimic stroke. Bell’s palsy, labyrinthitis, vestibular neuronitis, peripheral nerve palsy, and demyelinating diseases may all mimic stroke. Ménière’s disease may be difficult to distinguish from a posterior circulation stroke or TIA. Dizziness, vertigo, hearing loss, and tinnitus in Ménière’s disease are common, whereas

CHAPTER 91  Stroke

Los Angeles Prehospital Stroke Scale (LAPSS)

Patient name: Rater name: Date:

Screening criteria

Yes

No

4. Age over 45 years 5. No prior history of seizure disorder 6. New onset of neurologic symptoms in last 24 hours 7. Patient was ambulatory at baseline (prior to event) 8. Blood glucose between 60 and 400

9. Exam: Look for obvious asymmetry Normal

Right

Left

Facial smile / grimace:

Droop

Droop

Grip:

Weak grip No grip

Weak grip No grip

Arm weakness:

Drifts down Falls rapidly

Drifts down Falls rapidly

Based on exam, patient has only unilateral (and not bilateral) weakness: Yes 10. If yes (or unknown) to all items above LAPSS screening criteria met:

Yes

No No

11. If LAPSS criteria for stroke met, call receiving hospital with “CODE STROKE,” if not then return to the appropriate treatment protocol. (Note: The patient may still be experiencing a stroke if even if LAPSS criteria are not met.)

Provided by the internet stroke center — www.strokecenter.org

Fig. 91.2.  Los Angeles Prehospital Stroke Screen. (Adapted from Kidwell CS, Starkman S, Eckstein M, et al: Identifying stroke in the field: prospective validation of the Los Angeles Prehospital Stroke Screen [LAPSS]. Stroke 31:71-76, 2000.)

difficulties with vision or speech or other focal symptoms are uncommon. Like stroke, giant cell arteritis is a disease of older adults. It may cause severe headache, visual disturbances, and, rarely, aphasia and hemiparesis. Other symptoms include intermittent fever, malaise, jaw claudication, morning stiffness, and myalgias. The diagnosis should be suspected in patients with a very high erythrocyte sedimentation rate (ESR) and is confirmed by temporal artery biopsy. Collagen vascular diseases such as polyarteritis

nodosa, lupus, and other types of vasculitis may cause stroke syndromes. Cerebral venous sinus thrombosis (CVST) is another cause of focal neurologic symptoms that most commonly affects the superior sagittal sinus and lateral sinuses (see Chapter 93).8 The diagnosis of CVST can be difficult because of the nonspecific nature of symptoms, as well as the variable time frame of symptom onset (from hours to a few weeks). Patients may have generalized headaches, nausea, vomiting, paresis, visual disturbances, depressed

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TABLE 91.1 

National Institutes of Health Stroke Scale Scoring Form ITEM

SCORING DEFINITIONS

1a. Level of consciousness (LOC)

0 = Alert and responsive 1 = Arousable to minor stimulation 2 = Arousable only to painful stimulation 3 = Reflex responses or unarousable

1b. LOC-related questions: Ask patient’s age and month. Must be exact.

0 = Both correct 1 = One correct (or dysarthria, intubated, foreign language) 2 = Neither correct

1c. Commands: Open and close eyes, grip and release nonparetic hand. (Other one-step commands or mimic also acceptable.)

0 = Both correct (acceptable if impaired by weakness) 1 = One correct 2 = Neither correct

SCORE

2. Best gaze: Horizontal EOM by voluntary or doll’s eye maneuver.

0 = Normal 1 = Partial gaze palsy; abnormal gaze in one or both eyes 2 = Forced eye deviation or total paresis that cannot be overcome by doll’s eye maneuver

3. Visual field: Use visual threat if necessary. If monocular, score field of good eye.

0 = No visual loss 1 = Partial hemianopsia, quadrantanopia, extinction 2 = Complete hemianopsia 3 = Bilateral hemianopsia or blindness

4. Facial palsy: If patient is stuporous, check symmetry of grimace to pain.

0 = Normal 1 = Minor paralysis, flat NLF, asymmetrical smile 2 = Partial paralysis (lower face = UMN lesion) 3 = Complete paralysis (upper and lower face)

5. Motor arm: Arms outstretched 90 degrees (sitting) or 45 degrees (supine) for 10 seconds. Encourage best effort. Indicate paretic limb in score box.

0 = No drift for 10 seconds 1 = Drift but does not hit bed 2 = Some antigravity effort, but cannot sustain 3 = No antigravity effort, but even minimal movement counts 4 = No movement at all X = Unable to assess owing to amputation, fusion, fracture, and so on

L or R

6. Motor leg: Raise leg to 30 degrees (from supine) for 5 seconds. Indicate paretic limb in score box.

0 = No drift for 5 seconds 1 = Drift but does not hit bed 2 = Some antigravity effort, but cannot sustain 3 = No antigravity effort, but even minimal movement counts 4 = No movement at all X = Unable to assess owing to amputation, fusion, fracture, and so on

L or R

7. Limb ataxia: Check finger-nose-finger, heel-shin position sense; and score only if out of proportion to paralysis.

0 = No ataxia (or aphasic, hemiplegic) 1 = Ataxia in upper or lower extremity 2 = Ataxia in upper and lower extremity X = Unable to assess owing to amputation, fusion, fracture, and so on

L or R

8. Sensory: Use safety pin. Check grimace or withdrawal if patient is stuporous. Score only stroke-related losses.

0 = Normal 1 = Mild-moderate unilateral loss but patient aware of touch (or aphasic, confused) 2 = Total loss, patient unaware of touch; coma, bilateral loss

9. Best language: Describe cookie jar picture, name objects, read sentences. May use repeating, writing, stereognosis.

0 = Normal 1 = Mild-moderate aphasia (speech difficult to understand but partly comprehensible) 2 = Severe aphasia (almost no information exchanged) 3 = Mute, global aphasia, coma; no one-step commands

10. Dysarthria: Read list of words.

0 = Normal 1 = Mild-moderate; slurred but intelligible 2 = Severe; unintelligible or mute X = Intubation or mechanical barrier

11. Extinction or neglect: Simultaneously touch patient on both hands, show fingers in both visual fields, ask about deficit, left hand.

0 = Normal, none detected (visual loss alone) 1 = Neglects or extinguishes to double simultaneous stimulation in any modality (visual, auditory, sensation, spatial, body parts) 2 = Profound neglect in more than one modality

Android Free App: https://play.google.com/store/apps/details?id=com.myprograms.nihss Apple Free App: https://itunes.apple.com/us/app/nih-stroke-scale-from-statcoder/id408788598?mt=8 Online NIHSS Calculator: www.mdcalc.com/nih-stroke-scale-score-nihss/ EOM, Extraocular movement; L, left; LOC, level of consciousness; NLF, nasolabial fold; R, right; UMN, upper motor neuron. Modified from Massachusetts General Hospital Stroke Service. NIH stroke scale materials. Scoring form. Available at www2.massgeneral.org/stopstroke/pdfs/scoring _form.pdf.

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CHAPTER 91  Stroke

TABLE 91.2 

TABLE 91.3 

Glasgow Coma Scale Score*

Intracerebral Hemorrhage Score Predicting Mortality After Acute Intracerebral Hemorrhage

EYE OPENING (E)

VERBAL RESPONSE (V)

MOTOR RESPONSE (M)

4 = Spontaneous 3 = To voice 2 = To pain 1 = None

5 = Normal conversation 4 = Disoriented conversation 3 = Words, but not coherent 2 = No words; only sounds 1 = None

6 = Normal 5 = Localizes to pain 4 = Withdraws to pain 3 = Decorticate posture 2 = Decerebrate posture 1 = None

*Total score = E + V + M Shoestring Graphics: Glasgow coma score. Available at www.ssgfx.com/CP2020/medtech/glossary/glasgow.htm.

FEATURE

POINTS

GLASGOW COMA SCALE SCORE 3 to 4

2

5 to 12

1

13 to 15

0

INTRACEREBRAL HEMORRHAGE VOLUME >30 mL

1

≤30 mL

0

INTRAVENTRICULAR HEMORRHAGE (INTRAVENTRICULAR BLOOD) Present

1

Absent

0

INTRACEREBRAL HEMORRHAGE LOCATION Infratentorial

1

Supratentorial

0

AGE A B

≥80 years

1

185 mm Hg or diastolic >110 mm Hg Labetalol 10 to 20 mg IV over 1 to 2 minutes; may repeat 1 time or Nicardipine infusion, 5 mg/hr; titrate up by 2.5 mg/hr at 5- to 15-minute intervals, maximum dose 15 mg/hr; when desired BP attained, reduce to 3 mg/hr Other agents (hydralazine, enalaprilat, and so on) may be considered when appropriate. If BP does not decline and remains >185/110 mm Hg, do not administer rtPA.

MANAGEMENT OF BLOOD PRESSURE DURING AND AFTER TREATMENT WITH RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR OR OTHER ACUTE REPERFUSION INTERVENTION Monitor BP every 15 minutes during treatment and then for another 2 hours, then every 30 minutes for 6 hours, and then every hour for 16 hours.

Blood Pressure Level Systolic 180 to 230 mm Hg or diastolic 105 to 120 mm Hg Labetalol 10 mg IV over 1 to 2 minutes; may repeat every 10 to 20 minutes; maximum dose of 300 mg or Labetalol 10 mg IV followed by an infusion at 2 to 8 mg/min Systolic >230 mm Hg or diastolic 121 to 140 mm Hg Labetalol 10 mg IV over 1 to 2 minutes; may repeat every 10 to 20 minutes; maximum dose of 300 mg or Labetalol 10 mg IV followed by an infusion at 2 to 8 mg/min or Nicardipine infusion, 5 mg/hr; titrate up to desired effect by increasing 2.5 mg/hr every 5 minutes to maximum of 15 mg/hr If BP not controlled, consider sodium nitroprusside. BP, Blood pressure; IV, intravenous; rtPA, recombinant tissue plasminogen activator. Adapted from Jauch EC, Saver JL, Adams HP Jr, et al: Guidelines for the early management of adults with ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44(3):870-947, 2013.

nifedipine or sublingual nitroglycerin are not recommended, because either agent can produce a precipitous drop in BP. If fibrinolytic therapy is planned, stringent control of BP is indicated to reduce the potential for intracranial hemorrhage after the thrombolytic is administered (see Box 91.2). Thrombolytic therapy is not recommended for patients whose systolic pressure is consistently higher than 185 mm Hg or whose diastolic pressure is 110 mm Hg at the time of treatment. Simple measures can be used to try lowering BP below this level. Recommended approaches include the use of IV labetalol 10 to 20 mg or continuous nicardipine. Once thrombolytic therapy has been initiated, BP must be monitored closely and hypertension treated aggressively. Just as problematic as high BP can be, low BP can be quite detrimental to patients with ischemic stroke. Normally normotensive stroke patients with low BP or normally hypertensive stroke patients with low or even low-normal BP are given a fluid bolus to try to increase cerebral perfusion. This is especially important in patients in a dehydrated state. If initial fluid challenge is ineffective, the patient may require vasopressor therapy (eg, with dopamine) to gradually increase MAP and improve cerebral perfusion.

Thrombolytic Therapy To date, the only IV thrombolytic agent approved by the U.S. Food and Drug Administration (FDA) for treatment of patients with acute ischemic stroke is the recombinant tissue plasminogen activator (rtPA), alteplase (Activase). Approval was initially based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) trial, although subsequent analysis of other studies has supported its use.15,16 There was initial concern regarding the safety of alteplase when used in community practice; however, a meta-analysis of non–trial-related use in community practice has demonstrated efficacy and safety similar to that reported in the NINDS trial; this was also replicated within a cluster randomized controlled trial performed in Michigan.17 The recommended dose for rtPA is 0.9 mg/kg IV to a maximum of 90 mg (10% of the dose given as a bolus followed by an infusion lasting 60 minutes). Although the initial recommended time window for IV rtPA administration was 3 hours because the patient was last known to be at their neurologic baseline, a subsequent study has demonstrated the usefulness of IV rtPA at 3 to 4.5 hours in a carefully selected subgroup of acute ischemic stroke patients (Table 91.5 and Box 91.3). A larger open-label randomized trial focusing on patients presenting with “reasonable uncertainty” regarding the expected benefit of rtPA found reduced death and dependency at 6 months; a large proportion of patients in this study were quite old, or had old stroke (>4.5 hours), or both.18 These results should not influence clinical practice, because the bulk of the population included in this large trial was markedly different from the population of stroke patients who receive thrombolysis within the context of current guidelines. The American Stroke Association recommends that rtPA be given within 60 minutes of arrival to appropriately selected ischemic stroke patients. Recent guidelines from the American College of Emergency Physicians concur but also emphasize that proper systems of care must also be in place to ensure safety and to maximize good outcomes.19 Studies suggests that patients with mild or rapidly resolving symptoms may still benefit from the use of IV rtPA, and a clinical trial is ongoing in this area. A promising early phase trial of tenecteplase was recently completed for patients with mild stroke and high-grade large-vessel stenosis. However, this strategy cannot be recommended yet if feasible clinicians should consider urgent transfer of patients with mild symptoms and high grade stenosis for potential reperfusion strategies, including mechanical

CHAPTER 91  Stroke

TABLE 91.5 

Comparison of AHA/ASA Acute Stroke Management Guidelines and Previous and New FDA Prescribing Information for Alteplase (Activase) Treatment in Acute Ischemic Stroke Inclusion criteria for fibrinolytic therapy • Diagnosis of ischemic stroke causing measurable neurological deficit • Onset of symptoms less than 3 hours before beginning treatment CRITERION

AHA/ASA ACUTE STROKE MANAGEMENT GUIDELINE 2013a

OLD ALTEPLASE (ACTIVASE) PI (UPDATED 2009)

NEW ALTEPLASE (ACTIVASE) PI (FEBRUARY 2015)

Prior stroke

Exclusion: prior stroke within 3 mo

Contraindication: recent (within 3 mo) previous stroke

Removed entirely

Seizure at onset

Relative exclusion: seizure at onset with postictal neurological impairments

Contraindication: seizure at the onset of stroke

Removed entirely

Bleeding diathesis/ OACs

Exclusion: Platelet count 1.7 or PT >15 s Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests

Contraindication: known bleeding diathesis including but not limited to: Current use of OACs (eg, warfarin sodium), an INR >I.7, or a PT >15 s Administration of heparin within 48 h preceding the onset of stroke with an elevated aPTT at presentation Platelet count 85 mm Hg or diastolic >10 mm Hg)

Contraindication: uncontrolled hypertension at the time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic)

Contraindication: current severe uncontrolled hypertension remains, specific BP values removed Warning for BP >175/110 mm Hg remains for all alteplase (Activase) indications

Blood glucose

Exclusion: blood glucose 400 mg/dL

Removed entirely

Severe stroke

Not listed

Warning: patients with severe neurological deficit (NIHSS score >22) at presentation; there is an increased risk of ICH in these patients

Removed entirely

Mild stroke

Relative exclusion: only minor or rapidly improving stroke symptoms (clearing spontaneously)

Warning: safety and efficacy in patients with minor neurological deficit or with rapidly improving symptoms have not been evaluated; therefore, treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended

Removed entirely

Neuroimaging findings

Exclusion: CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Warning: Major early infarct sign (substantial edema, mass effect, or midline shift on CT)

Removed entirely

SAH

Exclusion: symptoms suggest SAH

Contraindication: Suspicion of SAH on pretreatment evaluation

Contraindication: subarachnoid hemorrhage Continued

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TABLE 91.5 

Comparison of AHA/ASA Acute Stroke Management Guidelines and Previous and New FDA Prescribing Information for Alteplase (Activase) Treatment in Acute Ischemic Stroke—cont’d CRITERION

AHA/ASA ACUTE STROKE MANAGEMENT GUIDELINE 2013a

OLD ALTEPLASE (ACTIVASE) PI (UPDATED 2009)

NEW ALTEPLASE (ACTIVASE) PI (FEBRUARY 2015)

Use in specific populations   Pregnancy

Relative exclusion

Warning: pregnancy Category C Not mentioned Indicated for adults Warning for all indications: advanced age (eg, >75 y) may increase risks

No change

Warning: gastrointestinal or genitourinary bleeding within the past 21 d

Warning: gastrointestinal or genitourinary bleeding

  Nursing mothers   Children   Elderly

Gastrointestinal or genitourinary bleeding

Not listed Inclusion: ≥18 y of age Not listed

Warning: gastrointestinal or genitourinary bleeding within the past 21 d

Unknown risk Pediatric use not established Warning added: age >77 y was 1 of several interrelated baseline characteristics associated with an increased risk of ICH; efficacy results suggest a reduced but still favorable clinical outcome

a

From Jauch EC, Saver JL, Adams HP Jr, et al; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870–947, 2013. AHA/ASA, American Heart Association/American Stroke Association; aPTT, activated partial thromboplastin time; BP, blood pressure; CT, computed tomography; FDA, US Food and Drug Administration; ICH, intracerebral hemorrhage; INR, international normalized ratio; NIHSS, National Institute of Health Stroke Scale; OAC, oral anticoagulant; PI, prescribing information; PT, prothrombin time; SAH, subarachnoid hemorrhage. From Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al; American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 47(2):581–641, 2016.

BOX 91.3 

Fibrinolytic Therapy for Acute Ischemic Stroke in the 3- to 4.5-Hour Time Window Inclusion and Exclusion Criteria INCLUSION CRITERIA

Diagnosis of ischemic stroke causing measurable neurological deficit Onset of symptoms within 3 to 4.5 hours before beginning treatment

RELATIVE EXCLUSION CRITERIA

Older than 80 years old Severe stroke (NIHSS > 25) Taking an oral anticoagulant regardless of INR History of both diabetes and prior ischemic stroke INR, International normalized ratio; IV, intravenous; NIHSS, National Institutes of Health Stroke Scale; rtPA, recombinant tissue plasminogen activator.

thrombectomy.20 Less favorable outcomes without thrombolysis have been demonstrated in this population of minor stroke patients in particular. Because the risk of symptomatic intracranial hemorrhage (SICH) is proportional to severity, we recommend carefully discussing the benefits and risks with patients when considering rtPA in patients with minor or improving (but not cleared) deficits. These patients are at lower risk of complications relative to patients with moderate to severe stroke, yet many who are not treated still have significant long-term disability.21 IV tPA is not recommended when the time of stroke onset cannot be ascertained reliably, including strokes recognized on awakening. Although the aggregate risk of symptomatic ICH is about 6% in trials and observational studies, each individual

patient will have differing probabilities of benefits and risks. Optimal methods of communicating benefits and risks promptly have not been developed or widely disseminated, because all reviewed decision aids have methodological deficiencies.22 However, younger patients and milder strokes (NIHSS < 10) clearly have a lower risk of SICH. It is reasonable to adjust outcome expectations when discussing benefits and risks with older patients with more severe strokes (including significant early CT changes). The risk of severe disability and death is quite high in this population with or without fibrinolysis. Prompt fibrinolysis of severe strokes will shift the outcomes of a population of treated patients toward less disability.23 Several recent trials suggest these outcomes can be further improved with careful selection of patients for endovascular rescue therapy.

Endovascular Rescue Therapy The results of several concurrent trials investigating prompt endovascular rescue therapy (usually following IV thrombolysis) versus medical management were published in late 2014 and early 2015. These studies have conclusively demonstrated that patients with severe strokes and evidence of proximal large vessel occlusions have significantly better functional outcomes when treated with the new generation devices.24-26 Each of these trials used different imaging and clinical selection criteria, although the presence of a proximal occlusion and prompt treatment, preferably within 3 hours, were common to all of the protocols. These trials emphasize the need for better regionalization of stroke care to reduce the time to definitive reperfusion.27 Unlike acute ischemic stroke, non-acute cases of intracranial occlusions are best treated with medical therapy and not permanent intracranial stents.28 Intra-arterial thrombolysis currently does not have a defined role in the treatment of acute ischemic stroke.

CHAPTER 91  Stroke

The recent trials demonstrating clear benefit of endovascular thrombectomy come after a decade of negative studies. The difference in results is due to a combination of improved devices, emphasis on early intervention, and careful patient selection.29-31 Data from two large trials involving almost 40,000 patients indicate that early use of aspirin in patients with acute ischemic stroke who were not treated with a fibrinolytic agent was associated with a small but significant reduction in rates of stroke recurrence and mortality. These studies in combination suggest a number needed to treat of 77 (ie, 77 stroke patients would need to be treated with daily aspirin therapy to prevent a poor outcome, such as death, dependency at discharge, or at 6 months after stroke, in one patient). The more recent CHANCE trial found that dualantiplatelet therapy with aspirin and clopidogrel for 90 days significantly reduced recurrent stroke (from 11.7% to 8.2%) in patients initially presenting with high-risk TIA or mild stroke (NIHSS below 4).32 Aspirin should not be given for the first 24 hours to patients who have received a fibrinolytic agent and not until a swallowing study has been performed.

Anticoagulation The use of therapeutic dosing of low–molecular-weight heparin (LMWH) or unfractionated heparin is now generally abandoned in the routine care of stroke patients; prophylactic dosing to prevent venous thromboembolism however is a hospital level quality measure and publically reported.33 It may be that any reduction in risk of subsequent ischemic stroke is balanced by an increased risk of hemorrhagic stroke. To date, no studies have definitively established the efficacy of anticoagulants in the management of patients with acute ischemic stroke, and current AHA guidelines recommend against the routine use of heparinoids in this population.4 However, heparin is sometimes considered by vascular neurologists in select patients at high risk for stroke progression, including patients with crescendo TIAs or TIA from a cardioembolic source (eg, atrial fibrillation, patients with a highgrade carotid artery stenosis, patients with posterior circulation TIA, and patients with evolving strokes). Heparin or LMWH is often instituted to treat carotid and vertebral artery dissection, unless a contraindication such as intracranial extension is present. If a dissection is diagnosed and the patient has no symptoms of ischemia, treatment with antiplatelet therapy alone may be an option. Heparin therapy should not be initiated in patients with suspected endocarditis or in any patient until a CT scan has ruled out intracranial bleeding.

Intracerebral Hemorrhage No specific therapy has been demonstrated to substantially improve the outcome of patients with ICH. One of the strongest predictors of mortality when considering ICH patients with comparable severity is the implementation of early care limitations. When health care providers initiate early do not resuscitate (DNR) orders, patients with otherwise equivalent prognoses are more likely to die. As a result, we believe that early prognostication in the ED should be avoided. Current evidence supports the benefit of aggressive medical care. Patients admitted to a specialized unit, patients who are expedited to the intensive care unit (ICU), those admitted on a weekday, and those treated more aggressively appear to have better neurologic outcomes.61-63 Therefore, even in the absence of therapies specifically proven in phase III trials, multidisciplinary care by specially trained care teams appears to provide benefit. The patient with suspected ICH requires rapid assessment and transport to a care center with rapid neuroimaging and intensive care management facilities. Out-of-hospital management is similar to that for ischemic stroke, including determination of

time of onset, concomitant medications, and application of a prehospital stroke scale. Supportive care involving attention to airway management and perfusion is of the highest priority. Patients with hemorrhagic stroke are more likely to have an altered level of consciousness that may rapidly progress to unresponsiveness requiring emergent endotracheal intubation. After intubation, a short-acting medication for sedation should be considered so that a neurologic examination can be repeatedly performed and the findings evaluated. Standard care includes establishing IV access and cardiac monitoring. Evaluation of blood glucose and appropriate dextrose and naloxone administration are essential in any patient with altered mental status. Patients seen early after symptom onset are at high risk of ongoing bleeding. Approximately 30% of such patients will have significant hematoma expansion on presentation, leading to neurologic deterioration and worse outcome. Major therapies aimed at reducing this risk include BP reduction, anticoagulation reversal, and hemostatic therapy. BP control is commonly performed after ICH. This intervention is controversial, because hypertension may potentiate further bleeding, but lowering BP in a patient with chronic hypertension may decrease CBF, worsening brain injury. One randomized trial found that lowering systolic BP to below 140 reduced ongoing bleeding, but there was no change in neurologic outcome, suggesting that this therapy may not provide clinical benefit in unselected patients. A larger trial focused on functional outcomes demonstrated that prompt reduction to a systolic blood pressure (SBP) of 140 mm Hg may slightly reduce disability and was generally safe.34 The current consensus regarding management of ICH is to provide antihypertensive treatment with parenteral agents for systolic pressures higher than 160 to 180 mm Hg or MAP higher than 130 mm Hg. Recommended agents include labetalol, esmolol, nicardipine, clevidipine, and hydralazine.3 Many patients are coagulopathic at the time of their ICH; and for patients on anticoagulants, emergency reversal will theoretically minimize the risk of further bleeding, although this is not backed up by clinical trial evidence. For patients on warfarin, reversal is achieved using IV vitamin K (10 mg IV or subcutaneously), supplemented with either fresh frozen plasma (FFP) (2 to 4 units) or prothrombin complex concentrate (PCC) (Kcentra 25 to 50 units/kg depending on INR—dosing varies for other PCCs by formulation).3 Of the new generation oral anticoagulants, at this time only dabigatran has a specific antidote (idarucizumab) proven to reverse coagulant effects in human clinical trials.35 Fourfactor PCC is likely to be the most quickly available reversal agent for apixaban and rivaroxaban; hemodialysis will rapidly eliminate dabigatran from the circulation but is not generally practical for patients with serious bleeding.36 Hemostatic therapy (treatment with procoagulant agents; eg, recombinant activated factor VII in patients without baseline coagulopathy) was initially promising; however, a phase III trial showed no clinical benefit. To consider other iatrogenic coagulopathies, post-thrombolytic symptomatic intracranial hemorrhage is a serious complication. Although various protocols have been employed for postthrombolysis intracranial hemorrhage, a comparative observational study comparing reversal with FFP or cryoprecipitate versus conservative management (no reversal) demonstrated poor outcomes in both groups. Mortality was slightly higher in the reversal group, although this study only included 48 patients.37 Based on the limited evidence, at this point in time we would recommend administering cryoprecipitate (6 to 8 units) for thrombolytic associated ICH that occurs shortly (0 to 3 hours) after alteplase administration. Later ICH (3 hours to days) is unlikely to be associated with a persistent coagulopathy, because the fibrinogen depletion following alteplase administration is transient; therefore, reversal

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agents appear to confer risk without a potential biological benefit in this time window. Finally, the data on treatment of patients with spontaneous ICH who are on preexisting antiplatelet treatments, such as aspirin or clopidogrel, is conflicting. A small subgroup of an observational trial (27 patients) suggested patients receiving a platelet infusion within 12 hours of onset had an increased odds of a good functional outcome.38 At this time, the data do not support platelet transfusions in patients with spontaneous ICH being treated with antiplatelet agents, unless a new thrombocytopenia (platelet count 60 years old

1

Initial BP >140/90 mm Hg

1

Unilateral weakness

2

SPEECH IMPAIRMENT

DISPOSITION

Without weakness

1

Ischemic Stroke and Transient Ischemic Attacks

Symptoms 10 to 59 minutes

1

Symptoms ≥60 minutes

2

History of diabetes

1

“Stroke center” definitions have been established, and there is a national certification process for primary stroke centers (PSCs) and comprehensive stroke centers (CSCs) in the United States. In broad terms, institutional certification as a PSC requires the establishment of a stroke infrastructure (ie, a stroke team, stroke unit, patient care protocols, and support services, including CT scanning and laboratory testing availability), as well as institutional administrative support and strong leadership.4,39 CSCs offer advanced imaging modalities, perform surgical and endovascular

RESULT 0 to 3 = Low risk (1% risk of stroke in 48 hours) 4 to 5 = Moderate risk (4.1% risk of stroke in 48 hours) ≥6 = High risk (8% risk of stroke in 48 hours) BP, Blood pressure.

CHAPTER 91  Stroke

risk (who might therefore be safe for expedited outpatient evaluation) is the ABCD2 score (Table 91.6). In addition, most patients without a contraindication will be started on antithrombotic therapy in the ED after consultation with a neurologist.

The majority of patients with an acute hemorrhagic stroke should be admitted to an ICU in which specialty consultation is available. If this is unavailable at the evaluating institution, the patient should be transported to an appropriate institution.

KEY CONCEPTS • Anterior circulation strokes result in contralateral hemiparesis of the face and body. • Vertebrobasilar strokes result in ipsilateral CN deficits and contralateral hemiparesis. • Posterior cerebral artery stroke causes ipsilateral CN III palsy and contralateral homonymous hemianopsia. • Wallenberg’s syndrome (lateral medullary syndrome) causes vertigo, Horner’s syndrome, ipsilateral facial numbness, loss of corneal reflex, and contralateral loss of pain/temperature. • Cervical artery dissection is a common cause of stroke in young patients; TIAs preceding stroke in these patients are often missed. • The goal for eligible patients is to receive thrombolytics within 90 minutes of symptoms onset; the dose of alteplase is 0.9 mg per kg with 10% given as a bolus and the remaining 90% given over 1 hour. • Acute ischemic stroke patients receiving alteplase are at risk of developing a spontaneous intracranial hemorrhage; the risk is lowest in patients with a low stroke score, no hypertension, no diabetes, and age younger than 70.

• In acute ischemic stroke, the patient and or their families should be informed of the risk and benefit of treatment with alteplase. • Patients with a hemorrhagic stroke on coumadin should be promptly reversed using vitamin K and either FFP or PCC. • Prognosis is worse in acute stroke in the setting of fever, hypotension, hypoxia, and hyperglycemia. • Carotid Doppler, MRA, or CTA studies are recommended before discharge of a patient with TIA from the ED. • Overly aggressive BP management should be avoided in patients with acute ischemic stroke. • Accurate identification of the last time a patient was known to be at his or her neurologic baseline should be documented in all patients with stroke. • IV alteplase followed by endovascular thrombectomy is recommended in patients with large anterior circulation artery occlusion.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Kernan WN, Ovbiagele B, Black HR, et al: Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236, 2014. 2. Mozaffarian D, Benjamin EJ, Go AS, et al: Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131:e29–e322, 2015. 3. Morgenstern LB, Hemphill JC, Anderson C, et al: Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 41:2108–2129, 2010. 4. Jauch EC, Saver JL, Adams HP, et al: Guidelines for the early management of patients with acute ischemic stroke a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870–947, 2013. 5. Kissela BM, Khoury JC, Alwell K, et al: Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology 79:1781–1787, 2012. 6. Sarikaya H, da Costa BR, Baumgartner RW, et al: Antiplatelets versus anticoagulants for the treatment of cervical artery dissection: Bayesian meta-analysis. PLoS ONE 8:e72697, 2013. 7. Zinkstok SM, Vergouwen MDI, Engelter ST, et al: Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data. Stroke 42:2515–2520, 2011. 8. Saposnik G, Barinagarrementeria F, Brown RD, Jr, et al: Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42(4):1158–1192, 2011. 9. Gee C, Dawson M, Bledsoe J, et al: Sensitivity of newer-generation computed tomography scanners for subarachnoid hemorrhage: a Bayesian analysis. J Emerg Med 43(1):13–18, 2012. 10. Wintermark M, Sanelli PC, Albers GW, et al: Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. AJNR Am J Neuroradiol 34(11):E117–E127, 2013. 11. Holmes M, Rathbone J, Littlewood C, et al: Routine echocardiography in the management of stroke and transient ischaemic attack: a systematic review and economic evaluation. Health Technol Assess 18(16):1–176, 2014. 12. Poisson S, Johnston SC: Prevention of stroke following transient ischemic attack. Curr Atheroscler Rep 13:330–337, 2011. 13. Jauch EC, Cucchiara B, Adeoye O, et al: Part 11: Adult Stroke: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 122(18 Suppl 3):S818–S828, 2010. 14. Lin CB, Peterson ED, Smith EE, et al: Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke. Circ Cardiovasc Qual Outcomes 5(4):514–522, 2012. 15. Wardlaw JM, Murray V, Berge E, et al: Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev (7):CD000213, 2014. 16. Lees KR, Bluhmki E, von Kummer R, et al: Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375(9727):1695–1703, 2010. 17. Scott PA, Meurer WJ, Frederiksen SM, et al: A multilevel intervention to increase community hospital use of alteplase for acute stroke (INSTINCT): a clusterrandomised controlled trial. Lancet Neurol 12:139–148, 2013. 18. Sandercock P, Wardlaw JM, Lindley RI, et al: The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 379:2352–2363, 2012.

19. Brown M, Burton J, Nazarian D, et al: Clinical policy: use of intravenous tissue plasminogen activator for the management of acute ischemic stroke in the emergency department. Ann Emerg Med 66:322–333, 2015. 20. Coutts SB, Dubuc V, Mandzia J, et al: Tenecteplase–tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke 46:769–774, 2015. 21. Khatri P, Conaway M, Jouhnson K: Ninety day outcome rates of a prospective cohort of consecutive mild ischemic stroke patients. Stroke 43:560–562, 2012. 22. Flynn D, Ford GA, Stobbart L, et al: A review of decision support, risk communication and patient information tools for thrombolytic treatment in acute stroke: lessons for tool developers. BMC Health Serv Res 13:225, 2013. 23. Mishra NK, Lyden P, Grotta JC, et al: Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke 41(11):2612–2617, 2010. 24. Berkhemer OA, Fransen PSS, Beumer D, et al: A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 372(1):11–20, 2015. 25. Campbell BCV, Mitchell PJ, Kleinig TJ, et al: Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 372:1009–1018, 2015. 26. Goyal M, Demchuk AM, Menon BK, et al: Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 372:1019–1030, 2015. 27. Fargen KM, Fiorella D, Albuquerque F, et al: Systematic regionalization of stroke care. J Neurointerv Surg 7(4):229–230, 2015. 28. Derdeyn CP, Chimowitz MI, Lynn MJ, et al: Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 383:333–341, 2014. 29. Ciccone A, Valvassori L, Nichelatti M, et al: Endovascular treatment for acute ischemic stroke. N Engl J Med 368:904–913, 2013. 30. Broderick JP, Palesch YY, Demchuk AM, et al: Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893–903, 2013. 31. Saver JL, Jahan R, Levy EI, et al: Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallelgroup, non-inferiority trial. Lancet 380:1241–1249, 2012. 32. Wang Y, Wang Y, Zhao X, et al: Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 369:11–19, 2013. 33. Fonarow GC, Alberts MJ, Broderick JP, et al: Stroke outcomes measures must be appropriately risk adjusted to ensure quality care of patients: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 45:1589– 1601, 2014. 34. Anderson CS, Heeley E, Huang Y, et al: Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 368:2355–2365, 2013. 35. Pollack CV, Jr, Reilly PA, Eikelboom J, et al: Idarucizumab for dabigatran reversal. N Engl J Med 373(6):511–520, 2015. 36. Kaatz S, Kouides PA, Garcia DA, et al: Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 87(Suppl 1):S141–S145, 2012. 37. Alderazi YJ, Barot NV, Peng H, et al: Clotting factors to treat thrombolysis-related symptomatic intracranial hemorrhage in acute ischemic stroke. J Stroke Cerebrovasc Dis 23:e207–e214, 2014. 38. Naidech AM, Liebling SM, Rosenberg NF, et al: Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care 16(1):82–87, 2012. 39. Alberts MJ, Latchaw RE, Jagoda A, et al: Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition. Stroke 42(9):2651–2665, 2011. 40. Alberts MJ, Wechsler LR, Jensen ME, et al: Formation and function of acute strokeready hospitals within a stroke system of care recommendations from the brain attack coalition. Stroke 44(12):3382–3393, 2013.

CHAPTER 91: QUESTIONS & ANSWERS 91.1. Which of the following statements concerning ischemic stroke is true? A. Anterior circulation strokes are more likely than posterior strokes to show evidence of progression at the time of presentation. B. Anterior circulation strokes rarely present with complete loss of consciousness. C. Posterior cerebral artery strokes are associated with incontinence, leg weakness greater than arm weakness, and gait clumsiness. D. The presence of aphasia suggests an anterior cerebral artery (ACA) distribution stroke, typically left sided. E. The presence of diplopia suggests an anterior circulation stroke.

has been a previous contralateral stroke. ACA strokes primarily affect frontal lobe functions and may also present with primitive grasp and such reflexes. In addition to contralateral motor and sensory defects, MCA strokes may present with expressive aphasia, agnosia, and ipsilateral hemianopsia.

Answer: B. Forty percent of posterior and 20% of anterior circulation strokes present with progressive symptoms. It is rare for anterior circulation (carotid, ACA, and middle cerebral artery [MCA]) strokes to significantly alter consciousness, unless there

Answer: B. Posterior circulation (vertebrobasilar) strokes involve the vertebral, basilar, and posterior cerebral arteries. Because this system supplies the reticular activating system, cerebellum, brainstem, occipital lobe, and brainstem vomiting centers, loss of

91.2. Which of the following is not associated with posterior circulation strokes? A. Diplopia B. Homonymous cranial nerve (CN) and extremity motor deficits C. Loss of consciousness D. Loss of visual object recognition E. Nausea, vomiting, and ataxia

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consciousness with vomiting, visual changes, and cerebral ataxia may be seen. Ipsilateral CN deficits (because these nuclei largely reside in the brainstem) occur with contralateral “body” deficits resulting from motor/sensory fiber decussation. 91.3. Headache, vomiting, and a decreased level of consciousness are most commonly seen with which of the following disorders? A. Ischemic stroke B. Intracranial hemorrhage C. Migraine headache D. Subarachnoid hemorrhage (SAH) E. Tic douloureux Answer: D. The incidence of headache is highest by far in patients with SAH. Vomiting and depressed loss of consciousness are also generally more common in this group. Pure migraine headache rarely, if ever, causes a depressed loss of consciousness. Tic headaches do not cause loss of consciousness. 91.4. What percentage of patients with hemorrhagic stroke experience clinical deterioration because of growth in hemorrhage volume within the first hours? A. 10% B. 20% C. 30% D. 50% E. 75% Answer: C. Thirty percent of patients with intracerebral hemorrhage (ICH) experience early hemorrhage expansion. Progression of neurologic deficits and decreasing mental status suggest the diagnosis. 91.5. A 69-year-old male presents with headache, vomiting, aphasia, a right lower facial palsy, and right upper greater than right lower extremity weakness. The symptoms began approximately 4 hours before arrival. Vital signs are temperature 99° C, blood pressure (BP) 180/90 mm Hg, respiratory rate 18 breaths per minute, heart rate 92 beats per minute, and oxygen saturation 96% on room air. Emergent computed tomography (CT) scan shows a left temporal intracerebral hemorrhage (ICH). Soon after presentation, the patient experiences increased vomiting and a diminishing level of consciousness. What is the most likely explanation for this deterioration? A. Accompanying subarachnoid hemorrhage (SAH) B. Acute brainstem herniation C. Hypoxia from neurogenic pulmonary edema D. Increase in volume of the ICH E. Myocardial infarction with cardiogenic shock Answer: D. Approximately one-third of patients with ICH experience early hemorrhage volume expansion. Although brainstem herniation is a possibility, this is typically a later sequelae with a more gradual presentation. Acute myocardial infarction may be associated with intracranial emergencies but would not likely cause an abrupt mental status change. Neurogenic pulmonary edema may accompany any condition with elevated intracranial pressure (ICP) but, again, would not likely cause an abrupt mental status change. 91.6. After complete occlusion of cerebral vessels, irreversible neurologic deficits are expected to reliably occur within how many hours? A. 2 B. 3 C. 4

D. 5 E. 6 Answer: E. Thus ischemic stroke trials, using fibrinolytic or antiplatelet agents, have attempted to recanalize occluded arteries and reperfuse ischemic areas of the brain within a 2- to 6-hour therapeutic window. 91.7. Which of the following areas of the brain is perfused by the posterior circulation? A. Internal capsule B. Posterior aspect of the temporal lobe C. Putamen D. Speech areas of the temporal lobe E. Thalamus Answer: E. The thalamus is perfused by the posterior circulation. The other areas are perfused by the anterior circulation. 91.8. Which of the following statements regarding stroke etiology is true? A. Lacunar strokes reliably cause a pure motor deficit. B. Less than 1% of strokes occur in the 15- to 45-yearold age group. C. One-third of ischemic strokes are thrombotic. D. Strokes resulting from atrial fibrillation likely involve small vessels. E. Two-thirds of ischemic strokes are cardioembolic. Answer: C. One-third of ischemic strokes are thrombotic. Lacunar strokes may cause a pure motor, pure sensory, or ataxic/hemiparesis stroke. Vessel occlusion resulting from atrial fibrillation–induced emboli more likely involves the large vessels. Three percent to 4% of ischemic strokes occur in the 15- to 45-year-old age group. 91.9. A 29-year-old female presents with a left-sided headache after a moderate-speed motor vehicle collision (MVC). She suffered no loss of consciousness and has no other complaints or obvious injuries. Physical examination is remarkable only for drooping of the left eyelid and slight miosis of the left pupil compared with the right. Which of the following would be the diagnostic test of choice? A. Brain magnetic resonance imaging (MRI) with gadolinium B. Contrasted computed tomography (CT) scan of the brain C. CT angiogram of the carotid arteries D. Uncontrasted CT scan of the brain E. Urine drug screen Answer: C. Carotid or vertebral artery dissection can occur after trauma or mild events, such as yoga, twisting, or prolonged static positions looking upward. The hallmark is unilateral neck pain, face pain, or headache, often with accompanying Horner’s syndrome. Acutely, cerebral ischemic changes would not be seen on brain imaging. Carotid and vertebral dissection is not a contraindication for thrombolytic therapy in the eligible patient. 91.10. What percentage of patients who experience a transient ischemic attack (TIA) will develop a stroke within 3 months? A. 5% B. 10% C. 15% D. 20% E. 25% Answer: B. One-tenth of them will occur within 2 days of the sentinel event.

CHAPTER 91  Stroke

91.11. A 28-year-old G3P3 woman who is 2-weeks postpartum after an uncomplicated vaginal delivery presents with acute onset of mild headache, lethargy, and double vision. Physical examination is remarkable for normal vital signs and a left eye lateral gaze palsy. The most appropriate intervention is likely to be which of the following? A. Computed tomography (CT) scan of the brain with possible lumbar puncture B. CT scan of the brain and intravenous (IV) heparin C. Erythrocyte sedimentation rate (ESR) and IV corticosteroids D. IV magnesium E. Lumbar puncture and IV antibiotics Answer: B. Cerebral venous thrombosis may present with headache, lethargy, cranial nerve (CN) deficits, seizures, or even psychiatric complaints. CT scan and/or magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) are likely to reveal the diagnosis. Treatment includes heparin. Neurosurgical consultation is not useful. Subarachnoid hemorrhage (SAH) would not be expected to cause a focal neurologic deficit. Eclampsia and meningitis would be expected to give characteristic findings on history and examination. 91.12. Which of the following statements is true regarding management of acute ischemic stroke? A. Heparin is indicated for patients in whom thrombolysis is not an option. B. If the initial computed tomography (CT) scan shows a large left middle cerebral artery (MCA) distribution stroke but no hemorrhage, thrombolysis would be indicated. C. Initial blood pressure (BP) greater than 185/110 mm Hg would contraindicate thrombolytic treatment. D. Mechanical thrombectomy may be indicated up to 6 hours after stroke onset. E. No clot retrieval devices have been U.S. Food and Drug Administration (FDA) approved for acute ischemic stroke management. Answer: D. Intra-arterial thrombolysis may offer benefit up to 6 hours past stroke onset. BPs higher than 185/110 mm Hg are not an absolute contraindication to thrombolysis if they can be lowered to this level with one or two doses of a parenteral agent, such as labetalol or enalapril. The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retrieval device was FDA approved in 2004, and several newer stent-retriever devices have been approved since then. In recent trials of thrombectomy, improved outcomes were demonstrated at least to 6 hours; and outcomes were even better when patients received reperfusion within 4.5 hours of onset. Aspirin has a proven benefit in patients who do not receive tissue plasminogen activator (tPA). There is no proven benefit to heparin, although some practitioners use it in cases at high risk of stroke progression. 91.13. An 82-year-old male presents with an apparent stroke. He is rapidly evaluated and determined to be within the 3- to 4.5-hour window for fibrinolytic therapy. Which of the following exclusion criteria applies only to the 3- to 4.5-hour criteria and not the 0- to 3-hour criteria? A. Administration of heparin within the 48 hours preceding the stroke onset B. Age older than 80 years C. High clinical suspicion for subarachnoid hemorrhage (SAH)

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D. Seizure at the onset of the stroke E. Symptoms rapidly improving Answer: B. In the 3- to 4.5-hour window, patients cannot exceed 80 years of age. Heparin administration within the 48 hours preceding stroke onset is a contraindication in both the 0- to 3-hour window as well as the 3- to 4.5-hour window. Similarly, high clinical suspicion for SAH, seizure at the onset of the stroke symptoms, and rapidly improving symptoms are contraindications to fibrinolysis in both time windows. 91.14. A 66-year-old female presents with a possible transient ischemic attack (TIA). Approximately 1 hour before her arrival, she had a 15-minute episode of strictly right arm and right leg weakness, and her symptoms have now resolved. Her blood pressure (BP) is 165/92 mm Hg. Her prior medical history is significant for hypertension, high cholesterol, and diabetes mellitus. What is her ABCD2 score? A. 4 B. 5 C. 6 D. 7 E. 8 Answer: C. The patient’s ABCD2 score is 6 (age >60 years, BP >140/90 mm Hg, unilateral weakness, symptoms lasting 10 to 59 minutes, and history of diabetes). No speech impairment is reported. 91.15. A 72-year-old male presents with an apparent stroke. Computed tomography (CT) imaging of the brain demonstrates only a hyperdense middle cerebral artery (MCA) sign and no other ischemic changes. He was last seen neurologically normal 4 hours earlier. Which of the following is a contraindication to fibrinolytic therapy in this patient? A. His blood glucose is 372 mg/dL. B. His National Institutes of Health (NIH) Stroke Scale score is 24. C. His platelet count is 110,000/mm3. D. His systolic blood pressure (BP) is 180 mm Hg. E. He takes warfarin daily. Answer: E. Any oral anticoagulant treatment (regardless of the patient’s international normalized ratio [INR]) is a contraindication to fibrinolysis in the 3- to 4.5-hour treatment window. Other contraindications include an NIH stroke scale score greater than 25, platelet count less than 100,000/mm3, blood glucose greater than 400 mg/dL, and systolic BP greater than 185 mm Hg. 91.16. A 75-year-old man is brought to the emergency department (ED) for altered mental status. After computed tomography (CT) imaging of the brain is performed, he is found to have a large intracerebral hemorrhage (ICH). Which of the following options is not an appropriate strategy for lowering intracranial pressure (ICP)? A. Barbiturate-induced coma B. Hyperthermia induction C. Hypertonic saline administration D. Hyperventilation E. Mannitol administration Answer: B. Hypothermia is an experimental modality for lower ICP. Hyperventilation can serve as a temporizing measure for reducing ICP. Mannitol and/or hypertonic saline can also be administered. Inducing a barbiturate coma is also an experimental modality.

C H A P T E R 92 

Seizures Elaine Rabin  |  Andy S. Jagoda PRINCIPLES Background and Classification Seizures are excessive abnormal neuron activity associated with alterations in sensory, motor, autonomic, and/or cognitive function. Convulsion refers specifically to the motor manifestations of a seizure. The ictal period is the time during which a seizure or seizure-like activity occurs. A postictal period is an interval of altered mental status immediately following a seizure, generally lasting less than 1 hour. Seizures may be provoked by, or secondary to, an acute clinical process (eg, acute central nervous system [CNS] insults, toxins, and acute metabolic derangements) (Box 92.1). Conversely, primary seizures are unprovoked and have no acute inciting pathology. Epilepsy refers to a condition of recurrent unprovoked seizures. For example, a patient who suffers head trauma might have a seizure but would not be considered to have epilepsy unless there are recurrent unprovoked ictal events as a result of the brain injury. Many cases of epilepsy are idiopathic, and the onset of these typically occurs during childhood or adolescence. Unprovoked seizures may begin de novo in adulthood, but this is rare and thus a diagnosis of exclusion. Unprovoked seizures may recur randomly or predictably. Cyclic recurrence has been reported with awakening, sleep deprivation, emotional or physical stress, and menses. A specific sensory stimulus, such as flashing lights or a specific smell, may trigger seizures in certain patients. Note that seizures are still considered “unprovoked” when they are triggered by a process that would not cause a seizure in the nonepileptic patient. Seizures are classified as partial (focal) or generalized (Fig. 92.1). Partial seizures involve abnormal neuronal firing within a confined population of neurons in one brain hemisphere, and the clinical manifestations tend to reflect the area of electrical activity. Simple focal seizure traditionally refers to focal seizure with preserved mental status, whereas complex focal seizures involve some degree of impaired consciousness. Generalized seizure denotes abnormal neuronal firing throughout both brain hemispheres and always involves alterations of consciousness. Secondarily generalized seizures start as a focal seizure and then progresses to a generalized event. Subclassification of focal seizures, although no longer used, is clinically useful to describe the ictal origin and manifestation.1 Symptoms can be motor (such as, facial twitching or rhythmic ipsilateral extremity movements), autonomic (such as, tachycardia or diaphoresis), somatosensory (such as, tingling or perceiving a certain smell), or psychic (such as, sense of déjà-vu). Psychic and somatosensory seizures, which involve only subjective, nonobservable symptoms, are referred to as auras when they precede a generalized seizure. The symptoms of generalized seizures are more global. One subtype, absence seizures, manifest as brief dissociative states, often without muscle or postural changes. Other generalized seizures are classified by their specific type of motor activity: tonic (stiffening), clonic (rhythmic jerking), tonic-clonic, myoclonic 1256

(discrete violent muscle contractions), or atonic (loss of muscle tone). The common term grand mal seizure refers to generalized tonic-clonic seizures. Status epilepticus is unremitting seizure activity of greater than 5 minutes’ duration, or recurrent seizure activity without intervening return to baseline mental status.2 Previous definitions of status epilepticus required 30 minutes of continuous activity based on the time thought to be required for seizures to inflict secondary damage. However, secondary effects can occur in under 30 minutes, and seizure activity is unlikely to cease spontaneously once it has continued for 5 minutes.2,3 Status epilepticus is divided into two basic categories: generalized convulsive status epilepticus (GCSE) and nonconvulsive status epilepticus (NCSE). GCSE typically involves tonic-clonic seizures and is a medical emergency, with mortality directly correlated with the duration of the event. NCSE presents clinically as an alteration in behavior that is associated with continuous epileptiform discharges on electroencephalogram (EEG). The altered mental status may range from a subtle change to coma, and it may be associated with subtle motor signs, such as twitching, blinking, eye deviation, persistent aphasia, or somatosensory findings. NCSE should be considered in patients in coma of undetermined etiology and patients who appear to have a prolonged post-ictal event. NCSE may be present in 10% or more of hospitalized patients with prolonged decreased cognition of undetermined etiology.4 A patient is considered to be in refractory status epilepticus when the seizure does not terminate after treatment with a benzodiazepine and a second antiepileptic drug. See Chapter 15 for a detailed discussion of the management of status epilepticus. A relevant question for the emergency clinician treating the seizing patient is whether the number or duration of seizures carries any significance with regard to the potential for recurrence and how this might influence cognitive outcomes. Patients with provoked seizures show equal incidence of later development of epilepsy regardless of whether or not treatment with antiepileptic drugs was initiated immediately after the inciting event.5 For patients with unprovoked seizures, the evidence is less straightforward. Whether recurrent or prolonged seizure activity can lead to cognitive deterioration remains a subject of debate. In general, current data challenge the idea of a common seizure-dependent mechanism for epilepsy progression and intellectual impairment. Although some studies have proposed that status epilepticus alone may result in cognitive impairment, independent of the inciting cause, most recent studies demonstrate that the majority of patients with epilepsy do not show a progressive disorder. The rare cases of intellectual decline and progressive worsening of seizures are limited to specific epileptic events (eg, mesial temporal lobe epilepsy, which can follow a progressive course induced by recurrent seizure activity).6

Epidemiology Patients presenting to the emergency department (ED) with seizures have a bimodal distribution, with the highest incidence

CHAPTER 92  Seizures

BOX 92.1 

Etiology of Status Epilepticus: Common Causative Disorders METABOLIC DISTURBANCES

Eclampsia Head trauma Intracerebral hemorrhage Neoplasm Neurosurgery Posterior reversible leukoencephalopathy Remote structural injury

Hepatic encephalopathy Hypocalcemia Hypoglycemia or hyperglycemia Hyponatremia Uremia

INFECTIOUS PROCESSES

INTOXICATION

CNS abscess Encephalitis Meningitis

Bupropion Camphor Clozapine Cyclosporine Flumazenil Fluoroquinolones Imipenem Isoniazid Lead Lidocaine Lithium MDMA Metronidazole Synthetic cannabinoids Theophylline Tricyclic antidepressants

WITHDRAWAL SYNDROMES Alcohol Antiepileptic drugs Baclofen Barbiturates Benzodiazepams

CENTRAL NERVOUS SYSTEM LESIONS Acute hydrocephalus Anoxic or hypoxic insult Arteriovenous malformations Brain metastases Cerebrovascular accident Chronic epilepsy

CNS, Central nervous system; MDMA, N-methyl-3,4-methylenedioxyamphetamine.

Seizures

Partial or focal

Simple partial

Complex partial

Secondarily generalized

Generalized

Absence

Myoclonic

Tonic

Clonic

Tonic-clonic

Atonic Fig. 92.1.  Simplified classification of seizures. (From ILAE proposal for revised terminology for organization of seizures and epilepsies 2010. Available at: www.ilae.org/commission/class/documents/ILAE%20 HandoutV10.pdf.)

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among infants and individuals older than 75 years old. This is explained by the high prevalence of febrile seizures in infants and structural brain damage in elders. Up to 45% of adults presenting with a first unprovoked seizure will experience another within 2 years, most occurring in the first year. The risk is higher with known brain lesions, imaging abnormalities, or nocturnal seizures. Up to 50% of patients with epilepsy have recurrent seizures despite initiation of therapy.

Pathophysiology When normal neurophysiology exists, neuronal cell membranes are stabilized by electrochemical gradients across the membranes and by equilibrium among inhibitory neurotransmitters, such as gamma-aminobutyric acid (GABA), and excitatory neurotransmitters, including glutamate and acetylcholine. Seizures start when the equilibrium across the cell membrane is disturbed, leading to abnormal electrical discharge of cortical and subcortical neurons. Infection, toxins, electrolyte imbalances, and other pathologic processes can disrupt the neuronal equilibrium locally and trigger electrical activity, resulting in a seizure. Electrical activity, in turn, can lead to recruitment of nearby neurons, and a partial seizure can spread. This is the underlying mechanism for Jacksonian March, when focal motor seizure symptoms spread in a step-wise fashion. When the electrical activity extends below the cortex to deeper structures, the reticular activating system in the brainstem may be affected, altering consciousness. In generalized seizures, the focus often is subcortical and midline, which likely explains the prompt loss of consciousness and bilateral involvement. Typically seizures are self-limited; at some point, the hyperpolarization subsides and the electrical discharges from the focus terminate. This termination may be related to reflex inhibition, loss of synchrony, neuronal exhaustion, or alteration of the local balance of acetylcholine and GABA in favor of inhibition. Most drugs used to interrupt seizures act on GABAA subtype receptors, therefore enhancing inhibitory activity. During ongoing seizure activity, neuronal GABAA receptors may be degraded and internalized whereas excitatory N-methylD-aspartate (NMDA) receptors may be upregulated. This perpetuates an excitatory state and leads to sustained seizure activity, making it the physiologic basis for the old adage, “seizures beget seizures.” Loss of GABAA receptors in status epilepticus can decrease response to GABAergic drugs, such as benzodiazepines, barbiturates, and propofol.3 Seizures produce a number of secondary physiologic derangements. Sympathetic stimulation leads to increases in body temperature, heart rate, respiratory rate, serum glucose, and lactic acid. Elevated lactate occurs within 60 seconds of a convulsive event and normalizes within an hour after ictus. A rise in the peripheral white blood cell count without an increase in bands is also often seen. With more prolonged convulsions, hypoglycemia, neurogenic pulmonary edema, skeletal muscle damage, and, rarely, frank rhabdomyolysis may ensue. Autonomic discharge and bulbar muscle involvement may result in urinary or fecal incontinence, vomiting, tongue biting, and potential airway impairment. Also rarely, the force generated by the muscle contractions in these seizures can be strong enough to cause posterior shoulder dislocations or fractures.

CLINICAL FEATURES In caring for patients who may have seized, one must first attempt to determine whether the event in question was a seizure. A common clinical scenario for the emergency clinician is the

patient who presents with a history of having had a seizure-like episode, usually involving sudden loss of consciousness and some type of motor activity. However, neurogenic seizures are not the only process that can cause these symptoms. (See the Differential Diagnosis section later for discussion of common seizure mimics.) Identifying the circumstances surrounding the event, such as possible inciting factors and progression and duration of symptoms, will provide important clues regarding whether the episode was a seizure. However, as a general rule, no single clinical feature or diagnostic modality is 100% confirmatory for occurrence of a neurogenic seizure. A prospective study that assessed which clinical aspects help distinguish seizures from syncope found a seizure to be five times more likely than syncope if the patient was disoriented after the event and three times more likely if the patient was older than 45 years old. Remarkably, incontinence and trauma were not discriminative findings between seizure, syncope, and nonepileptic attack disorder. Additional studies have shown that postictal confusion, tongue biting, cyanosis, confirmed unresponsiveness, preceding déjà vu or jamais vu, head or eye turning to one side, and rhythmic limb shaking or dystonic posturing are also strong markers of seizure. For the patient who is presumed to have seized or be seizing, the clinician should treat any persisting seizure activity and then consider the likelihood of underlying pathology requiring emergent treatment. A thorough history and physical examination largely directs the evaluation and can usually prevent the need for broad-based diagnostic testing. Unfortunately, the actively-seizing or postictal patient is often unable to provide reliable history or to cooperate during the initial examination. Witnesses, relatives, paramedics, medical alert bracelets, old medical records, and medication lists or containers often provide critical clues to assessing these patients.

Clinical History The clinician should obtain any history of trauma (either before or during the seizure), alcohol intoxication or abuse, and pregnancy. See the Special Cases section for separate discussions of seizures in these contexts. Although febrile seizures are common in children (see separate discussion of seizures in pediatric patients in Chapter 174) this is not true of adults, and fever preceding a seizure can indicate CNS infection. Patients who are immunocompromised, had recent neurosurgery, or have CNS hardware (such as, a shunt) are at particularly high risk. Fifteen percent of patients with bacterial meningitis will have at least one seizure, and surviving patients have an increased residual risk of epilepsy. Severe headache prior to seizure raises concern for intracranial bleeding, especially in elders and anticoagulated patients. Patients with indwelling shunts and a headache prior to seizure may have shunt failure. Headache after a seizure may be indicative of bleeding but may also be part of a post-ictal syndrome. Seizure patients with preceding neurologic deficits may have a seizure as a symptom of an acute stroke. Ischemic or hemorrhagic stroke is a leading cause of new-onset seizures in elders.7,8 The overall incidence of seizures with stroke ranges from 5% to 15%; more than one-half occur within the first week after stroke. The incidence of epilepsy after stroke is 4% to 9%. Seizures that occur acutely with stroke are thought to result from local metabolic alterations in the CNS. These events are transient, and the seizures often are focal and self-limited. Stroke-related seizures that develop later are more likely to be generalized. Symptomatic dysrhythmias can cause cerebral hypoperfusion and hypoxia, which can lead to seizure activity. Prolonged QT syndrome has been misdiagnosed as a primary seizure disorder. A careful history may identify preceding cardiac symptoms, such

CHAPTER 92  Seizures

as palpitations, lightheadedness, or diaphoresis. An electrocardiogram (ECG) may be diagnostic; but when it is not clear, a concurrent cardiac evaluation may be indicated. As these examples demonstrate, obtaining a history of nonneurologic comorbid disease plays an important role in identifying underlying pathology requiring treatment. In addition to testing prompted by known or suspected cardiac disease, the existence of renal failure, immunosuppression, or recent electrolyte abnormality may drive laboratory investigations of electrolytes and uremia. Diabetes raises concern for hypoglycemia. Patients with a psychiatric history may have psychogenic seizures, but they may also suffer from hyponatremia due to pathologic water intoxication or as an adverse effect of a psychiatric medication. Those with depression or psychosis may be at higher risk for drug- or toxin-related seizures. Patients with malignancy may have a new or enlarging CNS lesion. Alzheimer’s disease has been noted to increase the risk of epilepsy by tenfold. The patient’s social history is also important. Noncompliance with anticonvulsants is the most common cause for the ED presentation of recurrent seizures. Certain recreational drugs (such as, cocaine, phencyclidine, and ecstasy) are known to decrease the seizure threshold. Common causes of adult-onset partial seizures in the developing world include neurocysticercosis (especially Central and South America) and malaria, both of which should be considered in travelers and immigrants. Finally, investigation of potential precipitants (such as, sleep deprivation, infection, or new medications, especially those that can lower the seizure threshold or affect later antiepileptic drug metabolism) is key to managing the patient with a known seizure disorder who has a typical event while on medications.

Physical Examination An accurate set of vital signs is the foundation of any physical examination. Although a low-grade fever is common immediately after a prolonged convulsion, a persistently high temperature suggests infection or drug reaction. Hypertension with bradycardia may be the result of rising intracranial pressure and impending herniation. Irregular heart rate may accompany a stroke. Anticholinergic and sympathomimetic syndromes may suggest a drug-related seizure, which may make a significant difference in management. If the patient presents actively seizing, observe the specifics of the motor activity. Focal abnormalities and eye deviation are signs of an epileptic focus. Anecdotally, pupils are often reported to be dilated during or after a seizure; persistent mydriasis may reflect anticholinergic or sympathomimetic toxicity. Some patients in NCSE are mistakenly assumed to be postictal instead of actively seizing. Mental status should be carefully documented and observed for change. When possible, recruit family members or contacts who know the patient’s baseline mental status. Postictal confusion usually resolves within 1 hour; failure to improve should prompt a search for alternate explanations (Box 92.2). A thorough neurologic examination is the key component of the evaluation. Hyperreflexia and extensor plantar responses are suggestive of a recent seizure and should resolve during the immediate postictal period. Neurologic deficits may represent an old lesion, new intracranial pathology, or postictal (Todd’s) paralysis. Todd’s paralysis is a focal motor deficit that may persist up to 24 hours after generalized or complex partial seizures and may be caused by transient focal cerebral hypoperfusion.9 Clinical presentation ranges from weakness of one extremity to a complete hemiparesis. Todd’s paralysis is associated with a high likelihood of an underlying structural cause for the seizure. In the case of suspected Todd paralysis that does not quickly resolve, the physician must rule out a new structural lesion.

BOX 92.2 

Differential Diagnosis of Altered Mental Status in the Patient Who Has Seized POSTICTAL PERIOD

NCSE or subtle convulsive status epilepticus (can mimic the following): • Hypoglycemia • CNS infection • CNS vascular event • Drug toxicity • Psychiatric disorder • Metabolic encephalopathy • Migraine • Transient global amnesia CNS, Central nervous system; NCSE, nonconvulsive status epilepticus.

Seizures are often associated with injury, and the patient must be evaluated for both soft-tissue and skeletal trauma. Head trauma and tongue lacerations are common. Seizure activity can also produce dislocations and fractures. Posterior shoulder dislocations are extremely rare but, when present, should prompt suspicion that a seizure has occurred. Seizure-induced fractures are also rare but commonly missed; the humerus, thoracic spine, and femur are most commonly involved.

DIFFERENTIAL DIAGNOSIS Convulsive Syncope Syncope associated with seizure-like movements, convulsive syncope, is most commonly associated with bradycardia. In these cases, as heart rate returns to normal, abnormal muscle activity ceases, and there is no post-ictal period.10 Based on observational studies in blood donors, up to 40% of patients with syncope will have some component of motor activity, most commonly involving tonic extension of the trunk or myoclonic jerks of the extremities. This phenomenon has been observed in patients who are in a seated position. These events are usually not associated with tonic-clonic movements, tongue biting, cyanosis, incontinence, or postictal confusion. Nausea or sweating before the event makes seizure much less likely than syncope.

Nonepileptic Attacks Also referred to as nonepileptic spells, these are nonepileptic paroxysmal neurologic events that may resemble seizures in appearance but do not result from abnormal cortical discharge. Etiologies for these include breath-holding spells, involuntary movements, decerebrate or decorticate posturing, and psychogenic seizures. Psychogenic seizures (also known as pseudoseizures or nonepileptic seizures) have been reported in 12% to 18% of patients with transient loss of consciousness and can exist concomitantly with neurogenic seizures.11 Psychogenic seizures are rarely caused by malingering but instead are more commonly a functional neurological symptom disorder, formerly called a conversion disorder. Characteristic features of a psychogenic seizure include out-ofphase tonic-clonic activity, forward pelvic thrusting, and voluntary eye movements away from the examiner.

DIAGNOSTIC TESTING Laboratory Studies If a patient with a new-onset seizure has no significant comorbid disease and a normal examination (including mental status), the

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likelihood of an electrolyte disorder is extremely low. The American College of Emergency Physicians (ACEP) published an evidence-based clinical policy on the initial approach to patients presenting with seizures in 2014. The guidelines emphasize that extensive metabolic testing in patients who had returned to a normal baseline after a first-time seizure is not indicated.12 Also, only a serum glucose and sodium level, as well as a pregnancy test (in women of childbearing age), are likely necessary in patients who are otherwise healthy with a new-onset seizure and normal neurologic status. This is the same conclusion reached in a practice parameter published in 2007 by the American Academy of Neurology on the evaluation of first-time seizures. Patients with persistent alteration of mental status, those in status epilepticus, and those who have fever or new neurologic deficit are unique in that they require extensive diagnostic testing. This includes serum glucose, electrolytes, urea nitrogen, creatinine, magnesium, calcium, complete blood count, pregnancy tests in women of childbearing age, antiepileptic drug levels, liver function tests, and drugs-of-abuse screening. Hypoglycemia is a common metabolic cause of provoked seizures. Ictal activity can occur at a plasma glucose level less than 45 mg/dL, although some patients may have a seizure at higher levels. Convulsive and nonconvulsive generalized seizures and focal seizures all may occur during hypoglycemia. Note that prolonged seizures can cause hypoglycemia. Seizures that do not cease after correction of low blood glucose deserve further evaluation and treatment for alternative causes. If an arterial blood gas analysis is obtained in a convulsing patient (although it is not routinely indicated), it may show an anion gap metabolic acidosis secondary to lactic acidosis. The anion gap acidosis should resolve within an hour after the seizure ends. Persistence beyond this time suggests an underlying process, such as sepsis, ketosis (alcoholic or diabetic), or poisoning (methanol, iron, isoniazid, ethylene glycol, salicylates, carbon monoxide, or cyanide). A drug-of-abuse screen and alcohol level should be considered in patients with first-time seizures, although there is no evidence that such testing changes outcome. A positive drug-of-abuse screen does not prove causation, and the patient would still require an EEG and neuroimaging study to direct management. The screen may, however, suggest an etiology and help with future medical and psychiatric disposition. Seizure due to alcohol intoxication or withdrawal is a diagnosis of exclusion, because alcoholics are at increased risk for electrolyte abnormalities and traumatic injuries. Both creatine phosphokinase and prolactin have been investigated as markers of seizures. Neither has been found sufficiently sensitive or specific to be used in the ED.

Lumbar puncture should be considered in patients with fever, severe headache, or persistent altered mental status. Asymptomatic patients with a history or strong suspicion of immunocompromise are also candidates for a lumbar puncture. There are no cases in the literature of a bacterial CNS infection presenting as isolated seizure without fever or abnormal neurologic findings in immunocompetent individuals. Theoretically, an exception may occur in cases of partially treated meningitis. A transient cerebrospinal fluid (CSF) pleocytosis of up to 20 white blood cells/mm3 has been reported in up to 23% of patients with seizures. However, one is obligated to assume that the presence of white blood cells in the CSF of a seizing patient represents meningitis until proven otherwise.

Electrocardiogram

Electroencephalogram

Patients with a history of cardiac disease, preceding or ongoing cardiac symptoms, and those who continue to seize may benefit from cardiac monitoring. The same is true of patients suspected of overdose. An ECG is also an early screen for drug toxicity. Tricyclic cardiotoxicity may manifest as a QRS complex lasting more than 0.1 second or a rightward shift of the terminal 40 ms of the frontal plane QRS complex (a prominent R wave in lead aVR). The ECG can also identify a prolonged QT, a delta wave, Brugada pattern, or heart block, which might contribute further insight into the seizure etiology.

The EEG is the definitive test for diagnosing a seizure disorder, although its sensitivity varies depending on timing and location of the seizure focus. It is particularly helpful when the diagnosis is in doubt, such as in acute confusion states and coma, as well as for the diagnosis of NCSE.14 NCSE has been identified in up to 25% of patients treated for GCSE who were thought to no longer be seizing. Delay in diagnosis of NCSE is associated with increased mortality.15

Neuroimaging

For the patient who has had a seizure prior to hospital arrival or in the ED but is not actively convulsing, only supportive care may be needed. Restraints may be needed during post-ictal confusion to prevent falls, especially in Todd’s paralysis patients who have motor weakness in addition to confusion. However, the use of

There is general agreement that neuroimaging is indicated in patients with a first-time nonfebrile seizure, though in select patients who have returned to a normal baseline and who have

BOX 92.3 

Factors Associated With Abnormal Computed Tomography Findings in Patients Presenting to the Emergency Department With Seizure • • • • • • • • • •

Focal abnormality on neurological examination Malignancy Closed head injury Neurocutaneous disorder Focal onset of seizure Absence of a history of alcohol abuse History of cysticercosis Altered mental status Patient older than 65 years old Seizure duration more than 15 minutes

access to follow up care, imaging can be obtained as an outpatient. The Academy of Neurology guidelines reinforce this, as do studies suggesting that computed tomography (CT) will change acute management of patients with a new seizure in up to 17% of cases.13,15 The usefulness of emergent imaging otherwise depends on the clinical situation. Box 92.3 summarizes useful criteria in determining who will benefit from a CT scan while in the ED. Magnetic resonance imaging (MRI) is generally the diagnostic test preferred by neurologists in evaluating first-time seizure, because it is better than CT in identifying small lesions. MRI is not better than CT for detecting acute hemorrhage, however, and there are no ED-based studies that have evaluated MRI utility in seizure management.

Lumbar Puncture

MANAGEMENT

CHAPTER 92  Seizures

TABLE 92.1 

Management of “Special Situation” Seizures in the Emergency Department CLINICAL SITUATION

AGENT OF CHOICE

DOSAGE/COMMENT

Hyponatremia

Hypertonic (3%) saline

2 to 3 mL/kg of 3% NaCl in rapid sequential boluses until seizures stop

Hypocalcemia

Calcium chloride or gluconate

Sequential ampules until seizures stop

Tricyclic antidepressant overdose

Alkalization

Administer 0.5 to 1.0 mEq/kg IV bolus; repeat as needed to maintain a blood pH of 7.4 to 7.5

Salicylate overdose

Alkalization; hemodialysis for severe cases

Administer 0.5 to 1.0 mEq/kg IV bolus; repeat as needed to maintain a blood pH of 7.4 to 7.5

Isoniazid overdose

Pyridoxine

5 g IV (adult) or 70 mg/kg (pediatric) As per idiopathic seizures

Cocaine intoxication

Benzodiazepines

Lithium toxicity

Hemodialysis

Alcohol-associated seizure

Lorazepam

0.05 to 0.10 mg/kg

MDMA

Benzodiazepines

Be aware of possible hyperthermia or hyponatremia

Eclampsia

Magnesium

IV loading dose of 4 to 6 g over 15 to 20 minutes, then 1 to 2 g/h infusion; monitor patients for hyporeflexia; alternatively, lorazepam (Ativan) 4 mg IV over 2 to 5 minutes or diazepam (Valium) 5 to 10 mg IV slowly can be used to terminate the seizure, after which magnesium sulfate is administered

IV, Intravenous; MDMA, N-methyl-3,4-methylenedioxyamphetamine; NaCl, sodium chloride.

restraints requires careful monitoring, and they should be removed as quickly as possible. Seizure pads may be protective in the case of seizure recurrence. Vascular access should be obtained in case the patient requires future abortive treatment, and the patient should be monitored for improvement to baseline. The management of a patient experiencing a seizure begins with active, anticipatory airway management. A jaw thrust, use of a nasopharyngeal airway, and supplemental oxygen may be required. In generalized ictus, the gag reflex is suppressed and vomiting or aspiration may occur. Suction should be available and, if possible, the patient should be placed in a left lateral decubitus position to lessen chances of aspiration. Care should be taken to avoid iatrogenic trauma from forceful placement of intraoral devices. The patient should be protected from accidental trauma during the seizure, with bed rails raised and seizure pads used as available. If not already present, an intravenous (IV) line should be placed in case abortive treatment is required. Most seizures are self-limited and resolve in a few minutes; however, clinicians should anticipate the need for aggressive care if status epilepticus develops. Table 92.1 lists specific treatments for active seizures due to certain underlying pathology. Management of status epilepticus is discussed in Chapter 15.

Initiation of Antiepileptic Drugs First-Time Seizures Based on the best available evidence, the current ACEP Clinical Policy states that emergency clinicians do not need to initiate an antiepileptic drug in patients who have had a first provoked or a first unprovoked seizure without evidence of brain disease or injury.12 Rather, the patient should be discharged with referral for neurologic consultation. The rationale for this approach is threefold. First, the diagnosis may be incorrect, especially if the seizurelike activity was not witnessed by experienced medical personnel. It is estimated that 20% to 25% of patients diagnosed as having seizures are eventually determined not to have seizures, with the most frequent alternative diagnoses being cardiovascular and psychopathologic etiologies.

Second, the patient may not have a recurrent seizure. It is estimated that less than 50% of patients who have had a single unprovoked seizure will experience a recurrent seizure within 2 years. The presence of EEG abnormalities suggests greater risk, but this information usually is unavailable in the ED setting. Other factors associated with an increased risk of recurrence are focal (versus generalized) ictus, status epilepticus, a history of intracranial surgery or trauma, and the presence of a persistent neurologic abnormality, such as Todd’s paralysis. Furthermore, whereas treatment decreases the risk of early recurrent seizure, it does not affect long-term prognosis of epilepsy, nor does it have an impact on patient quality of life, with the exception of driving limitations. Third, antiepileptic medications have side effects that may outweigh the benefit of treatment, especially in women of childbearing age (owing to their teratogenicity); in patients with liver, kidney, or hematologic disorders; and in patients already taking multiple medications. (The American Academy of Neurology’s evidence-based guideline notes that these are usually mild and reversible.) For patients with a history of stroke, brain trauma, tumor, or other CNS disease or injury, the ACEP guideline states that antiepileptic drug therapy may be initiated but advises that it is best done by a neurologist in coordination with the patient’s primary care provider. The reason for beginning antiepileptic drugs in this group of patients is their higher probability of recurrence. See Table 92.2 for antiepileptic drug dosing.

Patients With a History of Seizures Antiepileptic drug noncompliance and subtherapeutic antiepileptic drug levels in a patient who has had a seizure are commonly encountered in the ED. Serum antiepileptic drug levels should be checked in these patients when possible, and repleted if found to be low. Literature to support the recommendation of one route of antiepileptic drug administration over another (oral versus parenteral) is inconclusive, mainly because most available studies used antiepileptic drug serum concentration levels instead of early seizure recurrence as a primary outcome measure. Within this

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TABLE 92.2 

Loading Dose Route of Administration for Antiepileptic Drugs When Resuming Treatment in the   Emergency Department DRUG

LOADING DOSE, ROUTE

POTENTIAL ADVERSE EFFECTS

Carbamazepine

8 mg/kg oral suspension, single oral load IV not available

Drowsiness, nausea, dizziness

Gabapentin

900 mg/day oral at 300 mg tid for 3 days IV not available

Somnolence, dizziness, ataxia, fatigue

Lacosamide

Oral and IV preps available but loading dose not studied

Dizziness, headache

Lamotrigine

6.5 mg/kg single oral load IV not available

Nausea

Levetiracetam

1500 mg oral load Rapid IV load up to 60 mg/kg

Fatigue, dizziness

Phenytoin

20 mg/kg divided in maximum doses of 400 mg every 2 hours orally; or 18 mg/kg IV at ≤50 mg/min

IV: Hypotension, bradyarrhythmias, extravasation injuries

Fosphenytoin

20 PE/kg at maximum rate of 150 PE/min; can also give IM

Less prominent than with phenytoin

Valproate

Up to 30 mg/kg IV at maximum rate of 10 mg/kg/min

Local irritation

IM, Intramuscular; IV, intravenous; PE, phenytoin sodium equivalents. Data from Bacon D, Fisher RS, Morris JC, et al: American Academy of Neurology position statement on physician reporting of medical conditions that may affect driving competence. Neurology 68(15):1174–1177, 2007.

limited evidence, most studies have compared phenytoin and fosphenytoin in oral and IV routes. Oral loading has been reported to have fewer adverse drug events (eg, hypotension) than either of the IV loading methods. As expected, therapeutic plasma concentrations are achieved significantly faster with the IV route. Some emergency clinicians still prefer parenteral loading of phenytoin or fosphenytoin to ensure adequate serum level on discharge. However, there is no good evidence that this practice decreases risk of seizure recurrence.

SPECIAL CASES Alcohol-Related Seizures Of seizure patients presenting to an ED, 20% to 40% have seizures related to alcohol abuse. Alcohol-withdrawal seizures account for a substantial portion of these alcohol-related seizures, but alcohol abuse and dependence puts patients at risk of seizure in a plethora of other ways, such as increased incidence of traumatic brain injury, hypomagnesemia due to malnutrition, and possible co-ingestion of other toxins. In more than 50% of cases, alcoholrelated seizures occur as an adjunct to other risk factors, including preexisting epilepsy, structural brain lesions, and the use of recreational drugs. A first-time “withdrawal” seizure must be evaluated as any first-time seizure, even in alcoholics who claim to have had seizures in the past but for whom no documentation of previous seizures or evaluation is available. Other conditions need to be ruled out by history, physical examination, and diagnostic testing, including electrolytes, glucose, and brain CT scan. The diagnostic yield for CT following a first alcohol-related seizure is high. A 1988 Denver study reported head CT scan results in 259 patients with a first alcohol-related convulsion. A clinically significant lesion was found in 16 (6.2%) patients, seven of whom were alert and had nonfocal neurologic examinations and no history of trauma. Nearly 4% had CT findings that changed clinical management (eg, subdural hematoma, aneurysm, subarachnoid hemorrhage, and neurocysticercosis). In these patients, the history and physical examination did not predict the CT abnor-

mality. This study highlights the need to strongly consider neuroimaging in this special group of patients. The diagnosis of alcohol-withdrawal seizure, after exclusion of other etiologies, is based on a history of recurrent events temporally related to stopping or significantly decreasing alcohol intake. Alcohol-withdrawal seizures are usually generalized events and occur between 6 and 48 hours after cessation of drinking. Seizures occur in one-third of these patients.16 Once a diagnosis of alcohol-withdrawal seizure is made, management focuses on patient safety, minimizing the risk for a second withdrawal seizure, and patient education. Recurrent seizures have been reported in 13% to 60% of these patients, with most occurring within 12 hours of onset. Clinical findings cannot predict who is likely to have a recurrent seizure in the ED. The patient may or may not have other signs of alcohol withdrawal (such as, tachycardia, confusion, or tremors) that may indicate a likelihood of developing a seizure. Benzodiazepines are the treatment of choice in alcoholwithdrawal seizure. They offer cross-tolerance with alcohol by acting at the GABA receptor site and reduce the signs and symptoms of alcohol withdrawal. All benzodiazepines appear to be equally efficacious in terminating an alcohol-withdrawal seizure; however, lorazepam is the only benzodiazepine that has been shown to decrease the incidence of seizure recurrence and decrease the need for hospitalization. The number needed to treat to prevent one further withdrawal seizure at 6 hours is five. Phenytoin does not have a role in managing pure alcoholrelated seizures in the ED.17

Toxins Toxins can alter the brain equilibrium of excitatory and inhibitory neurotransmitters to cause seizures. Many illicit drugs disrupt the equilibrium, including cocaine and other stimulants and narcotics. Tonic-clonic seizures have been reported with use of synthetic cannabinoids (eg, “spice” and “K2”).18 Marijuana, however, is not commonly associated with seizures, and some forms of severe epilepsy may be treated with medical marijuana.19 Seizures occurring after abuse of N-methyl-3,4-methylenedioxyamphetamine (MDMA) compounds (eg, “ecstasy” and “Molly”) may be due to

CHAPTER 92  Seizures

associated hyponatremia and hyperthermia. Seizures can also result from withdrawal from benzodiazepines or barbiturates. Cases of toxin-induced refractory status epilepticus pose a particular challenge, because the mechanism of status epilepticus may be different from status epilepticus with other causes. Some toxins (eg, isoniazid) cause depletion of GABA neurotransmitter; and because some of the typical pharmacologic agents act by sensitizing the GABA receptor, they are less effective. In these cases, early administration of pyridoxine may be advantageous, because it replenishes GABA in the brain. It is initially dosed at 5 g IV in adults and 70 mg/kg IV in children. Most drug-induced seizures, particularly those resulting from cocaine and other stimulants, respond best to benzodiazepine therapy. Barbiturates or propofol are also good options. As with alcohol-induced seizures, phenytoin is ineffective for most druginduced seizures; and in some cases, it may be harmful such as in theophylline or tricyclic overdose. Phenytoin administration is generally contraindicated in cases of ingestion, because its sodium channel blocking actions can worsen the hemodynamic impact of the ingestion.20

Post-Traumatic Seizures The incidence of seizure after head trauma is related to injury severity. After minor head injury (Glasgow Coma Score [GCS] >12) the incidence is 1.5%, whereas the incidence increases to 17% after a severe traumatic brain injury (GCS 250 mm in adults >280 mm in children Normal CSF diagnostic studies Normal neuroimaging studies No other cause of increased ICP identified CN, Cranial nerve; CSF, cerebrospinal fluid; ICP, intracranial pressure.

CHAPTER 93  Headache Disorders

from sleep and is exacerbated by bending forward and the Valsalva maneuver, both of which impede cerebral venous return. Visual complaints are common, and patients may experience transient visual obscurations (TVOs), which are momentary blackouts of vision most likely due to temporary disruption of the microcirculation to the optic nerve head. They usually occur with postural changes and are not predictive of permanent visual loss. Patients may also complain of nausea, vomiting, dizziness, and pulsatile tinnitus. The physical examination will reveal papilledema and visual field defects or visual loss occurs in up to 50% of patients. Fortunately, in the majority of patients, visual defects are reversible with treatment.54 On occasion, a sixth nerve palsy (ie, a false lateralizing sign) is noted.

Differential Diagnoses The differential diagnoses of IIH include other causes of increased ICP in a patient presenting with headache. Important considerations include CVT, mass lesions, obstructive hydrocephalus, and leptomeningeal infiltration by neoplastic or infectious processes.

Diagnostic Testing MRI with MRV is the preferred modality for diagnosing IIH because of its ability to not only detect mass lesions and hydrocephalus but also CVT and other meningeal processes. If neuroimaging is normal, a LP should be performed in the lateral decubitus position to measure CSF opening pressure and to obtain CSF diagnostic studies, including cell counts, protein, glucose, cultures, and cytology. An opening pressure of 250 mm H2O or more (normal 70 to 180 mm H2O) is necessary to make the diagnosis. An ophthalmology consult should also be ordered for detailed visual field testing.

Management Many patients present without visual field loss, and symptomatic therapy is all that is necessary. Removal of a large amount of CSF (>20 mL) to decrease CSF pressure to relieve the patient’s headache is recommended in all treatment guidelines for IHH. We believe this should be considered for all patients with headache caused by IIH, although the benefit of this practice has not been established in clinical studies. CSF is produced relatively quickly, which limits the duration of benefit. In patients with evidence of visual field loss, treatment with medications to lower ICP is indicated. Acetazolamide is the most potent medication for lowering ICP, and the usual starting dosage is 500 mg twice a day. Other medications that have been used include furosemide, topiramate, and steroids. If a patient is not responsive to medications or has progressive symptoms, referral to an ophthalmologist for optic nerve sheath decompression or a neurosurgeon for a CSF diversion procedure (eg, lumboperitoneal or ventriculoperitoneal shunt) may be indicated.54

Disposition Because visual loss can occur early or late in the course of IIH, appropriate specialists including ophthalmology and neurology should be involved in the patient’s evaluation, treatment, and disposition.

Post–Dural Puncture Headache Principles Post-dural puncture headache (PDPH) is a frequent complication of dural puncture, whether performed for diagnostic or therapeu-

tic purposes or accidentally, as a complication of epidural anesthesia. The incidence is highest in the 18- to 30-year age group, and it is uncommon in young children and in adults older than 60 years old. Other than age, risk factors include female gender, low body mass index (BMI), and history of chronic headache.55 The pathophysiology of PDPH is not entirely clear. The most likely explanation is a persistent CSF leak that exceeds CSF production, resulting in CSF hypotension. If sufficient CSF is lost, the brain descends in the cranial vault when the patient assumes the upright position, leading to increased traction on the pain fibers. Thus the headache is characteristically positional and increases with the upright position and decreases with recumbency. The amount of time a patient remains recumbent after LP does not appear to affect the incidence of headache. Certain equipment related factors have been implicated as causes of PDPH, including the size or diameter of the spinal needle, the orientation of the bevel during the procedure, and the amount of fluid withdrawn. Smaller-diameter needles (eg, 20- or 22-gauge cutting needle) cause less leakage, and it is postulated that insertion of the needle with the bevel up (ie, bevel pointing up when the patient is in the lateral position) minimizes damage to the dural fibers. Use of atraumatic needles (eg, Whitaker or Sprotte) also has been shown to reduce the incidence of PDPH.56 If atraumatic needles are not available, we recommend using a 20- or 22-gauge cutting needle when possible.

Clinical Features The cardinal feature of PDPH is orthostatic or positional headache that is precipitated by the upright position and relieved when the patient lies down. About 90% occur within the first 72 hours after the LP and typically resolve within 1 week.57 The headache is often described as bilateral and throbbing, frequently in the frontal or occipital regions. Associated signs and symptoms include neck stiffness, nausea, vomiting, auditory disturbances including tinnitus and hypoacusis, and photophobia.

Differential Diagnoses For most patients, PDPH is a benign disorder. However, in patients who do not respond to standard treatment modalities, other secondary headache disorders must be considered. This is especially true in postpartum period where CVT is an important consideration.

Diagnostic Testing The diagnosis of PDPH is based on clinical features, and most patients have a benign course that requires no diagnostic testing. Spontaneous CSF leaks present with orthostatic headaches, which are sometimes severe and should be considered in the absence of a recent LP. The diagnosis is made when low CSF pressures are found on LP. In the postpartum period, CVT can be excluded with MRV.

Management Most PDPHs resolve spontaneously within 5 to 7 days with bed rest, adequate hydration, and mild analgesics. For persistent headaches, methylxanthine agents (such as, caffeine and aminophylline) have been used, but their efficacy has not been proven. We do not recommend their routine use in the ED. For severe headaches that do not respond to conservative measures, an epidural blood patch (EBP) should be used. This procedure involves the injection of 15–30 mL of autologous blood into the epidural space near the site of the original dural puncture resulting in a

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blood clot that seals off the dural hole. EBP has a very high success rate and should be used for PDPH that does not respond to conservative measures.58

Disposition The vast majority of patients with PDPH will have a benign course requiring only conservative treatment. For patients with persistent complaints, consultation with anesthesia or radiology for an EBP should be considered. If a patient does not respond to an EBP, other secondary causes of PDPH should be considered, especially in postpartum patients.

Management There is insufficient evidence to determine the optimal treatment of PTHA. We recommend the same armamentarium of medications used to treat acute primary headaches, specifically, antiemetic dopamine antagonists such as metoclopramide or prochlorperazine, and NSAIDs. Opioids should be avoided.

Disposition Patients with PTHA should be discharged home with outpatient follow-up.

Post-Traumatic Headache

Hypertensive Headache

Principles

Principles

Headache is the most common symptom following a concussion or other traumatic brain injury (TBI). It is often part of a complex post-concussive syndrome that can include dizziness, fatigue, insomnia, irritability, memory loss, and difficulty with concentration. Persistent headache occurs in over 50% of patients who have suffered a TBI.59 Paradoxically, patients with milder injuries are more likely to report persistence of symptoms, as are patients with preexisting headache disorders. For the emergency clinician, management of post-traumatic headache (PTHA) is different in the immediate aftermath of trauma, when excluding life-threatening causes are of paramount importance, versus dealing with the ramifications of PTHA during the days, weeks, and months that follow the trauma when it has become clear that no neurosurgical emergencies exist. The pathophysiologic mechanism for the symptoms is unclear and may have both anatomic and functional components.

The relationship between elevated blood pressure and headache is unclear. Ambulatory blood pressure monitoring studies have not demonstrated an association, although these studies are limited by relatively modest blood pressure elevations during the study period.2 In the ED, nearly one-quarter of patients who present to an ED with headache have a systolic blood pressure above 150 mm Hg or diastolic blood pressure over 95 mm Hg. Patients who present with headache are more likely to have a markedly elevated blood pressure than patients with other chief complaints. However, the causal pathway, if one exists, is not apparent based on current evidence. In fact, both chronic hypertension and acute elevation in blood pressure have been linked to decreased pain sensitivity in animal and human models. International criteria attribute headache to elevated blood pressure when the pressure is greater than 180 mm Hg systolic or 120 mm Hg diastolic and when the headache resolves with resolution of the elevated blood pressure.42

Clinical Features By international criteria, PTHA develops within 7 days of the injury or regaining consciousness. Acute PTHA resolves within 3 months, whereas persistent PTHA persists beyond 3 months. Patients in whom PTHA develops after minor head injuries have normal findings on neurologic examination and neuroimaging studies. Most patients are concerned about the cause of the headache more than about the headache itself. PTHA may assume a variety of characteristics, including the pulsating unilateral pain and associated features of migraine, the bland, squeezing pain of tension-type headache, or nonspecific headache often relating to the musculature of the neck.

Differential Diagnoses In the acute setting, pathological causes of headache including intracranial hemorrhage, or skull or cervical fractures should be excluded. Cervical strain and subtle oculomotor nerve palsies are additional etiologies of PTHA that should be considered. Beyond the acute setting, it may be difficult to distinguish PTHA from migraine or tension-type headache, a distinction that, as time passes, becomes less important.

Diagnostic Testing In the acute setting following TBI, traumatic injuries to the brain, skull, and neck should be evaluated using available clinical decision rules (see Chapter 34). Patients who return to the ED with persistent symptoms after normal initial imaging should be reassured that follow-up imaging is not required, assuming the patient has a normal neurologic examination and is not using anticoagulants or antiplatelet medication.

Clinical Features The headache of severe hypertension is generally characterized as bilateral and throbbing. Early reports of a typical hypertensive headache come from patients with marked, untreated hypertension, who had early morning headaches that were of greatest intensity before the patient arose and typically resolved as the patient engaged in morning activities.

Differential Diagnoses Based on population prevalence, the most likely diagnoses in patients with elevated blood pressure and headache are migraine or tension-type headache with concomitant hypertension.60 Pre-eclampsia, a disorder characterized by elevated blood pressure and headache, should be considered in patients in the latter stages of pregnancy and the recent postpartum period. Posterior reversible encephalopathy syndrome is characterized by white matter changes on diagnostic imaging. Malignant hypertension, including drug-induced hypertension, requires evidence of end organ damage.

Diagnostic Testing Absent focal neurological deficits, abnormal findings on retinal examination, or visual deficits, a diagnostic evalutation is not indicated.

Management It is uncertain if strategies aimed at lowering the blood pressure acutely will alleviate the headache. We recommend use of

CHAPTER 93  Headache Disorders

antidopaminergic or nonsteroidal agents, with use of antihypertensive agents reserved for patients with evidence of end organ damage. Oral antihypertensive therapy may be prescribed in the ED if timely outpatient follow-up cannot be assured.

Disposition In the absence of objective neurological symptoms, patients with hypertensive headache do not require admission to the hospital. Elevated blood pressure should be treated on an outpatient basis.

Reversible Cranial Vasoconstriction Syndrome Principles Reversible cranial vasoconstriction syndrome (RCVS), also referred to as Call-Fleming syndrome, is a cerebral arteriopathy characterized by segmental areas of vasoconstriction within largeand medium-sized vessels. It is the same disease as postpartum angiopathy or migrainous vasospasm. RCVS causes recurrent thunderclap headache in susceptible patients and may cause ischemic or hemorrhagic stroke. The prevalence of this presumably rare disorder is not known. RCVS is being reported with more frequency given the wide availability of noninvasive neurovascular imaging. Some data suggest that this disorder may cause the majority of thunderclap headaches.61

Clinical Features The headache of RCVS is characteristically a thunderclap headache, abrupt in onset, and severe. It is often throbbing and associated with nausea, vomiting, and photophobia. The headache may be provoked by use of vasoactive medications or substances.

Differential Diagnoses The differential diagnoses for thunderclap headache include SAH and other hemorrhagic strokes, CVT, CAD, and pituitary apoplexy. Unlike these other pathological diagnoses, RCVS is characterized by recurrent thunderclap headache within a discrete period of time. Thunderclap headache during sexual activity may occur pre- or post-orgasm and is classified as primary headache associated with sexual activity after other causes of thunderclap headaches have been excluded. Once that happens, a diagnosis of primary thunderclap headache is assigned.

Diagnostic Testing Patients with the initial presentation of thunderclap headache should have a head CT and LP performed to exclude SAH and other intracranial pathology. Repeat neurovascular imaging, or diagnostic angiography, should be pursued in patients with recurrent thunderclap headache.

Management There are no evidence-based treatment options available for RCVS. Goals of treatment include prevention of ischemic and hemorrhagic stroke and elimination of headache. To date, the natural history of this disorder is incompletely understood. Treatment with calcium channel blockers has been described, although when to initiate treatment is unclear.

Disposition Patients with thunderclap headache who have received an appropriate diagnostic evalutation in the ED may be discharged home with appropriate follow-up.

KEY CONCEPTS • The goals of headache evaluation in the ED are (1) to distinguish between benign primary headache disorders and potentially life-threatening secondary causes of headache and (2) to treat the headache pain effectively and rapidly without causing undue side-effects. • Patients with the following headache presentations are at risk for serious underlying disease: sudden explosive headache; first or “worst-ever” headache; new-onset headache after the age of 50 years; headache associated with papilledema, alteration in or loss of consciousness, or focal neurologic symptoms; subacute headache with increasing frequency or severity; headache associated with fever, cancer, or immunosuppression; and headache triggered by exertion, sexual activity, or Valsalva maneuver. • The need for diagnostic studies is dictated by the suspected secondary cause of headache. • Sumatriptan medications are the first line therapy for migraine headaches. • Patients with migraine treated in the ED need to be discharged with a “rescue plan” if the headache reoccurs. • High-flow oxygen will terminate the majority of cluster headaches. • Opioids are not first line treatment for primary headaches and are reserved for cases refractory to other interventions. • The differential diagnosis of sudden severe headache includes SAH, CVT, CAD, and IIH. • CVT should be suspected in women who have a new type of headache and are pregnant or on birth control pills. • Carotid artery dissection may result in headache, ptosis, and miosis. • Patients suspected of having a PTHA should be evaluated for a CN IV or VI neurapraxia and for cervical strain as a cause of their headache.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Friedman BW, Hochberg ML, Esses D, et al: Applying the International Classification of Headache Disorders to the emergency department: an assessment of reproducibility and the frequency with which a unique diagnosis can be assigned to every acute headache presentation. Ann Emerg Med 49:409–419, 19 e1-9, 2007. 2. Olesen J, Bendtsen L, Dodick D, et al: The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33(9):629–808, 2013. 3. Friedman BW, West J, Vinson DR, et al: Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia 35(4):301–309, 2015. 4. Lipton RB, Bigal ME, Diamond M, et al: Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68:343–349, 2007. 5. Sprenger T, Goadsby PJ: Migraine pathogenesis and state of pharmacological treatment options. BMC Med 7:71, 2009. 6. Loder E, Weizenbaum E, Frishberg B, et al: Choosing wisely in headache medicine: the American Headache Society’s list of five things physicians and patients should question. Headache 53:1651–1659, 2013. 7. Edlow JA, Panagos PD, Godwin SA, et al: Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with acute headache. Ann Emerg Med 52:407–436, 2008. 8. Marmura MJ, Silberstein SD, Schwedt TJ: The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache 55:3–20, 2015. 9. Charbit AR, Akerman S, Goadsby PJ: Dopamine: what’s new in migraine? Curr Opin Neurol 23:275–281, 2010. 10. Erdur B, Tura P, Aydin B, et al: A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia. Am J Emerg Med 30:84–91, 2012. 11. Marmura MJ, Goldberg SW: Inpatient management of migraine. Curr Neurol Neurosci Rep 15:13, 2015. 12. Friedman BW, Hochberg ML, Esses D, et al: Recurrence of primary headache disorders after emergency department discharge: frequency and predictors of poor pain and functional outcomes. Ann Emerg Med 52:696–704, 2008. 13. Colman I, Friedman BW, Brown MD, et al: Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ 336:1359–1361, 2008. 14. Friedman BW, Solorzano C, Esses D, et al: Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan. Ann Emerg Med 56:7–17, 2010. 15. Pringsheim T, Davenport W, Mackie G, et al: Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci 39:S1–S59, 2012. 16. Nesbitt AD, Goadsby PJ: Cluster headache. BMJ 344:e2407, 2012. 17. Leone M, D’Amico D, Frediani F, et al: Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo. Neurology 54:1382–1385, 2000. 18. Weinman D, Nicastro O, Akala O, et al: Parenteral treatment of episodic tension-type headache: a systematic review. Headache 54:260–268, 2014. 19. Linde K, Allais G, Brinkhaus B, et al: Acupuncture for tension-type headache. Cochrane Database Syst Rev (1):CD007587, 2009. 20. Perry JJ, Stiell IG, Sivilotti ML, et al: High risk clinical characteristics for subarachnoid haemorrhage in patients with acute headache: prospective cohort study. BMJ 341:c5204, 2010. 21. Polmear A: Sentinel headaches in aneurysmal subarachnoid haemorrhage: what is the true incidence? A systematic review. Cephalalgia 23:935–941, 2003. 22. McCormack RF, Hutson A: Can computed tomography angiography of the brain replace lumbar puncture in the evaluation of acute-onset headache after a negative noncontrast cranial computed tomography scan? Acad Emerg Med 17:444–451, 2010. 23. Perry JJ, Stiell IG, Sivilotti ML, et al: Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ 343:d4277, 2011. 24. Perry JJ, Sivilotti ML, Stiell IG, et al: Should spectrophotometry be used to identify xanthochromia in the cerebrospinal fluid of alert patients suspected of having subarachnoid hemorrhage? Stroke 37:2467–2472, 2006. 25. Chu K, Hann A, Greenslade J, et al: Spectrophotometry or visual inspection to most reliably detect xanthochromia in subarachnoid hemorrhage: systematic review. Ann Emerg Med 64:256–264 e5, 2014. 26. Perry JJ, Alyahya B, Sivilotti ML, et al: Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study. BMJ 350:h568, 2015. 27. Savitz SI, Levitan EB, Wears R, et al: Pooled analysis of patients with thunderclap headache evaluated by CT and LP: is angiography necessary in patients with negative evaluations? J Neurol Sci 276:123–125, 2009. 28. Perry JJ, Stiell IG, Sivilotti ML, et al: Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA 310(12):1248–1255, 2013. 29. Connolly ES, Jr, Rabinstein AA, Carhuapoma JR, et al: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare profes-

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sionals from the American Heart Association/American Stroke Association. Stroke 43:1711–1737, 2012. Dorhout Mees SM, Rinkel GJ, Feigin VL, et al: Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev (3):CD000277, 2007. Feigin VL, Anderson N, Rinkel GJ, et al: Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev (3):CD004583, 2005. Molyneux AJ, Birks J, Clarke A, et al: The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT). Lancet 385:691– 697, 2015. Valentinis L, Tuniz F, Valent F, et al: Headache attributed to intracranial tumours: a prospective cohort study. Cephalalgia 30:389–398, 2010. Kirby S, Purdy RA: Headaches and brain tumors. Neurol Clin 32:423–432, 2014. Tremont-Lukats IW, Ratilal BO, Armstrong T, et al: Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst Rev (2):CD004424, 2008. Weyand CM, Goronzy JJ: Clinical practice: giant-cell arteritis and polymyalgia rheumatica. N Engl J Med 371:50–57, 2014. Nordborg E, Nordborg C: Giant cell arteritis: strategies in diagnosis and treatment. Curr Opin Rheumatol 16:25–30, 2004. Hellmann DB: Temporal arteritis: a cough, toothache, and tongue infarction. JAMA 287:2996–3000, 2002. Borchers AT, Gershwin ME: Giant cell arteritis: a review of classification, patho­ physiology, geoepidemiology and treatment. Autoimmun Rev 11(6–7):A544–A554, 2012. Parikh M, Miller NR, Lee AG, et al: Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis. Ophthalmology 113(10):1842–1845, 2006. Walvick MD, Walvick MP: Giant cell arteritis: laboratory predictors of a positive temporal artery biopsy. Ophthalmology 118:1201–1204, 2011. CADISS Trial Investigators, Markus HS, Hayter E, et al: Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol 14(4):361–367, 2015. Norris JW, Beletsky V: Cervical arterial dissection. Adv Neurol 92:119–125, 2003. Arnold M, Bousser MG, Fahrni G, et al: Vertebral artery dissection: presenting findings and predictors of outcome. Stroke 37:2499–2503, 2006. Nebelsieck J, Sengelhoff C, Nassenstein I, et al: Sensitivity of neurovascular ultrasound for the detection of spontaneous cervical artery dissection. J Clin Neurosci 16:79–82, 2009. Lyrer P, Engelter S: Antithrombotic drugs for carotid artery dissection. Cochrane Database Syst Rev (10):CD000255, 2010. Gulati D, Strbian D, Sundararajan S: Cerebral venous thrombosis: diagnosis and management. Stroke 45:e16–e18, 2014. Ferro JM, Canhao P, Stam J, et al: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 35:664–670, 2004. Kosinski CM, Mull M, Schwarz M, et al: Do normal D-dimer levels reliably exclude cerebral sinus thrombosis? Stroke 35:2820–2825, 2004. Crassard I, Soria C, Tzourio C, et al: A negative D-dimer assay does not rule out cerebral venous thrombosis: a series of seventy-three patients. Stroke 36:1716–1719, 2005. Bousser MG, Ferro JM: Cerebral venous thrombosis: an update. Lancet Neurol 6:162–170, 2007. Einhaupl K, Stam J, Bousser MG, et al: EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol 17:1229–1235, 2010. Friedman DI, Liu GT, Digre KB: Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 81:1159–1165, 2013. Kosmorsky GS: Idiopathic intracranial hypertension: pseudotumor cerebri. Headache 54:389–393, 2014. Bezov D, Ashina S, Lipton R: Post-dural puncture headache: Part II—prevention, management, and prognosis. Headache 50:1482–1498, 2010. Richman JM, Joe EM, Cohen SR, et al: Bevel direction and postdural puncture headache: a meta-analysis. Neurologist 12(4):224–228, 2006. Bezov D, Lipton RB, Ashina S: Post-dural puncture headache: part I diagnosis, epidemiology, etiology, and pathophysiology. Headache 50:1144–1152, 2010. Boonmak P, Boonmak S: Epidural blood patching for preventing and treating postdural puncture headache. Cochrane Database Syst Rev (1):CD001791, 2010. Nampiaparampil DE: Prevalence of chronic pain after traumatic brain injury: a systematic review. JAMA 300:711–719, 2008. Lukovits TG: Expert commentary. Teaching case: hypertensive headache. Headache 53:686–688, 2013. Cheng YC, Kuo KH, Lai TH: A common cause of sudden and thunderclap headaches: reversible cerebral vasoconstriction syndrome. J Headache Pain 15:13, 2014.

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CHAPTER 93: QUESTIONS & ANSWERS 93.1. Which of the following mechanisms is least likely to play a role in the pathophysiology of migraine headaches? A. Cortical spreading depression B. Pathologic cerebrovascular dilation activates surrounding afferent nerve endings, causing typical pulsating pain C. Sensitization of higher-order nociceptive centers in the brainstem and thalamus D. Sterile neuropeptide induced inflammatory process E. Trigeminal nerve activation Answer: B. Trigeminovascular activation, possibly triggered by cortical spreading depression or a sterile neurogenic inflammation, causes activation and sensitization of higher-order nociceptive centers in the brainstem and thalamus. A primary vascular etiology of migraine pain is not supported by available evidence. 93.2. A 42-year-old male presents with the acute onset of a left-sided headache. He had one similar headache approximately 1 year ago that lasted 3 hours, subsided rapidly, and like this one, was associated with alcohol intake. Physical examination is remarkable for an obviously uncomfortable healthy male pacing and rubbing his left temple. You note left conjunctival injection with tearing. What should be the next step? A. Computed tomography (CT) scan B. Dexamethasone 10 mg intravenously C. High-flow oxygen by face mask D. Measurement of intraocular pressure E. Morphine 10 mg intravenously Answer: C. Cluster headaches occur predominantly in men, occur suddenly, and often abate quickly. These headaches are typically unilateral and characterized by a sharp stabbing ocular pain that may be accompanied by a “conjunctivitis” picture, a partial Horner’s syndrome, or unilateral nasal congestion. Alcohol may precipitate. Standard antimigraine agents may be helpful (eg, sumatriptan, antiemetics), but high-flow oxygen is highly effective and very well tolerated. Calcium channel blockers and corticosteroids are useful for preventing subsequent attacks of cluster headache. As with migraines, opioids should be reserved for refractory pain. 93.3. A 29-year-old female presents within 1 hour of the sudden onset of a severe, diffuse headache accompanied by meningismus and vomiting. Emergent computed tomography (CT) scan is negative. Lumbar puncture (LP) reveal 50,000 red blood cells (RBCs) in tube 1 and 30,000 RBCs in tube 4. Opening pressures are normal, and the sample is negative for xanthochromia. What would be the most appropriate next step? A. Admission and observation B. Cerebrovascular imaging study C. Hydration, analgesics

D. Magnetic resonance imaging (MRI) scan with gadolinium E. Subcutaneous sumatriptan 6 mg Answer: B. CT scan provides a sensitivity of approximately 90% for the detection of subarachnoid hemorrhage (SAH). A traumatic LP, even with diminishing RBC counts with sequential tubes, cannot differentiate between a SAH and traumatic tap. The lack of xanthochromia is predictable, given the acute onset of headache and the 12 hours required for cerebrospinal fluid (CSF) xanthochromia to develop. A cerebrovascular imaging study, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), or standard angiography would be required next to exclude a source of bleeding, such as an aneurysm or arteriovenous malformation (AVM). 93.4. A 69-year-old male presents with several months of intermittent left-sided headaches that have been worse at night and occasionally on exposure to cold air. On several occasions, he has noted increased pain while eating. He has had no other symptoms other than modest fatigue. Physical examination is unremarkable with normal vital signs and ophthalmologic and neurologic survey. Laboratory evaluation shows only a mild anemia, with a hemoglobin of 11 mg/dL and normocytic indices. What would be the most appropriate next step? A. Computed tomography (CT) scan of the brain B. Electrocardiogram C. Erythrocyte sedimentation rate (ESR) D. Neurology consultation E. Ophthalmology consultation Answer: C. Temporal arteritis may present with intermittent or continuous symptoms, sometimes associated with fatigue, myalgias, jaw claudication, and mild anemia. The ESR is usually, but not always, diagnostic and would confirm the diagnosis if elevated. Steroids and ophthalmology consultation would then follow. The presence of temporal artery tenderness may be variable because the vasculitis may affect any artery. The diagnosis must be suspected in any elderly patient with recurrent or continuous headaches. 93.5. With cavernous sinus thrombosis, the clinical picture is usually dominated by which of the following? A. Facial pain B. Lethargy C. Nausea and vomiting D. Ocular findings such as pain and proptosis E. Seizures Answer: D. The symptoms may also include paralysis of extraocular movements. Ocular symptoms are most common with thrombosis of the cavernous sinus, rather than one of the other sinuses.

C H A P T E R 94 

Delirium and Dementia Gallane Abraham  |  Leslie S. Zun OVERVIEW Cognition is a composite of attention, orientation, memory, language, visual-spacial ability, and executive function. Both delirium and dementia affect cognition but in very different ways and over very different time courses; that said, delirium can occur concomitantly in a patient with dementia making the diagnosis challenging. In the past, terms such as acute confusional state, sundowning, and organic brain syndrome have been used to describe a number of abnormal cognitive states. Organic brain syndrome is a nebulous term that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) eschews because the “organic” connotation implies that so-called functional mental disorders are without a biologic basis.1 The preferred terms are medical or psychiatric etiology. Although the DSM-5 still uses the terms delirium, dementia, amnestic, and other cognitive disorders, the preferred terminology is neurocognitive disorders. Delirium is characterized by a fluctuating neurobehavioral disturbance typically progressing over a short period. It is a direct consequence of an acute systemic or central nervous system (CNS) stressor. Dementia, on the other hand, tends to follow a more gradual course, with evolution occurring over months to years. Although patients with dementia exhibit confusion, unlike delirium, manifestations of autonomic nervous system abnormalities are minimal or absent and a disturbance in level of consciousness usually is not a feature. The evaluation of patients who present to the emergency department (ED) with a neurobehavioral disturbance is best conducted in accordance with the following basic guidelines: 1. The first step is to determine whether this state represents delirium or dementia by obtaining a careful history from the patient, family members, and caregivers, employing screening tools for delirium and cognitive assessments for dementia. The clinical findings may be subtle and establishment of the diagnosis can be challenging, especially because delirium may be superimposed on dementia, and dementia remains an independent risk factor for delirium. 2. The second step is to rapidly treat the underlying disorder in patients with delirium. 3. The third step is to establish a supportive environment and employ pharmacological adjuncts as needed.

DELIRIUM Principles Background Delirium is an acute or subacute state of cognitive dysfunction caused by an underlying physiologic condition. Several key features are necessary for a diagnosis of delirium (Box 94.1). Patients with delirium may have disturbances in consciousness, memory, cognition, and perception. These disturbances tend to develop during a short time (hours to days) and are characterized as acute delirium if the symptoms last hours to days or persistent delirium 1278

if the symptoms last weeks to months.1 The disturbance in consciousness may be manifested initially as an inability to focus attention. The fluctuating course of symptoms and inattention are the hallmarks of delirium. Deficiencies in cognition may be manifested by disorientation and memory deficits. Perceptual disturbances include hallucinations and delusions. The delirious patient may be somnolent or agitated, and the thought process may range from mildly disturbed to grossly disorganized. The clinical presentation may be subdued or explosive. The patient’s sleep-wake cycle may be altered or reversed; agitation often is present during the night. There are three types of delirium: hyperactive, hypoactive, and mixed level of activity. Hyperactive type demonstrates hyperactivity with emotional lability, agitation, and may include refusal of care; the hypoactive type demonstrates sluggishness and lethargy; the mixed type is found in a person with a normal level of activity but with disturbance of attention and awareness or fluctuations in activity levels. Delirium has been reported to be present in up to 24% of the older adults treated in the ED.2,3 It is a frequently missed diagnosis when standardized screening tools are not used. This is problematic because the mortality rate rises from 10% of those diagnosed in the ED to 36% when it is missed. This increased mortality is associated with a high rate of incontinence, decubiti, and malnutrition. Predisposing factors for delirium include comorbid illness, dementia, older age, male gender, medications, neurologic deficits, and psychiatric illness (Table 94.1). Precipitating factors include infections, endocrine and metabolic disorders, medications, CNS events, cardiovascular disorders, and iatrogenic related events. Drug intoxication or withdrawal (including ethanol) are the most common cause of delirium in the younger adult population. Within the older population, drugs are also a common cause of delirium; drugs with anticholinergic properties are often implicated but almost every drug class can be a precipitant. Industrial exposures (eg, carbon disulfide, heavy metals, insecticides, cyanide, carbon monoxide), herbal medications, and ingestion of certain plants (eg, nutmeg, foxglove, jimsonweed, psilocybin-containing mushrooms) are yet other causes of delirium to consider. Delirium can be a prominent feature of any CNS or systemic infection, particularly in the very young, elders, and immunocompromised patients. All metabolic disorders put patients at risk for delirium with hypoglycemia and hypoxia being the most common. Delirium is also associated with strokes, particularly strokes in the distribution of the nondominant middle cerebral artery and the posterior cerebral artery. CNS vasculitis and paraneoplastic syndromes are additional considerations.

Pathophysiology At a cellular level, delirium is the result of a widespread alteration in cerebral metabolic activity, with secondary deregulation of neurotransmitter synthesis and metabolism. Both the cerebral cortex and the subcortical structures are affected, producing changes in arousal, alertness, attention, information processing, and the normal sleep-wake cycle.

CHAPTER 94  Delirium and Dementia

BOX 94.1 

Diagnostic Criteria for Delirium FOUR KEY CHARACTERISTICS

• Disturbance in attention and awareness. • The disturbance develops over a short time period, represents a change from baseline attention and awareness, and tends to fluctuate in severity during the day. • There are additional disturbances in cognition, such as memory, disorientation language, visual spatial ability, or perception. • The disturbances are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in context of a coma. Adapted from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

TABLE 94.1 

Predisposing and Precipitating Factors for Delirium FACTORS

LEVEL OF EVIDENCE

PREDISPOSING VARIABLES Age

Strong

Gender

No evidence

Alcohol use

Inconclusive

Nicotine use

Inconclusive

Dementia

Strong

Hypertension

Strong

American Society of Anesthesiologists (ASA) physical status*

Inconclusive

Cardiac disease

Inconclusive

PRECIPITATING VARIABLES Coma

Strong

Previous delirium

Strong

Emergency surgery

Strong

Mechanical ventilation

Strong

Acute respiratory disease

Inconclusive

Kidney function

Inconclusive

Medical admission

Inconclusive

Organ failure

Moderate

Trauma

Strong

MEDICATIONS Analgesics/sedatives

Inconclusive

Benzodiazepines

Inconclusive

Opioids

Inconclusive

REDUCED DELIRIUM OCCURRENCE Dexmedetomidine

Strong

*American Society of Anesthesiologists (ASA) Physical Status Classification System. Adapted from Zaal IJ, Devlin JW, Peelen LM, et al: A systematic review of risk factors for delirium in the ICU. Crit Care Med 43(1):40-47, 2015.

Although the exact pathophysiologic process is not well understood, multiple neurotransmitters have been implicated in causing delirium. Delirium is often associated with a derangement of central cholinergic transmission. Serum anticholinergic activity is increased, and low levels of acetylcholine are seen in elders with delirium. This is most pronounced in patients experiencing delirium secondary to anticholinergic drugs. Increased serotonin levels have been found in hepatic encephalopathy, serotonin syndrome, sepsis, and psychedelic drug ingestion. Some of the disturbances that occur in delirium are deficiencies of substrates for oxidative metabolism (eg, glucose, oxygen); disturbances of ionic passage through excitable membranes; increase in cytokines; imbalance of normal noradrenergic, serotoninergic, dopaminergic, and cholinergic homeostasis; and, in some cases, synthesis of false neurotransmitters. Drugs and exogenous toxins can produce delirium through direct effects on the CNS. Although the limbic system appears to be particularly vulnerable to the effects of drugs, the cerebral hemispheres and the brainstem also can be profoundly affected. Tricyclic antidepressants can cause delirium by cholinergic inhibition; sedative-hypnotics depress activity in the CNS, especially in the limbic system, thalamus, and hypothalamus. Narcotics affect CNS activity primarily by interacting with various opioid receptor sites. Psychedelic drugs probably act as agonists at serotonin receptor sites. Phencyclidine (PCP) inhibits reuptake of dopamine, norepinephrine, serotonin, and α-aminobutyric acid and also may act as a false neurotransmitter. Hyperthermia and hypothermia can cause delirium due to changes in the cerebral metabolic rate. In hypothermia, cerebral metabolism decreases 6% to 7% for each 1° C decrease in temperature from 35° to 25° C. In hyperthermia, cellular damage with uncoupling of oxidative phosphorylation begins to occur at temperatures higher than 42° C. Patients suffering from heatstroke may have cerebral edema, degenerative neuronal changes (especially involving Purkinje cells of the cerebellum), and petechiae in the walls of the third and fourth ventricles. Delirium occurring at temperatures below 40° C is multifactorial in origin and not caused solely by increased core temperature. Delirium caused by metabolic abnormalities, such as hyponatremia, hypernatremia, hyperosmolarity, hypercapnia, and hyperglycemic disorders, is associated with a variety of metabolic disturbances at the neuronal and astrocyte levels. Such disturbances may include impairments in energy supplies, changes in resting membrane potentials, changes in cellular morphology, and changes in the brain water volume. Most patients with delirium have reduced cerebral metabolic activity. This reduction in cerebral metabolism is reflected by a decrease in the frequency of background electrical activity on the electroencephalogram (EEG). Exceptions are hyperthermia, sedative-hypnotic withdrawal, delirium tremens, and certain drug-induced states, in which the cerebral metabolism is either normal or increased.

Clinical Features Delirium is often the first manifestation of underlying disease. The natural history of a patient’s delirium can progress from apathy to marked agitation in the course of hours (see Box 94.1). Nonspecific prodromal symptoms such as anxiety, restlessness, and insomnia typically emerge during hours to days. Key aspects of cognitive impairment should become evident during a careful history and physical examination. Disturbance in attention is central to the diagnosis of delirium. The patient is easily distractible and has difficulty remaining focused on a particular topic or interacting with a single person. Disorientation often accompanies the inattention but is not an invariable feature. The patient usually is disoriented with respect to time and

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TABLE 94.2 

Common Emergency Department Assessments for Dementia TEST Mini-Mental State Examination (MMSE) Clock drawing test

ITEM(S)

APPLICATION

ADMINISTERED BY

TIME (MINUTES)

30

Clinical, screening

Interviewer

5 to 10

1

Clinical, screening

Patient

3

Short Portable Mental Status Questionnaire (SPMSQ)

10

Screening

Interviewer

5

Cognitive Capacity Screening Examination (CCSE)

10

Clinical

Expert

5 to 15

Adapted from Woodford HJ, George J: Cognitive assessment in the elderly: a review of clinical methods. QJ Med 100:469-484, 2007; Wong CL, Holroyd-Leduc J, Simel DL, et al: Does this patient have delirium? Value of bedside instruments. JAMA 304(7):779-786, 2010.

occasionally to place; in extreme cases, disorientation to person also may be noted. Delirium, however, may be present in a patient who is completely oriented to person, place, and time. A mental status examination that consists solely of questions that assess orientation will not detect delirium in these instances. The patient with delirium always has some degree of memory impairment, with the greatest impact on short-term memory. Thought processes and speech may be disorganized. Disturbance in the sleep-wake cycle often occurs early in the course of delirium. Perceptual disturbances, including misperception of the environment, poorly formed delusions, and hallucinations, are common. The delirious patient may experience visual, auditory, tactile, gustatory, or olfactory hallucinations. In addition, the delirious patient has a reduced capacity to modulate fine emotional expression and may demonstrate extreme emotional lability. The cognitively impaired patient may provide an unreliable history. Valuable information often can be obtained from family, friends, and out-of-hospital personnel. Specific inquiry should be made about the patient’s current medical problems and previous medical history, including diabetes, hypertension, kidney or liver disease, immune status, and any neurologic or psychiatric problems. A detailed medication history, including the use of prescribed and over-the-counter medications, dietary supplements, and alcohol or other substances, is essential. Out-of-hospital personnel should be able to provide information about the home environment, medication bottles belonging to the patient or found near the patient, and the possibility of trauma. The physical examination should begin with a careful assessment of vital signs including pulse oximetry and a pain assessment. The delirious patient often exhibits autonomic nervous system abnormalities on evaluation, including elevated or decreased pulse, blood pressure, respiratory rate, and temperature. The examination also includes assessment of the head for signs of trauma and the pupils for symmetry and light reflex; funduscopic examination for hemorrhage or papilledema; examination of the ears for hemotympanum; evaluation of the neck for nuchal rigidity, bruits, and thyroid enlargement; assessment of the heart and lungs; evaluation of the abdomen for organomegaly and ascites; and examination of the extremities for cyanosis. The skin should be carefully examined for rashes, petechiae, ecchymosis, splinter hemorrhages, and needle tracks. The neurologic examination includes assessment of the cranial nerves, motor strength, sensation, reflexes, and presence of abnormal movements (eg, ophthalmoplegia, tremor, asterixis, myoclonus). A specific constellation of neurologic findings may suggest a specific diagnosis. One such example is the classic triad of Wernicke’s encephalopathy: ophthalmoplegia, ataxia, and confusion. The reflexes are assessed for symmetry and presence of hyperreflexia or hyporeflexia. Findings that typically suggest either a metabolic or a structural neurologic problem are not necessarily specific for that category of disorder. For example, asterixis is a

hallmark of metabolic encephalopathy but can be seen in focal brain disease. Likewise, focal neurologic signs that typically are associated with structural CNS lesions also can be present in various metabolic abnormalities, such as hypoglycemia, hyperglycemia, hepatic encephalopathy, uremia, and hypercalcemia. The physical examination is not often helpful in determining the specific drug or class of drugs causing acute cognitive impairment. The one exception to this rule is the presence of a “toxidrome,” which is a constellations of signs and symptoms characteristic of intoxication with certain drugs or classes of drugs (see Chapter 139). Although there are a number of delirium scales found in the literature, the Confusion Assessment Method (CAM) is a validated tool that has a sensitivity of 93% to 100% and specificity of 90% to 95%. Performing the CAM takes 5 minutes, and it is often used in conjunction with other tests (eg, the Mini-Mental State Examination [MMSE] or Richmond Agitation-Sedation Scale [RASS]) to provide a composite baseline of cognition in patients exhibiting symptoms of delirium and dementia (Table 94.2).4-7 The CAM has four key features used in screening for delirium: (1) acute onset and fluctuating course, (2) inattention, (3) disorganized thinking, and (4) altered level of consciousness. For a definitive diagnosis of delirium, the first two features and one of the last two must be present. It has proved to be a valuable tool because of its ease of administration and high interobserver reliability. In addition, it has been shown to be more sensitive than clinical impression alone.

Differential Diagnosis Considerations in the differential diagnosis for delirium include dementia and psychiatric disorders. Dementia, depression, mania, paranoia, and schizophrenia all may resemble delirium but can be distinguished using historical and clinical features such as onset, time course, fluctuating mental status, and inattention (Table 94.3). Unlike delirium, dementia and psychiatric disorders tend to be insidious processes that develop during months to years. Typically, the patient’s vital signs are normal. In addition, cognitive impairment of dementia exhibits little fluctuation during hours or days and occurs primarily in elders. A point worthy of emphasis is that patients with dementia are more likely to develop delirium.

Diagnostic Studies Because delirium is generally the manifestation of an underlying disorder, a comprehensive evaluation looking for structural, metabolic, and infectious etiologies is indicated (Table 94.4). Despite these diagnostic evaluations, no cause is found for delirium in up to 16% of patients. An elevated anion gap (>15 mEq/L) may indicate the presence of unmeasured anions, such as ketoacids in diabetic or alcoholic ketoacidosis; lactate in postictal states or

CHAPTER 94  Delirium and Dementia

associated with hypotension; sulfate in renal failure; and exogenous toxins, such as ethylene glycol, methanol, and salicylates. In addition to a pulse oximetry measurement to screen for hypoxemia, an arterial blood gas analysis is warranted in patients at risk for respiratory failure with hypercarbia. Urinalysis and chest radiography should be obtained to exclude an occult infection, which is frequently the cause of delirium in elders. An electrocardiogram and troponin should be obtained to exclude a silent acute coronary syndrome. Furthermore, additional laboratory studies outside the scope of the ED evaluation may be appropriate when the cause of delirium remains unknown. These additional studies may include thyroid function studies, vitamin B12 and folic acid assays, rapid plasma reagin test, measurement of serum antinuclear antibodies, urinary porphobilinogen assay, and screens for heavy metals.

TABLE 94.3 

Comparison of Delirium and Dementia Onset

DELIRIUM

DEMENTIA

Acute

Slow

Awareness

Reduced

Clear

Alertness

Fluctuates

Normal

Orientation

Impaired

Impaired

Memory

Impaired

Impaired

Perception

Hallucinations

Intact

Thinking

Disorganized

Vague

Language

Slow

Word finding difficulty

Adverse drug events, including drug-drug interactions, account for 30% of cases of delirium; they may occur at therapeutic doses and levels. A comprehensive review of all medications and testing for levels when available is recommended. Standard toxicology screens are overused as diagnostic tests and have limited usefulness in the evaluation of most patients with delirium. Neuroimaging with a head computed tomography (CT) scan should be performed on patients with a history of trauma (especially those taking anticoagulant medications), previous neurosurgical procedures, immunodeficiency, or focal neurologic signs to detect structural lesions causing delirium. Additional imaging or lumbar puncture (LP) is required for early infarctions, small brainstem lesions, meningitis or encephalitis, closed head injuries, sagittal vein thrombosis, and small isodense subdural hematomas that may be missed on a CT scan. In addition, a small percent of acute subarachnoid hemorrhages are not detected by head CT scan and require LP for diagnosis. The role of magnetic resonance imaging (MRI) in the evaluation of the delirious patient has not been clearly established. MRI is superior to CT for detection of small intracerebral and brainstem lesions, small brain contusions, certain encephalitides, and abnormalities of white matter (eg, leukoencephalopathy). MRI perfusion scans are more sensitive in detecting an acute vascular event. Cerebrospinal fluid (CSF) analysis is an essential part of the evaluation in selected patients with delirium. In patients with fever and cognitive dysfunction, even without meningismus, a LP should be performed to rule out infectious, inflammatory or neoplastic etiologies. This test is particularly important in the very young, elders, and immunocompromised patients, who are less likely to show classic signs of meningitis. Patients with focal neurologic deficits, immunocompromised states, or evidence of increased intracranial pressure should undergo head CT before LP, and they should receive antibiotics before the CT scan.

TABLE 94.4 

Delirium Diagnostic Studies and Clinical Findings DIAGNOSTIC STUDIES

EXAMPLES OF CLINICAL FINDINGS

Vital signs

Hypoxemia, hypotension/hypertension, hypothermia/hyperthermia, pain

Fingerstick glucose

Hypoglycemia/hyperglycemia

Blood gas

Hypoxemia, hypercarbia, respiratory alkalosis, metabolic acidosis

CBC: Hemoglobin, leukocyte count with differential, platelet count, mean corpuscle volume

Anemia, occult infection, thrombocytopenic purpura, megaloblastic anemia, hyperviscosity from myelogenous leukemia, polycythemia

Serum electrolytes: Glucose, sodium, calcium, chloride, bicarbonate, BUN, creatinine, magnesium, phosphate, osmolality

Hypoglycemia/hyperglycemia, hyponatremia/hypernatremia, uremia, hypo-osmolar/hyperosmolar, anion gap acidosis

Urinalysis: Nitrites, leukocytes, ketones

Occult infection, acidosis

Chest x-ray

Occult infection, pneumothorax

Drug levels

Digoxin, lithium, quinidine, salicylate, antiepileptics

Myocardial infarction, liver failure, hypothyroid/hyperthyroid, bleeding Additional tests: Troponin, liver and thyroid function studies, ammonia, PT, disorder, excess anticoagulation, vitamin B12 or folate deficiency, occult PTT, INR, vitamin B12 and folic acid assays, rapid plasma reagin test, measurement of serum antinuclear antibodies, urinary porphobilinogen assay, infections, vasculitis, acute porphyria, toxins screens for heavy metals, toxic screens of blood and urine, methanol, ethylene glycol, carbon monoxide, cyanide CT head/MRI

Cerebrovascular accident, structural lesions, traumatic head injury

LP/CSF analysis

Meningitis, encephalitis, subarachnoid hemorrhage

EEG

Nonconvulsive status epilepticus, delirium

BUN, Blood urea nitrogen; CBC, complete blood count; CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; INR, international normalized ratio; LP, lumbar puncture; MRI, magnetic resonance imaging; PT, prothrombin time; PTT, partial thromboplastin time.

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Although it is rarely practical in the ED setting, the EEG can be a valuable diagnostic tool in assessing for nonconvulsive status epilepticus and determining the presence of delirium. Bilateral diffuse symmetrical electroencephalographic abnormalities are a relatively consistent feature of delirium. In most cases, the changes consist of a nonspecific generalized slowing from the baseline activity and can be useful in distinguishing delirium from other neurobehavioral abnormalities.

Management Delirium is a medical emergency. The outcome depends on the cause, the patient’s overall health status, and the timeliness of treatment. The presence of hyperactive or hypoactive delirium has some prognostic significance. The hypoactive form of delirium tends to be more common in elders and carries a worse overall prognosis, perhaps because it often goes unrecognized. Acute recognition and management of delirium in elders is essential because delirium in this population is associated with increased risk of long-term institutionalization, development of dementia, and increased overall mortality.8 Patients who present with acute delirium should be screened quickly for readily reversible causes, such as hypoglycemia, hypoxia, and narcotic overdose. Acute intoxication requires prompt attention and antidotes provided when available. Other conditions requiring immediate medical intervention include infections. Patients with signs of acute meningitis or sepsis should rapidly receive antibiotics along with fluid resuscitation. Antibiotics for meningitis should be dosed according to age and predisposing factors (see Chapter 99). Other emergent conditions that may be manifested with delirium and necessitate immediate intervention include severe hypothermia, hyperthermia, and CNS vascular conditions, including hypertensive encephalopathy, acute epidural or subdural hematoma, subarachnoid hemorrhage, and stroke. Patients with Wernicke’s encephalopathy require immediate treatment with 100 mg of intravenous (IV) thiamine, with titration of additional doses until the ophthalmoplegia resolves. Resistance to thiamine may result from hypomagnesemia because magnesium is a cofactor for thiamine transketolase. Glucose administration in patients with severe thiamine deficiency may precipitate Wernicke’s encephalopathy. The specific treatment of delirium tremens (and other alcohol withdrawal syndromes) involves the substitution of a long-acting drug that is crosstolerant with the alcohol. Benzodiazepines are the agents of choice to reduce agitation and other hyperactive symptoms in delirium tremens (see Chapter 142). Delirium secondary to dehydration, hyponatremia, hypernatremia, hypercalcemia, and hepatic or renal disease gradually resolves during hours to days with fluid and electrolyte replacement. Supportive care for all patients with delirium ideally includes an environment with adequate lighting and minimization of sensory overload; the patient should be placed in an area that can be easily observed by staff, and use of stretcher side rails to prevent falls. Use of “sitters” may be necessary to provide continuous supervision. The patient must be protected from self-harm or from injuring other patients or staff. In cases of hyperactive delirium, the patient may need to be initially restrained physically until pharmacologic control takes effect. Physical restraints should be viewed only as a temporizing action, because they can increase agitation and the risk of injury to the patient. They have been associated with injuries and even death by asphyxiation and are not a substitute for pharmacologic control. Pharmacologic interventions are a cornerstone of behavioral management while the underlying medical condition that caused the delirium is being addressed. The ideal sedating drug should have the following characteristics: low toxicity with minimal

anticholinergic effects, ease of administration, short half-life, minimal effects on the cardiovascular and respiratory systems, and no effect on the seizure threshold. Antipsychotics and benzodiazepines have been used in the management of acute agitation in the undifferentiated patient with delirium. The opioids have no role in the management of delirium. Antipsychotic medications used to treat delirium include the typical antipsychotics, especially the butyrophenones, and the newer atypical antipsychotic agents. Although no one drug is ideal, the typical antipsychotic, haloperidol, continues to be recommended as monotherapy for controlling agitation in acute delirium on the basis of extensive clinical experience.9 The use of the atypical antipsychotic agents for delirium and acute agitation is not well characterized. The newer atypical antipsychotic agents (risperidone, olanzapine, ziprasidone, aripiprazole) may have equal or better efficacy and fewer side effects (especially akathisia and dystonia) for management of acute agitation in the psychiatric population. As the primary drug for control of hyperactive delirium, haloperidol is a potent dopamine-blocking medication with less anticholinergic and minimal hypotensive effects. The main effect of the drug acutely is tranquilization. The incidence of extrapyramidal side effects in patients receiving IV haloperidol for management of delirium with agitation is relatively low. Studies of the acute administration of haloperidol report an 8% to 30% incidence of extrapyramidal side effects with akathisias being most common and acute dystonia occurring in less than 10% of patients. Haloperidol can prolong the QTc interval, more so when given intravenously, but this effect is clinically insignificant in most patients and does not require a pretreatment electrocardiogram. Caution is warranted with use of this agent in patients taking medications that prolong the QTc (eg, class IA and class III antiarrhythmics, certain antibiotics, inhibitors of the cytochrome P450 system) and in patients with acute coronary ischemia, uncompensated congestive heart failure, or hepatic dysfunction. The QTc effect is not usually concerning when the haloperidol is given intramuscularly. Haloperidol dosing should vary with the patient’s level of agitation, age, weight, and response to treatment. In most patients, 2.5 to 10 mg intramuscularly (adjusted according to weight and comorbidities) is well tolerated as an initial dose, and levels can be titrated as needed. For elders, a lower initial dose of 0.5 to 1.0 mg is recommended. Higher doses may be required for younger patients. The atypical antipsychotics can be used acutely for management of agitation. These drugs have been studied for use in the psychotic patients and patients with Parkinson’s disease presenting with acute agitation. The mechanism of action includes antagonism of alpha2-adrenergic, serotonin, muscarinic, dopamine, and histamine receptors. These drugs block the reuptake of dopamine and serotonin, and the newer drugs also have dopamine agonist effects (aripiprazole). Compared with haloperidol, several of these atypical agents (ziprasidone, risperidone, clozapine, and olanzapine) have been shown in nonrandomized case series to control agitation as effectively with less sedation and fewer extrapyramidal side effects. Because of the limited dopamine antagonism effect, atypical antipsychotics are the preferred agent for patients with Parkinsonism and agitation. Benzodiazepines are also considered effective as monotherapy or used in combination with the typical antipsychotics for the management of acute undifferentiated agitation, intoxication, or withdrawal syndromes.10,11 Lorazepam, a shorter-acting benzodiazepine that undergoes glucuronide conjugation with rapid renal clearance, is the preferred agent for treatment of withdrawal symptoms. Diazepam should be avoided as an agent for treatment of agitated behavior in most delirious patients because of its long

CHAPTER 94  Delirium and Dementia

half-life and risk of drug accumulation with repeated dosing. Long-term use of benzodiazepines can worsen confusion and falls. The management of delirium has been identified by The National Institutes of Health Task Force on Research in Emergency Medicine as a specific area requiring further research. Based upon the best available evidence, we recommend screening and treatment of readily reversible causes of delirium and initial nonpharmacological management followed by a selection of pharmacological agents based upon the etiology of delirium and patient comorbidities.12 We recommend either a benzodiazepine or antipsychotic (typical or atypical) used as monotherapy. As an alternative, a combination of a low-dose antipsychotic plus benzodiazepine (eg, haloperidol 5 mg IM plus lorazepam 2 mg) can be used. The combination approach has been found to be superior to either class alone in the treatment of undifferentiated acute agitation and has the added benefit of minimizing adverse effects.12

Disposition Patients with delirium secondary to acute drug intoxication may be discharged from the ED provided the process readily reverses itself during a short period of observation and the drug has no potentially serious delayed toxicity. For most patients delirious from metabolic, infectious, or CNS processes, hospitalization is necessary for further diagnostic evaluation and treatment. The only readily reversible metabolic problem associated with delirium that can be completely managed in the ED is hypoglycemia. For most patients without underlying medical illness who have delirium, the outcome is full recovery. After an episode of acute delirium, younger patients may experience mild cognitive dysfunction that lasts weeks to months. Elders, on the other hand, often experience persistent decline in their baseline level of functioning, with loss of at least one activity of daily living after acute delirium. Delirium in older adults hospitalized without baseline dementia is associated with higher 1-year mortality rates, higher rates of institutionalization, and a greater risk for development of dementia. For older adults, an episode of delirium, especially for those with baseline cognitive impairment, can have long-term consequences despite good supportive multidisciplinary care.

DEMENTIA Principles Background Dementia is not a single disease entity but rather a highly variable clinical syndrome characterized by a gradually progressive deterioration of cognitive function. Prognosis depends on the underlying cause (Box 94.2). Dementia is classified as either irreversible (primary degenerative) or potentially reversible (secondary); it is further classified according to the degree of cognitive impairment. Mild dementia implies some impairment of work and social activities; however, the capacity for independent living remains intact. With moderate dementia, independent living is hazardous, and some degree of supervision is necessary. With severe dementia, continual supervision and often custodial care are needed. Primary degenerative dementias include Alzheimer’s disease, dementia with Lewy bodies, subcortical dementias involving the basal ganglia and thalamus (eg, progressive supranuclear palsy, Huntington’s chorea, Parkinson’s disease), and dementia of the frontal lobe type, which includes Pick’s disease. Dementia with Lewy bodies, clinically manifested by persistent, well-formed visual hallucinations and prominent extrapyramidal movements, has been found to be the third most common type of dementia. With advanced aging, dementia may have mixed causes, with Alzheimer’s disease and vascular dementia frequently coexisting.

BOX 94.2 

Causes of Dementia PRIMARY DEGENERATIVE DEMENTIAS Alzheimer’s disease Lewy bodies disease Frontal lobe disease (Pick’s disease)

SUBCORTICAL DEMENTIAS Parkinson’s disease Huntington’s disease

VASCULAR DEMENTIA Multi-infarct dementia

INTRACRANIAL PROCESSES

Space occupying lesions (tumor, subdural hematoma) Hydrocephalus CNS infections (HIV-1, neurosyphilis, chronic meningitis) Repetitive head trauma

ENDOCRINOPATHIES

Addinson’s and Cushing’s diseases Thyroid and parathyroid disease

NUTRITIONAL DEFICIENCIES Thiamine Niacin Folate Vitamin B12

TOXIC EXPOSURES Heavy metals Carbon monoxide Carbon disulfide

DRUGS

Psychotropics Antihypertensives Anticonvulsants Anticholinergics

DEPRESSION

Pseudo-dementia CNS, Central nervous system; HIV-1, human immunodeficiency virus type 1. Adapted from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

A smaller percentage of dementias are attributable to causes, such as anoxic encephalopathy, hepatolenticular degeneration, tumors, and slow virus infections. Potentially reversible dementias are caused by adverse drug reactions, endocrinopathies, metabolic abnormalities, intracranial processes, and depression. The clinical manifestation is either an acute delirium or an acute or gradual progressive cognitive impairment that reverses once the underlying etiology is addressed and resolved. Drug-induced dementia occurs primarily in elders and can be caused by various psychotropic drugs, antihypertensive medications, anticonvulsants, anticholinergics, and miscellaneous medications, such as l-dopa. Dementia also may be caused by heavy metals and other exogenous agents, such as carbon monoxide, carbon disulfide, and trichloroethylene. Endocrinopathies and metabolic abnormalities that can cause secondary and potentially reversible dementia include hypothyroidism, hyperthyroidism, parathyroid disease, Addison’s disease,

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Cushing’s disease, and panhypopituitarism. Metabolic abnormalities such as nutritional deficiencies that cause dementia include thiamine deficiency (Wernicke’s syndrome), niacin deficiency (pellagra), vitamin B12 deficiency, and folate deficiency. Intracranial processes, space-occupying lesions, and hydrocephalus may also cause dementia. Repetitive intracranial trauma resulting from contact sports can produce a chronic organic brain syndrome without evidence of hematoma or significant contusion (dementia pugilistica). Intracranial processes that may eventually lead to a chronic organic brain syndrome include infections with slow viruses, human immunodeficiency virus type 1 (HIV-1) infection, chronic meningitis (tubercular or fungal), brain abscess, and neurosyphilis. In addition to primary HIV-1 CNS infection, toxoplasmosis, cryptococcal meningitis, malignant disease, and infections due to herpesvirus, cytomegalovirus, varicella-zoster virus, and papovavirus (progressive multifocal leukoencephalopathy) can cause progressive cognitive impairment in this compromised group of patients and must be excluded. There are two categories of primary degenerative dementias that are collectively referred to as dementia and that have the same neuropathologic changes: (1) a presenile dementia seen in younger patients, and (2) senile dementia. Alzheimer’s disease accounts for 60% to 80% of all dementias; vascular dementia (with or without Alzheimer’s disease) accounts for 20%, and the remaining 20% of cases are attributable to more than 50 known causes. Worldwide, approximately 24.3 million persons suffer from dementia, and 4.6 million new cases are diagnosed yearly. The prevalence is approximately 1% at 60 years old but doubles every 5 years until it reaches 30% to 50% by 85 years old. In 2014, the estimated prevalence of Alzheimer’s dementia was 5 million for adults in the United States aged 65 years or older and is projected to increase to 16 million by the year 2050.13 ED based studies of cognitive impairment report that up to 70% of older adults seen with cognitive impairment have undiagnosed dementia. Dementia is a strong predictor of mortality, which varies with age and subtype. DSM-5 criteria for the diagnosis of dementia are presented in Box 94.3. There must be cognitive impairment that interferes with independence in one of six domains: complex attention, executive function, learning and memory, language, perceptual-motor function, or social cognition.1 Several clinical features deserve emphasis. Impairment in memory must involve both short-term and long-term memory. The cognitive impairment commonly involves abstract thinking, judgment, and other higher cortical functions. The cognitive impairment must interfere with interpersonal relationships, work, and social activities. Although mild decline in intellectual functioning characterized as inability to learn and retain new information without impairment of daily

BOX 94.3 

Diagnostic Criteria for Dementia A. Cognitive decline from a previous level of performance in one or more cognitive domains: Complex attention, executive function, learning and memory, language, perceptual motor function, or social cognition. B. The disorder has an insidious onset and gradual progression. C. The deficits do not occur exclusively during the course of a delirium. D. The cognitive deficits are not better explained by another mental disorder, such as major depression or schizophrenia. Adapted from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

functions can be part of the normal aging process, gross intellectual impairment of short- and long-term memory or confusion is not normal. Mild cognitive impairment is distinct from early dementia. The goals of ED evaluation for suspected dementia are (1) to recognize the signs and symptoms of undiagnosed and potentially reversible forms of dementia, (2) to identify the manifestations of acute illness in the demented patient promptly, and (3) to assess the clinical findings in lieu of the patient’s cognitive impairment and facilitate a safe disposition and expedited follow-up.

Pathophysiology Alzheimer’s disease is the best-understood dementia and involves several characteristic anatomic, pathologic, and neurochemical changes. The predominant change is cortical atrophy most prominent in the temporal and hippocampal regions caused by progressive synaptic and neuronal loss in the cerebral gray matter. This atrophy generally is followed by loss of white matter (subcortical atrophy). There is no ischemic component to Alzheimer’s disease. Cell loss does occur with the normal aging process but not to the extent seen in dementia. Not all patients with dementia have gross cerebral atrophy. Histologic features characteristic of Alzheimer’s disease include extracellular deposition of β-amyloid protein and intracellular neurofibrillary tangles contributing to neuron loss. The abnormal processing of β-amyloid protein is likely central to the pathogenesis of Alzheimer’s disease. The neurofibrillary tangles are intraneuronal paired helical filaments composed of the abnormally phosphorylated protein tau, the structural protein involved in the regeneration of neurites. Senile plaques are extracellular lesions composed of the degenerating neuronal processes and abnormal β-amyloid protein. These plaques are extensively spread throughout the cerebral cortex and do not correlate with the severity of dementia. Other consistent neurohistopathologic changes in Alzheimer’s disease include granulovascular degeneration, Hirano bodies, β-amyloid deposition in the small cortical blood vessels, and neuronal loss in the limbic area. Many biochemical abnormalities have been described in patients with Alzheimer’s disease. A decrease in the neurotransmitter acetylcholine is characteristic. Levels of the enzyme choline acetyltransferase, which synthesizes acetylcholine in the brain, can be reduced to 20% of that in age-matched control subjects. Several risk factors for Alzheimer’s disease are recognized, including advancing age, family history, low education level, hypercholesterolemia, and head trauma. The apolipoprotein E epsilon 4 allele on chromosome 19 has been associated with both familial and sporadic late-onset Alzheimer’s disease. Apolipoprotein E is responsible for transporting of the cholesterol and phospholipids necessary for dendritic and synaptic repair. There are several allelic variants, but those homozygous or heterozygous for the E4 variant have an increased risk for the development and expression of the disease. Abnormalities on chromosomes 1 and 14 also have been associated with Alzheimer’s disease. The frontotemporal dementias are less prevalent than Alzheimer’s disease and are categorized by a frontal and temporal atrophy caused by cell death. The most common histologic finding in the frontotemporal dementias is the combination of prominent cell loss and gliosis in frontal and temporal regions of the cortex, termed dementia lacking distinctive histology. Approximately 15% to 20% of dementias are caused by multiple vascular insults to the CNS; the resulting deficit is termed multi-infarct dementia. The multiple infarcts typically involve the cerebral hemispheres and basal ganglia. Multi-infarct dementia often has an earlier age at onset than Alzheimer’s disease and occurs more often in adult men and patients who have risk factors for atherosclerosis. Approximately 29% of dementias are a mixed

CHAPTER 94  Delirium and Dementia

variety, with components of both ischemic cerebrovascular disease and Alzheimer’s dementia.13 Inflammatory conditions of the CNS caused by conventional viruses include subacute sclerosing panencephalitis from measles virus infection, progressive multifocal leukoencephalopathy from infection by the John Cunningham (JC) virus (a papovavirus), progressive rubella encephalitis, and infection associated with HIV disease. The unconventional viral infections include kuru, Creutzfeldt-Jakob disease (CJD), and variant CJD (which appears to be linked to bovine spongiform encephalopathy, the pathologic process in “mad cow disease”) and are associated with minimal inflammatory histopathologic changes in the CNS; these diseases cause a fine vacuolation of the nervous tissue and hence are referred to as subacute spongiform viral encephalopathies. Slow virus infections of the CNS can cause a progressive dementia that is irreversible. With these infections, months to years pass between infection with the virus and the appearance of clinical illness. Slow virus infections of the CNS are caused by both conventional viruses and unconventional virus like agents known as prions. A prion is a proteinaceous infectious particle with the apparent ability to start a chain reaction that changes the shape of benign protein molecules into abnormal, slowly destructive forms. Prions are present in CJD and variant CJD. One of the most prevalent slow virus infections causing progressive dementia is HIV-1 infection. HIV may produce a primary neurotrophic disorder in addition to causing the immunologic compromise that permits other viruses to replicate and damage nervous tissue. HIV dementia or acquired immunodeficiency syndrome (AIDS) dementia complex occurs in approximately onefourth of patients with AIDS. It is believed to be caused by the HIV-1 virus targeting the microglial cells and the macrophages, which may produce cytotoxic substances, such as tumor necrosis factor and interleukins. Pathologic changes occur mostly in the hippocampus and basal ganglia and include atrophy, ventricular dilation, and fibrosis. Several of the potentially reversible causes of dementia also are associated with neuropathologic or neurochemical abnormalities. Normal-pressure hydrocephalus generally affects younger people; 50% of patients are younger than 60 years. Most of the conditions that cause hydrocephalus involve a defect in uptake of CSF by arachnoid villi, which results in gradual ventricular dilation. Chronic, heavy ethanol consumption is associated with dementia. The neurotoxicity of ethanol appears to be independent of thiamine deficiency. Heavy chronic alcohol consumption causes cerebral cortical atrophy, but no single alcohol-related dementia syndrome exists.

Clinical Features Family or friends usually bring the patient to the ED because of a sudden worsening in mental status, a change in the patient’s activities (eg, refusal to eat), or a change in the ability of the caregiver to manage the patient. Presentations vary by the cause of the dementia and the stage of progression. Many elders with dementia have a superimposed delirium on presentation. The symptoms, signs, and progression of chronic cognitive impairment rarely are so diagnostic as to permit identification of the specific cause of the dementia. Alzheimer’s disease begins insidiously. Signs and symptoms of cognitive dysfunction may be present for months to years before the diagnosis is made. The earliest symptoms and signs of Alzheimer’s disease often are vague and nonspecific; patients manifest anxiety, depression, insomnia, frustration, and somatic complaints that often are more prominent than the memory loss. Patients often deny any cognitive deficits and change the subject of the conversation frequently rather than admit their increasing forgetfulness. Physicians often overlook the subtle signs of dementia in this phase of the disease.

Various tests in the cognitive function can be used to improve the detection rate of subtle cases, document a change in their level of cognition or used to assist in determination of competency (see Table 94.2). Depression often is the initial manifestation of Alzheimer’s disease and is present in up to 40% of cases. Early in the illness, short-term memory is affected with forgetfulness of recent events, such as appointments and names of new acquaintances. Patients often repeat questions. The memory impairment may cause them to withdraw from social situations and recreational pursuits. Attempts to perform complex tasks may produce anxiety and confusion. The patient often has difficulty with interpersonal relationships. Affect may be shallow and labile, and minor events may trigger inappropriate laughter or tears. Compensation for early deficits includes excessive orderliness and avoidance of situations in which the defects may be observed. Patients in this early phase who are treated with antidepressants with anticholinergic properties may experience worsening of their symptoms. Sedativehypnotics prescribed for anxiety also may accelerate cognitive dysfunction. As the dementia progresses, cognitive deficits are more obvious and should be readily apparent on a mental status examination. Problems with recent memory, impairment of remote memory, language deficits, and difficulty with spontaneous speech may be noted. With moderate severity of the disease, patients have difficulty naming objects (dysnomia). As many as 50% of patients have delusions, usually of the paranoid type. Atypical presentations of Alzheimer’s disease include aphasia, visual agnosia, right parietal lobe syndrome, focal neurologic findings, extrapyramidal signs, gait disturbances, and pure memory loss. In the final stage of dementia, patients exhibit marked cognitive impairment, apraxia, and significant personality changes. They often are bedridden and unable to perform the routine activities of daily living. Because Pick’s disease dementia affects the frontal and temporal lobes, patients often have frontal lobe release signs, including dramatic behavioral changes of disinhibition and social inappropriateness. Basal ganglia degenerative disorders that have dementia as a prominent feature are Huntington’s chorea, Parkinson’s disease, and Wilson’s disease. One of several features that distinguish cortical from subcortical dementias is a prominent movement disorder, including posturing, ataxia, tremor, and chorea, that tends to occur early in the illness. Other features of these dementias include slowness of speech, hypotonia, and dysarthria, which can progress to mutism. Patients with vascular dementia have a stepwise deterioration in memory and cognitive function with each cerebrovascular insult. The clinical presentation may follow one of two scenarios. In the more common scenario, the patient suffers several strokes that involve large volumes of cortical and subcortical structures in both hemispheres. The patient then exhibits dementia along with other neurologic disabilities (eg, focal weakness, hyperreflexia, extensor plantar response). In a second group of patients, the presentation is more subtle. These patients characteristically are hypertensive and suffer multiple tiny infarcts (lacunae) that involve deep subcortical structures. There may be no focal neurologic residua except progressive dementia with psychomotor retardation. Antihypertensive management in elders does not reduce the incidence of dementia. The clinical manifestations of slow virus CNS infections are protean. After an insidious onset of mental deterioration in subacute sclerosing panencephalitis, a rapid progression ensues that is associated with myoclonic jerks, incoordination, and ataxia. In progressive multifocal leukoencephalopathy, neurologic signs and symptoms reflect diffuse asymmetrical involvement of both cerebral hemispheres. Sporadic CJD, of unknown etiology, tends to affect older people, with a rate of disease among those 50 to 70 years old of one case per million. Among these patients, rapidly

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evolving dementia with myoclonus is characteristic. The hallmarks of the disorder are mental deterioration, multisystem neurologic signs, myoclonus, and typical electroencephalographic changes that evolve during months. Variant CJD affects younger patients (median age of 24 years) with key features that include early affective symptoms progressing to cognitive impairment and gait disturbances and ultimately leading to progressive neurologic deterioration. The incubation period appears to be in the range of 10 to 15 years, and most patients die within 14 months after the clinical onset of symptoms. The classic triad of progressive dementia, ataxia, and urinary incontinence occurs in patients with normal-pressure hydrocephalus, which typically affects patients who are younger than those with primary degenerative dementia. More than half of the reported cases are in persons younger than 60 years old. Hydrocephalus secondary to previous head trauma or infection carries a more favorable prognosis than that for primary hydrocephalus. In approximately 20% of the reversible cases, dementia is secondary to an intracranial mass. Patients may exhibit focal or nonfocal neurologic signs. Of the reversible dementias, 10% to 15% are caused by medications or chemical intoxications, frequently compounding a history of heavy alcohol use. Elders have increased susceptibility to the toxicities owing to polypharmacy and agerelated changes in metabolism. The clinical presentation of a patient with a drug-related or toxin-related dementia may be indistinguishable from that of a patient with a primary degenerative process. In addition, chronic traumatic encephalopathy (CTE) caused by repetitive mild traumatic brain injury and characterized by progressive neurodegeneration and deposition of hyperphosphorylated tau (p-tau) as neurofibrillary tangles may present as dementia and cognitive impairment.14 This form of encephalopathy develops 8 to 10 years after trauma and progresses to dementia, gait, and speech abnormalities and Parkinsonism. CTE may be clinically mistaken for Alzheimer’s disease or frontotemporal dementia.14

dementia were depressed. Depression, anxiety, and apathy are common in the prodrome and course of Alzheimer’s disease. A number of distinguishing features suggest that the problem is depression rather than dementia: the onset of cognitive changes in pseudodementia often can be pinpointed, and symptoms usually are of short duration before medical help is sought. The progression of symptoms is rapid, and the family usually is aware of the severity of the dysfunction. A history of psychiatric illness is common. Patients with pseudodementia usually complain of cognitive dysfunction and emphasize their failures and disabilities. The affective change often is pervasive, and the patient makes little effort to perform simple tasks. Loss of social skills usually occurs early in the illness, and patients communicate a strong sense of distress and inability to function. Intellectual functioning in pseudodementia often is difficult to assess because of lack of patient cooperation or inconsistent findings on neuropsychometric testing. Attention and concentration often are intact, but patients commonly give answers such as “I don’t know” on tests of orientation, concentration, and memory. Memory losses for recent and remote events usually are equally severe, and variability in the performance of tasks with similar degrees of difficulty may be marked. Tasks of high capacity (eg, testing of delayed memory with distraction) may be helpful in identifying the depressed patient.

Differential Diagnosis

Cognitive Evaluation

Senescent Forgetfulness

A mental status examination should be performed in all patients suspected to have cognitive dysfunction. In the demented patient, mental status testing can uncover subtle forms of delirium. Assessment of orientation to person, place, and time are not sensitive enough to establish cognitive dysfunction. A cognitive assessment should include both psychiatric and neurologic components (Box 94.4). Several standardized tools for the cognitive assessment have been successfully applied in the ED. Mental status testing includes assessment of orientation, memory, attention, and concentration; several tests also incorporate assessments of constructional tasks,

Subacute or chronic cognitive decline may be caused by a dementing illness or can be a manifestation of senescent forgetfulness, delirium, or depression. Senescent forgetfulness is an almost inevitable reality of aging. Mild impairment of both short-term and long-term memory is usual. Unlike dementia, the cognitive disturbance in senescent forgetfulness does not interfere with work or customary social activity.

Delirium In most cases, the clinical distinction between delirium and dementia is obvious (see Table 94.3). The onset of symptoms, progression of signs and symptoms, perceptual disturbances, abnormalities on assessment of vital signs, and fluctuations in the level of consciousness are key distinguishing features.13 However, dementia is a risk factor for delirium, and it is more difficult to differentiate delirium when superimposed on a patient with dementia.

Depression Depression in older adults may closely mimic dementia. Diagnosis of pseudodementia or depression masquerading as dementia can be difficult and may require therapeutic interventions to confirm the clinical diagnosis. Confounding the issue, depression often coexists with dementia; one study found that 40% of patients with

Diagnostic Strategies The evaluation of the patient with suspected dementia includes a focused medical, psychiatric, and medication history plus a collateral history from family and friends. Physical examination should include a detailed neurologic examination with a mental status evaluation. Dementia often goes unrecognized in the patient who is alert, pleasant, and cooperative. A validated cognitive evaluation test can play a key role in the early identification of dementia in patients who have maintained social and conversational ability.

BOX 94.4 

Elements of the Mental Status Examination in the Evaluation of Dementia ROUTINELY OBSERVED

Appearance, behavior, and attitude Mood and affect

REQUIRE INQUIRY

Disorders of thought: Suicidal and homicidal ideation Insight and judgment: Knowledge about illness Disorder of perception: Hallucinations and delusions Sensorium and intelligence: Cognitive impairment

CHAPTER 94  Delirium and Dementia

spatial discrimination, arithmetic ability, and writing. Cognitive functioning can be rapidly assessed in approximately 7 to 10 minutes. Memory assessment requires testing of the patient’s ability to repeat short series of words or numbers (immediate recall), to learn new information (short-term memory), and to retrieve previously stored information (long-term memory). Constructional apraxia is assessed by having the patient perform tasks, such as drawing interlocking geometric figures or clock faces and connecting dots. Dysnomia (inability to name objects correctly) and dysgraphia (impaired writing ability) are two of the most sensitive indicators of delirium superimposed on dementia. Almost all acutely confused patients exhibit writing impairments, including spatial disorganization, misspelling, and tremor. Therefore, if patients screen positive for delirium the standardized tools cannot be used to assess for dementia. No single bedside cognitive test that can be administered quickly is ideal. There are various tests of cognitive function, some of which have been tested in the ED (see Table 94.2). The MMSE developed by Folstein and colleagues has been validated more than any other test and most frequently is recommended as a rapid screening tool. For hospitalized patients, this test has a sensitivity of 87% and a specificity of 82% for detection of organic brain syndrome. The MMSE does not measure executive function and is insensitive for detection of early signs of mild cognitive impairment (without dementia) or early dementia. The MMSE consists of a short series of questions that test orientation, registration (memory), attention, calculation, recall, and language scored on a 30-point scale. The time for the test to be administered can be reduced to 5 minutes by elimination of the writing and drawing components with only a modest reduction in sensitivity. The registration section tests both immediate and short-term memory; the recall section also assesses shortterm memory. The ability to recall two of three objects has 81% sensitivity and 74% specificity for exclusion of organic brain syndrome. Asking the patient to subtract “serial sevens” backward from 100 assesses attention, concentration, and arithmetic ability. This test is specific but not sensitive for absence of an organic brain syndrome; up to 40% of nondelirious, nondemented people fail to perform the tasks of this test correctly, reflecting limitations due to language ability and education. A total score of 23 or less is considered markedly abnormal and indicates an organic brain syndrome. As a general rule, patients with mild cognitive impairment have a score of 18 to 26 out of 30, those with moderate impairment have a score of 10 to 18, and those with severe impairment have a score of less than 10. Another frequently used test is the clock drawing test. It is scored on a 6-point scale from no errors to no reasonable representation of a clock. Patients with a score of 1 to 2 points are without impairment, and those with 3 to 6 points have cognitive impairment. All bedside tests of cognition have limitations and can miss mild degrees of impairment. The patient’s level of education and general intelligence can substantially affect the outcome. Furthermore, a single bedside test reflects a patient’s cognitive functioning at only one point in time. Alzheimer’s disease is a clinical diagnosis typically made on probability; no routine available laboratory tests have been found to confirm the presence of the disorder (although MRI scan, functional scans looking at regional blood flow or glucose metabolism, assay for specific biomarkers, and CSF analysis can increase the probability of the presence of the disease). The physical examination is rarely helpful in detecting treatable dementias because of the considerable clinical overlap with irreversible dementias.

Laboratory Tests and Imaging Studies Data clearly supporting or refuting the ordering of “routine” laboratory studies for evaluation of dementia are lacking; however,

a number of studies are recommended to exclude treatable causes (see Box 94.2). For patients with suspected undiagnosed dementia presenting to the ED, a baseline laboratory evaluation, including CBC, comprehensive metabolic panel, and urinalysis, is indicated. If neurosyphilis is clinically suspected, a serum fluorescent treponemal antibody absorption test should be performed in addition to a Venereal Disease Research Laboratory (VDRL) test because the serum VDRL assay may yield negative results in patients with tertiary syphilis. The radiologic evaluation should include a non– contrast-enhanced head CT scan. The CT scan is used to diagnose or to exclude the presence of hydrocephalus or space-occupying lesions, and CT findings may support a vascular etiology for the dementia. Patients require additional laboratory tests on follow-up evaluation; such tests may include determination of serum vitamin B12 and folate levels, thyroid function studies, erythrocyte sedimentation rate, fluorescent antinuclear antibody assay, measurement of urine corticosteroid levels, and, if indicated by history, urine screens for drugs and heavy metals. Selected patients should undergo a LP with CSF analysis, MRI, positron emission tomography scan, electroencephalography (in CJD, characteristic slowing and periodic complexes may be electroencephalographic features), neuropsychological testing, and testing of visual evoked potentials, brainstem auditory evoked potentials, and somatosensory evoked potentials. The EEG rarely is helpful in establishing the diagnosis of senile dementia. An MRI finding of medial temporal atrophy suggests Alzheimer’s disease but is not specific or sensitive for diagnosis of this disorder. Neuroimaging with head CT or MRI is controversial but indicated in patients with acute onset or rapid deterioration of cognitive impairment to identify rapidly progressive dementia and cerebrovascular accidents.

Summary The diagnostic evaluation of the patient with suspected dementia includes a focused medical, psychiatric, and medication history, detailed neurologic and psychiatric examination with assessment of mental status and cognition followed by a baseline laboratory evaluation, including CBC, comprehensive metabolic panel, and urinalysis and non-contrast head CT. Additional evaluation should be guided by history and physical examination. Mental status and cognitive assessment can be performed with several standardized tools that have been successfully applied in the ED. Initial mental status testing with the CAM may identify subtle forms of delirium. The CAM has four key features used in screening for delirium: (1) acute onset and fluctuating course, (2) inattention, (3) disorganized thinking, and (4) altered level of consciousness. For a definitive diagnosis of delirium, the first two features and one of the last two must be present. If the patient is CAM negative then further testing of cognition is warranted to identify dementia. The MMSE is a validated test of cognitive function that consists of a short series of questions that test orientation, registration (memory), attention, calculation, recall, and language. The clock drawing test is an alternate test of cognitive impairment that may be useful in the ED setting. All tests of mental status and cognition may be affected by the level of education and general intelligence and reflect a patient’s cognitive functioning at only one point in time. Patient’s identified with cognitive impairment in the ED should undergo further neuropsychiatric testing and treatment.

Management Reversible dementias and conditions that cause worsening of baseline dementia require early diagnosis and treatment. Determination of reversible causes of dementia during the ED

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evaluation occasionally is possible on the basis of the history (including medication history), physical examination, and head CT scan. Patients with acute changes in mental status or a relatively rapid onset of symptoms will require hospitalization for comprehensive evaluation. Patients presenting with recent gradual decline in cognitive function without an underlying acute medical condition can undergo further evaluation on an outpatient basis. Pharmacotherapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate Alzheimer’s disease includes the cholinesterase inhibitors donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). There are multiple randomized, placebo-controlled, large-scale clinical trials with these drugs establishing efficacy in improving cognitive functions and activities of daily living in patients with mild to moderate dementia. These drugs are not considered disease modifying, and there are limited data at present on the benefit of these drugs beyond 2 or 3 years (a significant number of patients discontinue medications because of side effects). The most common side effect of these agents is due to the cholinergic effects, including nausea, vomiting, and diarrhea. In 2003, the FDA approved memantine (Namenda), a diseasemodifying agent that helps regulate the excitatory effects of glutamate by antagonizing the N-methyl-d-aspartate receptor. Whether this drug alters the underlying disease process is unclear, but short-term studies show improved cognition in patients with moderate and moderate to severe Alzheimer’s disease. There are conflicting studies on the effectiveness of other agents, such as gingko biloba, vitamin E, nonsteroidal agents, and statins. Estrogen replacement is not indicated for cognitive improvement or maintenance in women with Alzheimer’s disease and can be detrimental. Ultimately, the key to altering the course of the disease is halting neuron loss. In severe dementia, the goal of management is supportive care. Many therapies currently are under investigation for the modulation and early treatment of Alzheimer’s disease. These therapies include antibiotics (directed against Chlamydophila pneumoniae), secretase modulators to reduce serum β-amyloid levels, immunization to reduce amyloid plaque burden, chelators to promote dissolution of β-amyloid, nonsteroidal antiinflammatory medications, supplementation with omega-3 fatty acids, and testosterone. Increasing evidence suggests that certain nonpharmacologic measures, including behavioral methods and avoidance of environmental triggers, may be effective in reducing agitation and anxiety in patients with dementia.16 On occasion, medications are needed for behavioral symptoms of dementia. Affected patients typically do not improve with anxiolytics. Adverse effects offset the modest advantages in the efficacy of antipsychotic drugs for the treatment of psychosis, aggression, or agitation in many patients with Alzheimer’s disease, and these drugs should be avoided when possible. However, despite the lack of consensus in the indication for use and dosages in older demented patients, butyrophenone (such as, haloperidol, 0.5 to 5 mg IM) or atypical antipsychotic olanzapine (2.5 to 5 mg IM) have been found to be effective in the management of acute agitation. Clozapine may be effective in treating psychosis associated with both Alzheimer- and Parkinson-type dementias. However, in April 2005, the FDA issued a black box warning that the use of atypical antipsychotics to treat older patients with dementia related psychosis was associated with an increased risk for death compared with placebo, thus the risks and benefits of using these drugs must be considered. A clear treatment choice for agitation and psychosis in those with dementia has not been identified. The antipsychotics raise a concern for QT prolongation, extrapyramidal symptoms, seda-

tion, and anticholinergic and drug-drug interaction; the benzodiazepines have a fall risk, confusion, memory impairment, and oversedation. Regardless of intervention used, the lowest dose possible should be used and then titrated carefully to effect. Agitation in patient with dementia may occasionally be due to unrecognized depression or pain. A trial of selective serotonin reuptake inhibitors (SSRIs) (such as, citalopram 20 mg PO) and adequate pain management may be warranted. Selection of a SSRI should be based upon side effect profile and drug interactions. Sleep disturbances may be treated with temazepam (7.5 mg oral), which is the drug of choice. The half-life of temazepam is 8 to 10 hours for patients of all ages, and the drug bypasses the oxidative hepatic enzyme system.

Disposition Patients with dementia present to the ED because of an acute deterioration, behavioral change, or crisis due to family stress. A brief observation, acute inpatient medical or psychiatric hospitalization, nursing home stay, or other institutional stay (respite program) may stabilize patient and give the family time to mobilize resources to resume the home care regimen. Social workers can play a vital role in attempting to facilitate continued management. A key to successful disposition planning is to use screening tools to assess the cognitive, functional, and psychosocial status of patients with delirium and dementia. Anticipating and addressing cognitive or functional barriers to compliance with discharge plan and transitional care plan is essential.

KEY CONCEPTS • Delirium is an acute condition characterized by an altered level of consciousness, disorganized thinking, and inattention. It develops during a short time, and symptoms tend to fluctuate during hours to days. • Delirium is commonly caused by medications, drug intoxication or withdrawal, infections, metabolic disorders, CNS and cardiovascular events, and autonomic nervous system disturbances. • Dementia is a chronic condition characterized by cognitive impairment. It is slow in onset and progressive in nature. This disorder has many causes, some of which are reversible with treatment. It is essential to search for reversible underlying etiologies that may be worsening a cognitive impairment. • Patients with either dementia or psychiatric disorders may present with superimposed delirium, often making identification of the underlying cause of their abnormal behavior difficult. • The clinician should be wary of attributing behavioral disturbances to psychiatric illness in the presence of abnormal vital signs or abnormal sensorium. • Nonpharmacologic methods including behavioral methods and avoidance of environmental triggers should be considered in the treatment of agitation in patients with dementia. • Antipsychotics and benzodiazepines are used cautiously, in the management of acute agitation in delirium and dementia. The choice of agent is determined by side effect profile and etiology of delirium or acute agitation. • Antipsychotics and benzodiazepines are not approved for the long-term treatment of the behavioral symptoms of dementia. • Antipsychotics may cause QTc prolongation and increased mortality especially when given intravenously. • Lower doses of medications may be appropriate in older adults to decrease risk of adverse effects while effectively treating acute agitation.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 94  Delirium and Dementia

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REFERENCES 1. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, (DSM-5), Arlington, VA, 2013, American Psychiatric Association Publishing. 2. LaMantia MA, et al: Screening for delirium in the emergency department: a systematic review. Ann Emerg Med 6:551–560, 2014. 3. Barron EA, Holmes J: Delirium within the emergency care setting, occurrence and detection: a systematic review. Emerg Med J 30:263–268, 2013. 4. Wong CL, et al: Does this patient have delirium?: value of bedside instruments. JAMA 304:779–786, 2010. 5. Riker RR, et al: Clinical monitoring scales in acute brain injury: assessment of coma, pain, agitation, and delirium. Neurocrit Care 21 Suppl 2:S27–S37, 2014. 6. Han JH, et al: Validation of the confusion assessment method for the intensive care unit in older emergency department patients. Acad Emerg Med 21:180–187, 2014. 7. Han JH, Wilson A, Vasilevskis EE, et al: Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method. Ann Emerg Med 62:457–465, 2013. 8. Witlox J, et al: Delirium in elderly patients and the risk of post-discharge mortality, institutionalization, and dementia: a meta analysis. JAMA 304:443–451, 2010. 9. Bush SH, et al: Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development. J Pain Symptom Manage 48:2, 2014.

10. Chan EW, Taylor DM, Knott JC, et al: Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med 61:72–81, 2013. 11. Gillies D, Sampson S, Beck A, et al: Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev (9):CD003079, 2013. 12. Wong N, Abraham G: Managing delirium in the emergency department: tools for targeting underlying etiology. Emerg Med Pract 17(10):1–24, 2015. 13. Hebert LE, Weuve J, Scherr PA, et al: Alzheimer disease in the United States (2010– 2050) estimated using the 2010 Census. Neurology 80:1778–1783, 2013. 13. Day GS, Tang-Wai DF: When dementia progresses quickly: a practical approach to the diagnosis and management of rapidly progressive dementia. Neurodegen Dis Manag 4(1):41–56, 2014. 14. McKee AC, Stein RA, Nowinski CJ, et al: The spectrum of disease in chronic traumatic encephalopathy. Brain 136(Pt 1):43–64, 2013. 15. Azermai M, Petrovic M, Elseviers MM, et al: Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Res Rev 11(1):78–86, 2012. 16. Azermai M, Petrovic M, Elseviers MM, et al: Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Res Rev 11(1):78–86, 2012.

CHAPTER 94: QUESTIONS & ANSWERS 94.1. Which of the following characteristics helps distinguish dementia from delirium? A. Autonomic nervous system derangements B. Cranial nerve dysfunction C. Disorientation D. Focal weakness E. Pain Answer: A. Delirium is characterized by a disturbance in level of consciousness with confusion. Demented patients present with a much more gradual onset of symptoms with typically no change in level of consciousness. Delirium is further characterized by autonomic nervous system abnormalities and the presence of an underlying disease process. The disturbance also tends to fluctuate in severity during the course of the day. 94.2. A 78-year-old woman presents with 3 days of decreasing ability to concentrate, memory and cognition breakdown, sleep cycle disruption, and fluctuating levels of agitation. Her current medications include levofloxacin (Levaquin) 500 mg/day for a bladder infection, tramadol prn for knee arthritis, and hydrochlorothiazide 25 mg/day for essential hypertension. Her examination is normal except for a baseline tachycardia, moderate agitation and restlessness, and orientation to person only. Laboratory analysis shows glucose 198 mg/dL, sodium 131 mEq/L, potassium 3.8 mEq/L, creatinine 1.4 mg/dL, white blood cell (WBC) count 11,300 cells/mm3, hemoglobin 12 g/dL, bicarbonate 25 mEq/L, and a normal urinalysis. What is the most likely etiology for her delirium? A. Early sepsis B. Hyperglycemia C. Hyponatremia D. Intracranial hemorrhage E. Medication effect Answer: E. Medications are the most common cause of delirium in the older adult population. Common inciting medications include antibiotics (quinolones and macrolides), analgesics, sympathomimetics, antiinflammatories, sedatives, and cardiovascular agents. This level of hyponatremia would not be expected to cause a delirium. Likewise, a modest hyperglycemia without associated acidosis would be an unlikely culprit. 94.3. An 82-year-old man presents with acute delirium. On examination, he is alert and mildly agitated. He is oriented to person and place but not time. He is easily distracted and exhibits a mild bilateral upper extremity resting tremor without asterixis. His neurologic examination is nonfocal. His short-term memory is impaired. What is the

central component most key to the diagnosis of delirium in this case? A. Agitation B. Disorientation C. Inattention D. Memory dysfunction E. Tremor Answer: C. Disturbance in attention is central to the diagnosis of delirium. Disorientation often accompanies this but is not invariably present. The patient is usually disoriented to time and, less often, place. The delirious patient may also experience visual, auditory, tactile, and olfactory hallucinations; may lose the ability to modulate emotional expression; and often exhibits fluctuating symptoms. Short-term memory is usually impaired, but this is also seen in dementia. 94.4. Which of the following associations is correct? A. Droperidol: QT prolongation B. Haloperidol: Dysphoria C. Lorazepam Excessive half-life D. Meperidine: Cholinergic effects E. Phenothiazines: Hypocalcemia Answer: A. This may also be seen, although less so, with haloperidol and the phenothiazines. Meperidine causes dysphoria and possibly some anticholinergic effects. Diazepam results in the longest terminal T12 of the benzodiazepines. 94.5. A 63-year-old man presents with acute-onset delirium. He is a known alcoholic, and the family reports a cessation of alcohol intake 36 hours before presentation. He has no other known medical problems. Examination is remarkable for an acutely delirious patient who has active visual and auditory hallucinations and a mild tremor. Neurologic examination is otherwise negative, except for a left sixth cranial palsy. Finger-stick glucose is normal. Thiamine 100 mg intravenously fails to improve his symptoms. Which of the following is the intervention most likely to immediately improve his function? A. Dextrose B. Haloperidol C. Lorazepam D. Magnesium E. More thiamine Answer: D. Magnesium is a cofactor in the utilization of thiamine. In chronically magnesium-depleted patients, Wernicke’s encephalopathy may be refractory to thiamine until magnesium is also administered.

C H A P T E R 95 

Brain and Cranial Nerve Disorders Brian A. Stettler

TRIGEMINAL NEURALGIA (CRANIAL NERVE V)

lancinating pain of trigeminal neuralgia, the distribution is similar and these diagnoses should be considered before anchoring on a diagnosis of trigeminal neuralgia. Two percent to 4% of patients with trigeminal neuralgia also have MS, which should be considered in patients who present with neurologic findings that do not fit a specific pattern.

Principles

Diagnostic Strategies

Trigeminal neuralgia, or tic douloureux, is a syndrome featuring painful paroxysms in one or more distributions of the trigeminal nerve (CN V). Trigeminal neuralgia is more common in women than in men, with a female-to-male ratio of 2 : 1. Affected persons typically are between 50 and 69 years old, and symptoms occur more frequently on the right side of the face. Trigeminal neuralgia is an idiopathic disorder, although evidence points to vascular compression of the trigeminal nerve root in many cases. This compression commonly is caused by a tortuous arterial or venous loop in the posterior fossa, an arteriovenous malformation, or rarely a tumor. Although structural lesions are not found in all patients, surgical case series report up to 90% of cases having vascular compression of the trigeminal nerve root.

Patients with normal findings on the head and neck examination and no neurologic deficits who have episodic, unilateral facial pain associated with nonpainful triggers are likely to have trigeminal neuralgia. The presence of a neurologic deficit should prompt suspicion of a structural lesion, such as aneurysm, tumor, or other intracranial lesion (eg, from MS). Patients with a neurologic deficit require urgent imaging studies, typically magnetic resonance imaging (MRI), to rule out a mass or vascular abnormality.

This chapter discusses cranial nerve (CN) problems, cerebral venous thrombosis (CVT), and multiple sclerosis (MS)—neurologic disorders that often provide diagnostic and therapeutic challenges in the emergency department (ED) setting (Table 95.1).

Clinical Features Trigeminal neuralgia is manifested with unilateral facial pain, which is typically characterized as lancinating paroxysms of pain in the lips, teeth, gums, or chin. The pain is commonly associated with physical triggers, such as chewing, brushing the teeth, shaving, washing or touching the affected area of the face, swallowing, or exposure to hot or cold temperature in the affected area. The maxillary and mandibular divisions of the trigeminal nerve are most commonly involved; rarely, the ophthalmic division alone is involved. Patients tend to experience the pain in clustered episodes that last a few seconds to several minutes. The attacks can occur during the day or night but rarely arise during sleep. The physical examination in patients with facial pain includes an evaluation of the sinuses, teeth, and the CNs. Given the location of the pain, the ears must be examined for signs of otitis, the teeth and face examined for evidence of odontogenic infection (such as, facial swelling or gingival fullness), and the skin and scalp examined for the painful vesicular eruption of zoster. Purulent drainage from the sinus indicates sinusitis as a possible underlying cause requiring treatment before continued pursuit of a diagnosis of trigeminal neuralgia.

Differential Diagnosis Other painful facial conditions that are considered in patients with facial pain include odontogenic infections, sinus disease, otitis media, acute glaucoma, temporomandibular joint disease, and herpes zoster. Although the temporal components of the pain in these conditions are not similar to the sudden onset,

Management The medical treatment of choice for trigeminal neuralgia is carbamazepine. The mechanism of action of anticonvulsant therapy for trigeminal neuralgia is unclear, but carbamazepine appears to be an effective and well-tolerated treatment. The initial dosage is 100 mg twice daily, increased to three times daily after 1 week. The dose may then be increased by 100 mg/day, up to a maximum of 1200 mg/day. A complete blood count and liver function studies are performed periodically in patients who are taking carbamazepine to monitor for hematologic and hepatic side effects. Additional agents that have been used for treatment of trigeminal neuralgia include phenytoin, baclofen, valproate sodium, lamotrigine, gabapentin, and levetiracetam. None has been shown to be more effective than carbamazepine. Several recent studies have investigated the use of onabotulinum toxin A for refractory pain management in trigeminal neuralgia. Although the studies are small, there are two randomized controlled trials that have shown decreased pain scores and increased quality of life with this therapy when combined with conventional medications.1,2 Both peripheral and central surgical interventions for trigeminal neuralgia are management options for difficult cases. Peripheral strategies include medication injection and cryotherapy techniques designed to temporarily block or permanently ablate branches of the peripheral trigeminal nerve. Although these procedures are relatively effective initially, recurrence is common. Central procedures include percutaneous destruction of the trigeminal ganglion, although these procedures carry the risk of corneal anesthesia, oculomotor paresis, or masticatory weakness.3 Open surgical management includes microvascular decompression of the nerve with or without partial ablation. Although pain relief is achieved in 80% to 95% of patients, the surgery is associated with the risk of complications. Gamma knife radiosurgery, a minimally invasive, precision-directed stereotactic radiosurgery, has shown good outcomes.4 1289

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TABLE 95.1 

The Cranial Nerves: Normal Function and Pathologic Considerations CRANIAL NERVE

CLINICAL FUNCTION RELEVANT TO EMERGENCY MEDICINE PATHOLOGIC FEATURES

CN I: Olfactory nerve

Sense of smell

Unilateral anosmia

Trauma: Skull fracture or shear injury interrupting olfactory fibers traversing the cribriform plate Tumor: Frontal lobe masses compressing the nerve

CN II: Optic nerve

Vision

Unilateral vision loss

Trauma: Traumatic optic neuropathy Tumor: Orbital compressive lesion Inflammatory: Optic neuritis (MS) Ischemic: Ischemic optic neuropathy

CN III: Oculomotor nerve

Extra oculomotor function via motor fibers to levator palpebrae, superior rectus, medial rectus, inferior rectus, inferior oblique muscles Pupillary constriction via parasympathetic fibers to constrictor pupillae and ciliary muscles

Ptosis caused by loss of levator palpebrae function Eye deviated laterally and down Diplopia Dilated, nonreactive pupil Loss of accommodation

Trauma: Herniation of the temporal lobe through the tentorial opening, causing compression and stretch injury to the nerve Ischemic: Especially in diabetes; microvascular ischemic injury to nerve causes extraocular muscle paralysis but usually is papillary sparing (often painful) Vascular: Intracranial aneurysms may press on the nerve, leading to dysfunction Myasthenia gravis can lead to atraumatic ocular muscle palsy

CN IV: Trochlear nerve

Motor supply to the superior oblique muscle

Inability to move eye downward and laterally Diplopia Patients tilt head toward unaffected eye to overcome inward rotation of affected eye

Trauma is the most common cause of nerve dysfunction

CN V: Trigeminal nerve

Motor supply to muscles of mastication and to tensor tympani Sensory to face, scalp, oral cavity (including tongue and teeth)

Partial facial anesthesia Episodic, lancinating facial pain associated with benign triggers, such as chewing, brushing teeth, light touch

Trauma: Facial bone fracture may injure one section, leading to area of facial anesthesia Tic douloureux

CN VI: Abducens nerve

Motor supply to the lateral rectus muscle

Inability to move affected eye laterally Diplopia on attempting lateral gaze

Tumor: Lesions in the cerebellopontine angle Any lesion, vascular or otherwise, in the cavernous sinus may compress nerve Elevated ICP: Because of its position and long intracranial length, increased ICP from any cause may lead to injury and dysfunction of the nerve

CN VII: Facial nerve

Motor supply to muscles of facial expression Parasympathetic stimulation of the lacrimal, submandibular, and sublingual glands Sensation to the ear canal and tympanic membrane

Hemifacial paresis: Lower motor neuron lesion leaves entire side of face paralyzed Upper motor neuron lesion leaves forehead musculature functioning Abnormal taste Sensory deficit around ear Intolerance to sudden loud noises

Lower motor neuron: Infection (viral): The likely cause of Bell’s palsy Lyme disease: The most common cause of bilateral CN VII palsy in areas where Lyme disease is endemic   Bacterial infection extending from otitis media Upper motor neuron: Stroke, tumor

CN VIII: Vestibulocochlear Hearing and balance nerve

Unilateral hearing loss Tinnitus Vertigo, unsteadiness

Tumor: Acoustic neuroma Mimics Ménière’s disease, perilymphatic fistula

CN IX: Glossopharyngeal nerve

Clinical pathology referable to the nerve in isolation is very rare Occasionally painful paroxysms beginning in the throat and radiating down the side of the neck in front of the ear but behind the mandible

Brainstem lesion Glossopharyngeal neuralgia

General sensation to posterior third of tongue Taste for posterior third of tongue Motor supply to the stylopharyngeus

POSSIBLE CAUSES

CHAPTER 95  Brain and Cranial Nerve Disorders

TABLE 95.1 

The Cranial Nerves: Normal Function and Pathologic Considerations—cont’d CRANIAL NERVE

CLINICAL FUNCTION RELEVANT TO EMERGENCY MEDICINE PATHOLOGIC FEATURES

POSSIBLE CAUSES

CN X: Vagus nerve

Motor to striated muscles and muscles of the pharynx, larynx, and tensor (veli) palatini Motor to smooth muscles and glands of the pharynx, larynx, thoracic and abdominal viscera Sensory from larynx, trachea, esophagus, thoracic and abdominal viscera

Unilateral loss of palatal elevation: Patients complain that on drinking liquids, the fluid refluxes through the nose Unilateral vocal cord paralysis: Hoarse voice

Brainstem lesion Injury to the recurrent laryngeal nerve during surgery

CN XI: Spinal accessory nerve

Motor supply to the sternocleidomastoid and trapezius muscles

Downward and lateral rotation of the scapula and shoulder drop

Trauma to the nerve

CN XII: Hypoglossal nerve

Motor supply to the intrinsic and extrinsic muscles of the tongue

Stroke or tumor can cause upper motor Tongue deviations: neuron lesion Upper motor neuron lesion causes the tongue to deviate toward the Amyotrophic lateral sclerosis can cause bilateral lower motor neuron lesion with opposite side atrophy Lower motor neuron lesion causes the tongue to deviate toward the Metastatic disease to the skull base may involve the nerve side of the lesion, and the affected side atrophies over time

CN, Cranial nerve; ICP, intracranial pressure; MS, multiple sclerosis.

Disposition Patients with newly suspected trigeminal neuralgia should be referred for specialty evaluation. Coordination with a neurologist will help in therapeutic decision making. Patients with an established diagnosis who present with uncontrolled pain refractory to maximum pharmacologic management may require a neurosurgical consultation for an operative intervention.

FACIAL NERVE PARALYSIS (CRANIAL NERVE VII) Principles Peripheral paralysis has no geographic, gender, or race predilection; pregnancy is a risk factor.5 The facial nerve (CN VII) innervates the muscles of facial expression and the muscles of the scalp and external ear in addition to the buccinator, platysma, stapedius, stylohyoid, and posterior belly of the digastric muscles. The sensory portion of the nerve supplies the anterior two-thirds of the tongue with taste and sensation to portions of the external auditory meatus, soft palate, and adjacent pharynx. The parasympathetic portion supplies secretomotor fibers for the submandibular, sublingual, lacrimal, nasal, and palatine glands. The nerve originates from the pontomedullary junction of the brainstem and enters the internal auditory meatus with CN VIII. Within the temporal bone, the facial nerve has four major branches: the greater and lesser superficial petrosal nerves, the nerve to the stapedius muscle, and the chorda tympani. The facial nerve exits the temporal bone at the stylomastoid foramen and then enters the parotid gland, where it divides to supply the muscles of facial expression.

Clinical Features The medical history in patients with facial paralysis focuses on onset of the paralysis, concentrating on timing and rapidity of onset and associated signs and symptoms. The most common

causes of a CN VII palsy are Bell’s palsy, Ramsey Hunt syndrome, Lyme disease, and bacterial infections of the middle ear, mastoid, or external auditory canal.

Bell’s Palsy Bell’s palsy, also commonly called idiopathic facial paralysis, is postulated but not confirmed to have a viral cause. It is characterized by an abrupt onset of a lower motor neuron paresis that typically develops over 72 hours and can progress during 1 to 7 days to complete paralysis. A prodromal viral-like illness is described by 60% of patients. Symptoms and signs frequently associated with the facial paresis include ear pain, perception of sensory change on the involved side of the face, decreased tearing, overflow of tears on the cheek (epiphora), abnormally acute hearing (hyperacusis), and impairment or perversion of taste (dysgeusia). To make the diagnosis of Bell’s palsy, both the upper and lower facial muscles must be involved. If only lower face involvement can be elicited, there should be a suspicion for a central lesion, such as a cerebral infarct or neoplasm. Lid closure is assessed by asking the patient blink rapidly; if the patient is unable to fully close the eye, a diagnosis of Bell’s palsy suspected.

Ramsey Hunt Syndrome Ramsay Hunt syndrome (herpes zoster oticus) is characterized by unilateral facial paralysis, a herpetiform vesicular eruption, and vestibulocochlear dysfunction. The vesicular eruption, which may follow the facial paralysis by a few days, may occur on the pinna, external auditory canal, tympanic membrane, soft palate, oral cavity, face, and neck as far down as the shoulder. The pain is considerably more severe than that associated with Bell’s palsy, and it frequently is out of proportion to physical findings. In addition, outcomes are worse than with Bell’s palsy, with a lower incidence of complete facial recovery and the possibility of sensorineural hearing loss.

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Lyme Disease Systemic symptoms or bilateral facial paresis, especially in endemic areas, should raise the possibility of Lyme disease. Lyme disease is the most frequent vector-borne infection in the United States. It is caused by the spirochete Borrelia burgdorferi and is spread by the bite of Ixodes genus ticks. Neurologic manifestations can arise in any phase of the disease, and facial palsy accounts for up to 50% of the neurologic presentations. In regions in which Lyme disease is endemic, it has been shown to be the leading cause of facial paralysis in children. Bilateral facial nerve paralysis is rare but can occur with systemic infections. The two diseases most commonly associated with bilateral simultaneous onset of facial paralysis are Lyme disease and infectious mononucleosis. Bilateral facial paralysis should be considered to be a manifestation of Lyme disease until further testing excludes this diagnosis. The evaluation and treatment of Lyme disease are discussed in Chapter 126.

Bacterial Ear Infections Facial paralysis can be caused by acute bacterial infections of the middle ear, mastoid, or external auditory canal. In the preantibiotic era, facial paralysis was associated with acute otitis media in approximately 2% of cases; today, however, it occurs in only 0.2% of cases. Malignant otitis externa can be associated with facial paralysis. This disease entity is most commonly seen in immunocompromised patients and usually is caused by Pseudomonas infection.

Differential Diagnosis In addition to the disorders previously discussed, paralysis of CN VII can be caused by facial trauma where temporal bone fracture can cause nerve transection and neoplasia. A history of recurrent ipsilateral paralysis or slow progression of symptoms is more characteristic of a tumor. Associated CN abnormalities, such as a gaze paresis, point to the possibility of a tumor or cerebral ischemic insult. Patients will occasionally describe “numbness” in the same distribution as the weakness to the face, although they rarely experience the dense sensory loss or weakness of mastication seen in CN V lesions. Potential involvement of multiple CNs suggests a stroke or a mass lesion. Tumors of the facial nerve itself or tumors anywhere along its course that invade or compress the nerve may lead to facial paralysis. The course is typically progressive for at least 3 weeks and typically of slower onset than that which is found in Bell’s palsy, although up to 25% of tumors will present with a history of sudden onset of paralysis. Although very rare overall, a neoplastic cause should be suspected in patients who suffer from recurrent ipsilateral facial paralysis, significant pain, prolonged symptoms, or any other concomitant CN abnormality.

Diagnostic Strategies The diagnostic evaluation of acute facial nerve paresis is based on whether the clinical picture is suggestive of a disease process other than Bell’s palsy. If the clinical history is classic for Bell’s palsy, the American Academy of Otolaryngology recommends no imaging or laboratory studies.6 A history that poses potential exposure to Lyme warrants serologic evaluation for the disease. Although outpatient testing including electroneurography may ultimately be performed, this usually is not part of the initial evaluation. The presence of a “central” seventh nerve paralysis (upper face sparing) should prompt imaging with computed tomography (CT) or MRI, and consideration given to the possibility of an acute stroke or other hemispheric lesion. History or physical

findings suggestive of a possible tumor require imaging to rule out a neoplasm. The study of choice will depend on the institution and preferences of the consultant but typically involves MRI.

Management Bell’s Palsy Both medical and surgical treatments of Bell’s palsy are available. The primary medical therapies for Bell’s palsy center on reducing inflammatory changes to the nerve with corticosteroids and treating the presumed viral cause. If these therapies are unsuccessful, surgical decompression may be considered. Available evidence strongly favors the use of corticosteroids for the treatment of Bell’s palsy, and earlier treatment is associated with better outcomes.7,8 Steroid therapy is believed to inhibit edema of the nerve, confined within the facial canal, which is thought to cause or contribute to the nerve injury. Based on the results of high quality, randomized trials, we recommend treatment with prednisolone, 50 to 60 mg/day per day for 10 days, with or without a short taper. Therapy should be started as soon as possible, ideally within the first 24 hours, but it is still recommended for patients without contraindications who seek treatment within 1 week of symptom onset. A number of studies have supported the contention that Bell’s palsy may be caused by herpes virus infection. Herpes simplex virus type 1 DNA has been demonstrated in the endoneurial tissue of Bell’s palsy patients, although there is conflicting evidence on the efficacy of antiviral treatment. Some studies have found treatment with corticosteroids plus antiviral medications to be superior to steroids alone, particularly in the setting of severe palsy or in those treated within 24 hours of symptom onset.9 Other studies have found conflicting results.10 Summary statements from the American Academy of Otolaryngology recommend that antivirals “be considered” in the treatment of Bell’s palsy, although they should only be offered in combination with oral steroids and should be considered more strongly for severe loss of function.10 We recommend valacyclovir, 1000 mg orally three times daily for 7 days, or famciclovir, 750 mg orally for 7 days (Table 95.2). Valacyclovir and famciclovir have better oral absorption, are better tolerated, and are dosed less frequently, resulting in higher compliance than with acyclovir treatment. Although earlier treatment is preferred, treatment should be considered for patients presenting within 1 week of symptom onset.

Ramsay Hunt Syndrome The treatment of Ramset Hunt syndrome is similar to that of Bell’s palsy, although antiviral treatment is more strongly recommended in this disease process in addition to steroid therapy. Both prednisone and antiviral therapy should be continued for 7 to 10 days.

TABLE 95.2 

Treatment of Bell’s Palsy MILD/MODERATE DISEASE

SEVERE DISEASE

Steroids

Prednisolone 50 to 60 mg daily for 10 days, with or without taper

Prednisolone 50 to 60 mg daily for 10 days, with or without taper

Antivirals

Not recommended

Consider in addition to steroids, valacyclovir 1000 mg tid or famciclovir 750 qD for 7 days

CHAPTER 95  Brain and Cranial Nerve Disorders

Lyme Disease

Differential Diagnosis

The treatment of Lyme disease is discussed in Chapter 126.

A majority of disease entities included in the differential diagnosis for vestibular schwannoma cause symmetrical sensorineural hearing loss. Asymmetrical sensorineural hearing loss has few causes other than vestibular schwannoma. Ménière’s disease may present with asymmetrical findings, but it can be differentiated from vestibular schwannoma in that the tinnitus of Ménière’s disease usually is intermittent, whereas the tinnitus of vestibular schwannoma typically is continuous. In addition, patients with Ménière’s disease typically describe true vertigo, whereas patients with a vestibular schwannoma are more likely to describe imbalance or dysequilibrium. Vestibular schwannomas account for 80% of all cerebellopontine angle tumors, meningiomas are the second most common. Meningiomas more frequently cause symptoms of facial palsy or trigeminal nerve abnormality. Of note, however, considerable similarity between the clinical picture of a meningioma and that of vestibular schwannoma in the cerebellopontine angle has been described.

Bacterial Infections Treatment bacterial infections causing a CN VII palsy involves prolonged intravenous (IV) antipseudomonal antibiotic therapy and may require surgical débridement.

Disposition Most patients who have a seventh CN paralysis will have a clinical diagnosis of Bell’s palsy and may be discharged with referral for short-term follow-up. Patients with a possible hemispheric process, such as stroke or tumor, require further evaluation and often hospitalization. Patients thought to have Lyme disease require immediate initiation of antibiotic therapy. In patients with a complete facial nerve paralysis and inability to close the eye, the ipsilateral eye should be patched. Patients should be advised of the risk for corneal abrasion and corneal dryness, which is associated with the inability to blink properly or to close the eye completely. Patients should be counselled regarding their expected timeline for recovery. Although mild paresis typically recovers within 2 to 3 weeks, complete paralysis may take up to 6 to 12 months for recovery. Patients with a complete facial nerve paralysis should be provided with an urgent referral to a head and neck surgeon.

Diagnostic Strategies

VESTIBULAR SCHWANNOMA (CRANIAL NERVE VIII)

When vestibular schwannoma is suspected, the patient is evaluated by audiometry or gadolinium-enhanced MRI. This imaging technique is extremely sensitive and has led to earlier diagnosis and a decrease in mean size at detection of vestibular schwannoma. CT lacks the necessary sensitivity in the posterior cranial fossa to reliably rule out the presence of vestibular schwannoma. The smaller the tumor at the time of diagnosis, the more options there are for therapy and the better the prognosis.

Principles

Management

Vestibular schwannoma, formally referred to as acoustic neuroma, is a rare but important cause of sensorineural hearing loss. It occurs in middle-aged individuals and is usually unilateral in nature. Vestibular schwannoma is rarely bilateral, occurring in approximately 5% of cases and generally associated with type 2 neurofibromatosis. Although histologically benign, vestibular schwannoma can cause neurologic damage by direct compression on CN VIII and the other structures in the cerebellopontine angle. Vestibular schwannomas arise from the Schwann cells covering the vestibular branch of the CN VIII as it passes through the internal auditory canal. The tumor may compress the cochlear (acoustic) branch of the CN VIII, causing hearing loss, tinnitus, and dysequilibrium. Continued growth of the tumor may result in compression of structures in the cerebellopontine angle, where CN V and CN VII may be compressed and damaged. Larger tumors may further encroach on the brainstem and, if large enough, may compress the fourth ventricle, ultimately resulting in signs of increased intracranial pressure (ICP).

Vestibular schwannoma may be removed surgically or ablated with stereotactic radiation therapy. In appropriately selected patients, there is little difference in long-term quality-of-life segregated by type of treatment.11 In general, tumors larger than 3 cm are recommended for microsurgery because radiation treatments, such as with the gamma knife, are less effective for local control and growth arrest in larger masses.12 Smaller tumors are amenable to use of stereotactic radiation therapy. Stereotactic radiation therapy generally has good long-term outcomes of local growth arrest, with nerve salvage approaching 90% or greater. In patients who are minimally symptomatic with small tumors, serial monitoring with MRI is a viable option.

Clinical Features

DIABETIC CRANIAL MONONEUROPATHY

Asymmetrical sensorineural hearing loss is the hallmark of vestibular schwannoma. Up to 15% of patients with this tumor, however, will have normal results on audiometry. These patients typically have symptoms, such as unilateral tinnitus, imbalance, headache, fullness in the ear, otalgia, and facial nerve weakness. Thus, patients with asymmetrical symptoms should be further evaluated for vestibular schwannoma even with normal findings on audiometry. Vestibular schwannomas are extremely slow-growing tumors, averaging an approximately 1-mm increase per year, although many do not grow at all. The median time from symptom onset to diagnosis is 12 months.

Principles

Disposition Patients with suspected acoustic neuroma should be referred for audiometry or MRI and evaluation by a specialist in either otolaryngology or neurosurgery.

Cranial mononeuropathies occur uncommonly, and usually are a complication of diabetes. They most often affect the extraocular muscles. The oculomotor nerve (CN III) is most commonly affected, followed by the trochlear (CN IV) and abducens (CN VI) nerves. CN palsies occur in 1% of diabetics versus 0.1% among nondiabetics. Whereas ophthalmoplegia appears to be closely related to diabetes, facial palsy is less strongly correlated with this disease.13 The pathologic basis of diabetic mononeuropathy appears to be ischemia caused by occlusion of an intraneural nutrient artery

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serving the nerve. This occlusion leads to injury located primarily in the core fibers, whereas the peripheral nerve fibers are less affected because they also are supplied by collateral vessels. In the oculomotor nerve, the preservation of the circumferentially located parasympathetic fibers explains the pupillary sparing that usually is found in this syndrome.

Infectious causes of CVT include systemic infections and local infections, such as sinusitis, otitis media, and facial cellulitis. Noninfectious causes include direct injury to the cerebral venous system from trauma, surgery, dehydration, or any other conditions causing hypercoagulable states, including the presence of a malignant neoplasm or the use of oral contraceptive agents.

Clinical Features

Clinical Features

Patients typically describe acute onset of unilateral retro-ocular and supraorbital pain, diplopia, and ptosis. The physical manifestations of a CN III palsy include the inability to move the eye superiorly and medially, accompanied by ptosis. The pupillary light reflex usually is present. Although it is a less common finding, CN IV and CN VI may be affected. Patients with a CN IV palsy are unable to move the eye inferolaterally, and those with a CN VI palsy are unable to move the eye laterally. Because of the long intracranial course of CN VI, a patient with an isolated sixth nerve palsy should be evaluated for an intracranial lesion or increased ICP.

Patients with CVT often present with symptoms of intracranial hypertension, especially headache; patients with CVT are more prone to hemorrhagic infarction and localizing neurologic deficits. Lethargy, seizures, decreased level of consciousness, or mental status changes may be noted. A patient’s symptom onset will vary in accordance with the extent of collateral vessel growth in the venous territory. Symptoms will appear only when the compensation for venous thrombosis is no longer sufficient or when hemorrhagic infarction occurs. Variability in collateralization between patients also adds to the variability and time course of symptoms. The average time from symptom onset to diagnosis of 7 days, reflecting the difficulty in diagnosis of this rare disease entity. Because of the broad spectrum of possible clinical features, the diagnosis of CVT may be difficult but should be a consideration in any patient with unexplained headache, especially in combination with focal neurologic deficit, papilledema, or seizures. Patients with CVT will sometimes complain of diplopia or will be observed to have a dysconjugate gaze secondary to involvement of CN IV and CN VI. This can occur due to thrombosis of the cavernous sinus or simply from elevated ICP. In the presence of headache or a visual complaint, a funduscopic examination should be performed to look for papilledema, which is noted in up to 45% of patients with CVT.

Differential Diagnosis Diabetic mononeuropathy generally is a diagnosis of exclusion. Considerations in the differential diagnosis include trauma, tumor, vertebrobasilar ischemia, aneurysm, and brainstem hemorrhage.

Diagnostic Studies Diagnostic imaging is not required in the setting of a “classic” oculomotor mononeuropathy. If a diabetic patient presents with an isolated CN III palsy with sparing of the pupillary light reflex in the absence of other CN or neurologic abnormalities, the diagnosis can be made presumptively. If the pupillary reflex is lost in the affected eye, one must be concerned about aneurysm and a computerized tomographic angiogram (CTA) is indicated. If other CNs are involved or there are other acute neurologic deficits present, stroke remains a consideration and CT or MRI should be obtained. In a patient who presents with a cranial mononeuropathy but without a history of diabetes, a hemoglobin A1c might be helpful for the providers who assume care of the patient.

Management Treatment consists of patching the affected eye and administration of analgesics and antiplatelet therapy. Although there is no specific cure, patient education regarding glucose control is important. The prognosis is good and the neuropathy generally resolves within 3 to 6 months. Antioxidant preparations, including α-lipoic acid, have been used therapeutically and have not shown harm, but such agents have yet to be shown to have convincing clinical effect.14

CEREBRAL VENOUS THROMBOSIS Principles Cerebral blood is drained by several major veins that lead into the dural sinuses. The major dural sinuses are the superior sagittal sinus, the inferior sagittal sinus, the straight sinus, the lateral sinuses, and the sigmoid sinuses. The variability in symptoms and signs in patients who present with CVT stems from differences in thrombus location and acuity of thrombus formation. Women represent 60% to 75% of those diagnosed. The shortterm mortality of CVT can be quite high, depending upon time to diagnosis and severity of neurological symptoms at the time of presentation.15 With early diagnosis and treatment, mortality rates are low.

Differential Diagnosis The differential diagnosis of CVT is broad and includes the conditions that cause patients to present with the new onset of neurologic deficits, alteration in consciousness, or severe headache.

Diagnostic Strategies Non-contrast CT scanning is commonly employed in the evaluation of patients with severe or unusual headaches, it is neither sensitive nor specific enough to reliably confirm or exclude the diagnosis of CVT. Findings on CT that are consistent with CVT include hyperdensity of a thrombosed sinus or deep vein (referred to as the cord sign or attenuated vein sign, respectively), brain edema, and hemorrhage secondary to venous congestion. MRI can demonstrate local changes secondary to venous congestion, such as brain edema and hemorrhage. In addition, MRI can demonstrate the possibility of CVT by the lack of a “flow void.” On conventional MRI, a flow void indicates the presence of moving blood within the sinus, whereas the absence of a flow void indicates a possible thrombus. Diagnostic accuracy, however, is greatly improved through use of magnetic resonance venography (MRV). This technique takes advantage of the MRI signal characteristics of flowing blood to create images of venous structures. Combination of these imaging techniques further enhances diagnostic accuracy. For imaging of a particular dural sinus, presence of the sinus on conventional MRI and lack of flow on MRV are diagnostic of a sinus thrombosis. This combined approach has diagnostic sensitivity similar to that of conventional angiography. MRV and CT venography have similar sensitivities for the diagnosis of CVT when the CT study is performed on a multidetector row CT scanner; the sensitivity of CT venography for CVT approaches 100% and is comparable to that of MRV both in sensitivity and in inter-rater reliability. The sensitivity of CT

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venography performed by scanners that do not use multidetector row technology is unknown. Based on the best available evidence, we recommend MRI/MRV as the diagnostic study of choice when CVT is suspected, because this continues to be the gold standard against which all other diagnostic studies are compared. D-dimer assays may have a role as a screening tool to exclude CVT, particularly when MRI or CT venography is not available. Although the reported sensitivity rates are fair at 83% to 100%, larger prospective studies are needed. In general, although a normal D-dimer level does not exclude the diagnosis of CVT, the diagnosis is much less likely, particularly in a patient with symptoms of less than 2 weeks in duration.

Management CVT is a relatively rare disease, and controlled studies evaluating its treatment are lacking. Current therapeutic consensus strongly recommends systemic anticoagulation with low–molecularweight heparin (LMWH) or unfractionated heparin to prevent further clot formation and to promote recanalization, even in patients with intracranial hemorrhage on initial imaging. A registry comparing outcomes of patients treated with unfractionated heparin compared with LMWH found more benefit in the LMWH group, although the effect was modest.16 Despite a paucity of randomized controlled trials, expert opinion favors anticoagulation in all groups unless another contraindication is present. Catheter-based intervention with thrombolysis has shown promise in the management of CVT. Two case series have shown good outcomes in patients with altered mental status or coma at the time of presentation. All were treated in a non-randomized fashion with catheter-based thrombolysis with urokinase or tissue plasminogen activator (tPA), with 75% of patients recovering to a modified Rankin Scale of 0 or 1.17,18 This promising therapy is typically considered only for patients with symptoms of decreased level of consciousness, elevated ICP, or rapid neurologic deterioration.

Disposition All patients with suspected CVT should be admitted to a unit capable of providing a high level of care with neurologic consultation. Patients should be anticoagulated if no contraindication exists, and catheter-based thrombolysis should be considered in patients with depressed mental status or focal findings on neurologic examination.

MULTIPLE SCLEROSIS Principles MS is an inflammatory disease that affects the central nervous system (CNS). The pathologic manifestation of this inflammatory disease is a demyelination of discrete regions (plaques) within the CNS with a relative sparing of axons. The clinical picture is highly variable, but it is classically characterized by episodes of neurologic dysfunction that evolve over days and resolve over weeks. The peak age at onset is 25 to 30 years old; women are slightly younger than men at onset. The incidence in women exceeds that of men by a ratio of 1.8 : 1. MS is more common in temperate climates. The worldwide prevalence is greatest in the United Kingdom, Scandinavia, and North America. Epidemiologic studies indicate that both genetic and environmental factors are associated with an increased incidence of MS. It is rare in Africans and Asians, but African Americans have a higher incidence than their relatives who remain in Africa. Thus, an environmental cause superimposed on genetic susceptibility appears to be a likely etiologic scenario.

MS is considered to be an organ-specific autoimmune disease. One theory proposes that genetic factors interact with an environmental trigger or infection to establish pathologically autoreactive T cells in the CNS. After a long and variable latency period (typically 10 to 20 years), a systemic trigger, such as a viral infection or superantigen, activates these T cells. The activated T cells, on reexposure to the autoantigen, initiate the inflammatory response. This sets off a complex immunologic cascade that leads to the demyelination characteristic of MS. This demyelination process releases CNS antigens that are hypothesized to initiate further episodes of autoimmune-induced inflammation.

Clinical Features The clinical picture in MS is one of marked heterogeneity. The classic clinical syndrome consists of recurring episodes of neurologic symptoms that rapidly evolve over days and slowly resolve over weeks. Variability occurs in age at onset, location of CNS lesions, frequency and severity of relapses, and degree and time course of progression. The clinical features of MS can be divided into areas of specific CNS impairment: cognition; CNs; motor pathways; sensory pathways; cerebellar pathways; and bowel, bladder, and sexual dysfunction. Patients with MS have frequent complaints of poor memory, distractibility, and decreased capacity for sustained mental effort. Formal neuropsychological testing suggests that cognitive involvement is common and underreported, affecting up to 65% of patients. A correlation has been found between the MRI-based total lesion load and presence of cognitive impairment. CN dysfunction is common in MS. The most common associated CN abnormality is optic neuritis, which is a unilateral syndrome characterized by pain in the eye and a variable degree of visual loss affecting primarily central vision. It is often the first symptom of MS. Within 2 years of an attack of optic neuritis, the risk of MS is approximately 20%, and within 15 years, it is approximately 45% to 80%. As a result of lesions in the vestibulo-ocular connections, the oculomotor pathways also may be affected. The deficit may be manifested as diplopia or nystagmus. The nystagmus may be severe enough that the patient may complain of oscillopsia (a subjective oscillation of objects in the visual field). CN impairment also may include impairment of facial sensation, which is relatively common. Unilateral facial paresis also may occur. In addition, the occurrence of trigeminal neuralgia in a young person may be an early sign of MS. Motor pathways also are commonly involved; specifically, corticospinal tract dysfunction. Paraparesis or paraplegia occurs with greater frequency than upper extremity lesions owing to the common occurrence of lesions in the motor tracts of the spinal cord. In patients with significant motor weakness, spasms of the legs and trunk may occur on attempts to stand from a seated position. This dysfunction is manifested on physical examination as spasticity that typically is worse in the legs than in the arms. The deep tendon reflexes are markedly exaggerated, and sustained clonus may be demonstrated. Although these symptoms frequently are bilateral, they generally are asymmetrical. Sensory manifestations are a frequent initial feature of MS and will be present in nearly all patients at some point during the course of the disease. Sensory symptoms are commonly described as numbness, tingling, “pins and needles” paresthesias, coldness, or a sensation of swelling of the limbs or trunk. Impairment of the cerebellar pathway may result in gait imbalance, difficulty with coordinated actions, and dysarthria. Physical examination reveals the typical features of cerebellar dysfunction, including dysmetria, dysdiadochokinesis (an impairment of rapid alternating movements), breakdown in the ability to perform

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complex movements, intention tremor in the limbs and head, truncal ataxia, and dysarthria. Impairment of bowel, bladder, and sexual function also is common. The extent of sphincter and sexual dysfunction usually parallels the motor impairment in the lower extremities. Urinary frequency may progress to urinary incontinence as the disease advances. An atonic bladder may develop, which empties by simple overflow and often is associated with the loss of perception of bladder fullness and with anal and genital hypoesthesia. Constipation becomes common in time, and almost all patients with paraplegia require special measures to maintain effective bowel habits. Sexual dysfunction, although frequently overlooked, is common in MS. Approximately 50% of patients become completely sexually inactive as a result of this disease.

Differential Diagnosis Other diseases that affect the CNS white matter may be clinically and radiographically similar to MS. These include CNS tumors (especially lymphomas and gliomas), spinal cord compression, vasculitides, Behçet’s disease, neuro-sarcoidosis, postinfectious and postvaccinal encephalomyelitis, human immunodeficiency virus (HIV) encephalopathy, Lyme disease, and vitamin B12 deficiency.

Diagnostic Strategies MS is a relapsing-remitting disorder with symptoms that fluctuate over time. Therefore, the clinical diagnosis rests on occurrence of at least two clinical episodes with different neurologic symptoms at different times. Although no laboratory tests are diagnostic for MS, one clinical feature remains unique to this disease: Uhthoff ’s phenomenon, temporary worsening of current or preexisting signs or symptoms of MS secondary to small increases in the patient’s body temperature. Accordingly, exercise, a hot bath, exposure to a warm environment, or fever can bring about Uhthoff ’s phenomenon. This phenomenon reflects subclinical demyelination or preexisting injury to nerves without obvious significant clinical involvement before heat exposure or temperature elevation. Lumbar puncture is recommended for evaluation of patients with suspected MS, but mass lesions and elevated ICP should be ruled out before lumbar puncture is attempted. CSF analysis is abnormal in 90% of the cases. Fifty percent of patients will have pleocytosis, with more than five lymphocytes per high-power field. Approximately 70% of patients will have an elevated gamma globulin level, with immunoglobulin G (IgG) ranging from 10% to 30% of the CSF total protein. Electrophoresis of the CSF demonstrates oligoclonal bands of IgG in 85% to 95% of patients who carry a diagnosis of MS; however, oligoclonal bands of IgG also are seen with neurosyphilis, fungal meningitis, and other CNS infections. The initial imaging test to aid in the diagnosis of MS is gadolinium-enhanced MRI of the brain and spinal cord. MRI is a sensitive test for the detection of lesions consistent with MS and also is useful to assess disease severity. Lesions usually are multiple and commonly are found in the periventricular white matter. In patients with an initial neurologic event consistent with CNS demyelination and an MRI cranial study showing multiple white matter lesions, the 5-year risk for development of MS is 60%. Patients with similar clinical syndromes and a normal MRI appearance have less than a 5% risk.

(2) treatment of acute exacerbations, and (3) therapies designed to modify complications.

Treatment of Disease Progression Although there are many therapies under development for treatment of early or established disease, standard therapies aimed at halting disease progression are based primarily on the use of either interferon-β or glatiramer acetate. The interferons are a group of natural compounds with antiviral and immunomodulatory actions used in therapy for MS. Side effects of the agents interferon-β1a and interferon-β1b include influenza-like symptoms, depression, anxiety, and confusion. Interferon-β1a lowers relapse rate, prolongs time to first relapse, and lowers the accumulation of brain lesions on MRI. Interferon-β also has been shown to retard progression to clinically definite MS and to decrease the total number of brain lesions seen on subsequent MRI studies in patients who have their first demyelinating episode with MRI abnormalities at initial presentation. This finding highlights the importance of early evaluation and treatment. Glatiramer acetate is a mixture of synthetic polypeptides designed to mimic myelin basic protein, which has successfully been used in the treatment of MS. The mechanism of action by which glatiramer acetate exerts its effect is unknown, but it is thought to modify the immune processes responsible for the pathogenesis of MS. Patients receiving glatiramer acetate experience significantly fewer relapses and are more likely to demonstrate neurologic improvement. It has also been shown to slow the progression to clinically definite MS after a first clinical demyelinating episode. Current recommendations for management of relapsingremitting MS are to initiate treatment with interferon-β or glatiramer acetate.19 Such regimens have been demonstrated to decrease the volume of plaques seen on MRI and to diminish relapses. Newer disease-modifying agents include fingolimod, laquinimod, daclizumab, natalizumab, and teriflunomide; their role is yet to be fully defined.

Treatment of Acute Exacerbations Acute exacerbations of MS will generally resolve without therapy; however, steroids diminish the duration. More than 85% of patients with relapsing-remitting MS show improvement with IV methylprednisolone. IV steroids have been shown in controlled trials to speed the recovery from the visual loss of optic neuritis compared with placebo. In addition, when patients with acute optic neuritis are treated with high-dose IV steroids, the 2-year rate of development of MS is reduced, although this effect diminishes over time. Oral prednisone is not helpful and is associated with a potential increase in disease flares. The current standard therapy for an acute exacerbation in MS is IV methylprednisolone, 250 to 500 mg every 12 hours for 3 to 7 days. Whether this should be followed by an oral prednisolone taper remains controversial. Potential adverse effects of methylprednisolone therapy include fluid retention, gastrointestinal hemorrhage, anxiety, psychosis, infection, and osteoporosis. Diagnostic diligence should be exercised in the evaluation of an acute exacerbation of MS, because many exacerbations are brought on by other medical issues, including infection. This is especially true of patients with severe preexisting disease.14

Management

Treatment of Complications

Management of patients with MS has essentially three aspects: (1) therapies aimed at halting the progression of the disease,

Several therapies directed toward the complications of MS may be helpful. The associated spasticity generally is treated with

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baclofen starting at 5 mg tid and eventually increasing up to 20 mg tid. This is a highly effective therapy aimed at reducing the painful flexor and extensor spasms. A major side effect is drowsiness, which generally diminishes with continued use. Higher-dose therapy can cause confusion, especially in the setting of baseline cognitive impairment. For patients with intractable spasticity, baclofen is available for intrathecal administration by either bolus therapy or continuous implanted pump therapy. Additional therapeutic agents for control of spasticity include tizanidine, diazepam, and dantrolene. The tremor and ataxia associated with MS occasionally are treated with propranolol, diazepam, or clonazepam. The results of these therapies, however, generally are unsatisfactory. Pain often is associated with MS and affects the shoulders, pelvic girdle, and face. The facial pain may be indistinguishable from that of trigeminal neuralgia. Treatment options include carbamazepine, baclofen, and tricyclic antidepressants.

Disposition Patients with a history of MS who seek treatment for significant symptoms must first be evaluated to rule out other, non– MS-related pathologic processes. Other systemic illnesses, especially infections, which can worsen the symptoms of MS, should be excluded. If the problem is thought to be a significant exacerbation of MS, most patients will require hospital admission for IV steroid therapy. Depending on the patient’s neurologic status, an alternative to hospitalization may be the initiation of IV steroids in the ED followed by a next-day appointment with the patient’s primary care physician or neurologist for ongoing IV steroid administration. Patients with the new onset of symptoms suggestive of MS should be admitted or referred to a neurologist, because early treatment has been shown to significantly decrease progression of the disease.

KEY CONCEPTS Trigeminal Neuralgia

• Patients with unilateral, intermittent, lancinating facial pain without abnormalities on physical examination are likely to have trigeminal neuralgia. • Carbamazepine starting at 100 mg bid is the first-line agent for medical treatment, with a typical therapeutic dose of 600 to 800 mg/day in divided doses. • Patients who do not tolerate treatment or whose pain is refractory to medical management may be candidates for microvascular decompression or ablation.

Facial Nerve Paralysis

• Patients who have facial muscle paresis with intact forehead movement should be considered to have a central (upper motor neuron) lesion until the diagnostic investigation proves otherwise. • Slowly progressive or recurrent facial paralysis is suggestive of a neoplasm. Recurrent unilateral paralysis may occur with Bell’s palsy but frequently (30%) is seen in patients with tumor. • Simultaneous bilateral facial paralysis is suggestive of Lyme disease, especially in endemic regions. • Patients with Bell’s palsy should be treated early in the course with corticosteroids, prednisolone at 50 mg/day for 10 days. Antiviral medication, valacyclovir, 1000 mg orally three times daily for 7 days, or famciclovir, 750 mg orally for 7 days should be considered in patients with severe loss of function.

Vestibular Schwannoma

• The onset of unilateral auditory symptoms, especially sensorineural hearing loss, requires evaluation and referral to an ear, nose, and throat specialist. • Neurologic symptoms of lower CN dysfunction, ataxia, or raised ICP may be caused by a benign tumor at the cerebellopontine angle.

Diabetic Cranial Mononeuropathy

• Diabetic neuropathy is a diagnosis of exclusion because no definitive diagnostic testing is available, although a CN III palsy with sparing of

the pupillary response in a patient with a history of diabetes is classic for the presentation. • Both ischemic and hemorrhagic brainstem lesions must be ruled out in the case of an acute ophthalmoplegia. • Extraocular mononeuropathy is sufficiently common in patients with diabetes mellitus that its occurrence in isolation warrants evaluation of the patient for previously undiagnosed diabetes.

Cerebral Venous Thrombosis

• The differential diagnosis for CVT includes other conditions that present with new-onset neurologic deficits, alteration in consciousness, or severe headache. CVT is more likely to be present in these patients when the etiology is unclear, the patient is thought to have a hypercoagulable state, and the head CT is normal in appearance or shows subtle signs of CVT. • Non–contrast-enhanced CT scanning is not adequate to rule out CVT. MRI with MRV is recommended, although multidetector row CT venography is an acceptable alternative. • Treatment of most patients with CVT includes systemic anticoagulation, even in the setting of hemorrhagic cerebral infarcts, unless another contraindication exists.

Multiple Sclerosis

• MS should be suspected in patients who present with episodes of neurologic dysfunction that evolve over days and resolve over weeks. • Apparent exacerbations of known MS can be brought on by other medical problems, most commonly infections. • Therapy for patients with MS will require consultation with the patient’s primary care provider or neurologist to provide consistent disease management. • IV methylprednisolone, 250 to 500 mg every 12 hours for 3 to 7 days effectively promotes earlier resolution of recurrences. • IV methylprednisolone has been shown to speed the recovery from vision loss from optic neuritis associated with MS.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Zuniga C, et al: Acute treatment of trigeminal neuralgia with onabotulinum toxin A. Clin Neuropharmacols 36:146, 2013. 2. Wu C, et al: Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia 32:443, 2012. 3. Kouzounias K: Comparison of percutaneous balloon compression and glycerol rhizotomy for the treatment of trigeminal neuralgia. J Neurosurg 113:486, 2010. 4. Baschnagel AM, et al: Trigeminal neuralgia pain relief after gamma knife sterotactic radiosurgery. Clin Neurol Neurosurg 117:107, 2014. 5. Katz A, et al: Bell’s palsy during pregnancy: is it associated with adverse perinatal outcome? Laryngoscope 121:1395, 2011. 6. Baugh RF, et al: Clinical practice guideline: Bell’s palsy. Otolaryngol Head Neck Surg 149:S1, 2013. 7. Salinas RA, Alvarez G, Daly F, et al: Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev (3):CD001942, 2010. 8. Berg T, et al: The effect of prednisolone on sequelae in Bell’s palsy. Arch Otolaryngol Head Neck Surg 138:445, 2012. 9. Lee HY, et al: Steroid-antiviral treatment improves the recovery rate in patients with severe Bell’s palsy. Am J Med 126:336, 2013. 10. Axelsson S, et al: Bell’s palsy—the effect of prednisolone and/or valacyclovir versus placebo in relation to baseline severity in a randomized controlled trial. Clin Otolaryngol 37:283, 2012.

11. Brooker JE, et al: Quality of life among acoustic neuroma patients managed by microsurgery, radiation, or observation. Otol Neurotol 31:977, 2010. 12. Boari N, et al: Gamma knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients. J Neurosurg 121:123, 2014. 13. Greco D, Gambina F, Pisciotta M, et al: Clinical characteristics and associated comorbidities in diabetic patients with cranial nerve palsies. J Endocrinol Invest 35:146–149, 2012. 14. Oynhausen S, et al: Emergency medical care of multiple sclerosis patients: primary data from the Mount Sinai resource utilization in multiple sclerosis project. J Clin Neurol 10:21, 2014. 15. Dentali F, et al: Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study. J Thromb Haemost 10:1297, 2012. 16. Coutinho JM, et al: Unfractionated or low-molecular weight heparin for the treatment of cerebral venous thrombosis. Stroke 41:2575–2580, 2010. 17. Li G, et al: Safety and validity of mechanical thrombectomy and thrombolysis on severe cerebral venous sinus thrombosis. Neurosurgery 72:730, 2013. 18. Mohammadian R, et al: Treatment of progressive cerebral sinuses thrombosis with local thrombolysis. Interv Neuroradiol 18:89, 2012. 19. Sorenson PS: New management algorithms in multiple sclerosis. Curr Opin Neurol 27:246, 2014.

CHAPTER 95: QUESTIONS & ANSWERS 95.1. A 53-year-old woman presents with complaints of increasing left facial pain. She describes a pattern of brief, excruciatingly painful lancinating sensations along the left jaw associated with chewing and brushing her teeth. She notes intermittent clusters of pain that last seconds to a minute and have not occurred at night. Physical examination is normal except for triggered left jaw and buccal pain with palpation of the left mandibular area. What is the most likely finding in this patient? A. Analgesia from a left inferior alveolar nerve block B. Analgesia from subcutaneous sumatriptan C. Immediate pain relief with high-flow oxygen D. Magnetic resonance imaging (MRI) evidence of multiple sclerosis (MS) E. Vascular compression of the trigeminal nucleus Answer: E. In 80% to 90% of cases of trigeminal neuralgia, a vascular compression of the trigeminal nucleus is found in series of surgical cases. Microvascular decompression of the trigeminal nerve is curative in a high percentage of patients who fail to respond to medical management. Approximately 5% of patients with trigeminal neuralgia have MS. Cluster headache and migraine treatments are not effective. Peripheral nerve block is also ineffective because the pathologic process is more central at the nucleus. 95.2. A 26-year-old man presents with complaints of left facial drooping. The symptoms began painlessly 3 days ago without a prodrome. Examination reveals a left facial droop with an inability to wrinkle the forehead without other associated physical examination abnormalities. Which of the following will provide the largest potential benefit to the patient’s recovery? A. High-volume lumbar puncture B. Initiation of oral antiviral treatments C. Initiation of oral corticosteroids D. Intravenous (IV) thrombolysis E. Urgent non–contrast-enhanced computed tomography (CT) scan of the head Answer: C. The patient has Bell’s palsy, which is a painless left facial nerve palsy. The primary symptom is a left peripheral nerve paralysis often with unilateral dysgeusia, hyperacusis (stapedius muscle paralysis), and external canal and pharyngeal numbness. Facial sensation is intact. Corticosteroids are helpful, and they

should be initiated as far out as a week after onset, although they should be started within 24 hours if possible. Initiation of oral antiviral treatment has shown benefit in some trials, although conflicting evidence exists. In the absence of a contraindication and in a patient who can afford the medicine, antivirals should be considered. Given the classic picture and lack of other associated neurologic findings, CT scan of the head is not required and is not likely to provide benefit. Testing for Lyme disease is indicated in Lyme endemic areas or in patients with a history of a tick bite. 95.3. A 43-year-old woman presents with her fourth episode of left facial paralysis in 1 year. She denies prodrome or associated symptoms. Examination is consistent with an isolated left peripheral facial nerve paralysis. What should be the next step in her management? A. Antinuclear antibody level and erythrocyte sedimentation rate B. Carotid angiography C. Initiation of antivirals and corticosteroids D. Magnetic resonance imaging (MRI) scan E. Neurology referral Answer: D. A neoplastic cause should be suspected in patients who suffer from recurrent facial paralysis, significant pain, prolonged symptoms, or any associated cranial nerve (CN) dysfunction. 95.4. Which of the following statements regarding acoustic neuroma is true? A. An audiogram has a sensitivity of greater than 95%. B. Gadolinium-enhanced magnetic resonance imaging (MRI) is the diagnostic test of choice. C. Symptom onset is generally during 1 to 3 months. D. Symptoms of increased intracranial pressure (ICP) are common. E. The symptoms of Ménière’s disease are essentially identical. Answer: B. Computed tomography (CT) lacks the posterior fossa sensitivity to detect small tumors. Although asymmetrical hearing loss is the hallmark of this disease, audiograms may be normal in up to 15% of cases. Symptom onset is generally during years rather than months. Although increased ICP can happen, it is uncommon. The tinnitus of Ménière’s disease is typically intermittent rather than continuous.

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95.5. Which of the following symptoms is not associated with diabetic cranial mononeuropathy? A. Diplopia B. Inability to move the eye inferolaterally C. Nonreactive pupil D. Orbital pain E. Ptosis Answer: C. Diabetic cranial mononeuropathy may affect the third, fourth, or sixth cranial nerve (CN). Pain, diplopia, and ptosis are common. Pupillary reactivity is usually preserved because these fibers are on the third nerve periphery and less affected by the occlusion of the “penetrating” neural nutrient artery affecting the core motor fibers. Inferolateral movement paralysis may be seen with a fourth nerve palsy and lateral paralysis with a sixth nerve palsy. 95.6. A 64-year-old diabetic woman presents with the acute onset of painless diplopia. She has a 25-year history of type 2 diabetes. Her only other past history is hypertension. Physical examination reveals normal vital signs and a normal neurologic examination with the exception of an inability to look laterally with the left eye. What is the most appropriate next step? A. Cerebral angiography B. Contrast-enhanced computed tomography (CT) scan C. Magnetic resonance imaging (MRI) scan D. Ophthalmology consultation E. Patching the affected eye and initiation of antiplatelet therapy Answer: C. Diabetic cranial mononeuropathy may affect the third, fourth, or sixth cranial nerve (CN). It is a diagnosis of exclusion, and brainstem ischemic or hemorrhagic lesions should also be considered. The long intracranial course of the sixth nerve makes MRI scanning particularly indicated to rule out a mass lesion. Once it is diagnosed, patching, analgesics, and antiplatelet therapy should be considered for management of this diabetic complication. 95.7. A 38-year-old woman presents 8 weeks postpartum with a 1-week history of severe headache and progressively altered mental status, which culminated in a seizure several minutes before presentation. On examination, she is normotensive, appears postictal, but has no focal neurologic findings. Ophthalmoscopic examination reveals papilledema, and non–contrast-enhanced head computed

tomography (CT) reveals a dense sagittal sinus and a small venous hemorrhage in the occipital region. The next most appropriate management step is: A. 325 mg aspirin per rectum B. Dexamethasone 10 mg IV push C. Hypertonic saline 500-mL bolus D. Mannitol 1 g/kg E. Systemic anticoagulation with unfractioned heparin or low–molecular-weight heparin (LMWH) Answer: E. The patient presents with a dural sinus thrombosis. Although large, randomized trial data do not exist, case series and expert consensus strongly suggest improved outcomes with systemic anticoagulation, even in the setting of venous hemorrhage on head CT. Osmotic agents and steroids have no proven benefit in the management of sinus thrombosis and may cause harm. Antiplatelet agents may be considered if absolute contraindications to anticoagulation exist but probably have lower therapeutic efficacy. 95.8. A 20-year-old female college student presents with her third episode of bilateral foot numbness after a game of volleyball. Each episode has occurred approximately 1 or 2 hours after a full game of indoor volleyball, which she had no trouble completing. Each of the episodes of foot numbness resolved during 2 or 3 days with no residual symptoms. Her only other complaint is of falling grades in school due to subjective poor memory and distractibility. What would be the most likely finding in this patient? A. Elevated cerebrospinal fluid (CSF) protein levels B. Elevated erythrocyte sedimentation rate C. Hypocalcemia D. Increased intracranial pressure (ICP) on lumbar puncture E. Thrombocytopenia Answer: A. Presenting symptoms for multiple sclerosis (MS) may be myriad. Uhthoff ’s phenomenon is the finding in MS in which small increases in body temperature exacerbate neurologic symptoms temporarily. Almost any neurologic complaint or finding may be a feature of MS, with up to 60% having cognitive impairment. CSF analysis is abnormal in 90% of cases with a pleocytosis and elevated protein with oligoclonal bands. ICP is normal. Lumbar puncture is undertaken after magnetic resonance imaging (MRI), which is the initial imaging test of choice.

C H A P T E R 96 

Spinal Cord Disorders Andrew D. Perron  |  J. Stephen Huff

PRINCIPLES This chapter focuses on nontraumatic processes affecting the spinal cord and its vascular supply, as well as processes compressing the spinal cord. The ultimate neurologic outcome of patients with many of these disorders depends on expeditious recognition and management in the emergency department (ED).

Anatomy In adults, the spinal cord is approximately 40 cm long and extends from the foramen magnum, where it is continuous with the medulla oblongata, to the body of the first or second lumbar vertebra. Like the brain, the spinal cord is covered by three meningeal layers: (1) the inner pial layer, (2) the arachnoid, and (3) the outer dural layer. At its lower end, the spinal cord tapers into the conus medullaris, where several segmental levels are represented in a small area. The lumbar and sacral nerve roots form the cauda equina as they descend caudally in the thecal sac before exiting the spinal canal at the respective foramina. The non-neural filum terminale runs from the tip of the conus and inserts into the dura at the level of the second sacral vertebra. Two symmetrical enlargements of the spinal cord contain the segments that innervate the limbs. The cervical enlargement (cord level C5 to T1) gives rise to the brachial plexus and subsequently to the peripheral nerves of the upper extremity. The lumbar enlargement (L2 to S3) gives rise to the lumbosacral plexus and peripheral nerves of the lower extremity. The space surrounding the spinal cord within the spinal canal is reduced in the area of the enlargements, potentially leaving the cord more vulnerable to compression in these regions. At each segmental level, anterior (ventral) and posterior (dorsal) roots arise from rootlets along the anterolateral and posterolateral surfaces of the cord. At each level, the anterior root conveys the outflow of the motor neurons in the anterior horn of the spinal cord, and the posterior root contains sensory neurons and fibers that convey sensory inflow. The arterial supply of the spinal cord is derived primarily from two sources. The single anterior spinal artery arises from the paired vertebral arteries. This anterior spinal artery runs the entire length of the cord in the midline anterior median sulcus and supplies roughly the anterior two thirds of the spinal cord. Blood supply to the posterior third of the spinal cord is derived from the smaller paired posterior spinal arteries. The anterior and the posterior spinal arteries receive segmental contributions from radicular arteries, the largest being the radicular artery of Adamkiewicz, which typically originates from the aorta between T8 and L4. The venous drainage of the cord largely parallels the arterial supply. The internal anatomy of the spinal cord is divided into central gray matter, which contains cell bodies and their processes, and surrounding white matter, where the ascending and descending myelinated fiber tracts are located. These fiber tracts are organized into discrete bundles; the ascending tracts convey sensory information, and the descending tracts convey the efferent motor impulses and visceral innervation. 1298

For clinical purposes, neuroanatomy of the spinal cord may be greatly simplified, as depicted in Figure 96.1. Tracts are named with the point of origin first; the spinothalamic tract, for example, arises in the spinal cord and travels to the thalamus. Major ascending sensory tracts are represented on the right side of the figure, with motor tracts on the left side. The posterior columns carry afferent ascending proprioceptive and vibratory information on the ipsilateral side of the cord to the area stimulated; decussation of these fibers occurs in the medulla so that contralateral cortical representation is consistent. The lateral spinothalamic tract conveys afferent information about pain and temperature in a portion of the lateral column of white matter. The tract is laminated so that sacral fibers are represented most laterally. Crossing of fibers from this tract occurs near the level of entry of the spinal nerve; a cord lesion affecting only one lateral spinothalamic tract results in decreased or absent pain and temperature perception below the level of injury on the contralateral side of the body. For clinical purposes, the major descending motor tract is represented in the lateral corticospinal tract (which, as the name implies, originates in the cortex and descends to the spinal cord). This tract also is anatomically organized, with efferent motor axons to the cervical area located medially and the sacral efferent axons located laterally. Decussation of this descending tract occurs in the medulla. The cell bodies of the lower motor neurons (anterior horn cells) are in the ventral (anterior) portion of the gray matter of the spinal cord.

Classification of Spinal Cord Syndromes The anatomic organization of the spinal cord lends itself to a corresponding anatomic-pathophysiologic classification of cord dysfunction. Any of the different anatomic syndromes may be the final clinical picture of a variety of clinical processes. The syndromes frequently exist in partial or incomplete forms, adding to the diagnostic challenge.

Complete (Transverse) Spinal Cord Syndrome Complete spinal cord lesions may be manifested as either acute or subacute pathologic processes. A complete spinal cord lesion is defined as a total loss of sensory, autonomic, and voluntary motor innervation distal to the spinal cord level of injury. Reflex responses mediated at the spinal level, such as muscle stretch (deep tendon) reflexes, may persist, although they also may be absent or abnormal. Autonomic dysfunction may be manifested acutely with hypotension (neurogenic shock) or priapism. The most common cause of the complete transverse cord syndrome is trauma, although this anatomic syndrome may apply to any pathologic etiology. Other causes of acute complete cord syndrome include infarction, hemorrhage, and entities causing extrinsic compression. In patients with acute complete transverse syndromes that persist for more than 24 hours, functional recovery almost never occurs. Any evidence of preserved cord function below the level of injury denotes a partial rather than a complete lesion. Signs

CHAPTER 96  Spinal Cord Disorders

Lateral corticospinal tract Descending tract Voluntary movement

Posterior columns Ascending proprioceptive and vibratory senses

Lateral spinothalamic tract Ascending pain and temperature information Fig. 96.1.  Simplified spinal cord anatomy showing clinically essential motor and sensory tracts. (Photomicrograph courtesy John Sundsten, Digital Anatomist Project, University of Washington.)

such as persistent perineal sensation (sacral sparing), reflex rectal sphincter tone or voluntary rectal sphincter contraction, and even slight voluntary toe movement suggest a partial cord lesion, which carries a better prognosis than a complete lesion.1 Spinal shock refers to the loss of muscle tone and reflexes with complete cord syndrome during the acute phase of injury. Spinal shock typically lasts less than 24 hours but has been reported occasionally to last days to weeks. A marker of spinal shock is loss of the bulbocavernosus reflex, which is a normal cord-mediated reflex that may be preserved in complete cord lesions. The bulbocavernosus reflex involves involuntary reflex contraction of the anal sphincter in response to a squeeze of the glans penis or a tug on the Foley catheter. The termination of the spinal shock phase of injury is heralded by the return of the bulbocavernosus reflex; increased muscle tone and hyperreflexia follow later.

Incomplete Spinal Cord Lesions Incomplete spinal lesions are characterized by preservation of function of various portions of the spinal cord. Of all incomplete spinal lesions, most can be classified generally as one of three clinical syndromes: (1) central cord syndrome, (2) Brown-Séquard syndrome, or (3) anterior cord syndrome (Table 96.1). Central Cord Syndrome.  Central cord syndrome is the most common of the partial cord syndromes. Because of the anatomic organization of the spinal cord, a central cord injury is characterized by bilateral motor paresis; upper extremities are affected to a greater degree than lower extremities, and distal muscle groups are affected to a greater degree than proximal muscle groups. Sensory impairment and bladder dysfunction are variable features. At times, burning dysesthesias in the upper extremities may be the dominant clinical feature. Central cord injury affects the central gray matter and the central portions of the corticospinal and spinothalamic tracts. It is caused most often by a hyperextension injury; the postulated mechanism is squeezing or pinching of the spinal cord anteriorly and posteriorly by inward bulging of the ligamentum flavum. The most common causes are falls and motor vehicle accidents. The result is contusion to the spinal cord, with the central portion being most affected. This injury often occurs in elders with degenerative arthritis and spinal stenosis in the cervical area but may

affect any patient with cervical canal narrowing of any etiology (eg, congenital narrow canal as seen in achondroplasia or acquired canal narrowing from disk protrusion or tumor). The prognosis with central cord syndrome depends on the degree of injury at presentation and the patient’s age, with older age predicting a decreased functional outcome. In patients younger than 50 years old, more than 80% regain bladder continence and approximately 90% return to full ambulatory status. In patients older than 50 years old, only 30% regain bladder function and approximately 50% regain the ability to ambulate. Brown-Séquard Syndrome.  Brown-Séquard syndrome is the result of an anatomic or functional hemisection of the spinal cord. Usually associated with penetrating injuries, Brown-Séquard syndrome also may be seen with compressive or intrinsic lesions. The syndrome has been reported in association with spinal cord tumors, spinal epidural hematoma, vascular malformations, cervical spondylosis, degenerative disk disease, herpes zoster myelitis, and radiation injury and as a complication of spinal instrumentation.1 The syndrome in its pure form is characterized by ipsilateral loss of motor function and proprioception or vibration, with contralateral loss of pain and temperature sensation below the spinal cord level of injury. Because fibers associated with the lateral spinothalamic tract ascend or descend one or two spinal cord segments before crossing to the contralateral side, ipsilateral anesthesia (pain and temperature modalities) may be noted one or two segments above the lesion, although this observation is variable. Most patients with Brown-Séquard syndrome incur only partial sensory and motor impairment, and the classic pattern is not seen. Brown-Séquard syndrome carries the best prognosis of any of the incomplete spinal cord syndromes. Fully 80% to 90% of patients with Brown-Séquard syndrome regain bowel and bladder function, 75% regain ambulatory status, and 70% become independent in their activities of daily living. Anterior Cord Syndrome.  Anterior cord syndrome is characterized by loss of motor function, pinprick, and light touch below the level of the lesion with preservation of posterior column modalities, including some touch, position, and vibratory sensation. Although most reported cases of anterior spinal cord syndrome follow aortic surgery, the syndrome also may occur after severe hypotension, infection, myocardial infarction, vasospasm from drug reaction, and aortic angiography.2 The anatomic lesion may be caused by a cervical hyperflexion injury resulting in a cord contusion or by protrusion of bone fragments or herniated cervical disk material into the spinal canal. Rarely, it is produced by laceration or thrombosis of the anterior spinal artery or a major radicular feeding vessel. Patients present with characteristic mixed motor and sensory neurologic findings. Functional recovery varies; most improvement occurs during the first 24 hours, but little improvement is expected thereafter.3 Although anterior cord lesions from ischemia usually are incomplete, patients without motor function at 30 days have little or no likelihood of regaining any motor function by 1 year. Overall, only 10% to 20% of patients with this entity regain some muscle function, and even in this group there is little power or coordination.

Conus Medullaris and Cauda Equina Syndromes The separation of conus medullaris and cauda equina lesions in clinical practice is difficult because the clinical features of the disorders overlap. In addition, a combined lesion may occur that masks clear clinical symptoms or signs of either an upper or a lower motor neuron type of injury. The conus medullaris is the terminal end of the spinal cord, located at approximately the L1 level in adults.

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TABLE 96.1 

Spinal Cord Syndromes SYNDROME

SENSORY

MOTOR

SPHINCTER INVOLVEMENT

Variable

Upper extremity weakness, distal > proximal

Variable

Ipsilateral position and vibration sense loss Contralateral pain and temperature sensation loss

Motor loss ipsilateral to cord lesion

Variable

Loss of pin and touch sensation Vibration, position sense preserved

Motor loss or weakness below cord level

Variable

Loss of sensation below level of cord injury

Loss of voluntary motor function below cord level

Sphincter control lost

Conus medullaris syndrome

Saddle anesthesia may be present, or sensory loss may range from patchy to complete transverse pattern

Weakness may be of upper motor neuron type

Sphincter control impaired

Cauda equina syndrome

Saddle anesthesia may be present, or sensory loss may range from patchy to complete transverse pattern

Weakness may be of lower motor neuron type

Sphincter control impaired

Central cord syndrome

Brown-Séquard syndrome

Anterior cord syndrome

Transverse cord syndrome—complete

The conus medullaris syndrome may involve disturbances of urination (usually from a denervated, spastic, autonomic bladder that is manifested clinically with overflow incontinence) and sphincter impairment or sexual dysfunction. Sensory involvement may affect the sacral and coccygeal segments, resulting in saddle anesthesia. Pure lesions of the conus medullaris are rare. Upper motor neuron signs, such as increased motor tone and abnormal reflexes, may be present, but their absence does not exclude the syndrome. The conus medullaris syndrome can be caused by central disk herniation, neoplasm, trauma, or vascular insufficiency. Because the conus is such a small structure, with lumbar and sacral segments represented in a small area, a lesion usually causes bilateral symptoms. This finding may help distinguish conus medullaris lesions from those of the cauda equina, which often are unilateral.

The cauda equina (Latin for “horse’s tail”) is the name given to the lumbar and sacral nerve roots that continue on within the dural sac caudal to the conus medullaris. Not a true “cord syndrome,” cauda equina syndrome represents dysfunction at the level of nerve roots, but the anatomic clustering of nerve roots within the lumbar dural sac allows injury to several nerve roots to occur simultaneously. The etiologic lesion in the cauda equina syndrome usually is a midline rupture of an intervertebral disk, most commonly at the L4 to L5 level. Tumors and other compressive masses also may cause the syndrome. As in the conus medullaris syndrome, patients generally present with progressive symptoms of fecal or urinary incontinence, impotence, distal motor weakness, and sensory loss in a saddle distribution. Muscle stretch reflexes also may be reduced. Urinary retention is the most consistent finding, with a

CHAPTER 96  Spinal Cord Disorders

sensitivity of 90%. A complaint of low back pain may or may not be present with cauda equina syndrome.

CLINICAL FEATURES History Weakness, sensory abnormalities, and autonomic dysfunction are the cardinal manifestations of spinal cord dysfunction. The tempo and degree of impairment often reflect the disease process. Past medical history is vital because a history of coagulopathy or other systemic processes may be elicited. A history of cancer should suggest the possibility of metastatic disease. Recent trauma raises the possibility of vertebral fracture or disk protrusion. The acuity of pain may help narrow the differential diagnosis. Sudden immediate pain or dysfunction is more likely to be a vascular catastrophe, whereas slower onset, midline location, and historical presence of fever points toward an infectious source.

Physical Examination The physical examination pertinent to spinal cord dysfunction involves testing in three areas: (1) motor function, (2) sensory function, and (3) reflexes. Each component is best tested with the anatomic organization of the spinal cord in mind to help determine the level of the spinal cord dysfunction.

Motor Function Testing of motor function encompasses examination of muscle bulk, tone, and strength. Muscle bulk is easily examined in large motor groups, such as the thigh or calf muscles, the biceps, and the triceps. Inspection of the intrinsic hand muscles also may be helpful for determination of muscle bulk; wasting may be evident as hollowed or recessed regions of the hand. Decreased mass, asymmetry, or fasciculations should be noted. Tone is tested with repeated passive knee, elbow, or wrist flexion, with the examiner assessing for abnormally increased or decreased resistance. Rapid pronation-supination of the forearm is another useful method to check tone. Increased tone may indicate spasticity or an upper motor neuron lesion, whereas decreased tone corresponds with lower motor neuron, motor end-plate, or muscle problems. Finally, motor strength is graded in the upper and the lower extremities. Motor grading for the neurologic examination is relatively straightforward. Note that a tremendous gradient of strength is within the fourth grade of the scale. Scored on a scale of 0 to 5, neuromuscular functioning is graded as shown in Table 96.2. A rectal examination and the bulbocavernosus reflex are performed to assess voluntary sphincter contraction, and resting

TABLE 96.2 

Grading of Neuromuscular Weakness GRADE

PHYSICAL FINDINGS

0

No firing of the muscle is present.

1

The muscle fires but is unable to move the intended part.

2

The muscle is able to move the intended part with gravity eliminated.

3

The muscle is able to move the intended part against gravity.

4

The muscle is able to move the intended part but not at full strength.

5

Full muscle strength is present.

tone. Although it is not commonly thought of as a physical examination maneuver, a post-void residual urine volume is useful to evaluate bladder function. A post-void residual volume of more than 100 to 200 mL in a patient without prior voiding difficulty might suggest bladder dysfunction of neurologic cause.

Sensory Function Sensory testing requires a cooperative patient and an attentive examiner. The spinal cord–related modalities that may be clinically useful include testing for pinprick and light touch (contralateral lateral spinothalamic tract) and proprioception (ipsilateral posterior column). Assessment of the patient’s response to pinprick, light touch, and proprioception in all four extremities is necessary if a neurologic injury is suspected. Testing of sacral dermatomes is indicated in patients with suspected cord injury in that sacral sparing suggests that spinal cord dysfunction may be incomplete. The sensory fibers from sacral dermatomes are more peripherally located in the ascending fiber bundles; central or partial cord lesions may ablate sensation in the extremities yet allow some perception of sensation in the sacral area.

Reflexes Muscle stretch (deep tendon) reflexes are graded on a scale of 0 to 4+, with 2 being normal. Hyperactive reflexes suggest upper motor neuron disease (affecting the neurons or their outflow from the brain or spinal cord), as do sustained clonus and Babinski’s sign. If present, hyperactive or abnormally brisk reflexes may be a key finding suggesting a myelopathy. However, absence of hyperreflexia does not exclude a myelopathy. Reflexes may be diminished or absent when sensation is lost or when spinal shock is present. Diseases of muscles or neuromuscular junctions also may decrease reflexes. In acute cord injury, reflexes may be diminished in the acute phase. The bulbocavernosus reflex may be helpful in this assessment.

DIFFERENTIAL DIAGNOSIS The prime principle in management of spinal cord dysfunction is to consider and exclude potentially treatable clinical conditions. The clinician should rule out any nonstructural cause of neurologic dysfunction (eg, hypoglycemia, hypokalemia) early in the evaluation process. The next step, once a neurologic entity is suspected, is to try to differentiate the location of the lesion (brain versus spinal cord versus motor end-plate). When the pathologic process is suspected to be spinal in origin, liberal use of consultation and imaging is recommended. Spinal cord diseases may mimic many other disease processes, and neither the history nor physical examination may allow diagnosis until appreciable neurologic dysfunction has developed. The picture of a complete transverse spinal cord syndrome with paraplegia, sensory loss at a clear anatomic level, and sphincter dysfunction cannot be fully simulated by other anatomic lesions. Incomplete or evolving spinal cord syndromes may be imitated by other disease processes. Ataxia may be a finding in cerebellar disease but also has rarely been reported as an isolated finding with spinal cord compression. Another example is rapidly progressive paralysis in a patient with areflexia and quadriplegia; ascending paralysis (Landry-Guillain-Barré syndrome) at times may mimic an acute cord lesion. In general, pathologic processes involving the spinal cord may be divided into processes affecting the cord or its blood supply primarily, such as demyelination, infection, or infarction, and processes that compress the cord, most often originating outside the dura (see Table 96.2). Myelitis is a comprehensive term for spinal cord inflammation with dysfunction, and the potential causes are

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Pre-gadolinium

A

Post-gadolinium

B Fig. 96.2.  90-year-old female with recent pyelonephritis presenting with severe neck pain. Pre-gadolinium sequence (A) compared with post-gadolinium sequence (B) demonstrates posterior spinal epidural abscess (SEA) (yellow arrowheads).

legion. The clinical presentation is often similar across the variety of entities that may cause cord compression. The tempo of the process may yield a different clinical picture. In chronic compression, muscle wasting and abnormal reflexes may be present, whereas both of these may be lacking in acute compression. A neurologic deficit in concert with back pain strongly suggests a spinal cord lesion causing compression of neural elements, necessitating prompt investigation to identify a specific cause.

DIAGNOSTIC TESTING The basic strategy for diagnostic testing in patients suspected of having spinal cord dysfunction is to detect or exclude extrinsic compressive lesions or other potentially treatable entities. Though plain radiographs and computed tomography (CT) scans may show bone and some soft tissue abnormalities, magnetic resonance imaging (MRI) has changed the diagnostic approach. Conventional radiographs and CT scans are required in patients with trauma or suspected bone involvement by tumor or degenerative processes, but MRI shows many of these abnormalities and defines the spinal cord, as well as the soft tissue structures associated with it. MRI may also detect tissue damage patterns within the cord, such as hemorrhage and edema. When MRI is used to assess the spinal cord, assessment of the entire spine should be considered because frequently there are lesions at multiple levels. Gadolinium contrast enhancement with MRI is indicated when looking for pathology that will affect the blood–central nervous system (CNS) barrier. Specific indications include a search for primary or metastatic tumor, multiple sclerosis (MS), and spinal infections, including spinal epidural hematoma, discitis and osteomyelitis. An example of the utility of gadoliniumenhancement when searching for an infectious etiology is seen in Figure 96.2. CT myelography is an option when an MRI is unavailable or contraindicated, although it does not yield the same level of detail. After imaging studies exclude compressive lesions or other masses affecting the spinal cord, the possibility of inflammatory or demyelinating disorders remains. In these cases, lumbar puncture with cerebrospinal fluid (CSF) analysis may be diagnostic.

MANAGEMENT The treatment of many of the disease processes causing spinal cord dysfunction is nonspecific and based on limited evidence.

BOX 96.1 

Nontraumatic Causes of Spinal Cord Dysfunction PROCESSES AFFECTING THE SPINAL CORD OR BLOOD SUPPLY DIRECTLY MS Transverse myelitis Spinal arteriovenous malformation, subarachnoid hemorrhage Syringomyelia HIV myelopathy Other myelopathies Spinal cord infarction

COMPRESSIVE LESIONS AFFECTING THE SPINAL CORD Spinal epidural hematoma SEA Diskitis Neoplasm Metastatic Primary CNS

CNS, Central nervous system; HIV, human immunodeficiency virus; MS, multiple sclerosis; SEA, spinal epidural abscess.

Steroid administration had been traditionally recommended as therapy in spinal cord trauma, although the benefit has been seriously questioned (Chapter 36).3 Steroids have also been used with many nontraumatic causes of cord compression despite the lack of rigorous clinical studies supporting this use (Box 96.1). Based on available evidence, we cannot recommend the use of steroids for the acute management of spinal cord compression syndromes. Radiation treatment is recommended for cord compression by tumor. Surgical consultation for decompression may be considered, although the indications and timing for surgery are controversial.

SPECIFIC DISEASE PROCESSES Spinal cord disorders are grouped into lesions resulting from processes intrinsic to the cord or vasculature and lesions causing extrinsic compression (see Table 96.2).

CHAPTER 96  Spinal Cord Disorders

T2

Post contrast

Fig. 96.3.  Cervical spine magnetic resonance imaging (MRI) (T2 [A] and post-gadolinium [B] enhancement) demonstrating characteristic findings of demyelination associated with multiple sclerosis (MS).

Intrinsic Cord Lesions Multiple Sclerosis Demyelination denotes a disease process with the prominent feature of partial or complete loss of the myelin surrounding the axons of the CNS. MS is the most common example of such a process; spinal cord involvement may dominate the clinical picture. The spinal cord will be involved with MS in as many as 90% of patients. In approximately 20% of patients with MS, the spinal cord lesions will be the only area where plaques are identified (Fig. 96.3).4 The pathophysiology, diagnosis, and management of MS is discussed in Chapter 95.

Transverse Myelitis

Differential Diagnosis.  Considerations in the differential diagnosis for transverse myelitis include MS, SEA or hematoma, primary or metastatic spinal neoplasm, and spinal cord infarct. Diagnostic Strategies.  MRI with gadolinium enhancement is the diagnostic modality of choice for patients with suspected transverse myelitis. In cases of diagnostic uncertainty, a lumbar puncture may be performed; however, the results of CSF studies are normal in 40% of cases, with only mildly elevated protein level or pleocytosis in the remaining 60%. The most essential aspect of the evaluation is to eliminate a potentially treatable cause, such as SEA, neoplasm, or hematoma. Management.  Treatment of transverse myelitis is tailored to the suspected underlying etiology. There are no good studies supporting a role for steroids. Neurologic consultation is suggested, and hospitalization usually is required. The clinical course of acute transverse myelitis varies widely, ranging from complete recovery to death from progressive neurologic compromise. Most patients with idiopathic disease have at least partial recovery, which usually begins within 1 to 3 months. Maximal improvement usually is obtained within 3 to 6 months with 30% of patients having a good recovery, 25% a fair recovery, and 30% a poor outcome; there is 15% mortality at 5 years.

Principles.  Acute transverse myelitis refers to acute or subacute spinal cord dysfunction characterized by paraplegia, a transverse level of sensory impairment, and sphincter disturbance. It describes a heterogeneous group of inflammatory disease processes that can affect the spinal cord by interruption of the ascending or descending pathways in the spinal cord.5 The presentation may be mimicked by compressive lesions, trauma, infection, or malignant infiltration. The pathogenesis of transverse myelitis is unknown, although it is noted to follow viral infection in approximately 30% of patients and commonly is termed postinfectious myelitis. Other postulated etiologic categories include infectious, autoimmune, and idiopathic. It can also be seen with a wide variety of connective tissue diseases, such as lupus, Sjögren’s syndrome, antiphospholipid syndrome, and other mixed-connective tissue diseases. No apparent cause of acute transverse myelitis is identified in 30% of the patients. Progression of symptoms usually is rapid, with 66% of the cases reaching maximal deficit by 24 hours. Symptoms may progress, however, over days to weeks. The thoracic cord region is affected in 60% to 70% of cases.38 The cervical spinal cord is rarely affected.

Principles.  Intraspinal hemorrhage is rare and may occur in the same anatomic locations as intracranial hemorrhages; epidural, subdural, subarachnoid, and intramedullary hemorrhages are all possible.4 Spinal subarachnoid hemorrhage usually is caused by an arteriovenous malformation.5 Hemorrhage from tumors or cavernous angiomas and spontaneous hemorrhage secondary to anticoagulation therapy also have been reported. Bleeding may occur exclusively in the subarachnoid space or within the substance of the spinal cord itself.

Clinical Features.  In addition to motor, sensory, and urinary disturbances, patients with acute transverse myelitis may complain of back pain and may have low-grade fever, raising concern for spinal epidural abscess (SEA). As with MS, the examination may reveal weakness progressing to paresis, hypertonia, hyperreflexia, clonus, and Babinski’s response. Spinal cord involvement also can result in dysautonomias (ie, dysfunction of the autonomic nervous system).

Clinical Features.  Patients with spinal subarachnoid hemorrhage present with excruciating back pain of sudden and severe onset at the level of the hemorrhage. This pain also may be in a radicular distribution or extend into the flank. Patients may complain of headache and exhibit cervical rigidity if the blood migrates into the intracranial subarachnoid space, simulating an intracranial subarachnoid hemorrhage. Variable neurologic deficits depend on the magnitude and anatomic location of the

Spinal Subarachnoid Hemorrhage

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hemorrhage. These deficits typically include extremity numbness, weakness, and sphincter dysfunction. Nuchal rigidity or signs of meningeal irritation may also be present. Although this is a rare etiology, when the back pain or neurologic dysfunction is sudden in onset, spinal hemorrhage should be considered. Differential Diagnosis.  Considerations in the differential diagnosis include epidural abscess, tumor, transverse myelitis, ischemia from aortic dissection, and anterior spinal artery thrombosis. Diagnostic Testing.  Because bone artifact may obscure presence of blood in the spine, the diagnostic study of choice in patients with suspected spinal subarachnoid hemorrhage is a MRI without contrast. Lumbar puncture also can confirm the presence of blood in the CSF. Angiography may be recommended if arteriovenous malformation is suspected. Management.  The treatment of spinal subarachnoid hemorrhage depends on the etiology of the hemorrhage. Neurosurgical referral is obtained for further evaluation and for clot evacuation if compression is present.

Syringomyelia Principles.  Syringomyelia is the presence of a cavitary lesion within the substance of the spinal cord. A syrinx usually is a chronic progressive lesion, and its location within the cord determines the constellation of neurologic findings on examination. Ninety percent of patients with syringomyelia have Arnold-Chiari I malformation (projection of cerebellar tonsils and medulla into the spinal canal). Syringomyelia also may result from spinal cord trauma (often months to years later) or compressive tumors, or it may follow meningitis. Clinical Features.  Headache and neck pain are the most common presenting complaints of patients with a syrinx, followed by sensory disturbance, gait disorder, and lower cranial nerve dysfunction. Symptoms may be exacerbated by a sneeze, cough, or Valsalva maneuver. The symptoms of syringomyelia develop and progress in accordance with the intracavitary pressure and location of the syrinx. The most common features on physical examination are lower limb hyperreflexia, weakness and wasting in the hands and arms, dissociated sensory loss, and gait disorder. The classic pattern of sensory deficit involves a loss of pain and temperature sensation in the upper extremities with preservation of proprioception and light touch. This phenomenon is described as a “dissociative anesthesia” because of the discrepant loss of sensory modalities. The sensory deficit often is described as being in a “capelike” distribution over the shoulders and arms. The anatomic basis for the neurologic features of a syrinx is the location near the central canal. Crossing fibers of the lateral spinothalamic tract carrying pain and temperature fibers may be impaired. Crude touch, position, and vibratory sensation typically are unaffected. Sensory fibers from the lower limbs are similarly spared. Differential Diagnosis.  Considerations in the differential diagnosis for syrinx include intrinsic spinal tumor and demyelination. Diagnostic Testing.  Syringomyelia is best seen on MRI. No other study currently in widespread use is equal to MRI in diagnostic ability. Management.  When the diagnosis of syringomyelia is considered, emergent imaging in the ED is not necessary if follow-

up evaluation can be arranged; in approximately two thirds of patients this condition is a slowly progressive process. In patients for whom MRI studies are obtained and the diagnosis is made, referral to a neurosurgeon is indicated.

Human Immunodeficiency Virus Myelopathy Human immunodeficiency virus (HIV) myelopathy typically occurs in patients with advanced disease. Weakness, gait disturbance, sphincter dysfunction, sensory abnormalities, and signs of spasticity are features of this progressive process. This is a diagnosis of exclusion because disorders such as toxoplasmosis, lymphoma, varicella-zoster, and cytomegalovirus infection may produce a similar clinical picture in immunocompromised patients. On pathologic examination, vacuolization of myelin sheaths in the cord may be found. Treatment is directed at the retroviral infection.

Spinal Cord Infarction Spinal cord infarction is another diagnosis of exclusion. Aortic dissection, surgery, and global ischemia are the more common causes, although this disorder may occur as a complication of systemic lupus erythematosus, vasculitis, or may be cryptogenic. An anterior spinal cord syndrome is the most common clinical picture. Recovery is variable and depends on the etiology.

Extrinsic Cord Lesions Spinal Epidural Hematoma Principles.  Spinal epidural hematoma is a relatively rare condition. The etiology may be traumatic after lumbar puncture, epidural anesthesia, or spinal surgery. Spinal epidural hematoma is more likely to occur in anticoagulated or thrombocytopenic patients or in patients with liver disease or alcoholism. Spontaneous bleeding is rare but may arise from spinal or dural arteriovenous malformation or vertebral hemangioma. Approximately one fourth to one third of all cases are associated with anticoagulation therapy, including low-molecular-weight heparin. Clinical Features.  The patient with a spinal epidural hematoma usually presents with sudden, severe, constant back pain with a radicular component. Onset may follow a straining episode. The pain is often worsened by percussion over the spine and maneuvers that increase intraspinal pressure, such as coughing, sneezing, or straining.6 The pain often causes the patient to seek care before the development of neurologic signs, possibly leading to delays in diagnosis. Neurologic deficits follow and may progress during hours to days. The patient usually is in significant distress from the pain. Motor and sensory findings depend on the level and size of the hematoma and can include weakness, paresis, loss of bowel or bladder function, and virtually any sensory deficit. Differential Diagnosis.  Considerations in the differential diagnosis include abscess, epidural neoplasm, acute disk herniation, and spinal subarachnoid hemorrhage. Diagnostic Testing.  MRI (with and without intravenous [IV] contrast) is the diagnostic study of choice. Management.  In patients with a spinal epidural hematoma, recovery without surgery is rare. Neurosurgical consultation for emergent decompressive laminectomy is indicated as soon as the diagnosis is considered. Functional recovery is related primarily to the length of time the symptoms are present. Recovery after 72

CHAPTER 96  Spinal Cord Disorders

hours of symptoms is rare but has been reported even without surgery.

parameningeal infection, showing elevation of protein and some increase in inflammatory cells.

Spinal Epidural Abscess

Management.  Urgent surgical consultation for decompression usually is required. Antibiotics effective against the most common pathogens (particularly S. aureus) should be started empirically. One possible regimen that covers gram-positive and gram-negative organisms consists of a third-generation cephalosporin (ceftriaxone 2000 mg every 24 hours) plus vancomycin (15 to 20 mg/kg IV every 8 to 12 hours), both given intravenously, plus rifampin (10 mg/kg by mouth or IV once a day). Outcome is related to the speed of diagnosis before the development of myelopathic signs. The disease is fatal in up to 25% of cases, and patients with neurologic deficit rarely improve if surgical intervention is delayed more than 12 to 36 hours after onset of paralysis. Patients operated on before development of neurologic symptoms generally have good outcomes.

Principles.  SEA is an infectious process usually confined to the adipose tissue of the dorsal epidural space, where there is a rich venous plexus. Major risk factors include diabetes, injection drug abuse, chronic renal failure, alcoholism, and immunosuppression, although the disease can be seen in patients who have none of these conditions.7,8 Recent infection is also a described risk factor. Whereas the disease may be manifested in subacute and chronic forms, the acute presentation is seen most frequently in the ED. Thoracic and lumbar sites of infection predominate, with cervical epidural abscess being much less common. Infection typically extends over four or five spinal vertebral segments. The dura mater limits the spread of an epidural infection, making subdural or intraspinal spread uncommon. Hematogenous spread of infection to the epidural space is the most common source (seen in 26% to 50% of cases), either to the epidural space or to the vertebra with extension to the epidural space. Skin and soft tissue infections are the most frequently identified source, reported in 15% of cases; Staphylococcus aureus is the most prevalent organism, being cultured in more than 50% of cases. Other frequently identified pathogens include aerobic and anaerobic streptococci, Escherichia coli, and Pseudomonas aeruginosa. Multiple organisms are identified in approximately 10% of cases; no organism is identified in 40%.With SEA, damage to the spinal cord can be caused by direct compression on neural or vascular structures, by thrombosis and thrombophlebitis of nearby veins, or by a focal vasculitis mediated by bacterial and inflammatory substances. Clinical Features.  The classic clinical presentation of SEA begins with a backache that progresses to localized back pain often associated with tenderness to percussion. The duration of symptoms is typically a few days but may extend for weeks. Fever, sweats, and rigors are reported in 30% to 75% of patients. The classic triad of back pain, fever, and progressive neurologic deficits is present in only a few patients, however, and delayed clinical diagnosis is common. Radicular symptoms may not be present initially but usually develop as the disease progresses. Without treatment, myelopathic signs will develop, usually beginning with bowel and bladder disturbance. Weakness ensues, followed by paraplegia or quadriplegia. Approximately 10% of patients with SEA present with delirium. Differential Diagnosis.  Any compressive spinal lesion can mimic SEA. Diagnostic Testing.  MRI with IV contrast is the imaging modality of choice and should be performed emergently if the diagnosis of SEA is entertained. Spinal CT is not recommended due to bone artifact. A complete blood count may support the diagnosis, although it is neither a sensitive nor specific test; a leukocytosis is commonly present with a typical white blood cell count of 13,000 to 16,000/µL. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests, although not specific for epidural abscess, are virtually always elevated with this condition and have been used as screening tests for SEA in an “at-risk” population.8 In one study, an elevated ESR or CRP had a sensitivity of 100% and a specificity of 67% for identifying an SEA. External validation is needed, but this may be a future promising risk-stratification method.11 Lumbar puncture is relatively contraindicated with known epidural abscess. If performed, CSF findings are consistent with a

Diskitis Principles.  Diskitis is an uncommon primary infection of the nucleus pulposus, with secondary involvement of the cartilaginous endplate and vertebral body. It may occur after surgical procedures or spontaneously, the latter being more common in pediatric patients.9 An increased incidence of diskitis has been noted in immunocompromised patients and in patients with systemic infections. The lumbar spine is the most common site of disease. Both a chronic disease and a more common acute course have been described.9 Clinical Features.  Patients present with moderate to severe pain, localized to the level of involvement and exacerbated by almost any movement of the spine. Elevated temperature is noted in more than 90% of patients. Radicular symptoms are present in 50% to 90% of cases. However, neurologic deficits are the exception with diskitis. Often there is a latent period (2 to 8 weeks) between the onset of back pain and the development of other clinical symptoms or abnormalities on the physical examination. S. aureus is the most common pathogen, but gram-negative, fungal, and tuberculous infections all have been recognized. Differential Diagnosis.  Considerations in the differential diagnosis include vertebral osteomyelitis, SEA, neoplasm, and hematoma. Diagnostic Testing.  Plain radiographs usually are not helpful for early diagnosis of diskitis, but destruction of the disk space is highly suggestive if present. The radiographic findings become abnormal after 2 to 4 weeks of disease. In addition to disk space narrowing, plain films may show irregular destruction of the vertebral body endplates. MRI with IV contrast is the radiographic study of choice, because it not only diagnoses diskitis but also rules out paravertebral or epidural abscess. Laboratory studies often show an elevated ESR, but the white blood cell count usually is normal.13 Management.  With timely diagnosis and treatment, outcome generally is good, and medical treatment with IV antibiotics that cover staphylococcus and streptococcus in accordance with local resistance patterns is usually curative. We recommend a combination of IV vancomycin (10 to 15 mg/kg) plus IV ceftriaxone (2 gm). If the infectious agent is known or suspected to be pseudomonas, then cefepime (2 gm) could be substituted for ceftriaxone. In patients with a severe penicillin allergy or contraindication to a cephalosporin, meropenem (2 gm) or aztreonam (2 gm) may be substituted for ceftriaxone. Finally, in patients

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with a vancomycin allergy or high resistance, linezolid (600 mg) is recommended. Surgery is generally not necessary.

Neoplasm Principles.  Spinal cord tumors are classified according to their relationship to the dura and spinal cord (extradural, intradural extramedullary, and intradural intramedullary). Spinal cord tumors produce neurologic symptoms by compression, invasion, or destruction of myelinated tracts. The resulting neurologic symptoms are directly related to the growth rate and the location of the tumor. Spinal cord tumors account for 4% to 10% of CNS tumors but for only 1% of all cancers. Most tumors affecting the spinal cord are metastatic. Approximately 10% of patients with known cancer are diagnosed with a spinal metastasis at some point in the course of their disease, and 5% to 10% of patients ultimately diagnosed with cancer first present with a spinal metastasis.2 Lung cancer, breast cancer, and lymphoma represent more than 50% of the primary malignant neoplasms that subsequently develop spinal metastasis, spreading by both the hematogenous route and direct extension. Most metastases occur in the thoracic spine, and nearly 20% of patients with tumor spread to the spine will have disease at multiple levels. Clinical Features.  In 95% of patients with spinal neoplasm, the initial complaint is pain, either in the back at the level of the tumor or in a radicular distribution. Pain often is characterized as dull, constant, and aching and commonly is said to worsen with recumbency (in contrast with the pain of herniated disk). Nighttime pain that is severe is characteristic of spinal neoplasm. Any action that increases intraspinal pressure (Valsalva maneuver,

sneeze, cough) may be associated with increased pain. Neurologic deficits vary by the location of the lesion. Besides a thorough neurologic examination, a search for possible primary sites should be done on the physical examination. Differential Diagnosis.  Considerations in the differential diagnosis include any of the compressive lesions (eg, hematoma, infection). Tumor can also mimic intrinsic spinal cord lesions, such as transverse myelopathy and cord infarction. Diagnostic Testing.  Plain radiographs are usually the initial imaging modality in patients with new back pain and no known diagnosis of cancer. The sensitivity and specificity of plain radiographs in detecting abnormalities consistent with malignancy are 60% and 95%, respectively. In the presence of normal radiographs, a normal ESR is diagnostically helpful, in that cancer is very unlikely in a patients with an ESR lower extremity effect marked by weakness > sensory deficits. • Anterior cord syndrome is marked by symmetrical motor loss but intact proprioception and vibration sense. • In patients with sudden severe back pain, consider spinal subarachnoid hemorrhage or spinal epidural abscess (SEA). • Myelitis is an inflammation of the spinal cord often caused by a viral infection; steroids have no proven benefit. MRI with contrast enhancement is the diagnostic modality of choice.

• Cauda equina syndrome can be difficult to differentiate from conus lesions because both can result in overflow bladder/fecal incontinence, leg weakness, and sensory loss in the perineum. Conus lesions are more typically bilateral, whereas cauda equina syndrome is unilateral. Upper motor neuron findings are expected with conus lesions but not cauda equina syndrome. • The diagnostic imaging of choice in the majority of suspected spinal disorders is a MRI with contrast. • A syrinx is a cavitary lesion in the spinal cord that presents with a sensory disassociation predominately in the upper extremities. With progression, it can lead to upper extremity weakness/wasting. Exacerbation with cough or Valsalva is typical. • With compressive lesions of the spinal cord, duration of neurologic dysfunction is directly related to ultimate neurologic outcome. The diagnosis should be made expeditiously and definitive therapy begun as soon as possible.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 96  Spinal Cord Disorders

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REFERENCES 1. Hosaka AI, Nakamagoe K, Watanabe M, et al: Magnetic resonance images of herpes zoster myelitis presenting with Brown-Séquard syndrome. Arch Neurol 67:506, 2010. 2. Ullery BW, Cheung AT, Fairman RM, et al: Risk factors, outcomes, and clinical manifestations of spinal cord ischemia following thoracic endovascular aortic repair. J Vasc Surg 54:677–684, 2011. 3. Harrison DM: Multiple sclerosis. Ann Int Med 160(7):ITC 4, 2014. 4. Wang VY, Chou D, Chin C: Spine and spinal cord emergencies: vascular and infectious causes. Neuroimaging Clin N Am 20:639–650, 2010. 5. Muralidharan R, Saladino A, Lanzino G, et al: The clinical and radiological presentation of spinal dural arteriovenous fistula. Spine 36:1641–1647, 2011.

6. Mukerji N, Todd N: Spinal epidural haematoma: factors influencing outcome. Br J Neurosurg 27:712, 2013. 7. Duarte RM, Vaccaro AR: Spinal infection: state of the art and management algorithm. Eur Spine J 22:2787, 2013. 8. Davis DP, Salazar A, Chan TC, et al: Prospective evaluation of a clinical decision guideline to diagnose spinal epidural abscess in patients who present to the emergency department with spine pain. J Neurosurg Spine 14:765–770, 2011. 9. Amini MA, Salzman GA: Infectious spondylodiscitis: diagnosis and treatment. Mo Med 110:121, 2013.

CHAPTER 96: QUESTIONS & ANSWERS 96.1. Which of the following physical findings indicates a partial rather than a complete cervical spinal cord lesion? A. Horner’s syndrome B. Hypotension C. Intact perineal sensation D. Priapism E. Reflex tachycardia Answer: C. Persistent perineal sensation, rectal sphincter tone, or even trace toe movement suggests a partial spinal cord lesion. This offers a far better prognosis than a complete transection. 96.2. Which of the following physical findings is a marker for spinal shock? A. Babinski’s response present B. Bulbocavernosus reflex absent C. Lower extremity hyperreflexia present D. Perineal sensation present E. Priapism present Answer: B. The bulbocavernosus reflex is a cord-mediated reflex signified by reflex contraction of the anal sphincter in response to squeezing of the glans penis or tugging on the Foley catheter. The termination of spinal shock is heralded by return of this reflex followed by increased muscle tone and hyperreflexia. 96.3. A 49-year-old man presents after a moderate-speed motor vehicle collision. He was an unrestrained driver who was rear-ended at a stop light. He suffered no head impact but reported a whiplash mechanism and complains of neck pain and a mild burning sensation in both palms. Vital signs and physical examination are unremarkable except for posterior cervical paraspinous muscle tenderness and modest allodynia of both palms and fingertips in a nondermatomal distribution. What is the expected finding on magnetic resonance imaging (MRI)? A. Anterior spinal cord ischemia B. C5–6 traumatic spondylolisthesis C. Cervical canal stenosis D. Normal MRI E. Unilateral C5–6 disk protrusion Answer: C. Central cord syndrome is a typically post-traumatic event in either elderly individuals with degenerative cervical canal narrowing (osteophytes, ligamentum flavum hypertrophy, facet overgrowth) or younger individuals with congenitally narrowed canals. A hyperextension mechanism in the setting of a narrow canal produces a central cord impingement with an upper > lower extremity motor > sensory deficit pattern. Bladder dysfunction is variable. Early MRI may show no actual cord changes and only the canal narrowing. Upper extremity dysesthesia may be the only symptom. 96.4. A 73-year-old man is brought to the ED by family members for weakness. His only past history is peripheral

vascular disease. He is found to be in septic shock and resuscitated with fluid, antibiotics, blood, and vasopressors. He ultimately requires both dopamine and norepinephrine for maintenance of a mean arterial pressure greater than 60 mm Hg. Approximately 5 hours after arrival, he develops bilateral lower extremity weakness. He has no prior history of back pain or neurologic problems. Which of the following is likely? A. A similar neurologic syndrome after a cervical hyperflexion injury B. Finding of a mass lesion on MRI C. Finding of an epidural hematoma D. Preservation of lower extremity temperature sensation E. Progressive return of function after 24 hours Answer: A. Anterior cord syndrome is typically characterized by symmetrical loss of motor function and pain and temperature sensation (both tracts being located in the anterior portion of the cord). Proprioception and vibration sense are usually maintained. Although it may occur after a cervical flexion injury, it is most likely seen after periods of hypotension or instability, such as shock, infection, and myocardial infarction. Most improvement occurs in the first 24 hours. 96.5. What feature most likely distinguishes a conus medullaris from a cauda equina lesion? A. Back pain B. Bilateral symptoms C. Distal motor weakness D. Sacral anesthesia E. Urinary incontinence Answer: B. Isolated conus lesions are rare, but because of the small size, they frequently result in bilateral symptoms. Cauda equina syndrome more frequently results in unilateral findings. An additional distinguishing feature may be the presence of upper motor neuron findings in conus medullaris syndrome. Both syndromes may cause overflow bladder incontinence, fecal incontinence, leg weakness, and sensory loss in the perineum. 96.6. A 27-year-old woman presents with complaints of back pain and difficulty walking. Her symptoms have been progressive for 2 days. She has no significant past medical history. Her only other symptom was a bout of influenza approximately 3 weeks prior. Physical examination is remarkable for lower extremity hyperreflexia, moderate symmetrical lower extremity weakness, moderate increased tone, a T10 level of sensory loss, and a postvoid residual urine volume of 350 mL. What should be the next intervention? A. Antibiotics B. Complete blood count, erythrocyte sedimentation rate (ESR), and antinuclear antibody levels C. MRI scan

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D. Neurology consultation E. Steroids Answer: C. Transverse myelitis is postinfectious in 30% of cases and also idiopathic in 30%. Other causes are autoimmune disorders and infections. Symptoms are typically rapid in onset and progress during 1 or 2 days. Back pain may accompany it. Emergent MRI is indicated to rule out other causes. There is no proven efficacious treatment, although steroids have been used. There is an association with multiple sclerosis (MS). Prognosis for recovery is only fair. 96.7. Which of the following characteristics is a feature of syringomyelia? A. Absence of neck pain B. Exacerbation with cough or Valsalva maneuver

C. Loss of vibrating sensation in the arms D. Normal cervical MRI E. Normal lower extremity examination Answer: B. Syringomyelia typically presents with headache, neck pain, and variable upper extremity dissociative anesthesia: symmetrical loss of pain and temperature sensation with preserved posterior column function. With progression, upper extremity weakness or wasting and lower extremity upper motor neuron changes are expected. Exacerbation with cough and the Valsalva maneuver is typical. There is a 90% association with type I ArnoldChiari malformation (cerebellar tonsils and medulla projecting into the spinal canal—often the cause of the typical occipital headaches). MRI is diagnostic.

C H A P T E R 97 

Peripheral Nerve Disorders David C. Snow  |  E. Bradshaw Bunney OVERVIEW Principles The nervous system is divided into central nervous system (CNS) and peripheral nervous system (PNS) components. The PNS is subdivided into 12 cranial and 31 spinal nerves. Disorders of the cranial nerves are discussed in Chapter 95. Because diseases of the neuromuscular junction and the myopathies are located distal to the neuron itself, they are also considered separately in Chapter 98. Radiculopathies, which are disorders of the roots of the PNS, are so commonly associated with musculoskeletal neck and back pain that they are mentioned only briefly here and are discussed in detail in Chapter 47. Current estimates suggest that about 2.4% of the population suffers from peripheral neuropathy, rising to 8% for those over 50 years of age.1 Diabetes mellitus is a leading contributor. The simplest approach to diseases of the PNS parallels the CNS model of separating focal from nonfocal disease. In the PNS, the first broad category is the focal group, which can be divided into those with evidence of single versus multiple lesions of peripheral nerves, known respectively as simple mononeuropathies and multiple mononeuropathies (or mononeuropathy multiplex). The second broad category, which constitutes the nonfocal group of peripheral neuropathies, contains the polyneuropathies. These tend to produce bilaterally symmetrical symptoms and signs, reflecting the widespread nature of the underlying pathologic processes. The evaluation of PNS disease involves a goal-directed history and physical examination targeted at answering the following three questions, each of which corresponds to a stratum of the algorithm presented in Figure 97.1: 1. Are the sensorimotor signs and symptoms symmetrical or asymmetrical? 2. Are the sensorimotor signs and symptoms distal or both proximal and distal? 3. Is the modality involved exclusively motor, sensory, or mixed sensorimotor? By systematically combining responses to these questions, seven discrete categories of peripheral neuropathy are identified, each of which contains a finite set of possible diagnoses. Because pure motor or sensory findings tend to occur mainly in an asymmetrical, distal distribution, this is the only category in Figure 97.1 subdivided into pure motor and pure sensory abnormalities. The spinal component of the PNS is shown schematically in Figure 97.2. The anterior and posterior nerve roots exit the spinal cord at each segmental level. Just distal to the dorsal root ganglion they converge to form a mixed (motor and sensory) spinal nerve, of which there are 31 pairs: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. The spinal nerves immediately bifurcate into anterior (ventral) and posterior (dorsal) rami. The posterior ramus travels to the back. The anterior ramus innervates the anterolateral portion of the body and supplies all peripheral nerves for the upper and lower extremities through the brachial

and lumbosacral plexus, respectively. Interweaving of fibers occurs within a plexus, producing a mixed sensorimotor innervation of peripheral nerves exiting the plexus. In addition to the motor and sensory modalities of the PNS, the autonomic nervous system has a peripheral component. Anatomically and functionally, the autonomic nervous system is divided into two parts: (1) a sympathetic (thoracolumbar) component and (2) a parasympathetic (craniosacral) component. Autonomic dysfunction may cause systemic abnormalities, such as orthostasis, or local problems, such as atrophic, dry skin. The PNS has three basic responses to pathologic stimuli (see Fig. 97.2): (1) the myelinopathies, in which the primary site of involvement is limited to the myelin sheath surrounding the axon; (2) the axonopathies, in which the primary site of involvement is the axon, with or without secondary demyelination; and (3) the neuronopathies, in which the cell body of the neuron itself is the primary site of involvement, ultimately affecting the entire peripheral nerve. Although overlap occurs, each of these prototypes has a distinctive clinical presentation, electrophysiologic profile, and microscopic appearance.

Differential Diagnosis The differential diagnosis for any patient presenting with sensory, motor, or sensorimotor complaints, particularly if they are localized to the extremities, should include a peripheral neuropathy. Within this group, patients with focal weakness are most concerning, because they are at greatest risk for respiratory compromise. Box 97.1 lists the causes of acute, emergent weakness that may affect respiration. As soon as the emergent causes of weakness have been excluded, the individuals with focal weakness should be assessed next to exclude CNS disease (eg, stroke; Chapter 91), after which the systematic evaluation of peripheral neuropathy is performed with the distinguishing features of each of the seven peripheral neuropathic patterns described by distribution and modality and represented by a disease prototype (see Fig. 97.1; Table 97.1).

Diagnostic Testing Testing in the evaluation of the patient with a suspected peripheral neuropathy is presented in Box 97.2. Electrophysiologic testing (nerve conduction studies [NCSs] and needle electromyography [EMG]) detects underlying pathologic abnormalities. Because neither test is readily available in the acute care setting, they are discussed only briefly here. Information gathered from these tests can be used to obtain objective information regarding the anatomic distribution of involvement (symmetrical versus asymmetrical and distal versus proximal and distal) and the modalities involved (sensory, motor, or mixed). NCSs and EMG can also identify the level of the neuraxis affected by the disease process (ie, root, plexus, or nerve); if the nerve is affected, electrophysiologic testing can help determine whether the lesion is mononeuropathic (either an isolated mononeuropathy or mononeuropathy multiplex) or polyneuropathic. 1307

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SYMMETRICAL

ASYMMETRICAL

Proximal/distal

Distal

Proximal/distal

Mixed

Mixed

Mixed

1. AIDP/CIDP Primary myelinopathy

2. DSPN Primary axonopathy

3. Plexopathy/ radiculopathy*

Distal

Mixed

Pure

6. Motor neuronopathy

4. Mononeuropathy*

7. Sensory neuronopathy

5. Mononeuropathy multiplex*

Fig. 97.1.  An approach to peripheral neuropathy in the emergency department. AIDP, Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome); CIDP, chronic inflammatory demyelinating polyneuropathy; DSPN, distal symmetrical polyneuropathy. *A proximal distribution of sensorimotor findings may dominate the clinical picture in patterns 3, 4, and 5, depending on the location of the lesions. Posterior cord Dorsal root

Neuromuscular junction Dorsal root ganglion

Ventral root

Posterior ramus

Anterior ramus Mixed spinal nerve

Peripheral nerve axon Myelin sheath

Anterior cord

CNS

Muscle

PNS

Fig. 97.2.  Schematic representation of macroscopic and microscopic anatomy of the peripheral nervous system (PNS) and its interface with the central nervous system (CNS). See the text for an explanation.

Finally, EMG and NCSs can distinguish axonal from myelin disease, further narrowing the differential diagnosis. Prognosis is determined by the nature of pathologic involvement of the PNS. Primary demyelination spares the axon and thus carries the best prognosis. The prognosis is worse in axonopathies because reestablishment of nerve function is dependent on the much slower process of axonal regeneration. Neuronopathies, which begin with primary destruction of the nerve cell body, produce pure motor or pure sensory syndromes. Eventually the entire nerve is affected, resulting in the worst prognosis of the three. Expensive batteries of tests purporting to measure a wide variety of antibodies to components of peripheral neuropathies are commercially available but have not been shown to be useful as screening tests.

SPECIFIC TYPES OF NEUROPATHIES Type 1: Demyelinating Polyneuropathy (Guillian-Barré Syndrome) Principles The pattern of symmetrical weakness, usually worse distally, accompanied by variable sensory findings is characteristic of acute Guillain-Barré syndrome (GBS). It is a heterogeneous and unpredictable disorder, characterized by areflexic paralysis with albuminocytologic dissociation, with marked variation in latency between antecedent infection and symptom onset. Up to 20% of patients remain disabled from this disease process, and about 5% will die despite therapy.1

CHAPTER 97  Peripheral Nerve Disorders

BOX 97.1 

TABLE 97.1 

Causes of Acute, Emergent Weakness and Possible Respiratory Compromise

Patterns and Prototypes of Peripheral Neuropathies

Note: Although several of the disorders listed are myopathies (see Chapter 1098), rather than peripheral neuropathies, they are lumped together here because it is important to identify patients at risk for respiratory failure early in the course of evaluation. Autoimmune Demyelinating Guillain-Barré syndrome (GBS) Chronic inflammatory demyelinating polyneuropathy Myasthenia gravis Toxic Botulism Buckthorn Seafood Paralytic shellfish toxin Tetrodotoxin (puffer fish, newts) Tick paralysis Metals Arsenic Thallium Metabolic Dyskalemic syndromes Acquired (especially with thyrotoxicosis) Familial Hypophosphatemia Hypermagnesemia Porphyria Infectious Poliomyelitis Diphtheria

PROTOTYPICAL DISEASE MODALITIES

TYPE

PATTERN DISTRIBUTION

1

Proximal and distal, symmetrical, sensorimotor polyneuropathy Proximal and distal Motor > sensory

GBS

Distal, symmetrical, sensorimotor polyneuropathy Distal Sensory > motor

Diabetic DSPN

Proximal and distal, asymmetrical, sensorimotor neuropathy Proximal and distal Sensory and motor

Brachial plexopathy

4

Distal, asymmetrical, sensorimotor mononeuropathy Distal Sensory and motor

CTS (median mononeuropathy) Asymmetrical

5

Distal, asymmetrical, sensorimotor mononeuropathy multiplex Distal Sensory and motor

Vasculitic mononeuropathy multiplex Asymmetrical

6

Distal, asymmetrical, pure motor neuronopathy Distal Motor

ALS

Distal, asymmetrical, pure sensory neuronopathy Distal Sensory

Pyridoxine toxicity

2

3

7

Symmetrical

Symmetrical

Asymmetrical

Asymmetrical

Asymmetrical

ALS, Amyotrophic lateral sclerosis; CTS, carpal tunnel syndrome; DSPN, distal symmetrical polyneuropathy; GBS, Guillain-Barré syndrome.

BOX 97.2 

Ancillary Diagnostic Testing in Suspected Peripheral Neuropathy OBTAINED IN MOST PATIENTS Complete blood count Erythrocyte sedimentation rate Glucose Creatine kinase Creatinine

OBTAINED IN SOME PATIENTS BASED ON HISTORY

Human chorionic gonadotropin Magnesium Phosphate Vitamin B12 Hemoglobin A1c Serum protein electrophoresis with immune fixation electrophoresis Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin screen with fluorescent treponemal antibody absorption test, as appropriate Thyroid function Human immunodeficiency virus (HIV) titer

Lyme enzyme-linked immunosorbent assay and Western blot Rheumatoid factor and antinuclear antibody Blood, urine, hair, or nails for metal, depending on suspected chronicity of exposure Specific serum antibodies to components of peripheral nervous system (PNS) Cerebrospinal fluid (CSF) for cells, protein, Lyme titer Electrodiagnostic testing Nerve conduction studies (NCS) Electromyography (EMG) Neurodiagnostic imaging Magnetic resonance imaging (MRI) Computed tomography (CT) Sonography Quantitative sensory testing Nerve biopsy Sural Intraepidermal nerve fiber density

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BOX 97.3 

Demyelinating Polyneuropathies Guillain-Barré syndrome (GBS) Acute inflammatory demyelinating polyradiculoneuropathy Acute motor axonal neuropathy Acute motor and sensory axonal neuropathy Miller Fisher syndrome Chronic inflammatory demyelinating polyradiculoplexoneuropathy Malignant disease Human immunodeficiency virus (HIV) infection Hepatitis B Buckthorn Diphtheria

The most common form of GBS is an acute inflammatory demyelinating polyneuropathy, representing 90% of the cases seen in the United States. Less common variants are acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and the Miller Fisher syndrome. Acute motor axonal neuropathy, which accounts for most of the remaining cases seen in the United States, afflicts those of Asian descent more often. Miller Fisher syndrome is a rare form of GBS characterized by the triad of ophthalmoplegia, ataxia, and areflexia (Box 97.3). The most common infectious organisms associated with GBS is Campylobacter jejuni, with 30% noted in one study.2 Cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumonia are also associated with subsequent development of GBS.

Clinical Features The majority of patients seek treatment days to weeks after resolution of an upper respiratory or gastrointestinal illness, presenting with progressive, symmetrical distal (and usually to a lesser extent proximal) weakness. Symptoms can progress over a period of up to 28 days, casting doubt on the diagnosis in a patient with rapidly developing symptoms. Signs and symptoms are usually worse in the lower extremities and are associated with diminution or loss of deep tendon reflexes (DTRs), variable sensory findings, and sparing of the anal sphincter. The presence of distal paresthesias increases the likelihood of GBS as the diagnosis. The GBS disability score, which combines age, presence or absence of diarrhea, and a score of the patient’s ability to ambulate independently at 2 weeks, has been shown to be predictive of prognosis at 6 months, particularly related to independent activity. Tongue weakness has been found to be associated with the development of respiratory compromise and the need for mechanical ventilation in patients with GBS.3 Compared with adults, children who have GBS have neuropathic pain more often (80%) and require mechanical ventilation less often (13%).4

Diagnostic Testing GBS is typically diagnosed on clinical findings, but additional testing is available when the diagnosis is uncertain. EMG can be used in such instances. Signs of demyelination including nerve conduction slowing with prolonged distal motor latency the most frequent demyelinating parameter. In addition to electrophysiologic testing, cerebrospinal fluid (CSF) analysis, and respiratory function testing may aid in the diagnosis of GBS. CSF analysis is useful when it demonstrates the characteristic picture of markedly elevated protein with only a mild pleocytosis (albuminocytologic dissociation). In the clinical setting of suspected GBS, this finding is highly specific. Early in the disease, however, patients may have normal CSF values. One

study noted only 50% of patients with this finding in the first week of symptoms, rising to 75% in the third week. Consequently, a normal CSF value cannot be used to exclude GBS. Individuals with suspected GBS should have their respiratory function tested. A decrease in forced vital capacity (FVC) correlates with the need for intubation in patients with GBS. A FVC of less than 20 mL/kg is associated with pending respiratory failure and the need for intubation, whereas patients with an FVC of more than 40 mL/kg do not usually require intubation.3 Likewise, patients with a negative inspiratory force of less than 30 cm H2O are more likely to require mechanical ventilation. Other tests, such as the forced expiratory volume in 1 second (FEV1) and peak flow rate (PFR), can also be used to assess respiratory function. Patients unable to perform these tests and those with less than 100% of predicted values should have an arterial blood gas sample obtained.

Management In practice, patients with symmetrical weakness of relatively acute onset, decreased or absent DTRs, and variable degrees of sensory loss are managed as if they have GBS or one of its variants. These patients have a greater risk for respiratory compromise, which develops in 20% to 30% of patients.3 Conversely, patients with predominantly sensory signs and symptoms are less likely to develop acute respiratory distress and have a more favorable prognosis. About half of patients with GBS have autonomic dysfunction, experience a peak of disease severity within a week of onset, have some form of cranial nerve involvement (usually VII), and suffer long-term sequelae of their illness. The definitive treatments for GBS are plasma exchange or intravenous immune globulin (IVIG). Both of these treatments are supported by well-designed studies, although there are no studies comparing IVIG to placebo. Combination or sequential therapy confers no therapeutic advantage over either intervention alone. Plasma exchange is cumbersome and not available at many hospitals. IVIG is more readily available and is usually administered in a dose of 400 mg/kg per day for 5 days.5 However, IVIG is expensive, costing roughly double a standard course of plasma exchange. Corticosteroids are not recommended; oral steroids have been shown to delay recovery, and intravenous steroids alone have been shown to impart no benefit. The combination of intravenous steroids and IVIG appears to hasten recovery but does not effect on long-term outcome and is not currently recommended.6,7

Disposition Patients with probable GBS should receive neurologic consultation and admission for airway monitoring and treatment with either plasma exchange or IVIG. Evidence of alveolar hypoventilation (elevated carbon dioxide [Pco2]) in a patient with an unsecured airway requires an intensive care level of monitoring and considered for early, prophylactic intubation.

Type 2: Distal Symmetrical Polyneuropathy Principles Distal symmetrical polyneuropathy (DSPN) is the most common type of peripheral neuropathy. Diabetes, alcoholism, human immunodeficiency virus (HIV) disease, and toxic metabolic causes are the most frequent etiologies (Box 97.4). DSPN in diabetics, termed diabetic polyneuropathy, is the most common chronic complication of diabetes mellitus.7 Although the association between alcoholism and peripheral neuropathy has been well established for centuries, demonstration

CHAPTER 97  Peripheral Nerve Disorders

BOX 97.4 

Distal Sensorimotor Polyneuropathies Diabetes mellitus Alcoholism Neoplastic or paraneoplastic Hereditary motor and sensory neuropathies (Charcot-Marie-Tooth) Cryptogenic sensorimotor polyneuropathies HIV infection Toxins Organic or industrial agents Acrylamide Allyl chloride Carbon disulfide Ethylene oxide Hexacarbons Methyl bromide Organophosphate-induced delayed polyneuropathy Polychlorinated biphenyls Trichloroethylene Vacor Metals Arsenic Gold Mercury (inorganic) Thallium Therapeutic agents Amiodarone Antiretrovirals

Dapsone Disulfiram Isoniazid Metronidazole Nitrofurantoin Paclitaxel (Taxol) Phenytoin Statins (HMG-CoA reductase inhibitors) Thalidomide Vinca alkaloids (vincristine, vinblastine) Nutritional Beriberi (thiamine or vitamin B1) Pellagra (niacin, B vitamins) Pernicious anemia (vitamin B12) Pyridoxine deficiency (vitamin B6) End-organ dysfunction Acromegaly Chronic pulmonary disease Hypothyroidism Renal failure (uremic neuropathy) Paraproteinemias Amyloidosis Monoclonal gammopathy of unknown significance Multiple myeloma Waldenström’s macroglobulinemia Porphyria

HIV, Human immunodeficiency virus; HMG-CoA, hydroxymethylglutaryl coenzyme A.

of a direct neurotoxic effect of alcohol remains elusive. The preponderance of evidence from both observational studies in humans and experimental data from animal models suggests that the association between alcohol and peripheral neuropathy may be confounded by nutritional status (ie, deficiency states might be the true underlying cause of alcoholic peripheral neuropathy). With the widespread use of highly active and effective antiretroviral treatment, peripheral neuropathies have become the most common neurologic complication of HIV infection. The typical HIV neuropathy is a DSPN, estimated to affect up to 35% of the HIV population, with a currently unknown pathogenesis.

Clinical Findings Most polyneuropathies are characterized by a pattern of distal, symmetrical sensorimotor findings, worse in the lower than in the upper extremities, with a stocking-glove distribution of sensory abnormalities that gradually diminishes as one moves proximally. Motor weakness and loss of DTRs, which lag behind the sensory features, follow a similar pattern of progression from distal to proximal. The diffuse, distal, symmetrical nature of this pattern is most consistent with a toxic-metabolic disease process that causes a length-dependent axonopathy. Initial symptoms usually consist of “positive” sensory complaints (eg, dysesthesias, such as tingling and burning) beginning on the plantar surfaces of both feet. At the early stages of a typical DSPN, there may be some asymmetry. At this juncture, it may be impossible to distinguish a focal neuropathic process such as a mononeuropathy from a polyneuropathy, although in this location, prior probability strongly favors a polyneuropathy. As the process advances, the plantar surfaces of both feet become dysesthetic before the dorsum of either foot is involved.

Weakness of dorsiflexion of the big toe is usually the first motor sign, followed by weakness of foot dorsiflexion, footdrop, loss of the Achilles reflex, and later a “steppage gait,” in which footdrop causes the toes to point downward and scrape the ground while walking, requiring the patient to lift the leg higher than normal when walking. Sensory loss continues to move proximally, and before it reaches the knees, the fingertips are usually involved. DTRs are progressively lost, as is proprioception. If loss of proprioception becomes severe, patients may develop sensory ataxia. As the neuropathy continues to progress, sensory abnormalities ultimately involve all modalities and extend to a diamond-shaped periumbilical area. Far-advanced disease may affect sensation over the skull vertex and facial midline structures. Atrophy and areflexia occur as weakness worsens. Severely impaired patients may be unable to ambulate or to grasp objects. These symptoms have a significant impact on the patient’s quality of life, affecting not only physical functioning but also sleep and emotional and social functioning. Many of these patients display signs of depression or anxiety. Polyneuropathies can be difficult to diagnose and are best approached by the performance of electrodiagnostic studies for patients with a constellation of symptoms and signs suggesting a particular neuropathy. Diabetic foot ulcers are a common complication of diabetes, ranging from 2% to 10% of the population. Unperceived trauma is the leading cause, likely from the associated polyneuropathy.8 The clinical picture of alcoholic neuropathy is similar to that of diabetic DSPN. However, in alcoholism, severe myopathy and cerebellar degeneration often complicate the clinical picture. Autonomic skin changes with atrophy and hair loss accompany the sensorimotor abnormalities. Often, other systemic effects of alcoholism are so severe that the patient may not notice the neuropathic symptoms.

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Differential Diagnosis

BOX 97.5 

Box 97.4 lists the differential diagnoses of DSPN. On the basis of results from a case-control study, the statins have been added to the list of drugs that are implicated.

Asymmetrical Proximal and Distal Peripheral Neuropathies

Diagnostic Testing Electrodiagnostic studies are commonly employed in the evaluation for this entity. This includes both NCSs and needle electromyelography. Screening laboratory tests should be considered for all patients who present with this condition. The tests that provide the highest yield include blood glucose, serum B12, and serum protein immunofixation electrophoresis.

Management Diabetic DSPN, the first step in the treatment, is intensive diabetes therapy aimed at near normoglycemia. If discomfort is severe, the etiology of the neuropathy seems likely to be diabetic, and if referral is delayed, it may be necessary to provide the patient with some symptomatic relief. Because treatment of neuropathic pain has traditionally been linked to etiology rather than to an underlying mechanism, the choice of pharmacologic agents is empirical, with substantial practice variation in the United States and worldwide. Nonsteroidal antiinflammatory drugs (NSAIDs) should not be considered first-line treatment, because they have little proven efficacy and a high potential for renal impairment. High level evidence supports the use of tricyclic antidepressants, anticonvulsants, and the serotonin and norepinephrine reuptake inhibitor nuloxetine. Imipramine or amitriptyline may be started at a daily dose of 25 mg at bedtime (10 mg in elders) and titrated slowly up to a dose of 150 mg. Carbamazepine at a dose of 200 to 400 mg every 8 hours and gabapentin at a dose of 900 to 3600 mg per day are also effective treatments. Tramadol, a mixed opioid with low potential for dependency, has been shown in two studies to have a NNT (number needed to treat) below 5.9 Tramadol combined with acetaminophen has been found to be as effective as gabapentin in the treatment of painful diabetic neuropathy. Pregabalin 150 to 600 mg per day, a more recent treatment option, has a mechanism of action similar to that of gabapentin. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has been found effective at a dose of 60 mg/day. Tapentadol ER 100 to 250 mg twice daily was also found to provide pain relief in patients with diabetic neuropathy.10 Topical capsaicin provides relief in some patients, but the burning associated with its application has limited its use. Topical lidocaine patches, 5%, are another treatment option, showing similar efficacy to pregabalin. In addition to pain management as discussed earlier, all patients with suspected alcoholic DSPN should receive dietary supplements and referral for outpatient management. Lamotrigine has been shown to be effective in the treatment of HIV-associated painful neuropathies, especially for those patients on highly active antiretroviral therapy (HAART). However, there are no comparative studies to support its use over the other pain medications.

Type 3: Asymmetric Proximal and Distal Peripheral Neuropathies (Radiculopathies and Plexopathies) Radiculopathies (see Chapter 47) and plexopathies often result from trauma (Box 97.5). In general, a plexopathy, whether brachial or lumbosacral, is identified by a process of elimination (ie, a pattern of sensorimotor and reflex abnormalities that fit neither a radicular nor an individual peripheral nerve distribution). Although this approach does not exclude a mononeuropathy

BRACHIAL PLEXOPATHY

Open Direct plexus injury (knife or gunshot wound) Neurovascular (plexus ischemia) Iatrogenic (central line insertion) Closed Traction injuries “Stingers” Traction neurapraxia Partial or complete nerve root avulsion Radiation Neoplastic Idiopathic brachial plexitis Thoracic outlet

LUMBOSACRAL PLEXOPATHIES

Open Closed Traction injuries Pelvic double vertical shearing fracture Posterior hip dislocation Retroperitoneal hemorrhage Vasospastic (deep buttock injection) Neoplastic Radiation Idiopathic lumbosacral plexitis Infectious Herpesvirus (sacrococcygeal) Herpes simplex 2 Herpes zoster Cytomegalovirus polyradiculopathy (HIV infection) HIV, Human immunodeficiency virus.

multiplex on physical examination alone, a careful history should determine whether the patient is at risk for development of a mononeuropathy or plexopathy on the basis of underlying disease Most plexopathies are seen in young men after motor vehicle accidents. Most present for evaluation of radicular pain several months after the initial injury. Therapeutic intervention is often delayed to maximize the potential for spontaneous recovery. Several surgical repairs exist, including neurotization and nerve transfer. Radiation (actinic) plexopathy occurs after a variable period of latency following treatment, which may extend to 20 years or more. Almost all series include women who received radiation treatment for breast cancer. Among neoplastic causes, most originate from the lung or breast. Patients with probable neoplastic brachial plexopathy need imaging studies and may require immediate radiation therapy. Pain control is the focus of management. Thoracic outlet syndrome (TOS) describes a constellation of symptoms caused by compression of the neurovascular bundle at the thoracic outlet. As our understanding of this condition has improved, treatment has evolved but remains controversial.11 Manifestations include both neurogenic and vascular (arterial or venous) TOS. It is estimated that over 90% of cases are neurogenic in origin, 3% to 5% are venous, and less than 1% are arterial. Neurogenic TOS is caused by compression of the brachial plexus, presenting with upper extremity weakness, numbness, paresthesias, and pain in a nonradicular distribution. Symptoms are usually present during normal daily activities and sleep.

CHAPTER 97  Peripheral Nerve Disorders

Treatment is typically nonsurgical, involving education, activity modification, and physical therapy. Vascular TOS can be either arterial or venous and is characterized by swelling of the upper extremity, pain, and a feeling of heaviness after exertion. Discoloration can also be seen. If arterial TOS is occurring, caused by compression of the subclavian artery, the typical findings of arterial insufficiency can be seen—pain, numbness, coolness, pallor. Treatment is typically surgical, involving decompression of the thoracic outlet. Because of the complexity of plexopathies, there is no reason to expect that one can or should do more in the ED than localize the probable pathologic process to the brachial or lumbosacral plexus. Depending on severity and suspected etiology, the patient should either be admitted or referred to a neurologist with experience in PNS disease.

Type 4: Isolated Mononeuropathies The pattern of asymmetrical, sensorimotor, usually distal, peripheral neuropathy is characteristic of a mononeuropathy. Mononeuropathies are of two main types: isolated and multiple. The isolated mononeuropathies are discussed in this section; the multiple mononeuropathies, also termed mononeuropathy multiplex, are discussed in the next section as a type 5 peripheral neuropathy. Isolated mononeuropathies are usually caused by trauma, either blunt or penetrating (Box 97.6). If the trauma is blunt, the injury may be secondary to compression from an internal or external source. Entrapment neuropathies are a subset of compression neuropathies occurring at anatomic locations where nerves traverse potentially constricting compartments or tunnels. Isolated mononeuropathies may be acute, intermittent, or chronic and continuous. Antecedent peripheral neuropathy may be a risk factor for development of compression neuropathy (so-called double-crush syndrome), particularly in diabetics.

Radial Mononeuropathy Principles.  The radial nerve arises from the C5 to T1 roots. After exiting the brachial plexus, it passes behind the proximal humerus in the spiral groove and takes a lateral (radial) course down the upper arm (Fig. 97.3). At about the level of the antecubital fossa, it bifurcates into the posterior interosseous (pure motor) and superficial radial (pure sensory) nerves. The radial nerve controls extension of the fingers, thumb, wrist, and elbow (triceps). In contrast to the median and ulnar nerves, the radial nerve provides only extrinsic motor innervation to the hand (ie, it does not supply motor fibers to any muscles that both originate and insert within the hand). In further contrast to the median and ulnar nerves, which supply most of the Posterior cord, brachial plexus

Axillary nerve Posterior cutaneous nerve of forearm

to Latissimus dorsi to Triceps to Brachioradialis Superficial radial nerve Extensor digitorum Extensor digiti quinti to Extensor carpi ulnaris Extensor pollicis longus/brevis Abductor pollicis longus

to triceps Intermuscular septum to Extensor carpi radialis longus to Extensor carpi radialis brevis Posterior interosseous nerve

Arcade of Frohse

Supinator muscle

Fig. 97.3.  Radial nerve, major branches, right arm, lateral view. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.)

BOX 97.6 

Isolated Mononeuropathies UPPER EXTREMITY

Radial nerve Axilla Humerus Elbow (posterior interosseous neuropathy) Wrist (superficial cutaneous radial neuropathy) Ulnar nerve Axilla Humerus Elbow Condylar groove Cubital tunnel Wrist (Guyon’s canal) Hand Superficial terminal ulnar neuropathy Deep terminal ulnar neuropathy: proximal hypothenar; distal hypothenar Median nerve Axilla Humerus (musculocutaneous mononeuropathy) Forearm Anterior interosseus Pronator syndrome Wrist (carpal tunnel) Hand (recurrent motor branch)

Suprascapular mononeuropathy Axillary mononeuropathy

LOWER EXTREMITY

Sciatic nerve Femoral nerve Iliacus compartment (proximal) Saphenous mononeuropathy (distal) Lateral femoral cutaneous (meralgia paresthetica) Peroneal nerve Common peroneal mononeuropathy (fibular head, popliteal fossa) Deep peroneal mononeuropathy (anterior compartment) Tibial nerve Popliteal fossa (proximal) Tarsal tunnel (distal) Sural nerve Popliteal fossa, calf (proximal) Fifth metatarsal base (distal) Plantar nerve Distal to tarsal tunnel Interdigital neuropathies (Morton’s neuroma) Obturator mononeuropathy

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sensation to the hand, the radial nerve makes a contribution only to a cutaneous dorsal area overlying the first dorsal interosseus muscle, sometimes extending part of the way up the dorsa of the thumb, index, and long fingers. Radial mononeuropathy caused by involvement at the level of the axilla is uncommon. When it occurs, it is usually associated with other upper extremity mononeuropathies or a brachial plexopathy. Although improper use of crutches may cause this syndrome, it usually occurs after an extended period of unconsciousness during which the arm is positioned in such a way that prolonged, deep compression is applied to the axilla. Axillary radial mononeuropathy is distinguished from the more common humeral form by the finding of triceps involvement in addition to typical wrist and finger drop. Triceps involvement occurs because the innervation to the triceps is proximal to the point where the nerve is most vulnerable as it winds around the humeral shaft (see Fig. 97.3). Most radial mononeuropathies are due to so-called Saturday night palsies. The euphemism is derived from the association of radial mononeuropathy with improper positioning of the arm during deep, commonly inebriated sleep. Consequently, the radial nerve is trapped for a prolonged period between the humeral shaft and some firm surface, causing an external compression mononeuropathy. “Bridegroom’s palsy” is another eponym for radial mononeuropathy, so named because the radial nerve may be compressed by the bride’s head resting on the bridegroom’s arm during sleep. Clinical Findings.  Because innervation of the wrist and finger extensors occurs distal to this area of the humeral shaft, findings are characterized by wrist and finger drop and mild numbness over the skin of the first dorsal interosseus muscle. Depending on the level, degree, and duration of compression, some fascicles of the nerve may remain functional, resulting in a partial radial mononeuropathy. Thus the superficial radial nerve may remain intact, resulting in no loss of sensation, or loss of wrist and finger extension may be incomplete. Because the finger drop of radial mononeuropathy places the hand at a mechanical disadvantage, examination of ulnar function by testing of the interossei may produce false-positive findings of weakness. To adjust for this, the examiner should ask the patient to place the palm on a horizontal supporting surface, such as a stretcher. With the fingers extended and no longer “dropped” at the metacarpophalangeal joints, interosseous strength can now be fairly tested. Failure to perform this maneuver may cause misdiagnosis of a simple radial mononeuropathy as a brachial plexopathy in an effort to explain what appears to be radial and partial ulnar nerve involvement. About 90% of radial nerve palsies occurring during sleep, coma, or anesthesia recover fully, usually within 6 to 8 weeks. Evidence of denervation on EMG studies predicts a slower rate of recovery. Tourniquet injuries to the radial nerve usually recover spontaneously within 2 to 4 months. If axonal degeneration is seen on electrophysiologic testing, recovery may take longer, although virtually all radial mononeuropathies caused by tourniquets eventually resolve. The radial nerve courses closely to the humerus, so it follows that about 22% of humeral shaft fractures are associated with radial nerve injury, with “wrist drop” the hallmark injury.12 Spontaneous resolution has been reported between 60% and 92%, so many authors suggest observation of these injuries is appropriate. In contrast, surgical intervention is needed to free the nerve from entrapment associated with complex fractures. Diagnostic Testing.  There exists no diagnostic test per se for this disease entity outside of the physical examination. EMG testing is employed to aid in predicting recovery times.

Management.  While patients are waiting for spontaneous recovery to occur, the hand should be maintained in about 60 degrees of dorsiflexion. Although a simple dorsal plaster or fiberglass splint treats the wristdrop, atrophy and contractures can be minimized and function of the hand can be improved if wide rubber bands anchored to the splint at a point proximal to the wrist are attached to individual fingers to provide passive dorsiflexion.

Ulnar Mononeuropathy Principles and Clinical Findings.  The ulnar nerve includes C7 to T1 roots and passes through the brachial plexus to descend medially, without branching, to the ulnar (medial) condylar groove at the elbow. It then enters the cubital canal, where it gives off branches to the ulnar wrist flexor and the deep flexors of the fourth and fifth digits. Just proximal to the wrist, two important sensory branches leave the main trunk to supply cutaneous sensation to part of the hand (Fig. 97.4). These are the palmar and dorsal cutaneous branches, which do not pass through Guyon’s canal. The palmar branch supplies sensation to the hypothenar eminence and the dorsal branch innervates the ulnar side of the dorsum of the hand, extending out nearly to the tip of the fifth and ulnar half of the fourth digit. At the wrist, the nerve enters Guyon’s canal (Fig. 97.5) between the pisiform and hook of the hamate, then bifurcates into the superficial terminal sensory branch and the deep motor branch. The superficial sensory nerve supplies ulnar sensation to the palmar side of the fifth and half of the fourth digit (see Fig. 97.5). The deep motor nerve supplies the hypothenar muscles, then crosses to the radial side of the palm to innervate the ulnar intrinsics (all interossei and the ulnar lumbricals of the fourth and fifth

Medial cord, brachial plexus

to Flexor carpi ulnaris to Flexor digitorum profundus (digits 4, 5) Palmar cutaneous branch Superficial terminal branch Deep motor branch

Dorsal ulnar cutaneous branch

Fig. 97.4.  Ulnar nerve, major branches, right arm, anterior view. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.)

CHAPTER 97  Peripheral Nerve Disorders

Superficial terminal branch Deep terminal branch Pisiform



3

4 2

Hamate 1

Fig. 97.5.  Distal ulnar nerve and branches, right hand, palmar view. Numbers indicate four main sites of distal ulnar mononeuropathy in the wrist and hand. Asterisk (*) denotes hypothenar branches. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.)

digits), terminating in the first dorsal interosseus. The interossei abduct and adduct the fingers and are all innervated by the ulnar nerve. The lumbrical muscles flex the metacarpophalangeal joints and are evenly divided between the ulnar (fourth and fifth) and median (second and third) digits. The ulnar nerve can be thought of as the complement to the median nerve in the hand, because it supplies all of the muscles and all palmar sensation not innervated by the median nerve. The ulnar nerve may be injured at two locations near the elbow: in the ulnar condylar groove and distally in the cubital canal. Because the condylar groove is shallow, the ulnar nerve runs superficially in this location and is vulnerable to injury, usually from external pressure or from a fracture or dislocation. The ulnar nerve has a propensity to develop a “tardy ulnar palsy,” occurring years after a traumatic event. Many of these delayed ulnar mononeuropathies can be localized to the elbow on electrophysiologic testing. Some ulnar mononeuropathies occur secondary to compression just proximal to entry into the cubital canal or are entrapped within the canal itself. Transient symptoms may occur during prolonged flexion or with repeated flexion and extension at the elbow. Although it is difficult to distinguish a condylar from a cubital ulnar mononeuropathy, it is usually possible to localize the problem to the region of the elbow or the wrist. In addition to prior probability heavily favoring the elbow, the presence of sensory abnormalities in an ulnar distribution in the hand and fingers (ie, usually including the fifth digit and “splitting” the fourth digit) strongly suggests that the lesion is at the level of the elbow rather than the wrist. The ulnar cutaneous innervation to the hand branches off from the main trunk proximal to the nerve entering Guyon’s canal (see Figs. 97.4 and 97.5). Thus a lesion at the wrist should not produce sensory abnormalities, whereas one at the elbow would be expected to do so. Compression of the ulnar nerve within Guyon’s canal is rare. When it does occur, it affects all of the ulnar intrinsics (ie, the two ulnar [fourth and fifth] lumbricals) and all the interossei. However, the ulnar extrinsics (ie, the deep flexors of the fourth and fifth digits) are not affected, nor is the ulnar flexor of the wrist. The only sensory abnormalities are those in the distribution of the

superficial terminal sensory branch, sparing other areas of ulnar innervation (see Fig. 97.5). There are three ulnar mononeuropathies that occur distal to Guyon’s canal in the hand. The two most common ones involve the deep terminal branch, either proximal or distal to the separation of the hypothenar branches (see Fig. 97.5). If the lesion is proximal, it produces weakness of all the ulnar-innervated muscles of the hand without sensory loss. If it is distal, the hypothenar ulnar intrinsics are spared, but the picture is otherwise similar. Usually, this occurs secondary to a laceration or repeated compression in the hand from use of certain tools, a cane, or the handle of a crutch. Involvement of the superficial terminal branch (see Fig. 97.5) produces a pure sensory loss of the palmar surface of the fifth digit and ulnar half of the fourth digit caused by direct compression of this branch just distal to Guyon’s canal. The dorsal surface of these two digits should have normal sensation except for the distal tips. This configuration of findings is due to the intact innervation provided by the dorsal and palmar cutaneous branches that enter the hand without passing through Guyon’s canal (see Fig. 97.4). Diagnostic Testing.  There exists no true diagnostic entity for this disease process outside of the physical examination. Management.  Most ulnar mononeuropathies will spontaneously resolve. However, if muscle atrophy, particularly in the hypothenar area, is detected, surgery may be considered. There is no noted difference in outcomes between the two surgical options of simple decompression and decompression with transposition.13

Median Mononeuropathy Principles.  The median nerve arises from the C5 to T1 spinal nerve roots and exits the brachial plexus through the lower trunk (Fig. 97.6). Median mononeuropathy is usually diagnosed as carpal tunnel syndrome (CTS), which is the most common of all entrapment neuropathies. CTS is estimated to occur in 3.8% of the United States population, with a prevalence of 9.2% in women and 6% in men.14 It is defined by the Academy of Orthopedic Surgeons as “a symptomatic compression neuropathy of the median nerve at the level of the wrist.” Clinical Findings.  Although the patient may complain of bilateral symptoms, a careful history usually reveals that symptoms in one hand preceded those in the other. A common symptom of CTS is awakening at night and shaking the hand. Symptoms are often worsened by activity. For unclear reasons, the pain may spread as high as the arm or shoulder, although the paresthesias are generally confined to the fingers. Many patients on initial questioning state that their entire hand is involved, although this is not supported by careful sensory examination. Patients frequently note that their hands are clumsy or weak, especially when holding a glass or opening a screw-top container.15 The skin of the fingers innervated by the median nerve may be drier and rougher to the touch than the corresponding ulnar skin, depending on the duration of entrapment. When motor involvement occurs in CTS, it is confined to the median intrinsics, which innervate the lumbricals (flexion of the metacarpophalangeal joints) and subserve thumb opposition, abduction, and flexion, known as the LOAF muscles. However, the hallmark of CTS is sensory involvement, with motor abnormalities occurring later. The typical pattern of sensory innervation of the hand by the median, ulnar, and radial nerves shows marked individual variation. The most specific finding for CTS is splitting of the fourth digit (ie, normal sensation of the ring finger on the ulnar palmar side with abnormal sensation on the median [radial]

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Pronator teres muscle (superficial and deep heads) Anterior interosseous nerve “Sublimis bridge”

Flexor digitorum superficialis muscle

Palmar cutaneous branch Transverse carpal ligament

Fig. 97.6.  Median nerve, major branches, right arm, anterior view. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.)

BOX 97.7 

Conditions Associated With Carpal Tunnel Syndrome Acromegaly Amyloid Diabetes mellitus Hypothyroidism Obesity Pregnancy Renal failure Rheumatoid arthritis

palmar side of the same finger). The most sensitive finding is abnormal sensation of the distal palmar tip of the index finger. If sensory findings are absent in the presence of motor findings consistent with median nerve involvement, it is highly unlikely that the patient has CTS, and an alternative diagnosis should be sought. CTS appears to be associated with the conditions listed in Box 97.7. Of these, the two most common are diabetes mellitus and pregnancy.16 CTS associated with systemic illness is commonly bilateral. CTS in pregnancy appears to be common, but the prevalence varies widely literature from 31% to 62%.17 Most cases of pregnancy related CTS resolve spontaneously, up to 85% in some studies.

Diagnostic Testing.  Tinel’s sign (percussion of the median nerve at the wrist) and Phalen’s sign (maximal palmar flexion at the wrist) have been classically taught as provocative tests to reproduce the sensory symptoms of CTS if neither sensory nor motor symptoms are evident on initial examination. However, more recent evaluation has shown that Tinel’s and Phalen’s signs do not have adequate sensitivity or specificity to determine which patients should be referred for electrodiagnostic studies. Dropping of objects is indicative of severe CTS. The best way to examine patients for sensory findings is to touch the distal palmar tips very lightly, asking the patient whether the sensation feels “abnormal.” NCS is considered to be the gold standard in the diagnosis of CTS, because it is an objective test that provides information on the physiological health of the median nerve across the carpal tunnel. Magnetic resonance imaging (MRI) allows for good imaging of the soft tissue structures of the carpal tunnel and revealing the cause of the nerve compression. It has a sensitivity of 96% but a specificity of 33% to 38%.16 Ultrasonography has been shown to be useful, particularly in patients with symptoms and a normal NCS. The most reliable ultrasonographic measurement is to obtain the cross-sectional area of the median nerve at the level of the pisiform. Thus, if all diagnostic studies in a symptomatic patient have normal findings, or if only the MRI result is abnormal, they should be repeated within a few months if symptoms do not resolve. This recommendation is based on the theory that the CTS will progress over time to the point that an objective indicator, such as the NCS, will become positive. Management.  There are a variety of nonsurgical treatments, with splinting and steroid injections being the most common. Neutral wrist splinting has commonly been used as the initial treatment, but a recent Cochrane review found poor evidence to support this being more effective than no treatment in the short term.18 Steroid injection has been shown to be a temporizing measure in the treatment of CTS. One recent study using methylprednisolone showed significant symptom relief at 10 weeks and also reduced the rate of surgery at 1 year.19 Because of the possibility of a disabling “median hand” after inadvertent direct injection of the median nerve, it is recommended that emergency clinicians defer the injection of the carpal tunnel with steroids to the consulting hand surgeon. This physician can obtain NCS and determine splinting, injection, or surgical division of the transverse carpal ligament is indicated. Surgical treatment involves the division of the transverse carpal ligament, which reduces pressure on the median nerve by increasing the space in the carpal tunnel. This carpal tunnel “release” surgery can be performed open or endoscopic with no significant difference in outcomes noted.16

Sciatic Mononeuropathy Principles.  The sciatic nerve includes L4 to S3 spinal nerve roots that pass through the lumbosacral plexus and divides into two terminal branches: the common peroneal and tibial nerves. The nerve exits the pelvis through the sciatic notch, passes behind the hip, and remains deep in the thigh until its terminal bifurcation in the proximal popliteal fossa (Fig. 97.7). Lesions of the sciatic nerve occur with posterior hip dislocation or with virtually any form of penetrating or blunt trauma that causes formation of a buttock hematoma. Other causes include deep gluteal injection and prolonged supine immobilization on a firm surface. Because the sciatic nerve innervates the hamstrings and provides all sensorimotor function distal to the knee, a complete sciatic mononeuropathy is a devastating injury. Clinical Findings.  Ambulation is extremely difficult because of inability to flex the knee and a flail foot (ie, neither flexion nor

CHAPTER 97  Peripheral Nerve Disorders

Superior gluteal nerve

Sciatic nerve

Sciatic nerve Inferior gluteal nerve

Post. cutaneous nerve of thigh

Tibial nerve Common peroneal nerve

Fibular tunnel Peroneus longus muscle

Semitendinosus

Superficial peroneal nerve

Semimembranosus Biceps, long head

Biceps, short head

to Peroneus brevis

Adductor magnus

Deep peroneal nerve to Tibialis anterior to Extensor digitorum longus to Extensor hallucis longus

Tibial nerve Common peroneal nerve

to Extensor digitorum brevis

Fig. 97.8.  Common peroneal nerve, major branches, right leg, anterolateral view. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.) Fig. 97.7.  Sciatic nerve, major branches, right leg, posterior view. (From Stewart JD: Focal peripheral neuropathies, ed 3, Philadelphia, 2000, Lippincott Williams & Wilkins.)

Diagnostic Testing.  There is no diagnostic test for this disease process outside of the physical examination. extension is possible at the ankle). Fortunately, many sciatic mononeuropathies are incomplete. For unknown reasons, a partial lesion typically involves only the trunk of the sciatic nerve, which subsequently becomes the common peroneal nerve, sometimes making the two difficult to distinguish from one another clinically. Diagnostic Testing.  This condition is mainly diagnosed by physical findings. If used, electrophysiologic studies show evidence of involvement of gluteal muscles or of any muscles innervated by the tibial nerve. This readily distinguishes a partial sciatic mononeuropathy from a lesion of the common peroneal nerve. Management.  Treatment of footdrop requires a posterior splint to maintain the ankle at 90 degrees until a brace can be obtained (see the Common Peroneal Mononeuropathy section).

Lateral Femoral Cutaneous Mononeuropathy Principles.  Lateral femoral cutaneous mononeuropathy (meralgia paresthetica) is a common syndrome believed to be caused by injury to this pure sensory nerve as it passes through or over the inguinal ligament, where it may become entrapped or kinked. Along with facial nerve neuropathy, meralgia paresthetica is one of the most commonly reported mononeuropathies associated with HIV infection. Clinical Findings.  Numbness and dysesthesia over the skin of the upper lateral thigh is typically found on physical examination.

Management.  Regression usually occurs spontaneously, but recurrence is common and may require a release procedure for the inguinal ligament.

Common Peroneal Mononeuropathy Principles.  The common peroneal nerve is a continuation of one trunk of the sciatic nerve. It is most vulnerable to injury where it winds around the fibular neck (Fig. 97.8). It then passes through the fibular canal and bifurcates into its terminal branches, the superficial and deep peroneal nerves. The superficial peroneal nerve innervates the peroneal muscles (foot everters) and supplies sensation to the lateral, distal lower leg and dorsum of the foot. The deep peroneal nerve traverses the anterior compartment and supplies innervation to the dorsiflexors of the foot and toes plus cutaneous sensation between the first and second toes. Most common peroneal mononeuropathies are idiopathic and thought to be related to compression where the nerve is superficially located lateral to the fibular neck. Because this common neuropathy is often noted on awakening, it may be secondary to position during sleep. Leg crossing may also be a risk factor for development of this mononeuropathy. Clinical Findings.  The most striking feature of a complete common peroneal mononeuropathy is footdrop caused by weakness of foot dorsiflexion. At testing, the everters of the foot are also weak, but the inverters, which are innervated by the tibial nerve, remain strong. This is the single most reliable clinical feature distinguishing sciatic from common peroneal mononeuropathy. Analogous to radial mononeuropathy in the upper

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extremity, sensory abnormalities in the leg and foot are inconstant and easily overlooked in peroneal mononeuropathy. Diagnostic Testing.  Most patients with peroneal palsy recover. Those who do not should be studied electrophysiologically to ensure that the point of compression is not proximal to the fibular neck (ie, in the popliteal fossa). If the point of peroneal injury appears to be in the region of or distal to the fibular neck on EMG, patients whose footdrop does not resolve should be considered candidates for exploration to determine whether the nerve is compressed within the fibular canal. Management.  Treatment of common peroneal palsy requires a posterior splint to maintain the ankle at 90 degrees until the nerve regenerates. This splinting prevents the foot from falling into sustained equinus (plantar flexion), which in turn allows the intermalleolar distance to narrow, effectively locking the talus out of the ankle mortise. The treatment of isolated mononeuropathies depends on their etiology, location, and natural history of spontaneous recovery. All penetrating neuropathies should have surgical exploration and repair performed. Blunt trauma may cause a mononeuropathy indirectly by entrapment of a nerve within a fracture, hematoma, or compartment, requiring surgical intervention. Alternatively, nerves may be injured at a point where they are superficial, either by a single direct blow or by sustained pressure caused by immobility (pressure palsies). Most of these resolve spontaneously over time, depending on the severity of injury and length of the nerve. If entrapment can be confirmed by imaging or electrophysiologic studies, a release procedure is indicated. The mononeuropathies that do not require timely surgical exploration should be referred for further evaluation to confirm the location of the neuropathic lesion.

Type 5: Mononeuropathy Multiplex Principles Mononeuropathy multiplex is characterized by an asymmetrical, sensorimotor, usually distal pattern of peripheral neuropathy (Box 97.8). Common causes include vasculitis, diabetes, and Lyme disease.

Clinical Findings As with isolated mononeuropathies, sensory abnormalities tend to be located in the same general anatomic region as the accompanying motor findings. Whether DTRs are affected depends on which nerves are involved. For example, if the process includes the femoral nerve, the patellar reflex is likely to be diminished or absent. Lyme Disease.  The PNS manifestations of Lyme disease are divided into early and late. The early PNS syndromes commonly include facial nerve involvement (rarely other cranial nerve palsies) and radiculoneuritis. Late PNS involvement occurs as a DSPN, mononeuropathy multiplex, or radiculoneuropathy. The most common neurologic abnormality in Lyme disease is unilateral or bilateral facial nerve palsy, usually occurring within a month of exposure. Patients may also complain of headache and constitutional symptoms. Early in the course of Lyme disease, severe neuritic pain may develop in a radicular distribution, often in or near the dermatome where the tick bite occurred. There may also be associated sensory changes, motor weakness, and decreased reflexes consistent with nerve root involvement. Patients with chronic Lyme disease present with sensory symptoms, particularly distal paresthesias in the lower extremities. Less commonly, they develop a picture consistent with mononeuropathy multiplex or a radiculopathy, which is much less severe than the early radiculoneuritis of Lyme disease. The diagnosis and management of Lyme disease is discussed in Chapter 126.

Diagnostic Testing Vasculitis related multiple mononeuropathy is diagnosed with a sural nerve biopsy. The most useful diagnostic tests for patients with suspected Lyme disease are a serum enzyme-linked immunosorbent assay, Western blot, and CSF examination. CSF abnormalities suggestive of Lyme disease are a lymphocytic pleocytosis, elevated protein level, and normal glucose concentration. The CSF is almost always abnormal in early radiculitis, sometimes abnormal with isolated facial palsy, and typically normal in chronic Lyme disease.

Management BOX 97.8 

Mononeuropathy Multiplex Vasculitis Systemic vasculitis Polyarteritis nodosa Rheumatoid arthritis Systemic lupus erythematosus Sjögren’s syndrome (keratoconjunctivitis sicca) Nonsystemic vasculitis Diabetes mellitus Neoplastic Paraneoplastic Direct infiltration Infectious Lyme disease HIV infection Sarcoid Toxic (lead) Transient (polycythemia vera) Cryoglobulinemia (hepatitis C) HIV, Human immunodeficiency virus.

Facial nerve palsy in Lyme disease without CSF abnormalities may be treated with oral doxycycline 100 mg twice a day for 2 weeks. Intravenous (IV) ceftriaxone is the drug of choice for all other neurologic syndromes associated with Lyme disease. The adult dosage is 2 g/day, and the pediatric dosage is 75 to 100 mg/kg per day. The standard course of treatment with IV ceftriaxone is at least 2 weeks.

Type 6: Amyotrophic Lateral Sclerosis Principles Although amyotrophic lateral sclerosis (ALS) and motor neuron disease (MND) are often used synonymously, the latter represents a spectrum of diseases ranging from primary lateral sclerosis, in which degeneration is confined to upper motor neurons, to progressive muscle atrophy, in which only lower motor neurons are involved. ALS, which requires the presence of both upper and lower motor neuron findings, resides in the middle of this spectrum, representing the most common form of MND. The incidence of ALS is 1.5 to 2.5 per 100,000. Most develop symptoms in middle-adult life, with motor weakness in the extremities,

CHAPTER 97  Peripheral Nerve Disorders

BOX 97.9 

BOX 97.10 

Objective Clinical Findings Consistent With Amyotrophic Lateral Sclerosis

Sensory Neuronopathies (Ganglionopathies)

UPPER MOTOR NEURON SIGNS

Hyperreflexia Sustained clonus, especially at ankle Finger flexors and jaw jerk Spasticity, especially of gait Presence of Babinski’s sign

LOWER MOTOR NEURON SIGNS Positive motor phenomena Fasciculations Cramps Negative motor phenomena Asymmetrical distal weakness Atrophy

COMBINED UPPER AND LOWER MOTOR NEURON SIGNS Dysarthria Dysphagia Respiratory compromise

spasticity, paralysis, and eventually death, typically within 3 to 5 years of symptom onset.20 In ALS, the primary pathologic process in the PNS component of the disease is a neuronopathy of the anterior horn cell. Because this structure is located proximal to the point where motor and sensory fibers merge to form mixed spinal nerve roots, the signs and symptoms of MND are purely motor (see Fig. 97.2). In the CNS, there is a loss of Betz cells from the motor cortex with secondary degeneration of the corticospinal tracts.

Clinical Findings Box 97.9 lists some representative upper, lower, and mixed motor signs. Patients typically demonstrate asymmetrical distal weakness without sensory findings. Positive motor phenomena in the form of fasciculations are found in almost all patients at diagnosis but are rarely an initial complaint. Although there is electrophysiologic evidence of autonomic involvement in ALS, this is generally subclinical.

Diagnostic Testing All patients in whom this diagnosis is suspected should be referred for electrophysiologic confirmation against standardized criteria, with denervation combined with the physical findings typically confirming the diagnosis. Confirmation is particularly important because multifocal motor neuropathy, a rare disease that masquerades as ALS, responds dramatically to cyclophosphamide and immune globulin administration.

Herpes Herpes simplex 1 and 2 Varicella-zoster (shingles) Inflammatory sensory polyganglionopathy Paraneoplastic Primary biliary cirrhosis Sjögren’s syndrome (keratoconjunctivitis sicca) Toxin induced Pyridoxine (vitamin B6) overdose Metals Platinum (cisplatin) Methyl mercury Vitamin E deficiency

Management The only drug to demonstrate survival benefit in humans with ALS is riluzole, prolonging mean survival from 12 to 15 months.21 The development of a multidisciplinary team approach has had a much higher impact on overall quality of life for patients with ALS. This team includes ALS-focused neurologists, nurses, occupational therapy, and speech therapy amongst others.22

Type 7: Sensory Neuronopathy (Ganglionopathy) Principles This category of peripheral neuropathy is characterized by a selective or predominant involvement of the dorsal root ganglion, producing a relatively pure sensory syndrome analogous to the pure motor syndrome of ALS.

Clinical Findings Although all sensory modalities are affected, proprioception is profoundly altered, leading to sensory ataxia and loss of DTRs without weakness. The distribution is typically asymmetrical and distal at the outset, but depending on severity and extent of progression, it may become functionally symmetrical.

Diagnostic Testing Sensory ganglionopathies can be confirmed by MRI of the spinal cord and surrounding areas, showing degeneration of central sensory projections that localize the disease process to the dorsal root ganglion. Some of the more common causes of this type of peripheral neuropathy are listed in Box 97.10.

Management The management of sensory neuropathies is symptomatic in nature and best left to the patient’s primary physician.

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KEY CONCEPTS • It is not usually possible to arrive at the diagnosis of a specific peripheral neuropathy in the ED because of the need for confirmatory ancillary testing. One should focus on identifying one of seven categorical patterns of peripheral neuropathy, shown in Figure 97.1 and listed in Table 97.1. • One of these seven patterns can usually be identified by combining three clinical features that are readily obtainable from a goaldirected history and physical: (1) right-left symmetry or asymmetry, (2) proximal-distal location, and (3) sensorimotor modalities affected. • Identification of the type of peripheral neuropathy determines the need for ancillary diagnostic testing, therapeutic intervention, disposition, and timing of neurologic referral. • Any patient with symmetrical weakness, distributed both proximally and distally, with loss or diminution of DTRs and variable sensory abnormalities should be treated as having GBS. • Respiratory compromise is the primary life-threatening event seen in some peripheral neuropathies; GBS is by far the most common peripheral neuropathic cause of respiratory arrest. • The definitive treatments for GBS are plasma exchange or intravenous immune globulin (IVIG). • Most polyneuropathies are characterized by a pattern of distal, symmetrical sensorimotor findings, worse in the lower than in the upper extremities, with a stocking-glove distribution of sensory abnormalities that gradually diminishes as one moves proximally. • High level evidence supports the use of tricyclic antidepressants, anticonvulsants, and the serotonin and norepinephrine reuptake inhibitor nuloxetine treating diabetic DSPN.

• Radial nerve mononeuropathies are characterized by wrist and finger drop and mild numbness over the skin of the first dorsal interosseus muscle. • Humeral shaft fractures are associated with radial nerve injury, with “wrist drop” the hallmark clinical finding. • The ulnar cutaneous innervation to the hand branches from the main trunk proximal to the nerve entering Guyon’s canal thus a lesion at the wrist should not produce sensory abnormalities, whereas one at the elbow would be expected to do so. • The most specific finding for carpal tunnel syndrome (CTS) is splitting of the fourth digit (ie, normal sensation of the ring finger on the ulnar palmar side with abnormal sensation on the median [radial] palmar side of the same finger). • Lateral femoral cutaneous mononeuropathy (meralgia paresthetica) is caused by injury to this pure sensory nerve as it passes through or over the inguinal ligament, where it may become entrapped or kinked. • The most striking feature of a complete common peroneal mononeuropathy is footdrop caused by weakness of foot dorsiflexion. • The most common neurologic abnormality in Lyme disease is unilateral or bilateral facial nerve palsy, usually occurring within a month of exposure. • ALS requires the presence of both upper and lower motor neuron findings, and is the most common form of motor neuron disease (MND).

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Sejvar JJ, et al: Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology 36(2):123–133, 2011. 2. Poropatich KO, et al: Quantifying the association between Campylobacter infection and Guillain-Barré syndrome: a systematic review. J Health Popul Nutr 28:545–552, 2010. 3. Walgaard C, et al: Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol 67:781–787, 2010. 4. Kannan Kanikannan MA, et al: Simple bedside predictors of mechanical ventilation in patients with Guillain-Barré syndrome. J Crit Care 29:219–223, 2014. 5. Deleted in review. 6. Winters JL, et al: Cost-minimization analysis of the direct costs of TPE and IVIg in the treatment of Guillain-Barré syndrome. BMC Health Serv Res 11:101–109, 2011. 7. Kasznicki J: Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy. Arch Med Sci 10(2):345–354, 2014. 8. Tesfaye S, et al: Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments on behalf of the Toronto Diabetic Neuropathy Expert Group. Diabetes Care 33:2285–2293, 2010. 9. Ko SH, et al: Comparison of the efficacy and safety of tramadol/acetaminophen combination therapy and gabapentin in the treatment of painful diabetic neuropathy. Diabet Med 27:1033, 2010. 10. Schwartz S, et al: Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin 27:151, 2011.

11. Kuhn JE, et al: Thoracic outlet syndrome. J Am Acad Orthop Surg 23:222–232, 2015. 12. Ljungquist KL, et al: Radial nerve injuries. J Hand Surg Am 40:166–172, 2015. 13. Caliandro P, et al: Treatment for ulnar neuropathy at the elbow. Cochrane Database Syst Rev (7):CD006839, 2012. 14. Ghasemi-Rad M, et al: A handy review of carpal tunnel syndrome: From anatomy to diagnosis and treatment. World J Radiol 6:284–300, 2014. 15. Pazzaglia C, et al: “Dropping objects”: a potential index of severe carpal tunnel syndrome. Neurol Sci 31:437, 2010. 16. Ibrahim I, et al: Carpal tunnel syndrome: a review of the recent literature. Open Orthop J 6:69–76, 2012. 17. Padua L, et al: Systematic review of pregnancy-related carpal tunnel syndrome. Muscle Nerve 42:697, 2010. 18. Page MJ: Splinting for carpal tunnel syndrome. Cochrane Database Syst Rev (7):CD010003, 2012. 19. Atroshi I: Methylprednisolone injections for the carpal tunnel syndrome: a randomized, placebo-controlled trial. Ann Intern Med 159:309–317, 2013. 20. Wood LK, et al: Motor neuron disease: a chemical perspective. J Med Chem 57(15):6316–6331, 2014. 21. Bäumer D, et al: Advances in motor neurone disease. J R Soc Med 107:14–21, 2014. 22. Hardiman O, et al: Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 7:639–649, 2011.

CHAPTER 97: QUESTIONS & ANSWERS 97.1. Which category of peripheral neuropathy tends to occur in an asymmetrical, distal distribution? A. Autonomic neuropathy B. Large-fiber neuropathy C. Mixed motor and sensory neuropathy D. Neuropathy from vasculitis E. Pure motor neuropathy Answer: E. Pure motor and pure sensory peripheral neuropathies tend to occur in an asymmetrical distal pattern. 97.2. A 26-year-old woman presents with a chief complaint of weakness. She notes a 1- or 2-day onset of easy fatigability and diminished ability to navigate stairs. She has no past history and takes no medications. Vital signs are normal. Physical examination reveals absent lower extremity deep tendon reflexes (DTRs); symmetrical weakness of the quadriceps, calf muscles, and foot/toe dorsiflexion; and minimal sensory loss. Cranial nerve and upper extremity examination is normal. Which of the following is likely? A. An antecedent viral illness B. Lack of anal sphincter tone C. Onset of ocular muscle dysfunction D. Sparing of the autonomic nervous system E. Urinary retention Answer: A. Guillain-Barré syndrome (GBS) is characterized by fairly acute onset of ascending weakness, loss of deep tendon reflexes (DTRs), and variable sensory loss. Antecedent infections often trigger, with common organisms being campylobacter, cytomegalovirus, Epstein-Barr virus, and mycoplasma. Rarely, symptoms begin in the upper extremities. Urinary retention is common, but anal tone is preserved. Ocular muscles are usually spared. Autonomic neuropathy is common, with marked variations in heart rate and blood pressure. Patients with predominantly sensory symptoms tend to have less risk of respiratory embarrassment and a more favorable prognosis. Lumbar puncture shows cerebrospinal fluid (CSF) pleocytosis or may be normal early on. 97.3. A 26-year-old woman presents with lower extremity weakness and difficulty walking. Examination is remarkable for lower extremity symmetrical weakness with mild symmetrical sensory loss and absent lower

extremity deep tendon reflexes (DTRs). Symptom onset has been during 2 days. What should be the next step? A. Emergent magnetic resonance imaging (MRI) B. Intravenous immune globulin (IVIG) C. Lumbar puncture and antibiotics D. Pulmonary function studies E. Urgent neurologic consultation Answer: D. All patients with Guillain-Barré syndrome (GBS) are at risk of respiratory failure. A forced vital capacity (FVC) of less than 20 mL/kg and a negative inspiratory force of less than 30 cm H2O are associated with impending ventilatory failure and the need for intubation. 97.4. Among patients with Guillain-Barré syndrome (GBS) who have normal pulmonary function, which of the following can be monitored to predict impending ventilatory failure? A. Deltoid strength B. Extensor neck strength C. Hand grip strength D. Masseter strength E. Rectus abdominis strength Answer: B. Extensor muscle strength has been shown to correlate with ventilatory muscle strength. 97.5. A 53-year-old diabetic presents with a complaint of increasing difficulty walking in the last several months. He has no other past history but has been an insulindependent diabetic for 23 years. Current glucose level is 138 mg/dL, and chemistries and complete blood count are otherwise unremarkable. Examination is remarkable for bilateral lower extremity numbness extending symmetrically to above the knees, loss of the Achilles reflex bilaterally with footdrop, and steppage gait. Which of the following is true? A. Autonomic neuropathy is unlikely. B. Facial numbness would necessitate MRI. C. Hand numbness is expected. D. Erythrocyte sedimentation rate is likely to be elevated. E. Lumbar spine MRI will likely show a pathologic process.

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Answer: C. Diabetic neuropathy is a progressive, ascending mixed polyneuropathy. Hand numbness and upper extremity symptoms usually begin before the lower extremity symptoms ascend to the knees. Extensive motor loss can occur with gait and grip abnormalities. Skull and face numbness can occur. Autonomic dysfunction is expected. 97.6. A 53-year-old diabetic presents with increasing symmetrical dysesthetic pain from his well-documented severe diabetic neuropathy. His only medications are insulin and over-the-counter analgesics. Laboratory evaluation is remarkable for a glucose concentration of 183 mg/dL and a creatinine level of 2.1 mg/dL with normal chemistries. Which of the following is indicated as a first-line analgesic in this patient? A. Amitriptyline B. Hydrocodone with acetaminophen C. Naprosyn sodium D. Paroxetine E. Tramadol Answer: A. First-line agents for neuropathic pain are the anticonvulsants and cyclic antidepressants. Specifically, gabapentin, pregabalin, amitriptyline, imipramine, and nortriptyline are useful. Tramadol and opiates may be effective but less so. Tramadol is renally excreted (as is gabapentin), and doses must be adjusted for falling creatinine clearances. Nonsteroidal antiinflammatory drugs (NSAIDs) do not have great usefulness for neuropathic pain (there is no “inflammatory” component) and would be contraindicated with elevated creatinine. Opiates may be beneficial, but issues of tolerance are significant. Selective serotonin reuptake inhibitors may be effective but are second-line agents (the norepinephrine-modulating ability of tricyclic antidepressants makes them more effective analgesics than the serotonin-specific agents). 97.7. Which of the following characteristics separates the clinical picture of alcoholic versus diabetic neuropathy? A. Autonomic changes B. Incontinence C. Myopathy D. Sensory loss E. Weakness

Answer: C. The presence of myopathy and cerebellar degeneration helps distinguish alcoholic neuropathy. Otherwise, the clinical pictures are similar. Incontinence is not a typical feature of either. 97.8. What is the most common neurologic complication of HIV infection? A. Autonomic neuropathy B. Cerebellar dysfunction C. Cranial nerve dysfunction D. Peripheral neuropathy E. Spinal anterior horn degeneration Answer: D. It is typically a distal mixed motor and sensory polyneuropathy. It is triggered by a combination of poorly defined immune mechanisms and dideoxynucleoside therapy. 97.9. A 53-year-old woman presents with progressive pain involving her left shoulder and upper arm. She describes a deep aching pain that is poorly localized and is occasionally accompanied by tingling sensations in the left hand in a nondermatomal pattern. Her medical history is negative except for a history of left-sided breast cancer 6 years prior for which she underwent a total mastectomy followed by field irradiation and oral antiestrogen therapy. She currently takes no medications. Review of systems and laboratory results are negative. Physical examination shows only left shoulder dysesthesias. The chest radiograph is normal. What should be the next step? A. Computed tomography scan of the chest B. Gabapentin in titrated doses C. Hydrocodone with acetaminophen and reassurance D. MRI scan of the brachial plexus E. Referral for upper extremity electromyography (EMG) and nerve conduction studies (NCSs) Answer: D. Although plexopathies are most commonly posttraumatic, radiation, postviral, and infiltrative processes also occur. In a patient who is status post an oncologic diagnosis and radiation therapy, oncologic recurrence must be ruled out with an imaging study. Radiation plexopathy, which can occur up to 20 years out, is most often a diagnosis of exclusion and ultimately requires symptomatic treatment of neuropathic pain.

C H A P T E R 98 

Neuromuscular Disorders Peter Shearer PRINCIPLES Disorders of the neuromuscular unit can result in clinical presentations that range from subtle symptoms to acute respiratory failure with significant morbidity and mortality. In most cases, the pathophysiologic mechanism of these disorders is well understood and permits an organization and understanding based on the level of the nervous system affected. This facilitates an approach that interprets signs and symptoms, the findings of which direct the urgency of diagnostic testing and treatment. The neuromuscular unit has four components: the anterior horn cells of the spinal cord, the peripheral nerve, the neuromuscular junction, and the muscle innervated. The level of the pathologic process determines associated signs and symptoms (Fig. 98.1 and Table 98.1). Myelopathies involve the spinal cord; radiculopathies involve the nerve roots as they leave the spinal cord; neuropathies involve the peripheral nerves; and myopathies involve the muscle. The use of physical signs to differentiate these disorders is discussed in Chapter 10. Neuropathies involve the axon or the myelin sheath of the nerve. Nerve conduction studies can differentiate the locations of involvement. As the conduction along the axon is disrupted, the subsequent delay in transmission first causes symptoms in the muscles controlled by longer nerve axons, resulting in a history of ascending weakness. As the myelin destruction or axonal degeneration progresses, patients usually note a slowly progressive course of symptoms. The neuromuscular junction is composed of the presynaptic membrane, the postsynaptic membrane, and the synaptic cleft. The neurotransmitter is acetylcholine (ACh). The motor synapse is a nicotinic receptor, whereas muscarinic synapses link the central nervous system (CNS) with the autonomic nervous system. Disorders of the postsynaptic nicotinic receptors produce weakness. Postsynaptic ACh receptors are continually turned over at a rate that is related to the amount of stimulation. A disorder of transmission often leads to increased production of ACh receptors. Myasthenia gravis is the prototype of neuromuscular junction diseases.

Historical elements might explain the presenting complaint: a preexisting neuromuscular disorder that could lead to deterioration; prior episodes or a family history of weakness suggesting periodic paralysis; a recent respiratory or diarrhea illness suggesting a postinfectious, autoimmune process, such as Guillain-Barré syndrome or enterovirus D68, which has been reported to cause muscle weakness and paralysis in children; a cancer history suggesting a metastatic tumor as the cause of a compressive myelopathy; and a food or travel history suggesting botulism or tick exposure.1

Physical Examination

CLINICAL FEATURES

The examination should first assess the patient’s ability to breathe and ventilate and then evaluate the degree of weakness and the location of the lesion. The presence of swallowing and a strong cough suggest that the patient has sufficient protective and ventilatory reserve. The muscles used to lift the head off the bed may weaken before those of respiration and should be assessed. A patient who is not yet intubated but is complaining of shortness of breath or difficulty in breathing should have frequent measurements of forced vital capacity (FVC). Normal FVC ranges from 60 to 70 mL/kg; when the FVC reaches 15 mL/kg, ventilatory support is necessary. If vital capacity cannot be measured, a maximal negative inspiratory force (NIF) is easily determined. NIF of less than 15 cm H2O suggests the need for intubation. Blood gas analysis is not helpful because functional reserve can be severely diminished by the time a patient has either hypercarbia or hypoxia. Some causes of weakness may result in dysregulation of the autonomic system and abnormal vital signs. A systematic neurologic examination assesses the patient’s mental status, cranial nerves, motor and sensory function, deep tendon reflexes, and coordination, including cerebellar function. The motor examination begins by determining whether the weakness is unilateral or bilateral and which muscle groups are involved. Key components of the examination include motor strength, muscle bulk, and presence of fasciculations. Box 98.1 provides the grading system used in motor strength assessment. Table 98.2 provides the findings used to distinguish upper motor neuron from lower motor neuron processes.

History

DIFFERENTIAL DIAGNOSIS

The history of patients with complaints of weakness focuses on the acuity and the potential for airway compromise. Any complaint of difficulty in breathing or swallowing raises suspicion of bulbar involvement and concern for life-threatening deterioration. Weakness is the inability to exert normal force, whereas fatigue implies a decrease in force with repetitive use and the clinical history should distinguish which is present. When muscle weakness exists, the clinician should determine whether it is focal or generalized, proximal or distal. The history of present illness should include the duration of symptoms, exacerbating and mitigating factors, and presence of associated symptoms, such as fever, weight loss, and bowel or bladder changes.

Myelopathies Myelopathies are spinal cord disorders that are manifested with signs of upper motor neuron dysfunction, such as muscle weakness with increased spinal reflexes, including an extensor plantar reflex (Babinski’s response). There may be bladder and bowel involvement. When sensory findings are present, they often define the level of the lesion. The presence of back pain suggests a compressive lesion, such as a herniated intravertebral disk, epidural hematoma, abscess, or tumor. Acute, painless spinal cord lesions include transverse myelitis and spinal cord infarction. Myelopathies are discussed in Chapter 96. 1321

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Motor Neuron Disease The characteristic findings of motor neuron disease combine signs of both upper and lower motor neuron dysfunction, including hyperreflexia, muscle wasting, and fasciculations. Pain is not a component of the clinical picture. Amyotrophic lateral sclerosis is the prototypical motor neuron disease Root (ie, radiculopathy) Dorsal root ganglion (ie, sensory ganglioneuronopathy) Root (ie, radiculopathy)

Anterior horn cell (ie, SMA, ALS)

Plexus (ie, radiation plexitis) Autonomic nerve

Peripheral nerve (ie, demyelinating neuropathies, axonal neuropathies)

Unmyelinated fiber

Myelinated fibers (ie, demyelinating neuropathies CIDP)

Poliomyelitis affects the anterior horn cells and results in lower motor neuron disease without sensory involvement. The weakness can be symmetrical, although more often it is asymmetrical. Patients initially have a clinical picture similar to that of viral meningitis with fever and neck stiffness. Currently, most cases follow exposure of an immunocompromised host to the oral polio vaccine, and this should be sought in the history. The cerebrospinal fluid (CSF) analysis resembles that of viral meningitis.

Neuropathies Weakness from a neuropathy is often noted first in distal muscles and then ascends. Decreased grip strength and foot drop are common presentations. The differential diagnosis includes Guillain-Barré syndrome, toxic neuropathies, diabetic neuropathy, and tick paralysis (which is caused by inhibition of both nerve conduction and function of the neuromuscular junction). Neuropathies are discussed in Chapter 97.

Diseases of the Neuromuscular Junction Disorders of the neuromuscular junction cause motor fatigability. The initial depolarization at the nerve endplate stimulates a

Neuromuscular junction (ie, Eaton-Lambert syndrome, myasthenia gravis)

BOX 98.1 

Grading Score for Motor Strength

Muscle (ie, myopathies) Fig. 98.1.  The anatomic elements of the peripheral nervous system and related neurologic disorders. ALS, Amyotrophic lateral sclerosis; CIDP, chronic inflammatory demyelinating polyneuropathy; SMA, spinal muscular atrophy. (From Bertorini TE: Neuromuscular anatomy and function in neuromuscular case studies. In: Neuromuscular case studies, Philadelphia, 2008, Butterworth-Heinemann/Elsevier.)

5 = Normal strength 4 = Weak but able to resist examiner 3 = Moves against gravity but unable to resist examiner 2 = Moves but unable to resist gravity 1 = Flicker but no movement 0 = No movement

TABLE 98.1 

Clinical Characteristics of Neuromuscular Diseases DISEASE

HISTORY

STRENGTH

DEEP TENDON REFLEX SENSATION

Myelopathy

Trauma, infection, cancer

Normal to decreased Increased

Motor neuron disease (ALS) Progressive difficulty swallowing, Decreased speaking, walking

WASTING

Normal to decreased No

Increased

Normal

Yes

Neuropathy

Recent infection Ascending weakness

Normal or decreased Decreased Distal > proximal

Decreased

Yes

Neuromuscular junction disease

Food (canned goods) Tick exposure Easy fatigability

Normal to fatigue

Normal

Normal

No

Myopathy

Thyroid disease Previous similar episodes

Decreased Proximal > distal

Normal

Normal

Yes

ALS, Amyotrophic lateral sclerosis.

TABLE 98.2 

Distinguishing Upper Motor Neuron From Lower Motor Neuron Involvement MOTOR NEURON

DEEP TENDON REFLEX

MUSCLE TONE

ATROPHY

FASCICULATIONS

BABINSKI’S RESPONSE

Upper motor neuron

Increased

Increased

No*

No

Present

Lower motor neuron

Decreased

Decreased

Yes

Yes

Absent

*Not significant but can occur.

CHAPTER 98  Neuromuscular Disorders

maximum number of ACh receptors on the muscle cell, producing a normal or nearly normal strength response. Repeated stimulation leads to diminishing motor strength, which is caused by one of three mechanisms: blockage of the receptors, as in myasthenia gravis; decrease in the amount of ACh released, as in botulism; or inactivation of ACh by irreversible binding, as in organophosphate poisoning. A decrease in the release of ACh can cause a combination of nicotinic and muscarinic effects. The clinical manifestations of this are anticholinergic findings, such as decreased visual acuity, confusion, urinary retention, tachycardia, low-grade fever, and dry, flushed skin. In the case of Lambert-Eaton myasthenic syndrome, weakness is more pronounced at the beginning of muscle use and improves with repeated use as more ACh builds up in the synaptic cleft with each stimulation. Diseases of the neuromuscular junction are considered in patients who present with generalized weakness in association with an acute cranial nerve deficit. Muscle tone is generally diminished and sensation is preserved in diseases of the neuromuscular junction.

Myopathies

effects are multifactorial: direct blocking of the receptor, complement mediated destruction of the folds, and internalization and degradation of the receptors (Fig. 98.2). With repeated stimulation, fewer and fewer receptor sites are available for ACh binding, and fatigue develops. Fatigability and muscle weakness are the hallmarks of myasthenia gravis. The clinical progression of myasthenia gravis is slow, and the likelihood of short-term complications is low, so the most important aspect of emergency care is early recognition and proper referral for further evaluation when the disease is suspected. Many commonly used drugs can adversely affect patients with myasthenia gravis (Box 98.2). Myasthenic Crisis.  Myasthenic crisis is defined as respiratory failure leading to mechanical ventilation. It occurs in 15% to 20% of patients with myasthenia gravis, usually within the first 2 years

AChR blocking

AChR degradation

Complement activation

A

B

C

Myopathies produce generalized, symmetrical weakness. Reflexes are diminished, muscle tone is usually diminished, but sensation is preserved. Myopathies due to inflammatory disorders (polymyositis, dermatomyositis, polymyalgia rheumatica, and viral myositis) cause muscle pain and tenderness. Metabolic disorders affecting muscle strength (eg, electrolyte and endocrine disorders) are painless in nature.

DIAGNOSTIC TESTING Laboratory Studies Serum potassium, calcium, and phosphorus concentrations should be assessed in patients with acute weakness. Thyroid function tests are recommended in cases of suspected myopathies. A creatine kinase (CK) level assesses for muscle inflammation; urinalysis should be performed to test for the presence of myoglobinuria and possible rhabdomyolysis, and renal function studies should be obtained when rhabdomyolysis is present.

C1

Membrane attack complex C5b C59 C6 C7 C8

Membrane flattening Transmission block

Internalization degradation

Decrease of muscle contraction

Decrease of AChR density

Fig. 98.2.  Mechanisms of action of acetylcholine receptor (AChR) autoantibodies. Neuromuscular synapse in myasthenia gravis. AChR antibodies interfere with signal transduction by direct blocking of AChR (A), by cross-linking and increased degradation (B), or by immune mediated destruction including complement activation (C). (From Sommer N, Tackenberg B, Hohlfeld R: The immunopathogenesis of myasthenia gravis. In Engel AG, editor: Handbook of clinical neurology, volume 91, neuromuscular junction disorders, St Louis, 2008, Elsevier, pp 169–212.)

Special Studies Magnetic resonance imaging (MRI) is the preferred test for suspected cases of acute myelopathy. Computed tomography (CT) of the spinal cord with myelography can help differentiate compressive (herniation, abscess, tumor) from noncompressive causes when MRI is not available. CSF analysis is indicated when Guillain-Barré syndrome or transverse myelitis is suspected.

DISORDERS OF THE NEUROMUSCULAR JUNCTION Myasthenia Gravis Principles The age at onset of myasthenia gravis is bimodal; women are most commonly affected between 20 and 40 years old and men between 50 and 70 years old. Whereas new cases of myasthenia gravis are occasionally diagnosed in the emergency department (ED), it is much more common for patients with established disease to present with exacerbations of their disorder, often caused by precipitating factors. In most patients with myasthenia gravis, weakness and fatigue result from circulating autoantibodies against the ACh receptor on the junctional folds on the post synaptic membrane. The

BOX 98.2 

Drugs That May Exacerbate Myasthenia Gravis Cardiovascular Beta-blockers Calcium channel blockers Quinidine Lidocaine Procainamide Antibiotics Aminoglycosides Tetracyclines Clindamycin Lincomycin Polymyxin B Colistin Other Phenytoin Neuromuscular blockers Corticosteroids Thyroid replacement

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of disease onset. Although it is potentially life-threatening, the mortality from this complication of myasthenia gravis has declined dramatically with aggressive care in the intensive care unit (ICU) and the use of plasma exchange or immunomodulatory therapy with intravenous immune globulin (IVIG). Crises are most often precipitated by underlying infection, aspiration, and medication changes, such as stopping anticholinergic medications or taking a new medication that precipitates weakness. Other precipitants can be surgery and pregnancy (see Box 98.2). Lambert-Eaton Syndrome.  Lambert-Eaton myasthenic syndrome is a rare disorder. Almost 50% of cases are associated with small cell carcinoma of the lung. Autoantibodies cause inadequate release of ACh from nerve terminals, affecting both nicotinic and muscarinic receptors. With repeated stimulation, the amount of ACh in the synaptic cleft increases, leading to an increase in strength, which is the opposite of that seen with myasthenia gravis. The classic syndrome includes weakness that improves with use of muscles, particularly proximal hip and shoulder muscles; hyporeflexia; and autonomic dysfunction, most commonly seen as dry mouth. Management primarily focuses on treatment of the underlying neoplastic disorder, although IVIG has been reported to be useful.

Clinical Features Patients with myasthenia gravis present with easy fatigability— progressive weakness with repeated activity of affected muscle groups. Ocular symptoms are often the first manifestation of myasthenia gravis; typical symptoms are ptosis, diplopia, and blurred vision. Ocular muscle weakness is the first sign in up to 40% of patients, although 85% of patients with myasthenia gravis eventually have ocular involvement. When ptosis is present, it is often worse toward the end of the day. Respiratory failure is rarely the initial symptom of myasthenia gravis. Even so, up to 17% of patients may have weakness of the muscles of respiration. Bulbar muscles may be involved, producing dysarthria or dysphagia.

Diagnostic Testing The diagnosis of new-onset myasthenia gravis is based on clinical findings and a combination of serologic testing, electromyographic testing, and bedside testing with either edrophonium or the ice bag test. Serum testing for ACh receptor antibodies is positive in 80% to 90% of patients with myasthenia gravis, but it is not available in the ED. The edrophonium test and ice bag test are performed at the bedside for patients with suspected myasthenia gravis and ptosis. The results based on the effect of the intervention on the ptosis. Edrophonium is a short-acting acetylcholinesterase-blocking agent that produces an increase of ACh in the synaptic cleft and a reduction in ptosis after intravenous (IV) administration. With the ice bag test, cooling decreases symptoms in myasthenia gravis, whereas heat exacerbates symptoms. In both tests, the amount of ptosis is measured before and after administration of edrophonium or application of an ice bag. The distance from the upper to the lower eyelid in the most severely affected eye is measured first. If edrophonium is given, an IV test dose of 1 to 2 mg is given first because some patients have a severe reaction. If no adverse reaction is found and the patient does not dramatically improve in 30 to 90 seconds, a second dose of 3 mg is given. If there is still no response, a final dose of 5 mg is given for a total maximum dose of 10 mg. Atropine should be available at the bedside during the test. Because of the potential for cholinergic-induced increased airway secretions, this test should be used with caution in asthmatics and patients with chronic obstructive pulmonary disease.

If the ice bag test is used, an ice pack is applied to the affected eye for approximately 2 minutes. An improvement in the amount of ptosis of at least 2 mm is considered positive. The pooled sensitivity and specificity of the ice bag test for detecting ocular myasthenia is 0.94 and 0.97, respectively.

Management The initial step in managing the patient in crisis is stabilization of the airway. Biphasic positive airway pressure (BiPAP) is effective in managing patients who need ventilatory support. All patients with myasthenia gravis who present to the ED should be assessed for signs of myasthenic crisis even when they do not complain of weakness. Cholinesterase Inhibitors.  Pyridostigmine (60 to 120 mg by mouth every 4 to 6 hours) and neostigmine (0.5 mg SC/IM) prolong the presence and activity of ACh in the synaptic cleft. They are the backbone of chronic outpatient therapy and provide symptomatic improvement. The most common side effects are those of excessive cholinergic stimulation, such as increased airway secretions and increased bowel motility. At extremes, there may be bradycardia or even worsening of weakness, simulating a myasthenic crisis. These drugs are often used as adjunctive therapy to control symptoms while other therapy is being instituted, after which they are usually discontinued. IV cholinergic drug therapy, such as pyridostigmine, is not recommended for the treatment of myasthenic crises in the ED, because plasmapheresis and IVIG are both safe and highly effective therapies. Immunosuppressant Drugs.  Immunosuppressant drugs are used for the chronic control of myasthenia gravis. Although they have no role in the acute management of a myasthenic crisis, they may be started before extubation of a patient recovering from a crisis. A Cochrane review in 2005 found support for the use of corticosteroids, although cyclosporine, cyclophosphamide, azathioprine, or mycophenolate mofetil are used to decrease the need for steroids or for refractory cases. Of note, the initiation of corticosteroids in patients with moderate to severe weakness may actually precipitate a worsening of weakness or even myasthenic crisis. Thymectomy.  Whereas the association between thymoma and myasthenia gravis is not fully elaborated, it is well known that thymectomy for patients with thymoma can lead to remission of myasthenia gravis or enable a reduction in other medications. Thymectomy for patients with myasthenia gravis without thymoma is recommended as a treatment option, although its use is not supported by randomized controlled trials. Immunomodulatory Therapy.  Plasma exchange and IVIG are used for patients with an acute exacerbation of myasthenia gravis or preoperatively in patients with stable myasthenia gravis. Plasma exchange removes the ACh receptor antibodies and other immune complexes from the blood. The fall in ACh receptor levels is associated with improvement in symptoms of myasthenia gravis. There is a risk of complications from hypotension or anticoagulation. One small trial of IVIG versus placebo demonstrated the benefit of IVIG, whereas other trials have failed to show a difference between IVIG and plasma exchange.2 In a cohort of myasthenia gravis patients managed in an ICU over 12 years, 87% were managed with IVIG and only 18% received plasma exchange. In the years preceding this cohort, only 11.4% received IVIG and 60% received plasma exchange reflecting the change in practice patterns.3 At the current time, the decision to institute one therapy over the other is based on the input of the consulting neurologist and the resources most rapidly available.

CHAPTER 98  Neuromuscular Disorders

Studies suggest that rituximab, a monoclonal antibody that decreases B-cell function, has an emerging role in refractory cases of myasthenia gravis.4 Newer monoclonal antibody therapies directed at the complement mediated destruction of the ACh receptor are under investigation. Steroids in the form or oral prednisone (1 to 1.5 mg/kg) or prednisolone (1 to 1.5 mg/kg) are often given for acute exacerbations of myasthenia gravis. In the 12-year cohort, above 97% of patients received prednisolone. The evidence supporting the efficacy of corticosteroids is limited.

Disposition The decision to admit or to discharge a patient with myasthenia gravis from the ED should take into account the potential for neuromuscular deterioration with consideration of admitting a patient to an observation unit. Patients being admitted to the hospital should have a NIF or FVC measured to help determine the level of monitoring and care needed. These measurements need to be trended during the admission.

Botulism Principles Botulism is a toxin-mediated illness that can cause weakness leading to respiratory insufficiency. In 2012, the Centers for Disease Control and Prevention (CDC) reported 160 cases of botulism in the United States: 16% food-borne, 76% infant botulism, 5% wound botulism, and 3% unknown etiology.5 Clostridium botulinum is an anaerobic, spore-forming bacterium. Three of eight known toxins produced by C. botulinum (types A, B, and E) cause human disease. There have been outbreaks of wound botulism in Washington, California, England, Germany, and Norway associated with injection drug use.6 In 2011, there was an outbreak among eight prisoners in Utah who drank “pruno,” a prison-made wine.7 Three of the eight required intubation. Botulism is also thought to be a potential agent for bioterrorism. The botulinum toxin works by binding irreversibly to the presynaptic membrane of peripheral and cranial nerves, inhibiting the release of ACh at the peripheral nerve synapse. As new receptors are generated, the patient improves.

Clinical Features The botulinum toxin blocks both voluntary motor and autonomic functions. There is no pain or sensory deficit. The onset of symptoms is 6 to 48 hours after the ingestion of tainted food. Symptoms of gastroenteritis may or may not be present. The classic feature of botulism is a descending, symmetrical, flaccid paralysis. Cranial nerves and bulbar muscles are affected first, causing diplopia, dysarthria, and dysphagia, followed later by generalized weakness. Because the toxin decreases cholinergic output, anticholinergic signs may be present: constipation, urinary retention, dry skin and eyes, and increased temperature and dilated, non-reactive pupils. This can help differentiate botulism toxicity from myasthenia gravis. Deep tendon reflexes are normal or diminished. Infantile botulism results from the ingestion of C. botulinum spores that are able to germinate and produce toxin in the high pH of the gastrointestinal tract of infants. Botulism spores can survive in honey, so it is recommended that honey not be fed to infants. The clinical presentation includes constipation, poor feeding, lethargy, and weak cry; consequently, this diagnosis must be included in the differential diagnosis of the floppy infant.

Diagnostic Testing The diagnosis is made by both clinical findings and exclusion of other processes. The toxin can be identified in serum and stool, but the assay is not commonly available in most hospitals and requires a prolonged turnaround time. If the suspected food source is available, it should also be tested for the toxin.

Management Treatment is initially focused on stabilization of the airway and supportive measures. In 2010, the CDC announced a new equine heptavalent botulinum antitoxin (HBAT) that is now the only antitoxin available in the United States for non-infant botulism.8 For suspected cases and to obtain HBAT, clinicians should contact their state health departments. The CDC also maintains a botulism duty officer at the CDC Emergency Operations Center (770488-7100). An IV human-derived botulism immune globulin (BabyBIG) has been developed for treatment of infantile botulism and is available through the California Department of Public Health Infant Botulism Treatment and Prevention Program on-call physician at 510-231-7600.

Disposition All patients being treated for botulism need to be hospitalized, and most will be admitted to an ICU setting given the likelihood of progression of neuromuscular weakness. Infants and children will need to be transferred to the most appropriate neonatal intensive care unit (NICU) or pediatric intensive care unit (PICU) setting.

Tick Paralysis Principles This extraordinarily rare cause of an acute, ascending, flaccid paralysis is most often found in North America (Rocky Mountain region, US Pacific Northwest, and Southwestern Canada) and the east coast of Australia. Although the pathogenesis of tick paralysis is not fully understood, it is thought that a salivary toxin is injected while the tick feeds. The toxin functions like botulinum toxin to decrease the release of ACh from the presynaptic membrane of the neuromuscular junction.9

Clinical Features Tick paralysis causes an acute, ascending, flaccid motor paralysis that can be confused with Guillain-Barré syndrome, botulism, and myasthenia gravis. Symptoms usually begin 1 to 2 days after the female tick has attached and begun to feed, although delays of up to 6 days have been reported. There may be associated ocular signs, such as fixed and dilated pupils, that can help distinguish it from Guillain-Barré syndrome.

Management The management is supportive care and tick removal. A tick can be removed by use of forceps to grasp it as closely as possible to the point of attachment. Care should be taken not to leave mouth parts in the patient’s tissue. Although symptoms may resolve rapidly after removal of the tick, supportive measures such as intubation should not be withheld pending resolution of symptoms. Although there is little new research on the topic, there are many reports of cases misdiagnosed as other causes of weakness (Guillain-Barré syndrome, acute inflammatory demyelinating

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polyneuropathy, and so on) until the offending tick is found and removed.

Disposition These patients may begin to show improvement upon removal of the tick and may be able to be discharged from the ED. There should be strong consideration of admission to an observation unit if the patient is slow to improve.

DISORDERS OF THE MUSCLES Newly acquired weakness originating at the muscle level can be divided into two types: inflammatory and toxic-metabolic. Inflammatory disorders usually produce pain and tenderness, whereas metabolic disorders do not.

Inflammatory Disorders Principles The most common inflammatory myopathies are polymyositis and dermatomyositis. Polymyositis may be idiopathic in nature, occur secondary to infections (viral or bacterial), or be seen in conjunction with other disorders, such as sarcoidosis and hypereosinophilic syndromes. Inflammatory myopathies cause weakness, pain, and tenderness of the muscles involved.

Clinical Features Dermatomyositis and polymyositis can occur at any age, although adults are more often affected than children. They can be associated with various malignant neoplasms, such as of the breast, ovary, lung, and gastrointestinal tract, and lymphoproliferative disorders. Proximal muscle weakness predominates and leads to complaints of difficulty in rising from a seated position or climbing stairs and weakness in lifting the arms over the head. There is often pain and tenderness in these proximal muscles as well. There is a decrease in reflexes that is in proportion to the decrease in strength. Fasciculations are not seen, and atrophy is a very late finding. Dermatomyositis is similar to polymyositis, but it is also associated with classic skin findings. These are more prominent in childhood but are also found in adults. They include a periorbital heliotrope and erythema and swelling of the extensor surfaces of joints. The facial rash is usually photosensitive and may also involve the exposed areas of the chest and neck.

Diagnostic Testing Electrolyte abnormalities must be ruled out and the serum CK level checked. The CK level should be interpreted in light of the entire clinical picture; an elevated CK level does not establish the cause of weakness as a myopathy because some neuropathies can also produce an elevated CK level. Similarly, a normal CK level does not rule out a myopathy as the cause of weakness. Electromyography and muscle biopsy are used to confirm the diagnosis. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are often normal or only mildly elevated; thus they have no role in diagnosis or prognosis.

Management Polymyositis and dermatomyositis are usually managed with oral prednisone in a dose of 1 to 2 mg/kg/day. When steroids prove ineffective and during acute exacerbations, cytotoxic drugs such as azathioprine (initial dose of 50 mg/day) and methotrexate

(initial dose of 15 mg/week) are added. Fortunately, the degree of rhabdomyolysis seen with the inflammatory myopathies is not sufficient to cause renal impairment.

Disposition The majority of these patients will likely be discharged, some following an observation period. Hospitalization should be considered for patients with comorbidities, elders, and those who do not improve with treatment in the ED or observation unit.

Metabolic Disorders Acute, generalized muscle weakness can be seen with a number of severe electrolyte abnormalities of any cause: hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypophosphatemia. Acute painless myopathies can also be seen with endocrine disorders involving the thyroid, parathyroid, or adrenal glands. Of particular interest are several disorders referred to collectively as the periodic paralyses, which include periodic paralysis of the hyperkalemic and hypokalemic forms and thyrotoxic periodic paralysis, which is similar to hypokalemic periodic paralysis except that it is associated with hyperthyroidism.

Periodic Paralysis Principles.  Periodic paralysis of the hypo- and hyperkalemic forms are rare hereditary disorders of ion channels resulting in intermittent attacks of flaccid extremity weakness. The hypokalemic form is more common than the hyperkalemic form. Periodic paralysis is most often associated with an inherited genetic mutation. Patients usually report a personal and family history of similar episodes. Thyrotoxic periodic paralysis is an acquired rather than inherited form of hypokalemic periodic paralysis. The clinical picture of thyrotoxic periodic paralysis is almost identical to that of periodic paralysis, and indeed a small number of patients with hypokalemic periodic paralysis have hyperthyroidism. In thyrotoxic periodic paralysis, symptoms related to hyperthyroidism are often present at the same time the patient has weakness. The relation of the hyperthyroidism to hypokalemia is probably due to increased sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) pump, which causes a rapid shift of potassium from the extracellular into the intracellular compartment. There is probably a genetic feature underlying this disorder, because there is a higher incidence of repeated attacks of hypokalemic periodic paralysis among Japanese and Chinese patients with hyperthyroidism.10 It is important that all patients have thyroid function testing performed after a first episode of hypokalemic paralysis. Clinical Features.  Patients may suffer either isolated or recurrent episodes of flaccid paralysis. The lower limbs are involved more often than the upper, although both can be affected. Bulbar, ocular, and respiratory muscles are usually not involved. Onset is rapid often following a high oral carbohydrate intake (with subsequent insulin rise) and a period of rest. This reflects the intracellular shift of potassium rather than the total body depletion of potassium. A typical complaint is acute weakness noted on waking the morning after a large meal. Diagnostic Testing.  The electrocardiogram may demonstrate signs of hyperkalemia or hypokalemia. An immediate determination of potassium level should be obtained; in the hypokalemic form, the potassium level during an attack falls to values well below 3.0 mEq/L.

CHAPTER 98  Neuromuscular Disorders

Management.  Many cases resolve spontaneously with supportive care alone. The mainstay of management is the treatment of the underlying electrolyte imbalance. In the hypokalemic state, the total body potassium concentration is not depleted but has shifted intracellularly. Thus, in the repletion of potassium, caution is necessary to prevent overtreatment. For this reason, IV potassium should be used sparingly; one or two 10-mEq IV doses of potassium chloride, each over 1 hour, is the maximum IV dose. This can be done in parallel with 40 mEq oral potassium repletion and retesting of serum potassium levels. IV hydration helps redistribute the body’s potassium stores. Magnesium supplementation is not necessary. Treatment of the hyperthyroid symptoms in thyrotoxic periodic paralysis, such as tachycardia, may help the

paralysis as well. There are case reports of thyrotoxic periodic paralysis in which the patient’s weakness did not respond to potassium replacement until propranolol was given to treat tachycardia. However, there is insufficient evidence to make specific management recommendations in this regard. Disposition.  In the past, most cases of periodic paralysis needed to be hospitalized, but with the increased availability of observation units they can likely be managed in less than 24 hours. Admission can be considered for patients with their first episode of periodic paralysis for patients needing management of thyrotoxicosis.

KEY CONCEPTS • The approach to evaluation of patients with acute neuromuscular weakness is facilitated by first determining the location of the lesion (spinal cord, nerve, neuromuscular junction, or muscle) and then considering the most common disorders that affect the area in question. • In patients presenting with acute neuromuscular weakness, complaints of difficulty in breathing or swallowing should heighten suspicion of bulbar involvement with possible airway compromise. In such patients, FVC of less than 15 mL/kg or maximal NIF of less than 15 mm H2O is a potential indication for mechanical ventilation. • Patients with a neuromuscular decline in respiratory function can be given a trial of noninvasive ventilation. • The edrophonium and ice bag tests can be useful bedside tests in the evaluation of a suspected new diagnosis of myasthenia gravis. • Plasma exchange therapy and IVIG are both useful for the treatment of myasthenic crises with the choice dependent on which is available and preferred in the ICU.

• Botulism usually arises as a painless descending paralysis, often first affecting the cranial nerves and bulbar muscles, without sensory deficits or significant alteration of consciousness. The treatment is airway management and administration of antitoxin. • Injection drug use remains an important cause of wound botulism outbreaks. • Botulism must be considered in the evaluation of a weak and floppy infant. • In hypokalemic periodic paralysis, the total body potassium level is not depleted, only shifted intracellularly: treatment should keep this in mind as potassium is administered with frequent checks of serum potassium levels. • In newly diagnosed hypokalemic periodic paralysis, the patient should be evaluated and treated for hyperthyroidism if present.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Enterovirus D68: the unexpected guest. Lancet Infect Dis 14(11):1023, 2014. 2. Gajdos P, Chevret S, Toyka KV: Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev (12):CD002277, 2012. 3. Spillane J, Hirsch NP, Kullmann DM, et al: Myasthenia gravis—treatment of acute severe exacerbations in the intensive care unit results in a favourable long-term prognosis. Eur J Neurol 21:171–173, 2014. 4. Iorio R, Damato V, Alboini PE, et al: Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol 262(5):1115–1119, 2015. 5. Centers for Disease Control and Prevention (CDC): National enteric disease surveillance: botulism annual summary, 2012. Available at .

6. MacDonald E, Arnesen TM, Brantsaeter AB, et al: Outbreak of wound botulism in people who inject drugs, Norway, October to November 2013. Euro Surveill 18(45):20630, 2013. 7. Williams BT, Schlein SM, Caravati EM, et al: Emergency department identification and critical care management of a Utah prison botulism outbreak. Ann Emerg Med 64(1):26–31, 2014. 8. Centers for Disease Control and Prevention (CDC): Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. MMWR Morb Mortal Wkly Rep 59(10):299, 2010. 9. Edlow JA: Tick paralysis. Curr Treat Options Neurol 12:167, 2010. 10. Falhammar H, Thorén M, Calissendorff J: Thyrotoxic periodic paralysis: clinical and molecular aspects. Endocrine 43(2):274–284, 2013.

CHAPTER 98: QUESTIONS & ANSWERS 98.1. Which of the following is an indication for intubation in a 70-kg patient with weakness due to neuromuscular disease? A. Arterial Pco2 of 42 mm Hg B. Forced vital capacity (FVC) of 950 mL C. Negative inspiratory force (NIF) of 18 mm Hg D. Oxygen saturation of 95% on room air E. Respiratory rate of 24 breaths per minute Answer: B. An FVC less than 15 mL/kg or an NIF less than 15 mm Hg are indications for intubations. Regarding arterial blood gas analysis, functional reserve can be severely diminished by the time a patient develops hypoxia or hypercarbia. 98.2. Match the following pathologic conditions with their correct associated finding(s): A. Motor neuron disease—upper/lower motor neuron findings B. Myelopathy—preserved sensation C. Myopathy—distal weakness that ascends D. Neuromuscular junction disease—Babinski’s response E. Neuropathy—acute cranial nerve deficit Answer: A. Amyotrophic lateral sclerosis (ALS) and polio are the classic cases of motor neuron disease. The typical presentation is a mix of upper and lower motor neuron findings. The following are other correct associations: Myopathy—preserved sensation Neuromuscular junction disease—acute cranial nerve deficit Myelopathy—Babinski’s response Neuropathy—distal weakness that ascends

98.3. You have intubated a patient in myasthenic crisis but do not have plasmapheresis immediately available in your hospital. Your next choice of therapy would be: A. Begin intravenous (IV) pyridostigmine B. Begin IV immune globulin 1 g/kg daily C. Edrophonium 1 mg IV test dose followed by 3–5 mg IV D. Start rituximab Answer: B. Although evidence supporting IV immune globulin is weak, it is an accepted alternative to plasmapheresis. Pyridostigmine and neostigmine are used orally for maintenance and not for acute crisis, and the IV dose might cause complications from the cholinergic excess, such as increased secretions. 98.4. A 24-year-old Mexican male presents with hypokalemic periodic paralysis. His potassium level is 1.6 mEq/L. After receiving 2 L of normal saline IV and KCl 30 mEq IV over 3 hours, his vital signs are blood pressure 178/96, heart rate 126, temperature 38° C, and respiratory rate 16. His weakness is not improving. What is the most appropriate next therapeutic option? A. KCl 20 mEq IV bolus B. Plasmapheresis C. Prophylactic intubation for airway protection D. Propranolol 40 mg by mouth Answer: D. For patients with thyrotoxic periodic paralysis, the weakness often does not correct if the hyperthyroid state is not treated along with the hypokalemia. Thyrotoxic periodic paralysis is more common in Japanese and Hispanic men. Such patients also do not usually manifest paralysis unless their potassium level drops while they are hyperthyroid.

C H A P T E R 99 

Central Nervous System Infections David M. Somand  |  William J. Meurer PRINCIPLES Overview Meningitis is an inflammation of the membranes of the brain or spinal cord and is also called arachnoiditis or leptomeningitis. Encephalitis denotes inflammation of the brain itself; myelitis refers to inflammation of the spinal cord. The terms meningoencephalitis and encephalomyelitis describe more diffuse inflammatory processes. Collections of infective and purulent materials may form within the central nervous system (CNS) as abscesses. Brain abscesses may be intraparenchymal, in epidural or subdural intracranial locations, or may be found in intramedullary or epidural spinal locations. The etiologic spectrum of CNS infection has changed considerably as a result of the development and use of antibiotics and the epidemic emergence of diseases and conditions that impair the immune system (eg, human immunodeficiency virus [HIV]). Likewise, diagnostic tools have been developed that allow precise pathogen identification, including polymerase chain reaction (PCR) tests for viral nucleic acids in cerebrospinal fluid (CSF). The use of pneumococcal, Haemophilus influenza type b (Hib), and meningococcal vaccines has led to dramatic reductions in the incidence of meningitis. Unfortunately, despite advances, the morbidity and mortality of these disorders remain considerable.

Bacterial Meningitis Meningeal inflammation may be caused by a variety of disease processes, but infectious etiologies predominate. Common pathogens of CNS infections are Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes, and H. influenza. Although the incidence of S. pneumoniae has declined, it remains the predominant pathogen in adult patients, followed by N. meningitidis and L. monocytogenes.1,2 N. meningitidis is the predominant organism in adults younger than 45 years old. Five major serogroups cause most meningococcal disease worldwide (A, B, C, Y, and W-135). Serogroup A accounts for the majority of cases of meningococcal meningitis in developing nations. A new vaccine for serogroup A may potentially reduce the impact of this disease in nearly half a billion individuals at risk.3 Serogroup distribution for invasive disease has changed markedly in the United States, with B, C, and Y now most commonly responsible. Interestingly, higher case fatality has been observed in N. meningitis outbreaks versus sporadic cases, likely due to increased virulence of outbreak-related strains. Meningeal infection may also occur in association with a dural leak secondary to neurosurgery or neurotrauma. S. pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and coliform bacteria are seen most commonly in this population. The pathogenetic sequence in bacterial meningitis generally begins with nasopharyngeal colonization and mucosal invasion. Virulent microbes secrete immunoglobulin A proteases, induce ciliostasis of mucosal cells, and survive intravascularly by evasion of the complement pathway. The varying capsular properties of each organism protect the bacteria. Once bacteria cross the 1328

blood-brain barrier to enter the CSF, host defense mechanisms within the CSF are often ineffective due to low levels of complement, immunoglobulin, and opsonic activity. Bacterial proliferation then occurs, which stimulates a convergence of leukocytes into the CSF. Meningeal and subarachnoid space inflammation is associated with the release of cytokines into the CSF, most notably tumor necrosis factor and interleukins 1 and 6. These cytokines incite an inflammatory cascade that promotes increased permeability of the blood-brain barrier, cerebral vasculitis, edema, and increased intracranial pressure (ICP). A subsequent decrease in cerebral blood flow leads to cerebral hypoxia. Glucose transport into the CSF is decreased concomitantly with increased glucose utilization resulting in cellular metabolic failure. The case fatality rate for pneumococcal meningitis has improved and is less than 20%, with higher fatality rates occurring in patients with serious underlying disease or advanced age. The prognosis is related to the degree of neurological impairment on presentation. Overall, 20% to 30% of the survivors of pneumococcal meningitis have some residual neurological deficit. The case fatality rate for Listeria meningitis may be as high as 40%.

Tuberculous Meningitis Death from tuberculous meningitis in the adult age group ranges from 10% to 50% of cases, with the incidence directly proportional to the patient’s age and the duration of symptoms before presentation. Focal ischemic stroke may result from the associated cerebral vasculitis. In advanced disease, up to 25% of patients may require some neurosurgical procedure for obstruction (ventriculoperitoneal shunt or drainage). In most patients some neurological deficit develops, but severe long-term sequelae among survivors are unusual.

Viral Meningitis and Encephalitis The actual incidence of viral meningitis is unknown because most cases go unreported. A prominent increase of cases is seen in summer months, which is concurrent with seasonal predominance of the enterovirus group of the picornaviruses. The same organisms responsible for viral meningitis may also be associated with encephalitis.4 A common mechanism of transmission is via insect vectors; arbovirus infection is an example, although clinical disease develops in only a small percentage of the people bitten. Herpetic encephalitis is believed to occur via direct neuronal transmission from a peripheral site via a cranial nerve. Viruses enter the human host through the skin (ie, insect vectors); through the respiratory, gastrointestinal, or urogenital tract; or by receipt of infected blood products or donor organs. Viral replication subsequently occurs outside the CNS, most often followed by hematogenous spread to the CNS. Additional routes into the CNS include retrograde transmission along neuronal axons and direct invasion of the subarachnoid space after infection of the olfactory submucosa. The development of a viral CNS infection is linked to the virulence of the specific virus, the viral inoculum level, and the state

CHAPTER 99  Central Nervous System Infections

of immunity of the human host. The tropism of the virus for specific CNS cell types also influences the focality of disease and its manifestations. Particular viruses may preferentially attack cortical, limbic, or spinal neurons, oligodendria, or ependymal cells. An example is the tropism of herpes simplex virus (HSV) for the temporal lobes and the development of temporal lobe seizures and behavioral changes in afflicted patients. With rare exceptions, the overall prognosis for complete recovery from viral meningitis is excellent. Various complications related to the systemic effects of the particular virus include orchitis, parotitis, pancreatitis, and various dermatoses. Usually all of these complications resolve without sequelae. Interestingly, HSV meningitis is often associated with the initial outbreak of genital herpes, and in contrast to HSV encephalitis the outcome is usually good. The outcomes in viral encephalitis are dependent on the infecting agent. The mortality from HSV encephalitis before the use of acyclovir was 60% to 70%. Acyclovir treatment has reduced the mortality to approximately 30%.4 Common complications observed among survivors include seizures, motor deficits, and changes in mentation. Encephalitis caused by Japanese encephalitis virus, Eastern equine virus, and St. Louis encephalitis virus is severe, with high mortality rates and virtually universal neurological sequelae among survivors. West Nile virus produces encephalitis in only 0.5% of those infected, yet it resulted in 120 deaths in 2003. Western equine virus and California encephalitis virus cause milder infections, and death is rare. The incidence of neurological sequelae is highly variable and appears to depend on both the host and the infecting agent. Tickborne encephalitis is endemic to parts of Europe and is an important consideration for residents and recent travelers to those regions. Reports of influenza A H1N1 encephalitis in adults have emerged, which bear striking resemblance to “encephalitis lethargica” reported as a complication of influenza like illnesses in the 1920s. Although post-infectious encephalomyelitis (PIE) is not directly caused by CNS invasion of the measles virus, it is useful to consider the complications of PIE. Predominantly affecting adolescents, up to one quarter of measles patients with PIE will die, and many survivors have dramatic neurological sequelae and permanent disability; this process appears mediated by an immune system response that attacks myelin basic protein. The flaccid paralysis associated with enterovirus D68 left some affected children with permanent deficits similar to polio.

Fungal Meningitis Fungal meningitis probably develops in much the same way as bacterial meningitis, although this has been incompletely studied. Pulmonary exposure followed by hematogenous spread is the primary pathogenic mechanism in most cases. Immune system defects or immunosuppressive medications compromise host defense mechanisms, with ensuing development of CNS infection. Iatrogenic injection with contaminated methylprednisolone was responsible for the largest fungal meningitis outbreak in the United States.5 Common CNS complications of fungal meningitis include abscesses, increased ICP, neurological deficits, seizures, bone invasion, and fluid collections. Direct invasion of the optic nerve results in ocular abnormalities in up to 40% of patients with cryptococcal meningitis. The mortality rate is high but variable and is related to the timeliness of diagnosis, underlying illness, and therapeutic regimens.

Fig. 99.1.  Central nervous system (CNS) abscess: Computed tomography (CT) of an intraparenchymal abscess (arrows).

infections, intravenous (IV) drug use, neurological surgery, and cranial trauma. Brain abscess secondary to otitis media most often occurs in pediatric or older adult populations. When associated with sinusitis, it most often arises among young adults. Increasingly, CNS abscesses are seen in the immunocompromised population, particularly those with HIV infection, and among bone marrow and solid organ transplant recipients. However, antimicrobial prophylaxis in immunosuppressed patients and more aggressive treatment of otitis and sinusitis have decreased the incidence of CNS abscesses. Intraparenchymal brain abscesses, subdural empyema, or intracranial or spinal epidural abscesses result from inoculation of the CNS from either contiguous spread of organisms from a sinus, middle ear, or dental infection, or from metastatic seeding from a distant site (eg, a pulmonary infection or endocarditis). The primary infection can be identified in 75% to 85% of cases. These conditions may also follow surgery or penetrating cranial trauma, particularly when bone fragments are retained in brain tissue. Otogenic abscesses occur most commonly in the temporal lobe in adults and cerebellum in children, whereas sinogenic abscesses typically occur in frontal areas. Multiple brain abscesses suggest hematogenous spread of organisms, most commonly from the pulmonary system, although solitary lesions may also occur (Fig. 99.1). The mortality rate from brain abscess has declined dramatically from approximately 50% to less than 20% due to a number of factors including early diagnosis afforded by the use of the cranial computed tomography (CT) scan; improved antimicrobial therapy; and combined management approaches with surgery, aspiration, and medical therapy.

CLINICAL FEATURES

Central Nervous System Abscess

Meningitis

CNS abscesses may occur at any age and any time of year. They are associated with local contiguous and remote systemic

Numerous host factors have been implicated in the acquisition of meningitis, although disease also occurs when none are present

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BOX 99.1 

BOX 99.2 

Host Factors Predisposing to Meningitis

Complications of Bacterial Meningitis

Age younger than 5 years old Age older than 60 years old Male gender Low socioeconomic status Crowding (eg, military recruits) Splenectomy Sickle cell disease African-American race Alcoholism and cirrhosis Diabetes Immunologic defects Recent colonization Dural defect (eg, traumatic, surgical, congenital) Continuous infection (eg, sinusitis) Household contact with meningitis patient Thalassemia major Intravenous (IV) drug abuse Bacterial endocarditis Ventriculoperitoneal shunt Malignancy

IMMEDIATE

(Box 99.1). The constellation of symptoms that may classically occur in an acute CNS infection consists of fever, headache, photophobia, nuchal rigidity, lethargy, malaise, altered sensorium, seizures, vomiting, and chills.6 Unfortunately, subtle presentations are also common especially in immunosuppressed and geriatric patients where an alternation in mental status may be the only finding. However, good quality literature suggests that the absence of fever, stiff neck, and mental status change excludes meningitis in immunocompetent adults. A systematic review of prospective data in children found clinical factors useful in increasing the likelihood of bacterial meningitis included bulging fontanel, neck stiffness, and seizures in children outside the age typical for febrile convulsions.6 No combination of factors have been identified that rule in or rule out the disease, which is not surprising given the diversity of presentations in children.7 The presentation of fungal meningitis can be obscure even in the healthy adult population. Headache, low-grade fever, lassitude, and weight loss may be present but often to such a mild degree that the correct diagnosis is not initially considered. This is also true of tuberculous meningitis, which often has a protracted course and a vague nonspecific presentation consisting of fever, weight loss, night sweats, and malaise, with or without headache and meningismus. The physical findings in meningitis vary, depending on the host, causative organism, and severity of the illness. Kernig’s sign (inability to straighten leg to a position of full knee extension when patient is lying supine with hip flexed to a right angle) and Brudzinski’s sign (attempts to flex the neck passively are accompanied by flexion of the hips) are present in approximately 50% of adults. When patients with suspected meningitis were evaluated, the sensitivity of Kernig’s sign, Brudzinski’s sign, and the presence of nuchal rigidity are 5%, 5%, and 30%, respectively, suggesting that these physical findings have limited diagnostic value. On the other hand, at least in children, the 2010 National Institute for Health and Clinical Excellence guidelines found that 85% to 95% of children with meningitis had fever, 66% had Brudzinski’s sign, 53% had Kernig’s sign or neck stiffness, and 83% had at least one of the three objective findings.8 Deep tendon reflexes may be increased, and ophthalmoplegia may be present, especially of the lateral rectus muscles. Papilledema, if observed, or lack of venous pulsations, are consistent with increased ICP

Coma Loss of airway reflexes Seizures Cerebral edema Vasomotor collapse Disseminated intravascular coagulation (DIC) Respiratory arrest Dehydration Pericardial effusion Death Others

DELAYED

Seizure disorder Focal paralysis Subdural effusion Hydrocephalus Intellectual deficits Sensorineural hearing loss Ataxia Blindness Bilateral adrenal hemorrhage Death Cerebral venous thrombosis Others

and should raise the concern for a structural lesion. In addition, patients with coma (Glasgow Coma Score [GCS] of 1000 mg/dL) in the presence of a relatively benign clinical presentation suggests fungal disease.

India Ink Preparation Historically, an India ink staining of the CSF was performed to diagnose cryptococcal meningitis. This has been replaced by cryptococcal antigen testing, which has a similar sensitivity when measured in serum, CSF, or urine.

Lactic Acid and Other Markers Although nonspecific, elevations in CSF lactic acid concentrations (>2.8 mmol/L) are potentially indicative of bacterial meningitis,

and lactate may rise prior to the decline in glucose. Normal lactate levels (4; polymorphonuclear (PMN) count = 0 B. Total cell count >5; PMN count = 1 C. Total cell count >6; PMN count = 2 D. Total cell count >8; PMN count = 3 E. Total cell count >10; PMN count = 4 Answer: B. Normal CSF contains at most five leukocytes with at most one PMN leukocyte. 99.8. A 27-year-old woman presents with fever, headache, and mild neck pain. Physical examination is unremarkable except for neck pain with mild meningismus and a fever

of 39.5° C. Blood tests, chest radiograph, and urinalysis are negative. Lumbar puncture (LP) results are lymphocytes 3 cells/mm3 and polymorphonuclear (PMN) leukocyte is 0. Glucose and protein levels are normal. No organisms are seen on gram stain. What should be the next step? A. Computed tomography (CT) scan with intravenous (IV) contrast B. IV antibiotics and admission C. IV ceftriaxone and a 24-hour recheck D. Magnetic resonance imaging (MRI) scan E. Reassurance and analgesics Answer: B. Normal cell counts and differential diagnoses, in the face of a compatible clinical picture, do not rule out meningitis. Such patients require antibiotics, admission, reevaluation, and sometimes repeat lumbar puncture (LP). Brain abscesses and parameningeal infections may likewise present with normal cerebrospinal fluid (CSF). 99.9. Cerebrospinal fluid (CSF) xanthochromia may persist for up to how long? A. 24 hours B. 2 days C. 7 days D. 14 days E. 1 month Answer: E. CSF xanthochromia may persist for up to 1 month. Also, if a traumatic tap introduces enough protein to raise the CSF level to 150 mg/dL, blood pigments may cause xanthochromia.

SECTION EIGHT

Psychiatric and Behavioral Disorders C H A P T E R 100 

Thought Disorders Matthew P. Kelly  |  Dag Shapshak PRINCIPLES Patients with a history of mental illness have a higher rate of emergency department (ED) visits then the general population. Patients with at least one primary psychiatric visit to an ED were over four times more likely to become frequent ED users compared to patients with none.1 Psychiatric patients accounted for almost 10% of all ED visits in 2010.2 Patients are often brought to the ED by family, police, or emergency medical service (EMS) with concerning symptoms of disorganized thought or behavior. They may express language and ideas found to be inappropriate and disruptive to accepted patterns of social interaction. Whether the issue involves thought content (delusions) or thought form (structure of thinking), the clinical impression is that of psychosis (detachment from reality and societal norms). Acutely psychotic patients raise concerns of safety for themselves and those around them. The emergency clinician’s role is to first prevent and control violent and disruptive behavior and then determine if the underlying etiology of the thought disorder is functional (psychiatric) versus organic (medical) in nature. Functional causes include schizophrenia and schizophrenia-like illness, mania or mood disorder–associated psychosis. Organic causes can mimic the psychotic behavior of functional psychosis. Medication effects, substance abuse, and certain medical disorders need to be excluded before psychosis can be attributed to an underlying psychiatric illness. Schizophrenia often manifests as a thought disorder or psychosis. The prevalence of schizophrenia approaches 1% internationally. The incidence is approximately 1.5 new cases annually per 10,000 people. Slightly more men than women are diagnosed (1.4 : 1), and women tend to be diagnosed later in life.3 The mortality rate for schizophrenia is 2.5 times that of the general population and continues to grow. Migrants, urban dwellers, those with low social economic status, and those who live at higher latitude have an increased risk for the disease. Although the etiology of schizophrenia is multifactorial, it has a substantial genetic component with 80% of the variation in the trait of the disease attributed to genetic factors. Alterations in the dopaminergic, serotonergic, cholinergic, and glutamatergic dependent pathways have all been implicated in the pathophysiology of schizophrenia.4 Neuro-inflammation and white matter pathology may be associated with the disease. Neuropathological and neuroimaging studies provide consistent evidence of an association between schizophrenia and microglial activation and proliferation.5 Schizophrenia is also postulated to be related to environmental factors interacting with neurodevelopmental factors thereby increasing risk of the disease. Stress, perinatal hypoxia, poor nutrition, infections, vitamin D deficiency,

and zinc deficiency have all been associated with the development of schizophrenia.6 Evidence supports the existence of a progressive continuum of psychotic illness, beginning with unipolar depression and progressing to bipolar disease, schizoaffective psychosis, and finally schizophrenia. Research has shown that primary cerebellar insults may occur early during brain development long before the illness is clinically expressed. Interactions between early neurodevelopmental disturbances and pathological events in postnatal brain maturation seem necessary to trigger the onset of overt schizophrenia.7

CLINICAL FEATURES Thought disorders broadly affect mental activity and can be associated with varying degrees of functional impairment. The core psychopathology of schizophrenia and other thought disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes hallucinations, delusions, disorganization, cognitive impairment, and negative symptoms.8,9 The positive symptoms of schizophrenia manifest in many forms, including distortion of reality. Hallucinations are the perception of a sensory process in the absence of an external source. They can be auditory, olfactory, visual, gustatory, or somatic in nature. The vast majority of people with schizophrenia experience auditory hallucinations. Another impairment present in most schizophrenics is delusional thinking. Delusions are fixed, false beliefs that persist in the face of overwhelming contradictory evidence. Due to impaired insight, patients with thought disorders often have delusional explanations for their hallucinations. Delusions can be bizarre and clearly implausible, or they can be reasonable and understandable yet untrue. Patients with schizophrenia typically display disorganization of behavior and thinking. Their use of disjointed speech patterns reflects their internal poor organization of thought. This results in a lack of a coherent focus of ideas. The most commonly observed abnormal speech patterns are tangentiality and circumstantiality where the narrative wanders away from the initial topic of conversation. More severe thought disorders include derailment, neologisms, word salad, and perseverations. In severe cases, there may be no understandable content and speech is utterly incomprehensible. A separate group of patients with a more extreme deficit in communication are those suffering from catatonia. This behavior includes immobility, stupor, mutism, resistance to instructions, oppositionalism, echo phenomena, and withdrawal. Although classically associated with schizophrenia because of the profound communication and thought deficiencies, more recent studies highlight a strong association of catatonia with mood and medical disorders. Despite their similar 1341

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presentations, only a minority of catatonic patients suffer with schizophrenia.10 Along with disorganization, thought disorders can be associated with significant cognitive impairment. These difficulties with attention, memory, reasoning, verbal comprehension, and decision-making usually precede the onset of positive symptoms.11 These features are increasingly considered a core feature of thought disorders and not the byproduct of other symptoms or medications. Negative symptoms represent an absence or diminution of normal cerebral processes. Negative symptoms include blunted affect, emotional withdrawal, social withdrawal, poor rapport with other people, difficulty with abstract thinking, loss of spontaneous conversation, and stereotyped thinking. The negative symptoms of schizophrenia are associated with an insidious onset of disease, fewer remissions, and poorer long-term prognosis. They are also associated with worse premorbid interpersonal skills, lower intelligence quotient (IQ), and tend to progress over time. The development of schizophrenia involves three phases. The premorbid phase is characterized by the development of negative symptoms with deterioration in personal, social, and intellectual functioning. The patients are often young and may progressively withdraw from social actions. They may neglect personal appearance and hygiene. They experience deterioration of work, school, and home life. The progressive phase is often precipitated by a stressful event with the development of positive symptoms. The progressive phase can be said to begin when the patient develops the classical characteristics of schizophrenia mentioned earlier. Patients can become agitated or exhibit a hypervigilant withdrawal state characterized by rocking or staring and the patient may be violent and acting bizarrely. It is during the progressive phase that the patient is most likely to be brought to the ED by family, friends, police, or concerned bystanders. The residual phase is characterized by persistence of residual symptoms and disability. Impaired social and cognitive ability, poor hygiene, delusions, bizarre behavior, and social isolation can occur. On average, functional outcome is poor and patients may have varying levels of treatment resistance. Mortality is substantially increased due to elevated suicide risk and increased rates of poorly controlled medical comorbidities.

DIFFERENTIAL DIAGNOSIS Medical Disorders Numerous acute and chronic medical conditions can precipitate thought disorders (Box 100.1). Additionally, patients with underlying psychiatric disease may develop medical disorders that can exacerbate behavioral symptoms and cloud the distinction between psychiatric and organic brain disease. Factors associated with primary medical conditions include new onset of symptoms, acute change in mental status, recent fluctuation in behavioral symptoms, onset in fifth decade of life or older, onset of symptoms after the patient has already been admitted to a medical care setting, and the presence of nonauditory hallucinations, lethargy, abnormal vital signs, and poor performance on cognitive function testing, particularly orientation to time, place, and person. Primary psychiatric conditions are more commonly associated with auditory hallucinations, a family history of psychosis, and an insidious onset in the late teens to mid-twenties. Medical delirium is common in elders; therefore, special attention should be paid to symptoms of psychosis in this population. Health care providers frequently ascribe medical delirium to other causes, such as dementia, psychosis, or depression.12 Medical delirium can be frequently missed in elders brought to the ED for alterations in behavior.13

BOX 100.1 

Medical Disorders That May Cause Acute Psychosis METABOLIC DISORDERS • • • • •

Hypercalcemia Hypercarbia Hypoglycemia Hyponatremia Hypoxia

INFLAMMATORY DISORDERS • Sarcoidosis • Systemic lupus erythematosus • Temporal (giant cell) arteritis

ORGAN FAILURE

• Hepatic encephalopathy • Uremia

NEUROLOGIC DISORDERS • • • • • • • • • • • •

Alzheimer’s disease Cerebrovascular disease Encephalitis (including HIV infection) Encephalopathies Epilepsy Huntington’s disease Multiple sclerosis Neoplasms Normal-pressure hydrocephalus Parkinson’s disease Pick’s disease Wilson’s disease

ENDOCRINE DISORDERS • • • • • • • •

Addison’s disease Cushing’s disease Panhypopituitarism Parathyroid disease Postpartum psychosis Recurrent menstrual psychosis Sydenham’s chorea Thyroid disease

DEFICIENCY STATES

• Niacin • Thiamine • Vitamin B12 and folate HIV, Human immunodeficiency virus.

Patients intoxicated with drugs of abuse are often brought to the ED because of bizarre or dangerous behavior. Street drugs such as cocaine, amphetamines, bath salts, hallucinogens, and synthetic cannabis affect the serotonergic and dopaminergic pathways and can provoke psychotic reactions resembling a primary psychotic disease or can disclose latent schizophrenia.14 Certain pharmacologic agents may also cause acute psychosis and mimic a thought disorder (Box 100.2).

Psychiatric Disorders Once medical causes have been ruled out and the etiology is believed to be psychiatric, it can be helpful to classify which type of psychosis the patient is experiencing. The DSM-5 uses four classes of information to distinguish among the various types of

CHAPTER 100  Thought Disorders

BOX 100.2 

BOX 100.3 

Pharmacologic Agents That May Cause Acute Psychosis

Diagnostic Criteria for Schizophrenia From Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

ANTIANXIETY AGENTS • • • • • •

Alprazolam Chlordiazepoxide Clonazepam Clorazepate Diazepam Ethchlorvynol

ANTIBIOTICS • Isoniazid • Rifampin

ANTICONVULSANTS • • • •

Ethosuximide Phenobarbital Phenytoin Primidone

ANTIDEPRESSANTS • • • • •

Amitriptyline Doxepin Imipramine Protriptyline Trimipramine

CARDIOVASCULAR DRUGS • • • • • • •

Captopril Digitalis Disopyramide Methyldopa Procainamide Propranolol Reserpine

DRUGS OF ABUSE • • • • • • • •

Alcohol Amphetamines Cannabis Cocaine Hallucinogens Opioids Phencyclidine Sedative-hypnotics

1. Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be (1), (2), or (3): A. Delusions B. Hallucinations C. Disorganized speech (eg, frequent derailment or incoherence) D. Grossly disorganized or catatonic behavior E. Negative symptoms (ie, diminished emotional expression or avolition) 2. For a significant portion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning). 3. Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (ie, activephase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or by two or more symptoms listed in Criterion A present in an attenuated form (eg, odd beliefs, unusual perceptual experiences). 4. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms, or (2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness. 5. The disturbance is not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition. 6. If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated). Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (Copyright ©2000). American Psychiatric Association. All Rights Reserved.

MISCELLANEOUS DRUGS • • • • • • •

Antihistamines Antineoplastics Bromides Cimetidine Corticosteroids Disulfiram Heavy metals

psychosis: type of psychotic symptom, course of illness, consequences of illness, and exclusions.15 Each category can help distinguish schizophrenia from other disorders that include psychosis among their symptoms. The DSM-5 definition of schizophrenia is included in Box 100.3. A brief psychotic disorder involves the sudden onset of psychotic symptoms in response to major stress and lasts from several days up to 1 month. Peripartum psychosis is included under the diagnosis of brief psychotic disorder. Patients with schizophreniform

disorder have similar symptoms to a brief psychotic disorder and last from longer than 1 month to less than 6 months. Up to one-third of patients with schizophreniform disorder can recover within 6 months; the other two-thirds develop clinical schizophrenia.16 Patients with mood disorders may develop psychotic symptoms as part of their disease. If psychotic symptoms develop during periods of mood disturbances, the diagnosis of mood disorder with psychotic features applies. If symptoms consistent with schizophrenia persist for more than 2 weeks in the absence of prominent mood episode, the diagnosis of schizoaffective disorder is made. Patients with personality disorders may occasionally develop brief psychotic episodes especially under stress. None of the aforementioned disturbances can be attributable to the effects of a substance or another medical condition.9 Delusional disorder is characterized by one or more delusions that are present for longer than 1 month and the criteria for schizophrenia have not been met. Patients may believe famous

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people are in love with them (erotomanic) or that they have extraordinary powers or possess a special relationship with a deity or famous person (grandiose type). Other common delusions are of sexual partners being unfaithful (jealous type), that they are being malevolently treated (persecutory type), or that they have some physical defect or medical condition (somatic type). Function is not typically severely impaired, and behavior may not be bizarre apart from the impact of the delusions. Individuals may appear and behave normally if not actively discussing delusions, but social, marital, work, and legal problems can result from delusional beliefs.

DIAGNOSTIC TESTING Diagnostic tests are indicated when a patient’s clinical scenario cannot be explained by the history and physical examination alone. Often there is not enough information readily available to the clinician to accurately ensure that the patient is suffering from a thought disorder alone. The potential medical causes of thought disorders are very broad; therefore, if a medical evaluation is indicated, testing should be patient specific and based on the particular medical processes that the clinician feels may be causing or exacerbating the thought disorder. The clinical judgment of the treating physician, rather than panels of routine tests, should be used to efficiently and appropriately guide diagnostic test ordering. The evaluation of a “first-time” psychosis or thought disorder presentation in an emergency patient differs substantially from the evaluation of a patient with chronic disease and recurrent symptoms. The evaluation for the first time thought disorder patient may include a larger, more detailed laboratory and radiological evaluation. Complete blood counts, electrolyte panels, glucose levels, thyroid function, urine testing, cortisol levels, vitamin B12, methylmalonic acid levels, and rapid plasma regain (RPR) testing could be useful in certain clinical situations and ordered as needed for individual patients. Whether to obtain neuroimaging on the initial evaluation of patients with thought disorders remains controversial. Incidental findings on computed tomography (CT) or magnetic resonance imaging (MRI) occur at similar rates to control patients and rarely lead to the discovery of clinically relevant disorders in the absence of neurological signs.17 Neuroimaging for intra-cranial injury, vasculitis, demyelinating diseases, tumor, cerebrovascular disease, or abscess may be indicated based upon findings noted on the history and physical examination. Given the long-term costs of schizophrenia, neuroimaging in a young person with a first time psychosis will exclude rare and treatable causes of psychosis and can support the diagnosis of schizophrenia, and it should be considered by the treating clinician on a case by case basis. Ancillary testing beyond that required for medical clearance of psychiatric emergency patients rarely alters care, especially for patients with an established diagnosis of schizophrenia or other chronic thought disorders. Policies that require panels of testing prior to psychiatric admission are costly and unnecessary. One of the largest unnecessary costs is incurred with the routine use of urine drug screens, which have been found to rarely alter disposition for psychiatric patients from the ED especially when combined with a good substance abuse history.18 Greater emphasis should be placed on identifying a clinical toxidrome and history of use when attempting to determine if drugs and medications are contributing to the symptoms of psychosis.

MANAGEMENT Patient safety and ED staff safety are a principle concern when a patient presents with aggressive and unpredictable psychotic behavior. Risk factors for violence in patients with schizophrenia

include gross excitement, prior violence, auditory hallucinations, systematization of delusions, incoherence of speech, and long duration of illness. In contrast, traits such as substance abuse and antisocial episodes are not recognized as significant violenceassociated factors.19 Strategies to control disruptive and violent behavior in psychosis and thought disorders include de-escalation techniques, chemical sedation, and physical restraints. Although chemical and physical intervention can be appropriate when patients are demonstrating dangerous behavior, nonphysical intervention, such as verbal de-escaltion should be considered first. The clinician should demonstrate a calm, nonjudgmental demeanor while showing appropriate concern and avoiding excessive stimulation, posturing, and prolonged eye contact. The patient should be given an opportunity to express their concerns, as well as identify unmet needs that can be easily corrected (eg, inadequate pain control, communication failures, or social concerns). If available, consider recruiting trusted others (eg, family, friends, case managers) to help prevent further agitation.20 When verbal de-escalation is ineffective or inappropriate, physical restraint or use of seclusion may be necessary. Risk factors for the use of restraint or seclusion include referrals initiated by a third party, patients arriving to the ED in restraints, and clinician perception of the patient as severely disruptive, already exhibiting psychosis, or experiencing a manic episode.21 Chemical restraint for psychomotor agitation is a common and necessary intervention. Speed of onset and reliability of delivery are two important factors to consider when selecting a route of administration of sedation in the behaviorally disturbed patient. Oral sedation is indicated when the patient can be safely verbally de-escalated, is not at imminent risk of harm to self, and agrees to take oral medications. When more expedient sedation is required, parenteral route has the advantages of immediate effect and titration of dosing. The goal of titration in this setting is the induction of rousable sleep, not unconsciousness.22 Benzodiazepines and antipsychotics are the two medications most commonly used for chemical restraint. Using a single agent or, for more disturbed patients, a combination of the two classes, can be considered. Common agents and dosages are listed in Table 100.1. Combined with concurrent physical restraint and the risk of previously ingested intoxicants, there is significant risk for oversedation and respiratory compromise. The combination of haloperidol and lorazepam causes respiratory depression in up to 50% of patients with a significant number also experiencing a hypoxic event. Fortunately, most episodes are quickly corrected with verbal stimulation or airway repositioning. As a result, we recommend the use of pulse oximetry or CO2 monitoring in chemically restrained patients to detect early signs of respiratory TABLE 100.1 

Common Drugs for Sedation DRUG

USUAL ADULT DOSE

ADVERSE EVENTS

Midazolam

2.5 to 5 mg IM (rapid onset) 1 to 2 mg PO or IM 5 to 10 mg PO or IM (longer acting)

Respiratory depression Oversedation Hypotension Paradoxical excitation reaction in patients with organic brain disease

5 to 10 mg PO or IM 10 to 20 mg PO or IM 10 mg PO or IM

Increased mortality risk in elderly dementia-related psychosis Caution in prolonged QT or history of neutropenia

Lorazepam Diazepam

Haloperidol Ziprasidone Olanzapine

IM, Intramuscular; PO, per os (by mouth).

CHAPTER 100  Thought Disorders

depression.15 In addition to monitoring of airway and level of consciousness, sedated and restrained patients should have frequent behavioral monitoring. The use of physical restraints may cause excess pressure on the patient’s neck, chest or abdomen, and requires ongoing direct visualization. Potentially hazardous articles and possessions should be removed from the patient’s area. Restrained patients are known to forcibly remove Foley catheters without deflation of the balloon if their limbs are released prior to removal of the catheter, resulting in urethral injury. A detailed discussion of the use of physical and chemical restraints is provided in Chapter 189.

DISPOSITION Making an appropriate disposition for patients with decompensated thought disorders is often difficult in today’s emergency medicine practice environment. Although institutional and community psychiatric resources vary widely by region, there appears to be a nationwide trend of diminishing psychiatric referral resources in the presence of rising numbers of psychiatric-related ED visits.23 The number of inpatient psychiatric beds nationwide has decreased dramatically, and many EDs “board” psychiatric patients for extended periods of time. Appropriate disposition is based on the etiology of the underlying psychosis, response to treatment, consideration of patient and community safety, and an appropriate outpatient follow-up plan. Patients who are actively suicidal, dangerous to others, possess severe mental debilitation precluding self-care, or are having their

first psychotic episode should be admitted. The decision for inpatient psychiatric admission is not always precise. There may be disagreement between emergency clinicians and consulting psychiatrists regarding need for involuntary hold and final disposition, but psychiatric consultation can help confirm safety for discharge, help facilitate inpatient admission, and aid in outpatient follow-up.24 Telemedicine is emerging as a technology that may ease the growing lack of adequate psychiatric resources for ED patients by facilitating urgent psychiatric consultation. A recent study demonstrated that telemedicine can be used safely and is not associated with significant differences in care when compared with face-toface psychiatric evaluations.25 Medication noncompliance is a common reason for a known schizophrenic to present to the ED with a decompensated psychotic episode. A patient whose psychosis stabilizes in the ED with medication can sometimes be safely discharged back into the community. Safe discharge planning can be accomplished provided that the patient has adequate ability to care for self and does not pose a risk of harm to self or others. Insight by the patient and judgment to adhere to an agreed course of action, including taking medication, is typically required. Patients with severe underlying psychiatric illnesses may have some degree of persistent mental disability even when optimally treated. For these patients, recruiting family or friends familiar with the patient can help establish that the patient is back to his or her baseline to ensure safety. A safe transition to the community setting requires adequate social support, including follow-up with a mental health service.21

KEY CONCEPTS • Thought disorder symptoms can be precipitated by psychiatric, underlying medical, and toxicologic etiologies. • Diagnostic testing should be patient specific and based on the particular medical processes that the clinician feels may be causing or exacerbating the thought disorder, rather than panels of routine tests. • Consider nonphysical intervention first when appropriate, but chemical sedation and physical restraint are immediately

necessary for patients who demonstrate aggressive and dangerous behavior. • Appropriate disposition depends on the etiology of the underlying psychosis, response to treatment, and patient and community safety considerations and, more often than not, includes psychiatric consultation.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Brennan JJ, et al: Emergency department utilization among frequent users with psychiatric visits. Acad Emerg Med 21(9):1015–1022, 2014. 2. Centers for Disease Control and Prevention: Emergency department visits by patients with mental health disorders—North Carolina, 2008-2010. Morb Mortal Wkly Rep 62(23):469–472, 2013. 3. Abel KM, Drake R, Goldstein JM: Sex differences in schizophrenia. Int Rev Psychiatry 22(5):417–428, 2010. 4. Moghaddam B, Javitt D: From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment. Neuropsychopharmacology 37(1):4–15, 2012. 5. Najjar S, Pearlman DM: Neuroinflammation and white matter pathology in schizophrenia: systematic review. Schizophr Res 161(1):102–212, 2015. 6. Consoli A, et al: Diagnostic transition towards schizophrenia in adolescents with severe bipolar disorder type I: an 8-year follow-up study. Schizophr Res 159(2– 3):284–291, 2014. 7. Meyer U: Developmental neuroinflammation and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 42:20–34, 2013. 8. Strauss GP, et al: Deconstructing negative symptoms of schizophrenia: avolitionapathy and diminished expression clusters predict clinical presentation and functional outcome. J Psychiatr Res 47(6):783–790, 2013. 9. American Psychiatric Association and American Psychiatric Association, DSM-5 Task Force: Diagnostic and statistical manual of mental disorders, ed 5, Washington DC, 2013, American Psychiatric Association, p xliv, 947. 10. Sienaert P, et al: A clinical review of the treatment of catatonia. Front Psychiatry 5:181, 2014. 11. Bora E, Murray RM: Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophr Bull 40(4):744–755, 2014. 12. Han JH, Schnelle JF, Ely EW: The relationship between a chief complaint of “altered mental status” and delirium in older emergency department patients. Acad Emerg Med 21(8):937–940, 2014.

13. Han JH, et al: Delirium in older emergency department patients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med 16(3):193–200, 2009. 14. Testa A, et al: Psychiatric emergencies (part II): psychiatric disorders coexisting with organic diseases. Eur Rev Med Pharmacol Sci 17(Suppl 1):65–85, 2013. 15. Deitch K, et al: Unrecognized hypoxia and respiratory depression in emergency department patients sedated for psychomotor agitation: pilot study. West J Emerg Med 15(4):430–437, 2014. 16. Bromet EJ, et al: Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry 168(11):1186–1194, 2011. 17. Sommer IE, et al: How frequent are radiological abnormalities in patients with psychosis? A review of 1379 MRI scans. Schizophr Bull 39(4):815–819, 2013. 18. Parmar P, et al: Value of mandatory screening studies in emergency department patients cleared for psychiatric admission. West J Emerg Med 13(5):388–393, 2012. 19. Imai A, et al: Factors associated with violence among Japanese patients with schizophrenia prior to psychiatric emergency hospitalization: a case-controlled study. Schizophr Res 160(1–3):27–32, 2014. 20. Fulde G, Preisz P: Managing aggressive and violent patients. Australian Prescriber 34(4):115–118, 2011. 21. Simpson SA, et al: Risk for physical restraint or seclusion in the psychiatric emergency service (PES). Gen Hosp Psychiatry 36(1):113–118, 2014. 22. Mental Health and Drug and Alcohol Office: Mental health for emergency departments—a reference guide, Sydney, 2009, NSW Department of Health. 23. Owens PL, Mutter R, Stocks C: Mental health and substance abuse-related emergency department visits among adults, 2007, HCUP Statistical Brief #92. Available at . 24. Douglass AM, Luo J, Baraff LJ: Emergency medicine and psychiatry agreement on diagnosis and disposition of emergency department patients with behavioral emergencies. Acad Emerg Med 18(4):368–373, 2011. 25. Seidel RW, Kilgus MD: Agreement between telepsychiatry assessment and face-toface assessment for emergency department psychiatry patients. J Telemed Telecare 20(2):59–62, 2014.

CHAPTER 100: QUESTIONS & ANSWERS 100.1. Which of the following pharmacologic agents have been implicated in causing acute psychosis? A. Aripiprazole, hydralazine, nitroglycerin B. Diazepam, rifampin, captopril C. Hydrochlorothiazide, acetaminophen, albuterol D. Lorazepam, salsalate, rocuronium E. Penicillin, ceftriaxone, risperidone Answer: B. Box 100.2 provides an extensive list of other agents that may cause psychosis. 100.2. Rapid tranquilization using a neuroleptic agent would be indicated in which of the following cases? A. An intoxicated schizophrenic B. Anticholinergic psychosis C. A lactating schizophrenic D. A phencyclidine overdose E. A pregnant schizophrenic Answer: A. Neuroleptics are contraindicated in choices B to E. They should not be the sole agent for alcohol withdrawal but would be useful for acute psychotic agitation. 100.3. A 45-year-old woman presents to the emergency department (ED) for a complaint of severe anxiety and unrest. Her past history is significant only for moderate schizophrenia, for which she was placed on olanzapine 2 months prior. She has been compliant. Physical examination is remarkable for the presence of anxiety, clear sensorium and orientation, and normal speech. She is restlessly pacing the room and reports being compelled to keep moving. Urine drug screen is negative. What would be the most appropriate therapy? A. Benztropine orally B. Lorazepam orally C. Olanzapine intravenously D. Psychiatry consultation E. Ziprasidone intravenously

Answer: A. Akathisia is a state of motor restlessness characterized by a physical need to be constantly moving. The patient does not want to do so but feels compelled. It is most commonly seen in middle-aged patients within the first few months of starting treatment. It may be mistaken for an acute deterioration, but psychotic features are not increased. Treatment is with oral beta-blockers and anticholinergics (benztropine). 100.4. What is the most common adverse effect seen with neuroleptic agents? A. Akinesia B. Dystonia C. Orthostatic hypotension D. Pseudoparkinsonism E. Tardive dyskinesia Answer: B. Dystonia occurs in 1% to 5% of this patient population. The reaction occurs because of a dopaminergic pathway disruption with a resulting cholinergic predominance. Anticholinergics should be administered parenterally (Benadryl 25 to 50 mg intravenous [IV] or Cogentin 1 or 2 mg IV), followed by 48 to 72 hours of oral follow-up treatment to prevent recurrence. Patients may experience tongue protrusion (buccolingual crisis), upward eye deviation (oculogyric crisis), back arching (opisthotonus), and, rarely, laryngospasm. Symptoms may lessen with voluntary muscle action and increase with stress. 100.5. A 27-year-old known schizophrenic is brought to the emergency department (ED) for altered mental status. His only known medication is clozapine, which he started 4 weeks ago with subsequent dose increases. He has no other past history. Physical examination is remarkable for a muscular black man who is somnolent and diaphoretic. He withdraws all extremities stiffly and grimaces to pain. Vital signs are temperature, 40.5° C; heart rate, 146 beats per minute; blood pressure, 205/125 mm Hg; and respiratory rate 28 breaths per

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minute. Rectal examination is guaiac positive. Foley placement shows brown urine. What should be the next diagnostic maneuver? A. Creatine kinase level B. Head computed tomography (CT) scan C. Lumbar puncture D. Thyroid hormone levels E. Urine drug screen Answer: A. Neuroleptic malignant syndrome is an idiopathic condition clinically similar to serotonin syndrome and malignant

hyperthermia. Milder cases may be confused with serotonin syndrome. Severe cases, related to possible hypothalamic dysfunction, present with fever, rigidity, altered mental status, autonomic instability, and elevated creatine phosphokinase (CPK) and possibly rhabdomyolysis. It is seen with both typical and atypical antipsychotics and generally occurs in the first few weeks of treatment. Complications may include hepatic/renal failure, gastrointestinal (GI) hemorrhage, and respiratory failure. Severe cases may require intravenous dantrolene or dopamine agonists (eg, bromocriptine).

C H A P T E R 101 

Mood Disorders Leslie S. Zun  |  Kimberly Nordstrom PRINCIPLES Mood is a subjective emotional state. It is normal human experience to have fluctuations in mood in response to occurrences in everyday life. A change in mood becomes a “mood disorder” when it significantly impairs functioning. In the emergency department (ED), patients with mood disorders often present grossly debilitated, with thoughts of suicide, homicide, or profound self-neglect. These patients frequently present in emotional crisis, but this may not be their presenting complaint. Approximately, one-fourth to one-third of ED patients screen positive for mood disorders. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), divides mood disorders into two broad categories: depressive disorders and bipolar disorders.1 Mood disorders may also be due to a general medical condition or substanceinduced mood disorders. Because the specific pathophysiologic mechanisms of these disorders are not fully understood, they are categorized by groupings of symptoms that persist for defined lengths of time.

EPIDEMIOLOGY Mental health patients are the fastest growing group of patients presenting to the ED. In 2007, 13% of the 94 million ED visits in the United States were for psychiatric reasons, which was an increase from 5% in 2000.2 This increase is nearly double what would have been expected by population growth alone.3 Up to 50% of Americans will meet the criteria for a DSM-5 disorder sometime in their life, with an estimated 21% having a mood disorder. The World Health Organization (WHO) ranks major depressive disorder as one of the most prevalent and disabling diseases in the world. The 12-month prevalence for major depressive disorder is 5% and the lifetime prevalence is 13%. Patients with major depressive disorder frequently have other comorbid mental health issues, including anxiety disorders, personality disorders, and substance use disorders. The lifetime prevalence of bipolar spectrum disorders is approximately 4%. Both severe depression and mania are serious and potentially life-threatening. Up to 80% of patients with bipolar disorder will exhibit suicidal behavior, and half will attempt suicide. Suicidal behavior can occur during all phases of bipolar disorder, but patients experiencing a depressed or a mixed episode are at higher risk, especially those with severe depressive symptoms and a sense of hopelessness.

PATHOPHYSIOLOGY The pathophysiology of the mood disorders is not well established, but much is known about the neurophysiology, genetics, and psychosocial aspects of the disorders.4

Neurophysiology Antidepressants work by increasing the availability and activity of serotonin and norepinephrine at the synapse to stimulate the 1346

postsynaptic neuron. This is done by direct binding to the presynaptic and postsynaptic receptors, blocking reuptake of the neurotransmitter or inhibiting the enzymatic breakdown of the neurotransmitter. Because norepinephrine and serotonin systems traverse large portions of the brain, monoamine deficiency is hypothesized as a cause of depression. Depletion of oral tryptophan and tyrosine, amino acids essential for the production of serotonin and norepinephrine, respectively, can induce a depressive episode in subjects with a history of depression but not in healthy controls. Monoamine metabolite levels in cerebrospinal fluid, plasma, urine, and postmortem brains of patients with depression have not been reliably found to be deficient, indicating that there could be downstream effects involving secondmessenger systems, such as cyclic adenosine monophosphate and phosphatidylinositol. Other neurotransmitter systems may play a role in the development of depression. Decreased levels of both glutamate and γ-aminobutyric acid have been found in the prefrontal cortex of depressed subjects. Intravenous ketamine, an N-methyl-daspartate (NMDA) antagonist, induces a rapid antidepressant effect and suggests a role for glutamate in the pathophysiologic process of depression. The brain relies on the actions of protective and regenerative cytokines, such as brain-derived neurotrophic factor (BDNF). All known antidepressants raise levels of BDNF and subsequently result in neurogenesis of certain brain regions, such as the hippocampus. Other theories include the melatonergic system and related abnormalities in circadian rhythm, decreased neurosteroid synthesis, impaired endogenous opioid functioning, monoamine-acetylcholine imbalance, inflammatory effects of cytokines, and dysfunction of specific brain structures and circuits. The neurophysiology of bipolar disorder is less well understood than unipolar depression, in part because of the fluctuating mood states and the heterogeneity of the disorder. Bipolar disorder may in part arise from abnormalities in the connections within and between structures in the brain.5 Specifically implicated are circuits interconnecting the amygdala, hypothalamus, striatum, and subdivisions of the frontal cortex, all of which are involved in both the generation and regulation of emotion.5

Neuroanatomy Neuroimaging studies of the brain suggest that abnormalities in certain areas and the interconnections between those areas may be involved mood disorders. A common magnetic resonance imaging (MRI) finding in patients with mood disorders, especially bipolar disorder, is an increased occurrence of subcortical hyperintensities in the periventricular areas, basal ganglia, and thalamus. High-resolution MRI demonstrates reduced volumes in the hippocampus, orbital cortex, and anterior cingulate. These findings are associated with more severe illness, bipolar disorder, and increased cortisol levels. Volume reduction in the hippocampus is associated with high illness chronicity. The amygdala is a clustering of nuclei that process emotional stimuli, especially fear, anger, and sadness. Functional neuroimaging suggests that amygdala activity is increased when the subject

CHAPTER 101  Mood Disorders

is exposed to emotionally relevant stimuli. The amygdala has connections throughout the brain. A decreased amygdala volume has been associated with unipolar depression.

Endocrine System Physiologic changes such as increased alertness, decreased appetite, increased heart rate, and activation of the hypothalamicpituitary-adrenal (HPA) axis occur when a person is stressed. The HPA axis may play a role in depression, especially in cases of early childhood and chronic stress.4 Activation of the HPA axis releases corticotropin-releasing hormone (CRH) from the hypothalamus. Although not specific, patients with depression may have increased levels of free cortisol in the plasma, cerebrospinal fluid, and urine. Increased CRH has been demonstrated in cerebrospinal fluid, and increased levels of CRH messenger RNA and protein have been demonstrated in limbic brain regions. Although none of these measures is reliable as a diagnostic tool, successful treatment to remission has been shown to reverse some of these abnormalities.

Genetics Genetic vulnerability to mood disorders has not been traced to a single gene. It is likely to be due to the additive effects of many genes and environmental influences on how these genes are expressed. Family, twin, and adoption studies provide evidence that major depressive disorder is a familial disorder but is less heritable than bipolar disorder. Bipolar disorder is one of the most heritable medical illnesses with a heritability of 80% to 85% and a monozygotic twin concordance of about 40%.

Psychosocial Factors The etiology of most psychiatric problems, including mood disorders, involves complex interactions between both biologic and psychosocial factors.4 The complex neural mechanism that regulates mood responds to and is modified by each person’s experience, including events in early childhood, such as childhood sexual abuse, reward and punishment during growth and development, other lifetime trauma, marital problems, low social support, and various kinds of loss. Psychosocial theories of mood disorder form the basis for psychotherapy.4

CLINICAL FEATURES Major Depressive Disorder Major depressive disorder is characterized by one or more major depressive episodes, as defined by DSM-5 criteria (Boxes 101.1 and 101.2).1 A major depressive episode is characterized by disturbances in four major areas: mood, psychomotor activity, cognition, and vegetative function. The patient must have at least five symptoms for a minimum of 2 weeks and one of the five must be depressed mood or anhedonia (decreased interest or pleasure).1

Mood Disturbances Patients in a depressed state often feel profoundly hopeless and helpless. There are many words and phrases that can be used to describe feeling depressed; some patients will not recognize that they are “depressed” but rather they may describe the feeling in some other manner. Someone feeling no emotion (profoundly depressed) may answer “no” when asked about depressed mood. On the other hand, a person may meet criteria for a major depressive episode and not be experiencing a depressed mood. Depression can also be manifested as a decreased capacity to

BOX 101.1 

Summary of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Criteria for a Major Depressive Episode A. Five or more of the following symptoms have been present almost every day during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Note: Do not include symptoms caused by a general medical condition. 1. Depressed mood (can be irritable mood in children and adolescents) 2. Loss of interest or pleasure in activities 3. Significant weight loss when not dieting or weight gain, or decrease or increase in appetite 4. Insomnia or hypersomnia 5. Psychomotor agitation or retardation 6. Fatigue or loss of energy 7. Feelings of worthlessness, or excessive or inappropriate guilt 8. Diminished ability to think or concentrate, or indecisiveness 9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation, or a suicide plan or attempt B. Symptoms cause clinically significant distress or impairment in social, occupational, or other functioning. C. Symptoms are not caused by direct physiologic effects of a substance (eg, drug of abuse, medication) or a general medical condition (eg, hypothyroidism). D. Symptoms are not better explained by another mental health disorder. E. There has never been a manic or hypomanic episode. Modified from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

BOX 101.2 

Mnemonics for the Symptoms of Depression and Mania MNEMONIC FOR THE SYMPTOMS OF DEPRESSION Sig E Caps Sleep amount increased or decreased Interest (anhedonia) Guilt Energy level decreased Concentration decreased Appetite increased or decreased Psychomotor activity increased or decreased Suicidal ideation

MNEMONIC FOR THE SYMPTOMS OF MANIA Dig Fast Distractibility Irritability Grandiosity Flight of ideas Activity increased Sleeplessness Thoughtlessness (impulsivity, increased risk taking)

experience pleasure or interest in otherwise pleasurable activities. This loss of interest is known as anhedonia. As noted previously, the patient must exhibit a depressed mood or anhedonia to meet DSM-5 criteria for a diagnosis of a major depressive episode.1

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Disturbances in Psychomotor Activity Physical activity in depression can be either increased or decreased. Psychomotor retardation is a significant slowing of physical activity. When suffering from psychomotor retardation, thinking and speaking can be slow, causing delayed responses to answers. Depressed patients often describe feeling fatigued with a general lack of energy and motivation. Conversely, patients may display psychomotor agitation, which can be manifested as fidgeting, pacing, hand wringing, or restlessness.

Vegetative Disturbances

Prepubertal children are more likely to have somatic complaints, psychomotor agitation, and mood-congruent hallucinations and less likely to have disturbances in sleep and appetite. Some children are misdiagnosed as having attention deficit disorder, especially if symptoms involve poor concentration, listlessness, agitation, and withdrawal from daily activities. Adolescents with depression may show increased irritability, oppositional behavior, and substance abuse. Other characteristics are social withdrawal, increased rejection sensitivity, and decline in school performance. Some adolescents may be first diagnosed with depression on receiving treatment for drug and alcohol problems.

Vegetative symptoms include disturbances in three major areas: sleep, appetite, and sexual function. Depressed patients may complain of insomnia or hypersomnia. Insomnia may be manifested as difficulty in falling asleep, frequent awakenings throughout the night, or early-morning wakening. Depressed patients with hypersomnia may report sleeping 12 to 14 hours or more a day. Alterations in appetite and eating patterns can also occur, resulting in significant weight gain or loss during a short time. Loss of interest in sexual activity and impaired sexual functioning may also accompany depression, although this is not listed as a DSM-5 criterion.

Disruptive Mood Dysregulation Disorder.  A newly described phenomenon for children who may have been previously diagnosed with depression or bipolar disorder is disruptive mood dysregulation disorder. Children and adolescents given this diagnosis display severe, recurrent outbursts that are out of proportion for the situation and are inconsistent with developmental level. The outbursts must occur three or more times a week, and the mood in between outbursts is irritable or angry most days. There are duration criteria of 12 months with no periods of three or more consecutive months not meeting criteria. Symptoms must occur prior to age 10.1

Thought Process and Content

Geriatric Patients.  Depression is more common in elders because of more frequent occurrences of loss, comorbid health issues, and loss of autonomy. The elderly have a tendency to report more somatic complaints when depressed. They are also more vulnerable to development of melancholic depression, which is characterized by early morning awakening, diurnal variation in mood, low self-esteem, and low mood reactivity. Older depressed patients can also present with symptoms involving memory loss, inattention, withdrawal from daily activities, and lapses in personal and social hygiene that suggest dementia rather than depression. When such symptoms are from depression, the condition is called pseudodementia. Serious depression in elders is a highly treatable, reversible condition.

Depressed patients often describe impaired concentration and forgetfulness. Executive functioning can also be impaired. In severe cases, this results in a decreased ability to perform basic activities of daily living. Thought content tends to be negatively biased, such as recurrent thoughts of guilt, failure, worthlessness, and self-criticism. Patients in a depressed episode are at increased risk for suicide. Suicidal thoughts may range from vague notions that life is not worth living (passive) to fully envisioned suicide plans with definitive intent to kill themselves (active). All depressed patients must be questioned about suicidal thoughts. Because patients are not often forthcoming with their thoughts on suicide, a thorough review of risk factors and protective factors needs to form the basis of clinical decisions for providing the necessary level of care. Patients with severe depression may have psychotic symptoms. The hallucinations and delusions that accompany depression are usually mood congruent, meaning that the themes of the psychotic content are consistent with the depressed mood.

Masked Depression Mood disorders may not be clear at presentation. The depressed patient may have only vague somatic symptoms. Common complaints include weakness, fatigue, headache, and abdominal pain with medical evaluations occurring in response. Patients may not be aware of their depression and are often heavy users of medical care. Over half of patients with major depressive disorder initially present with somatic symptoms only which can mask a hidden depression. Clues that suggest a mood disturbance include the recent onset of a set of unusual behaviors, significant social disturbance, such as job loss, financial stress and marital difficulties, and self-destructive behavior (eg, substance abuse, sexual promiscuity).

Special Considerations Children and Adolescents.  Criteria for depression in children and adolescents are the same as for depression in adults. Depression in these age groups can, however, present differently.

Other Depressive Disorders Postpartum Depression Postpartum depression is a depressive disorder that occurs during or within 4 weeks of delivery and would allow for the specifier “with peripartum onset.” Symptoms of depression are common in the perinatal period. As noted in the DSM-5, between 3% and 6% of women will experience the onset of major depression during pregnancy or within the following weeks to months.1 Similarly, but less severe, up to 65% of mothers report some depressed mood after childbirth, often called postpartum blues. Symptoms are generally mild and transient; although in 10% of mothers, it may lead to a full-fledged episode of major depression. Postpartum mood episodes with psychotic features can be particularly dangerous. Infanticide is most often associated with command hallucinations to kill the infant or associated delusions. The risk for this is most closely related to a past history of postpartum episodes with psychosis, a history of depression or bipolar disorder, or a family history of bipolar disorder.

Persistent Depressive Disorder Persistent depressive disorder is a new diagnosis that combines two former diagnoses: chronic major depressive disorder and dysthymic disorder. Specific criteria include the following: depressed mood most of the day, most days for at least 2 years;

CHAPTER 101  Mood Disorders

two or more of the following: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness; never more than 2 months of the 2 years without symptoms; and must cause significant distress or impairment in functioning. Exclusion criteria include a history of hypomania or mania and a history of psychotic illness. Also, it cannot be due to a substance or medical condition.1 There are multiple specifiers that can be applied to this diagnosis.

Premenstrual Dysphoric Disorder Premenstrual dysphoric syndrome is a new diagnosis included in the DSM-5. At least five of the listed symptoms must be present in the final week before the onset of menses and start to improve within a few days after the onset of menses and be absent or minimal in the week post menses. These symptoms must be present for most cycles over the preceding year. The onset can occur at any point after menarche. Risks for development include stress, history of interpersonal trauma, seasonal changes, and sociocultural aspects of female sexual behavior.

Seasonal Affective Disorder Seasonal affective disorder is not a separate mood disorder, but rather, a specifier of major depressive disorder. An example of the use of a specifier is “major depressive disorder, recurrent, moderate, with seasonal pattern.” This specifier can only be used with a recurrent major depressive disorder. The criteria for this include the following: a regular temporal relationship between onset of depressive episode and a particular time of year, full remissions at a specific time of year, two depressive episodes within 2 years that demonstrate a temporal relationship, no nonseasonal episodes within the same period, and substantially more seasonal depressive episodes than nonseasonal episodes over the person’s lifetime.1 Melatonin, a hormone secreted in the brain and produced at high levels in the dark, has been implicated in the etiology of this disorder. Phototherapy is an effective and safe treatment of seasonal depression. Light exposure to the eyes seems to be essential, but the exact mechanism of action is still unknown.

Bipolar Disorders Bipolar disorder is lifelong, with episodic exacerbation of symptoms and deterioration of function characterized by extreme mood episodes. Patients with bipolar disorder may require different forms and intensities of treatment at different stages of the illness. Bipolar I disorder includes at least one manic episode, and patients have typically had one or more major depressive episodes, although a depressive episode is not necessary for diagnosis. Bipolar II disorder involves a hypomanic episode and at least one major depressive episode. A hypomanic episode includes the features of a manic episode without psychosis, marked impairment of function, or the need for hospitalization.

Manic Episode During a manic episode (Boxes 101.2 and 101.3), the disturbance in mood must be severe enough to include psychosis, the need for hospitalization, or marked impairment in functioning. Bipolar disorders are much less common than major depressive disorder. The overall prevalence of a manic episode is about 2% in both women and men. In many cases, manic patients are brought to the ED by someone else (eg, family, police, or emergency medical services). Patients who are experiencing a manic episode may present

BOX 101.3 

Summary of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Criteria for a Manic Episode A. Distinct period of abnormally and persistently elevated, expansive, or irritable mood, and abnormally and persistently increased goal-directed activity or energy lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance and increased energy or activity, three or more of the following symptoms have persisted (four, if the mood is only irritable) and have been present to a significant degree: 1. Inflated self-esteem or grandiosity 2. Decreased need for sleep (eg, feels rested after only 3 hours of sleep) 3. More talkative than usual or pressure to keep talking 4. Flight of ideas or subjective experience that thoughts are racing 5. Distractibility (ie, attention too easily drawn to unimportant or irrelevant external stimuli) 6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (eg, buying sprees, sexual indiscretions, foolish investments) C. Mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or social activities or to necessitate hospitalization to prevent harm to self or others, or psychotic features are present. D. Symptoms are not caused by direct physiologic effects of a substance (eg, drug of abuse, medication) or a general medical condition (eg, hyperthyroidism). Modified from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

as gregarious, humorous, and engaging, which may suddenly alternate with belligerence and irritability. Patients may display pressured speech, in which they keep talking, often rapidly and loudly without pauses between thoughts or sentences, and are difficult to interrupt. The thought process in mania is characterized by illogical associations and flight of ideas. An inflated selfesteem and grandiose delusions may lead them to also be argumentative, impatient, and condescending. Grandiosity often centers on very broad dramatic or universal themes, such as religion or politics. The patient may describe a massive undertaking, such as “uniting the world’s churches” or “solving world poverty.” These severe symptoms are usually accompanied by a profound lack of insight. Despite obvious altered behavior, impaired judgment, and poor impulse control, the patient may insist that there is nothing wrong or blame problems on others. Manic patients have decreased or no need for sleep and typically report being awake for days. They may be involved in a massive project (eg, writing a novel), may completely disregard consequences of actions, may have difficulty with spending (eg, credit cards revoked), and may engage in risky behavior (eg, sexual liaisons with strangers, risky driving). Whenever possible, a corroborating history should also be obtained from family or others who know of the patient’s behavior. Manic patients may present as trauma patients, injured by an action reflecting the patient’s grandiosity (eg, attempting to fly), impulsivity, or belligerence (eg, fighting, resisting arrest). A manic episode may be punctuated by abrupt periods of tearfulness and profound depression, including suicidal ideation. When

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depressive and manic features occur concurrently in such a manner, the disorder is termed mixed or bipolar, mixed phase.

Cyclothymic Disorder Cyclothymic disorder is characterized by chronic mood swings that do not meet criteria for a hypomanic or depressive episode. The mood episodes must occur over at least 2 years, present for at least half the time, and the individual cannot be symptom free for more than 2 months at a time.1

Mood Disorders Caused by a General Medical Condition This diagnosis requires a prominent and persistent period of depressed mood or anhedonia that predominates the clinical picture, with evidence that the disturbance is the direct pathophysiological consequence of a medical condition, and not better explained by another mental disorder or occurring during the course of delirium.1 Bipolar disorder requires a prominent and persistent period of abnormally elevated, expansive, or irritable mood; and abnormally increased activity or energy that predominates the clinical picture, with evidence of direct pathophysiological consequence of another medical condition, and it is not better explained by another mental disorder or occurs during the course of delirium.1 Certain medical illnesses have a well-known association with mood disorder. In Parkinson’s disease, electrical stimulation to a certain area of the substantia nigra alleviates symptoms of depression. Stimulation of an area only 2 mm away can cause acute reversible symptoms of depression, such as crying, not wanting to live, and hopelessness. Parkinson’s disease has a well-known association with depression, with up to 40% of patients demonstrating major depression. Certain malignant neoplasms have a well-known association with depression, including pancreatic carcinoma, brain neoplasm, and disseminated malignant disease (eg, lymphoma). Coronary artery disease, myocardial infarction, stroke, end-stage renal disease, acquired immunodeficiency syndrome, several endocrine diseases, and connective tissue disease are also associated with major depressive disorder. After a myocardial infarction, patients with depression have a 3.5-fold increase in cardiovascular mortality compared with nondepressed patients. The development of stroke, diabetes, and osteoporosis is more likely in patients with depression than in those who are not depressed. Depression related to medical conditions may be different in some respects from primary depression and responds less favorably than primary depression to antidepressant medication.

Mood Disorders Caused by Medications or Other Substances These are very similar to mood disorders caused by medical conditions, with the exception of that the symptoms must develop during or soon after substance intoxication or withdrawal, or after exposure to a medication capable of producing the symptoms.1 Many medications are associated with symptoms of mood disorders. Multiple antihypertensives, anticonvulsants, and hormones have been associated with depressive symptoms, and certain antibiotics and steroids are associated with manic symptoms. Intoxication with or chronic heavy use of alcohol, sedatives, hypnotics, anxiolytics, narcotics, and other depressants can cause symptoms of a major depressive episode. Stimulants such as cocaine, phencyclidine, hallucinogens, and amphetamines can cause symptoms of a manic episode. Mood disorder symptoms can also develop during withdrawal. To qualify for this diagnosis, the symptoms must not occur exclusively during a course of

delirium, must cause significant distress or impairment of functioning, and must develop within a month of either substance intoxication or withdrawal. When the mood disorder predates the period of substance abuse or lasts longer than 1 month after the period of abuse, the diagnosis may be an underlying mood disorder, such as a major depressive disorder or bipolar disorder, with a comorbid substance abuse or dependence diagnosis.

DIFFERENTIAL DIAGNOSIS Medical Disorders, Medications, and Substance Abuse or Withdrawal Medical disorders, medications, and substance abuse or withdrawal can either cause or mimic mood disorders. The patient with symptoms and signs of depression may have an unrecognized malignant neoplasm or sedative intoxication. Differential diagnostic considerations for manic symptoms include stimulant abuse (eg, cocaine, amphetamines), hallucinogen abuse, alcohol or sedative withdrawal, delirium, hyperthyroidism, and other medical conditions causing agitation. See the previous section for further information. Patients may be treated with antidepressant medication for a variety of disorders other than depression, such as anxiety, obsessive-compulsive disorder, post-traumatic stress disorder, pain syndromes, smoking cessation, and vasodepressor syncope.

Grief and Bereavement Grief and bereavement are normal human reactions to the acute loss of another person, health, social position, or job. The period of mourning is characterized by sadness, diminished sense of well-being (somatic complaints), sleeplessness, and sadness triggered by thoughts of the loss. Normal grief, however, does not include guilt, loss of self-esteem, feelings of worthlessness, suicidal intent, psychomotor retardation, or occupational dysfunction. The duration of normal grief and bereavement differs among cultures and among individuals within cultures, but severe symptoms normally resolve within 6 to 12 months.

Adjustment Disorders Adjustment disorders are behavioral or emotional disorders that occur in response to an identifiable stress or stressors, with marked distress that is out of proportion to the severity of the stressor. The emotional component can involve sadness, low self-esteem, suicidal behavior, hopelessness, helplessness, or other selfthreatening behavior. Acute adjustment disorder occurs within 3 months of the stressor and does not last longer than 6 months.1 The stressors are typically not as severe as those precipitating bereavement reaction, and the responses are often more maladaptive.

Borderline Personality Disorder Borderline personality disorder is characterized by unstable personal relationships, unstable self-image, and self-destructive behaviors. The disorder may include chronic feelings of emptiness, which may be misdiagnosed as depression, or reactivity of mood, which may be mistaken for mania or hypomania. These patients typically live lives of crisis and constant conflict.

Dementia Dementia can be confused with depression but is characterized by abnormal mental status, including abnormalities in tests of memory, calculation, and judgment.

CHAPTER 101  Mood Disorders

Based on response to interventions, medication is now required

Agitation associated with delirium

Agitation due to intoxication Agitation associated with psychosis in patient with known psychiatric disorder

ETOH or BZN withdrawal not suspected

ETOH or BZN withdrawal is suspected

Identify and correct any underlying medical condition Avoid BZN 1. Oral secondgeneration antipsychotics Risperidone 2 mg Olanzapine 5–10 mg

DNS stimulant

1. Oral benzodiazepines Lorazepam 1–2 mg Chlordiazepoxide 50 mg Diazepa 5–10 mg 2. Parenteral benzodiazepines Lorazepam 1–2 mg IM or IV

Undifferentiated agitation or complex presentation

CNS depressant (eg, ETOH)

1. Oral first-generation antipsychotics Haloperidol 2–10 mg

1. Oral secondgeneration antipsychotics Risperidone 2 mg‡ Olanzapine 5–10 mg‡

2. Parenteral firstgeneration antipsychotics Haloperidol 2–10 mg IM

2. Oral first-generation antipsychotics Haloperidol 2–10 mg with BZN

Avoid BZN if possible

2. Oral first-generation antipsychotics Haloperidol (low dose)* 3. Parenteral secondgeneration antipsychotics Olanzapine 10 mg IM Ziprasidone 10–20 mg IM 4. Parenteral firstgeneration antipsychotics Haloperidol (low dose)# IM or IV (with caution)†

No psychosis evident Same as agitation due to withdrawal Psychosis evident Same as for primary psychiatric disorder

3. Parenteral secondgeneration antipsychotics Olanzapine 10 mg IM‡ Ziprasidone 10–20 mg IM‡ 4. Parenteral firstgeneration antipsychotics Haloperidol 2–10 mg with BZN

Fig. 101.1.  Protocol for treatment of agitation. BZN, Benzodiazepine; CNS, central nervous system; ETOH, ethyl alcohol; IM, intramuscular; IV, intravenous. *There is strong evidence that doses above 3 mg (per day) in patients with dellrium are associated with significant risk of extrapyramidal side effects (EPS), so patients receiving more than 3 mg/day should be assessed carefully for EPS. †See U.S. Food and Drug Administration (FDA) guidelines. ‡If an antipsychotic alone does not work sufficiently, add lorazepam 1 to 2 mg (oral or parenteral). (Redrawn from Wilson MP, Pepper D, Currier GW, et al: The psychopharmacology of agitation: consensus statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup. WJEM 13[1]:26-34, 2012.)

DIAGNOSTIC TESTING History and physical examination should focus on determining if the patient has a mood disorder or the possibility that drug abuse, medications, or a general medical condition may be responsible for the patient’s condition instead. It is essential to identify medical conditions that may exacerbate a psychiatric presentation. The psychiatric history should ask about current symptoms, precipitating events (eg, job loss or relationship), past psychiatric and substance history, history of self-harm or suicide attempts, and identification of support systems. Even if not suggested by the

patient, careful questioning of suicidal thoughts is necessary. If possible, history should be confirmed by speaking with the patient’s regular health care providers and interviewing family, friends, or eyewitnesses to the events that precipitated the ED visit. A tentative diagnosis can be established by use of DSM-5 criteria. Laboratory tests to investigate medical conditions may be necessary based on the specifics of the clinical presentation, but no tests can confirm or exclude mood disorders. Patients with new symptoms compatible with mood disorders need a more extensive medical and psychiatric investigation than those with a known disorder.

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MANAGEMENT Patients presenting with mood disorder symptomology are frequently in crisis, often overwhelmed, and frankly scared. The ED is a chaotic, stimulating environment that may cause or exacerbate the patients’ level of agitation. Creation of a safe and stable environment for the patient is a high priority. The patient with an acute manic episode may be disruptive, refuse medical evaluation, and make repeated attempts to leave the ED. The initial step in treating such a disruptive patient is to offer assistance in reducing the agitation. A recent consensus guideline produced by the American Association for Emergency Psychiatry, noted keys to de-escalation.6 One key is offering anxiolytic medication early in the patient’s presentation. If de-escalation techniques and medication do not resolve the agitation, the patient may need to be placed in seclusion or restraints for his or her safety and that of others. This is a last resort after other de-escalation measures have failed. Chapter 189 discusses the use of seclusion and restraints in the ED. If a medical cause for agitation is found, treatment is aimed at the underlying cause (eg, oxygen for hypoxic delirium). Often in the ED, treatment may need to begin prior to the cause of the agitation being fully recognized.7 Figure 101.1 shows a simple algorithm for approaching the agitated patient. Treatment of depression in the ED is more controversial. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are the main treatments for depression. For the patient who is awaiting inpatient psychiatric placement, these medications could be started in consultation with the admitting service. If the patient has a mild to moderate depression, not requiring hospitalization, they may be started on an SSRI as long as they have close follow-up arranged. SSRIs are known to have a myriad of side effects that can lead to premature discontinuation.8 For the patients who are already on psychotropic medications but have discontinued them for some reason, it is reasonable to restart these medications in the ED. A non-agitated manic patient may be able to inform the treatment team about what has worked well in the past. There are two medication choices for acute mania: antipsychotics and mood stabilizers. All of the atypical, or second generation, antipsychotics have been approved to treat acute mania as monotherapy or as an adjunctive therapy, except paliperidone and iloperidone. Lithium, valproic acid/divalproate, and carbamazepine are the most well

studied mood stabilizers. Lithium and carbamazepine need to be titrated, but valproic acid can be loaded in the ED at 20 to 30 mg/ kg a day (divided dose) in a healthy person with normal liver function. The atypical antipsychotic medicines including ziprasidone, risperidone, olanzapine, aripiprazole, and quetiapine, cause fewer side effects (such as, acute dystonia) than conventional antipsychotic agents. Oral doses should be offered first, and several agents, including risperidone, olanzapine, and aripiprazole, are available in rapidly dissolving tablet form. Three are available as an intramuscular injection: ziprasidone (Geodon), olanzapine (Zyprexa), and aripiprazole (Abilify). Ziprasidone 10 mg to 20 mg is effective; however, its use is limited to 40 mg per 24 hours. Olanzapine 2.5 mg to 10 mg is effective but is associated with postural hypotension, and it is not recommended in combination with parenteral benzodiazepines because of the risk of cardiopulmonary depression. Aripiprazole is the newest agent and at doses of 9.75 mg to 15 mg seems to be the least sedating of the atypicals, but it is more likely to cause nausea and vomiting. It is valuable to obtain psychiatric consultation during the initiation of agitation treatment, because these patients will generally require significant ED treatment or psychiatric hospitalization.

DISPOSITION To determine the appropriate disposition for patients presenting with a mood disorder, a suicide risk assessment is required. The Substance Abuse and Mental Health Services Administration developed a practical tool referred to as the Suicide Assessment Five-Step Evaluation and Triage (SAFE-T).9 Current suicidal thoughts, risk factors and protective factors should be identified, as well as past suicidal thoughts, plans, or acts. Chapter 105 provides an in-depth discussion of suicide assessment. It is only after considering this information that an appropriate intervention can be determined. With the help of social workers or a mental health worker, many patients can be safely discharged home with close follow-up. Patients receiving initial treatment in the ED, without a proper handoff to outpatient care, are at an increased risk for return. If available, it is preferred that a social worker or mental health worker connect discharged patients with outside agencies and services, rather than providing patients with a referral list.

KEY CONCEPTS • Patients with apparent mood disorders should be evaluated for medical disorders, medication effects, or substance abuse or withdrawal because these conditions can mimic both depression and mania. • Mood disorders should be suspected in patients with multiple, vague, nonspecific complaints and in patients who are frequent, heavy users of medical care.

• The differentiation of depression and dementia in elders can be difficult but is important because depression often responds dramatically to treatment. • Patients with mood disorders should be assessed for their suicide potential.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 101  Mood Disorders

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REFERENCES 1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association. 2. Chang G, et al: Hospital variability in emergency department length of stay for adult patients receiving psychiatric consultation: a prospective study. Ann Emerg Med 58: 127–136.e1, 2011. 3. Tang N, Stein J, Hsia RY, et al: Trends and characteristics of US emergency department visits, 1997-2007. JAMA 304(6):664–670, 2010. 4. Hasler G: Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 9:155–161, 2010. 5. Mahon K, Burdick KE, Szeszko PR: A role for white matter abnormalities in the pathophysiology of bipolar disorder. Neurosci Biobehav Rev 34:533–554, 2010. 6. Richmond JS, Berlin JS, Fishkind AB, et al: Verbal de-escalation of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project BETA De-Escalation Workgroup. West J Emerg Med 13(1):17–25, 2012.

7. Wilson MP, Pepper D, Currier GW, et al: The psychopharmacology of agitation: consensus statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup. West J Emerg Med 13(1):26–34, 2012. 8. Warden D, Madhukar H, Trivedi MD, et al: Early adverse events and attrition in SSRI treatment: a suicide assessment methodology study. J Clin Psychopharmacol 30: 259–266, 2010. 9. Substance Abuse and Mental Health Services Administration (SAMHSA): Suicide Assessment Five-Step Evaluation and Triage (SAFE-T). Available at .

CHAPTER 101: QUESTIONS & ANSWERS 101.1. What is the lifetime suicide risk for people with major untreated depression? A. 5% B. 10% C. 15% D. 20% E. 25% Answer: C. Patients with major depression have a high lifetime suicide risk, and although episodes of acute decompensation with even higher risk can be identified and treated, a certain number of patients succeed in committing suicide. 101.2. Which of the following imbalances of central nervous system neurotransmitters is seen in patients with clinical depression? A. Decreased hypothalamic-pituitary-adrenal (HPA) activity B. Depressed serotonin levels C. Elevated gamma-aminobutyric acid (GABA) levels D. Elevated norepinephrine levels E. Unchanged dopamine levels Answer: B. The central biochemical features toward which pharmacologic management is directed are depressed levels of norepinephrine and serotonin. Data are also emerging that suggest decreased dopamine levels. The HPA axis may also be altered with elevated cortisol levels. 101.3. Which of the following statements regarding depression in children and elders is true? A. Children with depression rarely present with somatic complaints. B. Depression in children may be manifested as attention deficit disorder (ADD). C. Depression presents differently from dementia in elders. D. Diagnostic criteria for depression in children are different. E. Serious depression in elders is generally refractory to treatment.

Answer: B. Depression in children and adolescents can be manifested as ADD. Somatic complaints are a common feature of children and adolescents presenting with depression, but the diagnostic criteria are not different. Geriatric depression may be manifested in a manner similar to dementia (pseudodementia), but unlike dementia, the depression is highly treatable and reversible once it is recognized. 101.4. A 31-year-old attorney is brought to the emergency department (ED) by his family for a chief complaint of agitation and a behavioral change. He has no past medical history and takes no medications. The family reports decreased sleep, increased talkativeness, marked increased time and involvement at work, and an uncharacteristic buying spree. Your examination is remarkable for distractibility, gregarious and pressured speech, flight of ideas, and mild psychomotor agitation. Laboratory examination and urine drug screen results are negative. The patient is adamant that he has important things to do and needs to leave. Which of the following statements is most true? A. Antipsychotic agents are not effective. B. Hallucinations would be atypical. C. If treated, intravenous valproic acid is indicated. D. Initiating treatment in the ED is not indicated. E. Multiple antibiotics can cause this clinical picture. Answer: E. This patient has a fairly classic presentation for acute mania with pressured speech, distractibility, grandiosity, increased involvement (in this case with work), and decreased need for sleep. Multiple drugs may precipitate this, including acyclovir, isoniazid, sulfonamides, the floxins, and chloroquine. An acute manic episode may be manifested with hallucinations and mimic an acute psychosis. ED treatment is usually indicated for this disorder. Acute stabilization is generally effective with major tranquilizers, such as haloperidol.

C H A P T E R 102 

Anxiety Disorders* Leslie S. Zun  |  Kimberly Nordstrom

PRINCIPLES Background Anxiety is a specific unpleasurable state of tension that forewarns the presence of danger, real or imagined, known or unrecognized, and is often verbalized as an intense feeling of worry. Up to a point, anxiety can improve performance; however, extreme responses can lead to deterioration of performance. As the level of dysfunction increases, the patient is much more likely to have a true anxiety disorder. Acute anxiety is common in emergency department (ED) patients who have primary anxiety disorders, concomitant anxiety disorders, and crisis situations. It is helpful to differentiate the origin of anxiety to offer appropriate treatment. As an example, many medical conditions mimic anxiety disorders, and up to 42% of patients initially thought to have anxiety disorders are later found to have organic disease. Emergency clinicians should be able to distinguish between anxiety disorders and medical illness (Box 102.1) and, if necessary, treat both entities. Because anxiety states cause an increase in metabolic demands, they can cause a marginally compensated organ system to fail. In a recent study, 48% of patients presenting for pain complaints were found to have moderate to severe anxiety and only 1% received anxiety treatment.1

Epidemiology Approximately 40 million Americans older than 18 years old, nearly 20% of adults, are affected by anxiety disorders each year. Many primary care patients have significant mood and anxiety symptoms, such as panic disorders, generalized anxiety disorders (GADs), and depression, but nearly half of these symptomatic patients never receive appropriate treatment. Patients with chronic illness and those who make frequent medical visits have higher rates of anxiety and depression. The prevalence of anxiety disorders surpasses that of any other mental health disorder, including substance abuse. There is a close relationship between alcohol abuse and anxiety disorders. The incidence of specific anxiety disorders varies: specific phobia is 7% to 9%, social anxiety is 7%, panic disorder is 3%, and GAD is 3%.2 The lifetime risk for post-traumatic stress disorder (PTSD) is about 9%, but the 12-month prevalence is approximately 4%. Substance or medication-induced anxiety and anxiety due to a medical condition have an unknown prevalence but may be relatively high in those seeking emergency medical care. A different form of anxiety, related to fear of suffering from an illness, now known as illness anxiety disorder (formerly hypochondriasis), may be as high as 8% in ambulatory medical populations.2 Patients may present with a physical complaint and try to disguise *The authors thank Rick McPheeters and Joshua L. Tobias for their contributions to this chapter in previous editions of this text.

their anxiety rather than bear the perceived stigma associated with psychiatric complaints, and they are distinct from patients who have a somatoform disorder.

Pathophysiology There are many forms of anxiety disorders, and the precise mechanisms underlying the development of anxiety have not been fully established. The serotonin system and the noradrenergic systems are common pathways implicated in anxiety. It is believed that low serotonin system activity and elevated noradrenergic system activity are involved, and thus selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are frequently used as treatment. There is also considerable comorbidity with depressive disorders, with evidence showing genetic and neurobiologic similarities, especially related to serotonin. The well-established effectiveness of benzodiazepines in the treatment of anxiety has led to the study of the gammaaminobutyric acid (GABA) system and its relationship to anxiety. GABA is the principal inhibitory neurotransmitter in the central nervous system, and benzodiazepines act on the GABAA receptors. Studies have focused on the role that corticosteroids may play in fear and anxiety. Steroids are thought to induce chemical changes in select neurons that strengthen or weaken certain neural pathways to affect behavior under stress.3 Family research suggests that genetic factors play a role in anxiety, but the precise nature of the inherited vulnerability is unknown. Five major anxiety disorders, panic disorder, GAD, phobias, obsessive-compulsive disorder (OCD), and PTSD, share genetic and environmental risk factors. Psychological and environmental factors also contribute in the generation of anxiety in biologically predisposed individuals.

CLINICAL FEATURES Many patients seeking care in the ED experience anxiety related to encountering internal and external dangers, such as assaults on body integrity in the form of uncomfortable procedures and forced intimacy with strangers. In addition, the patient may experience uncertainty about his or her illness and the potential implications of the illness. Anxiety may be a manifestation of a physical disorder or an expression of an underlying psychiatric disorder. It may be difficult to make the distinction between anxiety as a symptom and anxiety as a syndrome in the ED. The physical symptoms of autonomic arousal (eg, tachypnea, tachycardia, diaphoresis, lightheadedness) may be the only manifestations of anxiety. Classic panic disorder symptoms of chest pain, shortness of breath, and the sense of impending doom will often lead the patient to the ED, especially if it is the very first episode.3 Anxiety associated with medical disorders is more likely to be manifested by physical symptoms and less likely to be associated with avoidance behavior (see Box 102.1). 1353

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BOX 102.1 

BOX 102.3 

Predictors of Anxiety Caused by an Underlying Medical Issue

Characteristics of Post-Traumatic Stress Disorder*

Onset of anxiety symptoms after 35 years old Lack of personal or family history of an anxiety disorder Lack of childhood history of significant anxiety, phobias, or separation anxiety Lack of avoidance behavior Absence of significant life events generating or exacerbating the anxiety symptoms Poor response to anti-anxiety agents

Exposure to actual or threatened death, serious injury, or sexual violence. Presence of intrusion symptoms associated with the traumatic event. Persistent avoidance of stimuli associated with the traumatic event. Negative alterations in cognition and mood associated with the traumatic event. Marked alterations in arousal and reactivity associated with the event. Duration is greater than 1 month. Disturbance causes clinically significant distress or impairment. Disturbance is not attributable to the physiological effects of a substance or another medical condition.

BOX 102.2 

Characteristics of a Panic Attack Abrupt surge of intense fear or discomfort that reaches a peak within minutes, in which four or more of the following occur: Palpitations Sweating Trembling Shortness of breath or feeling of being smothered Feeling of choking Chest pain or discomfort Nausea or abdominal distress Feeling dizzy or light-headed Chills or heat sensations Paresthesias Derealization or depersonalization Fear of losing control or going “crazy” Fear of dying Adapted from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

Clinical manifestations of specific anxiety disorders are considerably different, warranting a review of each of the major types.

Panic Disorder Panic disorder is a diagnosis of exclusion, even in patients with known psychiatric illness, because several mental illnesses cause panic attacks as a secondary manifestation. For a diagnosis of panic disorder, one must experience recurrent, unexpected panic attacks (Box 102.2), as well as either persistent concern of future attacks or a maladaptive behavioral change related to the attacks. As with other disorders, the disturbance should not be better explained by substance use, another medical condition, or another psychiatric illness.2 A panic attack, differentiated for the disorder, is an abrupt fear or discomfort that reaches a peak within minutes and has associated physical and cognitive symptoms.2 It may occur with any anxiety disorder or as part of another mental or physical disorder. A panic attack is not a diagnosis but rather an indication of an underlying disorder. The presence of panic attacks often influences the treatment and outcome of the primary illness. An attack can be replicated by intentional hyperventilation. Intentional hyperventilation can be distinguished from medical hyperventilation by its irregularity and interruptions. When there is doubt, formal psychiatric evaluation is indicated, particularly before a potentially dangerous or addictive drug therapy is prescribed.

*Specifiers include “with dissociative symptoms” and “with delayed expression.” From American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

Generalized Anxiety Disorder GAD is defined as excessive worry that occurs most days over a 6-month period involving several events or activities.2 The anxiety must cause significant distress or impairment in functioning. GAD has been linked to overuse of medical services and often is not recognized, which leads to ineffective treatment.

Post-Traumatic Stress Disorder PTSD is caused by experiencing or witnessing a highly traumatic event. Those with PTSD manifest symptoms of re-experiencing the event, avoidance of triggers, changes in cognition and mood, and changes in arousal and reactivity (Box 102.3). Rates of PTSD are higher among military veterans and those whose occupation involves risk of traumatic exposure.2 ED staff are also at risk for experiencing PTSD related to unusual traumatic events and unexpected deaths and, unfortunately, the support for this tends to be minimal.4

Specific Phobias A phobia is an irrational fear that results in avoidance. Phobia becomes a disorder when it interferes with day-to-day function in an individual’s life. A social phobia, now termed social anxiety disorder, is characterized by clinically significant anxiety about one or more social situations in which the individual may be scrutinized.2 This fear often leads to avoidance behavior for such activities, such as public speaking, performing, visiting, using public showers or restrooms, or eating in public places.

Obsessive-Compulsive Disorder OCD is characterized by recurrent, obtrusive, unwanted thoughts (obsessions), such as fears of contamination, or compulsive behaviors or mental acts (compulsions) that a person feels compelled to perform, such as handwashing or counting. OCD is considered an anxiety disorder because (1) anxiety or tension is often associated with obsessions and resistance to compulsions, (2) anxiety or tension is often immediately relieved by yielding to compulsions, and (3) OCD often occurs in association with other anxiety disorders.2 In summary, the obsessions and intrusive thoughts increase anxiety, and the compulsions and repetitive behaviors decrease anxiety but with significant disruption of one’s life.

CHAPTER 102  Anxiety Disorders

Somatic Symptoms and Related Disorders Although not necessarily considered anxiety disorders, this group of disorders has an undefined, but established link to anxiety and depressive disorders. This group includes somatic symptom disorder, illness anxiety disorder (formerly hypochondriasis), conversion disorder (formerly functional neurological symptom disorder), and psychological factors affecting other medical conditions. With somatic disorders, the patient will complain about one or more physical symptoms, which cause impairment notwithstanding a negative evaluation. These symptoms are not intentionally feigned, as in the case of malingering or factitious disorder. A high utilization of medical services is correlated with these disorders, independent of comorbidity. Patients with panic disorder, however, seek at least as much psychiatric attention as do those with somatoform disorders.

DIFFERENTIAL DIAGNOSIS In patients who present with predominant symptoms of anxiety, even when the patients have known anxiety disorders, before considering which of the previously discussed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) anxiety-related diagnoses the patient might have, the emergency clinician should first consider the possibility of medical and pharmologic-related conditions associated with anxiety. Patients with anxiety disorders may present with apparent physical disease, and many physical diseases are strongly associated with symptoms of anxiety. Several factors help distinguish an anxiety syndrome caused by an underlying medical issue from a primary anxiety disorder (see Box 102.1). Anxiety disorder classifications in the DSM-5 include anxiety caused by another medical condition.2 Because anxiety may be the most obvious symptom of an underlying disease or condition, the patient should be evaluated for exacerbation of known preexisting disease, as well as for the onset of new illness, because anxiety increases the risk of acute medical exacerbation of chronic illness. The classic scenarios of pulmonary embolism and hyperthyroidism causing anxiety are well documented. Post–myocardial infarction patients with anxiety have poorer outcomes than those without documented anxiety. Patients with respiratory diseases, such as asthma and chronic obstructive pulmonary disease, often have anxiety associated with long-standing illnesses. In addition, many of the medications used to treat these illnesses may induce anxiety. One of the most common medical causes of anxiety is alcohol and drug use from either intoxication or, more typically, withdrawal states.

Cardiac Diseases Approximately 25% of patients with chest pain who present to the ED have panic disorder. Their disorder often goes undiagnosed, resulting in multiple visits and expensive cardiac evaluations. Symptoms of myocardial infarction and angina pectoris may include crushing chest pain, shortness of breath, nausea, palpitations, heavy perspiration, and a feeling of impending death. These are also the primary symptoms of acute anxiety, but the pain is usually described as atypical, and patients are generally female and younger. Because of the morbidity and mortality of cardiovascular disease, a patient warrants a full cardiac evaluation when the differentiation between myocardial infarction and acute anxiety is unclear. Cardiac dysrhythmias can cause palpitations, discomfort, dizziness, respiratory distress, and syncope. A panic attack has similar symptoms. Fortunately, most dysrhythmias can be documented

and characterized on cardiac monitors or by electrocardiography. Mitral valve prolapse syndrome can be associated with palpitations and panic attacks indistinguishable from a panic disorder. Benzodiazepines can be used to provide symptomatic relief to patients who experience chest pain due to anxiety.

Endocrine Diseases The most common endocrinologic conditions associated with anxiety states are hypoparathyroidism, hyperthyroidism and hypothyroidism, hypoglycemia, pheochromocytoma, and hyperadrenocorticism. Anxiety is the predominant symptom in 20% of patients with hypoparathyroidism. Studies indicate a higher incidence of anxiety in the subset of patients with surgically removed parathyroid glands. Even though other symptoms may improve with supplementation, patients have been found to have significant depression, anxiety, somatization and phobic anxiety, even after being given calcium and vitamin D. Anxiety symptoms are seen in up to 40% of diabetics, and 14% of diabetic patients suffer from anxiety disorders. There is evidence that diabetics who are treated with antianxiety medication not only reduce their anxiety but also decrease their glycosylated hemoglobin levels and high-density lipoprotein concentration. One study found that diabetics with mental health problems were less likely to improve glycemic control and suggested that psychological evaluation and therapy be used adjunctively.5 Pheochromocytomas are rare tumors that produce elevated levels of catecholamine in the body. Pheochromocytoma attacks may manifest similar to panic attacks and can be precipitated by emotional stress. Elevated urinary catecholamine or plasma metanephrine levels confirm a pheochromocytoma. Hyperthyroidism is one of the most frequently encountered endocrine diseases associated with anxiety. As with panic disorders, hyperthyroidism is associated with acute episodic anxiety. Thyrotoxicosis causes anxiety, palpitations, perspiration, hot skin, rapid pulse, active reflexes, diarrhea, weight loss, heat intolerance, proptosis, and lid lag. A substantial portion of patients continue to have psychiatric manifestations even after treatment. Psychiatric presentations can be the first sign of hypothyroidism, occurring as the initial symptom in 2% to 12% of reported cases along with deficits of impaired recent memory and learning. The severity of anxiety disorders in hypothyroid states is related to the rapidity of thyroid hormone level changes and not to the absolute hormone levels. In general, checking serum thyroidstimulating hormone and free thyroxine levels will suffice in the ED to establish the diagnosis of thyroid disease.

Respiratory Diseases Most conditions causing airway compromise or impairment of gas exchange do not mimic psychiatric disorders. However, some conditions that cause hypoxemia or hypercarbia may lead to the development of significant anxiety. Up to a third of the patients with chronic obstructive pulmonary disease meet the criteria for anxiety disorder. Patients who have severe asthma are twice as likely to have an anxiety disorder and almost five times as likely to have a phobia compared with nonasthmatics. Acute dyspnea from a pure panic attack with good air movement and normal lung sounds is easily differentiated from an asthma attack, but studies consistently show that anxiety disorders increase asthma morbidity and mortality. Acute shortness of breath in any patient should not be immediately attributed to anxiety, especially because pulmonary embolism can present with only shortness of breath as the major symptom. Fortunately, pulmonary embolism can almost always

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be distinguished by history and physical examination, assessment of risk factors for thromboembolic disease, and laboratory testing (eg, pulse oximetry, electrocardiography, chest radiography, and D-dimer assay) as indicated.

Neurologic Disorders Many neurologic conditions are associated with anxiety symptoms. For example, stress is one of the most common reported causes of seizures. Those who report stress as a trigger tend to have higher scores on anxiety tests, and the stress may be either acute or chronic.6 Temporal lobe seizures, complex partial seizures, tumors, arteriovenous malformation, and ischemia or infarction have all been reported with panic attacks. Anxiety disorders also occur in the aftermath of traumatic brain injury (TBI). Approximately 23% of those who sustain a mild TBI are at risk for developing an anxiety disorder; this is frequently found in military personnel. In Huntington’s disease, anxiety is the most common prodromal symptom. Anxiety occurs in up to 40% of patients with Parkinson’s disease and up to 37% of patients with multiple sclerosis. Similarly, anxiety symptoms are common in moderate Alzheimer’s disease.

Drug Intoxication and Withdrawal States Amphetamines, cocaine, and other sympathomimetic drugs are abused for their stimulant and mind-altering properties. Patients often present agitated, anxious, or when these drugs are taken in large doses and with prolonged use. Caffeine is a very commonly used stimulant, and studies suggest that 240 mg to 300 mg of caffeine per day should be the upper limit of healthy consumption. When consuming higher doses, considered caffeine intoxication, restlessness, nervousness, excitement, insomnia, diuresis, gastrointestinal disturbance, tachycardia, psychomotor agitation, as well as other unpleasant symptoms may occur.2 The acute symptoms of caffeine intoxication and GAD are almost identical. Marijuana users believe that the drug reduces their anxiety, but some experience a depersonalization that provokes severe anxiety, fearfulness, and symptoms of agoraphobia. Cannabis intoxication is associated with behavioral or psychological changes, such as anxiety, and physical signs, such as conjunctival injection, dry mouth, and tachycardia.5 Lysergic acid diethylamide (LSD), phencyclidine (PCP), and ecstasy (3,4-methylenedioxy-methamphetamine [MDMA]) are hallucinogens that can produce anxiety and paranoia from chronic use or “bad trips.” Flashbacks affect some users of LSD; the person may experience the symptoms of anxiety and paranoia weeks or months after use.7 Sedative, hypnotic or anxiolytic drugs (eg, benzodiazepines, barbiturates) are taken to relieve anxiety or sleeplessness, but their discontinuation can cause sedative withdrawal and rebound anxiety.2 The severity of the withdrawal syndrome depends on the drug, dosage, duration of use, and speed of elimination. Symptoms include hyperalertness, motor tension, muscle aches, agitation, anxiety, insomnia, tremulousness, nausea, vomiting, convulsions, delirium, and even death.2 Although antidepressants are rarely abused, their abrupt cessation can cause a discontinuation syndrome, which may present as sensory and gastrointestinal-related symptoms, insomnia, lethargy, and extreme anxiety.8 Alcohol withdrawal can appear 6 to 12 hours after the last drink or significant reduction in consumption. Patients often have a detectable serum alcohol level at this time. Anxiety is one of the first and most prominent symptoms and is seen within 24 to 48 hours of the withdrawal state.9 Symptoms of anxiety, insomnia, and autonomic dysfunction can last up to 3 to 6 months following alcohol withdrawal.2

DIAGNOSTIC TESTING The initial history and physical examination should focus on the presenting complaints to determine if the patient has an anxiety disorder or anxiety caused by drug abuse, medication use, or a general medical condition. The psychiatric history should, at minimum, include current symptoms, precipitating events (eg, job loss or relationship), past psychiatric and substance history, history of self-harm or suicide attempts, and identification of support systems. A thorough risk assessment for suicidality is key. Among ED patients, panic attacks have been found to be closely associated with suicidal ideation (43%) and intent (55%). Chapter 105 discusses suicide risk assessment. A physical examination focused on the area of complaint is necessary, even when there is no overt evidence of physical disease. Abnormal vital signs suggest an organic medical cause of the anxiety symptoms. Laboratory tests may be necessary based on the clinical presentation, but no tests can confirm or exclude anxiety disorders. Patients with new symptoms require a more extensive medical and psychiatric investigation than those with a known disorder.

MANAGEMENT The patient should be placed in a quiet area for evaluation. Some patients calm when they are removed from a chaotic ED environment. If that is not possible, reducing environmental stimulants, such as turning down the lights, can be helpful. If the emergency clinician encounters difficulty in calming the patient, supportive family members may help.

Pharmacologic Treatment Use of oral, intravenous, or intramuscular medication may be necessary when an anxiety state is so out of control that there is a significant threat to safety of self or others. Medication may also be appropriate for the anxious patient experiencing a significant medical illness or undergoing a medical procedure. Lorazepam in small increments can be helpful in alleviating the anxiety associated with substance withdrawal states. Midazolam reduces anxiety and increases amnesia for ED procedures. SSRIs and SNRIs have become first-line treatment of most anxiety disorders because of their broad spectrum of efficacy and high tolerability by most patients. They have a lower potential for dependence and are safer than older classes of antidepressants and anxiolytics. Improvement is usually seen in 4 to 6 weeks, but doses may have to be adjusted. Initiation of longer term medication is usually done by primary care physicians or psychiatrists. It is important to start the patient with low doses of SSRIs (usually half the normal starting doses used for depression) and to arrange for frequent short-term follow-up visits, because an initial increase in anxiety may be seen. We do not recommend that these medications be started in the ED unless accompanied by patient education and close follow-up with a primary care physician or psychiatrist. Benzodiazepines can be prescribed for motivated patients with acute exogenous anxiety for time-limited stress. Benzodiazepines are an attractive alternative to the delayed response of an SSRI when an immediate reduction of symptoms is desired or a shortterm treatment is needed. Benzodiazepines have a role in emergency medical treatment, but their use is questionable for long-term treatment. In most circumstances, benzodiazepines should be prescribed for a week or less. Patients who do not improve within a week are unlikely to benefit from the drug. Prescribers will commonly use a benzodiazepine for the first week while initiating SSRI or SNRI treatment. Patients with a history of alcoholism or drug abuse, who are excessively and emotionally

CHAPTER 102  Anxiety Disorders

dependent, or who become anxious in response to normal stress are at greater risk of drug dependency and are not good candidates for this treatment. Monoamine oxidase inhibitors and tricyclic antidepressants have been effective in treating anxiety but have been largely supplanted by SSRIs. Buspirone, a nonbenzodiazepine, has significant lag time and questionable efficacy, especially after the use of benzodiazepines. Patients with apparent or known anxiety disorders should be referred to a primary care physician or a psychiatrist for a thorough evaluation of the type of anxiety and to create a long-term treatment plan.

therapy may be helpful for individuals whose psychological makeup, coping style, interpersonal dynamics, and situational stressors contribute to their pathologic anxiety. The use of supportive, insight-oriented family therapy is helpful when these factors appear prominently in the patient’s presentation. Cognitive-behavioral therapy helps the patient correct the cognitive misperceptions and overreactions that occur. Cognitivebehavioral therapy is very effective but requires commitment from the patient. Meditation, biofeedback, and suggestive hypnosis may also have a role in long-term treatment.

Nonpharmacologic Therapy

Patients receiving initial treatment in the ED, without a proper handoff to outpatient care, are at an increased risk for return. If available, it is preferred that a social worker or mental health worker connect discharged patients with outside agencies and services, rather than providing patients with a referral list. Most patients with an anxiety disorder can be safely discharged with close primary care physician or psychiatrist follow-up. Patients with an anxiety disorder associated with suicidal or homicidal ideation or with severe depression require urgent psychiatric attention and admission to the hospital.

Supportive therapy can be used to calm patients and give them room to problem-solve. Emergency clinicians and staff can also use psychoeducation to normalize what is happening and to teach simple skills, such as breathing techniques. It is also particularly useful to educate the patient on the role that stimulants (eg, caffeine) and depressants (eg, alcohol) play in promoting anxiety. There are multiple longer-term therapies that can be helpful for anxiety but are not used in the acute care setting. Psycho-

DISPOSITION

KEY CONCEPTS • Patients who present with predominant symptoms of anxiety may be suffering from medical disorders, medication effects, or substance abuse or withdrawal. • Anxiety may accompany the onset of serious medical disease, cause significant metabolic demands, and stress a marginally compensated organ system. • Anxiety caused by physical illness is usually suggested by the patient’s physical findings but may require testing to further delineate the cause.

• Oral, intravenous, or intramuscular medication may be necessary for patients who are a significant threat to themselves or others and for anxious patients with significant medical illness. • Limited benzodiazepine therapy may be helpful for select patients.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Craven P, Orhan C, Madsen T: Patient anxiety may influence the efficacy of ED pain management. Am J Emerg Med 31(2):313–318, 2013. 2. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association. 3. Rowney J, Hermida T, Malone D: Disease management: anxiety disorders. Available at . 4. Lavoie S, Talbot LR, Mathieu L: Post-traumatic stress disorder symptoms among emergency nurses: their perspective and a ‘tailor-made’ solution. J Adv Nurs 67(7): 1514–1522, 2011. 5. Grant P, Dworakowska D, DeZoysa N, et al: The impact of anxiety and depression of patients within a large type 1 diabetes insulin pump population: an observational study. Diabetes Metab 39(5):439–444, 2013.

6. Privitera M, Walters M, Lee I, et al: Characteristics of people with self-reported stressprecipitated seizures. Epilepsy Behav 41:74–77, 2014. 7. D’Orazio JL: Hallucinogen toxicity. Available at . 8. Renoir T: Selective serotonin reuptake inhibitor antidepressant discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved. Front Pharmacol 4:45, 2013. 9. McKeown NJ: Withdrawal syndromes. Available at .

CHAPTER 102: QUESTIONS & ANSWERS 102.1. Which of the following is the most common mental health disorder? A. Anxiety B. Bipolar C. Depression D. Schizophrenia E. Substance abuse Answer: A. Many of these patients never receive appropriate care, in part because they choose to present with a physical complaint and disguise their anxiety. Patients with chronic illnesses have higher rates of anxiety and depression than the rest of the population. 102.2. What is the most common cause of organic anxiety, anxiety that results from a physiologic origin? A. Adrenal disorders B. Alcohol and drug use C. Cardiac disease D. Hyperthyroidism E. Pulmonary embolus Answer: B. This may be from intoxication or withdrawal states. 102.3. A 52-year-old woman presents with 2 months of recurrent episodes of anxiety, mild chest pain, subjective palpitations, hand paresthesias, and occasional muscle spasms. They have occurred weekly in the past but are now increasing in frequency. Her only past history is a thyroidectomy 4 months prior. She is taking levothyroxine (Synthroid) and had normal thyroid levels 2 weeks ago. Her vital signs, physical examination, and electrocardiogram are normal. Laboratory evaluation shows sodium 141 mEq/L, potassium 4.1 mEq/L, creatinine 1.0 mg/dL, bicarbonate 26 mEq/L, chloride 100 mEq/L, and calcium 7.1 mg/dL; a complete blood count is normal. Which of the following should be the next step in her management? A. Outpatient clonazepam B. Parathyroid hormone level C. Psychiatry consultation D. Thyroid hormone levels E. Urine drug screen Answer: B. Anxiety is the predominant symptom in 20% of patients with hypoparathyroidism. Other symptoms include paresthesia, muscle cramps, and spasms. Most cases are idiopathic or due to inadvertent parathyroid gland harvest during thyroidectomy. The diagnosis is suggested by a low serum calcium and an elevated phosphate and is confirmed by a depressed parathyroid level.

102.4. Which of the following statements regarding anxiety and endocrine disorders is true? A. Anxiety can often be traced to reactive hypoglycemia. B. Anxiety is not a manifestation of hypothyroidism. C. Diabetics treated with antianxiety agents have improved hemoglobin A1c levels. D. Less than 5% of diabetics experience anxiety. E. Patterns of diaphoresis in pheochromocytoma mimic those of a panic attack. Answer: C. Approximately 15% of diabetics have an anxiety disorder. Treatment improves hemoglobin A1c levels. Anxiety due to reactive hypoglycemia is rare despite the common perception among patients. Pheochromocytoma causes whole body diaphoresis, whereas panic disorders primarily cause sweaty palms. Hyperthyroidism or hypothyroidism can cause significant anxiety manifestations. It is more related to the rate of change than the level of thyroid hormones. 102.5. A 23-year-old woman with a history of asthma presents with increasingly frequent episodes of panic attacks. Her medications are an inhaled beta-agonist and an intermittent steroid inhaler. She reports subjective increasing asthma severity as her panic episodes have worsened. When counseling the patient, which of the following statements is most correct? A. An anxiety disorder in an asthmatic patient does not increase morbidity. B. Anxiety does not precipitate asthma attacks. C. Anxiety does not worsen airflow. D. Asthmatics are more likely to have an anxiety disorder. E. It is difficult to differentiate dyspnea related to asthma from anxiety. Answer: D. Anxiety can precipitate and prolong an asthma attack. Morbidity and mortality are increased in asthmatic patients who have a coexisting anxiety disorder. Patients who have asthma are twice as likely to have an anxiety disorder and five times as likely to have a phobia. Acute dyspnea from “panic” dyspnea can be differentiated from asthma by clear lungs on auscultation. 102.6. Which of the following syndromes is not associated with anxiety? A. Left hemispheric strokes B. Multiple sclerosis C. Right hemispheric strokes D. Transient ischemia attack E. All of the above can be associated with anxiety.

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Answer: E. Anxiety may be a component of seizures, tumors, arteriovenous malformations, and ischemic events. It may be the only manifestation of some disorders (eg, right hemispheric strokes and transient ischemic attacks [TIAs]). The coexistence of anxiety plays an important role in the prognosis and impairment of stroke patients. 102.7. A 38-year-old woman with a long history of anxiety and panic disorder presents with anhedonia, melancholy, sleep disruption, crying episodes, and some hostility feelings. She has no current anxiety symptoms. Her only medication is clonazepam. She has no known medical illness. Which of the following statements regarding this patient’s symptoms is true? A. Approximately 50% of patients with panic disorder develop major depression. B. Depression with anxiety and hostility is usually refractory to treatment. C. The first diagnostic step should be a thyroid panel. D. The majority of patients with depression have panic attacks. E. This is likely a drug-induced depression. Answer: A. Approximately 50% of patients with a primary panic disorder will later develop major depression. Twenty percent of patients with depression have panic attacks. Depression with panic attacks is less responsive to treatment, but depression with anxiety and hostility responds well to antidepressants. Although benzodiazepines can exacerbate symptoms of depression, there is already a high spontaneous rate of depression with anxiety disorders. 102.8. Which of the following statements regarding benzodiazepine use and anxiety is true? A. Benzodiazepines are first-line agents for anxiety disorders. B. Several weeks of treatment are indicated after initial diagnosis. C. Short-acting benzodiazepines produce a more severe abstinence syndrome. D. They are particularly useful in patients with alcohol abuse. E. Withdrawal rebound is less common than with selective serotonin reuptake inhibitors (SSRIs). Answer: C. SSRIs are the first-line agents for anxiety and panic disorders, but the primary disadvantage is the several-week lag needed for maximal clinical benefit. Benzodiazepines work best for motivated, dependable patients when an immediate reduction of symptoms is indicated or a short-term treatment is necessary. Patients who do not benefit from benzodiazepines within a week are unlikely to do so. Patients with a history of alcoholism or drug abuse, who are excessively/emotionally dependent, or who become anxious from normal stress are at greater risk for dependency. Rebound withdrawal is more likely after short-acting agents. 102.9. A 29-year-old Caucasian female presents with excessive daytime somnolence. She states that she had been suffering from anxiety associated with her paralegal occupation, and 1 week ago her psychiatrist had started her on a 2-week course of once-daily benzodiazepine therapy, which she takes in the morning. Her anxiety symptoms are well controlled. She asks if you can change her to a new medication because the somnolence is significantly affecting her job

performance. What would be the most appropriate course of action? A. Counsel the patient that she should continue the medication as prescribed because she will soon adapt and the somnolence will likely subside. B. Discontinue the benzodiazepine and refer her back to her psychiatrist. C. Have her try dosing the benzodiazepine at bedtime, because this will likely continue to control her anxiety and limit daytime somnolence. D. Switch the patient to a selective serotonin reuptake inhibitor (SSRI) and refer her back to her psychiatrist. E. Switch the patient to a shorter-acting benzodiazepine. Answer: C. Instituting an SSRI should be reserved for primary care physicians or psychiatrists who can monitor the patient more closely, because the response will be delayed. Some patients do adapt to the sedative effects of benzodiazepines but usually only after long-term use. Stopping the benzodiazepine may ultimately be necessary but at the risk of recurrent anxiety. Dosing benzodiazepines at bedtime may minimize daytime sedation and still provide an anxiolytic effect. Shorter-acting benzodiazepines produce a more severe abstinence syndrome when stopped abruptly, and thus most prescribers prefer longer-acting agents. 102.10. A 52-year-old male construction worker presents with chest pain. He states his symptoms began early this morning and have progressively worsened throughout the day. His symptoms include nervousness, tremors, chest pain, shortness of breath, and palpitations. He states that he has had anxiety for 30 years but has controlled it with the consumption of alcohol. He became unemployed 1 week ago, and his daily alcohol use has diminished significantly. His vital signs are blood pressure (BP) 185/95 mm Hg, heart rate 123 beats per minute, respiratory rate of 20 breaths per minute, and temperature of 98.9° F. His physical examination is remarkable for diaphoresis, tongue fasciculation, both resting and intention tremors, and mild psychomotor agitation while maintaining orientation with a congruent anxious mood and affect. What is the most likely etiology of this patient’s symptoms? A. Acute alcohol withdrawal syndrome B. Exacerbation of endogenous anxiety secondary to diminished alcohol intake C. Exacerbation of exogenous anxiety secondary to change in employment status D. Hypertensive emergency with acute coronary syndrome E. Reactive anxiety secondary to the onset of chest pain Answer: A. Hypertensive emergency is unlikely given the level of this patient’s BP. On the basis of the history alone, it may be difficult to differentiate organic versus functional anxiety or identify an exogenous trigger, but the abnormal vital signs and physical examination associated with a recent cessation of long-term alcohol consumption makes acute alcohol withdrawal the most likely cause. Given the significant morbidity associated with withdrawal states, this must be addressed acutely. Appropriate diagnosis and management of underlying psychiatric disease will be a secondary concern after the patient’s withdrawal is managed.

C H A P T E R 103 

Somatoform Disorders Adria Ottoboni Winter PRINCIPLES Somatic symptom disorders (SSDs), formerly known as somatoform disorders, are described as the borderland between psychiatry and medicine and are responsible for some of the most frustrating and the least understood patient encounters in the emergency department (ED). As such, it is important that emergency clinicians recognize and treat this disorder appropriately to avoid patient suffering, unnecessary testing, iatrogenic injuries, and inappropriate resource utilization. Patients with SSD are often labelled as “difficult” patients, yet appropriate mental health referrals are not made, while psychological and psychosocial causes for their presentation remain unaddressed.1 SSD patients present with multiple physical symptoms in the absence of detectable physical disease, and harbor excessive health concerns that are expressed emotionally, cognitively, and behaviorally.2 These patients perceive a wide range of severe symptoms including pain, gastrointestinal, cardiovascular, sexual, and pseudo-neurological symptoms, which cause inappropriate and persistent worry, distress, and social dysfunction. Biological, psychological, and psychosocial factors interact as precipitating, aggravating, and maintaining factors of psychopathology. Somatization is best understood by focusing on the abnormalities in the patient’s response to their somatic symptoms, rather than on the absence of a discernible medical cause for those symptoms. The patient’s maladaptive response to somatic symptoms is the reason this behavior is classified as a psychiatric disorder. The major diagnosis in this diagnostic class, of which SSD is the most prominent, hinges on the existence of the patient’s distinctive abnormal thoughts, feelings, and behaviors in response to somatic symptoms.3 Somatoform disorders because of their very nature and presentation have consistently been diagnoses that are difficult to make with any certainty, even after multiple visits with the same primary care physician. It is therefore a challenging diagnosis to make within the busy confines of a brief visit to the ED. For patients with functional symptoms, the strategy of pursuing a medical cause with invasive diagnostic procedures, unnecessary surgeries, and misdirected drug trials can be life-threatening, and the unwarranted costs of these measures strain limited medical resources. SSD are typically more common in women of low socioeconomic status who present between 20 and 30 years old, with a high incidence of comorbid anxiety or depression.4 The diagnosis of SSD is made when there are persistent and clinically significant physical complaints that are accompanied by excessive and disproportionate health-related thoughts, feelings, and behaviors regarding these symptoms.5 There has been much debate regarding how to name and define SSD patients, with the latest (fifth) version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reconceptualizing the category almost entirely. The previous criteria for SSD was criticized for being overly inclusive in certain areas and difficult to employ in either real life practice or research.5 The new diagnostic category of SSD in the DSM-5 is a radical construct 1358

change in which the number of symptoms plays only a minor role, while the distress of symptoms associated with psychological features and symptom consequences are emphasized.3,6 The term somatization was frequently used in the psychiatric literature in the past but is now disapproved of as often as its precursor hysteria. The DSM-5 no longer employs the term somatization and, in fact, has changed the criteria, as well as the nosology behind what was previously referred to as somatoform disorders. Recent publications refer to “medically unexplained physical or somatic symptoms,” rather than somatization. The definitions of somatoform disorders have been a subject of controversy and criticism among psychiatrists as well as primary care providers since they were first included in the DSM-III as a speculative category.2 SSD had a central defining premise in the concept of “medical unexplained symptoms.” There were several problems with this, not the least of which was that many physicians and researchers found it difficult to define a disorder based on the lack of evidence, rather than on the presence of tangible findings.3,5 The DSM-5 has attempted to solve many of these conflicts by restructuring and reconceptualizing the diagnosis. The major diagnosis in this diagnostic class, SSD, emphasizes that the diagnosis is made on the basis of distressing somatic symptoms plus maladaptive thoughts, feelings, and behaviors in response to these symptoms.3 Although experts may disagree on how to classify SSD, none disagree on the clinical importance of recognizing and appropriately managing these patients.2 Emergency care providers are trained to focus on physical complaints and findings and to rule out life-threatening conditions. They may consciously or unconsciously avoid asking difficult questions that would make a psychiatric diagnosis apparent or suspect. They may also be wary of ascribing the entirety of a patient’s complaints to a psychiatric disorder and risk missing the subtle presentation of medical illness and subsequently retreat into further testing. Proper recognition and management of somatoform disorders is, however, an essential component in minimizing the suffering of these patients and avoiding unnecessary diagnostic testing and the concurrent misallocation of resources.

CLINICAL FEATURES Somatic and related disorders encompass the diagnoses of SSD, as well as several other psychiatric diagnoses that all share a common feature: the experience of physical symptoms associated with significant distress and impairment that cannot be adequately explained by demonstrable physical pathology despite appropriate medical investigation (Box 103.1).5 Hypochondriasis as a DSM classification has been eliminated, and the majority of these patients would now be classified within the DSM-5 as having illness anxiety disorder. Illness anxiety disorder is considered a less stigmatized and pejorative term, and describes patients with a persistent preoccupation with having a serious illness, very high levels of health anxiety, a complete absence or very mild somatic symptoms, and excessive

CHAPTER 103  Somatoform Disorders

BOX 103.1 

BOX 103.2 

Somatic Symptom and Related Disorders

Differential Diagnosis of Somatic Symptom Disorder

Conditions manifested by abnormal thoughts, feelings, and behaviors in response to distressing somatic symptoms causing impairment: Somatic symptom disorder (SSD) Illness anxiety disorder (formerly hypochondriasis) Functional neurological symptom disorder (formerly conversion disorder) Factitious disorder Psychological factors affecting other medical conditions Other specified somatic symptom and related disorders Unspecified somatic symptom and related disorders Adapted from American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association.

health-related behaviors.5 A milder form of this disorder may be an exaggerated interest in body function and health that does not rise to the level of being classified as illness anxiety disorder. Typically, the patient with illness anxiety disorder commonly complains at length and in detail, using medical jargon. As part of their symptomatology, these patients often believe that they have lost control of their lives and will sometimes make an obvious effort to dominate the doctor-patient relationship to feel more powerful. Consequently, physicians perceive illness anxiety disorder patients as more angry and hostile than other patients. The terminology of patients with neurologic symptoms that remain unexplained even after appropriate medical investigation has undergone a series of changes. Once referred to as hysterical neurosis and later as conversion disorder, this particular subset of SSDs is now termed functional neurological symptom disorder. Functional neurological symptom disorder is characterized primarily by symptoms of altered voluntary motor or sensory function that are not better explained by a neurological or medical condition, and it causes clinically significant distress or functional impairment. The disorder can be further subcategorized into (1) weakness or paralysis; (2) abnormal movements; (3) swallowing symptoms; (4) dysphonia or slurred speech; (5) attacks or seizures; (6) anesthesia; and (7) visual, olfactory, or hearing disturbances. Typically, there is a sudden dramatic onset of a single symptom, simulating some nonpainful neurologic disorder for which there is no pathophysiologic or anatomic explanation.5 Some of these symptoms may provide gratification for unconscious dependency needs, whereas others may provide escape from painful emotional stimuli. Typical comorbid diagnoses include mood disorders, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, dissociative disorders, and obsessive-compulsive disorders. Patients with functional neurological symptom disorder (conversion disorder) often have a history of physical or sexual abuse. Although the classic description of these patients is one of inappropriate lack of concern for the sudden neurological deficit (“la belle indifference”), such presentations are, in fact, rare and should not be considered necessary for the diagnosis.7

DIFFERENTIAL DIAGNOSIS It is important to remember that there are psychiatric disorders other than SSD that are initially brought to medical attention with manifested somatic symptoms, including major depressive disorder and anxiety disorders. In addition, there are several medical diagnoses that can have very subtle presentations with multiple physical symptoms, including multiple sclerosis, porphyria, hyperparathyroidism, systemic lupus erythematosus, thyroid disorders,

Major depressive disorder Anxiety disorders Multiple sclerosis Porphyria Hyperparathyroidism Systemic lupus erythematosus Thyroid disease Wilson’s disease Substance abuse disorder Personality disorder Malingering

and Wilson’s disease. Other diagnoses to consider include anxiety, substance abuse disorders, personality disorders, and malingering (Box 103.2).4

DIAGNOSTIC TESTING It is challenging to evaluate a patient for potentially life-threatening disease while simultaneously entertaining a psychiatric diagnosis of SSD. Repetitive or extensive diagnostic testing rarely excludes organic disease with absolute certainty and may yield false-positive results. Testing should only be performed for diagnoses that are supported by a carefully performed history and physical examination. The exception to this rule is the neurological symptom disorder patient, previously termed conversion disorder. Several neurological diseases have subtle presentations, multiple sclerosis being a case in point. The pace of the ED and the limited scope of diagnostic evaluation may make it difficult to discern between neurological symptom disorder and neurological pathology with any confidence. It may require imaging studies and both neurologic and psychiatric consultations to avoid the misdiagnosis of a patient who requires intervention.

MANAGEMENT The success or failure of the emergency clinician to deal with patients who have SSD will depend on his or her ability to establish a rapport with the patient.8 Patients with these disorders can be more challenging to care for than patients with most other psychiatric disorders, and therefore physician knowledge and attitudes are key. It is important to build and maintain rapport with the patient with SSD by listening carefully and encouraging the patient to describe their symptoms. After developing a sound rapport, legitimize the patient’s complaints and then limit diagnostic investigations to address only clear cut findings of medical illness that are based on a careful history and physical examination. One should avoid confronting or challenging the SSD patient and instead, agree that there is a problem, and work with the patient to formulate a plan of care and referral. The priority is to listen and communicate an understanding of what the patient is feeling and the extent of the functional impairment that they are experiencing. If the provider acknowledges the legitimacy of the patients claim to illness and assures the SSD patient of ongoing care, limits may be set on the patient’s illness behavior. Suffering is a subjective phenomenon and, in that sense, is genuine in these patients. It is appropriate to legitimize the patient’s symptoms and then use diagnostic labels after considering the needs of the individual patient encounter.9 If one believes that the patient is

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amenable to the potential diagnosis of SSD, naming the diagnosis itself can help build a therapeutic alliance with the patient.10 The components of the SSD diagnosis, somatic symptoms, health related anxiety, preoccupation about health concerns, and dysfunctional illness behaviors have an array of beneficial treatments that may be tried, although typically at the discretion of the primary care provider or psychiatric consultant. The potential therapeutic endeavors include cognitive therapy, behavioral techniques, psychotherapies, and in some cases psychotropic medications. If a diagnosis of SSD is seriously considered by the emergency care provider, these patients will require referral to primary care and subsequently to psychiatric consultation for evaluation and management.

Disposition Patients with suspected SSD and those with a preexisting diagnosis of SSD should be referred to either their primary care physician or to psychiatry. They should be told that acute life-threatening diagnoses have been ruled out and that further testing and additional medications are not indicated at this time. It is appropriate to point out that continued care and periodic reassessment are indicated, although not in the ED. Patients with concurrent anxiety or depression should receive psychiatric consultation or referral, especially when they present with an acute decompensation of these symptoms.

KEY CONCEPTS • Somatoform disorders as a diagnosis has been eliminated from the DSM-5 and reconceptualized with the category of SSDs. • The patient with functional neurological symptom disorder, what was termed conversion disorder previously, requires a careful and complete neurological examination. Rather than miss the subtle presentation of a neurological disorder, it may be appropriate to perform imaging and obtain neurological and psychiatric consultation. Do not assume that the patient with neurological deficits has a psychiatric disorder. • Success with the SSD patient depends on establishing rapport with the patient and legitimizing their complaints to avoid a dysfunctional physician-patient interaction. • Avoid telling the SSD patient “it is all in your head” or “there is nothing wrong with you.” These patients are very sensitive to the idea that their suffering is being dismissed. • A useful approach is to discuss recent stressors with the patient and suggest to them that at times our bodies can be smarter than we

• • • •

are, telling us with physical symptoms that we need assistance. This approach alone may transform the ED visit from a standoff between physician and patient, to a grateful patient who develops greater insight and is amenable to referral. Avoid prescribing unnecessary or addictive medications to the SSD patient. If you suspect a diagnosis of SSD, refer the patient to primary care or psychiatry for further evaluation and treatment. Evaluate and refer appropriately for any concurrent anxiety or depression; psychiatric consultation is needed in the setting of acute decompensation. Patients with SSD are best cared for by establishing an ongoing relationship with a primary care provider, and it is appropriate to stress this with the SSD patient.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Jorg A, Martin H: Somatoform disorders. In Wright JD, editor: International encyclopedia of the social and behavioral sciences, ed 2, Philadelphia, 2015, Elsevier, pp 10–15. 2. Levenson JL: The somatoform disorders: 6 characters in search of an author. Psychiatr Clin North Am 34(3):515–524, 2011. 3. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 5, Arlington, VA, 2013, American Psychiatric Association. 4. Braun I, Greenberg D, Smith F, et al: Functional somatic symptoms, deception syndromes, and somatoform disorders. In Stern TA, Fricchione GL, Cassem NH, et al, editors: Massachusetts General Hospital handbook of general hospital psychiatry, ed 6, Philadelphia, 2010, Saunders/Elsevier, pp 173–187. 5. Dimsdale JE, Creed F, Escobar J, et al: Somatic symptom disorder: an important change in DSM. J Psychosom Res 75(3):223–228, 2013.

6. Rief W: Painting the picture of distressing somatic symptoms. J Psychosom Res 68(1):1–3, 2010. 7. Reus VI: Functional neurologic symptom disorders. In Aminoff MJ, Josephson AS, editors: Aminoff ’s neurology and general medicine, ed 5, London, 2014, Academic Press/Elsevier, pp 1069–1085. 8. Croicu C, Chwastiak L, Katon W: Approach to the patient with multiple somatic symptoms. Med Clin North Am 98(5):1079–1095, 2014. 9. Isaac ML, Paauw DS: Medically unexplained symptoms. Med Clin North Am 98(3):663–672, 2014. 10. Lemogne C, Consoli SM, Limonsin F, et al: Treating empty nose syndrome as a somatic symptom disorder. Gen Hosp Psychiatry 37(3):273.e9–273.e10, 2015.

CHAPTER 103: QUESTIONS & ANSWERS 103.1. Which of the following is most likely to occur from ordering of excessive diagnostic tests in patients with a somatic symptom disorder? A. A conclusive diagnosis B. An improved physician-patient relationship C. Morbidity from repeated diagnostic tests D. Patients who are reassured by excessive testing E. The exclusion of organic disease with absolute certainty Answer: C. Repeated diagnostic testing in somatizing patients not only leads to excessive use of health care services and iatrogenic harm but, in addition, does not lead to increased patient satisfaction, decreased suffering, or improved physician-patient relationship. The most reasonable approach to the patient with a potential diagnosis of somatic symptom disorder is a rational search for biomedical causes along with an open discussion of psychosocial issues from the start of the patient encounter. 103.2. Which of the following is more likely in patients with recent-onset somatic disorder compared with patients with long-term somatic disorder? A. Anxiety B. Depression C. Grief reaction D. All of the above Answer: D. Patients who present with the recent onset of somatization are more likely to have an acute psychological stressor that they are either unwilling or unable to directly report and may instead use somatic symptoms to legitimize their presentation to the emergency department. The diagnosis of somatization disorder requires multiple, recurrent, unexplained symptoms rather than an acute complaint in a single visit. 103.3. Which of the following approaches is the most appropriate for diagnosis and treatment of somatic symptom disorder? A. Confront the patient and explain that there is nothing “wrong.” B. Order multiple diagnostic tests. C. Proceed with the assumption that the patient is malingering. D. Refer the patient to insight-oriented psychotherapy. E. Use effective and appropriate communication skills. Answer: E. Effective and appropriate communication skills are key to the diagnosis and treatment of patients with a somatic symptom disorder. These patients do not meet the criteria for factitious disorder or malingering. Patients with a somatic symptom disorder have reduced symptoms and improved functioning when the physician does not attempt to minimize the

experience of symptoms with comments such as “It is all in your head.” In addition, these patients appear to derive very little benefit from insight-oriented psychotherapy; rather, they will maintain improved functional health status and require fewer physician visits if they have an ongoing and trust-based relationship with the primary care physician. 103.4. A patient presents with the sudden onset of blindness, which cannot be explained medically. Which of the following is the most likely to be true? A. The condition is under the patient’s voluntary control. B. The patient is more likely to have preexisting eye disease. C. The patient is unlikely to have any comorbid diagnosis, such as mood disorder, panic disorder, or post-traumatic stress disorder. D. The presentation represents the patient’s own perception of neurologic illness. Answer: D. Patients with a functional neurological disorder may present to the physician with what they believe represents a neurologic illness. They are likely to have an underlying comorbid diagnosis, such as mood disorder, panic disorder, or post-traumatic stress disorder. Interestingly, the presentation, such as blindness or paralysis of the lower extremities, is not under the patient’s voluntary control. 103.5. Which of the following statements regarding somatization disorder is true? A. A specific symptom may point to the diagnosis. B. More symptoms correlate with a higher likelihood of psychiatric illness. C. The symptoms may be feigned or voluntary. D. There is no direct association with anxiety. E. There is no direct association with depression. Answer: B. Women with more than five symptoms and men with more than three symptoms have a much higher likelihood of psychiatric illness. The symptom complaints are neither feigned nor voluntary but, rather, more a manifestation of some sort of distress. There is an association with both depression and anxiety. It is the multiplicity rather than the specificity of symptoms that suggests the diagnosis. 103.6. Which of the following statements regarding chronic pain syndrome (pain disorder) is true? A. Chronic pain behavior patterns are fixed after 2 weeks. B. It may be intentionally feigned. C. It often follows a specific traumatic event.

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D. The pain is limited to the single organ system or injury. E. There is typically a pathophysiologic explanation for the pain. Answer: C. Most cases of chronic pain follow a specific traumatic or industrial event. It is not intentionally feigned, usually involves

more than one organ system, and limits function, and the degree of pain or incapacitation cannot be explained medically. Pain behaviors are typically fixed at 3 months, and failure to improve or to return to normal function at 2 weeks should raise concerns and prompt review.

C H A P T E R 104 

Factitious Disorders and Malingering Jag S. Heer PRINCIPLES Patients may present to the emergency department (ED) with symptoms that are simulated or intentionally produced. The reasons that cause this behavior define two distinct varieties: factitious disorders and malingering. Factitious disorders are characterized by symptoms or signs that are intentionally produced or feigned by the patient in the absence of apparent external incentives.1,2 Factitious disorders have been present throughout history. In the second century, Galen described Roman patients inducing and feigning vomiting and rectal bleeding.3 Hector Gavin sought to categorize this behavior in 1834.3 These patients constitute approximately 1% of general psychiatric referrals, but this percentage is lower than that seen in emergency medicine because these patients rarely accept psychiatric treatment.1,4 Of patients referred to infectious disease specialists for fever of unknown origin, 9.3% of the disorders are factitious.5 Between 5% and 20% of patients observed in epilepsy clinics have psychogenic seizures, and the number reaches 44% in some primary care settings.6 Among patients submitting kidney stones for analysis, up to 3.5% are fraudulent.7 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) classifies factitious disorders into two types: factitious disorder imposed on self (FDIS) and factitious disorder imposed on another (FDIA). Munchausen syndrome, the most dramatic and exasperating of the FDIS, was originally described in 1951.8 This fortunately rare syndrome takes its name from Baron Karl F. von Munchausen (1720 to 1797), a revered German military officer and noted raconteur who had his embellished life stories stolen and parodied in a 1785 pamphlet.3 The diagnosis applies to only 10% to 20% of patients with factitious disorders.1,9 Other names applied include the “hospital hobo syndrome” (patients wander from hospital to hospital seeking admission), peregrinating (wandering) problem patients, hospital addict, polysurgical addiction, and hospital vagrant.4,10 FDIA, an especially pernicious variant that involves the simulation or production of factitious disease in children by a parent or caregiver, was first described in 1977.2,11 There are approximately 1200 estimated new cases of FDIA per year in the United States.3 The condition excludes straightforward physical abuse or neglect and simple failure to thrive; mere lying to cover up physical abuse is not FDIA.3,11 The key discriminator is motive: the mother is making the child ill so that she can vicariously assume the sick role with all its benefits. The mortality rate from FDIA is 9% to 31%.12 Children who die are generally younger than 3 years old, and the most frequent causes of death are suffocation and poisoning.13 Permanent disfigurement or permanent impairment of function resulting directly from induced disease or indirectly from invasive procedures, multiple medications, or major surgery occurs in at least 8% of these children.13,14 Other names applied include Polle’s syndrome (Polle was a child of Baron Munchausen who died mysteriously), factitious disorder by proxy, pediatric condition falsification, Munchausen syndrome by proxy, and Meadow’s syndrome.3,8,10,12

Malingering is the simulation of disease by the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives, such as avoidance of military conscription or duty, avoidance of work, obtainment of financial compensation, evasion of criminal prosecution, obtainment of drugs, gaining of hospital admission (for the purpose of obtaining free room and board), or securing of better living conditions.2,8,15 The most common goal among such “patients” presenting to the ED is to obtain drugs, whereas in the office or clinic the gain is more commonly insurance payments or industrial injury settlements. The true incidence of malingering is difficult to gauge because of underreporting, but estimates include a 1% incidence among mental health patients in civilian clinical practice, 5% in the military, and as high as 10% to 20% among patients presenting in a litigious context.8,9 The most likely conditions to be feigned are mild head injury, fibromyalgia, chronic fatigue syndrome, and chronic pain.9,15

CLINICAL FEATURES Factitious Disorders Factitious Disorders Imposed on Self The diagnosis of FDIS depends on specific criteria (Box 104.1).2 With a factitious disorder, the production of symptoms and signs is compulsive; the patient is unable to refrain from the behavior even when its risks are known. The behavior is voluntary only in the sense that it is deliberate and purposeful (intentional) but not in the sense that the acts can be fully controlled.2 The underlying motivation for producing these deceptions, securing the sick role, is primarily unconscious.6,8,9 Individuals who readily admit that they have produced their own injuries (eg, self-mutilation) are not included in the category of factitious disorders.9 Presentations may be acute, in response to an identifiable recent psychosocial stress (termination of romantic relationship, threats to selfesteem), or a chronic life pattern, reflective of the way in which the person deals with life in general.9 The symptoms involved may be either psychological or physical. Psychological Symptoms.  This disorder is the intentional production or feigning of psychological (often psychotic) symptoms suggestive of a mental disorder. Stimulants may be used to induce restlessness or insomnia; hallucinogens, to create altered levels of consciousness; and hypnotics, to produce lethargy. This psychological factitious condition is less common than factitious disorders with physical symptoms and is almost always superimposed on a severe personality disorder.2,9 Physical Symptoms.  The intentional production of physical symptoms may take the form of fabricating of symptoms without signs (eg, feigning abdominal pain), simulation of signs suggesting illness (eg, fraudulent pyuria, induced anemia), self-inflicted conditions (eg, the production of abscesses by injection of contaminated material under the skin), or genuine complications 1361

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BOX 104.1 

DSM-5 Criteria for the Diagnosis of Factitious Disorder Imposed on Self 1. Falsification of psychological or physical signs or symptoms, or induction of disease or injury associated with identified deception. 2. The individual presents to others as injured, ill, or impaired. 3. The deceptive behavior is apparent even in the absence of external incentives. 4. The behavior is not better explained by another mental disorder.

from the intentional misuse of medications (eg, diuretics, hypoglycemic agents).7,10,11,15 These patients are predominantly unmarried women younger than 40 years old. They typically accept their illness with few complaints and are generally well-educated, responsible workers or students with moral attitudes and otherwise conscientious behavior.9,15,16 Many are in health care occupations, including nurses, aides, and physicians. These patients are willing to undergo incredible hardship, limb amputation, organ loss, and even death to perpetuate the masquerade.10,15 Although multiple hospitalizations often lead to iatrogenic physical conditions, such as postoperative pain syndromes and drug addictions, patients continue to crave hospitalization for its own sake. They typically have a fragile and fragmented selfimage and are susceptible to psychotic and even suicidal episodes.15,16 Interactions with the health care system and relationships with caregivers provide the needed structure that stabilizes the patient’s sense of self. The hospital may be perceived as a refuge, sanctuary, or womblike environment.15,16 Some patients are apparently driven by the conviction that they have a real but as yet undiscovered illness. Consequently, artificial symptoms are contrived to convince the physician to continue a search for the elusive disease process.15,16 Factitious illness behavior has even emerged on the Internet. “Virtual support groups” offering person-to-person communications through chat rooms and bulletin boards have been perpetrated by individuals, under the pretense of illness or personal crisis, for the purpose of extracting attention or sympathy, acting out anger, or exercising control over others.8 Approach to Diagnosis.  The initial diagnosis of FDIS is often delayed because the possibility of factitious disease is not considered, physicians may be unfamiliar with this problem, or the patient does not exhibit the type of personality expected with this behavior.9 Diagnosis may be confounded by genuine medical illnesses predating and coexisting with a factitious disorder. For example, patients with factitious hypoglycemia may have a history of insulin-dependent diabetes mellitus, or factitious skin disorders may be preceded by true dermatologic diseases.1,15 Identification of a factitious disorder is usually made in one of four ways: (1) the patient is accidentally discovered in the act, (2) incriminating items are found, (3) laboratory values suggest nonorganic etiology, or (4) the diagnosis is made by exclusion.4,7 There has been increasing recognition of factitious illness produced by children. These children, ranging in age from 8 to 18 years old, are typically “bland, flat and indifferent during their extensive medical interventions … depressed, socially isolated, and often obese.”13 Among the most common presentations are fever without clear etiology, diabetic ketoacidosis, purpura, and recurrent infections. The prognosis is good if identification and psychotherapeutic intervention can be carried out at a young age.12

Munchausen Syndrome.  The uncommon patient with true Munchausen syndrome has a prolonged pattern of “medical imposture,” usually years in duration. The behavior usually begins before 20 years old and is diagnosed between 35 and 39 years old. Twice as many men as women are affected.8,15,16 Patients’ entire adult lives may consist of trying to gain admission to hospitals and then steadfastly resisting discharge. Their career of imposture usually lasts about 9 years but has continued unabated for as long as 50 years.4,15 The quest for repeated hospitalizations often takes these patients to numerous and widespread cities, states, and countries.2,8 These individuals see themselves as important people, or at least related to such persons, and their life events are depicted as exceptional.16 They possess extensive knowledge of medical terminology. There is frequently a history of genuine disease, and the individual may exhibit objective physical findings.16 The symptoms presented are “limited only by the person’s medical knowledge, sophistication, and imagination.”2 The alleged illnesses involved have been termed dilemma diagnoses in that investigators rarely can totally rule out the disorder, clarify the cause, or prove that it did not exist at one time.4 Common presentations are those that most reliably result in admission to the hospital, such as abdominal pain, self-injection of a foreign substance, feculent urine, bleeding disorders, hemoptysis, paroxysmal headaches, seizures, shortness of breath, asthma with respiratory failure, chronic pain, acute cardiovascular symptoms (eg, chest pain, induced hypertension and syncope), renal colic and spurious urolithiasis, fever of unknown origin (hyperpyrexia figmentatica), profound hypoglycemia, and coma with anisocoria.4-6,10,15,16 Some self-induced conditions are highly injurious or even lethal.10 The patient usually presents during evenings or on weekends so as to minimize accessibility to psychiatric consultants, personal physicians, and past medical records.16 In teaching institutions, these patients often present in July, shortly after the change in resident house officers.10 They relate their history in a precise, dramatic, even intriguing fashion, embellished with flourishes of pathologic lying and self-aggrandizement. Pseudologia fantastica, or pathologic lying, is a distinctive peculiarity of these patients. In a chronic, often lifelong behavior pattern, the patient typically takes a central and heroic role in these tales, which may function as a way to act out fantasy.17 The history quickly becomes vague and inconsistent, however, when the patient is questioned in detail about medical contacts.3 Attempts to manage the complaint on an outpatient basis are adamantly resisted.15 Once admitted, the patient initially appeals to the physician’s qualities of nurturance and omnipotence, lavishing praise on the caregivers. Behavior rapidly evolves, however, as the patient creates havoc on the ward by insisting on excessive attention while ignoring both hospital rules and the prescribed therapeutic regimen.15 When the hoax is uncovered and the patient confronted, fear of rejection abruptly changes into rage against the treating physician, closely followed by departure from the hospital against medical advice.15,18

Factitious Disorder Imposed on Another The diagnosis of FDIA depends on specific criteria (Box 104.2).2 The presenting complaints typically evade definitive diagnosis and are refractory to conventional therapy for no apparent reason.19 The symptoms are usually more than five in number, presented in a confused picture; they are unusual or serious and, by design, unverifiable. They invariably occur when the mother is alone with the child or otherwise unobserved.12 In 72% to 95% of cases, simulation, or production of illness occurs while the victim is hospitalized.11,12,14 Simulated illness, faked by the mother without producing direct harm to the child (eg, the addition of blood to a urine

CHAPTER 104  Factitious Disorders and Malingering

BOX 104.2 

BOX 104.3 

DSM-5 Criteria for the Diagnosis of Factitious Disorder Imposed on Another

Characteristics of Malingering

1. Falsification of psychological or physical signs or symptoms, or induction of disease or injury in another, associated with identified deception. 2. The individual presents another individual (victim) to others as injured, ill, or impaired. 3. The deceptive behavior is apparent even in the absence of external incentives. 4. The behavior is not better explained by another mental disorder.

specimen), is present in 25% of cases. Produced illness, which the mother actually inflicts on the child (eg, the injection of feces into an intravenous line), is found in 50% of cases. Both simulated and produced illnesses are found in 25% of cases.11-14 FDIA most commonly arises with factitious bleeding, seizures, central nervous system (CNS) depression, apnea, diarrhea, vomiting, fever, and rash.14 Reported techniques of simulation or production of disease include administration of drugs or toxins (eg, chronic arsenic poisoning, ipecac, warfarin, phenolphthalein, hydrocarbons, salt, imipramine, laxatives, CNS depressants), caustics applied to the skin, and nasal aspiration of cooking oil.11,14,18 Techniques of asphyxiation include (1) covering the mouth or nose with one or both hands, a cloth, or plastic film, and (2) inserting the fingers into the back of the mouth. In such instances, even struggling infants may sustain no cutaneous markings.19 Cases involving seizures are common and may involve third-party witnesses. On personal questioning, however, these witnesses frequently deny the occurrence of seizure activity.6,13,14 Perpetrator Characteristics.  Ninety-eight percent of perpetrators are biologic mothers who come from all socioeconomic groups.11-14 Many have a background in health professions or social work, or a past history of psychiatric treatment, marital problems, or suicide attempts.11-15 Depression, anxiety, and somatization are common, but frank psychotic behavior by the mother is atypical.14 Perpetrators of FDIA have an inherent skill in manipulating health care workers and child protection services.13 They are pleasant, socially adept, cooperative, and appreciative of good medical care. They often display a peculiar eagerness to have invasive procedures performed on their child.3 They often prefer to stay in the hospital with their child, cultivate unusually close relationships with hospital staff, and thrive on staff attention.11-14 This affable relationship with the medical team rapidly changes to excessive anger and denial when the perpetrator is confronted with suspicions.12,13 Most of these mothers have had an abusive experience early in life, and they use the health care system as a means to satisfy personal nurturing demands.3,12 They often cannot distinguish their needs from the child’s and satisfy their own needs first. They derive a sense of purpose from the medical and nursing attention gained when their children are in the hospital.11-13 Alternatively, the behavior may enable the mothers to escape from their own physical or psychological illnesses, marital difficulties, or social problems.13 Victim Characteristics.  Victims of FDIA are equally male and female children. The mean age at diagnosis is 40 months, and the mean duration from the onset of signs and symptoms to diagnosis is 15 months.11-13 A known physical illness that explains part of the symptoms is common among these children.13 Most

1. Medicolegal context of the presentation (eg, the patient was referred by his or her attorney) 2. Marked discrepancy between the person’s claimed stress or disability and objective findings 3. Poor cooperation during the diagnostic evaluation or poor compliance with previously prescribed treatment regimens 4. The person exhibits or has a history of antisocial behavior

have a history of significant failure to thrive and have been hospitalized in more than one institution. Delays in many areas of performance and learning, difficulty with family relationships, attention deficit disorder, or clinical depression may coexist.13 Some of these victims may have factitious disorder later in life.3 Elders may also be victims of FDIA, although this is uncommon.20 Approach to Diagnosis.  Suspected FDIA requires a detailed description of the event or illness and a search for caregiver witnesses, who should be interviewed personally. Although it is essential to see the child when the symptoms are present, the parents show great ingenuity at frustrating this effort.12,13 Additional history of unusual illness in siblings and parents should be sought. Child victims who are verbal should be interviewed in private about foods, medicines, and their recollection of the symptoms or events. Prior medical records of the victim and, if possible, the siblings should be examined, although parents may impede such data gathering. The major obstacle to early discovery of FDIA is its omission from the differential diagnosis. When it is considered, the diagnosis is generally made easily and quickly.11-13 A suspected diagnosis may be confirmed through separation of the parent from the child or individual (with consequent cessation of symptoms), covert video surveillance during hospitalization, or toxicologic screens.16 In the majority of cases, the caregiver attempts to induce episodes surreptitiously while in the hospital, often during the first day of admission.11-13

Malingering Malingering is frequently found in association with antisocial personality disorder. On questioning, malingerers are vague about prior hospitalizations or treatments. The physicians who previously treated them are usually unavailable. At times, malingerers may be careless about their symptoms and abandon them when they believe no one is watching.8 In some “patients,” such as those seeking drugs, homeless persons seeking hospital admission on a cold night, or prisoners wanting a holiday from incarceration, the secondary gain may be clear. In other persons, the external incentive may be obscure. In contrast to the person with factitious disorders, the malingerer prefers counterfeit mental illness, because it is objectively difficult to verify or to disprove. Amnesia is the most common psychological presentation, followed by paranoia, morbid depression, suicidal ideation, and psychosis.15 Malingering should be strongly suspected with any combination of certain factors (Box 104.3).2 A definitive diagnosis of malingering is rare and can be established only with the patient’s confession.3 Because malingering constitutes criminal behavior, documentation of this diagnosis should be made with care.15 In the absence of proof of wrongdoing, it is best to assume that the

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patient is not a malingerer but rather a common somatizer.15 Malingerers who pursue drugs may report an unusually large number of drug allergies to persuade the physician to prescribe their drug of choice or simply insist on a specific drug (eg, meperidine [Demerol] or hydromorphone [Dilaudid]).8 Unfortunately, the Internet offers a wide availability of quality medical advice on how to convincingly feign pain and disability.

DIFFERENTIAL DIAGNOSIS The most important diagnoses to be excluded are genuine medical and psychiatric conditions that might account for the presenting symptoms. Patients with conversion disorder, somatic disorder, delusional disorder of somatic type, and borderline personality disorder can present with symptoms similar to FDIS. The differences can be subtle and psychiatric consultation or referral is indicated. Patients with factitious disorders are distinguished from malingerers because their desired hospitalization or surgery seems to offer no secondary gain other than to play the sick role.2,10,15 The clinical presentation of the majority of patients with factitious disorders, unlike those with Munchausen syndrome, is relatively subtle and convincing. The complaints are generally chronic in nature rather than emergent and precipitous, and there are no obvious associated behavioral aberrations.15 The chronicity of malingering is usually less than that associated with factitious disorder, and malingerers are more reluctant to accept expensive, possibly painful, or dangerous tests or surgery.15

MANAGEMENT Factitious Disorders Treatment options for factitious disorders depend on the patient’s characteristics. Although it is challenging, management of common forms of factitious disorder can be more rewarding, especially with adolescents, than management of Munchausen syndrome.11,15 The prognosis is more favorable for cases with an underlying depression than for those associated with borderline personalities.11,14 The best approach to patients with factitious disorder, other than Munchausen syndrome and FDIA, is controversial. Direct non-accusatory confrontation has been advocated as “the foundation of effective management” when it is coupled with the assurance that an ongoing relationship with a physician will be provided.11,13,15 This may be the first step in the acceptance of outpatient therapy.15 Others point out that confrontation is ineffective in most patients and may even be counterproductive in that it threatens to undermine a needed psychological defense. Enforced recognition of external objective reality, while simultaneously disallowing the patient’s subjective experience, may generate even more dysfunction directed at legitimizing and maintaining symptoms and may even place the patient at risk for suicide.11,15 Some patients may relinquish this defense if they feel safe in doing so and may abandon a claim to disease if some face-saving option is offered. This approach, termed the therapeutic double bind or contingency management, involves informing the patient that a factitious disorder may exist. The patient is further told that failure to respond fully to medical care would constitute conclusive evidence that the patient’s problem is not organic but rather psychiatric. The problem is therefore reframed or redefined in such a way that (1) symptoms and their resolution are both legitimized and (2) the patient has little choice but to accept and respond to a proposed course of action or seek care elsewhere.15

Individuals with Munchausen syndrome typically demonstrate overt sociopathic traits or a borderline personality disorder and are demanding and manipulative, especially regarding analgesics.15 They have been described as “essentially untreatable,” and successful management of this condition is, in fact, considered reportable. Early confrontation or limit setting, especially regarding drug use, is advocated.8,10,15 Although Munchausen patients typically do not want to be examined extensively, a thorough physical examination should be performed to rule out physical disease. FDIA constitutes a form of child (or elder) abuse, and appropriate action to protect the victim, including notification of state social service agencies, should take immediate priority.13,14 If available, a pediatrician who has expertise in child abuse should assess the case. When the diagnosis has been established and the parents have been confronted, psychiatric care should be made immediately available to the parents because maternal suicide is a significant risk.13,15

Malingering Malingerers do not want to be treated. Because they are “gaming the system” for personal advantage, the last thing they want is an accurate identification of their behavior and appropriate intervention. The emergency clinician should maintain clinical neutrality, offering the reassurance that the symptoms and examination are not consistent with any serious disease. Some authors have characterized patients’ use of medical resources under false pretenses as criminal behavior, and several states have enacted legislation against the fraudulent acquisition of medical services with successful prosecution of such behavior.4,8 Conversely, patients with factitious disorders can and do sue. In dealing with such patients, it is advisable to involve hospital administration and risk management. Clandestine searches are inadvisable, and respect for the patient’s confidentiality should be maintained.15

DISPOSITION Patients suspected of having a factitious disorder should be referred for primary care follow-up, and if it is acceptable to the patient, psychiatric referral should also be arranged. Referral to other medical specialists or hospitalization should be avoided when possible. The manner of presentation and the unavailability of past medical history often allow patients with Munchausen syndrome to achieve hospital admission. If the patient is discharged from the ED, outpatient primary care follow-up and psychiatric referral should be offered, although both are likely to be refused.15 Because perpetrators of FDIA typically induce symptomatic episodes soon after hospitalization, admission of the victims (children or elders) without taking appropriate precautions may actually place them at increased risk.11,13,20 Visits by the suspected perpetrator should be closely supervised, and no food, drink, or medicines should be brought in by the family. Protective services should be notified. Out-of-home placement of children in established cases of FDIA is advisable, and the best outcomes are seen among children taken into long-term care at an early age without access to their mother. Children allowed to return home have a high rate of repeated abuse.3,12 In 20% of reported deaths, the parents had been confronted and the child sent home to them, subsequently to die.12,13 After courteous but assertive reassurance, suspected malingerers should be offered primary care follow-up if the symptoms do not resolve. These individuals may become threatening when they are either denied treatment or overtly confronted.15

CHAPTER 104  Factitious Disorders and Malingering

KEY CONCEPTS • Patients who have consciously synthesized symptoms and signs may be divided into two broad diagnostic categories: (1) those with obvious secondary gain (malingering), who control their actions, and (2) those with a motivation of achieving the sick role (factitious disorders), who cannot control their actions. • The initial management of patients suspected of fabricating disease should include a caring, nonjudgmental attitude and a search for objective clinical evidence of treatable medical or psychiatric illness.

Review of old medical records and interview of family members are often helpful. • Unnecessary tests, medications, and hospitalizations should be avoided in the absence of objective evidence of a medical or psychiatric disease, and patients should be referred for ongoing primary care. • In cases of suspected FDIA involving children or elders, protection of the victim takes first priority.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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CHAPTER 104  Factitious Disorders and Malingering

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REFERENCES 1. Kahn A, Boroff ES, Martin KA, et al: Factitious disorder in Crohn’s disease: recurrent pancytopenia caused by surreptitious ingestion of 6-mercaptopurine. Case Rep Gastroenterol 9(2):137–141, 2015. 2. American Psychiatric Association (APA): Diagnostic and statistical manual of mental disorders, ed 5, Washington, DC, 2013, APA, pp 324–326, 726. 3. Feldman MD: Playing sick? Untangling the web of Munchausen syndrome, Munchausen by proxy, malingering, and factitious disorder, New York, 2013, Routledge. 4. Kenedi CA, Shirey KG, Hoffa M, et al: Laboratory diagnosis of factitious disorder: a systematic review of tools useful in the diagnosis of Munchausen’s syndrome. N Z Med J 124(1342):66–81, 2011. 5. Kwon Y, Koene RJ, Cross C, et al: Fatal non-thrombotic pulmonary embolization in a patient with undiagnosed factitious disorder. BMC Res Notes 8:302, 2015. 6. Kanaan RA, Wessely SC: Factitious disorders in neurology: an analysis of reported cases. Psychosomatics 51:47, 2010. 7. Kinns H, Housley D, Freedman DB: Munchausen syndrome and factitious disorder: the role of the laboratory in its detection and diagnosis. Ann Clin Biochem 50(Pt 3):194–203, 2013. 8. Pulman A, Taylor J: Munchausen by Internet: current research and future directions. J Med Internet Res 14(4):e115, 2012. 9. Wills B, Kwan C, Bailey M, et al: Recalcitrant supraventricular tachycardia: occult albuterol toxicity due to a factitious disorder. J Emerg Med 49(4):436–438, 2015. 10. Vaduganathan M, McCullough SA, Fraser TN, et al: Death due to Munchausen syndrome: a case of idiopathic recurrent right ventricular failure and a review of the literature. Psychosomatics 6(55):668–672, 2014.

11. Bass C, Glaser D: Early recognition and management of fabricated or induced illness in children. Lancet 383(9926):1412–1421, 2014. 12. Grace E, Jagannathan N: Munchausen syndrome by proxy: a form of child abuse. Int J Child Adolesc Health 8(3):259, 2015. 13. Flaherty EG, Macmillan HL, Committee on Child Abuse and Neglect: Caregiverfabricated illness in a child: a manifestation of child maltreatment. Pediatrics 132(3):590–597, 2013. 14. Kucuker H, Demir T, Oral R: Pediatric condition falsification (Munchausen syndrome by Proxy) as a continuum of maternal factitious disorder (Munchausen syndrome). Pediatr Diabetes 11(8):572–578, 2010. 15. Bass C, Halligan P: Factitious disorders and malingering: challenges for clinical assessment and management. Lancet 383(9926):1422–1432, 2014. 16. Krahn LE, Li H, O’Connor MK: Patients who strive to be ill: factitious disorder with physical symptoms. Am J Psychiatry 160(6):1163–1168, 2003. 17. Gogineni R, Newmark T: Pseudologia fantastica: a fascinating case report. Psychiatr Ann 44:451–454, 2014. 18. Dumitrascu CI, Gallardo KE, Caplan JP: Malingering imposed on another: a diagnosis that is missing in action? Psychosomatics 56(6):609–614, 2015. 19. Byard R: Issues in the classification and pathological diagnosis of asphyxia. Aust J Forensic Sci 43(1):27–38, 2011. 20. Burton MC, Warren MB, Lapid MI, et al: Munchausen syndrome by adult proxy: a review of the literature. J Hosp Med 10(1):32–35, 2015.

CHAPTER 104: QUESTIONS & ANSWERS 104.1. Which of the following statements regarding factitious disorder is true? A. It involves voluntary and controllable symptom production. B. Patients are generally well educated and otherwise responsible. C. Presentations are not related to an identifiable event. D. The symptoms produced are always physical ones. E. The underlying motivation is a conscious one. Answer: B. Many such patients are actually employed in the health care industry. The act of producing symptoms is voluntary but not controllable and derives from a subconscious motivation. Presentations are very often related to a “traumatic” event, such as a breakup. Produced symptoms may be physical (eg, hematuria) or psychological. The typical patient is an unmarried female younger than 40 years. Despite undergoing invasive procedures and associated hardships, these patients seek more medical care and hospitalization. 104.2. Which of the following statements concerning Munchausen syndrome by proxy is true? A. A known physical illness in the child is common. B. Most maternal perpetuators are demanding, uncooperative, and socially inept. C. Most maternal perpetrators are not a biologic parent. D. Psychosis is common in the maternal perpetrator. E. The mean age of victim diagnosis is 7 to 9 years. Answer: A. Victim children often have a legitimate illness. Mean age at diagnosis is 40 months. Most have a history of failure to thrive and multiple hospitalizations. The perpetrator receives some personal fulfillment from the care and attention of the hospital staff, which is often admiration for her persistence, willingness to sacrifice and patience, and she is typically pleasant, medically savvy, and socially skilled. Invasive procedures on the child are often welcomed. Although psychosis is very unusual in the parent, depression, anxiety, and somatization are typical in the perpetrator. 104.3. A 2-year-old female presents with new onset seizures. Her past medical history is unremarkable. Laboratory

evaluation reveals blood glucose of 20 mg/dL. The patient’s mother denies a family history of diabetes or having medications the child might have ingested at home. She works as a nurse at a local hospital and has been with the child all day. The child’s symptoms improve with glucose administration and a meal. Your colleague remembers evaluating the child recently for hematuria with a negative evaluation. If you suspect Munchausen syndrome by proxy, which of the following tests would be most helpful in establishing the diagnosis? A. Basic metabolic panel B. Computed tomography (CT) scan of head C. C-peptide and insulin level D. Electroencephalography (EEG) Answer: C. The diagnostic criteria for factitious hypoglycemia include high serum insulin levels along with the absence of serum C-peptide. The C-peptide is removed during the purification of commercial insulin, and so its absence suggests the presence of endogenously administered insulin. In patients with insulinoma, both C-peptide and insulin levels are elevated and detectable. 104.4. A prison inmate presents after falling from the top bunk in his cell. He is complaining of lower lumbar pain and states he is unable to move or feel his lower extremities from his waist down. On physical examination, lower extremity reflexes are present but the patient denies feeling pain or light touch sensation below the waist. Lumbar spine CT and MRI are negative. Which of the following conditions is most likely? A. Cord contusion B. Factitious disorder C. Malingering D. Munchausen syndrome Answer: C. Malingering is the intentional symptom production for secondary gain. There is a marked discrepancy between claimed disability and the actual objective findings. Confessions and proof are rare.

C H A P T E R 105 

Suicide Marian E. Betz  |  Jeffrey M. Caterino

PRINCIPLES Background Emergency clinicians care for large numbers of patients with suicidal ideation and self-harm behaviors. Two facts are especially important to remember in the care of suicidal patients. First, many suicide attempts occur during an acute crisis, such as a personal loss or the exacerbation of an underlying psychiatric disorder. This acute crisis is usually time limited and may be resolvable or treatable. Second, suicidal patients are usually ambivalent about dying and grateful for help. An empathetic, patient-centered, and evidence-based approach offers the opportunity to save lives.

Epidemiology In 2011, suicide was the fourth leading cause of death in the United States for adults between 18 and 65 years old.1 There are more than one million suicide attempts and 41,000 suicide deaths in the United States, and rates are rising.2 Between 1999 and 2010, the age-adjusted suicide rate among 35 to 64 year olds increased 28.4%.3 In the United States, there are over 800,000 visits to emergency departments (EDs) each year for self-inflicted injuries.4 Many patients evaluated for suicidality are discharged; in 2008, only half of ED visits for suicide attempts resulted in hospitalization.5 Suicide rates vary with age and are highest in elders, particularly older white men (Fig. 105.1 and Table 105.1).6 Whites and Native Americans have higher rates of suicide than African Americans, Hispanics, or Asians. Women attempt suicide three to four times more often than men, whereas men are three to four times more likely to die after an attempt (due to use of more lethal methods) and have higher suicide death rates in all age groups (see Fig. 105.1).7 Both pregnancy and motherhood seem to protect against suicide, except in cases of postpartum depression. Sexual orientation is also associated with suicide risk because youth identifying as lesbian, gay, or bisexual have increased risk for suicidal ideation and attempts.8-9 Suicide also varies geographically, with higher rates in the Western United States, rural areas, at higher elevations, and in areas with higher levels of firearm ownership.2,10,11 Among military personnel, suicide risk is increased in males and those with psychiatric history, alcohol abuse, or previous deployment.12-14 In 2012, suicide surpassed war as the leading cause of death in the military.15

Risk Factors There are many factors associated with an increased risk of suicide (see Table 105.1), although it is important to recognize that some of these have stronger associations than others. Some risk factors are dynamic, whereas others are static; thus an individual patient’s 1366

risk may vary over time, but helping someone at a current low risk of suicide may prevent future escalation to high risk.16

Self-Harm A prior history of non-suicidal self-harm or suicide attempt, even in the remote past, is an important risk factor (see Table 105.1).17,18 Because 10% to 15 % of suicide attempters will ultimately die by suicide, prior suicide attempt is one of the most important predictors of a future attempt.19 At the same time, up to 80% of suicide completers have no prior history of attempts and die on the first known attempt.1,20

Mental Illness The presence of an affective disorder, especially major depression, is also a strong independent risk factor for suicide. There are increased rates of suicide in patients with schizophrenia, bipolar disorder, borderline personality traits or disorder, anxiety disorder, and post-traumatic stress disorder.21,22 Overall, the risk of suicide in patients with mental illness increases with the presence of prior attempts, recent psychiatric hospitalization, male gender, more severe symptoms, hopelessness, comorbid psychiatric disorders, use of alcohol or drugs, and family history of suicide. The presence of comorbid depression in the setting of other mental illness is a particularly strong factor. In patients hospitalized for psychiatric disorders, the risk for suicide is greatest in the first month after discharge, especially in the first week. Some patients, particularly children and adolescents, may have increased suicidal thoughts or attempts soon after the initiation of antidepressant medications.23 This may be due to the “mobilization of energy” theory, which suggests profoundly depressed patients have the energy to attempt suicide only as their condition improves with treatment. The clinician should recognize the time period around initiation of antidepressant therapy as one requiring heightened scrutiny for suicidal thoughts or behaviors.

Alcohol and Substance Abuse Both chronic and acute alcohol abuse are associated with suicide. Patients with chronic alcohol use have over nine times the risk of completed suicide. Alcoholics who die from suicide usually have multiple risk factors, including major depression, unemployment, medical illness, and interpersonal loss. Acute alcohol use is associated with increased risk of suicide in both those with and without chronic alcohol abuse, and this risk persists for 24 to 48 hours after drinking, particularly heavy drinking.24-26 This effect is largest among younger adults and is more often associated with violent means of suicide (eg, firearms or hanging).27 Substance abuse is associated with increased frequency, repetitiveness, and lethality in suicide attempts. Illicit substances are often detected at the time of suicide; of all suicides in 16 states in 2010, 33% tested positive

CHAPTER 105  Suicide

Male

Female

59 914 15 -1 20 9 -2 25 4 -2 30 9 -3 35 4 -3 40 9 45 44 -4 50 9 -5 55 4 -5 60 9 -6 65 4 -6 70 9 75 74 -7 80 9 -8 4 85 +

Rate per 100,000 population

2003-2013, United States suicide death rates 50 45 40 35 30 25 20 15 10 5 0

TABLE 105.2 

Additional Risk Factors for Suicide in Adolescence Demographic

Sexual orientation (lesbian; gay; bisexual; unsure)9

Biopsychosocial

Sedentary activities (≥3 hours day TV or video games; sleep 25,000/mm +LR for SA = 2.9 >50,000/mm3 +LR for SA = 7.7 >100,000/mm3 +LR for SA = 28

90% +LR for SA = 2.7

1500 cells/mm3), although this does not correlate well with the presence of active disease. MyeloperoxidaseANCA antibodies are seen in about 40% of cases. Pulmonary infiltrates are typically patchy and transient in nature (Löffler’s syndrome). The diagnosis of Churg-Strauss syndrome is made by a combination of clinical and histologic features; evidence of necrotizing vasculitis or extravascular granulomas on skin or lung biopsy in conjunction with eosinophilia, asthma, and allergy is highly suggestive of the disease. Management.  Corticosteroids are the mainstay of treatment, although immunomodulating agents such as cyclophosphamide may be added to achieve remission in cases complicated by cardiac, renal, or gastrointestinal involvement. The overall survival for patients with Churg-Strauss syndrome approaches 80%, with an increased relative risk of death predicted by the presence of renal and gastrointestinal symptoms.

Vasculitis With Characteristic Cutaneous Manifestations

Fig. 108.7.  Tender subcutaneous nodules associated with erythema nodosum. (From Kliegman R: Nelson textbook of pediatrics, ed 18, Philadelphia, 2007, WB Saunders.)

Cutaneous vasculitis involves inflammation of the blood vessels of the skin. The diseases listed here are associated with cutaneous manifestations that are often characteristic and an important element of disease recognition in the ED. Constitutional signs and symptoms of systemic multisystem disease may also be present.

chicine are reserved for the management of protracted or refractory disease.

Erythema Nodosum Principles.  Erythema nodosum, a vasculitis of the venules and veins of the skin, is characterized by tender, subcutaneous nodules on the tibial surfaces of the lower legs. Erythema nodosum is presumed to be a hypersensitivity response to systemic diseases or drug therapy, although no clear precipitant can be identified in 30% to 50% of cases. Peak incidence occurs in the spring or fall months among 18- to 34-year-olds, with a male-to-female ratio of approximately 1 : 4. Clinical Features.  The prodromal stage of erythema nodosum consists of nonspecific constitutional symptoms, fever, malaise, and myalgias. The distribution of subcutaneous nodules favors the lower extremities, although lesions may be appreciated on the forearm, trunk, and thigh (Fig. 108.7). The nodules tend to be erythematous, well circumscribed, and exquisitely tender to touch and develop a blue hue as they resolve. Arthralgias may be present in conjunction with or before the cutaneous eruption. Viral upper respiratory tract infections, streptococcal infection, tuberculosis, and sarcoidosis are common precipitants. Drugs associated with erythema nodosum include penicillins, sulfonamides, oral contraceptive medication, and phenytoin. Less common associations include autoimmune conditions, such as inflammatory bowel disease and SLE; histoplasmosis; Yersinia, Salmonella, and Chlamydia infections; coccidioidomycosis; and psittacosis. Management.  Management of erythema nodosum is generally supportive and directed toward symptom control and treatment or elimination of the underlying cause. Cutaneous nodules secondary to infection resolve within 6 to 7 weeks; in contrast, 30% of idiopathic cases may persist beyond 6 months. NSAIDs may be useful for control of arthralgias; corticosteroids and col-

Henoch-Schönlein Purpura Principles.  Henoch-Schönlein purpura is a small-vessel vasculitis characterized by palpable purpura and gastrointestinal and renal manifestations associated with immunoglobulin A immune complex deposition in blood vessels. The 1990 American College of Rheumatology criteria for Henoch-Schönlein purpura include the presence of two or more of the following: age at onset younger than 20 years old, palpable purpura, bowel angina, and vessel wall granulocytes on biopsy (sensitivity of 87.1%, specificity of 87.7%). Although the disease can affect adults, it is most commonly seen in children younger than 5 years old. Clinical Features and Diagnostic Testing.  Henoch-Schönlein purpura usually is manifested 1 to 2 weeks after a viral upper respiratory tract infection with a triad of palpable purpura, arthralgias, and abdominal pain. Purpuric lesions cluster in dependent regions with a predilection for the legs and buttocks (Fig. 108.8). Colicky abdominal pain and bloody stools can occur secondary to gastrointestinal vasculitis. A rare complication of Henoch-Schönlein purpura in children is enteroenteral intussusception (ileoileal, jejunojejunal, jejunoileal), which may be associated with severe abdominal pain, lethargy, bloody diarrhea, and signs of obstruction or perforation. Glomerulonephritis is typically mild and may be manifested as hematuria, red cell casts on urinalysis, and azotemia. Management.  Management in mild disease is generally supportive, and symptoms can intermittently recur for several weeks. NSAIDs control arthralgias in most cases but are avoided if renal impairment is present. Glomerulonephritis is treated more aggressively, with a combination of corticosteroids and cyclophosphamide, azathioprine, or mycophenolate mofetil, and generally demonstrates full resolution with time. Enteroenteral

CHAPTER 108  Systemic Lupus Erythematosus and the Vasculitides

Fig. 108.9.  Oral aphthae associated with Behçet’s disease. (From Firestein GS: Kelley’s textbook of rheumatology, ed 8, Philadelphia, 2008, WB Saunders.)

Fig. 108.8.  Purpuric lesions associated with Henoch-Schönlein purpura, some of which have coalesced and undergone central necrosis. (From Habif TP: Clinical dermatology, ed 5, New York, 2009, Mosby.)

intussusception can be difficult to diagnose with standard approaches (ultrasonography, air-contrast enema), and if the diagnosis is strongly suspected, patients should be assessed by a pediatric general surgeon. Polyarteritis Nodosa Principles.  Polyarteritis nodosa is a necrotizing vasculitis of unknown etiology affecting small and medium-sized blood vessels. The disease can involve multiple systems, most commonly the skin, nervous system, and gastrointestinal tract. Necrosis occurs preferentially at arterial bifurcations and branch sites, leading to microaneurysm formation, thrombosis, emboli, organ ischemia, and infarction. Polyarteritis nodosa affects men about twice as often as women, and onset occurs at any age, although the peak is typically the fourth to sixth decade of life. Annual incidence is between 2 and 9 cases per 1 million individuals. Clinical Features.  Whereas the initial presentation can be nonspecific, the combination of cutaneous lesions and adult-onset hypertension with evidence of systemic illness suggests polyarteritis nodosa. Cutaneous manifestations occur in one-third of patients. Palpable purpura with or without ulceration is noted in the fingers, ankles, malleoli, and pretibial areas. Digital cyanosis may be seen secondary to ischemia. Splinter hemorrhages and livedo reticularis may also be observed. Renovascular arteritis can cause hypertension, which may at times be severe. Peripheral neuropathies in the form of mononeuritis multiplex or polyneuropathy are present in up to 50% of patients. Mesenteric vasculitis can produce abdominal angina and in rare cases lead to frank mesenteric ischemia, infarction, and perforation, often with devastating consequences. Management.  Treatment generally begins with a corticosteroid (eg, prednisone 1 mg/kg), and a second immunosuppressive agent is added for severe or extensive disease. Abdominal catas-

trophes may require surgical intervention; prognosis in these cases is poor. Polyarteritis nodosa is almost always fatal if it is left untreated, although the prognosis has been much improved with the use of systemic corticosteroids. In a prospective study, the presence of two or more prognostic factors (azotemia, proteinuria, cardiomyopathy, gastrointestinal involvement, or neurologic signs) predicted a 5-year mortality of 46%; if none was present, the 5-year mortality was 12%. Behçet’s Disease Principles.  Behçet’s disease is a complex, chronic small-vessel vasculitis that may affect the mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary, urologic, musculoskeletal, and central nervous systems. Early descriptions of the disease date to the time of Hippocrates and the third book of endemic diseases. The disease is defined by the presence of aphthous oral ulcers plus two or more of the following: genital aphthae; cutaneous lesions; and neurologic, oral, or rheumatologic manifestations. The exact pathogenesis remains unknown. Behçet’s disease is found worldwide, with the highest prevalence in Turkey, Japan, the Middle East, and Mediterranean regions. The disease affects people of all ages, although patients often first present in the second or third decade of life. The male-to-female ratio varies somewhat according to geography; women are more commonly affected than men in northern Europe and the United States, with an estimated prevalence in these regions of about 1 in 150,000 individuals. Clinical Features and Diagnostic Testing.  The triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis in young adults is highly suggestive of Behçet’s disease. Oral aphthous ulcers are the defining characteristic of the disease (Fig. 108.9). The lesions are typically found on the tongue, lips, buccal mucosa, and gingiva; the tonsils, palate, and pharynx are less commonly affected. The ulcers are painful, have a yellow, necrotic base, and may appear alone or in crops of three to ten. Genital ulcers appear on the scrotum and penis in men and the vulva or vaginal mucosa in women. Skin lesions include erythema nodosum–like subcutaneous nodules, pyoderma gangrenosum, cutaneous thrombophlebitis, and pustular acne-like folliculitis. Ocular symptoms are common and constitute a major source of morbidity in Behçet’s disease. Findings may include uveitis, iritis, and optic neuritis. Hypopyon, once considered a characteristic feature of the disease, is uncommon. Visual symptoms may be bilateral or unilateral and

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Medicine and Surgery  | 

SECTION Nine 

Immunologic and Inflammatory

can occasionally lead to permanent vision loss. Neurologic manifestations include brainstem and corticospinal tract syndromes (neuro-Behçet’s), aseptic meningoencephalitis, increased intracranial pressure, and cerebral sinus thrombosis complicated by optic nerve ischemia and atrophy.140 Gastrointestinal ulcers can cause obstruction or ileocecal perforation. Inflammatory oligoarthritis of the ankles, knees, elbows, and wrists is present in 40% to 60% of patients. The diagnosis of Behçet’s disease is made primarily on clinical grounds. The appearance of genital lesions can be ambiguous, and other causes of painful genital ulcers need to be ruled out. Management.  Oral and genital ulcerations are often managed successfully with a topical steroid. Management of severe mucocutaneous disease involves systemic corticosteroids (eg, prednisone, 1 mg/kg), low-dose thalidomide, or methotrexate. Treatment of systemic disease may be accomplished with a corticosteroid alone or in combination with cyclophosphamide or azathioprine. Ocular manifestations, including uveitis, are usually managed with prednisone plus azathioprine and require a rapid referral to an ophthalmologist. The presence of cerebral venous sinus thrombosis is an indication for immediate heparinization. Behçet’s disease often has a complicated and protracted course, with morbidity related primarily to ophthalmologic complications. Death can occur from neurologic, cardiovascular, and gastrointestinal sequelae or from complications related to long-term immunosuppressive therapy.

Vasculitis Associated With Environmental or Foreign Antigen Exposure Vasculitis Caused by Cocaine Adulterated With Levamisole.  Levamisole is an immune-modulating agent that has been used to treat autoimmune disorders, various forms of cancer, and the nephrotic syndrome. The drug has been withdrawn from the drug market in the United States owing to the frequency and severity of side effects, including antibody-mediated agranulocytosis and autoimmune vasculitis. Since 2005, the incidence of cocaine cut with levamisole (added at the source of supply to add bulk and weight to the raw product) has been increasing, and some 70% of cocaine seized at United States borders contains levamisole to varying degrees. Levamisole is not detected by routine blood and urine toxicology testing, and specialized testing with gas chromatography or mass spectrometry is of limited clinical utility given the short half-life of the drug (5.6 hours); it is unlikely to be detected in the plasma or urine beyond 24 to 72 hours after the last exposure. The rash associated with levamisole involves tender palpable purpuric plaques with a predilection for the cheeks, nose, and earlobes (Fig. 108.10). Treatment is typically supportive; spontaneous resolution occurs with discontinuation of the offending agent. The agranulocytosis associated with levamisole is transient and fully reversible within a week to 10 days after discontinuation of the offending agent. Patients may present with asymptomatic agranulocytosis detected on routine blood work or with fever, sepsis, or signs of overwhelming infection. Febrile patients are treated with broad-spectrum antibiotics and a septic evaluation directed at the likely source of infection, similar to febrile neutropenia associated with chemotherapy. Afebrile patients are also

Fig. 108.10.  Vasculitic lesions caused by crack cocaine containing levamisole. (Courtesy Dr. Christopher Hicks, University of Toronto.)

often admitted for investigation and observation until their neutrophil count recovers. Cryoglobulinemic Vasculitis.  Cryoglobulins are immunoglobulins that precipitate from serum at cold temperatures. Damage to small and medium-sized blood vessels occurs when cryoglobulins bind to circulating antigens and deposit in vessel walls, prompting a complement-mediated inflammatory reaction and cryoglobulinemic vasculitis. Three types of cryoglobulinemic vasculitis syndromes have been identified. Type I is associated with Waldenström’s macroglobulinemia and multiple myeloma and produces a syndrome of hyperviscosity with symptoms of presyncope, altered mental status, and stroke. Types II and III are known as the mixed cryoglobulinemias and represent 80% of recognized cryoglobulinemic syndromes. There is a strong association between these subtypes and hepatitis C, Sjögren’s syndrome, and SLE. The mixed cryoglobulinemias are manifested with a triad of purpura, arthralgias, and myalgias along with glomerulonephropathy and vasculitic peripheral neuropathy. Purpuric lesions are typically multiple and confluent and appear preferentially in dependent areas and the lower extremities in particular. Renal failure is the most serious consequence of cryoglobulinemia and is present in 20% to 60% of patients. The diagnosis is based on the presence of serum cryoglobulins accompanied by typical clinical features; the most salient elements of the differential diagnosis include SLE and Henoch-Schönlein purpura. Skin biopsy can be helpful in confirming the diagnosis. Management involves identification and treatment of associated diseases, such as hepatitis C and multiple myeloma. Low-dose corticosteroids are helpful when systemic symptoms are present but should be avoided while antiviral therapy is being initiated. Plasmapheresis may be useful in life-threatening cases related to cryoprecipitation or serum hyperviscosity. Features associated with Buerger’s disease, serum sickness, and hypersensitivity vasculitis are outlined in Table 108.7.

CHAPTER 108  Systemic Lupus Erythematosus and the Vasculitides

TABLE 108.7 

Summary of Buerger’s Disease (Thromboangiitis Obliterans), Serum Sickness, and Hypersensitivity Vasculitis BUERGER’S DISEASE

SERUM SICKNESS

HYPERSENSITIVITY VASCULITIS

Pathophysiology

Small and medium-sized arteries and veins of the extremities

Immune complex deposition in blood vessel walls

Small vessel

Associated exposures

Heavy cigarette smoking Cold exposure

Foreign protein or serum Penicillin-based antimicrobials Sulfa drugs NSAIDs

β-lactam antibiotics NSAIDs Diuretics

Common symptoms

Pain, paresthesias Claudication Rest pain

Fever, arthralgias, and diffuse lymphadenopathy Pruritus, skin lesions

Typically confined to the skin (vs. serum sickness)

Physical examination findings

Poorly healing wounds, ulcerations Splinter hemorrhages Digital ischemia and necrosis Distal-to-proximal progression

Urticaria Purpuric skin lesions Scarlatiniform rash Erythema multiforme Azotemia, proteinuria Myocarditis, pericarditis

Palpable purpura in dependent regions, including legs and buttocks Urticarial vasculitis Livedo reticularis Skin nodules and ulcers

Diagnosis

Angiography: Demonstrates “corkscrew” pattern of collateral vessels; rule out other causes of ischemia

Clinical

Clinical

Management and outcome

Smoking cessation Meticulous wound care Protection from trauma and thermal injury

Supportive Systemic corticosteroids for severe disease Recovery generally within 4 to 6 weeks

Supportive Systemic corticosteroids for severe disease

Comments

Up to 50% of patients who continue to smoke will require amputation

Incidence has decreased with modern immunization programs and the use of products derived from human serum

In theory, any medication can cause a hypersensitivity vasculitis syndrome

NSAIDs, Nonsteroidal antiinflammatory drugs.

KEY CONCEPTS Systemic Lupus Erythematosus

• Systemic lupus erythematosus (SLE) may affect any organ system. Thus, a fundamental understanding of the disease is required to tailor the differential diagnosis and evaluation. • A 50-fold increased risk of coronary artery disease (CAD) and up to a 30-fold increased risk of venous thromboembolism in patients with SLE prompt chest pain evaluations in the emergency department (ED), even in young women. • An elevated C-reactive protein level is more closely linked to infection in SLE patients and is not reflective of SLE disease activity. • An isolated elevated partial thromboplastin time (PTT) in a patient with SLE prompts consideration for antiphospholipid (aPL) antibody carrier state and, if there is a history of thrombosis, antiphospholipid syndrome (APS). • Steroids are the mainstay for management of the majority of conditions that are associated with increased SLE disease activity, including musculoskeletal, cutaneous, renal, pleural, and pericardial disease.

• APS is common in patients with SLE and carries with it a risk of venous (typically deep venous thrombosis or pulmonary embolism) and arterial (most commonly stroke) thrombosis. • Consultation with a rheumatologist may be helpful in diagnostic, management, and disposition decisions for patients with SLE.

Vasculitides

• Vasculitis syndromes should be considered in the presence of systemic symptoms, such as fever, malaise, and weight loss plus pulmonary, renal, or cutaneous manifestations. • Massive hemoptysis and acute renal failure can occur in Wegener’s granulomatosis, Goodpasture’s disease, microscopic polyangiitis, and Churg-Strauss syndrome. Tracheal stenosis may be present in Wegener’s granulomatosis, further complicating airway management. • Many patients with established vasculitis are receiving high-dose or combination immune suppressive therapy, making them vulnerable to opportunistic infections and overwhelming sepsis.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. Panopalis P, et al: Frequent use of the emergency department among persons with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 62:401–408, 2010. 2. Pons-Estel G, Alarcón G, Scofield L, et al: Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum 39:257–268, 2010. 3. Ulas S, Ulger Z, Balkan S, et al: Cardiac tamponade as a first manifestation of possible systemic lupus erythematosus in a 3-year-old female child. Minerva Pediatr 62: 319–321, 2010. 4. Petri M, Orbai A, Alarcon GS, et al: Derivation and validation of systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686, 2012. 5. Sivalingam S, Saligram P, Natanasabapathy S, et al: Covert cryptococcal meningitis in a patient with systemic lupus erythematous. J Emerg Med 42:e101–e104, 2012.

6. Mohseni MM, Rogers ER: Cardiac tamponade as the initial manifestation of systemic lupus erythematosus. J Emerg Med 42(6):692–694, 2012. 7. Chng H, Tan B, Teh C, et al: Major gastrointestinal manifestations in lupus patients in Asia: lupus enteritis, intestinal pseudo-obstruction, and protein-losing gastroenteropathy. Lupus 19:1404–1413, 2010. 8. Ebert E, Hagspiel K: Gastrointestinal and hepatic manifestations of systemic lupus erythematosus. J Clin Gastroenterol 45:436–441, 2011. 9. Kuhn A, Ochsendorf F, Bonsmann G: Treatment of cutaneous lupus erythematosus. Lupus 19:1125–1136, 2010. 10. Firooz N, et al: High-sensitivity C-reactive protein and erythrocyte sedimentation rate in systemic lupus erythematosus. Lupus 20:588–597, 2011. 11. Belliveau MJ, Ten Hove MW: Giant cell arteritis. CMAJ 183(5):581, 2011.

CHAPTER 108: QUESTIONS & ANSWERS 108.1. Which of the following statements is true regarding tinea capitis? A. It is markedly contagious. B. It is not transmitted by household pets. C. Prednisone is contraindicated for the treatment. D. Topical treatment is effective. E. Treatment generally lasts 2 to 4 weeks. Answer: A. Tinea capitis is the dermatophytosis that is markedly contagious. Systemic treatment for 4 to 6 weeks is the minimum. It may be transmitted by pets. When a kerion develops, prednisone (along with the antifungal) should be used to decrease inflammation and scarring. 108.2. A 16-year-old male presents with complaints of a chronic recurrent pruritic rash. It has primarily presented in joint flexor areas and first began at approximately 2 years old. His only other past history is asthma and hay fever. Physical examination reveals bilateral antecubital and popliteal papulovesicular lichenification and hyperpigmentation. It is intensely pruritic. Which of the following statements is true? A. Adult-onset disease is common. B. Corticosteroids are contraindicated. C. Increased immunoglobulin E (IgE) levels are expected. D. More frequent exacerbations are expected in the summer. E. Skin changes are confined to the flexor areas of involvement. Answer: C. This patient meets almost all criteria for atopic dermatitis. Onset after 5 years old should raise the question of an alternative diagnosis. The mechanism is believed to be eosinophil, mast cell, and lymphocyte activation by T cell production of interleukin-4. Elevated IgE levels are expected. Diffuse skin dryness is another prominent finding. Exacerbations may be triggered by increased body heat or stress, but they are more common in winter. Corticosteroids are the treatment mainstay. 108.3. A 29-year-old inmate presents with recurrent skin abscesses. Previous cultures have documented methicillin-resistant Staphylococcus aureus (MRSA) as the causative agent. It is resistant to clindamycin and sulfonamides. Which of the following antibiotics should be used for this case? A. Cephalexin B. Ciprofloxacin C. Erythromycin D. Linezolid E. Rifamycin

Answer: D. MRSA is typically resistant to cephalosporins, macrolides, and fluoquinolones. Rifamycin is effective but should not be used as the sole agent due to rapid development of resistance. 108.4. A 23-year-old male presents with nonpurulent cellulitis of his left leg. There is no obvious abscess. He has no other medical problems. Which of the following should be the antibiotic of choice? A. Amoxicillin-clavulanate B. Ciprofloxacin C. Clindamycin D. Doxycycline E. Trimethoprim-sulfamethoxazole Answer: C. Nonpurulent cellulitis is typically caused by staphylococcus or group A streptococcus. Group A streptococcus is typically resistant to bactrim and tetracycline/doxycycline. The potential for methicillin-resistant Staphylococcus aureus (MRSA) would obviate the use of amoxicillin and clavulanate potassium (Augmentin) or ciprofloxacin. 108.5. What is the parenteral treatment of choice for severe invasive S. aureus infection? A. Bactrim B. Clindamycin C. Rifamycin D. Vancomycin E. Vancomycin and another antistaphylococcal agent Answer: E. The combination is likely more effective due to enhanced bactericidal potential. Clindamycin and rifamycin are not indicated as parenteral monotherapy. 108.6. Which of the following statements is true regarding gonococcal dermatitis? A. It affects primarily men. B. It occurs in 1% or 2% of patients with gonorrhea. C. Gonococci can usually be cultured from the lesions. D. The lesions have a predilection for the knees and elbows. E. The skin lesions are not tender. Answer: B. Women are affected primarily. The lesions have a predilection for distal joint skin. They begin as red or hemorrhagic papules that evolve into pustules or vesicles with a red base. They are tender and may be confused with meningococcemia. They may later have a gray necrotic or hemorrhagic center. Skin cultures are usually negative.

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108.7. Which of the following statements is true regarding drug eruptions? A. A given drug produces a consistent eruption in the same patient. B. A late-appearing drug reaction would suggest thiazide use. C. Drug reactions tend to appear within 24 hours of drug initiation. D. The most common cause of drug reactions are nonsteroidal antiinflammatory drugs (NSAIDs) and sulfa-based drugs. E. The most common eruptions are urticaria and rashes.

Answer: E. The most common drug eruptions are urticaria and morbilliform rashes. Drug eruptions tend to occur within a week of drug initiation with the exception of semisynthetic penicillins, which tend to occur later. Penicillin is the most common cause of drug reactions, and patients with eczema, atopy, or asthma are at increased risk. A given drug may give widely diverse presentations in different patients or in the same patient on different occasions.

C H A P T E R 109 

Allergy, Hypersensitivity, and Anaphylaxis Aaron N. Barksdale  |  Robert L. Muelleman

ALLERGY Principles Background and Terminology The human immune system is an assemblage of cellular and humoral components working together in a highly complex, coordinated, and elegant fashion to achieve the primary goal of protecting the human host (self) from harmful offenders (nonself). Exposure to offenders activates the various immune mechanisms to bring about immune responses aimed at neutralizing the dangerous nonself while preserving self. The immune system, however, can overreact to otherwise harmless nonself agents, producing inappropriate responses that are harmful to the host, thereby giving rise to allergy or allergic diseases. These hypersensitivity reactions are manifested in clinical symptoms ranging from mildly inconvenient to fatal. For practical purposes, the term allergy is used in this chapter to refer to mast cell–mediated hypersensitivity reactions. For most allergic diseases to occur, predisposed individuals need to be exposed to allergens through a process called sensitization. Substances that elicit an allergic reaction are referred to as allergens, and those that elicit an antibody response (activated by B- and T-cell receptors) are called antigens. On this allergic continuum, there are several important allergic syndromes frequently encountered in the emergency department (ED). Urticaria is a common allergic reaction to foods, drugs, or physical stimuli and is clinically characterized by an erythematous, raised, and pruritic rash. Angioedema is another important syndrome, mediated by either an allergic (histaminergic) mechanism in response to exposure to foods, drugs, physical stimuli, or a nonallergic (non-histaminergic) mechanism (eg, hereditary angioedema [HAE], or angiotensin-converting enzyme [ACE] inhibitor). Angioedema is characterized by edema of the subcutaneous or submucosal tissues, which can cause airway compromise if the tongue or larynx is involved.1 At the other extreme of this allergic continuum is anaphylaxis, a life-threatening systemic allergic reaction characterized by acute onset and multiorgan involvement. Mechanistically, anaphylaxis is a type I hypersensitivity reaction (allergic), mediated by immunoglobulin E (IgE). In its most common form, anaphylaxis is precipitated by exposure to allergens in previously sensitized individuals (immunologic).2 Previously, the term anaphylactoid reaction referred to a syndrome clinically similar to anaphylaxis that is not mediated by IgE (non-immunologic). Its clinical presentation and treatment are identical to that of anaphylaxis. Non-IgE (non-immunologic) reactions appear to result from direct degranulation of mast cells (and basophils) and may follow a single, first-time exposure to certain inciting agents. The current World Allergy Organization (WAO) guidelines use the term anaphylaxis to refer to both IgE- and non–IgE-mediated reactions, obviating the need for the term anaphylactoid reaction.2 1418

Pathophysiology Because allergy is intimately related to immunology, a brief review is included in this chapter. Immunologic responses to antigens in humans are coordinated by two systems: the ancient innate immune system, which humans inherited from invertebrates; and the recently evolved adaptive immune system, which is present in humans and vertebrates (Fig. 109.1). The innate immune system is considered the first line of defense, characterized by its nonspecific but rapid responses to offending agents or microbes. Its effector components include resident cells (epithelial cells, mast cells, macrophages, dendritic cells, antimicrobial proteins), infiltrative cells (natural killer cells, neutrophils, monocytes, dendritic cells), and various proteins (antimicrobial peptides, complements, cytokines, pathogenic pattern recognition receptor [PRR] system).3 The innate system responds to danger signals rapidly and nonspecifically, whereas the adaptive immune system takes time for antigen-specific cells (B and T cells) to amplify through a process known as clonal expansion, to mount a specific immune response. The T and B lymphocytes are capable of recognizing a myriad of antigens through a vast library of antibodies and receptors (up to 1015). This diversity is accomplished by somatic rearrangement of fewer than 400 genes. Development of the Immune System and Mechanism of Immune-Mediated Injury.  The adaptive and innate immune systems originate from the common pluripotential hematopoietic stem cells, which are derived from the yolk sac and later reside in the bone marrow. These stem cells differentiate and develop into the lymphoid precursor cells and megakaryocyte (CFU-GEMM) stem cells. The lymphoid precursor cells differentiate into bursa-equivalent lymphocytes (B cells), thymus-derived lymphocytes (T cells), and natural killer cells. The CFU-GEMM cells develop into mast cells, basophils, and others (see Fig. 109.1). When the host encounters a foreign antigen, the cellular components of the adaptive immune system interact with the cellular and protein components of the innate immune system to mount a concerted defense aimed at neutralization of the antigen. T-Cell Development.  Lymphoid precursor cells migrate from the bone marrow into the thymus, where they continue their ontogeny. Under regulation by cytokines and cell-to-cell interactions, these precursors undergo gene rearrangement and positive and negative selection. In the process, T cells acquire the T-cell antigen receptors and various surface markers. Two types of T cells mature and come out of the thymus: CD4+, also called T helper cells (60% to 70%), and CD8−, also called suppressor T cells (30% to 40%).3 Depending on the type of cytokine produced, T helper cells differentiate into type 1 helper (TH1) cells and type 2 helper (TH2) cells, with opposing activities. TH1 cells inhibit IgE production and IgE isotype switching, whereas TH2 cells stimulate IgE production and IgE isotype switching. The balance of these stimulatory and inhibitory activities of the TH1 and TH2 cells is believed to determine an individual’s propensity to develop

CHAPTER 109  Allergy, Hypersensitivity, and Anaphylaxis

Lymphoid precursor

T cell

Pluripotent stem cell

B cell

CFU-GEMM

Mast cell

CD8+ T cells

CD4+ T cells

Antibodies

Basophil

Eosinophil

Natural killer T cells

Dendritic cell

Erythrocytes

Platelet Neutrophil Adaptive immune system (delayed response)

Epithelial cells Macrophage Pattern recognition receptor (PRR) Innate immune system (rapid response)

Fig. 109.1.  Developmental pathways of the immune and hematopoietic systems. CFU-GEMM, Colonyforming unit for granulocyte, erythroid, myeloid, and megakaryocyte.

allergic disease or atopy and may help explain the increased prevalence of allergy in urbanized and Western societies in the past three decades.3 Early in utero and soon after birth, naïve T lymphocytes in the infant’s immune system are dominated by the allergy-prone TH2 cells and their associated cytokines (interleukins 4, 5, and 13). These cytokines are important inducers for production of IgE antibodies. Later, during infancy through early childhood and adolescence, the nonatopic infant’s immune system gradually shifts from this allergy-prone TH2 environment to an allergy-protective TH1 environment. The cytokines associated with this TH1 environment include interleukin-2 and interferon-γ. This shift is thought to be caused by the continual exposure of the young individual’s immune system to allergenic stimuli from the surrounding environment, mainly microbes. Features of Western lifestyles (such as, changes in infant diets, widespread use of antibiotics, smaller family size, and cleaner child care) are believed to reduce this stimulatory antigenic exposure in an individual’s early years, leading to an environment in which the immune system is dominated by a persistent allergy-prone TH2 system (the hygiene hypothesis). This imbalance between the two immune systems is thought to be what ultimately leads to atopy and an allergy-prone population. B-Cell Development and Immunoglobulins.  B-cell ontogeny is divided into antigen-independent and antigen-dependent stages. During the antigen-independent stage, B cells mature in primary lymphoid organs (bone marrow and fetal liver), where they undergo gene rearrangement and acquire various surface markers. Later during the antigen-dependent stage in the secondary lymphoid organs (lymph nodes and spleen), B cells differentiate into memory B cells and plasma cells and are ready to secrete immunoglobulins. Throughout B-cell ontogeny, B-cell maturation, isotype switching, and immunoglobulin production are driven by activated T cells, cytokines, and interaction with antigen and bone marrow stromal cells.3

Immunoglobulins are protein molecules composed of two identical polypeptide heavy chains and two identical polypeptide light chains, covalently linked by disulfide bonds (Fig. 109.2). The heavy (H) chains have one variable domain (VH) and three or four constant domains (CH). The light (L) chains have one variable domain (VL) and one constant domain (CL). The variable domains of the heavy and light chains together form a pair of identical antigen-binding sites and with the adjacent constant heavy domain pair make up the Fab (antibody-binding fragment) region of the immunoglobulin molecule. The remaining constant domains of the heavy chains together form the Fc (crystallizable fragment) region of the immunoglobulin molecule. The Fc binds to the surface receptors of effector cells, such as mast cells, B cells, or macrophages. There are five isotypes or classes of immunoglobulins (IgG, IgA, IgM, IgD, and IgE); isotype IgG has four subclasses (IgG1, IgG2, IgG3, and IgG4), and IgA has two subclasses (IgA1 and IgA2). The body usually produces IgM antibodies when it first encounters an antigen. Repeated antigenic exposure, however, may cause the constant region of the IgM to switch to another class (IgA, IgG, or IgE), a process known as isotype switching. Isotype IgE and IgG4 are the most important antibodies in the pathogenesis of allergic disease and anaphylaxis.3 Mast cells, basophils, and their mediators are the central effectors in allergy and anaphylaxis. Exposure of a genetically predisposed individual to an allergen leads to the synthesis and release of allergen-specific IgE by plasma cells into the circulation. Fixation of this allergen-specific IgE to surface receptors on mast cells completes the process known as sensitization. These IgE-bearing mast cells usually reside in the mucosal surfaces, submucosal tissue (around venules), and cutaneous surfaces, where they are capable of becoming activated on reexposure to a specific allergen. Cross-linking of the mast cell receptors by a specific multivalent allergen sets off a cascade of conformational and biochemical

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VL

VH

VL

NH2

CL CL

VH

CH1

CH1

CH2

CH2

CH3

CH3

Fab

Fc

Allergen COOH Immunoglobulin molecule Ig is composed of a pair of heavy chains and a pair of light chains with variable (V) and constant (C) domains.

IgE

Mast cell

Preformed mediators (histamine) Lipid mediators (leukotrienes, PAF, prostaglandins, thromboxane) Cytokines

Fig. 109.2.  Activation of mast cells with degranulation of mast cell mediators by antigen cross-linking of adjacent immunoglobulin E (IgE) on the cell surface. PAF, Platelet-activating factor.

events, causing the degranulation of preformed mediators, subsequent generation and release of arachidonic acid metabolites, elaboration of cytokines and chemokines, and activation of the cellular components by the innate and adaptive systems. These series of events ultimately lead to the clinical syndromes of allergy and anaphylaxis (see Fig. 109.2).

Classification of Reactions The term allergy is commonly used to describe clinical illnesses produced by excessive immune responses by a normal immune system to otherwise innocuous allergens. In this chapter, we adapt the classic Coombs and Gell classification to categorize these hypersensitivity reactions (Box 109.1). Type I reactions (immediate hypersensitivity) are IgE mediated and account for most allergic and anaphylactic reactions observed in humans. Exposure to sensitizing allergens causes mediators from mast cells and basophils to be released through both IgEdependent and IgE-independent (direct mast cell degranulation) mechanisms. Rhinitis caused by ragweed pollen and anaphylaxis caused by foods are examples of the IgE-dependent mechanism. Type II reactions (cytotoxic) denote antibody-mediated cytotoxic reactions. Complement-fixing IgG (or IgM) engages cellbound antigen, activating the classic complement pathway and leading to the fixation of membrane attack complexes on the cell surface and subsequent cell lysis. In the process, anaphylatoxins C3a and C5a cause mast cell mediators to be released, producing the same clinical syndrome seen in allergic anaphylaxis. Type III reactions (immune complex) are IgG or IgM complex mediated. Circulating soluble antigen-antibody immune complexes migrate from the circulation to be deposited in the perivas-

cular interstitial space, thereby activating the complement system. Anaphylactic reactions to blood transfusions and blood component therapy, including serotherapy (immunoglobulin administration), are examples of the overlap of type II and type III reactivity. They have therefore been classified as complementmediated or immune complex–mediated anaphylaxis. Type IV reactions (delayed hypersensitivity) are T-cell mediated and have no documented relationship to the pathogenesis of anaphylaxis.

ANAPHYLAXIS Principles Epidemiology and Risk Factors The exact incidence of anaphylaxis is not known, but recent evidence suggests that it is increasing and that currently there are approximately 1500 fatal cases in the United States per year.4,5 In the last decade, experts in the field have developed specific consensus criteria to allow a more objective approach to diagnosing anaphylaxis. Recent literature suggests that over 50% of those patients presenting to EDs were misdiagnosed, and up to 80% did not receive appropriate first line treatment.6 Pregnant women, infants, teenagers, and elders have been shown to have an increased incidence of anaphylaxis.7 Other risk factors include atopy (genetic predisposition to develop allergic disease), emotional stress, seasonal occurrence in summer to fall months, higher socioeconomic status, residing in northern locations (potentially correlating with vitamin D levels), and the presence of acute infection. Severe anaphylaxis has been associated

CHAPTER 109  Allergy, Hypersensitivity, and Anaphylaxis

BOX 109.1 

BOX 109.2 

Gell and Coombs Classification of Immune Reactions

Risk Factors for Anaphylaxis and Increased Anaphylaxis Severity and Mortality

TYPE I: IMMEDIATE HYPERSENSITIVITY

RISK FACTORS FOR HAVING ANAPHYLAXIS

Binding of multivalent antigens to IgE on the surface of mast cells and basophils leads to degranulation of mediators. In previously sensitized individuals, the reaction develops quickly (minutes). This type of hypersensitivity reaction is seen in allergic diseases (eg, hay fever, allergic asthma, urticaria, angioedema, and anaphylaxis). Nonimmunologic (anaphylactoid) reaction refers to the direct release of preformed mediators of mast cells independent of IgE.

TYPE II: CYTOTOXIC ANTIBODY REACTION

Antibody (IgM, IgG) binding of membrane-bound antigens leads to cytotoxicity and cell lysis of cells through the complement or mononuclear cell system (macrophages, neutrophils, and eosinophils). This type of reaction is seen in transfusion reaction and Rh incompatibility.

TYPE III: IMMUNE COMPLEX–MEDIATED REACTION

Binding of antibody (IgM, IgG) to antigens forms soluble immune complexes, which are deposited on vessel walls, causing a local inflammatory reaction (Arthus reaction) leading to inflammation and tissue injury. This type of reaction is seen in systemic lupus erythematosus and serum sickness (after antithymocyte globulin administration).

TYPE IV: CELL-MEDIATED DELAYED HYPERSENSITIVITY

Sensitized lymphocytes (TH1 cells) recognize the antigen, recruit additional lymphocytes and mononuclear cells to the site, and start the inflammatory reaction. No antibodies are involved. This type of reaction is seen in contact dermatitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. IgE, Immunoglobulin E; IgG, immunoglobulin G; IgM, immunoglobulin M; TH1, type 1 helper.

with poorly controlled asthma, history of mastocytosis, heavy physical exertion, exposure to a trigger during the concomitant use of certain medications (ACE inhibitors, beta-blockers, and nonsteroidal antiinflammatory drugs [NSAIDs]), and the history of a previous anaphylactic reaction (Box 109.2).8-10 In general, the more rapid an anaphylaxis reaction occurs after an exposure, the more likely it is to be severe and potentially fatal. The dose, frequency, duration, and route of administration of a drug can also affect the tendency to develop an anaphylactic reaction (eg, the parenteral route is more likely to lead to an anaphylactic reaction than the oral route). One interesting aspect of drug-related anaphylaxis is the constancy of administration. An anaphylactic reaction may not occur in an otherwise susceptible patient as long as a drug is administered at regular intervals. The same patient, however, may experience an anaphylactic reaction if the drug is resumed after an interruption of therapy. ACE inhibitors can cause an accumulation of kinins and bradykinin and thus can exacerbate the angioedema component of anaphylaxis. Beta-blockers may oppose the actions of adrenergic agents used in anaphylaxis treatment. A recent study evaluating anaphylaxis in the ED demonstrated that the current use of any antihypertensive medication was associated with multi-organ involvement, more severe reaction, and increased incidence of hospitalization.7

Common Triggers for Anaphylaxis Virtually any agent that is capable of activating mast cells or basophils can potentially precipitate an anaphylactic reaction. However,

Age and sex Pregnant women, infants, teenagers, elderly Route of administration Parenteral > oral Higher social economic status Time of the year Summer and fall (the outdoor seasons) History of atopy Emotional stress Acute infection Physical exertion History of mastocytosis

RISK FACTORS FOR INCREASED ANAPHYLAXIS SEVERITY AND MORTALITY

Extremes of age Very young (under-recognition) Elderly Comorbid conditions Cardiovascular disease (heart failure, ischemic heart disease, hypertension) Pulmonary disease (asthma, obstructive airway disease) Others Concurrent use of anti-hypertensive agents, specifically betablockers and angiotensin-converting enzyme (ACE) inhibitors Concurrent use of cognition-impairing drugs (eg, alcohol, recreational drugs, sedatives, tranquilizers) Recent anaphylaxis episode Modified from Simons ER, et al: World Allergy Organization anaphylaxis guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol 162:193-204, 2013; Muraro A, et al: Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy 69:1026–1045, 2014; Ben-Shoshan M, Clarke AE: Anaphylaxis: past, present and future. Allergy 66:1–14, 2011.

in up to 60% of adults and 10% of children, an inciting agent cannot be identified, and these reactions are classified as idiopathic anaphylaxis.11 When a trigger can be determined, foods, insect stings, and medications are the most common causes. Box 109.3 lists many of the common agents by their proposed immunologic mechanism.4,8 Foods.  Foods are the major identifiable causative agents, accounting for approximately one-third of the cases of anaphylaxis. The most commonly identified foods are tree nuts, peanuts, fish, shellfish, soy, cow’s milk, and egg. The majority of the severe and fatal reactions appear to be associated with peanut and tree nut exposure, especially if the patient has a history of asthma.8 The majority of these reactions occur after ingestion but may occur after inhalation of food particles or even after skin contact with vomit containing the instigating agent.7 For a person with a known allergy, it may be difficult to avoid allergic reactions, because the allergen’s identity may be obscured during processing of the product (eg, consuming wine contaminated with Hymenoptera venom). Insect Stings.  Insect stings are the second most common cause of anaphylactic reactions, with the majority of them associated with hymenoptera venoms (wasps, bees, ants, and saw flies) and fire ant stings. These reactions typically require a sensitizing exposure, but there have been numerous reports of anaphylactic

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BOX 109.3 

BOX 109.4 

Etiologic Agents Causing Anaphylaxis by Immunologic Mechanisms

A Standard Treatment Protocol for Patients With a History of RadiocontrastInduced Anaphylaxis

IMMUNOLOGIC MECHANISMS (IGE-DEPENDENT)

Foods: Egg, peanut, tree nut, milk, fruits, shellfish, soybean, sesame Medications: Antibiotics, NSAIDs, chemotherapeutic agents, immunomodulators Insect stings: Hymenoptera venoms, fire ant stings Natural rubber latex Hormones: Insulin, methylprednisolone, parathormone, estradiol, progesterone, corticotropin Local anesthetics: Mostly ester family (procaine, tetracaine, benzocaine) RCM Occupational allergens: Enzymes, animal protein, plant protein Aeroallergens: Pollen, dust, spores, per dander

IMMUNOLOGIC MECHANISMS (IGE INDEPENDENT) RCM NSAIDs Dextrans Biologic agents: Monoclonal antibodies, immunomodulators

NONIMMUNOLOGIC MECHANISMS (DIRECT MAST CELL ACTIVATIONS) Physical factors: Exercise, cold, heat, sunlight Ethanol Medications: Some opioids

IDIOPATHIC (NO APPARENT TRIGGER) IgE, Immunoglobulin E; NSAID, nonsteroidal antiinflammatory drug; RCM, radiocontrast media. Modified from Simons ER, et al: World Allergy Organization Guideline for the assessment and management of anaphylaxis. J Allergy Clin Immunol 127(3):593 e1–e23, 2011.

reactions following first known stings or bites. Children tend to experience a more systemic cutaneous reaction, whereas adults are more likely to suffer hemodynamic collapse. Individuals displaying a large local reaction in the area of the sting or bite are less likely to suffer from a systemic reation.2,8 Drugs.  Antibiotics, chemotherapeutic agents, NSAIDs, and immunomodulators are the most common reported triggers, and drugs as a class represent the third most frequent cause of anaphylactic reactions.4 Penicillin is the most common drug-induced cause of anaphylaxis. Although patients often report a history of penicillin allergy, this may not stand up to close scrutiny. Studies have shown that up to 90% of individuals with a reported history of penicillin allergy can safely use penicillin. These individuals are usually mislabeled as penicillin allergic or lose their allergy after years of avoidance. Parenterally administered penicillin is responsible for the majority of these anaphylactic reactions.2,12 Cephalosporins share the β-lactam ring structure and side chains of the penicillins, but allergic cross-reactivity appears to be low, somewhere between 1% to 8% of patients. Patients who have experienced urticaria or anaphylactic reactions after taking penicillin are more likely to have an adverse reaction to cephalosporins, but even in this setting, the risk of an anaphylactic reaction is very low. In patients with a history of penicillin allergy, a cephalosporin is considered safe if they have had a negative penicillin skin test. If penicillin skin testing is positive, they could undergo a graded challenge or rapid desensitization process.12 Aspirin and other NSAIDs are believed to cause anaphylaxis through interruption of arachidonic acid metabolism, a non-IgE

Prednisone 50 mg by mouth given 13 hours, 7 hours, and 1 hour before the procedure Diphenhydramine 50 mg PO given 1 hour before the procedure Consider ephedrine 25 mg by mouth given 1 hour before the procedure Consider an H2 antagonist, such as ranitidine 150 mg by mouth given 3 hours before the procedure

(non-immunologic) mediated process. The incidence of anaphylaxis to aspirin and NSAIDs varies widely, and these reactions appear to be drug specific and without cross-reactivity to other NSAIDs. Aspirin exacerbated respiratory distress (AERD) and NSAID-induced respiratory distress syndromes are unique in individuals with a history asthma or allergic rhinitis and are not considered anaphylactic reactions.12 Although corticosteroids are often used in the management of allergic syndromes and anaphylaxis, there have been reported anaphylactic reactions to these drugs. They appear to be rare, and the majority of them have been associated with the parenteral administration of methylprednisolone and hydrocortisone. When steroids are required in the management of other conditions, skin testing may demonstrate the specific agent responsible for the hypersensitivity, and allow for the substitution of a different class.12 Natural Rubber Latex.  Natural rubber latex (NRL) allergy is the result of sensitivity to the proteins or chemicals contained in the latex products. This sensitivity reaction can be delayed (type IV) contact dermatitis or an immediate hypersensitivity (type I) reaction (see Box 109.1). In addition to rubber gloves, NRL can be found in an array of other hospital supplies, including endotracheal tubes, blood pressure cuffs, stethoscope tubing, airway masks, tourniquets, and catheters. NRL is also found in balloons, condoms, pacifiers, sports equipment, and toys. In recent years, most health care settings have incorporated the use of non-NRL gloves and products, making anaphylactic reactions from latex an uncommon event.2,4 Radiocontrast Media.  Radiocontrast media (RCM) represents an important class of agents that can cause an anaphylactic reaction. Approximately 10 million radiologic studies using RCM are performed in the United States annually. Anaphylactic reactions to RCM are largely idiosyncratic, occur within minutes of infusion, and are independent of the dose. The pathophysiologic mechanism of anaphylactic reactions to RCM is unknown, but it is believed to be non-immunologic (non-IgE). Risk factors for an anaphylactic reaction include a previous adverse reaction to RCM, a history of atopy or allergic disease, asthma, and certain medications. A history of an allergy to fish or shellfish is not a contraindication to the use of the currently used RCM, nor does it increase the risk of an adverse reaction to RCM. Clinically, the risk for severe adverse reaction with ionic and nonionic contrast materials is less than 1%. The death rate from RCM reactions is estimated at 1 to 3 per 100,000 administrations of contrast material. Protocols have been developed to minimize risks of a serious allergic reaction in patients who have had a previous adverse reaction to RCM but who still require additional radiographic studies with contrast agents (Box 109.4).

CHAPTER 109  Allergy, Hypersensitivity, and Anaphylaxis

Exercise Induced Anaphylaxis.  In certain settings, exercise has been recognized as an inciting event for an anaphylactic-like reaction. The mechanism is unclear, but the release of mediators from mast cells and basophils has been implicated. Patients with exercise-induced anaphylaxis are generally dedicated athletes who may have a personal or family history of atopy. In some individuals, anaphylaxis only occurs if specific co-triggers or cofactors are present during or prior to initiating exercise and typically do not cause symptoms without physical exertion. These may include certain foods, medications, or increased pollen levels in the area. Provocative foods, if identified, should be avoided. Patients should discontinue the exercise at the onset of rash or pruritus. When exercise is continued beyond this point, clinical deterioration is likely in susceptible individuals. Prophylactic treatment with an antihistamine may be helpful.2,13 Idiopathic Anaphylaxis.  As previously mentioned, 30% to 60% of adults and up to 10% of children had no identifiable trigger for their anaphylactic reaction. The diagnosis of idiopathic anaphylaxis is often made after extensive evaluation by an allergist. In an attempt to prevent recurrent episodes, these patients are often treated with daily prophylactic medications, such as antihistamines and sometimes corticosteroids. Some women diagnosed with idiopathic anaphylaxis may actually represent “progesterone” anaphylaxis. Women suffering from this disorder experience recurrent episodes of anaphylaxis that are temporally related to their menstrual cycle.11

Mediators of Anaphylaxis The numerous mediators released by mast cells and basophils exert overlapping physiologic effects on target organs and tissues, making it difficult to ascribe specific clinical manifestations to any one mediator. Histamine is the most important mediator and an essential contributor to immediate hypersensitivity and inflammation. Its infusion has been shown to produce the majority of the clinical features seen during an anaphylactic reaction (Table 109.1). There are three classes of histamine receptors: H1, H2, and H3. H1 receptor stimulation produces bronchial, intestinal, and uterine smooth muscle contraction. It also leads to increased vascular permeability, nasal mucus production, and eosinophil and neutrophil chemokinesis and chemotaxis. H2 receptor stimulation increases the heart rate, force of ventricular contraction, gastric acid secretion, airway mucus production, and vascular permeability, while also causing bronchodilation and inhibition of basophil histamine release. H3 receptors are found in neurons in the central nervous system and peripheral tissues, and they control the synthesis and release of histamine.14

In addition to histamine, there are several lipid metabolites produced through the prostanoid and leukotriene pathways that contribute to the adverse physiologic effects induced by histamine. Prostaglandin D2 (PGD2) is the main arachidonic acid metabolite released by activated mast cells. PGD2 and thromboxanes are synthesized from arachidonic acid through the cyclooxygenase pathway (through both COX-1 and COX-2). PGD2 induces hypotension, inhibition of platelet aggregation, and is approximately 30 times more potent than histamine in causing bronchoconstriction. The leukotrienes LTB4, LTC4, LTD4, and LTE4 are synthesized from arachidonic acid through the lipoxygenase pathway. They are involved in cholinergic-independent bronchospasm, increased vascular permeability, and increased mucous gland production.14 Platelet-activating factor (PAF) is a phospholipid and a potent compound that triggers human platelet aggregation. Its other actions include neutrophil activation and chemotaxis, along with ileal and parenchymal lung smooth muscle contraction. The clinical effects of PAF include decreased myocardial contractile force, coronary vasoconstriction, pulmonary edema, and prolonged increase in total pulmonary resistance with a decrease in dynamic compliance.14,15 Recent data has highlighted the important roles that nitric oxide and sphingosine 1-phosphate play in anaphylaxis. Sphingosine 1-phosphate can trigger calcium influx, stimulating synthesis of cytokines and mast cell degranulation. Nitric oxide is synthesized in vascular endothelium and its action can be increased by histamine, leukotriene, tumor necrosis factor alpha (TNF-α), and PAF. It is a potent vasodilator that contributes to the hypotension sometimes seen in anaphylaxis.14

Clinical Features Anaphylactic reactions vary in duration and severity, but they are typically rapid in onset and may result in death. They often present as a combination of clinical characteristics, commonly affecting an array of organ systems including the skin (80% to 90% of episodes), respiratory tract (70% of episodes), gastrointestinal tract (30% to 45% of episodes), cardiovascular (10% to 45%), and the central nervous system (10% to 15% of episodes).5,8 Clinical presentations depend on the degree of an individual’s hypersensitivity; the quantity, route, and rate of antigen exposure; the pattern of mediator release; and the target organ sensitivity and responsiveness. Symptoms of anaphylaxis usually occur minutes after an exposure, although some reactions may develop hours after encountering the triggering agent.2 The National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) and WAO have adopted

TABLE 109.1 

Mediators in Anaphylaxis and Their Physiologic Actions and Clinical Manifestations MEDIATORS

PHYSIOLOGIC ACTIVITY

CLINICAL MANIFESTATION

Histamine, leukotrienes, thromboxane, prostaglandins, platelet-activating factor, nitric oxide

Vascular permeability, vasodilation, smooth muscle spasm, mucous gland secretion, nociceptor stimulation, myocardial depression

Generalized urticaria and angioedema, pruritus, wheezing, bronchoconstriction, rhinorrhea and bronchorrhea, coryza, conjunctivitis, syncope, tachycardia, hypotension, shock, abdominal pain, nausea, vomiting, diarrhea

Tryptase, carboxypeptidase, chymase, cathepsin G

Activation of complement system, chemoattraction, activation and degranulation of mast cells

Anaphylaxis response is amplified by recruitment and activation of the complement system and further degranulation of mast cell mediators

TNF-α, cytokines, chemokines, eosinophil chemotactic factors

Induction of anti–platelet-activating factor production, control migration of eosinophils and other inflammatory cells

May be responsible for the intensity, protracted symptoms, and multiphasic reaction of the anaphylaxis attack

TNF-α, Tumor necrosis factor alpha.

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BOX 109.5 

BOX 109.6 

Clinical Criteria for Diagnosis of Anaphylaxis

Differential Diagnosis of Anaphylaxis

Anaphylaxis is highly likely when any one of the following three criteria is fulfilled: 1. Sudden onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, itching or flushing, swollen lips-tongue-uvula) and at least one of the following: a. Respiratory compromise (eg, shortness of breath, wheeze, cough stridor, hypoxemia) b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence) 2. Two or more of the following occurring rapidly (minutes to several hours) after exposure to a likely allergen or other trigger for that patient: a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) b. Sudden respiratory compromise (eg, shortness of breath, wheeze, cough, stridor, hypoxemia) c. Sudden reduced BP or symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence) d. Sudden gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): a. Infants and children: Low systolic BP (age specific) or greater than 30% decrease in systolic BP* b. Adults: Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

Acute generalized urticaria Asthma exacerbation Myocardial infarction Pulmonary embolus Syncope Adverse cutaneous drug reaction Anxiety/panic attacks

*Low systolic blood pressure for children is defined as 50

Serum ketones

Present

Absent

Laboratory studies should include serum glucose, electrolyte, and blood gas levels. Although serum ketoacid levels are frequently measured, they are not necessary to diagnose DKA and make be elevated in non-DKA states (eg, starvation ketosis from inadequate utilization of glucose stores) or dehydration. If determination of the pH is the sole concern, venous blood gas samples correlate well with arterial pH. An arterial blood gas sample should be tested if there is concern for the adequacy of respiratory compensation or concern for a mixed acid-base disorder (eg, concomitant metabolic alkalosis from vomiting). Winter’s formula (expected Paco2 = [1.5 × serum HCO3−] + [8 ± 2]) can be applied to determine if there is appropriate respiratory compensation or the presence of multiple acid-base disorders. The glucose level is usually elevated above 350 mg/dL; however, euglycemic DKA (blood glucose level ≤ 300 mg/dL) has been reported in up to 18% of patients. Blood gas measurement usually reveals a low pH, with the aforementioned rare exception of a concomitant alkalemia, which may result in a pseudonormalization of the pH. Metabolic acidosis with an anion gap is primarily the result of elevated plasma levels of acetoacetate and β-hydroxybutyrate, although lactate, FFAs, phosphates, volume depletion, and several medications can also contribute. Rarely, a well-hydrated patient with DKA may have a pure hyperchloremic acidosis with no anion gap if they have been aggressively rehydrated with normal saline. Again, although rare, there have been case reports of a normal anion gap in a patient with DKA. This occurred if the vomiting was sufficient to cause a concomitant metabolic alkalosis to such a degree that the pH and bicarbonate level appear to be in the normal range because the combined derangements result in false normal-appearing laboratory values.9 If an immediate potassium level is not available through blood gas analysis, an electrocardiogram can reveal signs of hyperkalemia or hypokalemia. Initial serum potassium levels are typically normal or high in DKA due to intracellular potassium shifting out of cells in exchange for elevated serum hydrogen ions. However, as potassium is lost in the urine, the total body potassium usually declines by several hundred milliequivalents. This, in combination with the insulin doses administered in DKA, can result in life-threatening hypokalemia. A basic metabolic panel should be obtained to evaluate renal function, acid-base status, and glucose and electrolyte levels. Because magnesium and potassium deficits are common in DKA, we recommend determining these levels as well. Urinalysis, in addition to the presence of ketones, may also help confirm a urinary tract infection as a precipitant of DKA. Use of blood or urine cultures should be determined by the clinical picture. The serum sodium level is often misleading in DKA; it is often low in the presence of significant dehydration because it is strongly affected by hyperglycemia, hypertriglyceridemia, saltpoor fluid intake, increased GI and renal losses, and insensible loss. When hyperglycemia is marked, water flows from the cells

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into the vessels to decrease the osmolar gradient, thereby creating dilutional hyponatremia. Elevated lipid levels cause a pseudohyponatremia by decreasing the fraction of serum that is water. Newer autoanalyzers remove triglycerides before assay, thus eliminating this artifact. The true value of the sodium level may be approximated by adding 1.6 mEq/L to the sodium value on the laboratory report for every 100-mg/dL glucose above the norm. Thus, if the laboratory reports a serum sodium level of 130 mEq/L and blood glucose level of 700 mEq/L, the total serum sodium level is more accurately assessed to be 139.6 mEq/L. Acidosis and the hyperosmolarity induced by hyperglycemia shift potassium, magnesium, and phosphorus from the intracellular to extracellular space. Dehydration results in hemoconcentration, which contributes to normal or high initial serum potassium, magnesium, and phosphorus readings in DKA, even with profound total body deficits. The effect of acidosis on the serum potassium level determination can be corrected by subtracting 0.6 mEq/L from the laboratory potassium level for every 0.1-decrease in pH noted in the arterial blood gas analysis. Thus, if the potassium level is reported as 5 mEq/L and the pH is 6.94, the corrected potassium value would be only 2 mEq/L, representing severe hypokalemia. As insulin is administered and the hydrogen ion concentration decreases, the patient needs considerable potassium replacement. Finally, hyperglycemia and the anion gap have significant effects on the plasma potassium concentration, independent of acidosis. No conversion factor has been developed for the estimation of true magnesium levels, although initial values may be high. All laboratory determinations must be interpreted with caution. Serum creatinine level determinations made by autoanalyzer may be falsely elevated. Leukocytosis more closely reflects the degree of ketosis than the presence of infection. Only the elevation of band neutrophils has been demonstrated to indicate the presence of infection, with a sensitivity of 100% and specificity of 80% from a single small retrospective study. Historically, the diagnosis of pancreatitis in a patient with DKA could be confounded by the elevation of amylase levels in DKA. Given the strength of the current literature demonstrating greater specificity of lipase for the diagnosis of pancreatitis, lipase should be the blood test of choice if pancreatitis is a concern.

BOX 118.1 

Summary of Treatment of Diabetic Ketoacidosis Identify diabetic ketoacidosis—serum glucose, electrolyte, and ketone levels and arterial blood gas analysis; also obtain complete blood count with differential, urinalysis, chest radiograph, and electrocardiogram, if indicated. Supplement insulin. • Insulin replacement—0.1 unit/kg/hr regular insulin IV • Change IV solution to D5W/0.45% normal saline (NS) when glucose concentration is ≤300 mg/dL. Rehydrate. • 1–2 L NS IV during 1–3 hours • Children—20 mL/kg NS during first hour Correct electrolyte abnormalities. • Sodium—correct with administration of NS or 0.45% NS. • Potassium—ensure adequate renal function. Add 20–40 mEq KCl to each liter (when serum potassium < 5.5 mEq/L) of fluid until ketoacidosis is corrected and potassium is normalized. (Do not give insulin until potassium 3.3 mEq/L or greater.) • Phosphorus—usually unnecessary to replenish. • Magnesium—correct with 1–2 g MgSO4. Serum magnesium levels may not correlate with body stores. Correct acidosis. • Administer IV fluids and insulin. Search for and correct underlying precipitant. Monitor progress and keep meticulous flow sheets. • Vital signs • Fluid intake and urine output • Serum glucose, K+, Cl−, HCO3−, CO2, pH • Amount of insulin administered Admit to hospital or intensive care unit. • Consider outpatient therapy in children with reliable caregiver and • Initial pH ≥ 7.35 • Initial HCO3− ≥ 20 mEq/L • Can tolerate oral fluids • Resolution of symptoms after treatment in emergency department • No underlying precipitant requiring hospitalization

Differential Diagnoses Alcoholics, especially those who have recently abstained from drinking, with Kussmaul’s breathing, fruity odor to the breath, and acidemic arterial blood gas values may have alcoholic ketoacidosis. These patients may be euglycemic or hypoglycemic, and a large part of their acidosis is often caused by the unmeasured β-hydroxybutyric acid. Alcoholic ketoacidosis accounts for approximately 20% of all cases of ketoacidosis. Ketoacidosis can also develop with fasting, commonly in the third trimester of pregnancy and in nursing mothers who do not eat. The differential diagnosis for DKA is broad and includes any entity that may cause elevated anion gap acidosis, ketosis, or both. The presence of DKA should not exclude investigation for other causes of anion gap metabolic acidosis, such as sepsis, poisoning, or lactic acidosis, because physiologic stress from one of these other causes can precipitate DKA.

Management The comatose patient, especially if vomiting, requires intubation. Once the patient is intubated, maintenance of hyperventilation prevents worsening acidosis. The patient in hypovolemic shock requires aggressive fluid resuscitation with isotonic crystalloids rather than vasopressors; consider other possible causes of shock (eg, sepsis or myocardial dysfunction secondary to myocardial

infarction). Bedside ultrasonography may be of benefit in excluding other causes of hypotension and evaluating the volume status of an individual patient. Although it is not routinely used in the ED setting, in cases in which the volume status is difficult to ascertain because of complex underlying physiologic derangements (eg, congestive heart failure, renal failure), the rapid ultrasound for shock and hypotension examination (see Chapter e5) or invasive hemodynamic monitoring may be required to guide fluid therapy. When hyperglycemia, ketosis, and acidosis have been established, fluid, electrolyte, and insulin therapy should be initiated (Box 118.1).

Insulin DKA cannot be reversed without insulin, and insulin therapy should be initiated as soon as the diagnosis is certain. There have been no randomized trials comparing insulin with placebo or other therapies for DKA. However, the mortality from DKA was 90% in historical controls before the development of exogenous insulin and 50% after insulin was introduced; with appropriate supportive therapy, it has reached the current levels of 5% to 7%.9 Although the dosing of insulin infusions has been established, the value of an IV bolus before the infusion remains controversial

CHAPTER 118  Diabetes Mellitus and Disorders of Glucose Homeostasis

and is no longer routinely recommended. More recently, in selected patients with mild DKA, the subcutaneous or intramuscular administration of insulin has been proven safe and as effective as IV administration of insulin. In selected cases with good outpatient follow-up, treatment of DKA with intermittent bolus dosing of regular insulin by the subcutaneous or intramuscular route without admission has also been shown to be safe. Such a strategy requires a well-hydrated, mildly acidemic patient who is well versed in his or her disease management and has excellent outpatient follow-up. Poor perfusion may hamper the absorption of intramuscular or subcutaneous insulin, resulting in erratic absorption, making IV infusion the route of choice in sicker DKA patients.1,9 The current initial therapy of choice, as recommended by the ADA, is regular insulin infused at 0.1 units/ kg/hr up to 5 to 10 units/hr, mixed with IV fluids. Children with DKA pose additional management challenges. Whereas the general principles of fluid and electrolyte repletion in concert with insulin therapy remain the same, controversy exists about the dosing and administration of fluids and insulin because of concerns related to the risk of inducing cerebral edema in children with DKA. Despite frequently voiced concerns about this complication, it remains rare, with an overall incidence of 1% in pediatric DKA patients. Virtually all current evidence supporting the contention that the use of higher doses of insulin and aggressive fluid resuscitation contribute to the development of cerebral edema has come from retrospective reviews and small case studies. The best available evidence shows associations only with lower Paco2 and higher blood urea nitrogen levels, indicating that severity of disease, rather than treatment interventions, plays the most significant role. DKA-related cerebral edema is more likely in children younger than 5 years, and good prospective data are needed to help guide recommendations. Currently, there is an ongoing clinical trial to assess risk and outcomes prospectively (clinicaltrials.gov). Given currently available data, patients should be carefully monitored and receive mannitol at the earliest suspicion of cerebral edema. Because the half-life of regular insulin is 3 to 10 minutes, insulin should be administered IV by constant infusion rather than by repeated bolus. When the blood glucose concentration has dropped to 250 to 300 mg/dL, adding dextrose to the IV fluids reduces the risk of iatrogenic hypoglycemia and cerebral edema caused by rapid shifts in osmolarity. In patients with euglycemic DKA, dextrose should be added to the IV fluids at the start of insulin therapy. Insulin resistance occurs rarely in diabetic patients and requires an increase in dosage for a satisfactory response to be obtained. Resistance may be caused by obesity or accelerated insulin degradation.

Intravenous Fluids The severely dehydrated adult patient is likely to have a fluid deficit of 3 to 5 L. No uniformly accepted formula exists for the administration of fluid in this disorder. If the patient is in hypovolemic shock, isotonic crystalloid solution should be given as rapidly as possible in the adult or in boluses of 20 mL/kg in the child until a systolic pressure of 80 mm Hg is obtained. There is no consensus regarding the ideal fluid to use; concerns have been raised with the use of large amounts of normal saline exacerbating metabolic acidosis. At least one small trial has studied the use of a balanced crystalloid solution (Plasmalyte) in DKA, with reports of more rapid restoration of normal physiologic parameters. In the adult who has marked dehydration in the absence of clinical shock or heart failure, 1 L of fluid may be administered in the first hour. In general, 2 L of fluid resuscitation during the first 1 to 3 hours is followed by a slower infusion of a hypotonic solution, such as 0.45% normal saline solution. DKA patients

without extreme volume depletion may be successfully treated with a lower volume of IV fluid replacement. An initial bolus of 20 mL/kg during the first hour is the usual fluid resuscitation therapy for a child. The fluid rate should be adjusted according to age, cardiac status, and degree of dehydration to achieve a urine output of 1 to 2 mL/kg/hr. Fluid resuscitation alone may help lower hyperglycemia. Because a low level of circulating insulin may be present, increased perfusion may transport insulin to previously unreached receptor sites. In addition, a large volume of glucose may be cleared by the kidneys in response to improved renal perfusion. The mean plasma glucose concentration has been noted to drop by 18% after the administration of saline solution without insulin.1 Acidosis also decreases after fluid infusion because increased perfusion improves tissue oxygenation and diminishes the formation of lactate. Increased renal perfusion promotes renal hydrogen ion loss, and the improved action of insulin in the better hydrated patient inhibits ketogenesis. Although fluid administration decreases the serum glucose concentration and improves acidosis, the underlying deficiency in DKA still requires administration of insulin for correction of ketoacidosis.

Potassium Potassium replacement is invariably needed in DKA. The initial potassium level is often normal or high, despite a large deficit because of severe acidosis. Potassium levels often plummet with correction of acidosis and administration of insulin. Once potassium levels reach 5.0 to 5.5 mEq/L and the patient is making urine, potassium should be administered while monitoring renal function.1,2 In patients with relatively lower serum potassium concentration at presentation (3.3 to 5.0 mEq/L), hypokalemia may become life-threatening when insulin therapy is administered; therefore, IV administration of potassium in concentrations of 20 to 40 mEq/L should be given with insulin administration. In patients with hypokalemia (700 mg/dL) or those who are severely hypoperfused, in whom intramuscular or subcutaneous insulin absorption may be erratic. If an IV insulin infusion is used, it should be done at an infusion rate similar to that for DKA (0.1 unit/kg/hr).

Laboratory findings usually reveal a blood glucose level above 600 mg/dL and serum osmolarity above 350 mOsm/L. The blood urea nitrogen concentration is invariably elevated. Although patients with HHS do not have a ketoacidosis caused by diabetes, they may have a metabolic acidosis secondary to some combination of lactic acidosis, starvation ketosis, and retention of inorganic acids attributable to renal hypoperfusion. The patient with HHS typically has a more profound electrolyte imbalance than the patient with DKA. Levels of potassium, magnesium, and phosphorus may seem initially high, even in the presence of a marked total deficit. In the absence of acidemia, however, the discrepancy between the initial electrolyte reading and body stores is less than that of DKA. Initial serum sodium readings are inaccurate because of hyperglycemia.

Differential Diagnoses The differential diagnosis of HHS is identical to that of DKA. In addition, diabetic patients receiving chlorpropamide are subject to water intoxication with dilutional hyponatremia, which may be manifested as coma without acidosis that is clinically indistinguishable from HHS. The patient with HHS who has a sharply depressed sensorium may not be initially distinguishable from the patient with profound hypoglycemia. When the blood glucose concentration cannot be rapidly checked, the immediate administration of one ampule of D50W minimally worsens HHS and may be lifesaving for patients with hypoglycemia.

Management The fluid, electrolyte, and insulin regimens for the initial resuscitation in HHS are subject to the same controversies as the therapies for DKA (see Box 118.1). There have been varying recommendations about which IV fluids to administer, generally based on calculations of water deficits. There have been no well-done randomized trials comparing isotonic versus hypotonic fluid resuscitation; use of an isotonic crystalloid is a reasonable choice in the volume-depleted patient. Cerebral edema has been noted in isolated case reports in adults, especially with glucose levels above 700 mg/dL. An association between IV fluid resuscitation and cerebral edema has not been shown in the literature; previous reports of this association may have been due to the confounder that it is seen in sicker patients who often receive more aggressive fluid resuscitation.

Intravenous Fluids For patients in hypovolemic shock, initial IV fluid infusion is given as rapidly as possible. Glucose should be added to resuscitation fluids when the blood glucose level drops below 300 mg/dL. Because many HHS patients are older adults with coexisting disease, such as congestive heart failure and renal failure, noninvasive or invasive forms of hemodynamic monitoring may be required to guide fluid administration when there is clinical suspicion of pulmonary edema or volume overload.

Electrolytes Measurement of serum electrolyte levels should be used to guide replacement in the HHS patient. In particular, because the degree

Insulin

Other Considerations A vigorous search for the underlying precipitant of HHS should be pursued. Response to therapy should be followed in the manner described for patients in DKA. Phenytoin (Dilantin) is contraindicated for the seizures of HHS because it is often ineffective and may impair endogenous insulin release.1,9 Admitted patients should be given low-dose subcutaneous heparin to lessen the risk of thrombosis, which is increased by the volume depletion, hyperviscosity, hypotension, and inactivity associated with HHS.

Acute Complications Reasons for high morbidity and mortality rates are not always clear, but many patients with HHS are older adults who have underlying cardiac and renal disease. Pediatric HHS differs from adult HHS in that children have a much higher incidence of fatal cerebral edema. Other causes of morbidity and mortality are similar to those described for DKA. The mortality rate of treated HHS patients has been 40% to 70% in the past but now ranges from 8% to 25%.1,9

Disposition In general, patients with HHS require hospitalization for IV hydration, glucose control, and evaluation of precipitating and complicating conditions.

LATE COMPLICATIONS OF DIABETES Late complications of diabetes cause significant morbidity and mortality and develop approximately 15 to 20 years after the onset of overt hyperglycemia. The Diabetes Control and Complications Trial has shown that tight glycemic control significantly reduces the risk of microvascular disease, such as microalbuminuria (the earliest sign of nephropathy), neuropathy, and retinopathy, but at the expense of greatly increasing the risk of recurrent hypoglycemia.1

Vascular Complications Diabetes is associated with an increased risk for atherosclerosis and thromboembolic complications, which are a major cause of morbidity and premature death. The cause of accelerated atherosclerosis is unknown, although it is probably related to oxidated low-density lipoprotein and increased platelet activity. Atherosclerotic lesions are widespread, causing symptoms in many organ systems. Coronary artery disease and stroke are common. Diabetic patients have an increased incidence of so-called silent myocardial infarction, complicated myocardial infarctions, and congestive

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heart failure. Peripheral vascular disease is noted clinically by claudication, nonhealing ulcers, gangrene, and impotence. In addition, standard treadmill stress tests have a decreased sensitivity in the detection of coronary artery disease in diabetics. For this reason, exercise or pharmacologic stress echocardiography or a nuclear medicine imaging study should be considered when a provocative test is needed to evaluate the diabetic patient for acute coronary syndrome.1

Diabetic Nephropathy Renal disease is a leading cause of death and disability in diabetic patients. Approximately 50% of cases of end-stage renal disease in the United States is caused by diabetic nephropathy. The appearance of microalbuminuria correlates with the presence of coronary artery disease and retinopathy. Azotemia generally does not begin until 10 to 15 years after the diagnosis of diabetes. Progression of renal disease is accelerated by hypertension. Meticulous control of diabetes can reverse microalbuminuria and may slow the progression of nephropathy. Blood pressure should be aggressively managed; angiotensin-converting enzyme inhibitors are effective in controlling hypertension and lowering microalbuminuria. Chronic hemodialysis and renal transplantation are unfortunate endpoints for many diabetic patients with renal disease.

Retinopathy Diabetes is a leading cause of adult blindness in the United States. Approximately 11% to 18% of all diabetic patients have treatable diabetic retinopathy, ranging from mild to severe, and manifested in many forms. The severity of diabetic retinopathy is clearly related to the quality of glycemic control. Background retinopathy is found in most patients with prolonged diabetes and characterized by microaneurysms, small vessel obstruction, cotton wool spots, soft or hard exudates, and macular ischemia. Proliferative retinopathy defines an entity of new vessel formation and scarring, as well as associated vitreal hemorrhage and retinal detachment. The diabetic patient may present with complaints ranging from acute blurring of vision to sudden unilateral or even bilateral blindness. Less often, diabetic patients have more gradual vision loss caused by the common senile cataract (or snowflake cataract), which may disappear as the hyperglycemia is corrected. Diabetic patients with retinopathy should be referred to an ophthalmologist. Even in those with normal vision, ophthalmologic procedures may limit visual loss or prevent crises such as neovascular glaucoma.

Neuropathy Autonomic and peripheral neuropathies are well-known complications of diabetes. The prevalence of peripheral neuropathy ranges from 15% to 60%. The cause of the neuropathy is not clearly understood, but studies have suggested several factors in its development, including the effects of diabetic vascular disease on the vasa nervorum. Neurologic manifestations of diabetes may regress with improved glycemic control. Several distinct types of neuropathy have been recognized in diabetes.10 Peripheral symmetric neuropathy is a slowly progressive, primary sensory disorder manifested bilaterally with anesthesia, hyperesthesia, or pain. The pain is often severe and worse at night. It affects the upper and lower extremities, although the lower extremities and distalmost sections of the involved nerves are most often affected. There may be a motor deficiency as well. The pain may be very difficult to control; opioid analgesics have been used, but nonopioid medications such as gabapentin, pregabalin, and amitriptyline are preferred. Pregabalin is the newest of

these agents and seems to hold the most promise when used at higher dosages (up to 600 mg/day). Duloxetine at a dosage of 60 mg/day is also effective. Both pregabalin and duloxetine achieve significant pain control in at least 50% of patients. Gabapentin, 300 mg tid, has some efficacy, achieving significant pain relief in about one-third of patients; amitriptyline 25 mg daily demonstrates similar results. A reasonable approach for the emergency clinician is the initiation of duloxetine or pregabalin, because these have shown the best efficacy in pain control, with the understanding that it may take several days for a peak effect to be reached.11 Gabapentin in particular has a narrow toxic to therapeutic margin; for many patients, full therapeutic benefits do not occur until the dosage is 600 mg tid or more, at which point sedation frequently becomes severe enough to make the treatment intolerable. Mononeuropathy, or mononeuropathy multiplex, affects motor and sensory nerves, generally one nerve at a time. The onset is rapid, with wasting and tenderness of the involved muscles. There may be a sudden onset of wrist drop, foot drop, or paralysis of cranial nerves III, IV, and VI. Diabetic truncal mononeuropathy occurs rapidly in a radicular distribution. In contrast to other mononeuropathies, it is primarily if not exclusively sensory. If it causes pain, it may mimic that of a myocardial infarction or acute abdominal inflammation. Like diabetic mononeuropathy, it may be most bothersome at night and generally resolves in a few months. Whereas diabetic mononeuropathy is often the first indication of diabetes, truncal mononeuropathy is more often found in known diabetic patients. Management is similar to other diabetic neuropathies, with the exception of CN III palsy, which is usually expectant management. Autonomic neuropathy occurs in many forms. Neuropathy of the GI tract, with resultant gastroparesis, is manifested by difficulty in swallowing, delayed gastric emptying, constipation, and/ or nocturnal diarrhea. Impotence and bladder dysfunction or paralysis may occur. Orthostatic hypotension, syncope, and even cardiac arrest have resulted from autonomic neuropathy. Diabetic diarrhea responds to diphenoxylate and atropine, loperamide, or clonidine. Orthostatic hypotension is treated by sleeping with the head of the bed elevated, avoidance of sudden standing or sitting, and use of full-length elastic stockings. For gastroparesis, we recommend metoclopramide for its prokinetic and antiemetic properties. Many patients with gastroparesis present with abdominal pain; opioids are not recommended for this group due to the risk of worsening dysmotility of the GI tract.

The Diabetic Foot Approximately 20% of hospitalizations in diabetic patients are related to foot problems.1 Sensory neuropathy, ischemia, and infection are the principal contributors to diabetic foot disease. Loss of sensation leads to pressure necrosis from poorly fitting footwear and small wounds going unnoticed. The most common cause of injury is pressure on plantar bone prominences. All neuropathic foot ulcers should be assessed for infection, devitalized tissue débrided, and radiographs obtained to evaluate for the presence of foreign bodies, soft tissue gas, or bone abnormalities.1 Not all ulcers are infected. Infection is suggested by local inflammation or crepitation. Conversely, some uninflamed ulcers are associated with underlying osteomyelitis. Most mild infections are caused by gram-positive cocci, such as Staphylococcus aureus or streptococci, and may be treated with oral antibiotics with activity against gram-positive organisms, such as trimethoprimsulfamethoxazole, 800/160 mg bid, a first-generation cephalosporin such as cephalexin, 500 mg qid, or clindamycin, 300 mg qid. A strict non–weight-bearing regimen, meticulous wound care, and daily follow-up are also vitally important to wound healing.

CHAPTER 118  Diabetes Mellitus and Disorders of Glucose Homeostasis

TABLE 118.3 

TABLE 118.4 

Common Serious Infections in Diabetics and Their Antimicrobial Therapy

Common Oral Diabetic Medications MEDICATION

FUNCTION

DETAILS

INFECTIOUS CONDITION

ANTIMICROBIAL THERAPY Mild—consider trimethoprimsulfamethoxazole, 800/160 bid or clindamycin 300 mg q6h Moderate to severe—clindamycin, 600 mg IV q6h ± piperacillintazobactam (Zosyn), 3.375 g IV q6h and vancomycin,n 15 mg/kg IV q12h

Biguanides (metformin)

Decrease hepatic glycogenolysis

500–1000 mg bid

Diabetic foot infection

Sulfonylureas (glipizide, glimepiride)

Stimulate pancreatic insulin release

2.5–5 mg daily

Thiazolidinediones (pioglitazone, rosiglitazone)

Insulin sensitizers, decrease hepatic gluconeogenesis

Increased risk of adverse cardiac events

Meglitinides (repaglinide, nateglinide)

Stimulate postprandial insulin release

Take with meals only

Malignant otitis externa

Oral—ciprofloxacin, 500 mg PO bid for 10–14 days IV—ceftazidime, 2 g IV q8h ± gentamicin, 2 mg/kg IV q8h

Mucormycosis

Amphotericin B, 1–1.5 mg/kg/day Posaconazole, 400 mg bid

Mucocutaneous candidiasis

Ketoconazole, 200 mg PO daily; may need several weeks of therapy

Nonclostridial gas gangrene (including Fournier’s)

Clindamycin, 600 mg q6h + thirdgeneration cephalosporin + vancomycin, 15 mg/kg q12h

This approach may not be possible when patients are deemed unreliable, do not have good home support, or do not have ready access to follow-up care. Deeper, limb-threatening infections—as evidenced by fullthickness ulceration, cellulitis more than 2 cm in diameter, with or without lymphangitis, bone or joint involvement, or systemic toxicity—are usually polymicrobial in origin and caused by aerobic gram-positive cocci, gram-negative bacilli, and anaerobes. These patients require hospitalization and, after culture, broadspectrum IV empirical antimicrobial therapy (Table 118.3), strict non–weight-bearing status, tight glycemic control, early surgical intervention for débridement, and meticulous wound care. Occult osteomyelitis should be considered in all cases of neuropathic ulceration.1 Hyperbaric oxygen has been shown to have some efficacy in the treatment of complicated infection, especially with anaerobic organisms. Up to one-third of patients eventually undergo amputation.

Infections Diabetic patients are more susceptible to complications of infections because of their inability to limit microbial invasion with effective polymorphonuclear leukocytes and lymphocytes. They have an increased incidence of extremity infections and pyelonephritis compared with the general population. In addition, they are particularly susceptible to certain other infections, such as tuberculosis, mucocutaneous candidiasis, intertrigo, mucormycosis, soft tissue infections, nonclostridial gas gangrene, osteomyelitis, and malignant Pseudomonas otitis externa (Table 118.4); glycemic control and generally hospitalization are recommended.

Cutaneous Manifestations Dermal hypersensitivity is manifested by pruritic erythematous indurations that occur at insulin injection sites. The declining prevalence of this condition has paralleled the improved purification of insulin. Similarly, insulin lipoatrophy seems to be a result of insulin impurities and is manifested as subcutaneous depres-

Dipeptidyl peptidase 4 Decrease insulin inhibitors (sitagliptin) degradation and gluconeogenesis α-Glucosidase inhibitors (acarbose, miglitol)

Once daily; can be found in multiple combination medications

Delay breakdown of Major side effect is carbohydrates in the diarrhea intestines

sions at injection sites. Although lipoatrophy is now more common than dermal hypersensitivity, its prevalence has also declined sharply because of improved insulin preparations. Insulin lipohypertrophy is manifested by raised areas of subcutaneous fat deposits at insulin injection sites. These lesions generally reflect the failure of the patient to rotate injection sites adequately. They resolve spontaneously over months if insulin injection is avoided in the affected areas and sites are properly rotated. Insulin pumps are often associated with localized skin problems, usually a reaction to the tape securing the tubing and needles. On occasion, sensitivity to the catheters is seen. Skin infections at the site of injection are the most common complication of insulin pumps. Changing the patient from unbuffered beef-pork insulin to buffered pure pork is the only intervention that seems to reduce the rate of infection. A few patients have been noted to have hard nodules at the injection site. The cause of these nodules is uncertain. Diabetic patients who use oral hypoglycemic agents may have rashes associated with these medications. After consumption of ethanol, approximately 38% of type 2 patients taking chlorpropamide exhibit a flush consisting of redness of the face and neck and a sense of warmness or burning. Patients may demonstrate urticaria in response to insulin and oral hypoglycemics. Skin Conditions.  Diabetic skin conditions include fungal infections, acanthosis nigricans, necrobiosis lipoidica diabeticorum, xanthoma diabeticorum, bullosis diabeticorum, and diabetic dermopathy. Acanthosis Nigricans.  This is characterized by a velvety, brown-black thickening of the keratin layer, most often in the flexor surfaces. It is the cutaneous marker for a group of endocrine disorders with insulin resistance. Necrobiosis Lipoidica Diabeticorum.  This begins as erythematous papular or nodular lesions, usually in the pretibial area but in other areas as well. The early lesions may contain telangiectasias. These lesions spread and frequently form a single pigmented area of atrophic skin, often with a yellow and sometimes ulcerated center and an erythematous margin. A history of previous trauma is sometimes found. Xanthoma Diabeticorum.  This is evidence of the hyperlipidemia associated with diabetes. It is similar to the xanthoma

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found in nondiabetic hyperlipidemic patients. Xanthomas have an erythematous base and a yellowish hue. Bullosis Diabeticorum.  This is a rare occurrence. Bullae are usually filled with a clear fluid and are most often found on the extremities, especially the feet. The fluid is occasionally slightly hemorrhagic. The bullae usually heal spontaneously, without scarring. Diabetic Dermopathy.  Also known as skin spots, this is the most common finding in diabetes. It arises as discrete, depressed, and brownish lesions generally less than 15 mm in diameter and found in the pretibial area. Impetigo or Intertrigo.  Resistant, aggressive impetigo or intertrigo suggests diabetes.

DIABETES IN PREGNANCY Before the discovery of insulin in 1922, diabetes in pregnancy was associated with a fetal death rate of 60% to 72% and maternal morbidity of approximately 30%.12 In 1977, a linear relationship between glycemic control and perinatal mortality was discovered. Strict metabolic control is now a goal in all diabetic pregnancies.13 Pregnant patients should be watched extremely closely and aggressively treated for impending or actual DKA. For a variety of reasons, pregnant women have a special predisposition to glucose intolerance and excess ketone production. Although uncommon, DKA may reduce fetal oxygen delivery and cause perinatal asphyxia. Intellectual deficits in the offspring have been associated with maternal ketonuria from any cause. Hypoglycemia is common in pregnancy, in part because of intensive insulin treatment to maintain euglycemia. The effects of hypoglycemia on the fetus are unclear. Severe ketoacidosis is associated with a 50% to 90% fetal mortality rate due to hypoperfusion of the placenta.13

HYPOGLYCEMIA Principles Hypoglycemia is a common problem in patients with type 1 diabetes, especially if tight glycemic control is practiced; it is the most dangerous acute complication of diabetes. The estimated incidence of hypoglycemia in diabetic patients is 9 to 120 episodes/100 patient-years. As significant efforts continue to keep fasting and postprandial glucose concentrations within the normal range, the incidence of hypoglycemia may increase. The most common cause of coma associated with diabetes is an excess of administered insulin with respect to glucose intake. Severe hypoglycemia is usually associated with blood glucose levels below 40 to 50 mg/dL and impaired cognitive function. Protection against hypoglycemia is normally provided by cessation of insulin release and mobilization of counterregulatory hormones, which increase hepatic glucose production and decrease glucose use. Diabetic patients using insulin are vulnerable to hypoglycemia because of insulin excess and failure of the counterregulatory system. Hypoglycemia has many causes, such as missing a meal (decreased intake), increased energy output (exercise), and increased insulin dosage. It can also occur in the absence of any precipitant. Oral hypoglycemic agents have also been implicated in causing hypoglycemia, both during the course of therapy and as an agent of overdose. Hypoglycemia without warning symptoms, or hypoglycemia unawareness, is a dangerous complication of type 1 diabetes and is probably caused by previous exposure to low blood glucose concentrations,14 because even a single hypoglycemic episode can reduce neurohumoral counterregulatory responses to subsequent

episodes. Other factors associated with recurrent hypoglycemic attacks include overaggressive or intensified insulin therapy, longer history of diabetes, autonomic neuropathy, and decreased epinephrine secretion or sensitivity. The Somogyi phenomenon is a common problem associated with iatrogenic hypoglycemia in the type 1 diabetic patient. The phenomenon is initiated by excessive insulin dosing, resulting in an unrecognized hypoglycemic episode that usually occurs in the early morning while the patient is sleeping. The counterregulatory hormone response produces rebound hyperglycemia, evident when the patient awakens. Often, the patient and physician interpret this hyperglycemia as an indication to increase the insulin dosage, which exacerbates the problem. Instead, the insulin dosage should be lowered or the timing changed.

Clinical Features Symptomatic hypoglycemia occurs in most adults below a blood glucose level of 40 to 50 mg/dL. The rate at which the glucose level decreases, however, and the patient’s age, gender, size, overall health, and previous hypoglycemic reactions contribute to symptom development. Signs and symptoms of hypoglycemia are caused by excessive secretion of epinephrine and CNS dysfunction; these include sweating, nervousness, tremor, tachycardia, hunger, and neurologic symptoms, ranging from bizarre behavior and confusion to seizures and coma. In patients with hypoglycemia unawareness, the prodrome to marked hypoglycemia may be minimal or absent, and these individuals may rapidly become unarousable. They may have a seizure or show focal neurologic signs, which resolve with glucose administration.

Differential Diagnoses Hypoglycemia in the nondiabetic patient may be classified as postprandial or fasting. The most common cause of postprandial hypoglycemia is alimentary hyperinsulinism, such as that seen in patients who have undergone gastrectomy, gastrojejunostomy, pyloroplasty, or vagotomy. Fasting hypoglycemia is caused when there is an imbalance between glucose production and use. The causes of inadequate glucose production include hormone deficiencies, enzyme defects, substrate deficiencies, severe liver disease, and drugs. Causes of overuse of glucose include the presence of an insulinoma, exogenous insulin, sulfonylureas, drugs, endotoxic shock, extrapancreatic tumors, and a variety of enzyme deficiencies.

Diagnostic Testing The cardinal laboratory test for hypoglycemia is determination of the blood glucose concentration. It should be performed, if possible, before therapy is begun. As noted, fingerstick readings are helpful in permitting rapid, reasonably accurate blood glucose level estimates before therapy. Laboratory testing should address any suggested cause of the hypoglycemia, such as ethanol or other drug ingestion. If factitious hypoglycemia is suggested, testing for insulin antibodies or low levels of C peptide may be helpful. A patient who is surreptitiously administering exogenous insulin will have normal to low levels of C peptide and markedly elevated insulin levels.

Management In alert patients with mild symptoms, oral consumption of sugar-containing foods or beverages is often adequate. In other patients, after blood is drawn for glucose determination, one to three ampules of D50W is administered IV while the patient’s airway, breathing, and circulation are assessed and maintained.

CHAPTER 118  Diabetes Mellitus and Disorders of Glucose Homeostasis

Augmentation of the blood glucose level by administration of an ampule of D50W may range from less than 40 mg/dL to more than 350 mg/dL. If alcohol abuse is suggested, thiamine is administered. In children younger than 8 years, providers should use D25W or D10W. D25W may be prepared by diluting D50W 1 : 1 with sterile water. The dose is 0.5 to 1 g/kg body weight or 2 to 4 mL/kg when using D25W. If IV access cannot be rapidly obtained, 1 to 2 mg of glucagon may be given intramuscularly or subcutaneously. The onset of action is 10 to 20 minutes, and a peak response occurs in 30 to 60 minutes. It may be repeated as needed. Glucagon may also be administered IV; 1 mg has an effect similar to that of one ampule of D50W. Glucagon is ineffective in causes of hypoglycemia in which glycogen is absent, notably alcohol-induced hypoglycemia. Families of type 1 diabetic patients are often taught to administer glucagon intramuscularly at home. Of the families so instructed, only 9% to 42% actually inject the glucagon when indicated. Intranasal glucagon has not been widely used. All patients with severe hypoglycemic reactions require aspiration and seizure precautions. Although the response to IV administration of glucose is generally rapid, older patients may require several days for complete recovery. Treatment of hypoglycemia secondary to oral hypoglycemic agents depends on the agent. Metformin and the thiazolidinediones rarely cause significant or prolonged hypoglycemia, whereas sulfonylureas, which are insulin secretagogues, do cause hypoglycemia. Sulfonylurea oral hypoglycemic agents pose special problems because the hypoglycemia they induce tends to be prolonged and severe. Patients with an overdose of sulfonylurea hypoglycemic agents should be observed for a period of 24 hours if hypoglycemia recurs in the ED after management of the initial episode. Patients at risk for hypoglycemia from oral sulfonylureas include patients with impaired renal function, pediatric patients, and patients who are naïve to hypoglycemic agents. Although symptoms may occur after an overdose, several case reports in patients (eg, with renal failure and pediatric patients) have described refractory hypoglycemia after ingestion of a single pill. One case series of pediatric patients presenting with sulfonylurea ingestion who were euglycemic initially demonstrated an average time to onset of 8 hours to the initial hypoglycemic episode.15 However,

in some patients, onset of symptoms was delayed for up to 18 hours. As a result, we recommend 24 hours of observation for patients with known or suspected ingestion of hypoglycemic agents. A patient with hypoglycemia from sulfonylureas, in addition to standard glucose replacement, frequently requires treatment with an agent to inhibit further insulin release, such as octreotide, a somatostatin analogue. Several case series have described the use of octreotide in adult and pediatric patients suffering from sulfonylurea-induced hypoglycemia, frequently reporting successful results, with a significant decrease in the number of episodes of recurrent hypoglycemia. A randomized clinical trial has concluded that patients receiving octreotide had a decreased glucose supplementation requirement.16 No single set protocol for use has been described; however, typical adult doses have ranged from 50 to 100 µg IV or subcutaneously every 12 hours, with pediatric dosages of 0.1 mcg/kg IV or subcutaneously. Although experience thus far with octreotide has been positive, it does not obviate the need for prolonged observation and serial glucose level measurements.

Disposition Type 1 diabetic patients with brief episodes of hypoglycemia uncomplicated by other disease may be discharged from the ED if a cause of the hypoglycemia can be identified and corrected by instruction or medication. All patients should be given a meal before discharge to ensure their ability to tolerate oral feedings and to begin to replenish glycogen stores in glycogen-deficient patients. Patients who are discharged should receive short-term follow-up for ongoing evaluation. Patients with hypoglycemia caused by long-acting sulfonylurea medications should be observed in the hospital if they have recurrent hypoglycemia after a period of observation in the ED. Other agents, such as metformin, do not typically produce hypoglycemia, although they may have other issues, such as lactic acidosis, that may require admission. The determination of inpatient versus outpatient evaluation of hypoglycemia in a nondiabetic patient should be based on the suggested cause and nature of the episode (ie, factors such as severity, persistence, and recurrence).

KEY CONCEPTS • The diagnosis of diabetes can be determined by one or more of four methods—random plasma glucose level above 200 mg/dL, fasting plasma glucose concentration above 126 mg/dL, 2-hour, 75-g postload OGTT > 200 mg/dL, or HbA1c value above 6.5%. • DKA is diagnosed by the presence of hyperglycemia, anion gap metabolic acidosis, and elevated ketoacid levels. • The essential treatment of DKA includes restoration of insulin, correction of dehydration, correction of potassium level, correction of acidosis, and treatment of the underlying cause. • Use of sodium bicarbonate to correct acidosis in DKA has not demonstrated any benefit and may be associated with worse outcomes. • A hyperglycemic hyperosmolar state is usually seen in older adults with multiple comorbid conditions and is distinguished from DKA by the absence of ketoacidosis. In addition to fluid resuscitation and correction of hyperglycemia, treatment should address the underlying

• •





cause of the state, which includes infection, myocardial infarction, and cerebrovascular accident. Diabetic peripheral neuropathy is common and has multiple treatment modalities, including gabapentin, pregabalin, and duloxetine. Diabetic foot ulcers and other diabetic soft tissue infections (eg, gas gangrene, Fournier’s gangrene) are frequently polymicrobial and require broad-spectrum antibiotic therapy covering gram-positives, gram-negatives, and anaerobes. Hypoglycemia may be associated with significant morbidity and mortality. When the diagnosis is suggested and, if possible, confirmed by laboratory evaluation, therapy should be initiated immediately. Hypoglycemia caused by sulfonylurea oral hypoglycemic agents may be prolonged. Patients should be observed for an extended period or hospitalized.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

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REFERENCES 1. American Diabetes Association: Standards of medical care in diabetes—2014. Diabetes Care 37:S14–S80, 2014. 2. Waugh N, Cummins E, Royle P, et al: Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation. Health Technol Assess 14:1–248, 2010. 3. Medical Letter: Dapagliflozin: a new SGLT2 inhibitor56 (1436) February 17, 2014: 13-14. 4. Cengiz E: Closer to ideal insulin action: ultra-fast acting insulins. Phytomedicine 21(2):123–130, 2014. 5. Blumer I, Edelman S: Biosimilar insulins are coming: the top 10 things you should know. Postgrad Med 126(3):1070110, 2014. 6. Medical Letter: An Inhaled Insulin 57(1283) March 2, 2015: 34-35. 7. Fonseca VA: New developments in diabetes management: medications of the 21st century. Clin Ther 36(4):477–484, 2014. 8. Russell SJ, El-Khatib FH, Sinha M, et al: Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med 371:313–325, 2014. 9. Maletkovic J, Drexler A: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am 42(4):677–695, 2013. 10. Bril V, England J, Franklin GM, et al; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation: Evidence-based guideline: treatment of

11. 12.

13. 14. 15. 16.

painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 76:1758– 1765, 2011. Bennett WL, Maruthur NM, Singh S, et al: Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Int Med 154(9):602–613, 2011. Kashyap SR, Bhatt DL, Schauer PR: Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical therapy and medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE). Diabetes Obs Metab 12(5):52–54, 2010. Castroino K, Jovanovic L: Pregnancy and diabetes management: Advances and controversies. Clin Chem 57:221–230, 2011. Halimi S: Acute consequences of hypoglycaemia in diabetic patients. Diabetes Metab 36:S54–S58, 2010. Lung DD, Olson KR: Hypoglycemia in pediatric sulfonylurea ingestion: An 8 year poison center retrospective study. Pediatrics 127:e1558–e1564, 2011. Fasano CJ, O’Malley G, Dominici P, et al: Comparison of octreotide and standard therapy versus standard therapy alone for the treatment of sulfonylurea-induced hypoglycemia. Ann Emerg Med 51:400–406, 2008.

CHAPTER 118: QUESTIONS & ANSWERS 118.1. Which of the following statements regarding patients with impaired glucose tolerance is true? A. Spontaneous reversion to normal glucose tolerance is rare. B. The condition is associated with fewer complications than diabetes mellitus. C. The rate of decompensation to diabetes mellitus is greater than 10%/year. D. There is a predisposition to ketosis. E. There is no increased risk of cardiovascular complications. Answer: B. Patients with impaired glucose tolerance have a glucose level between normal and diabetic. They are at increased risk of cardiovascular disease and development of diabetes (1%–5%/year), but it is not associated with the same degree of complications as with true diabetes. Many patients spontaneously develop normal glucose levels. 118.2. What percentage of adults with type 2 diabetes are obese? A. 20% B. 40% C. 60% D. 80% E. 100% Answer: D. Nonobese patients form a subgroup with a different disease, more similar to type 1 diabetes. Young people with maturity-onset diabetes often have an autosomal dominant inheritance, are nonobese, and have a relatively mild disease course. 118.3. A 56-year-old man with a 10-year history of type 2 diabetes and poor glucose control (HbA1c = 10.7%) complains of constant burning pain in both feet. Which agent would be most appropriate to start in this patient for initial management of his symptoms? A. Aspirin, 325 mg PO daily B. Carbamazepine, 200 mg tid C. Naproxen, 500 mg bid D. Oxycodone/acetaminophen, 5/325 mg qid E. Pregabalin, 600 mg daily Answer: E. Pregabalin in a dose of 600 mg daily gives pain relief in approximately 50% of patients with diabetic neuropathy. Duloxetine, 60 mg daily, achieves similar results. Gabapentin,

300 mg once a day up to tid, and amitriptyline, 25 mg daily, provide pain relief in approximately 33% of patients. 118.4. A 27-year-old juvenile-onset diabetic is brought by emergency medical services (EMS) for a hypoglycemic coma. Fingerstick glucose level is 30 mg/dL. The paramedics were not able to obtain intravenous (IV) access, and two immediate attempts at IV cannulation failed in the emergency department (ED). What should be the next step in the patient’s management? A. Albuterol, 2.5 mg nebulized B. Central venous catheter placement, then D50W IV C. Epinephrine, 1 mg IV D. Glucagon, 2 mg intramuscularly E. Peripheral IV catheterization via cutdown and then D50W Answer: D. Intravenous dextrose (25–75 g for adults, 0.5–1 g/kg for children) is preferable but, if unable to obtain IV access, administer glucagon, 1 or 2 mg intramuscularly (IM) or subcutaneously (SC; 0.025–0.1 mg/kg IM or SC in children). Onset of action is 10 to 20 minutes. It is ineffective in cases of glycogen absence, such as alcohol-induced hypoglycemia. 118.5. A 33-year-old juvenile-onset, insulin-dependent diabetic suddenly faints without prodrome or warning while walking through the ED. Relatives report that diabetes is his only past history. Which of the following findings is most likely? A. Autonomic neuropathy on later orthostatic testing B. Fingerstick glucose 27 mg/dL C. Hemoccult-positive stool D. Positive enzyme-linked immunosorbent assay (ELISA) D-dimer E. Supraventricular tachycardia on electrocardiogram (ECG) Answer: B. Hypoglycemia without warning, or hypoglycemia unawareness, is a complication of type 1 diabetes caused by previous hypoglycemic episodes. A single hypoglycemic episode may blunt neurohormonal counterregulatory responses to later hypoglycemic episodes. Risk factors are overaggressive insulin therapy, longer history of diabetes, and autonomic neuropathy, which usually causes orthostasis on first standing or after being upright in a static position. These patients may become abruptly unarousable without warning.

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118.6. A 47-year-old man presents with hypoglycemia. He is a known type 2 diabetic on glyburide. Fingerstick glucose is 27 mg/dL. Twenty minutes after two ampules (50 g) of dextrose, his glucose level is 29 mg/dL. Which of the following agents is indicated? A. Adenosine B. Epinephrine C. Glucagon D. Hydrocortisone E. Octreotide Answer: E. A patient with hypoglycemia from sulfonylureas, in addition to standard glucose replacement, frequently requires treatment with an agent to inhibit further insulin release, such as octreotide (a somatostatin analogue). Sulfonylureas are insulin secretagogues. 118.7. What is the most important determinant of mental status in a patient with diabetic ketoacidosis (DKA)? A. Acidemia B. Calcium level C. Glucose level D. Osmolarity E. Potassium level

Answer: E. The finding of alkalemia with ketoacidosis should prompt the consideration of alcoholic ketoacidosis, in which the acidosis is counterbalanced by alkalosis from severe nausea and vomiting. This may also be seen with DKA but is less likely. 118.10. What percentage of cases of DKA occur in patients whose diabetes was previously undiagnosed? A. 10% B. 25% C. 50% D. 75% E. 90% Answer: B. 25%. 118.11. A 28-year-old juvenile-onset diabetic presents in DKA. Laboratory assessment reveals a sodium level of 130 mEq/L and serum glucose level of 700 mg/dL. What is the approximate total serum sodium value? A. 125 mEq/L B. 130 mEq/L C. 135 mEq/L D. 139 mEq/L E. 144 mEq/L

Answer: D. The hyperosmolarity produced by dehydration and hyperglycemia is the most important determinant of mental status during an episode of DKA.

Answer: D. The true value of sodium may be approximated by adding 1.6 mEq/L to the reported sodium value for every 100-mg/dL glucose over the norm.

118.8. A 73-year-old male patient presents with a draining sore on the bottom of his foot. He is noted to have a 3- × 4-cm ulcerated, malodorous lesion on his plantar foot, with surrounding erythema. Which antimicrobial agent should be included as part of the management of this infection? A. Cefazolin, 1 g qid B. Ceftriaxone, 1 g every 24 hours C. Levofloxacin, 500 mg every 24 hours D. Metronidazole, 500 mg qid E. Piperacillin/tazobactam, 3.375 g qid

118.12. A 31-year-old insulin-dependent diabetic presents in DKA. His reported serum potassium level is 5 mEq/L, with a pH of 6.90. What is his corrected potassium level value? A. 2 mEq/L B. 2.5 mEq/L C. 3 mEq/L D. 3.5 mEq/L E. 4 mEq/L

Answer: E. Piperacillin/tazobactam and vancomycin are considered the first-line agents for management of complicated diabetic foot infections. 118.9. A 43-year-old patient is brought to the ED with altered mental status. Other past history is unavailable, there are no signs of trauma, and the physical examination is normal except for the patient’s mental status. Laboratory assessment reveals the following: Sodium = 132 mEq/L Potassium = 3.0 mEq/L Chloride = 82 mEq/L Bicarbonate = 36 mEq/L Creatinine = 1.4 mg/dL Blood urea nitrogen (BUN) = 26 mg/dL Urine ketones—trace positive Arterial blood gases (ABG) Po2 = 90 mm Hg, Pco2 = 30 mm Hg pH = 7.49 What additional finding is the most likely? A. Elevated glucose level B. Elevated iron level C. Elevated salicylate level D. Evidence of toluene ingestion E. History of alcohol abuse

Answer: A. The effect of acidosis on the serum potassium can be corrected by subtracting 0.6 mEq/L from the laboratory potassium value for every 0.1 decrease in pH noted on the ABG analysis. For this patient, assuming a normal pH of 7.40, 7.40 − 6.90 = 0.5 (five 0.1 pH increments) 5 × 0.6 = 3 mEq/L correction factor 118.13. Which of the following statements regarding the laboratory evaluation of DKA is true? A. Amylase levels maintain their sensitivity for detecting pancreatitis. B. Creatinine levels may be falsely elevated. C. Hypertriglyceridemia is unusual. D. Leukocytosis is often present in the absence of infection. E. True magnesium levels may be estimated by a conversion factor. Answer: B. Serum creatinine levels may be falsely elevated if measured by autoanalyzer. No conversion factor exists for estimating magnesium. Leukocytosis typically parallels the degree of ketosis. A bandemia, however, indicates the presence of infection, with a sensitivity of 100% and specificity of 80%. Elevated triglyceride levels are seen routinely. Elevated amylase levels (salivary) are routinely seen; however, lipase maintains its sensitivity for pancreatitis.

CHAPTER 118  Diabetes Mellitus and Disorders of Glucose Homeostasis

118.14. Alcoholic ketoacidosis accounts for what percentage of all cases of ketoacidosis? A. 10% B. 20% C. 30% D. 40% E. 50% Answer: B. Ketoacidosis may also develop with fasting in the third trimester of pregnancy and in nursing mothers who do not eat well. 118.15. A 26-year-old known diabetic presents with altered mental status. EMS reports a fingerstick glucose of 750 mg/dL. The patient vomited once en route. The physical examination is remarkable for a comatose patient with the following vital signs—respiratory rate, 30 breaths/min; heart rate, is 140 beats/min; blood pressure, 85/40 mm Hg. Which of the following should be the first intervention? A. Dopamine, 10 µg/kg/min B. Endotracheal intubation C. Isotonic fluid bolus, 20 mL/kg D. Regular insulin 0.1 units/kg IV E. Sodium bicarbonate IV Answer: B. The comatose DKA patient, especially if vomiting, requires intubation. Hyperventilation should be rapidly initiated to prevent worsening acidosis. Isotonic fluid resuscitation, insulin bolus and infusion, and meticulous attention to electrolyte management must follow. 118.16. What is the half-life of regular insulin when administered intravenously? A. 3–10 minutes B. 10–15 minutes C. 15–20 minutes D. 20–25 minutes E. 25–30 minutes Answer: A. With a half-life of only 3 to 10 minutes, regular insulin requires an infusion rather than intermittent bolus therapy for optimal effect. 118.17. A patient with severe DKA is treated with fluid resuscitation and an insulin infusion. Six hours later, the patient develops confusion, disorientation, and hypercarbia from altered respiratory muscle performance. A repeat serum glucose level is 193 mg/ dL. Which of the following treatments is most appropriate? A. Calcium replenishment B. Magnesium replenishment C. Phosphorus replenishment D. Potassium replenishment E. Sodium bicarbonate replenishment Answer: C. Phosphorus levels may fall dramatically after initiation of standard DKA therapy. Hypophosphatemia may cause a left shift in the hemoglobin desaturation curve, depressed

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myocardial and respiratory muscle function, hemolysis, thrombocytopenia, platelet dysfunction, confusion, and disorientation. Cerebral edema would be in the differential diagnosis because it also occurs in the 6- to 10-hour range after initiating therapy. 118.18. Which of the following is not associated with cerebral edema after DKA? A. Bicarbonate therapy B. Blood glucose level > 350 mg/dL C. Elevated BUN level D. Hypocarbia E. Onset 6 to 10 hours after initiation of therapy Answer: B. Clinically evident cerebral edema does not usually occur unless the blood glucose level is less than 250 mg/dL and insulin is being used. The other listed factors are associated with this syndrome. 118.19. Which of the following may be associated with or cause the hyperglycemic hyperosmolar state (HHS)? A. All of these B. Anion gap metabolic acidosis C. Chlorpropamide use D. Choreoathetosis and segmental myoclonus E. Confusion with depressed sensorium from hypoglycemia Answer: A. HHS may be associated with many drugs and illnesses. Symptoms range from lethargy to focal neurologic changes and seizure or coma. Initial differentiation from hypoglycemic coma may be difficult until serum glucose levels are checked. Metabolic acidosis is not uncommon and may yield an elevated anion gap—lactic acidosis, starvation, and retention of inorganic acids. HHS may occur in nondiabetics after burns or peritoneal hemodialysis. 118.20. A 69-year-old patient presents with new-onset seizures, serum glucose level of 850 mg/dL, and serum osmolarity of 340 mOsm/L. His past history is remarkable for chronic renal insufficiency resulting from hypertension. His only current medications are amlodipine and furosemide. Which of the following statements regarding the patient’s condition is true? A. Emergent dialysis is indicated. B. Furosemide may have precipitated this event. C. Heparin has no therapeutic role. D. Insulin is contraindicated in cases of renal insufficiency. C. Phenytoin is indicated. Answer: B. Regardless of the cause, the management of the hyperosmolar hyperglycemic state (HHS) centers on aggressive fluid management and low-dose insulin. Phenytoin is contraindicated in hyperosmolar hyperglycemic nonketotic coma (HHNC) because of its impairment of endogenous insulin release and ability to precipitate HHNC. Low-dose heparin may be indicated to lessen the risk of thrombosis. Furosemide is one of many drugs that may precipitate HHNC.

C H A P T E R 119 

Rhabdomyolysis Ram Parekh PRINCIPLES Background Rhabdomyolysis is a potentially life-threatening condition characterized by the breakdown of skeletal muscle and the release into the circulatory system of intracellular contents, including creatine kinase, aspartate transaminase, lactate dehydrogenase, aldolase, the heme pigment myoglobin, and electrolytes. The severity of illness ranges from asymptomatic elevations in serum muscle enzyme levels to life-threatening electrolyte imbalances and acute renal failure. A healthy 70-kg man has approximately 28 kg of muscle. Skeletal muscle is 80% water and 20% protein, accounting for about half of the total body protein stores, and is the largest organ in the human body.

Physiology Even at rest, muscle function requires a large amount of adenosine triphosphate (ATP). ATP generation by muscle accounts for 30% of the body’s oxygen consumption at rest and up to 85% at extremes of physical activity. Resting muscle uses fatty acids for ATP generation. With activity, muscle draws on stored ATP for the first 8 seconds of activity, using the phosphagen (creatine phosphate) stores for the next 10 to 15 seconds. Finally, muscle depends on anaerobic glycogen metabolism to lactate for enough ATP for an additional 30 to 40 seconds of activity. Aerobic ATP production provides the bulk of the energy needed for muscle activity, but it requires oxygen. Glucose, amino acids, and fatty acids are incorporated into the Krebs cycle to produce much larger quantities of ATP by energy-rich compounds, such as the reduced forms of nicotinamide adenine dinucleotide and flavin adenine dinucleotide. Myoglobin, like hemoglobin, binds and releases oxygen and delivers it to active skeletal muscle. Unlike hemoglobin, myoblobin’s ability to deliver oxygen is unaffected by pH, resulting in a relatively increased affinity for oxygen in comparison to hemoglobin and delivery of oxygen to cellular mitochondria at low partial pressures of oxygen. The integrity of muscle cells is dependent on healthy cell membranes, which rely on ATP for proper membrane ion pump function. The sarcolemma, a thin membrane that encloses striated muscle fibers, contains numerous pumps that regulate electrochemical gradients. Under normal physiologic conditions, the sodium-potassium–adenosine triphosphatase (Na+,K+-ATPase) pump, located in the sarcolemma, maintains intracellular sodium concentrations of 10 mEq/L and intracellular potassium concentrations of 150 to 160 mEq/L. It achieves this by actively transporting sodium from the interior of the cell to the exterior, thereby making the interior of the cell more negative by the efflux of net positive charge—three sodium ions pumped out per two potassium ions pumped in. This electrical gradient pulls sodium to the interior of the cell through a separate channel in exchange for calcium, effectively removing calcium from the cytoplasm. Low 1548

intracellular calcium levels are also maintained by an active calcium exchanger (Ca2+-ATPase pump) that promotes calcium entry into the sarcoplasmic reticulum and mitochondria. As their names indicate, these ATPase pumps depend on ATP as a source of energy. Under normal physiologic conditions, the concentration of free ionized calcium in the extracellular space is approximately 10,000 times greater than that in the intracellular space. The high concentration of free calcium in the extracellular pool compared with the intracellular compartment and the resulting large electrochemical force on Ca2+ are particularly convenient to its role as an intracellular regulator. Even minor changes in the permeability of the plasma membrane to calcium will produce significant fluctuations in the cytosolic concentration, with potentially unfavorable consequences for the integrity of the cell. Several transmembrane proteins exist to regulate calcium homeostasis. The plasma membrane transmembrane proteins are the energy-consuming Ca2+ channels, Na+-Ca2+ exchangers, and Ca2+-ATPase pumps. The last removes Ca2+ from the intracellular space by transporting Ca2+ out of the cytosol into the extracellular space, as well as into the sarcoplasmic reticulum. Plasma membrane Ca2+ channels bring Ca2+ into the cytosol when activated at the neuromuscular junction. Na+-Ca2+ exchangers are complicated in that the direction of ion movement depends on the chemical and electrical gradients of each ion within the cell, which vary according to the contractile state of the myocyte (Fig. 119.1).

Pathophysiology Although the causes of rhabdomyolysis are diverse, the pathogenesis appears to follow a final common pathway—increased cytoplasmic calcium concentration, leading to myocyte destruction, with the release of muscle components into the circulation. There are two primary mechanisms whereby calcium pathologically accumulates in the cell, direct cell membrane damage and ATP depletion. Membrane damage from trauma and genetic or biochemical factors results in a massive influx of extracellular calcium into the cytoplasm driven by electrical and chemical gradients. ATP depletion results in failure of cellular transport and increased permeability to sodium ions. Any event that increases cytosolic sodium concentrations, whether from increased membrane permeability and inward Na+ traffic or decreased ATP-dependent pump removal of intracellular Na+, results in increased Na+-Ca2+ ion exchanger function and increased cytosolic calcium concentrations. ATP depletion results in dysfunction of energy-dependent ion pumps, such as Na+,K+-ATPase and Ca2+-ATPase in the sarcolemma. Na+,K+-ATPase pump dysfunction leads to increased intracellular Na+, causing a temporary increase in Na+-Ca2+ exchanger function and resultant increase in intracellular Ca2+. The Na+-Ca2+ exchanger requires ATP, however, and continued activity of the Na+-Ca2+ exchanger further deprives the cell of ATP, leading to increased Ca2+-ATPase dysfunction and rising intracellular Ca2+ levels. The sarcoplasmic reticulum and mitochondria are also equipped with these same energy-dependent transmembrane calcium transport

CHAPTER 119  Rhabdomyolysis

1 Ca2

2 Ca2

K

Na

Ca2

3 Na

K

1  ATP-dependent Ca2 pump 2  Na-Ca2 exchanger (3:1) 3  Na, K-ATPase pump (3:2) Fig. 119.1.  Normal membrane ionic pump function of skeletal muscle cell. When the ATP supply is impaired, the intracellular sodium concentration increases, reversing the function of the Na+-Ca2+ exchanger, with a subsequent increase in the intracellular calcium level.

mechanisms (Ca2+-ATPase) as well as an ATP-dependent Ca2+ uniporter, further exacerbating the cell’s inability to remove intracellular Ca2+ in the low-energy conditions resulting from by rhabdomyolysis. An abrupt increase in cytoplasmic Ca2+ leads to a corresponding increase in mitochondrial Ca2+ because the mitochondria serve as the Ca2+ safety net. In addition to triggering apoptotic cell death by upregulating expression of proapoptotic factors, this mitochondrial Ca2+ overload leads to dysfunction of oxidative phosphorylation through structural and functional alterations, disrupting ATP production and further worsening the ATP debt and intracellular homeostasis of Ca2+. Increased mitochondrial Ca2+ also leads to increased production of reactive oxygen species (ROS), which are a broad group of chemical substances that include free oxygen radicals (O2−, OH•) and powerful oxidants (hydrogen peroxide, nitric oxide) that lead to free radical production. Free radicals carry extra unpaired electrons (e−) that have a strong tendency to pair off, causing oxidation by extracting electrons from other chemical species. Under normal physiologic conditions, 2% to 5% of oxygen consumed by the mitochondria is transformed during electron transport to ROS that are neutralized by endogenous antioxidants such as glutathione. When the antioxidant capacity of the endogenous system is overwhelmed during times of intense, sustained physical activity or illness, so that rhabdomyolysis results, a condition termed oxidative stress ensues. The resulting ROS-induced destruction of lipids and proteins injures the structure of membranes as well as DNA with mutations, leading to disruptions in cellular architecture and mitochondrial respiratory protein integrity. The cumulative effect exacerbates the inability to regulate intracellular Ca2+ homeostasis. Whereas ROS may have adaptive physiologic functions in exercising muscles, significant damage to muscle cells occurs when ROS are triggered by pathologic stimuli. Damage of the sarcoplasmic reticulum and mitochondria results in the release of stored calcium ions into the cytoplasm. The decreased removal of Ca2+ into the extracellular fluid, along with inadequate intracellular storage and increased entry into the cytoplasm, leads to myocytic Ca2+ overload and initiation of the cascade of cellular death. Calcium-induced activation of proteases, phospholipases, and other proteolytic enzymes degrades the protein structure of myofibrils, cytoskeleton, and membrane composition, leading to further cellular damage. Increased Ca2+ leads to sustained contraction of the myofibrils, resulting in severe ATP depletion in the initial stages while leading to myofibrillar breakdown as rhabdomyolysis progresses. Breakdown of the myofibrillar network hastens the disintegration of the myocyte, whereas high Ca2+ concentrations within the mitochondria arrest cellular respiration and block ATP production.

Diminished ATP production after Ca2+-mediated activation of degradative cellular enzymes, with large metabolic energy requirements of their own, exacerbates the preexisting energy crisis within already ischemic cells. This process releases free fatty acids and lysophosphates, which cause direct toxic damage to the sarcolemma, intracellular organelles, and plasma membrane carrier proteins, effecting increased Ca2+ entry into the cytosol. Microelectrode studies of intercostal myocytes have shown that the intracellular calcium concentration rises to 1.27 µmol/L after induction of rhabdomyolysis by exhaustive physical exertion compared with 0.12 µmol/L in normal muscles, representing nearly an 11-fold increase in the intracellular calcium concentration. Dantrolene, a known inhibitor of Ca2+ release from the sarcoplasmic reticulum, has been shown to lead to an 83% reduction of cytosolic Ca2+ and an improvement in the clinical symptoms of muscle stiffness, rigidity, and pain, highlighting the essential role of increased cytosolic Ca2+ in the pathophysiologic process of rhabdomyolysis. Rhabdomyolysis results in muscle cell breakdown, with the release of toxic contents into the extracellular space and damage to adjacent capillaries, resulting in local edema, increased compartmental pressures, and regional ischemia, which further induces energy depletion and destroys more capillaries. Circulating leukocytes adhere to these damaged capillaries, become activated, and transmigrate to the site of myocyte injury, where they release ROS and proteolytic enzymes that injure the cell further. In cases in which ischemia is the inciting event (eg, crush syndrome, arterial thromboembolism) of rhabdomyolysis, myocyte destruction primarily takes place during reperfusion (Fig. 119.2). Rhabdomyolysis is classified into four basic pathophysiologic processes: 1. Impairment of the muscle’s production or use of ATP at the cellular level. ATP concentrations within the cell fall; energydependent mechanisms falter, including Na+,K+-ATPase pumps, leading to disruption of chemical gradients, sarcolemma and cell membrane compromise, and cell destruction. 2. Disruption in the delivery of oxygen, glucose, and other nutrients to skeletal muscle 3. Increases in metabolic demands beyond the ability of the organism to deliver oxygen and nutrients 4. Direct myocyte damage Box 119.1 lists the various causes of rhabdomyolysis.

CLINICAL FEATURES The clinical presentation of rhabdomyolysis is variable because of its many causes. Its course may be mild and subclinical or it may be severe and life-threatening, depending on the extent of muscle damage and associated complications. It may be evident from the patient’s primary complaint or found incidentally on laboratory evaluation. The identification of rhabdomyolysis in the trauma patient is straightforward, whereas the nontraumatic causes may pose a diagnostic challenge. Rhabdomyolysis should be suspected in patients who present with altered mentation and risk factors for the development of rhabdomyolysis (eg, intoxication, immobility, drug ingestion, electric shock, neuroleptic malignant syndrome). The presence of acute renal failure without another attributable cause also prompts consideration of rhabdomyolysis. The classic presentation of rhabdomyolysis includes localizing myalgias, muscle stiffness, cramping, swelling, tenderness, and tea-colored urine. The most frequently involved muscle groups are the thighs, calves, and lower back. Nonspecific constitutional symptoms include malaise, fever, nausea, and vomiting. Unfortunately, most cases do not have characteristic physical signs; up to 50% of patients do not report myalgias or muscle weakness,

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Medicine and Surgery  | 

SECTION Eleven 

Metabolism and Endocrinology

Ischemia Intense muscle exercise Drugs Electrolyte imbalance Metabolic disorders Genetic conditions

ATP

Trauma Toxins Drugs Intense muscle exercise

Na2, K-ATPase and Ca2-ATPase dysfunction

Activation of Na-Ca exchanger

Rupture of sarcolemma

Cac Apoptosis ROS

Cam

Phospholipase and protease activation

Mitochondrial dysfunction DNA, lipid, and protein peroxidation

ATP

Hypercontractibility of myocyte

Rhabdomyolysis Fig. 119.2.  Pathophysiology of rhabdomyolysis. Cac, cytosolic [Ca]; Cam, mitochrondrial [Ca].

despite serologically proven rhabdomyolysis. Children with rhabdomyolysis may lack many of the classic symptoms; muscle pain and weakness occur in most pediatric patients, but reports of dark urine have been found to be as low as 5%.1 History by first responders or witnesses can be helpful, especially when the patient has an altered mental status. In these cases, the physical examination and high clinical suspicion become increasingly important. Findings may include extremity swelling, tenderness, motor weakness, sensory deficits, pain with passive range of motion, and overlying skin changes (particularly in cases of limb ischemia). Muscle swelling may only be evident after resuscitation and rehydration with intravenous (IV) fluids.

Complications Early Complications Compartment Syndrome.  Most skeletal muscles are encased in compartments formed by bones, fascia, and other structures. The massive influx of calcium and sodium in rhabdomyolysis leads to the accumulation of large amounts of extracellular fluid in the muscle cells, causing local edema and raised intracompartmental pressures, further leading to increased muscle ischemia. Prolonged ischemia and infarction of muscle tissue can lead to replacement of muscle tissue with inelastic fibrous tissue, resulting in severe contractures (Volkmann’s contracture). Intracompartmental pressures above 50 mm Hg or sustained pressures of more than 30 mm Hg during a maximum 6-hour period are indications for fasciotomy. Patents with rhabdomyolysis from traumatic compartment syndrome are at high risk of developing

acute kidney injury, with concomitant illicit drug or alcohol use and ischemic injuries increasing the odds of injury.2 Electrolyte Disorders and Acidosis.  Potassium release by damaged muscle leads to potentially lethal hyperkalemia, the most serious complication of rhabdomyolysis. Most potassium, 98%, is found in the intracellular space; 60% to 70% of the total cellular mass of the human body consists of skeletal muscle. Therefore, necrosis of as little as 100 g of muscle mass could increase the serum potassium level by 1.0 mEq/L. For comparison, the average 45 year-old man has a total body muscle mass of approximately 30 kg. Acidemia contributes to hyperkalemia and can be exacerbated by oliguria. The resulting fluid sequestration or myoglobininduced kidney injury reduces the kidney’s ability to excrete acid. Metabolic acidosis is also induced by the release of organic acids (eg, lactic acid, uric acid, sulfur-containing proteins). The disruption of muscle cells releases large amounts of phosphoric components into circulation, leading to hyperphosphatemia and ectopic calcification, typically depositing in necrotic tissue. Calcium phosphate crystal deposition in damaged muscle can lead to early-phase hypocalcemia, with potentially fatal dysrhythmias. Hyperkalemia coupled with hypocalcemia predisposes patients to malignant dysrhythmias. Furthermore, excessively high phosphate levels shut down the 1α-hydroxylase enzyme of the kidneys through negative feedback, decreasing production of the active form of vitamin D, further reducing calcium absorption from the gut and contributing to early hypocalcemia. Late in the course of rhabdomyolysis, the calcium initially deposited in the cytoplasm of necrotic muscle cells can mobilize and reenter the plasma, resulting in late hypercalcemia.

CHAPTER 119  Rhabdomyolysis

BOX 119.1 

Causes of Rhabdomyolysis PROLONGED IMMOBILIZATION

Prolonged immobilization can cause rhabdomyolysis by pressure on gravity-dependent body parts. This pressure-related phenomenon may be enhanced by the underlying cause of the immobilization (eg, drugs or trauma).

EXCESSIVE MUSCLE ACTIVITY

ATP depletion from excessive muscle activity leads to a mismatch of cellular energy needs and ATP supply. This leads to malfunction of ATP-dependent cellular membrane ion pumps, net influx of ionized calcium, and subsequent rhabdomyolysis. Exertion-related cases of rhabdomyolysis have been reported in sporadic and prolonged muscle activity of high and low intensity.

MUSCLE ISCHEMIA

ATP production is limited by interruption of blood perfusion of any cause to muscle tissue, including arterial occlusion, carbon monoxide poisoning, and external compression. Muscle cell hypoxia leads to muscle damage in as little as 2 hours, with irreversible anatomic and functional changes within 4 hours and muscle necrosis in as little as 6 hours.

TEMPERATURE EXTREMES

Extremes of temperature are known to cause rhabdomyolysis by sarcolemma disruption. The physiologic concept of thermal maximum describes the core temperature and duration at which human cells break down. A core body temperature of 42° C (107.6° F) for more than 45 to 60 minutes leads to cellular damage. Heat stroke, neuroleptic malignant syndrome, and malignant hyperthermia are conditions known to lead to excess heat and muscle breakdown. Similarly, hypothermia causes sarcolemma membrane dysfunction below critical temperatures necessary for membrane protein structural integrity. Rhabdomyolysis has been attributed to therapeutic hypothermia in a post–cardiac arrest trauma victim.13

ELECTRICAL CURRENT

Muscle sarcolemma is directly injured by electrical current–induced membrane permeability (electroporation) and thermal injury; high-voltage electrical injury, including lighting, poses the highest risk. Secondary injury by coagulation of blood in muscle capillary beds may lead to localized muscle ischemia. Rhabdomyolysis has also been seen after cardioversion for refractory ventricular tachycardia and fibrillation.

ELECTROLYTE ABNORMALITIES

Hypokalemia by whatever mechanism can cause rhabdomyolysis. Extracellular potassium leads to localized microvascular vasodilation, and low concentrations can lead to focal muscle vasoconstriction and ischemia, with subsequent muscle injury. Hypophosphatemia may result in rhabdomyolysis in that phosphate groups are needed for ATPdependent cell functions. Hyponatremia has been reported to cause rhabdomyolysis in endurance athletes14 and in those with psychogenic polydipsia. Hypernatremia may also have direct links to rhabdomyolysis in the absence of other known causative agents.

ILLICIT DRUGS

A number of illicit drugs, such as opioids, antipsychotics, benzodiazepines, amphetamines, ecstasy, LSD, and synthetic cannabinoids,15,16 can result in rhabdomyolysis by direct or indirect

Hypovolemia.  In rhabdomyolysis, fluid moves from intravascular compartments into damaged muscle, causing profound intravascular volume depletion. This shift may exceed 15 L. Hepatic Dysfunction.  Large elevations in serum liver enzyme levels may occur after nontraumatic rhabdomyolysis.

effects, including immobilization with muscle tissue hypoperfusion and hypoxia, psychomotor agitation, direct myotoxicity, and electrolyte abnormalities, particularly hypokalemia and hypophosphatemia.

MEDICATIONS

Statin-induced rhabdomyolysis is well documented. Its precise mechanism is not fully known but is hypothesized to be due to membrane instability from inhibition of cholesterol synthesis by hydroxymethylglutaryl–coenzyme A reductase inhibition, impaired intracellular protein messaging from abnormally prenylated proteins, and abnormal mitochondrial respiration from coenzyme Q10 deficiency. Similarly, fibric acid derivatives, which decrease hepatic triglyceride production, have been associated with rhabdomyolysis. Many if not most other classes of prescription medications have been associated with rhabdomyolysis, including the typical and atypical antipsychotics.

INFECTIONS

Rhabdomyolysis has been reported after infections with bacterial, viral, fungal, and parasitic agents. Sepsis-induced tissue hypoxia, direct bacterial myocyte invasion, decreased glycolytic and oxidative enzyme activity, lysosomal enzyme activation, and endotoxin-related injury have all been implicated as pathogenetic mechanisms involved in infectious causes of rhabdomyolysis. Rhabdomyolysis has been found in patients with influenza A and should be considered in patients presenting with marked body aches and weakness during flu season.17 Legionella is the most common bacterial cause of rhabdomyolysis. It is unclear if rhabdomyolysis is caused by a common pathway of sepsis-related systemic inflammation or species-specific processes.

METABOLIC MYOPATHIES

Inherited disorders are manifested with enzyme deficiencies in carbohydrate and lipid metabolism or myopathies. These lead to defects in glycolysis, gluconeogenesis, fatty acid oxidation, and mitochondrial cellular respiration. These disorders are typically manifested during childhood and are recurrent.

CONNECTIVE TISSUE DISORDERS

Although rare, cases of rhabdomyolysis have been reported in conditions such as polymyositis, dermatomyositis, and Sjögren’s syndrome.

RHEUMATOLOGIC DISORDERS

Systemic lupus erythematosus, usually associated with mild myositis, has also been reported in a case of fulminant myositis with rhabdomyolysis.

ENDOCRINE DISORDERS

Hypothyroidism has been reported to cause rhabdomyolysis.

BIOLOGIC TOXINS

Snakebite, Africanized bees, wasps18,19 and honey bee envenomations are known to release myotoxic agents causing rhabdomyolysis.

OTHER AND UNKNOWN CAUSES

Case reports have documented the development of rhabdomyolysis after succinylcholine administration to patients with neuromuscular disorders,20 as well as in some bariatric surgery patients21 and patients undergoing cardiopulmonary resuscitation. Caffeine toxicity from an overdose can also cause rhabdomyolysis.22

The cause of this finding is not fully understood, but proteases released by muscle cells have been implicated. However, aspartate transaminase level elevations may also be of skeletal muscle origin. These derangements are generally reversible. Preexisting hepatic dysfunction can also potentiate statin-induced rhabdomyolysis.3

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Metabolism and Endocrinology

Late Complications Myoglobin-Induced Acute Kidney Injury.  Experimental evidence has suggested that the mechanisms involved in the pathophysiologic process of myoglobinuric acute renal failure are myoglobin cast formation in the distal convoluted tubules, direct cytotoxic action of myoglobin on the epithelial cells of the proximal convoluted tubules, and intrarenal vasoconstriction and ischemia (Fig. 119.3). Myoglobin becomes concentrated along the renal tubules and precipitates in acidic urine along with uric acid to form obstructive casts. This process is enhanced by volume depletion and renal vasoconstriction, which reduces blood flow and the glomerular filtration rate (GFR), promoting the accumulation of necrotic epithelial cells into tubular casts and further worsening the GFR. Tubule obstruction occurs at the level of the distal tubule, whereas direct tubule cytotoxicity occurs mainly in the proximal tubules. There remains some controversy about the exact mechanism of renal dysfunction in rhabdomyolysis; some experts believe that casts and tubular obstruction are not the cause but rather the consequence of poor tubular clearance. When the concentration of myoglobin filtered at the glomerulus exceeds the normal level, tubular cells at the proximal convoluted tubule increase their reabsorption capacity to limit the excretion of myoglobin into the urine, protecting the kidney from its nephrotoxic effects. At a urine pH of 5.6 or lower, myoglobin, an iron-containing heme protein, dissociates into free iron (Fe), ferrihemate (Fe-heme complex), and globin inside the proximal tubular epithelial cell. Free hydroxyl radicals are produced when ferrous oxide in the Fe-heme complex is oxidized by molecular oxygen (O2) and when free iron reacts with H2O2. Free iron may also act as a free radical, although its role in rhabdomyolysisinduced renal injury is unclear. Myoglobin itself has been shown to exhibit peroxidase-like enzyme activity. Ferrihemate causes direct nephrotoxic effects along with the resultant increased oxidative stress within the tubular epithelial cell, leading to acute tubular necrosis through lipid, protein, and DNA peroxidation. More recent evidence has argued against free iron’s role in oxidative stress–induced renal injury and emphasized the role of ferrihemate-induced lipid peroxidation in cell injury.

Fluid shifts and renal dysfunction lead to activation of the renin-angiotensin-aldosterone system and sympathetic nervous system and production of vasoconstricting molecules such as endothelin 1 and vasopressin. There is also decreased production of vasodilatory prostaglandins. Nitric oxide (NO), a potent vasodilatory agent, is known to be responsible for the maintenance of renal blood flow; myoglobin released from damaged muscle may act as a scavenger of NO in the renal microcirculation, itself reduced by NO buffering against oxidant injury by ferrihemate. When NO is overcome by increased myoglobin concentrations, the kidney is deprived of the ability to autoregulate organ blood flow and maintain adequate perfusion in times of shock. Thus, myoglobin is free to cause damage in proximal tubular epithelial cells (under appropriate acidotic conditions), as previously described. Other locally stimulated vascular mediators, such as thromboxane A2, tumor necrosis factor alpha, and F2-isoprostanes, which themselves are byproducts of free radical lipid peroxidation, have also been implicated in the reduction of renal blood flow as a result of endothelial disruption and inflammation, as well as oxidant injury. Disseminated Intravascular Coagulation.  Prothrombotic substances, mainly thromboplastin, released from destroyed muscle cells activate the coagulation cascade. They can lead to the formation of thrombi in the capillary tufts of the glomeruli.

DIAGNOSTIC TESTING Serum Creatine Kinase The definitive diagnosis of rhabdomyolysis is reliably made by serologic testing for creatine kinase (CK). This test can assist the clinician in assessing at-risk patients when historical and examination findings are lacking. Elevated levels of CK are the hallmark of rhabdomyolysis. CK functions as an energy reservoir for ATP: creatine + ATP = creatine kinase + ADP (adenosine diphosphate). CK has a half-life of 1.5 days; its level elevated in the first 12 hours, peaks during the first 3 days, and normalizes at around 5 days after injury. A CK level five times the upper limit of normal (≈1000 U/L), without apparent cardiac or brain injury, confirms the diagnosis.

Serum and Urine Myoglobin Myoglobin CK

0

24

48

72

96

120

Hours Fig. 119.3.  Variations of myoglobin and creatine kinase (CK) levels during the course of rhabdomyolysis. Myoglobin is the first enzyme that increases but, because of its rapid clearance from the plasma, it returns to normal levels within the first 24 hours after the onset of symptoms. The CK level increases a few hours later than myoglobin, reaches its peak value within the first 24 hours, and remains at these levels for 3 days. CK is considered to be a more useful marker for the diagnosis and assessment of the severity of muscle injury because of its delayed clearance from the plasma.

Myoglobin is a dark red protein composed of globin and a molecule of heme. Its normal function is to supply oxygen to skeletal and cardiac muscle in times of need. The excretion of myoglobin occurs renally. It is initially filtered at the glomerulus and reabsorbed by endocytosis in the convoluted tubules, where it is broken into its component parts, globin and heme, by proteolytic enzymes. As with all other low-molecular-weight proteins, a small amount is excreted in the urine. The normal concentration of myoglobin in the urine is less than 10 µg/L. A normal serum concentration of myoglobin is less than 100 µg/L. During rhabdomyolysis, myoglobin released by damaged muscle is increasingly filtered at the glomerulus. This leads to an initial increased reabsorptive capacity by glomerular and tubular epithelial cells, developed presumably as a protective response to increased filtered myoglobin. When serum myoglobin concentrations exceed 0.3 mg/L and the renal threshold of 1.0 mg/dL is met, this reabsorptive capacity is overwhelmed, and excess myoglobin appears in the urine. This myoglobin is detected by urine dipstick as positive for blood (Table 119.1). In the past, the diagnosis of rhabdomyolysis was made by serum myoglobin; however, myoglobin has a serum half-life of only 1 to 3 hours and is completely absent after 24 hours. This

CHAPTER 119  Rhabdomyolysis

TABLE 119.1 

Causes and Microscopic Features of Red and   Brown Urine RESULTS FOR BLOOD IN URINEa SEDIMENTb SUPERNATANT

CAUSE Hematuria

+++

Red

Yellow

Myoglobinuria

+++

Normal

Red to brown

Hemoglobinuria

+++

Normal

Red to brown



Normal

Red



Normal

Brown



Normal

Red to brown

Porphyria Bile pigments Food and drugs

c

a

Urine tested with dipstick test. Normal refers to white or yellow color. Food and drugs that can cause red urine include beets, blackberries, rhubarb, food coloring, fava beans, phenolphthalein, rifampin, doxorubicin, deferoxamine, chloroquine, ibuprofen, and methyldopa. Those that cause brown urine include levodopa, metronidazole, nitrofurantoin, iron sorbitol, chloroquine, and methyldopa. Adapted from Bosch X, Poch E, Grau JM: Rhabdomyolysis and acute kidney injury. N Engl J Med 361:62–79, 2009. b c

short window makes serum myoglobin an unreliable diagnostic test. This also applies to urine myoglobin levels, which depend on the degree of muscle injury, volume status of the patient, and urinary flow rate. A well-hydrated patient with normal renal function can rapidly clear plasma from the body. Although myoglobin is pathognomonic, because it is only detectable early in the course of disease, the absence of plasma or urine myoglobin does not rule out rhabdomyolysis (Fig. 119.4).4

Urine Dipstick and Urinalysis Myoglobinuria causes a positive result for blood in urine dipstick testing. The drawback of this test is its inability to distinguish among heme compounds. However, in myoglobinuria, microscopic analysis will show few if any red blood cells, thereby distinguishing between hemoglobin and hemoglobin-rich red blood cells (from hemolysis or hematuria). Myoglobinuria, in combination with an elevated plasma CK level, confirms rhabdomyolysis. At plasma concentrations above 100 to 300 mg/L, macroscopic myoglobinuria manifests as tea-colored urine. The urine dipstick test or urinalysis result is generally acidic in rhabdomyolysis, which plays a role in cast and uric acid crystal formation, as well as pathologic myoglobin metabolism in tubular epithelial cells. Proteinuria may also be noted because of the detection of the globin component of myoglobin. Urine sediment analysis will show myoglobin casts and dead epithelial cells (see Table 119.1).

Other Laboratory Findings Common electrolyte disturbances in patients with rhabdomyolysis include hyperkalemia, hyperphosphatemia, and early hypocalcemia followed by late hypercalcemia. Late hypercalcemia is postulated to be due to the mobilization of calcium that was initially sequestered in damaged muscle. Hyperuricemia from the release of muscle nucleic acids is especially common in patients with large muscle mass. Metabolic acidosis typically occurs from the generation of organic acids from damaged muscle—namely, lactate and uric acid. Hypoalbuminemia and anemia result from capillary damage and release into the extracellular space.

Both the blood urea nitrogen (BUN) and creatinine (Cr) concentrations increase, but with a characteristic decrease in the BUN/Cr ratio due to large amounts of creatinine released into the serum from damaged muscle. A normal BUN/Cr ratio is 10 : 1; in rhabdomyolysis, it can be 5 : 1 or even less. In severe cases, coagulation disorders such as disseminated intravascular coagulation (DIC) can ensue, triggered by the released thromboplastin from damaged tissue.

Prognostic Tests in Rhabdomyolysis Most studies evaluating the ability for the CK level to predict renal injury have been retrospective and conducted in admitted patients. In these reports, the degree of CK level elevation has not been found to be a reliable predictor of acute kidney injury, with most showing no correlation or a weak one.5,6 One study of admitted pediatric trauma patients did find a correlation between CK levels above 3000 U/L and acute kidney injury.7 This suggests that age and etiology of rhabdomyolysis may permit the use of CK as a predictor for kidney injury in certain populations. In one of the only studies of emergency department (ED) patients with rhabdomyolysis, the CK level did not correlate with the primary outcomes of need for dialysis or death at 30 days.8 However, the estimated glomerular filtration rate (eGFR), calculated as 175 × (Cr/88.4)−1.154 × (age)−0.203 for males, multiplied by 0.742 for females, did correlate with the primary outcomes, with no patients with an eGFR of less than 60mL/min/1.73 m2 developing acute kidney injury or dying. Based on the cumulative evidence, I recommend that the CK level should be used as a diagnostic marker for rhabdomyolysis and not as a prognostic indicator of acute renal injury. Once the diagnosis is made, the eGFR can be used to predict renal injury and determine the need for admission; I recommend using a computer application to calculate eGFR from the formula. The degree of creatinine level elevation at the time of admission has been shown to correlate with 30-day mortality rates.6

MANAGEMENT Management of rhabdomyolysis focuses on treatment of the cause, prevention of renal failure, and management of life- or limb-threatening complications.

Fluid Replacement and Urine Alkalinization Volume expansion is critical to avoiding myoglobin-induced acute renal failure. Fluid expansion increases renal blood flow and therefore glomerular filtration and urination. Patients with rhabdomyolysis typically present with severe dehydration due to fluid sequestration in the affected skeletal muscles. Several case series, mostly from victims of natural disasters (eg, earthquakes with building collapse), have shown that some degree of intravascular volume contraction is a prerequisite for developing acute renal failure. Because acute renal failure appears to develop in patients with a longer delay to supportive therapy, fluid resuscitation should be instituted early. For victims of mass casualty events with prolonged extrication times, fluid resuscitation should begin before complete extrication. Although the need for early volume expansion is universally accepted, the composition of the fluid is more controversial, especially regarding the concept of urine alkalinization. The principles of urine alkalinization have been derived empirically from animal data: (1) myoglobin precipitation is increased in acidic urine; (2) reduction-oxidation (redox) cycling of myoglobin and lipid peroxidation, and thus tubule injury, are inhibited by alkaline urine; and (3) myoglobin induces renal vasoconstriction only in an acidic medium. Myoglobin-induced lipid peroxidation occurs

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Metabolism and Endocrinology

Rhabdomyolysis H2O Na

Fluid sequestration

Volume depletion K

Hyperkalemia Hyperphosphatemia

P

Ca2 Hypocalcemia Fe2  H2O2 Myoglobin

Fe2

 OH  OH

Oxidant injury Lipid peroxidation ET NO TxA2 TNF F2IP

RAS activation SNS activation ADH release

Renal vasoconstriction

Filtered myoglobin Endothelial dysfunction Myoglobin-THP complex

Pigmented granular cast

Myoglobin oxidant injury

ATP depletion

Myoglobin oxidant injury

Ischemia Inflammation

Proximal tubule toxic and ischemic injury Distal tubule obstruction

Fig. 119.4.  Pathophysiologic mechanisms in rhabdomyolysis-induced acute kidney injury. ADH, Antidiuretic hormone; ATP, adenosine triphosphate; ET, endothelin; F2IP, F2-isoprostanes; NO, nitric oxide; RAS, renin-angiotensin system; SNS, sympathetic nervous system; THP, Tamm-Horsfall protein; TNFα, tumor necrosis factor alpha; TxA2, thromboxane A2. (Adapted from Bosch X, Poch E, Grau JM: Rhabdomyolysis and acute kidney injury. N Engl J Med 361:62–72, 2009.)

at concentrations several orders of magnitude lower than those that lead to the precipitation of casts in the distal tubules. The theory of alkalinization has been supported by the discovery that alkalinization inhibits redox cycling of myoglobin and lipid peroxidation.9 However, the clinical benefits of alkalinization compared with simple saline volume repletion are not firmly established, and sodium bicarbonate therapy has not been proven necessary or superior to normal saline diuresis at increasing urine pH. Comparative studies have been limited by their small sample sizes and variability in the severity of rhabdomyolysis, determined by CK level. They have been further complicated by the administration of multiple therapeutic measures (eg, bicarbonate plus mannitol), making the impact of any one measure difficult to interpret.

Although the precise benefit of alkaline therapy in rhabdomyolysis is unknown, what is known is the impact of large volumes of normal saline on the serum pH. Normal saline contains supraphysiologic concentrations of chloride ions. Massive infusion of normal saline leads to a disproportionate increase in serum chloride concentrations, inducing an iatrogenic metabolic (hyperchloremic) acidosis that exacerbates myoglobin precipitation, tubular obstruction, and risk of hyperkalemia-related complications. The administration of both normal saline and sodium bicarbonate, especially in patients with metabolic acidosis, may be one approach to fluid resuscitation. If sodium bicarbonate therapy is used, the urine and serum pH and serum bicarbonate, potassium, and calcium levels should be monitored. The urine should be

CHAPTER 119  Rhabdomyolysis

alkalinized to a pH above 6.5 and serum pH of 7.40 to 7.45. Bicarbonate therapy should be discontinued and switched to normal saline if calcium levels become dangerously low (total corrected calcium concentration < 9 mg/dL or ionized calcium concentration < 4.5 mg/dL), or if no improvement in urine pH is noted after 4 to 6 hours. If a saline-only approach is used, the serum chloride and pH levels should be monitored and the saline discontinued if a hyperchloremic metabolic acidosis is iatrogenically induced. In this case, a less acidifying solution (eg, Isolyte, lactated Ringer’s solution) can be used. Evidence for this approach is lacking but reasonable given current experimental and clinical knowledge. Precise guidelines for the duration of fluid administration are lacking, but IV fluid administration should be continued until the plasma CK concentration decreases to less than 1000 U/L. A total of 10 to 20 L of IV fluid is often administered in the first 24 hours, depending on the severity of illness and underlying comorbidities that may preclude large-volume fluid administration (eg, congestive heart failure). In general, titration to a urinary output of 300 mL/hr or more is a reasonable target for adults.10

Diuretics Mannitol Although mannitol is the only diuretic with evidence to support a benefit in rhabdomyolysis, its use remains controversial.10 As an osmotic diuretic, its theoretic benefit is its ability to increase urinary flow (ie, wash out nephrotoxic agents) and draw out fluid accumulated from damaged muscle into the intravascular space, thereby also improving hypovolemia. Mannitol is also a free radical scavenger; however, at the concentrations used therapeutically, these antioxidant properties are likely irrelevant. Most data on mannitol therapy have come from animal studies, which demonstrated that the bulk of its therapeutic effect is attributable to its osmotic diuretic action. In human studies, the addition of mannitol has not been shown to be more beneficial than fluid expansion alone, and no randomized controlled trials have shown any beneficial effect. Large accumulated doses of mannitol may be detrimental by causing renal vasoconstriction and tubular toxicity, a condition known as osmotic nephrosis. However, mannitol therapy, may be beneficial to relieve compartment pressures. If mannitol is used, the plasma osmolality and osmolal gap should be frequently monitored; treatment should be discontinued if adequate diuresis is not achieved or if the osmolal gap rises above 55 mOsm/kg.

Furosemide Loop diuretics also increase urinary flow, but no study has shown a clear benefit in patients with rhabdomyolysis. Therefore, they are not recommended as prophylaxis against myoglobin-induced renal failure.

Acetazolamide Carbonic anhydrase inhibitors for urine alkalinization have been used when bicarbonate therapy results in metabolic alkalosis with persistent acidic urine. Acetazolamide has theoretic advantages because it induces bicarbonate diuresis, with restorative effects on acid-base status from natriuresis. Case reports have shown potential benefit, but this has not been confirmed experimentally or clinically and cannot be recommended at this time.

Experimental Therapies Antioxidants such as glutathione and vitamin E analogues have shown promise in experimental animal models of myoglobininduced oxidant injury and may have a future role in management. Grape seed proanthocyanidin extract has been shown to have renoprotective effects in rat models of rhabdomyolysis.11 The xanthine oxidase inhibitor, allopurinol, is being studied as a prophylactic agent in nonathletes at risk for exertional rhabdomyolysis.12

Renal Replacement Therapy As with non–rhabdomyolysis-related causes of renal failure, the indications for emergent dialysis or filtration remain uncorrectable metabolic acidosis, life-threatening hyperkalemia and other electrolyte disturbances despite medical management, manifestations of uremia, and anuria or oliguria, despite volume expansion with complications related to fluid overload. Fluid overload is particularly problematic when it results in pulmonary edema or in patients with poor cardiac reserve. Conventional hemodialysis does not filter myoglobin effectively because of its large size. Renal replacement therapy (RRT) is indicated, with intermittent hemodialysis to correct electrolyte abnormalities rapidly. Con­ tinuous venovenous hemofiltration or hemodiafiltration has shown promise for the removal of myoglobin in case reports, although outcome data are lacking. Continuous renal replacement therapy (CRRT) may be more desirable than intermittent RRT because of the theoretic hemodynamic and homeostatic benefits of continuous versus intermittent therapy. However, three small, poorly designed randomized trials of CRRT have failed to show a decrease in mortality, despite more rapid removal of myoglobin and improvement in electrolyte, BUN, and creatinine levels.9 The need for RRT in the acute setting of rhabdomyolysis does not predict the need for long-term hemodialysis.

DISPOSITION The need for fluid resuscitation in rhabdomyolysis and close monitoring of renal function and electrolytes require hospitalization in most cases. Observation stays can be considered in milder cases but more complicated cases warrant admission to a monitored setting until resolution of metabolic and hemodynamic perturbations. The type of hospital bed is contingent on the cause of rhabdomyolysis, presence of comorbidities, and severity of illness at presentation. Fluid resuscitation should generally be initiated at CK levels more than five times the upper limit of normal (typically, 1000 IU/L) and should be continued until levels trend down and drop below this level.

Prognosis Rhabdomyolysis, when recognized and treated early, carries an excellent prognosis. With the exception of hyperkalemia-related death or the rare complication of DIC, acute kidney injury is the most serious complication of rhabdomyolysis, regardless of cause. Of patients who have acute renal failure, most will recover full renal function when treatment is instituted in a timely fashion. Mortality data for patients with renal failure vary widely in the literature according to the study population, cause, presence of multiple causative agents, and comorbidities; however, long-term survival among patients with rhabdomyolysis and acute renal injury tends to be very good when timely management is provided.

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KEY CONCEPTS • Rhabdomyolysis is generally a benign syndrome, but with potentially fatal complications. Acute renal failure and hyperkalemia are accompanied by high mortality. • Rhabdomyolysis should be suspected in at-risk patients (see Box 119.1) who present with muscle pain or altered mentation. • The diagnosis of rhabdomyolysis is confirmed with an elevated serum CK level (>1000 U/L). • In patients with rhabdomyolysis, the degree of CK elevation is not a reliable predictor of risk of acute renal injury.

• IV fluid administration should be aimed at maintaining a urine output of at least 300 mL/hr in the average-sized adult patient with rhabdomyolysis. • Diuretics have no role in the management of most cases of rhabdomyolysis. • Survivability hinges on prompt recognition and resuscitation with a liberal fluid strategy, with or without urine alkalinization.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 119  Rhabdomyolysis

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REFERENCES 1. Chen C, Lin Y, Zhao L, et al: Clinical spectrum of rhabdomyolysis presented to pediatric emergency department. BMC Pediatr 13:134, 2013. 2. Tsai W, Huang S, Liu W, et al: High risk of rhabdomyolysis and acute kidney injury after traumatic limb compartment syndrome. Ann Plast Surg 74:S158–S161, 2015. 3. Kolhe N, Lewis J, McCulloch TA: Risk of statin-induced rhabdomyolysis in patients with hepatic impairment. BMJ Case Rep 2014:2014. 4. Premru V, Kovac J, Ponikvar R: Use of myoglobin as a marker and predictor in myoglobinuric acute kidney injury. Ther Apher Dial 17:391–395, 2013. 5. Lee G: Exercise-induced rhabdomyolysis. R I Med J 97:22–24, 2013. 6. Baeza-Trinidad A, Brea-Hernando S, Morera-Rodriguez S, et al: Creatinine as predictor value of mortality and acute kidney injury in rhabdomyolysis. Intern Med J 45:1173–1178, 2015. 7. Talving P, Karamanos E, Skiada D, et al: Relationship of creatine kinase elevation and acute kidney injury in pediatric trauma patients. J Trauma Acute Care Surg 74: 912–916, 2013. 8. Grunau BE, Pourvali R, Wiens MO: Characteristics and thirty-day outcomes of emergency department patients with elevated creatine kinase. Acad Emerg Med 21:631–636, 2014. 9. Zeng X, Zhang L, Wu T, et al: Continuous renal replacement therapy (CRRT) for rhabdomyolysis. Cochrane Database Syst Rev (6):CD008566, 2014. 10. Scharman EJ, Troutman WG: Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother 47:90–105, 2013. 11. Ulusoy S, Ozkan G, Alkanat M, et al: Perspective on rhabdomyolysis-induced acute kidney injury and new treatment options. Am J Nephrol 38:368–378, 2013. 12. Sanchis-Gomar F, Pareja-Galeano H, Perez-Quilis C, et al: Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches? Cell Stress Chaperones 20:3–13, 2015.

13. Ciapetti M, di Valvasone S, Spina R, et al: Rhabdomyolysis following therapeutic hypothermia after traumatic cardiac arrest. Resuscitation 82:493, 2011. 14. Bruso JR, Hoffman MD, Rogers IR, et al: Rhabdomyolysis and hyponatremia: a cluster of five cases at the 161-km 2009 Western States Endurance Run. Wilderness Environ Med 21:303–308, 2010. 15. Mousavi SR, Vahabzadeh M, Mahdizadeh A, et al: Rhabdomyolysis in 114 patients with acute poisonings. J Res Med Sci 20:239–243, 2015. 16. Durand D, Delgado LL, de la Parra-Pellot DM, et al: Psychosis and severe rhabdomyolysis associated with synthetic cannabinoid use. Clin Schizophr Relat Psychoses 8:205–208, 2015. 17. Fadila MF, Wool KJ: Rhabdomyolysis secondary to influenza A infection: a case report and review of the literature. N Am J Med Sci 7:122–124, 2015. 18. Arya A, Jindal A: Acute kidney injury and rhabdomyolysis due to multiple wasp stings. Indian J Crit Care Med 18:697–698, 2014. 19. Radhakrishnan H: Acute kidney injury and rhabdomyolysis due to multiple wasp stings. Indian J Crit Care Med 18:470–472, 2014. 20. Tritakarn T, Teeratchanan T: Acute rhabdomyolysis and cardiac arrest following succinylcholine in a patient with Parry-Romberg syndrome. Anaesth Intensive Care 39:135–136, 2011. 21. Chakravartty S: Rhabdomyolysis in bariatric surgery: a systematic review. Obes Surg 23:1333–1340, 2013. 22. Golcuk Y, Ozsarac M, Golcuk B, et al: Caffeine-induced rhabdomyolysis. Am J Emerg Med 32:100, 2014.

CHAPTER 119: QUESTIONS & ANSWERS 119.1. Which of the following statements regarding muscle cell physiology and rhabdomyolysis is true? A. Acute renal failure from rhabdomyolysis is very rare. B. Hemoglobin has a higher oxygen affinity than myoglobin. C. The final common pathway of injury in rhabdomyolysis is cell membrane damage. D. The normal intracellular Na+ concentration is high. E. The normal intracellular Ca2+ concentration is low. Answer: E. Normal intracellular concentrations of Na+ are low, creating a negative intracellular environment. This allows more facilitated transfer of Ca2+ from the intracellular to extracellular space, maintaining low intracellular Ca2+ concentrations. The final common pathway of injury is sarcolemma damage with intracellular Ca2+ accumulation, proteolytic enzyme inhibition, actinmyosin coupling dysfunction, and cell damage with release of intracellular contents (eg, myoglobin, PO4−, uric acid, lactate dehydrogenase). Myoglobin, which has four times the O2 affinity of hemoglobin, overwhelms the haptoglobin-binding capacity, is filtered at the glomerulus, and precipitates in renal tubules. Approximately 5% to 15% of cases of acute renal failure in the United States are related to rhabdomyolysis. This myoglobin precipitation is markedly facilitated by acidosis. 119.2. Which of the following statements regarding exertion (exercise)-related rhabdomyolysis is true? A. Eccentric (lengthening) muscle work is more damaging than concentric. B. Hypocalcemia increases the risk for this syndrome. C. It is the result of voluntary muscle exertion. D. It is seen exclusively in untrained athletes. E. The mechanism is different than after a crush injury. Answer: A. Exertional rhabdomyolysis is seen in trained and untrained individuals as well as after exercise or situations of involuntary muscle activity (eg, psychoses, seizures, tetany, myoclonus). The mechanism (eg, failure of energy supplies, sarcolemma breakdown, intracellular calcium accumulation, enzyme dysfunction, cellular swelling) is the same. Hypokalemia is a risk factor

because a low potassium level limits microvascular dilation and muscle perfusion. 119.3. Which of the following statements regarding druginduced rhabdomyolysis is true? A. Cocaine myotoxicity is not related to the degree of intoxication. B. Colchicine and cyclosporine are myotoxins. C. Ethanol myotoxicity is potentiated by high carbohydrate intake. D. Statin myotoxicity is unrelated to state of hydration. E. The use of the drug ecstasy is not associated with rhabdomyolysis. Answer: B. Statins, ethanol, cocaine, colchicine, cyclosporine, and many other drugs are myotoxic. Illicit drugs include amphetamine, ecstasy, LSD, and other sympathomimetics. Ethanol is a direct muscle membrane toxin, and this effect is potentiated by starvation, binge drinking, and coexisting electrolyte abnormalities (low K+, PO4−, and Mg2+). Intravenous cocaine use is more myotoxic than inhaled cocaine, and the severity seems to parallel the degree of intoxication. 119.4. What is the most common viral cause for rhabdomyolysis? A. Cytomegalovirus B. Epstein-Barr virus C. Herpesvirus D. Human immunodeficiency virus E. Influenza virus Answer: E. Influenza is the most common viral etiology followed by HIV infection and enteroviral infection. 119.5. What is the most common bacterial cause for rhabdomyolysis? A. Legionella B. Pseudomonas C. Salmonella D. Staphylococcus E. Streptococcus

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Answer: A. Legionella is the bacterium classically associated with rhabdomyolysis in adult patients. The pathogenesis is believed to be due to direct invasion and toxic degeneration of muscle fibers. 119.6. Which of the following electrolyte abnormalities has not been associated with rhabdomyolysis? A. Hypermagnesemia B. Hypernatremia C. Hypocalcemia D. Hyponatremia E. Hypophosphatemia Answer: A. There are no reported cases of hypermagnesemia induced rhabdomyolysis to date. 119.7. A 53-year-old intoxicated alcoholic is brought to the ED by EMS after being found unconscious for an unknown reason. He is now awake but mildly lethargic. He has no complaints of pain or disability. The physical examination is nonfocal. Which of the following statements is true? A. A CK-MB fraction of 5% would indicate myocardial damage. B. A negative urine myoglobin level would exclude rhabdomyolysis. C. His lack of pain complaints would exclude rhabdomyolysis. D. Hypocalcemia would be expected in the presence of rhabdomyolysis. E. If rhabdomyolysis were found, normal phosphate level would be reassuring.

Answer: D. Hypocalcemia is the most common electrolyte abnormality after rhabdomyolysis. Hypercalcemia may follow later. Only 50% of patients with serum evidence of rhabdomyolysis have complaints of muscle pain. Likewise, the presence of urine myoglobin reflects the glomerular filtration rate, plasma myoglobin concentrations, urine flow, and plasma myoglobin binding. This test result may be negative, especially late in the course of the process. Hyperphosphatemia is expected, and a normal level raises the suspicion that hypophosphatemia was the cause of the rhabdomyolysis. CK-MB levels of 3% to 5% are often seen and reflect skeletal rather than cardiac muscle damage. 119.8. Which of the following is a proven cornerstone of management for rhabdomyolysis, along with saline hydration? A. Alkalinization B. Chelation therapy C. Furosemide D. Mannitol E. None of the above Answer: E. Furosemide is somewhat contraindicated because of its tendency to acidify the urine. Mannitol and alkalinization are not proven, although they are often used. Chelation therapy is under investigation.

C H A P T E R 120 

Thyroid and Adrenal Disorders Molly E.W. Thiessen

Thyroid dysfunction (hyperthyroidism and hypothyroidism) arguably represents the most common form of endocrine disorder. Together with adrenal insufficiency, these disease states are often manifested with nonspecific symptoms, such as fatigue and weakness, making them a diagnostic challenge. In their advanced states, classic manifestations develop, rendering each disorder more recognizable. Each disorder is also capable of producing lifethreatening symptoms when it is untreated or precipitated by other stressors.

HYPERTHYROIDISM Principles Background Hyperthyroidism is a condition caused by overproduction and increased circulation of thyroid hormone. The disorder runs the spectrum from subclinical hyperthyroidism to thyrotoxicosis, a life-threatening disorder. Thyrotoxicosis is a hypermetabolic condition that results from elevated levels of thyroid hormones— triiodothyronine (T3) and thyroxine (T4). This can occur from hormone overproduction (Graves’ disease, toxic multinodular goiter), increased thyroid hormone release from an injured gland (thyroiditis, trauma), or exogenous thyroid hormone (thyrotoxicosis factitia). Most cases of thyrotoxicosis (>80%) are due to autoimmune disease.1 For the purpose of this discussion, the terms hyperthyroidism and thyrotoxicosis are used interchangeably.

Anatomy and Physiology The normal adult thyroid gland is a highly vascular bilobar organ overlying the anterior trachea (Fig. 120.1). The thyroid’s function is to secrete two iodinated hormones, T3 and T4. Only about 20% of circulating T3 is directly secreted by the thyroid; the remainder is produced by peripheral conversion of T4 to the more biologically active T3. The thyroid is the only endocrine gland that stores large quantities of hormone, with enough for a 100-day supply. Hormone production is regulated by a negative feedback loop involving the hypothalamic-pituitary-thyroid axis (Fig. 120.2). As the serum levels of T4 and T3 fall, the hypothalamus releases the tripeptide thyrotropin-releasing hormone (TRH), which in turn stimulates the anterior pituitary gland’s release of the polypeptide thyroid-stimulating hormone (TSH) from its thyrotroph cells. TSH then binds to epithelial cells on the thyroid gland, stimulating follicular cells to synthesize and secrete the thyroid hormones T4 and T3. TRH release may also result from exercise, stress, malnutrition, hypoglycemia, and sleep. The function of thyroid hormone is to influence the metabolism of cells by increasing their basal metabolic rate. It has a role in protein synthesis and functions together with other hormones necessary for normal growth and development. Of note, T3 and T4 increase the expression and sensitivity of β-adrenergic receptors, dramatically increasing response to endogenous catecholamines.

Pathophysiology T4 is a prohormone with only mild intrinsic activity; its deiodination produces T3, the biologically active hormone. More than 99.5% of thyroid hormones are protein-bound in the serum to thyroxine-binding globulin (TBG) and other proteins, rendering them metabolically inactive. As a result, only free T4 and free T3 are clinically relevant. Although iodide is a necessary substrate for thyroid hormone production, excess iodide can have two opposing effects. In the Wolff-Chaikoff effect, excess iodine inhibits the release of thyroid hormone from the gland by blocking iodide trapping and thyroglobulin iodination. This inhibition is transient, typically lasting only a matter of days. Iodide load can induce hyperthyroidism (Jod-Basedow effect) in some patients with multinodular goiter and occult Graves’ disease. Graves’ Disease.  Graves’ disease is the most common form of hyperthyroidism in the United States; autoantibodies bind to the TSH receptor and stimulate thyroid hormone production and release. Graves’ disease has a strong genetic relationship, with frequent occurrence in the setting of other autoimmune disorders and positive family history,2 and 20% of cases have been found to be related to environmental causes, such as smoking. Toxic Multinodular Goiter.  Toxic multinodular goiter is the second leading cause of hyperthyroidism in the United States. Itis characterized by multiple autonomously functioning nodules, usually in women older than 50 years. The hyperthyroidism in toxic multinodular goiter is milder than Graves’ disease and gradual in onset, but acute presentations can occur when iodine replacement is given to an iodine-deficient individual. Toxic Adenoma.  A toxic adenoma is a single hyperfunctioning nodule within the thyroid. It typically affects the same population as toxic multinodular goiter, but is less common. Thyroiditis.  Any inflammatory process that results in thyroid gland inflammation can lead to thyroiditis. The inciting process may be autoimmune, drug-induced, infectious, or traumatic. Inflammation leads to follicular cell breakdown, with resultant release of preformed thyroid hormone, causing acute thyrotoxicosis. The most common form of thyroiditis in the United States is Hashimoto’s thyroiditis, an autoimmune disorder characterized by the presence of thyroid antibodies and lymphocytic infiltration of the thyroid gland. Typically, patients present with a painless goiter and hypothyroidism, but some have transient thyrotoxicosis (hashitoxicosis) that may last a few months. Silent Thyroiditis.  Painless, or silent, thyroiditis is typified by a small nontender goiter and mild symptoms. It is more common in women than men, with a peak from age 30 to 40 years. It has an autoimmune cause and is seen more commonly in areas of adequate iodine intake.3 1557

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Anterior view External carotid a.

Hyoid bone

Superior thyroid a. and v.

Thyrohyoid membrane Thyroid cartilage (lamina) Median cricothyroid lig.

Common carotid a.

Cricothyroid mm. Cricoid cartilage

Internal jugular v.

Pyramidal lobe (often absent or small) Thyroid Right lobe gland Left lobe Isthmus

Middle thyroid v. Inferior thyroid a. Inferior thyroid vv.

Pretracheal lymph nodes Thyrocervical trunk

Vagus n. (X)

Subclavian a. and v. 1st rib (cut)

Vagus n. (X)

Left recurrent laryngeal n.

Right recurrent laryngeal n.

Superior vena cava Aortic arch

Fig. 120.1.  Anatomy of the thyroid gland and related structures. (Netter illustration from www .netterimages.com. Copyright Elsevier. All rights reserved.)

Hypothalamus TRH







Pituitary gland TSH 

T4 & T3

Thyroid gland T4

T3

T4 & T3

Peripheral tissues T4 T3 Fig. 120.2.  Negative feedback loop of thyroid hormone regulation— hypothalamic-pituitary-thyroid axis. Thyroid hormone production is  regulated by the hypothalamus and pituitary gland. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin (TSH) synthesis and secretion. In turn, TSH stimulates the production and release of thyroxine (T4) triiodothyronine (T3) from the thyroid gland. Once released, T4 and T3 exert a negative feedback mechanism on the production of TRH and TSH. T4 is converted to T3 in the peripheral tissues.

Postpartum Thyroiditis.  Of pregnant women, 5% to 10% will develop postpartum thyroiditis. The diagnostic triad consists of the lack of previous history of thyroid disorder, an abnormal TSH concentration during the first postpartum year, and the absence of TSH receptor antibodies or a toxic nodule. Typically, these patients have a triphasic course: (1) thyrotoxicosis, 2 to 6 months postpartum, although this phase may be asymptomatic;

(2) a hypothyroid state lasting 2 to 3 months; and (3) finally, a euthyroid state by the end of the first postpartum year. Although this triphasic course is classically described, many have only thyrotoxicosis (20%–30%) or hypothyroidism (40%). The recurrence rate in subsequent pregnancy is estimated at 70% in genetically predisposed women; some women have permanent hypothyroidism.4 Subacute Thyroiditis.  Subacute thyroiditis (de Quervain’s thyroiditis) is thought to be caused by a viral infection of the thyroid. It is manifested with a viral prodrome—fever, fatigue, myalgias, and pharyngitis— followed by anterior neck pain. Pain may radiate to the jaw, ears, or occipital area. The thyroid is exquisitely tender, and pain can occur with head movement or swallowing. During the acute painful phase, about 50% of patients have symptoms of hyperthyroidism (diaphoresis, palpitations, and tremor) lasting 3 to 6 weeks. These symptoms are usually mild. About one-third of patients will then have hypothyroidism for up to 6 months. Subacute thyroiditis occurs most commonly in the fourth and fifth decades of life and is more common in women. Suppurative Thyroiditis.  Suppurative thyroiditis is a rare but potentially life-threatening infection of the thyroid. Patients present with fever and anterior neck pain, neck swelling, induration, and erythema, as well as dysphonia and dysphagia. Infectious causes are overwhelmingly bacterial (aerobic and anaerobic) and very rarely parasitic, mycobacterial, or fungal.4 Most patients have preexisting thyroid disease and are immunocompromised (eg, AIDS). Drug-Induced Thyroiditis.  Amiodarone contains a high amount of iodine (37%, about 400 times the daily requirement) and, as a result, has a significant effect on thyroid function. It is

CHAPTER 120  Thyroid and Adrenal Disorders

estimated that between 5% and 20% of patients treated with amiodarone will develop thyrotoxicosis, higher in areas of iodine deficiency. Two proposed mechanisms have been described, an iodine-induced hyperthyroidism and drug-induced destructive thyroiditis.5 It is thought that the iodine load may unmask hyperthyroidism in patients with multinodular goiter and subclinical Graves’ disease. More commonly, the cytotoxic effects of amiodarone destroy thyroid cells, resulting in a release of preformed hormone. An exacerbation of the tachyarrhythmia for which the patient is being treated or heart failure is the typical presentation of a patient with thyrotoxicosis related to amiodarone. Other drugs that may induce thyroiditis include interferon alpha, highly active antiretroviral therapies, tyrosine kinase inhibitors, interleukin-2, and lithium. Lithium induces sporadic thyroiditis by direct toxic effects.3,6 Factitious Thyroiditis.  Thyrotoxicosis factitia results from the ingestion of thyroid hormone. Most cases involve medical personnel with psychiatric illness who surreptitiously selfadminister the medication. Cases of factitious thyrotoxicosis have also been reported in patients taking nutritional supplements that are marketed to improve thyroid function or aid in weight loss. In some cases, these supplements include doses of thyroid hormone beyond that which is typically prescribed, even with the recommended dose.7 Subclinical Hyperthyroid.  Subclinical hyperthyroid, identified by a low TSH and normal concentrations of free T4 and T3, has recently been identified as a risk factor for cardiovascular morbidity and mortality. These patients have overall increased mortality and are at risk for coronary heart disease, events, and atrial fibrillation.8

Clinical Features History and Physical Examination Hyperthyroidism induces a hypermetabolic state and increases β-adrenergic activity. The resulting clinical manifestations range from vague constitutional symptoms to more organ-specific symptoms (Box 120.1). Variables that affect the severity of disease include age and disease duration and do not necessarily correlate with the degree of biochemical abnormality. Altered mental status

BOX 120.1 

Symptoms of Thyrotoxicosis Constitutional: Weight loss despite hyperphagia, fatigue, generalized weakness Hypermetabolic: Heat intolerance, cold preference, excessive perspiration Cardiorespiratory: Palpitations, dyspnea, dyspnea on exertion, chest pains, poor exercise tolerance Gastrointestinal: Nausea, vomiting, diarrhea, dysphagia Neuropsychiatric: Anxiety, restlessness, hyperkinesis, emotional lability, confusion, insomnia, poor attention Neuromuscular: Myopathy, myalgias, tremor, proximal muscle weakness (difficulty getting out of a chair or combing hair) Ophthalmologic: Tearing, irritation, wind sensitivity, diplopia, foreign body sensation Thyroid gland: Neck fullness, dysphagia, dysphonia Dermatologic: Flushed feeling, hair loss, pretibial swelling Reproductive: Oligomenorrhea, amenorrhea, menometrorhaggia, decreased libido, gynecomastia, erectile dysfunction, infertility

and coma typify thyroid storm, the most severe manifestation of disease. Hyperthyroidism in older adults often manifests in more subtle ways, often asymptomatic or with nonspecific symptoms of weight loss, shortness of breath, and/or dementia. Older adults are more prone to cardiac manifestations and often present with atrial fibrillation; older adults who smoke or have higher circulating thyroid hormone levels appear to have more severe symptoms.9 Thyrotoxic periodic paralysis is manifested as a sudden and profound muscle weakness progressing to flaccid paralysis. It closely resembles familial hypokalemic periodic paralysis. Superior vena cava syndrome and dyspnea can occur as a result of the compression of vascular and tracheal structures by an enlarged thyroid. Dysphagia is common and can be due to compression of the esophagus by an enlarged thyroid gland or dysmotility related to thyrotoxic myopathy. Ophthalmopathy is a classic finding in Graves’ disease; it is thought to result in a proliferation of orbital fibroblasts differentiating into adipocytes and orbital infiltration of inflammatory cells. Patients subsequently present with diplopia, photophobia, tearing, grittiness, and pain because of corneal exposure, as well as eyelid edema, hyperemia, conjunctival hyperemia, and chemosis.10 Graves’ ophthalmopathy is also associated with restrictive extraocular myopathy, and exophthalmos. As the disease progresses, patients may experience restriction of their upward gaze from infiltration of the inferior rectus muscle and visual loss from optic nerve involvement (compression by inflamed, enlarged orbital contents).10 Physical examination findings of hyperthyroidism depend largely on age (Box 120.2). Younger patients typically present with signs of sympathetic stimulation, whereas older adults often lack the same adrenergic response and present with weight loss and fatigue, more consistent with apathetic hyperthyroidism.11 In Graves’ disease, patients uncommonly have classic pretibial myxedema, in which mucopolysaccharide infiltration of the dermis yields marked thickening of the pretibial skin. These lesions are confluent, painless, reddish raised nodules and plaques over the pretibial area and dorsum of the feet, often described as orange skin. Hyperpigmentation and induration are present, but pitting is absent. Pretibial myxedema is almost always associated with Graves’ ophthalmopathy.10 Tachycardia is the most common cardiac finding. Other findings include a widened pulse pressure, bounding peripheral pulses BOX 120.2 

Physical Findings in Thyrotoxicosis Vital signs: Tachycardia, widened pulse pressure, bounding pulses, fever Cardiac: Hyperdynamic precordium, systolic flow murmur, prominent heart sounds, systolic rub (Means-Lerman scratch), tricuspid regurgitation, atrial fibrillation, evidence of heart failure Ophthalmologic: Widened palpebral fissures (stare), lid lag, globe lag, conjunctival injection, periorbital edema, proptosis, limitation of superior gaze Neurologic: Fine tremor, hyperreflexia, proximal muscle weakness Psychiatric: Fidgety, emotionally labile, poor concentration Dermatologic: Warm, moist, smooth skin; rosy cheeks, blushing face; fine brittle hair; alopecia, flushed facies; palmar erythema; hyperpigmented pretibial plaques, nodules, or induration that is nonpitting; onycholysis (Plummer’s nails, separation of the distal portion of the fingernail from the nail bed) Neck: Diffuse symmetric thyroid enlargement, sometimes with a bruit and palpable thrill; thyroid with multiple irregular nodules or a prominent single nodule; tracheal deviation, venous prominence with arm elevation (Pemberton’s sign)

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Metabolism and Endocrinology

and, rarely, a friction rub heard along the left sternal border (Means-Lerman scratch). Atrial fibrillation is more common in older adults, with an incidence of 13% in patients older than 65 years with hyperthyroidism. Dilated cardiomyopathy may develop as a complication of a high cardiac output state. Patients can also develop primary pulmonary hypertension, sometimes associated with tricuspid regurgitation and right-sided heart failure., Increased activity at the sympathetic innervation of the eyelids leads to widening of the palpebral fissures, resulting in the characteristic stare and lid lag of thyrotoxicosis. Most hyperthyroid patients have an enlarged thyroid gland. Enlargement is common in patients with toxic multinodular goiter or Graves’ disease. However, many older adults with Graves’ disease have nonpalpable thyroids. Retrosternal enlargement can occur, making detection difficult while causing the obstructive symptoms discussed earlier. Facial and neck vein engorgement can be elicited when arms are elevated above the head, Pemberton’s sign. Negligible to moderate thyroid enlargement can be seen in patients with Hashimoto’s or painless thyroiditis (postpartum and sporadic). The thyroid gland in subacute thyroiditis is slightly enlarged and exquisitely tender. The addition of overlying erythema or warmth is seen in suppurative thyroiditis. The absence of thyroid enlargement should suggest exogenous (factitious) thyroiditis as well as ectopic thyroid hormone production, such as a hydatidiform mole or struma ovarii, an ovarian tumor composed of some thyroid tissue.

TABLE 120.1 

Diagnostic Criteria for Thyroid Storm CRITERIA FEVER (° F) 99–99.9

Diagnostic Testing The initial diagnosis is based on the clinical picture coupled with confirmatory laboratory values. Measurement of the serum TSH level is the most sensitive test for hyperthyroidism; a normal TSH level excludes hyperthyroidism, and an elevated TSH level is generally diagnostic for hypothyroidism. In thyrotoxicosis, the serum TSH concentration is depressed or undetectable (6 yr, same dose as for adult 200 mg bid × 3 days Should be avoided in young children

500 mg qid × 10 days 650 mg tid × 20 days

40 mg/kg/day in 4 doses × 10 days (max, 2 g/day) 40 mg/kg/day in 3 doses × 20 days

750 mg tid × 5 days

35–50 mg/kg/day in 3 doses × 5 days

ANISAKIASIS (Anisakis) Treatment of choice

Surgical or endoscopic removal

ASCARIASIS (Ascaris lumbricoides) Roundworm

DRUGS OF CHOICE • Mebendazole • Albendazole • Nitazoxanide • Ivermectin

BALANTIDIASIS (Balantidium coli) DRUG OF CHOICE • Tetracycline ALTERNATIVES • Iodoquinol • Metronidazole CUTANEOUS LARVA MIGRANS Creeping eruption

DRUG OF CHOICE • Ivermectin

200 µg/kg once daily × 1 or 2 days

DRUG OF CHOICE • Metronidazole

750 mg tid × 5–10 days

ALTERNATIVE • Thiabendazole

25 mg/kg/day (max, 750 mg/day) in 2 doses × 10 days

50–75 mg/day bid × 3 days

50–75 mg/kg/day in 2 doses × 3 days

Single dose of 400 mg; repeat after 2 wk Single dose of 100 mg; repeat after 2 wk

11 mg/kg once (max, 1 g); repeat after 2 wk Single dose of 100 mg; repeat after 2 wk

Day 1: 50 mg PO Day 2: 50 mg tid Day 3: 100 mg tid Days 4–21: 6 mg/kg/day in 3 doses

Day 1: 1 mg/kg PO Day 2: 1 mg/kg tid Day 3: 1–2 mg/kg tid Days 4–21: 6 mg/kg/day in 3 doses

Day 1: 50 mg PO Day 2: 50 mg tid Day 3: 100 mg tid Days 4–21: 9 mg/kg/day in 3 doses

Day 1: 1 mg/kg PO Day 2: 1 mg/kg tid Day 3: 1–2 mg/kg tid Days 4–21: 6 mg/kg/day in 3 doses

Dracunculus medinensis Guinea worm; worm also needs to be extracted

Enterobius vermicularis Pinworm

DRUGS OF CHOICE • Albendazole • Mebendazole

FILARIASIS (Wuchereria bancrofti, Brugia malayi) DRUG OF CHOICE • Diethylcarbamazine

Loa loa

DRUG OF CHOICE • Diethylcarbamazine

Continued

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Infectious Diseases

TABLE 125.3 

Drug Regimens for Treatment of Parasitic Infections—cont’d DOSAGE a

INFECTION

DRUG

Onchocerca volvulus

DRUG OF CHOICE • Ivermectin

ADULTS

CHILDREN

150 µg/kg PO once, repeated every 3–12 mo

150 µg/kg PO once, repeated every 3–12 mo

HERMAPHRODITIC FLUKE

Clonorchis sinensis (Chinese liver fluke)

DRUG OF CHOICE • Praziquantel

25 mg/kg/day in 4–6 doses × 1 day

25 mg/kg/day in 4–6 doses × 1 day

Fasciola hepatica (sheep liver fluke)

DRUG OF CHOICE • Bithionol

30–50 mg/kg on alternate days × 10–15 doses

30–50 mg/kg on alternate days × 10–15 doses

Fasciolopsis buski (intestinal fluke)

DRUG OF CHOICE • Praziquantel

25 mg/kg/day in 4 to 6 doses × 1 day

25 mg/kg/day in 4 to 6 doses × 1 day

Opisthorchis felineus

DRUG OF CHOICE • Praziquantel

25 mg/kg/day in 4 to 6 doses × 1 day

25 mg/kg/day in 4 to 6 doses × 1 day

Paragonimus westermani (lung fluke)

DRUG OF CHOICE • Praziquantel ALTERNATIVE • Bithionol

25 mg/kg/day in 4 to 6 doses × 2 days 30–50 mg/kg on alternate days × 10–15 doses

25 mg/kg/day in 4 to 6 doses × 2 days 30–50 mg/kg on alternate days × 10–15 doses

DRUG OF CHOICE • Metronidazole

250 mg tid × 5 to 7 days

ALTERNATIVES • Nitazoxanide or • Tinidazole

15 mg/kg/day in 3 doses × 5 to 7 days

500 mg bid × 3 days 2 g as a single dose

200 mg PO bid × 3 days (>4 yr) 50 mg/kg as a single dose

Giardiasis (Giardia lamblia)

HOOKWORM INFECTION (Ancylostoma duodenale, Necator americanus) DRUGS OF CHOICE • Albendazole or • Mebendazole or • Pyrantel pamoate

400 mg × one dose 500 mg × one dose 11 mg/kg (max, 1 g) × 3 days

500 mg × one dose 11 mg/kg (max, 1 g) × 3 days

Not indicated in those ≤12 yr 20 mg/kg/day IV or IM × 20–28 days

2.5 mg/kg/day PO × 28 days 20 mg/kg/day IV or IM × 20–28 days

0.25–1 mg/kg by slow infusion daily or every 2 days for 8 wk

0.25–1 mg/kg by slow infusion daily or every 2 days for 8 wk

LEISHMANIASIS

Leishmania braziliensis, Leishmania mexicana, Leishmania tropica, Leishmania donovani (kala-azar, black fever)

DRUGS OF CHOICE • Miltefosine or • Stibogluconate sodium ALTERNATIVE • Amphotericin B

MALARIA, TREATMENT OF (Plasmodium falciparum, P. ovale, P. vivax, P. malariae) All Plasmodium Species (Except Chloroquine-Resistant P. falciparum) Oral

DRUG OF CHOICE Chloroquine phosphate

Parenteral

DRUGS OF CHOICE • Quinine dihydrochloride or 20 mg/kg loading dose in 10 mg/kg Same as adult dose 5% dextrose during 4 hr, followed by 10 mg/kg during 2–4 hr q8h (max, 1800 mg/day) until oral therapy can be started • Quinidine gluconate or 10 mg/kg loading dose (max, 600 mg) Same as adult dose in normal saline slowly during 1–2 hr, followed by continuous infusion of 0.02 mg/kg/min for 3 days max • Artesunate for treatment failure or adverse reactions from quinidine or quinine (available from the CDC)

600 mg base (1 g), then 300 mg base (500 mg) 6 hr later, then 300 mg base (500 mg) at 24 and 48 hr

10 mg base/kg (max, 600 mg base), then 5 mg base/kg 6 hr later, then 5 mg base/kg at 24 and 48 hr

CHAPTER 125  Parasites

TABLE 125.3 

Drug Regimens for Treatment of Parasitic Infections—cont’d DOSAGE INFECTION

DRUG

a

ADULTS

CHILDREN

200 mg base (250 mg) IM q6h if oral therapy cannot be started

0.83 mg base/kg/hr × 30 hr continuous infusion or 3.5 mg base/kg q6h IM or SC

DRUGS OF CHOICE • Quinine sulfate plus • Doxycycline or • Clindamycin

650 mg tid × 3 days 100 mg bid × 7 days 900 mg tid × 3–5 days

25 mg/kg/day in 3 doses × 3–7 days

ALTERNATIVES • Mefloquine • Atovaquone-proguanil • Artemether-lumefantrine

1250 mg once 1000/400 mg qd × 3 days 4 tabs bid × 3 days

25 mg/kg once (45 kg, 1 tablet 250/100 mg qd 1 day before travel, each day in endemic region, and for 1 week afterward 100 mg daily during exposure and for >8 yr: 2 mg/kg/day PO, up to 100 mg/ 4 wk afterward day

SCHISTOSOMIASIS

Schistosoma haematobium

DRUG OF CHOICE • Praziquantel

20 mg/kg/day in 4–6 doses × 1 day

20 mg/kg/day in 4–6 doses × 1 day

Schistosoma japonicum

DRUG OF CHOICE • Praziquantel

20 mg/kg/day in 4–6 doses × 1 day

20 mg kg/day in 4–6 doses × 1 day

20 mg/kg/day in 4–6 doses × 1 day

20 mg/kg/day in 4–6 doses × 1 day

15 mg/kg once

20 mg/kg/day in 2 doses × 1 day

20 mg/kg/day in 4–6 doses × 1 day

20 mg/kg/day in 4–6 doses × 1 day

200 µg/kg/day × 1–2 days 50 mg/kg/day in 2 doses (max, 3 g/ day) × 2 days

200 µg/kg/day × 1 or 2 days 50 mg/kg/day in 2 doses (max, 3 g/day) × 2 days

Schistosoma mansoni

Schistosoma mekongi

DRUG OF CHOICE • Praziquantel ALTERNATIVE • Oxamniquine DRUG OF CHOICE • Praziquantel

Strongyloidiasis (Strongyloides stercoralis) DRUGS OF CHOICE • Ivermectin or • Thiabendazole

Continued

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SECTION Twelve 

Infectious Diseases

TABLE 125.3 

Drug Regimens for Treatment of Parasitic Infections—cont’d DOSAGE INFECTION

DRUG

a

ADULTS

CHILDREN

TAPEWORM INFECTION Adult (Intestinal Stage)

Diphyllobothrium latum (fish), Taenia saginata (beef), Taenia solium (pork), Dipylidium caninum (dog)

DRUG OF CHOICE Praziquantel

5–10 mg/kg once

5–10 mg/kg once

Hymenolepis nana (dwarf tapeworm)

DRUG OF CHOICE • Praziquantel

25 mg/kg once

25 mg/kg once

400 mg bid × 28 days, repeated as necessary

15 mg/kg/day × 28 days, repeated as necessary

50 mg/kg/day in 3 doses × 15 days

50 mg/kg/day in 3 doses × 15 days

200–400 mg tid × 3 days, then 400–500 mg tid × 10 days

Same as adult dose

Tapeworm Infection, Larval (Tissue) Stage

Echinococcus granulosus (hydatid cysts)

DRUG OF CHOICE • Albendazole

Echinococcus multilocularis— treatment of choice

Surgical excision

Cysticercus cellulosae (cysticercosis)

DRUG OF CHOICE • Praziquantel ALTERNATIVE • Surgery

Trichinosis (Trichinella spiralis)

DRUGS OF CHOICE • Steroids for severe symptoms plus • Mebendazole

TRICHOMONIASIS (Trichomonas vaginalis) DRUG OF CHOICE • Metronidazole

2 g once or 250 mg tid or 375 mg bid 15 mg/kg/day PO in 3 doses × 7 days PO × 7 days

TRICHURIASIS (Trichuris trichiura, WHIPWORM) DRUGS OF CHOICE • Mebendazole or • Albendazole

100 mg bid × 3 days 400 mg once

100 mg bid × 3 days 400 mg once

8–10 mg/kg/day PO in 4 doses × 120 days

1–10 yr: 15–20 mg/kg/day in 4 doses × 90 days 11–16 yr: 12.5–15 mg/kg/day in 4 doses × 90 days Same as adult dose

TRYPANOSOMIASIS

Trypanosoma cruzi (South American trypanosomiasis, Chagas’ disease)

DRUG OF CHOICE • Nifurtimox

Alternative • Benznidazole

Trypanosoma brucei gambiense, DRUG OF CHOICE Trypanosoma brucei rhodesiense • Suramin (African trypanosomiasis, sleeping sickness), hemolymphatic stage ALTERNATIVE • Pentamidine isethionate Late disease with central nervous system involvement

DRUG OF CHOICE • Melarsoprol (Trypanosoma brucei rhodesiense)

5–7 mg/kg/day × 30–120 days

100–200 mg (test dose) IV, then 1 g IV on days 1, 3, 7, 14, and 21

20 mg/kg on days 1, 3, 7, 14, and 21

4 mg/kg/day IM × 10 days

4 mg/kg/day IM × 10 days

2–3.6 mg/kg/day IV × 3 days; after 1 wk, 3.6 mg/kg/day IV × 3 days; repeat again after 10–21 days

18–25 mg/kg total during 1 mo; initial dose of 0.36 mg/kg IV, increasing gradually to max, 3.6 mg/kg at intervals of 1–5 days for total of 9 or 10 doses

CHAPTER 125  Parasites

TABLE 125.3 

Drug Regimens for Treatment of Parasitic Infections—cont’d DOSAGE INFECTION

DRUG

a

ALTERNATIVES (T. b. gambiense only) • Tryparsamide

• Eflornithine plus • Suramin

ADULTS

CHILDREN

One injection of 30 mg/kg (max, 2 g) Unknown IV every 5 days to total of 12 injections; course may be repeated after 1 mo 400 mg/kg/day in 4 doses x 14 days Same as adult dose injections; course may be repeated after 1 mo One injection of 10 mg/kg IV every 5 Unknown days to total of 12 injections; course may be repeated after 1 mo

VISCERAL LARVA MIGRANS Toxocariasis

DRUG OF CHOICE • Diethylcarbamazine ALTERNATIVES • Mebendazole or • Albendazole

6 mg/kg/day in 3 doses × 7–10 days

6 mg/kg/day in 3 doses × 7–10 days

100–200 mg bid × 5 days 400 mg bid × 3–5 days

Same as adult dose 400 mg bid × 3–5 days

a

Some drugs may be available only from the CDC Drug Service, Centers for Disease Control and Prevention, Atlanta; telephone, 404-639-3670 (nights, weekends, and holidays: 404-639-2888). CDC, Centers for Disease Control and Prevention; max, Maximum. Adapted from Drugs for parasite infections. Med Lett Drugs Ther 37:99–108, 1995.

peripheral edema, visual impairment, skin complaints, and symptoms related to the pulmonary, cardiovascular, and gastrointestinal (GI) systems.

Fever Fever is an important presenting symptom for a number of parasitic diseases. The most prevalent and medically devastating globally is malaria, with its classic history of recurring bouts of shaking chills and drenching sweats.

Malaria The febrile patient with shaking chills and a time-appropriate history of travel to an endemic region requires evaluation for malaria. Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, and Plasmodium knowlesi are the species responsible for human malaria. More than 41% of the world’s population lives in malaria-endemic areas (eg, parts of Africa, Asia, Oceania, Central America, and South America). The World Health Organization (WHO) has estimated that in 2013 malaria caused 198 million clinical episodes and 500,000 deaths. Most of these deaths would be caused by P. falciparum.1 Approximately 1500 cases of malaria are diagnosed yearly in the United States. The female Anopheles mosquito is the arthropod vector that transmits malaria after ingesting gametocytes from infected humans. The gametocytes reproduce in the gut of the mosquito; sporozoites are then released from the salivary glands of Anopheles into a human host during a blood meal. Sporozoites rapidly penetrate the liver parenchymal cells of their host. The protozoans, now termed cryptozoites or exoerythrocytic schizonts, multiply rapidly. Eventual lysis of the hepatic cells results in the release of merozoites into the bloodstream, which invade erythrocytes. In P. vivax and P. ovale infection, dormant hypnozoites can reside in hepatocytes; recrudescence of infections can occur many months to years later.

After invading red blood cells (RBCs), the merozoites transform into trophozoites, which feed on the hemoglobin in RBCs. Trophozoites mature into schizonts, which divide asexually into additional merozoites. The RBCs undergo lysis, releasing merozoites into the blood. Although some merozoites are destroyed by the host’s immune system, many enter new erythrocytes. After several repetitions of this erythrocytic cycle, the cyclic process changes, and male or female macrogametocytes may develop instead of merozoites. These gametes subsequently complete the reproductive cycle by fusion, which is accomplished sexually within the gut of a new female Anopheles mosquito after she has taken a blood meal from an infected host. Most people contract malaria after being bitten by an infected vector mosquito in an endemic region. Other mechanisms of transmission have been reported, including blood transfusions, injection drug use with contaminated syringes, maternal-fetal perinatal transmission, transmission from infected organs after transplantation (worsened by immunosuppression), and so-called airport malaria. This occurs when the infected mosquito is transported from the endemic region and released when the plane arrives, surviving long enough to transmit the parasite to a human host and then dying without establishing itself in its new location.2 Clinical Features.  All patients presenting from a region endemic for malaria with a fever or acute illness should be evaluated for the possibility of malaria. Most patients with malaria present with cyclic or irregular fevers. Other signs and symptoms include anemia, headache, nausea, chills, lethargy, abdominal pain, and upper respiratory complaints.3 The important difference between P. falciparum and the other malaria species is the capability of P. falciparum to cause severe organ system damage and death. RBCs infected with P. falciparum are rendered sticky and sludgelike in small arterioles and capillaries, causing ischemia in the host’s metabolically sensitive organs. The manifestations of acute falciparum infection include cerebral malaria with cerebral edema and encephalopathy,

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Infectious Diseases

hypoglycemia (especially in children), metabolic acidosis, severe anemia, which may lead to high output cardiac failure, renal failure, pulmonary edema, disseminated intravascular coagulation, and death. In chronic malaria, increased cellularity from the host’s exuberant immune response may lead to hepatosplenomegaly. Within the liver, parasites and malarial pigment distend the Kupffer cells. Parasitized RBCs also adhere to the sinusoidal system of the spleen, reducing its immunologic effectiveness. Anemia results from acute and chronic hemolysis. Blackwater fever—hemoglobinuria caused by severe hemolysis—may occur in patients with chronic or acute falciparum malaria. Diagnostic Testing.  Light microscopic examination of thick and thin blood films remains the gold standard for the diagnosis of malaria. The emergency clinician may have to view several slides and multiple fields to make the diagnosis if the parasite burden is small. Peripheral blood smears are stained with Giemsa or Wright stain and examined with ordinary light microscopy. The diagnosis can be made in a simply equipped laboratory. Even if the parasite is not visualized in the smear, treatment of malaria is indicated if the disease is suspected on clinical grounds. The US Food and Drug Administration (FDA) has approved the use of an antigen-based rapid diagnostic test for screening of patients. The Alere BinaxNOW kit provides qualitative testing for all four species and is available on the Internet for approximately $5 per test. The test is not as sensitive as microscopy, which should still be performed for all patients who have positive antigen test results to determine the species and severity of parasitemia. Management.  In the past, chloroquine phosphate was the treatment of choice for acute uncomplicated attacks of malaria. Resistance to chloroquine has been steadily increasing, and the drug is now recommended only in regions of known chloroquine sensitivity—Haiti, Dominican Republic, Central America, and limited regions of the Middle East. For uncomplicated malarial infections in patients from chloroquine-resistant regions, oral quinine is given with doxycycline or clindamycin. Another suitable alternative combination is proguanil-atovaquone. For complicated P. falciparum infection (eg, cerebral malaria, involvement of multiple organ systems, inability to tolerate oral medication), intravenous (IV) quinine (not available in IV form in the United States) or quinidine is used. Rapid infusion of IV quinine can cause profound hypoglycemia, as well as hyponatremia and coma vigil, a neurologic impairment due to high rates of parasite destruction. Patients should not receive IV quinine without cardiac monitoring. The artemisinin agents are excellent antimalarials and are available as enteral and parenteral preparations. They have a rapid onset of action and are well tolerated. An oral agent known as artemether-lumefantrine (Coartem) is now available for uncomplicated malaria. The other artemisinins are not approved for use in the United States; however, parenteral artesunate is available as an investigational drug for patients who have complicated malaria not responding to quinidine. To obtain this drug, contact the Centers for Disease Control and Prevention (CDC) Malaria Hotline at 770-488-7788 (or, during off hours, at 770-448-7100).4 Primaquine is used to eliminate the hepatic phases of P. ovale and P. vivax to prevent recrudescent disease. Primaquine therapy is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency because it can precipitate severe hemolysis. Untreated falciparum malaria can lead to coma and death; early treatment reduces morbidity and mortality.

Babesiosis Babesiosis is a malaria-like illness that is becoming increasingly prevalent in the northeastern United States (Babesia microti),

northwestern United States (Babesia gibsoni), and Europe (Babesia divergens). Babesiosis is particularly endemic to Long Island, Cape Cod, Martha’s Vineyard, Nantucket, and Block Island and, is suspected, along with ehrlichiosis and Lyme disease, in patients on Cape Cod, Block Island, and Long Island who present with the summer flu. The organism is a protozoan, similar in structure and life cycle to the plasmodia. It is transmitted by the deer tick Ixodes dammini, the vector of Lyme disease. Several cases have been attributed to transfusions with infected blood.5 Patients with babesiosis experience fatigue, anorexia, malaise, and emotional lability, with myalgia, chills, high spiking fevers, sweats, headache, and dark urine. Other manifestations include hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, elevated liver enzyme levels (particularly the transaminases), and signs of hemolysis, with hyperbilirubinemia and decreased haptoglobin. In an otherwise healthy person, the disease may remit spontaneously. In asplenic, older, and immunocompromised patients, especially patients with AIDS and those taking corticosteroids, up to 85% of RBCs may contain organisms. Clinical Features.  Clinical syndromes in these patients include massive hemolysis, jaundice, renal failure, disseminated intravascular coagulation, hypotension, and adult respiratory distress syndrome (ARDS). Diagnosis is based on clinical suspicion, multiple thin and thick blood smears (Babesia organisms resemble plasmodia in blood smears), and serologic testing (convalescent titers may not be positive for several weeks after infection). Management.  The treatment of choice consists of atovaquone plus azithromycin or, for severe illness, quinine plus clindamycin.6 Patients infected with B. divergens tend to be sicker and require more supportive care. Coinfection with Borrelia burgdorferi, the agent of Lyme disease, results in more severe and prolonged illness.

Other Parasites Other parasitic illnesses that commonly cause significant fever include schistosomiasis, fascioliasis, African and American trypanosomiasis, leishmaniasis, toxoplasmosis, and amebic liver abscess. Katayama fever may be the initial phase of schistosomiasis. Infected patients report brief exposures to fresh water in endemic areas. Clinical manifestations include spiking fevers, diaphoresis, wheezing, and cough. Eosinophilia is common.7 Fascioliasis, caused by the liver fluke Fasciola hepatica, is endemic throughout all the continents except Antarctica and is found in over 50 countries, especially where sheep or cattle are reared. Infection begins with ingestion of the metacercariae often found in watercress. Within 6 weeks, patients exhibit right upper quadrant abdominal pain, fever, and eosinophilia.8 American trypanosomiasis (Chagas’ disease) is endemic to Central and South America. The vector, the reduviid bug, sheds trypomastigotes in its feces proximal to the bite site. The host responds to local inflammation and infection by excoriating the site, inoculating the wound with trypomastigotes and initiating systemic spread. Acute Chagas’ disease begins with a chagoma, an infected and swollen bite site, often periorbital, and quickly progresses to fever, malaise, facial swelling, and pedal edema. Parasitization of cardiac muscle leads to the dysrhythmias and ventricular dysfunction that are classically found in late disease (chronic Chagas’ cardiopathy).9 Leishmaniasis is spread to humans by the sandfly and is found in the Middle East, India, East Africa, Brazil, and along the Mediterranean coast. Although leishmaniasis can involve the skin (cutaneous) and mucosa (mucosal), fever is seen only in visceral

CHAPTER 125  Parasites

leishmaniasis in immunocompetent persons. Signs and symptoms also include massive hepatosplenomegaly, neutropenia, and weight loss.10 The patient who has amebic liver abscesses from Entamoeba histolytica infection presents with high fevers, right upper quadrant pain, and elevated white blood cell count.11

Neurologic Symptoms Headache, altered mental status, and seizures are common presenting symptoms of parasitic infections caused by organisms that are neurotrophic. Some of the most common are malaria, cysticercosis, echinococcosis, and trypanosomiasis.

Cerebral Malaria Cerebral malaria is a common, life-threatening complication of P. falciparum infection. Parasitized RBCs express malarial cell surface glycoproteins called knobs that are sticky. They adhere to capillary walls, causing sludging in the cerebral microvasculature, localized ischemia, capillary leak, and petechial hemorrhages. Clinical Features.  Clinical manifestations include fever, altered mentation, including obtundation, coma, and occasionally seizures. A careful history and early diagnosis and therapy are essential to prevent severe morbidity and death. Management.  Treatment of cerebral malaria consists of IV quinine, quinidine, or artemisinin (if available), supportive care, including mechanical ventilation for comatose patients and patients with noncardiogenic pulmonary edema, antiepileptics, and correction of acidosis and hypoglycemia, associated with quinine use and cerebral malaria. The mortality rate is high, especially in children but, if the patient recovers, neurologic sequelae are rare. Corticosteroids, including dexamethasone, provide no benefit and can worsen outcomes in those with cerebral malaria.

because neurocysticercosis is commonly associated with acute obstructive hydrocephalus.

Echinococcosis Principles and Clinical Features.  Echinococcus granulosus is another tapeworm capable of causing CNS disease. Cerebral hydatid cysts are loculated structures containing E. granulosus scolices (heads) and the remains of the germinal epithelium, termed hydatid sand. Common types of exposure include ingestion of food or water contaminated by the ova from feces of sheep or cattle infected by the adult worm and close contact with an infected sheep-herding dog that is shedding ova. Infection results in the liberation of the embryo oncosphere into the small intestine. After penetrating the intestinal wall, the larvae travel through the bloodstream to multiple sites for encystment. The liver is the target organ in nearly two-thirds of cases, but 7% of patients have brain involvement; infected patients may present with seizures or focal neurologic signs. Diagnostic Strategies and Management.  The diagnosis of hydatid cyst disease is suggested by the appearance and localization of the cyst on ultrasound examination or CT scan. Serologic evaluation of serum or cerebrospinal fluid (CSF) may help confirm the diagnosis. Aspiration of the cyst should not be attempted because of the risk of seeding the host’s body with metastatic cysts. Treatment options include albendazole and surgical resection. Resection of the cyst may cause an anaphylactoid reaction if there is spillage of hydatid sand, which contains parasite antigenic proteins (Figs. 125.1 and 125.2).14

Cysticercosis Cysticercosis is caused by the larval form of Taenia solium, a common central nervous system (CNS) pathogen in many tropical areas. Cysticercosis is acquired by humans when they eat undercooked pork containing the larval cysts. The adult worm matures in the small intestine; the larval forms may penetrate through the gut wall and end up anywhere in the body. They are trophic for the CNS, muscle, and soft tissue. Clinical Features.  In the brain, clusters of larvae of T. solium form an expanding cyst that induces an intense immunologic reaction from the host, including inflammation, fibrosis and, ultimately, calcification. Neurologic abnormalities develop when neural tissue cannot accommodate the enlarging cyst. Seizure activity is often the first indication of cysticercosis, which should be considered in the differential diagnosis of new-onset seizures in adults. The diagnosis of T. solium infection is established by the finding of characteristic proglottids (gravid segments) or scolices (worm heads) in stool preparations. Diagnostic Strategies and Management.  Cranial computed tomography (CT) with contrast enhancement or magnetic resonance imaging may reveal an enhancing ring lesion. These lesions can mimic a CNS abscess, metastatic malignant disease, or primary tumor such as glioblastoma multiforme. Albendazole is the therapeutic agent of choice, and corticosteroids and antiepileptics are important adjunct medications during therapy, because CNS cysts can release highly antigenic inflammatory material at the time of treatment.12,13 Neurosurgical consultation is warranted

Fig. 125.1.  Hydatid cysts removed surgically.

Fig. 125.2.  Additional hydatid cysts removed surgically.

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African Trypanosomiasis African sleeping sickness is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. This infection is endemic in limited areas of West and East Africa. Several recent cases have been reported in travelers who have returned from safari in East Africa. The motile organisms are transmitted by the bite of the Glossina (tsetse) fly, which introduces the infective form of the trypanosome into the host’s blood. A small lesion or boil may develop and persist for several days. The flagellated organism travels throughout the bloodstream, invading the lymph nodes and spleen. Clinical Features.  Winterbottom’s sign, which is posterior cervical lymphadenopathy, usually is apparent at the time of initial treatment. The patient generally is febrile, and a maculopapular rash can be seen in fair-skinned people. Once the parasite invades the CNS, cerebral inflammation causes severe headache. Patients may display a change of mental status, psychiatric symptoms, and eventually extreme sleepiness and lethargy. Coma and death from starvation and trypanotoxins are inevitable in untreated patients.15 Diagnostic Strategies and Management.  An appropriate exposure history and characteristic symptoms should prompt the clinician to obtain diagnostic studies. Trypanosomes in peripheral blood, CSF, or lymph node and bone marrow aspirates establish the diagnosis. The presence of parasites in the CSF indicates advanced progression of the disease. Suramin sodium is the treatment of choice for early infection with T. b. rhodesiense. Pentamidine isethionate is the preferred treatment for early T. b. gambiense infection. Melarsoprol is used in CNS disease from T. b. rhodesiense; eflornithine is used in CNS disease from T. b. gambiense infection.

Other Parasites Several other parasitic infections can lead to CNS findings. CNS involvement with Trichinella spiralis has been reported in severe cases; larval migration of this parasite into the brain and meninges leads to meningitis, encephalitis, seizures, paresis, coma, and death. The pathophysiologic changes may reflect obstruction of small cerebral arterioles by migrating larvae, with subsequent vasculitis or cerebral edema resulting from inflammatory immunologic reaction to the larvae or larval fragments. Therapy for trichinosis with severe muscle or CNS involvement includes mebendazole or thiabendazole as well as steroids, which depress the host’s inflammatory response to infection.16 Amebic abscess of the brain or meningoencephalitis caused by E. histolytica is a rare complication of infection with this intestinal parasite. Infestation occurs after ingestion of amebic cysts. Spread of amebae to the brain or meninges from the colonized large bowel wall is rare but should be considered in any patient with amebiasis and subsequent neurologic impairment. The diagnosis may be made by microscopic identification of trophozoites (motile amebae) in CSF; however, biopsy of affected tissue is more specific. CNS amebiasis is treated with IV metronidazole but may require neurosurgical intervention. Naegleria and Acanthamoeba are free-living freshwater amebae that infect patients while they are swimming and diving in ponds and lakes. They invade the CNS through the olfactory neuroepithelium or compromised corneal epithelium that has been violated by abrasion or contact lens wear, leading to amebic meningoencephalitis. The pharmacologic regimen of choice is amphotericin B plus miconazole when these motile amebae are identified in CSF.17

Strongyloides stercoralis infection is a common disease in the tropics. The worm enters through the skin and migrates to the small bowel. Infection with Strongyloides is more clinically significant in immunosuppressed patients, who may suffer larval dissemination, with subsequent encephalitis and pyogenic meningitis. Strongyloides infection is treated with thiabendazole or albendazole. Ivermectin has recently been found to be as effective, with fewer side effects.18 Granulomas may occur in the brain from egg deposition by Schistosoma. In general, they do not cause major symptoms; however, several cases of transverse myelitis with paraplegia have been reported when the immunogenic and inflammatory eggs lodged in the spinal cord of infected patients.

Anemia Anemia in the traveler may reflect hemolysis from malaria, intestinal bleeding from hookworm or whipworm, or nutritional deficiency from tapeworm. These organisms have a profound effect on populations where the disease is endemic, but can also cause symptoms in travelers.

Malaria Malaria infection often is associated with anemia, especially in children younger than 5 years (Fig. 125.3). Anemia may develop quickly, from massive hemolysis in acute infection, or may have a more insidious onset, developing over months. Mature merozoites lyse parasitized RBCs. Uninfected RBCs undergo immune destruction from cell surface antibodies produced in response to parasiteassociated changes in RBC surface proteins. This process of destruction is abetted by increased reticuloendothelial activity. The reticulocyte response in infected persons is blunted by the inhibition of erythropoietin secretion. The antimalarial drug primaquine can precipitate hemolysis in patients who have G6PD deficiency, which is common in many Africans and some Asians.

Fig. 125.3.  Severe life-threatening anemia (hematocrit of 9) in a 5-yearold child in association with chronic malaria.

CHAPTER 125  Parasites

Whipworm and Hookworm Infestation by the whipworm Trichuris trichiura, and especially by the two human hookworms Necator americanus and Ancylostoma duodenale, is a major cause of iron deficiency anemia worldwide. Adult worms penetrate into intestinal mucosa and feed, causing significant luminal blood loss. The host’s feces contain eggs that mature in the soil through a rhabditiform larval form to the infective filariform larva. These larvae penetrate the human skin, usually through the feet. In trichuriasis, anemia is seen only with massive parasite infestation. Ova from the whipworm are ingested through food and water contaminated with feces. Diagnosis of these infections requires identification of characteristic ova in the stool. As with most helminthic infections, peripheral eosinophilia is common. Mebendazole or albendazole effectively controls trichuriasis and hookworm infections in adults and children.19 Anemic patients should be further worked up and receive iron supplementation.

Tapeworm Infection with the fish tapeworm Diphyllobothrium latum is associated with pernicious anemia. This tapeworm competes with the human host, absorbing vitamin B12 from the host’s intestine. When the host ingests raw freshwater fish that contains the embryo plerocercoid larvae in its muscle fibers, the large adult tapeworm develops in the human small intestine. The diagnosis is made by identification of the ova in the feces. Praziquantel is the drug of choice for adults and children.20

Peripheral Edema Lymphedema is classically associated with filarial infection, although it can also be associated with parasite-induced malnutrition and hypoproteinemia.

Elephantiasis Elephantiasis, or filariasis, is manifested in the host by the development of massive peripheral edema, with distention and thickening of the overlying epidermis, which acquires the appearance and texture of elephant skin. Elephantiasis is caused by infection with the filarial worm Wuchereria bancrofti or Brugia malayi. The infection is confined to humans and is widely distributed in the equatorial regions of the world, including Africa, Asia, South America, and Oceania. More than 90% of all infections are found in Asia, where the disease has reached epidemic proportions. Even in endemic regions in which most residents are infected, the disease is rare among travelers. Infected mosquitoes introduce microfilariae into the bloodstream of the human host during a blood meal. After infecting the host, the worms migrate into the lymphatic system and mature into coiled gravid adults. The adult worm triggers a robust inflammatory reaction in the lymphatic vessels, particularly in the lower extremities and genitalia. The macrophages, lymphocytes, plasma cells, giant cells, and eosinophils migrate to the inflamed and fibrotic lymphatic vessel, which becomes erythematous, edematous, and tender, suggesting the diagnosis of filariasis. Clinical Features.  Chronic manifestations of filariasis include fibrosis of a lymphatic vessel containing a dead or calcified worm. Subsequent mechanical blockage of the lymphatic system leads inevitably to severe lower extremity and genital edema accompanied by thickening of the skin. Recurrent cellulitis is common in these patients; prevention of superinfection requires meticulous skin care.

Diagnostic Strategies and Management.  The adult female worm produces microfilariae, which reach the peripheral blood through the lymphatics, whereupon the patient experiences shaking chills and fever. Thick peripheral blood smears may show infection, particularly at night, when the release of microfilariae is most common. Diethylcarbamazine rapidly clears the microfilariae from the peripheral blood and slowly sterilizes the gravid female nematode. Combined therapy with diethylcarbamazine and albendazole, or ivermectin and albendazole, may be more effective.21 Established elephantiasis of the scrotum can be successfully treated surgically. Chronic lymphatic obstruction of the limbs rarely responds to operative intervention.

Dermatologic Symptoms Dermatologic symptoms reflecting parasitic infection are more likely to be encountered by physicians working in countries where the organisms are endemic, but can be seen in the United States in tourists returning from the Caribbean, Central, and South America.

Cutaneous Leishmaniasis Cutaneous leishmaniasis is one of the most important causes of painless, chronic, ulcerating skin lesions in the world. Leishmania braziliensis and Leishmania mexicana are responsible for New World leishmaniasis; Leishmania tropica and Leishmania major commonly cause Old World leishmaniasis. The female Phlebotomus sandfly transmits the promastigotes during a blood meal, which are ingested by host macrophages and survive in their leishmanial form in the skin. Clinical Features.  Skin papules and nodules are seen early in the course of infection at the site of the insect bite. A raised macule also can appear, which subsequently develops painless central ulceration and a raised border. Lymphocyte and macrophage invasions of the epidermis and dermis cause the induration that occurs at the ulcer border. Secondary bacterial infections of these ulcers increase the associated scarring. L. braziliensis braziliensis (subspecies of L. braziliensis) attacks the mucocutaneous skin borders (ie, in tissues of the nose and mouth). Mutilation of the face occurs after massive tissue and nasal cartilage destruction. The larynx and trachea also can be involved, compromising the airway. Disseminated cutaneous leishmaniasis (L. mexicana amazonensis in South America and L. tropica aethiopica in Ethiopia) is characterized by diffuse nodules and papules resembling those of lepromatous leprosy (Fig. 125.4). Persons with this manifesta-

Fig. 125.4.  Cutaneous leishmaniasis.

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tion of leishmaniasis are thought to have a defect in their cellmediated immunity response. Diagnostic Strategies and Management.  Definitive diagnosis of leishmaniasis is made by direct visualization of the parasite with light microscopy. Diagnosis can also be made by an indirect fluorescent antibody test. Results of intradermal skin testing often are negative during the acute stages of the disease. Many forms of cutaneous leishmaniasis, especially L. tropica and L. mexicana infection, are self-limited and require no treatment unless the wounds become secondarily infected. Treatment options for advanced disease include sodium stibogluconate, meglumine antimonate, and amphotericin B. In 2014, the FDA approved the first oral medication, miltefosine, which can be used to treat leishmaniasis.22 These treatments are rarely initiated in the ED setting.

Dracunculiasis Principles and Clinical Features.  Dracunculus medinensis, the fiery serpent, is also referred to commonly as guinea worm disease (GWD). GWD appears in the host as the adult worm migrates through the subcutaneous tissues of the leg. The head of the gravid adult female erodes through the skin of the leg and releases larvae into the water when the host wades in a pond or open well. The larvae promptly infect the Cyclops water flea. Humans who drink water containing the infected crustacean complete the cycle of infection. The patient may complain of rash, intense pruritus, nausea, vomiting, dyspnea, and diarrhea before the female worm erupts through the skin. Management.  The classic treatment in developing countries has been to wind the worm around a stick and slowly extract the parasite from the skin during the course of 1 or 2 days. If the worm breaks while it is being extracted, the patient experiences an intense inflammatory reaction, with cellulitis along the worm track. The diagnosis is confirmed when microscopic larvae are found in the fluid of the cutaneous ulcer or when the adult female worm is identified extruding from the skin. The use of metronidazole to shorten the time of extraction is controversial. WHO has set a goal to eradicate this disease through public health awareness—encouraging the covering of wells, filtering well water to remove the fleas, and keeping infected persons with active skin lesions out of potable water. These efforts have had a tremendous impact on the eradication of dracunculiasis from Africa.23

Other Parasites Cutaneous larva migrans, the creeping eruption, occurs in the host’s epidermis when the skin is penetrated by Ancylostoma braziliense (dog or cat hookworm) larvae. Exposure usually occurs after walking barefoot or lying on beaches or other warm soil contaminated by animal feces. The diagnosis is suggested by the presence of a characteristic meandering erythematous track on the skin surface caused by larval migration. Visceral larva migrans occurs in young children after the ingestion of soil containing ova from the dog ascarid Toxocara canis. Thiabendazole, ivermectin, or albendazole may be used for treatment of cutaneous larva migrans, and antipruritics give symptomatic relief. Diethylcarbamazine treats visceral larva migrans. An alternative is thiabendazole.24 Swimmer’s itch is a dermatitis that occurs when skin is penetrated by the nonhuman schistosome of avians and mammals, usually from swimming in northern US freshwater lakes. The infection spontaneously resolves when the nonhuman schistosome is destroyed by the human host’s immune system. A similar

dermatitis also can occur after infection with schistosome species that are trophic for humans. Treatment is symptomatic. Strongyloides can cause a transient pruritic rash that may appear and then disappear within hours. Taenia solium can cause cysts in the soft tissues and muscles. These cysts often are an incidental finding. Onchocerciasis (from Onchocerca volvulus), which is common in West Africa and parts of South America, can cause severe pruritus and the development of nodules on bony protuberances.

Visual Symptoms Onchocerciasis Onchocerciasis is a major cause of blindness in the world. Of all cases, 95% occur in Africa. The parasite is found only in humans and is transmitted by the bite of the Simulium fly. These flies live near rivers—hence, the common name of the disease, river blindness. Microfilariae of O. volvulus are released by adult nematodes, which coil in subcutaneous nodules in the infected host; the microfilariae then migrate through the dermis and epidermis. The presence of adult worms stimulates a brisk immune response, including the infiltration of lymphocytes, macrophages, plasma cells, and eosinophils. Clinical Features.  The skin becomes chronically edematous and pruritic; it then atrophies, resulting in loose thin folds of skin. River blindness is more likely to develop in patients with nodules in proximity to the eyes. When the microfilaria dies during its migration in the eye, the foreign tissue that is deposited in the iris musculature incites an immune sclerosing keratitis, which is the major cause of the ocular destruction and subsequent blindness (Fig. 125.5). Diagnostic Strategies and Management.  The diagnosis of onchocerciasis requires the identification of characteristic microfilariae in skin snipped from the patient. Ivermectin is the therapeutic drug of choice. In many countries in which the disease is endemic, the manufacturers of ivermectin have donated the drug in an attempt to eradicate the disease.25 Surgical excision of the subcutaneous nodules is recommended when they are located on the head.

Loiasis Clinical Features.  Another filarial infection that causes ocular problems is loiasis. Loiasis is confined to forest areas in West and Central Africa. Transmission of Loa loa occurs through

Fig. 125.5.  Patient with onchocerciasis (river blindness).

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the bite of flies of the genus Chrysops. The edema initially associated with migration of the worm is called a Calabar swelling. The disease is caused by migration of the adult worm in the subcutaneous tissue. The adult worm occasionally migrates through the subconjunctival tissues of the eye and can be surgically excised from the conjunctiva. Although it is upsetting to the patient, the disease is generally fairly benign. The adult worm releases sheathed microfilariae into the peripheral bloodstream during the daytime. Diagnostic Strategies and Management.  Microfilariae can be detected in a thick blood smear, securing the diagnosis of loiasis. The treatment of choice for L. loa infection is diethylcarbamazine. Corticosteroids or antihistamines should be used to supplement specific chemotherapy because of the intense allergic reaction that occurs when the killed adult worms and microfilariae disintegrate.

Other Parasites Toxocara canis (dog roundworm) has a trophism for the host’s eyes. Toxocariasis is a roundworm infection found in urban dogs. Humans ingest eggs by the fecal-oral route. The larvae migrate and often enter the retina, where they become trapped. They stimulate an immune response that culminates in granuloma formation. These granulomas can impair vision and sometimes are mistaken for retinal tumors. There is no means of direct diagnosis except tissue biopsy. Although serologic tests are available, results need to be interpreted with caution. Infection is treated with albendazole and steroids; larvae visible in the retina can be destroyed with a laser. Toxoplasma gondii infection can precipitate a vitreal inflammation with retinal hemorrhages. Immunocompromised patients may have chorioretinitis and optic neuritis, with visual field defects and ocular palsies. Erythrocytes with sticky knobs from P. falciparum infection can cause retinal vascular congestion and ischemia with hemorrhage, exudate, infarction, and macular destruction. Cerebral malaria can produce cortical blindness. Mucocutaneous leishmaniasis can involve the eyelids, tear glands, retina, and/or iris and may result in total ocular destruction. Acanthamoeba can cause a dangerous keratitis in contact lens wearers. The patient complains of severe pain, tearing, and photophobia. Early infection may be misdiagnosed as herpetic keratitis. The infection may become chronic and necessitate keratoplasty for preservation of vision. Many different worms migrate to or through the eye, causing inflammation, tissue destruction, and blindness. Echinococcus and Cysticercus can initiate destructive cystic lesions in the eye.

Pulmonary Symptoms A number of parasitic infections may be associated with pulmonary symptoms, although the presence of pulmonary findings may not be sufficient to differentiate between various forms of parasitic diseases. Patients with P. falciparum malaria initially may seek treatment for fever and cough, further necessitating the consideration of malaria in travelers with apparent respiratory symptoms. Early in the course of treatment for severe malaria, noncardiogenic pulmonary edema or ARDS may develop, necessitating mechanical ventilation with positive end-expiratory pressure. E. histolytica can cause sympathetic pleural effusions, pulmonary or pleural involvement by direct extension or rupture of an amebic liver abscess, or direct hematogenous seeding of the lungs, leading to considerable additional morbidity and mortality among patients with underlying amebic infection. Pneumocystis pneumonia, caused by Pneumocystis jiroveci (formerly Pneumocystis carinii), is one of the most common

respiratory opportunistic infections seen in patients with HIV infection in the United States and Europe; surprisingly, however, it is responsible for less than 10% of pulmonary opportunistic infections in Africa and the developing world. The reason for this discrepancy is unclear. Many patients with AIDS in these countries die with CD4+ cell counts higher than those associated with P. jiroveci pneumonia in the United States.26 Löffler’s syndrome, characterized by persistent and nonproductive cough, substernal chest pain, wheezing, rales, pulmonary infiltrates on the chest radiograph, and marked eosinophilia, often is seen when larvae from the roundworm Ascaris lumbricoides, the hookworms N. americanus and A. duodenale, and the threadworm S. stercoralis transit the lungs as part of their developmental cycles. Ascaris larvae penetrate the small intestinal wall to gain entry into the small venules of the GI tract and then migrate to the lungs. Strongyloides and the hookworm filariform larvae penetrate through the skin of the feet, entering small cutaneous venules before migrating to the lungs. The pulmonary infiltrates and symptoms are transient, resolving within 2 weeks. Diagnosis depends on the discovery of larvae in sputum or gastric aspirates. Negative stool examinations initially are nondiagnostic because eggs do not appear in the stool for at least 1 month after initial infection. The patient’s immune response to the microfilariae of W. bancrofti and B. malayi is the cause of tropical eosinophilic pneumonia. Affected persons present with malaise, weight loss, new-onset nocturnal wheezing and asthma, shortness of breath, and chest discomfort. Chest radiographs may show nodular or interstitial infiltrates, consolidations, or cavitation. Microfilariae can be seen in lung biopsy material. Untreated infection may result in obstructive or restrictive lung disease. Patients have marked eosinophilia and elevations of serum immunoglobulin E levels. Paragonimus westermani and echinococcal species are trophic for the lungs in their human hosts. P. westermani eggs are shed in stool, hatch in fresh water and, as miracidia, infect a snail intermediary. After further development, cercariae are released from the snail, penetrating and encysting in freshwater crabs or crayfish. If the human host consumes raw or undercooked shellfish, the metacercariae excyst within the host’s duodenum, penetrating the duodenal wall into the abdominal cavity. The larvae migrate from the peritoneal cavity through the diaphragm into the pleural cavity, finally migrating to the lungs, where they cause hemorrhage, necrosis, and a granulomatous response. Early in the process, patients may have infiltrates and eosinophilia; later disease is marked by bronchiectasis, chronic bronchitis, fever, hemoptysis, and cachexia. Pulmonary nodules and cysts may cavitate. Many of these patients may have a positive result on purified protein derivative (PPD) testing, and their symptoms and chest radiographic findings may mimic those of tuberculosis.27 Sputum often is blood-streaked and flecked with dark brown particles containing ova. Finding of ova in sputum is diagnostic. Radiography, stool examination, and immune testing of sputum and blood are all helpful in making the diagnosis. Praziquantel is the therapeutic agent of choice. E. granulosus causes pulmonary hydatid cyst disease; the host remains asymptomatic until a cyst grows large enough to cause a mass effect, becomes superinfected, or leaks cyst material, which is highly immunogenic and causes a severe anaphylactoid reaction. Pulmonary hydatid cysts also can be associated with cough, expectoration of sandlike material, chest pain, and hemoptysis. Primary hydatid disease in the liver can metastasize to the lungs or brain. A thoracic CT scan may show a unilocular lung cyst; on a plain radiograph, a ruptured cyst is said to resemble a water lily, a pathognomonic finding. Cysts can be treated with careful surgical excision and pharmacotherapy. Early schistosomal disease, or Katayama fever, manifests with fever, cough, eosinophilia, and diffuse pulmonary nodules as the

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schistosomula pass through the lungs. In long-standing disease, ova shed from worm pairs can lodge in the vasculature of the lungs, causing pseudotubercles, granulomatous lung disease, pulmonary hypertension, and cor pulmonale. In patients with longstanding, latent, and asymptomatic S. stercoralis infections who are started on corticosteroids or immunosuppressive therapy, the helminth disseminates widely. Fatal, massive pulmonary infections with radiographic whiteouts and unsupportable respiratory failure have been reported in patients who have received organ transplants; this clinical disaster usually occurs in patients who emigrate from developing countries and receive organ transplants and immunosuppressive therapy without being evaluated for Strongyloides infection.28 Strongyloides pulmonary infection can cause wheezing and cough, leading to an initial misdiagnosis of bronchospasm and asthma. If the patient is given steroids, the strongyloides may disseminate, with markedly increased morbidity and mortality.28

Cardiovascular Symptoms Chagas’ Disease Trypanosoma cruzi infection often leads to acute and chronic myocarditis. T. cruzi is endemic in South and Central America and causes Chagas’ disease. The vector is the reduviid bug (kissing bug) that inhabits the walls and roofs of thatched dwellings built adjacent to a forest. Urban transmigration has expanded the epidemiologic scope of Chagas’ disease, previously a disease of rural populations. The disease is not seen commonly in travelers. The reduviid bug’s bite is no longer the only source of T. cruzi infection; transfusion with blood containing live trypanosomes from infected hosts has been a growing source of infection. Oral transmission also has been reported.28 The reduviid bug bites the patient, often around the eye, and excretes feces containing the trypomastigote of T. cruzi. The trypomastigote enters the inflamed bite wound or other mucosal or conjunctival surfaces, causing a local swelling called a chagoma. Romaña’s sign (painless unilateral periorbital edema) is pathognomonic but rarely seen. The trypomastigote migrates to trophic tissues, including smooth muscle, cardiac muscle, and autonomic ganglia in the heart, esophagus, and colon, causing local inflammation and tissue destruction. Clinical Features.  Acute infection is heralded by fever, facial and dependent extremity edema, hepatosplenomegaly, lymphadenopathy, malaise, lymphocytosis on peripheral blood smear, and elevated liver transaminase levels. At this stage, fatal left ventricular dysfunction and dysrhythmias are uncommon. Early illness lasts 1 to 2 months and resolves spontaneously, resulting in a latency known as the indeterminate phase, which can persist throughout the patient’s lifetime. In approximately 25% of cases, the infection progresses to chronic Chagas’ disease, principally with cardiomyopathy and GI pathology. Amastigotes invade cardiac muscle and the cardiac conduction system, causing chronic inflammation, mononuclear cell infiltration, and fibrosis. Patients whose disease involves the conduction system may present with atrial bradydysrhythmias, right and left bundle branch blocks, complete heart block, and ventricular dysrhythmias, including ventricular fibrillation. Cardiac muscle is replaced by fibrosis and scarring, leading to the development of right and left ventricular dysfunction and dilated cardiomyopathy. Mural thrombi are common. The first indication of long-standing asymptomatic infection can be thromboembolic disease, such as pulmonary embolism, stroke, or peripheral arterial embolism. Congestive heart failure is generally rapidly progressive and fatal within months unless treated with pharmacologic intervention and transplantation.29

Diagnostic Strategies.  Acute Chagas’ disease can be diagnosed by the presence of motile trypomastigotes in anticoagulated blood specimens. The organism also can be cultured in special liquid media. Chronic Chagas’ disease can be diagnosed by one of several serologic tests, including complement fixation, enzymelinked immunosorbent assay (ELISA), and indirect immunofluorescence testing. The assays are nonspecific, cross-reacting with malaria, syphilis, leishmaniasis, and some collagen vascular diseases. Polymerase chain reaction (PCR) technology has been improving and soon will provide the gold standard modality for diagnosis.30 Management.  Nifurtimox and benznidazole are used for treatment of T. cruzi infection. Cure rates rarely exceed 50%. The duration of treatment with nifurtimox is prolonged, and the drug has many serious side effects. Its production has been discontinued; however, it is the only antitrypanosomal medication available in the United States today (it can be obtained from the CDC by calling 404-639-2888). Benznidazole has fewer side effects. It is now recommended for indeterminate-phase treatment. Late complications of chronic diseases are modulated by autoimmune activity and do not respond to antiparasitic pharmacotherapy. Chronic Chagas’ disease of the heart, esophagus, or colon is treated symptomatically. Automated implantable cardioverterdefibrillators decrease the incidence of sudden death in infected patients.31 Patients receiving immunosuppressive therapy to prevent rejection after cardiac transplantation have developed recurrent disease in the transplanted myocardium.

Other Parasites Aberrant migration of Ascaris to the myocardium, causing myocarditis and pericardial effusions, has been well described. E. histolytica abscesses of the liver also may cause pericardial effusions if they erode through the diaphragm.

Gastrointestinal Symptoms Diarrhea Diarrhea is one of the most common symptoms for which travelers seek medical attention. Gorbach wrote that “Travel expands the mind and loosens the bowels.”32 Diarrhea also is the leading cause of death in children younger than 5 years in developing countries and a major source of morbidity for older children and adults. Most diarrheal disease is viral or bacterial; however, some clinically significant diarrheal disease is caused by parasites. Cryptosporidium parvum and Cyclospora cayetanensis are foodborne and waterborne coccidians that cause watery diarrhea. Both are particularly significant causes of morbidity in malnourished children and patients with AIDS. Cryptosporidial oocysts can be seen in stool when an acid-fast stain is used. ELISA and immunofluorescent assays of stool also are available for this organism. Paromomycin decreases diarrheal frequency in patients with AIDS who have cryptosporidial infections, who would have prolonged disabling symptoms without treatment. Cyclospora oocysts can be detected in stool samples with a Ziehl-Neelsen stain. Trimethoprim-sulfamethoxazole treats this infection.33 E. histolytica causes an invasive or inflammatory diarrhea. Patients complain of fever, tenesmus, abdominal pain, and watery stool containing blood and mucus. Untreated disease can progress to widespread colitis and perforation of the bowel wall, with peritonitis and death. Stool examination reveals mobile trophozoites containing ingested RBCs. Cysts noted on stool studies do not necessarily reflect active infection because there are nonpathogenic ameba species that can be found in the bowel of healthy adults. Immune assays of stool can now differentiate between E.

CHAPTER 125  Parasites

histolytica and these nonpathogenic ameba species. Serologic tests may be useful for an infected patient from a nonendemic region but patients will not have a positive test result for 1 month after initial infection. Metronidazole is the drug of choice for treatment of amebiasis. Balantidium coli is another protozoan that can cause invasive diarrhea. It has trophism for the terminal ileum, sometimes causing a clinical picture suggestive of appendicitis. Tetracycline and metronidazole are active against B. coli. Giardia lamblia can cause persistent diarrhea, abdominal bloating, cramps, flatulence, and significant weight loss. The organism is ingested and reproduces exponentially in the small bowel. In severe infection, the entire jejunum becomes covered with organisms, and the patient has malabsorption with steatorrhea. The organisms are rarely seen in fresh stool preparations because they quickly break down and become indiscernible. Accordingly, an antigen test often is used to confirm the diagnosis. Giardia has many animal reservoirs, including the beaver—thus the reference to beaver fever. Campers who drink unfiltered, “pure” mountain spring water in the United States commonly contract Giardia infection. Metronidazole, tinidazole, or nitazoxanide treats the disease.33 S. stercoralis, Capillaria philippinensis, T. trichiura, and Schistosoma have been associated with diarrhea. Hyperinfection or dissemination of Strongyloides can cause persistent diarrhea, weight loss, and abdominal pain. Trichuris causes diarrhea when the parasite load in the intestine is high. Schistosomiasis can cause a chronic granulomatous colitis, which may resemble inflammatory bowel disease, or an acute, bloody, febrile colitis associated with Katayama fever in the immunologically naïve patient. In chronic schistosomiasis, worm pairs in patients’ mesenteric and portal venous systems lay eggs that become ensnared in the liver, causing intense local inflammation, scarring, and the classic pipestem cirrhosis, with periportal fibrosis. Clinical manifestations in these patients include portal hypertension, ascites, and esophageal varices (Figs. 125.6 and 125.7). Upper GI bleeding is not as common as in patients with alcoholic cirrhosis; however, a large number of patients are infected with schistosomiasis in endemic regions, so variceal bleeding is an important cause of GI hemorrhage in these populations.

A. lumbricoides (roundworm) can cause significant persistent or recurrent abdominal pain in adults and partial intestinal obstruction in children with significant worm loads. Anthelmintics and conservative supportive therapy usually eliminate the problem, thereby avoiding surgical intervention. Clinicians diagnose ascariasis by identifying eggs in the stool. Patients with large worm loads may excrete adult worms, especially after therapy is started. Severe intestinal amebiasis can be complicated by colonic perforation and peritonitis.35 Angiostrongylus costaricensis, a nematode known as the rat lung worm, is common in Central America. Infected children may appear clinically to have Meckel’s diverticulum or acute appendicitis. Manifestations of the infection include nausea, vomiting, fever, abdominal pain localized to the right lower quadrant, and a tender mass. Surgical exploration may uncover abscesses, obstruction, or intestinal infarction. Anisakiasis is characterized by severe abdominal pain after the ingestion of raw fish (sushi and sashimi primarily). Anisakis marina, a nematode that burrows into the intestine, is the pathogen. The liver fluke Fasciola hepatica causes a syndrome that mimics that of viral hepatitis—right upper quadrant pain, fever, nausea and vomiting, jaundice, tender enlarged liver, and elevated transaminase levels. Patients also have eosinophilia and urticaria. Imaging studies, including CT, show the tracks of burrowing flukes. Serologic testing establishes the diagnosis; the patient’s stool may not contain eggs for several months after ingestion.36 Eggs of schistosomes become trapped in the portal venules, where they trigger an inflammatory response, leading to granulomatous liver disease, fibrosis, and cirrhosis. Hepatic granulomas also are seen in disseminated strongyloidiasis and aberrant biliary ascariasis. E. histolytica can cause hepatic abscesses. Affected patients typically do not have amebic dysentery and do not shed Entamoeba in their stool, but results of serologic studies are almost always positive. Patients have fever, weight loss, anorexia, and right-sided abdominal pain, but no jaundice. These patients are

Abdominal Pain Several parasites have been identified in the pathologic examination of appendices of patients diagnosed with tropical appendicitis. These infections have included enterobiasis, amebiasis, ascariasis, trichuriasis, and taeniasis.34

Fig. 125.6.  Pipestem cirrhosis with extensive ascites in a patient with chronic schistosomiasis.

Fig. 125.7.  Extensive ascites in a child, which may be from schistosomiasis or kala-azar (leishmaniasis).

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treated with metronidazole or tinidazole and a luminal amebicide, such as iodoquinol.37 E. granulosus produces hydatid cysts of the liver that on CT contain septations and so-called daughter cysts. Pharmacotherapy with albendazole and careful excision remain the treatments of choice. Leaking cyst material can initiate a severe anaphylactoid reaction in the host. Jaundice may result from hemolysis secondary to direct infection of RBCs with Plasmodium or Babesia or from biliary obstruction with pigmented stones. Ascaris can cause biliary colic, pyogenic cholangitis, pancreatitis, or liver abscess. Dead worms can be the nidus for gallstone formation. Biliary imaging and endoscopic retrograde cholangiopancreatography will show worms in the biliary tree. Mechanical removal by endoscopy combined with anthelminthic therapy is curative. Clonorchis sinensis and F. hepatica are trophic for the biliary tree. These worms can be present without producing symptoms for years before eventually precipitating cholecystitis, cholangitis, or cholangiocarcinoma.

Pruritus Ani Enterobius vermicularis, or pinworm, causes pruritus ani, a syndrome of intense perianal itch occurring primarily in children. Autoinfection is common because children (and adults) scratch the pruritic anal area and then bite their nails or put their fingers in their mouth. The worm has a worldwide distribution. Diagnosis is clinical and is confirmed by finding the small adult worms wiggling about on the anal verge. Eggs are rarely seen in the stool but can be visualized by the tape test—transparent tape touched to the perianal region collects eggs, which can be seen with light microscopy. Albendazole or mebendazole is the drug of choice.

PARASITIC CO-INFECTIONS IN PATIENTS WITH HIV INFECTION AND AIDS HIV infection and AIDS are prevalent in developing countries. Heterosexual transmission and perinatal transmission are common; young children and young adults of both genders are primarily infected. Patients presenting to the ED may be coinfected with HIV and any other infectious agent, including all the parasites discussed in this chapter. HIV co-infection may worsen the symptoms and outcome, alter the presentation, increase the virulence, or assist the infective process. AIDS causes abnormalities in almost every aspect of a host’s immune response to infection; cell-mediated immunity, which is important in combating parasitic infection, is most affected.37 The diagnosis and response to therapy of many parasitic infections are monitored serologically. HIV infection interferes with this response, rendering many of these tests unreliable. Therapies that are extremely effective in the normal host may be ineffective in a patient with HIV infection. Pharmacologic agents may have to be given for long periods or for the patient’s entire life.

Specific Parasites Malaria is not an opportunistic infection in patients with AIDS; however, many patients, especially children, with recurrent malaria and anemia from hemolysis have required transfusions from blood supplies not screened for HIV and have become infected.37 In regions where malaria is endemic, it is a common practice to treat most febrile patients with antimalarials. Some antimalarials are sulfonamides. Patients with AIDS have more severe allergic reactions to drugs, especially sulfonamides. Fever alone is not predictive of malaria in patients with AIDS; therefore, diagnosis should precede therapy. Patients with HIV infection are at greater risk for severe clinical manifestations of babesiosis.6 Visceral leishmaniasis is usually disseminated and fatal in patients with AIDS. Latent leishmanial infections may be reacti-

vated, and a prolonged febrile illness in an HIV-positive patient with a lifetime history of travel in leishmaniasis-endemic areas of the world should prompt consideration of this co-infection. Cutaneous infection also may become disseminated in these patients. Several clinical trials have been examining the role of chemoprophylaxis for leishmaniasis in HIV-positive persons who live in endemic regions. Chagas’ disease in the indeterminate phase can be reactivated in patients infected with HIV. These patients frequently have CNS involvement, with meningoencephalitis and severe myocarditis.31 Single-drug therapy may be insufficient because benznidazole penetration into the CSF is minimal. T. gondii infection is well recognized throughout the world as a common opportunistic infection of patients with AIDS, with a particular trophism for the CNS. The coccidial organisms Isospora belli, C. parvum, and C. cayetanensis have been associated with prolonged diarrhea in patients with AIDS. These organisms cause infections that are difficult to treat and are almost impossible to eradicate in these patients. The diarrhea is extremely debilitating and can be as profuse as that seen in cholera. E. histolytica has a high prevalence among homosexual men who practice unprotected anal intercourse; however, invasive amebiasis is not an opportunistic infection associated with HIV infection. Schistosomiasis enhances the pathogenesis of HIV infection and is more difficult to treat and eradicate in patients who are HIV-positive. S. stercoralis infection is more likely to be manifested as hyperinfection and disseminated disease in patients who are HIV-positive.28 In patients who are at risk for HIV infection and parasitic illness, it is essential to consider coinfection in the differential diagnosis.

KEY CONCEPTS • Parasitic diseases may manifest with almost any symptom or constellation of signs and symptoms. Accordingly, a travel history should be obtained from all patients with clinically significant signs and symptoms of unclear cause. The combination of presenting signs and symptoms and a history of recent travel to specific geographic regions can lead to early diagnosis and the initiation of pharmacotherapy, decreasing morbidity and mortality and increasing the probability of eradication of the infection. • Parasitic coinfections are particularly common in patients with HIV infection and AIDS. A travel history is essential because the clinical presentation may be atypical, morbidity and mortality are more severe, and treatment and eradication of the parasite are often prolonged. • Acute malaria should be suspected in patients with irregular high fevers associated with headache, abdominal pain, or respiratory symptoms. Falciparum malaria, which has a unique morphology easily identifiable on the peripheral blood smear, is the only species of malaria that causes coma and death. Furthermore, it is the most highly resistant to chemotherapy, demanding close observation and clinical follow-up of patients. Patients who are clinically ill or who are suspected of having falciparum malaria should be hospitalized for evaluation and treatment. • Cysticercosis should be considered in the differential diagnosis for new-onset seizures, especially in immigrants from Central and South America. • Giardiasis should be suspected in patients with diarrhea who have recently been camping or drinking unfiltered mountain spring water. Patients may have tolerated several weeks of severe bloating, flatulence, eructation, and weight loss without fever before seeking medical attention.

The references for this chapter can be found online by accessing the accompanying Expert Consult website.

CHAPTER 125  Parasites

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REFERENCES 1. World Health Organization: World Malaria Report, Geneva, 2013, World Health Organization, p 2013. 2. Wesolowski A, Eagle N, Tatem AJ, et al: Quantifying the impact of human mobility on malaria. Science 338:267–270, 2012. 3. Tatem AJ, Smith DL, Hanson S: International population movements and regional Plasmodium falciparum malaria elimination strategies. Proc Natl Acad Sci USA 107:12222–12227, 2010. 4. Rottman M, McNamara C, Yeung BKS, et al: Spiroindolones, a potent compound class for the treatment of malaria. Science 329:1175–1180, 2010. 5. Herwadt BL, Linden JV, Bosserman E, et al: Transfusion-associated babesiosis in the United States: a description of cases. Ann Intern Med 155:509–519, 2011. 6. Centers for Disease Control and Prevention: Parasites—babesiosis. . 7. Clerinx J, Van Gompel A: Schistosomiasis in travellers and migrants. Travel Med Infect Dis 9:6–24, 2011. 8. Berkhout BW, Lloyd MM, Poulin R, et al: Variation among genotypes in responses to increasing temperature in a marine parasite: evolutionary potential in the face of global warming? Int J Parasitol 44:1019–1027, 2014. 9. Rassi A, Jr, Rassi A, Marin-Neto JA: Chagas disease. Lancet 375:1388–1402, 2010. 10. Dorlo TP, Balasegaram M, Beijnen JH, et al: Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 67:2576–2597, 2012. 11. Mackey-Lawrence NM, Petri WA, Jr: Amoebic dysentery. BMJ Clin Evid 2011: 2011. 12. Mahanty S, Garcia HH: Cysticercosis and neurocysticercosis as pathogens affecting the central nervous system. Prog Neurobiol 91:172–184, 2010. 13. Garcia HH, Nash TE, Del Brutto OH: Clinical symptoms, diagnosis, and treatment of neurocysticercosis. Lancet Neurol 13:1202–1215, 2014. 14. Brunetti E, Kern P, Vuyitton DA: Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop 144:1–16, 2010. 15. Baer A, Libassi L, Lloyd JK, et al: Risk factors for infections in international travelers: an analysis of travel-related notifiable communicable diseases. Travel Med Infect Dis 12:525–533, 2014. 16. Murrell KD, Pozio E: Worldwide occurrence and impact of human trichinellosis, 1986-2009. Emerg Infect Dis 17:2194–2202, 2011. 17. Visvesvara GS: Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis 23:590–594, 2010. 18. Bisoffi Z, Buonfrate D, Angheben A, et al: Randomized clinical trial of ivermectin versus thiabendazole for the treatment of strongyloidiasis. PLoS Negl Trop Dis 5:e1254, 2011. 19. Namwanje H, Kabatereine NB, Olsen A: Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda. Trans R Soc Trop Med Hyg 105:586–590, 2011. 20. Kuchta R, Brabec J, Kubáčková P, et al: Tapeworm Diphyllobothrium dendriticum (Cestoda)—neglected or emerging human parasite? PLoS Negl Trop Dis 7:e2535, 2013.

21. Nutman TB, Kazura J: Lymphatic filariasis. In Guerrant R, Walker DH, Weller PF, editors: Tropical infectious diseases: principles, pathogens and practice, ed 3, Philadelphia, 2011, Saunders Elsevier. 22. Dorlo TP, Balasegaram M, Beijnen JH, et al: Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 67:2576–2597, 2012. 23. Hopkins DR, Ruiz-Tiben E, Eberhard ML, et al: Progress toward global eradication of dracunculiasis—January 2013-June 2014. MMWR Morb Mortal Wkly Rep 63: 1050–1054, 2014. 24. The Medical Letter: Drugs for parasitic infections, ed 3. . 25. African Programme for Onchocerciasis Control: progress report, 2013-2014. Wkly Epidemiol Rec 89:551–560, 2014. 26. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents: Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. . 27. Kanpittaya J, Sawanyawisuth K, Vannavong A, et al: Different chest radiographic findings of pulmonary paragonimiasis in two endemic countries. Am J Trop Med Hyg 83:924–926, 2010. 28. Mejia R, Nutman TB: Screening, prevention, and treatment for hyperinfection syndrome and disseminated infections caused by Strongyloides stercoralis. Curr Opin Infect Dis 25:458–463, 2012. 29. de Noya BA, González ON: An ecological overview on the factors that drives to Trypanosoma cruzi oral transmission. Acta Trop 151:94–102, 2015. 30. Schijman AG, Bisio M, Orellana L, et al: International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA blood samples from Chagas disease patients. PLoS Negl Trop Dis 5:e931, 2011. 31. Sabino EC, Ribeiro AL, Salemi VM, et al: National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II (REDS-II), International Component: Tenyear incidence of Chagas cardiomyopathy among asymptomatic Trypanosoma cruziseropositive former blood donors. Circulation 127:1105–1115, 2013. 32. Soonawala D, Vlot JA, Visser LG: Inconvenience due to travelers’ diarrhea: a prospective follow-up study. BMC Infect Dis 11:322, 2011. 33. Rossignol JF: Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol 124:45–53, 2010. 34. Omotoso AJ, Nnoli MA, Bassey IE, et al: Histopathological analysis of appendectomy specimens in Calabar, south-southern Nigeria. IOSR-JVSP 2:42–46, 2013. 35. Diemert DJ: Ascariasis. In Guerrant R, Walker DH, Weller PF, editors: Tropical infectious diseases: principles, pathogens and practice, ed 3, Philadelphia, 2011, Saunders Elsevier. 36. Mahanty S, Maclean JD, Cross JH: Liver, lung, and intestinal fluke infections. In Guerrant R, Walker DH, Weller PF, editors: Tropical infectious diseases: principles, pathogens and practice, ed 3, Philadelphia, 2011, Saunders Elsevier, p 854. 37. UNAIDS: The Gap Report. , 2014.

CHAPTER 125: QUESTIONS & ANSWERS 125.1. A 33-year-old man presents with irregular fevers, shaking chills, intermittent abdominal pain, and fatigue. The fever comes in cycles during approximately 2 or 3 days. He has no medical history and takes no medications. He works as a baggage handler in Miami, Florida. Physical examination reveals a low-grade fever and mildly tender hepatosplenomegaly. Laboratory evaluation is remarkable for hemoglobin 9.6 g/dL, leukocytosis, lactate dehydrogenase 1850 IU/dL, elevated bilirubin, and urine dipstick “blood positive” but no red blood cells or white blood cells. He has had no international travel. Peripheral smear reveals few possible parasites with fragmented red blood cells. What is this patient’s most likely infection? A. Babesiosis B. Early sepsis C. Leishmaniasis D. Lyme disease E. Malaria Answer: E. Airport malaria has been reported in people who have never been in endemic areas but who work in or live near an international airport. The infected mosquito is transported from the endemic region and released when the plane arrives. Babesiosis is a parasitic illness with a clinical picture like that of malaria. It is tickborne and is endemic in the northeastern United States.

125.2. A 21-year-old Hispanic male immigrant presents with new onset of seizures. Paramedics report a right upper extremity focused seizure with loss of consciousness and postictal period of approximately 20 minutes. He has had no previous seizures, symptoms, medications, trauma, or ingestions. Laboratory examination is normal except for HCO3− 17 mmol/L. Which of the following statements regarding the most likely cause of this patient’s seizures is TRUE? A. A ring-enhancing lesion suggests HIV infection. B. Albendazole may be effective. C. Contaminated beef ingestion should be suspected. D. The stool examination will likely be negative. E. There is no role for corticosteroids. Answer: B. Taenia solium infection (cysticercosis) results from contaminated pork ingestion. The larvae penetrate the small intestine and may travel anywhere, with brain, muscle, and soft tissue being the likely areas of cyst occurrence with accompanying inflammatory reaction. The enlarging cyst (often a ring-enhancing lesion) causes the symptoms. Stool examination is diagnostic. Albendazole and corticosteroids are indicated for the central nervous system lesion. Postseizure acidosis is common and generally clears within 1 hour.

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PART III 

Medicine and Surgery  | 

SECTION Twelve 

Infectious Diseases

125.3. Fever, headaches, and posterior cervical adenopathy in a recent African traveler should suggest which of the following? A. Central nervous system amebiasis B. Cysticercosis C. Falciparum malaria D. Schistosomiasis E. Trypanosomiasis Answer: E. Trypanosomiasis causes central nervous system inflammation and headache that may progress to psychiatric symptoms, lethargy, and coma. The posterior cervical adenopathy in this scenario is called Winterbottom’s sign. 125.4. A macrocytic anemia would suggest infection from which parasite? A. Ancylostoma duodenale B. Diphyllobothrium latum C. Falciparum malaria D. Necator americanus E. Whipworm Answer: B. The fish tapeworm is associated with pernicious anemia. Hookworm and whipworm are associated with gastrointestinal iron loss and microcytic anemia. Malaria causes hemolytic anemia. 125.5. A 42-year-old man from Ethiopia presents with complaints of skin nodules and skin ulcerations. He has no known past illnesses, exposures, medication use, or systemic symptoms. Examination is remarkable for four 2- or 3-cm cutaneous ulcers on the arms and legs and scattered 1-cm nodules. Vital signs are normal, and physical examination is otherwise unrevealing. Which of the following statements regarding this infection is TRUE? A. Respiratory tract symptoms would suggest an alternative diagnosis. B. The lesions always require treatment. C. The lesions are likely painful to touch. D. The skin pattern may be confused with leprosy. E. This infection does not affect mucocutaneous areas. Answer: D. Leishmaniasis is transmitted by the sandfly bite. Skin papules and macules develop at bite sites. These may ulcerate into painless ulcers. A microcutaneous variant may be seen, and the inflammatory process may involve the larynx and trachea. Disseminated cutaneous leishmaniasis may resemble lepromatous leprosy. 125.6. Parasite-induced loss of vision would be suggested by which of the following? A. Cardiomegaly B. Edematous and pruritic skin C. Fever D. Hepatosplenomegaly E. Iron deficiency anemia Answer: B. Onchocerciasis is a major cause of blindness worldwide. Ninety-five percent of cases occur in Africa. The biting flies are found near rivers, and humans are the only host for the parasite. It occupies the skin, resulting in pruritus, edema, and later atrophy with redundant skin folds. The following are other causes of parasite-induced visual loss: Toxoplasma can cause retinal hemorrhages, Toxocara can cause inflammatory retinal granulomas, and Acanthamoeba may cause a keratitis in contact lens wearers.

125.7. Which of the following is the correct association between the type of parasitic infection and pulmonary symptoms? A. Hookworm—positive PPD response B. Leishmaniasis—pulmonary nodules C. Löffler’s syndrome—ascariasis D. Pneumocystis—90% of opportunistic infections in Africa E. Whipworm—anaphylaxis Answer: C. Ascariasis and hookworm may cause Löffler’s syndrome of chest pain, fever, rales, wheezing, and eosinophilia. The following are the other correct associations: Pneumocystis—less than 10% of pulmonary opportunistic infections in Africa Paragonimus westermani—positive tuberculin skin test response and chest radiograph resembling tuberculosis Echinococcus—anaphylaxis from leakage of cystic contents Schistosomiasis—diffuse pulmonary nodules (Katayama fever) 125.8. Which of the following statements regarding AIDS and parasitic infections is TRUE? A. AIDS patients have more severe reactions to antiparasitic agents. B. Diarrheal illness is reliably eradicable. C. Invasive amebiasis is an opportunistic infection. D. Malaria is an opportunistic infection. E. Parasitic illnesses do not enhance the pathogenesis of HIV infection. Answer: A. Isospora and coccidial organisms may cause an almost cholera-like diarrheal illness. Eradication is very difficult. Malaria and invasive amebiasis are not considered opportunistic infections. AIDS patients have much more severe allergic manifestations to the antiparasitics. Schistosomiasis enhances HIV pathogenesis. 125.9. A 34-year-old man presents with 2 weeks of fever with temperature of up to 102° F, anorexia, and 5-pound weight loss. He had recently been traveling in Central America in Belize, Nicaragua, and Guatemala. He had done some camping but mostly stayed in hostels. He never had nausea, vomiting, or diarrhea. His physical examination is noteworthy only for right upper quadrant tenderness and a palpable liver edge. He is not icteric or jaundiced and denies chalky stools or dark urine. He has a white blood cell count with a left shift. His transaminases are elevated, but otherwise his laboratory results are relatively normal. Stool examination for ova and parasites is negative. Hepatitis panel was sent but is still pending. What is the most likely diagnosis? A. Entamoeba histolytica infection B. Fasciola hepatica infection C. Hepatitis A D. Hepatitis B E. Schistosoma mansoni infection Answer: A. Entamoeba histolytica infection with a hepatic abscess. E. histolytica can cause hepatic abscesses. Affected patients typically do not have amebic dysentery and do not shed Entamoeba in their stool, but results of serologic studies almost always are positive. Patients have fever, weight loss, anorexia, and right-sided abdominal pain but no jaundice. Treatment is with metronidazole or tinidazole and a luminal amebicide, such as iodoquinol.

CHAPTER 125  Parasites

125.10. A 26-year-old female medical student presents with a 3-month history of diarrhea and a 20-pound weight loss. She has not had fevers, chills, cough, headache, or rash. Four months ago, she had done a rotation in Nepal working at a rural health clinic associated with an American medical school. Toward the end of her rotation, she began to develop diffuse abdominal bloating and discomfort. This was accompanied by flatulence and intermittent watery diarrhea. She felt like she had swallowed a basketball and all of her pants were “too tight.” “I thought I was pregnant, but my tests were all negative.” She had lost her appetite and was very worried by the weight loss. The results of her laboratory tests, including complete blood count, Chem-20, and stool for ova and parasites, were negative. What is the most likely diagnosis? A. Cryptosporidium parvum or Cyclospora cayetanensis infection B. Entamoeba histolytica infection C. Giardia lamblia infection D. Salmonella typhi infection E. Shigella dysenteriae infection Answer: C. Giardia lamblia can cause persistent diarrhea, abdominal bloating, cramps, flatulence, and significant weight loss. The organism is ingested and reproduces exponentially in the small bowel. In severe infection, the entire jejunum becomes covered with organisms, and the patient has malabsorption with steatorrhea. The organisms are rarely seen in fresh stool preparations because they quickly break down and become indiscernible. Accordingly, an antigen test often is used to confirm the diagnosis. Giardia has many animal reservoirs, including the beaver. Campers who drink unfiltered, pure mountain spring water in the United States commonly contract Giardia infection. Metronidazole, tinidazole, or nitazoxanide treats the disease. 125.11. A 64-year-old man recently emigrated from Laos is referred to the emergency department for fever, hemoptysis, anorexia, positive PPD response, and chest radiograph with several cavitary lesions. He had been

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started on a three-drug regimen for presumptive tuberculosis but seems to be getting worse. Several sputum samples had not grown out mycobacteria. He immigrated to the United States from Laos 6 months ago. He had lived in a rural district and worked farming rice before emigration. Through a translator, he reported having several bouts of pneumonia in the last year treated with antibiotics in Laos, but he never really got any better. He has had a persistent cough, which has gotten worse with recent hemoptysis. He has lost more than 20 pounds and appears cachectic and ill. Physical examination of the lungs reveals scattered rhonchi, rales, and wheezes. His complete blood count shows 12% eosinophils. What is the most likely diagnosis? A. Löffler’s syndrome from Ascaris lumbricoides infection B. Multiply drug resistant mycobacteria C. Paragonimus westermani infection D. Pseudomonas pseudomallei infection E. Tropical eosinophilic pneumonitis from Wuchereria bancrofti infection Answer: C. Paragonimus westermani is trophic for the lungs in their human hosts. If the human host consumes raw or undercooked shellfish, the metacercariae excyst within the host’s duodenum, penetrating the duodenal wall into the abdominal cavity. The larvae migrate from the peritoneal cavity through the diaphragm into the pleural cavity, finally migrating to the lungs, where they cause hemorrhage, necrosis, and a granulomatous response. Early in the process, patients may have infiltrates and eosinophilia; later disease is marked by bronchiectasis, chronic bronchitis, fever, hemoptysis, and cachexia. Pulmonary nodules and cysts may cavitate. Many of these patients may have a positive result on purified protein derivative (PPD) testing, and their symptoms and chest radiographic findings may mimic tuberculosis. Sputum often is blood streaked and flecked with dark brown particles containing ova. Finding of ova in sputum is diagnostic. Radiography, stool examination, and immune testing of sputum and blood are all helpful in making the diagnosis. Praziquantel is the therapeutic agent of choice.

C H A P T E R 126 

Tickborne Illnesses Edward B. Bolgiano  |  Joseph Sexton

OVERVIEW Ticks are hematophagous parasites of humans and animals, distributed worldwide. They transmit rickettsial, bacterial, spirochetal, viral, and protozoal diseases and cause disease by means of their own toxins (Table 126.1). As vectors of human disease, ticks rank second in importance only to mosquitoes. Although it is generally understood that people who travel during the summer months may return from endemic areas with tickborne disease, increasing reports of infection acquired within urban areas emphasize the need to consider tickborne illness, even in the absence of a history of travel to high-risk areas. In addition, tularemia and Q fever are now considered by the Centers for Disease Control and Prevention (CDC) to be significant threats during biologic warfare. For this reason, research involving ticks and tickborne diseases has become increasingly important. Reports on ticks, their feeding habits, and their possible relation to disease can be found from early human history. Pliny (ce 77), in Historia Naturalis, referred to “an animal living on blood with its head always fixed and swelling, being one of the animals which has no exit [anus] for its food, it bursts with over-repletion and dies from actual nourishment.”1 Tickborne illness was first recognized on the North American continent by Native Americans. According to legend, Shoshone men avoided the evil spirits that caused illness by sending only women into certain areas of the Rocky Mountain region known to be especially hazardous. The causative association of the tick vector with Rocky Mountain spotted fever (RMSF) was noted by missionaries and early settlers, who named the affliction tick fever, and physicians in Idaho and Montana recorded the classic clinical descriptions of the disease in 1899.

Identification of Ticks Ticks are arthropods but not insects. They have eight legs instead of six and generally two fusing body parts—a capitulum (head) and opisthosoma (abdomen)—instead of three. Identification of an arthropod as a tick and subsequent categorization into family and some genera are not difficult (Figs. 126.1 and 126.2). Speciation requires a trained acarologist. However, tick identification has limited importance in clinical decision making. Color, which varies seasonally, and size, which varies by amount of blood ingested at the time of presentation, are unreliable criteria for identification purposes.

Physiology of Tick Feeding An understanding of the physiology of feeding in arthropods is more essential than species identification when assessing the risks of transmission of diseases. Blood-sucking arthropods are divided into two groups according to their method of acquiring blood. The solenophagic feeders insert their mouthparts directly into capillaries to obtain blood. Telmophagic feeders insert their mouthparts indiscriminately, lyse tissue along with capillaries,

and feed on the resultant pool of blood, extracellular fluid, and tissue. Ticks and deer flies, for example, are telmophagic feeders, whereas mosquitoes are mostly solenophagic. Argasid ticks (soft-bodied ticks) are short, rapid feeders with preformed distensible endocuticles. They therefore need to feed for only minutes to hours to acquire a full meal. As a result, they tend to be found in nests and burrows where their hosts visit frequently. The genus Ornithodoros is the vector for relapsing fever. Ixodid ticks (hard-bodied ticks) include the genera Ixodes, Dermacentor, Amblyomma, and Rhipicephalus, which are those responsible for the remainder of human tickborne diseases in the United States discussed in this chapter. These ticks need to form a new exocuticle (phase I of feeding) and thus feed slowly during the first 12 to 24 hours. Once it is fully formed, the new endocuticle allows rapid feeding (phase II) and significant engorgement. In the capitulum of ticks, the sucking structure, consisting of the chelicerae, is surrounded by a sheath from which it protrudes during feeding. When a suitable location is found, adjacent cheliceral digits incise the skin, and the chelicerae and barbed hypostome are inserted. Two mechanisms prevent the tick from being removed from the skin—the barbed hypostome and a cement-like salivary secretion from the base of the hypostome, composed of lipoproteins and glycoproteins. This allows ixodid ticks to remain attached for as long as 2 weeks. Because argasids are much faster feeders, they secrete no cement substance. During a bite, trauma and salivary gland products can cause local inflammation, hyperemia, edema, hemorrhage, and skin thickening. The saliva injected during feeding contains many different substances. Hard and soft ticks produce a histolytic secretion that liquefies tissue, which is then sucked into the gut. Eventually, the secretion breaks down the walls of the dermal blood vessels and the released blood is ingested. To prevent hemostasis, the saliva contains a thrombokinase inhibitor, apyrase, which prevents platelet aggregation by depleting adenosine diphosphate, prostaglandin E2, and prostacyclin (prostaglandin I2) to prevent vasoconstriction, and cytolysins. Ixodes scapularis also secretes a carboxypeptidase that destroys other inflammatory mediators, such as anaphylatoxins and bradykinin, as well as anti– complement C3 factor. These other mediators normally would cause further inflammation, which would enhance hemostasis. All infectious agents and excretory liquids from some argasids are transmitted through this saliva. Transmission of a disease from Ixodes ticks is unlikely if the tick is not yet engorged with blood at the time of removal. Likewise, a tick removed within a few hours after attachment is unlikely to transmit disease. The neurotoxins responsible for tick paralysis also are found in tick saliva. The local physiologic changes associated with tick feeding produce the characteristic 1- to 4-mm erythematous mark typically seen on the skin after a tick bite. This is a common finding from most blood-sucking arthropods. The mark should not be confused with certain rashes associated with disease progression— for example, erythema migrans. Informing patients of this difference may be reassuring. 1657

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PART III 

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SECTION Twelve 

Infectious Diseases

TABLE 126.1 

Tickborne Illnesses TYPE

DISEASE

PATHOGEN

ARTHROPOD VECTOR

GEOGRAPHIC DISTRIBUTION

Bacterial (including spirochetal)

Lyme disease

Borrelia burgdorferi

Ixodes scapularis

Northeastern United States

Ixodes pacificus Ixodes ricinus

Upper Midwestern United States Pacific Coast Europe Southwest central United States

Rickettsial

Tularemia

Francisella tularensis

Ixodes scapularis Amblyomma americanum Dermacentor variabilis

Rocky Mountain spotted fever

Rickettsia rickettsii

Q fever Human monocytic ehrlichiosis

Coxiella burnetii Ehrlichia chaffeensis

Dermacentor andersoni Dermacentor variabilis Rhipicephalus sanguineus Dermacentor andersoni Amblyomma americanum

Human granulocytic anaplasmosis

Anaplasma phagocytophilum Ixodes scapularis Ixodes pacificus

Predominantly southeastern United States Arizona Worldwide South central and southeastern United States New England and north central United States Northern California

Babesia microti

Ixodes scapularis

Coastal New England

Colorado tick fever

Orbivirus

Dermacentor andersoni

Mountain areas of western United States and Canada

Tick paralysis

Ixobotoxin

Dermacentor andersoni Dermacentor variabilis Amblyomma americanum Ixodes scapularis Ixodes pacificus Ixodes holocyclus

Worldwide

Parasitic (protozoal) Babesiosis Viral

a

Miscellaneous

a

Many other viruses are transmitted to humans by ticks. In the United States, only Colorado tick fever occurs with any significant frequency.

LYME DISEASE Lyme disease, the most common vector-borne disease in the United States, is a tickborne illness caused by the spirochete Borrelia burgdorferi. The story of Lyme disease began in 1975, when health officials at the Connecticut State Department of Health and physicians at Yale University were alerted by two skeptical mothers to an unusually large number of cases of apparent juvenile rheumatoid arthritis occurring in their small coastal community of Old Lyme, Connecticut. Investigation led to the description of a new entity called Lyme arthritis. The causative agent of Lyme disease was isolated in 1982. Lyme disease occurs worldwide and has been reported on every continent except Antarctica. It now accounts for more than 95% of all reported cases of US vector-borne illness. The actual overall incidence of Lyme disease is unknown because many cases go unreported. Lyme disease occurs in people of all ages but is more common in children younger than 15 years and in adults 30 to 60 years of age.2 Persons at greatest risk live or vacation in endemic areas. In the United States, three distinct endemic foci are recognized—the northeastern coastal, Mid-Atlantic, and north central states. During 2000, a total of 17,730 cases of Lyme disease were reported from 44 states and the District of Columbia. Twelve states (Connecticut, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Vermont, Washington, and Wisconsin) accounted for 92% of US cases reported (Fig. 126.3).3 The principal tick vectors are I. scapularis in the Northeast and Midwest and Ixodes pacificus in the West. The I. scapularis population density depends on that of its preferred hosts, the white-footed field mouse, Peromyscus leucopus, for the larval and

nymphal forms, and the white-tailed deer, Odocoileus virginianus, for the adult form. The white-footed mouse readily becomes infected after being bitten by infected ticks and remains highly infectious for periods that approach its life span in nature, thereby providing an important reservoir for B. burgdorferi. Adult I. scapularis ticks feed primarily on deer, which are key hosts in the tick life cycle and in whose fur the adult tick may survive the winter. The repopulation of several areas in the United States by whitetailed deer preceded the recent emergence of Lyme disease in those regions. Although all stages of the tick may feed on humans, the nymph is primarily responsible for the transmission of Lyme disease. It is not surprising that more than two-thirds of patients with Lyme disease do not recall a tick bite, in view of the small size (1–2 mm) of nymphs (Fig. 126.4). The nymph feeds in the spring and summer, which correlates with a peak incidence of early Lyme disease occurring between May and August. In addition, recreational and occupational exposure is greatest during this time. Later manifestations of Lyme disease may appear throughout the year. The spirochete Borrelia burgdorferi persists and multiplies in the midgut of its tick vector, I. scapularis. Transmission of the spirochete to humans occurs during feeding, generally about 2 days after attachment. The mechanism of transmission probably is inoculation with infectious saliva or, alternatively, with tick gut fluids periodically regurgitated during the feeding process. After an incubation period that lasts several days to several weeks, spirochetemia develops, and Borrelia organisms may migrate outward in the blood or lymph to virtually any site in the body. The spirochete appears to be tropic for synovial tissue, skin, and cells of the nervous system, but the mechanism of this tropism

CHAPTER 126  Tickborne Illnesses

A

B

C

D

Fig. 126.1.  Scanning electron micrographs of two tick species. A, Dorsal view of adult female, Dermacentor variabilis. B, Dorsal view of adult female, Ixodes scapularis. C, Dorsal close-up view of D. variabilis head. D, Dorsal close-up view of I. scapularis head. (Courtesy Dr. J. E. Keirans, Georgia Southern University, Statesboro, Georgia.)

is not yet understood. Infection by the spirochete itself accounts for early clinical manifestations. It remains unclear whether late disease manifestations require the continued presence of viable spirochetes or whether an ongoing host immune response to initial infection is sufficient to cause some late disease effects. Although the exact roles of infecting spirochetes, spirochetal antigens, and host immune responses are unknown, it is likely that persistent live spirochetes are responsible for most later manifestations of the disease. The variable severity of Lyme disease may in part result from genetic variations in the human immune system. For example, patients with chronic Lyme arthritis have an increased frequency of human leukocyte antigen (HLA) specificity, in particular for HLA-DR4 and, less often, for HLA-DR2.

Clinical Features Lyme disease, a multisystem disorder, can be classified into three stages—early localized, early disseminated, and late disease. Virtually any clinical feature may occur alone or recur at intervals, and some patients who had no early symptoms may have late

symptoms. The disorder usually begins with a rash and associated constitutional signs and symptoms, suggesting a viral syndrome (early Lyme disease). Neurologic, joint, or cardiac manifestations may emerge weeks to months later (early disseminated Lyme disease), and chronic arthritic and neurologic abnormalities may appear weeks to years later (late Lyme disease). The time course for the clinical features of untreated Lyme disease is illustrated in Fig. 126.5.

Early Lyme Disease Ticks may attach to human hosts at the initial point of contact, generally around ankle level, or move about until they encounter an obstruction. The groin, popliteal fossae, gluteal folds, axillary folds, and earlobes are common sites of attachment. After transmission of B. burgdorferi through a tick bite, the initial site of infection is the skin at the site of the bite. After an incubation period of approximately 1 week (range, 1–36 days), the spirochetes cause a gradually spreading localized infection in the skin and a resultant skin lesion, erythema migrans. Erythema migrans

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KEY TO IDENTIFICATION OF IXODIDAE AND ARGASIDAE TICKS Scutum present, full head visible from above

No scutum, head ventral

= 1 mm

A Argasidae (soft ticks) (eg, Ornithodoros)

Ixodidae (hard ticks)

Long, oval bodies

Short, stout body

Long mouth parts

Short mouth parts

Ixodes

Dermacentor Rhipicephalus

A. americanum

I. scapularis

1 mm

Unengorged Engorged

D. variabilis

Amblyomma

Fig. 126.2.  Identification scheme for Ixodidae and Argasidae genera, the two primary disease-transmitting families of ticks.

B

I. scapularis nymph

Fig. 126.4.  A, Left to right, Larva, nymph, adult male, adult female, and engorged adult female Ixodes ticks and adult male and female Dermacentor ticks; actual size. B, Adult female Amblyomma americanum (Lone Star tick), adult female and nymphal Ixodes scapularis (deer tick), and adult female Dermacentor variabilis (dog tick). (From Hayes EB, Piesman J: How can we prevent Lyme disease? N Engl J Med 348:2424– 2430, 2003.)

Reported Cases of Lyme Disease—United States, 2013 One dot is placed randomly within the county of residence for each confirmed case. Although Lyme disease cases have been reported in nearly every state, cases are reported based on the county of residence, not necessarily the county of infection.

One dot placed randomly within county of residence for each confirmed case Fig. 126.3.  Reported cases of Lyme disease cases by county in the United States in 2013. The number of confirmed cases totaled 27,203. (Adapted from Centers for Disease Control and Prevention: Lyme disease maps. www.cdc.gov/lyme/ stats/maps/map2013.html.)

CHAPTER 126  Tickborne Illnesses

Clinical features Early Lyme disease

• Neurologic Cranial neuropathy Meningitis Radiculoneuropathy • Joint Acute inflammatory large joint arthritis • Carditis

Late Lyme disease • Neurologic Peripheral neuropathy Encephalopathy • Chronic arthritis

Relative frequency (%)

• Erythema migrans Localized erythema migrans Flulike illness Multiple erythema migrans

Early disseminated Lyme disease

Years

Serology

Months

lgG lgM

Months

Years

Fig. 126.5.  Natural history of serologic response, with clinical features, in untreated Lyme disease. IgG, Immunoglobulin G; IgM, immunoglobulin M. (Adapted from Rahn DW: Natural history of Lyme disease. In Rahn DW, Evans J, editors: Lyme disease. Philadelphia, 1998, American College of Physicians, pp 35–48.)

(EM) is the most characteristic clinical manifestation of Lyme disease and is recognized in 90% or more of patients. EM may go unnoticed if the entire skin surface is not examined. The characteristic rash begins at the site of the tick bite with an erythematous papule or macule. The lesion expands gradually (1–2 cm/day, a rate of expansion slower than that of cellulitis). The patch of erythema may be confluent or may have bands of normalappearing skin. Central clearing may occur but is not an invariable feature. The lesion borders usually are flat but may be raised. The lesions generally are sharply demarcated and blanch with pressure. Most lesions are oval or round, but triangular and elongated patches may occur. In patients presenting 1 to 7 days after the appearance of lesions, the average lesion size is approximately 8 by 10 cm (range, 2 by 3 cm to 25 by 25 cm). In some cases, the center of some early lesions becomes red and indurated or vesicular and necrotic. The lesion is warm to the touch and may be described by the patient as nontender to minimally tender (Figs. 126.6 and 126.7). Hematogenous spread of viable spirochetes (not additional tick bites) may result in one or more secondary lesions. These secondary lesions are smaller, migrate less, and typically spare the palms and soles. In all, 10% to 15% of patients have more than 20 such lesions; on rare occasions, they may number more than 100. Blistering and mucosal involvement do not occur. The primary and secondary skin lesions generally fade after approximately 28 days (range, 1 week to 14 months) without treatment

Fig. 126.6.  Lyme disease usually begins with a slowly expanding skin lesion, erythema migrans, which occurs at the site of the tick bite. The classic bull’s-eye or target lesion has partial central clearing, a bright red outer border, and a target center. (From Bhate C, Schwartz RA: Lyme disease. Part I. Advances and perspectives. J Am Acad Dermatol 64:619– 636, 2011.)

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Early Clinical Manifestations of Lyme Disease MANIFESTATION

NO. OF PATIENTS (%)

SIGNS Erythema chronicum migransa

314 (100)

Multiple annular lesions

150 (48)

Lymphadenopathy Regional

128 (41)

Generalized

63 (20)

Pain on neck flexion

52 (17)

Malar rash

41 (13)

Erythematous throat

38 (12)

Conjunctivitis

35 (11)

SYMPTOMS

Fig. 126.7.  Early erythema migrans on the lower leg. The erythematous nodular appearance could lead to misdiagnosis as a spider bite or MRSA cellulitis. (From Bhate C, Schwartz RA: Lyme disease. Part I. Advances and perspectives. J Am Acad Dermatol 64:619–636, 2011.)

and within several days of antibiotic therapy. Recurrent lesions may develop in patients who do not receive antibiotic therapy but apparently not in those who receive appropriate antibiotics. Constitutional signs and symptoms commonly appear in early Lyme disease (Table 126.2). Malaise, fatigue, and lethargy are most common (seen in ≈80% of patients) and may be severe. Fever typically is low grade and intermittent. Lymphadenopathy usually is regional in the distribution of EM or may be generalized; splenomegaly may occur. Musculoskeletal complaints, such as arthralgias and myalgias, are common, and the discomfort typically is short-lived and migratory, sometimes lasting only hours in one location. Frank arthritis may occur at this stage but is rare. Clinical manifestations of meningeal irritation are frequently seen. Headache, the most common symptom, usually is intermittent and localized. Nausea, vomiting, and photophobia occasionally accompany the headache. Kernig’s and Brudzinski’s signs typically are absent, and neck stiffness usually is noted only on extreme forward flexion. At this stage, the neurologic examination and cerebrospinal fluid (CSF) assessment usually yield normal findings. Signs and symptoms of hepatitis, including anorexia, abdominal pain, right upper quadrant tenderness, nausea, and vomiting, may be present. Mild pharyngitis also may be present, but other upper respiratory symptoms, such as rhinorrhea, do not occur. Although the systemic symptoms of early Lyme disease often are described as flulike, a term that can be misleading because clinically significant cough usually does not occur. Conjunctivitis develops in approximately 10% of patients. The incidence of Lyme disease without EM appears to be approximately 10%. Because of the variety of nonspecific signs and symptoms at this stage, in the absence of the characteristic rash or history of tick bite, early Lyme disease may be easily confused with a viral or collagen vascular disease. The intermittent and rapidly changing nature of the early signs and symptoms of Lyme disease may be a helpful distinguishing feature, especially in a patient from an endemic area. In untreated disease, early symptoms usually last for several weeks but may persist for months.

Malaise, fatigue, lethargy

251 (80)

Headache

200 (64)

Fever and chills

185 (59)

Stiff neck

151 (48)

Arthralgias

150 (48)

Myalgias

135 (43)

Backache

81 (26)

Anorexia

73 (23)

Sore throat

53 (17)

Nausea

53 (17)

Dysesthesia

35 (11)

Vomiting

32 (10)

a

Required for inclusion in this study. From Steere AC, Bartenhagen NH, Craft JE, et al: The early clinical manifestations of Lyme disease. Ann Intern Med 99:76–82, 1983.

Acute Disseminated Infection Shortly after disease onset, hematogenous spread can cause a variety of systemic signs and symptoms and result in secondary sites of infection. Organ systems commonly affected are the nervous system, heart, and joints. Less commonly, the eyes, liver, skeletal muscle, subcutaneous tissue, and spleen are infected. Neurologic Manifestations.  A relatively symptom-free interval usually occurs between early and disseminated infection; however, neurologic signs and symptoms may be the presenting manifestations of Lyme disease or may overlap with early or late manifestations. Beginning at an average of 4 weeks (range, 0–10 weeks) after the onset of erythema migrans, neurologic involvement occurs in approximately 15% of untreated patients. The most common neurologic manifestation of Lyme disease is a fluctuating meningoencephalitis, with superimposed symptoms of cranial neuropathy, peripheral neuropathy, or radiculopathy. A triad of meningitis, cranial neuropathies (usually Bell’s palsy), and radiculopathy has been described, but each entity may occur alone. Headache of variable intensity usually is present; other signs and symptoms of a mild meningoencephalitis may be noted, including lethargy or irritability, sleep disturbances, poor concentration, and memory loss. At this point, the disease often

CHAPTER 126  Tickborne Illnesses

is misdiagnosed as viral meningitis. As in early disease, Kernig’s and Brudzinski’s signs are absent and computed tomography (CT) findings are normal. Unlike in early disease, however, findings on CSF examination often are abnormal, with a lymphocytic pleocytosis and moderately elevated protein level. CSF glucose concentration usually is normal. Intrathecal B. burgdorferi antibody (usually immunoglobulin G [IgG] or IgA) is present in 80% to 90% of patients. CSF polymerase chain reaction (PCR) assay results are positive in less than 50% of patients, probably reflecting the low number of organisms usually present in spinal fluid. Routine testing of CSF by PCR assay is not recommended. Cranial neuropathies are common, occurring in approximately 50% of patients with Lyme meningitis; the seventh nerve is usually involved. Other cranial nerves are affected less often. Bell’s palsy is bilateral in approximately one-third of patients. Its duration usually is weeks to months, and the condition generally resolves spontaneously without treatment. Peripheral nervous system manifestations also may occur in early disseminated Lyme disease. The spinal root and plexus and peripheral nerves may be involved in the form of thoracic sensory radiculitis, brachial plexitis, mononeuritis, and motor radiculoneuritis in the extremities. Patients may complain of weakness, pain, or dysesthesia. Examination may reveal loss of reflexes. Involvement of the extremities usually is asymmetric, but cervical and thoracic dermatomes may be affected. Other rare neurologic abnormalities described in association with Lyme disease include chorea, transverse myelitis, ataxia, and pseudotumor cerebri. Cerebral vasculitis associated with Lyme disease also has been reported. Cardiac Manifestations.  Cardiac involvement in Lyme disease is uncommon. Estimates of the incidence of carditis in untreated patients with Lyme disease range from 4% to 10%. Cardiac involvement occurs during the early disseminated phase of the disease. The average time from initial illness to the development of carditis typically is 3 to 5 weeks (range, 4 days to 7 months). Direct myocardial invasion has been demonstrated with endomyocardial biopsy. Electrophysiologic testing has demonstrated widespread involvement of the conduction system. The most common cardiac manifestation of Lyme disease is atrioventricular (AV) block, although conduction defects may involve any level of the conducting system. Myopericarditis, tachydysrhythmias, and ventricular impairment occur less often. In a review of 105 reported cases of Lyme carditis, 49% of cases were third-degree, 16% were second-degree, and 12% were first-degree AV block. The degree of AV block seen in a specific patient may fluctuate rapidly. A commonly observed feature of AV block in patients with Lyme carditis is its gradual resolution, resembling that occurring after an acute inferior wall myocardial infarction and presumably related to the resolution of inflammation. Assessment of the level of the AV block is important to determine the prognosis of a patient with Lyme carditis. In most cases, the block appears to be at or above the level of the AV node; therefore, the prognosis is favorable. However, infranodal AV block does occur and may be characterized by slow escape rhythms of wide QRS pattern, asystole, or fluctuating left and right bundle branch block. Other electrocardiographic findings include nonspecific ST and T wave abnormalities and intraventricular conduction delay. Patients with high-degree AV block usually are symptomatic. Symptoms include lightheadedness, palpitations, syncope, chest pain, and dyspnea on exertion. The physical examination may reveal flow murmurs and murmurs of mild mitral regurgitation, pericardial friction rub, or evidence of congestive heart failure. Associated left ventricular dysfunction may be present and has been documented by two-dimensional echocardiography and radionuclide studies; in most reported cases, it has been mild and

transient. Sudden cardiac death attributable to Lyme disease has also been reported.2,4 Arthritis.  Although it is generally considered a sign of late Lyme disease, acute arthritis may begin during the acute disseminated stage. Monarticular or oligoarticular arthritis, primarily affecting large joints, especially the knee, may develop weeks to months after the onset of initial illness. In an early study of the natural history of Lyme arthritis, approximately 50% of untreated patients experienced one episode or multiple intermittent attacks of arthritis. Acute arthritis typically is monarticular, with involvement of only one knee. The shoulder, elbow, temporomandibular joint, ankle, wrist, hip, and small joints of the hands and feet are involved less commonly. Episodes of arthritis typically are brief (lasting weeks to months) and are separated by variable periods of remission. Arthrocentesis generally is nondiagnostic, yielding an inflammatory synovial fluid with a mean white blood cell count of approximately 25,000 cells/µL (75% polymorphonuclear leukocytes). Higher white blood cell counts have been reported, simulating septic arthritis. The synovial glucose concentration usually is normal, and protein levels are variable, ranging from 3 to 8 g/ dL. Cultures of the fluid rarely identify the causative spirochete. The complement level generally is greater than one-third that of serum. Synovial biopsy reveals hypertrophy, vascular proliferation, and a mononuclear cell infiltrate. Findings therefore are similar to those in rheumatoid arthritis, except that rheumatoid factor and antinuclear antibody assays yield a negative result in Lyme arthritis. Radiography may reveal nonspecific abnormalities such as juxtaarticular osteoporosis, cartilage loss, cortical or marginal bone erosions, and joint effusions. Ophthalmic Manifestations.  Ocular involvement also may be seen in early disseminated disease; manifestations include conjunctivitis, keratitis, choroiditis, retinal detachment, optic neuritis, and blindness. These findings also may be seen in late disease.

Late Lyme Disease The chronic phase of Lyme disease is characterized by arthritic and, less commonly, neurologic symptoms. Transition from a pattern of episodic inflammation in early disease to a more indolent persistent inflammation is observed over time. The term chronic (or late) Lyme disease is used to describe continuous inflammation in an organ system for more than 1 year. A pattern of exacerbation and remission of arthritis may extend for several years, with a gradual tendency toward less frequent and less severe occurrences. The spontaneous long-term remission rate approximates 10% to 20% annually in untreated patients. However, patients commonly have episodes of periarticular involvement, arthralgias, or fatigue interspersed between attacks of frank arthritis. During the second or third year of illness, attacks of joint swelling sometimes become longer in duration, lasting months rather than weeks. Chronic arthritis eventually develops in approximately 10% of patients. Late neurologic complications include a wide variety of abnormalities of the central and peripheral nervous systems, as well as fatigue syndromes. Diagnosis may be difficult because of the large number of other neurologic conditions that Lyme disease may imitate and because late neurologic symptoms may be the first symptoms of the disease. The manifestations of chronic neuroborreliosis usually appear months to years after the onset of infection. The most common late neurologic manifestation of Lyme disease is a chronic encephalopathy that is manifested as a mild to moderately severe impairment of memory and learning.

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Hypersomnolence and mild psychiatric disturbances (depression, irritability, paranoia) also may develop.5 Peripheral nervous system manifestations often are seen in late disease, with involvement of cranial nerves, spinal roots, spinal plexuses, and peripheral nerves. A predominantly sensory polyradiculoneuropathy that is manifested as radicular pain or distal paresthesia is common. Significant overlap occurs with early symptoms. Less commonly, a demyelinating condition resembling multiple sclerosis may appear in late disease. Symptoms are variable and, as in multiple sclerosis, may undergo exacerbations and remissions. CT and magnetic resonance imaging (MRI) may reveal multiple white matter lesions. Chronic inflammation also may occur in the skin, causing a seldom-recognized late cutaneous manifestation of Lyme disease, acrodermatitis chronica atrophicans. This condition usually involves the skin of distal extremities at the site of a tick bite. It is characterized in its initial stages by an edematous infiltration, which progresses to an atrophic lesion resembling localized scleroderma in its more established form. B. burgdorferi has been demonstrated in the skin of patients with acrodermatitis chronica atrophicans as well as positive findings on serologic studies.

Differential Diagnosis The diagnosis of Lyme disease should be considered on the basis of clinical and epidemiologic features. Identification of the disorder often is difficult, however, especially in the early stage. Although Lyme disease is manifested in many ways, each stage has characteristic clinical findings that are helpful in narrowing the scope of a differential diagnosis, which at first may seem overwhelmingly broad. Early Lyme disease (EM and associated constitutional symptoms) may be easily confused with a variety of other diseases, especially if the characteristic rash of EM is absent. A common clinical presentation is an influenza-like illness with headache, nausea, fever, chills, myalgias, arthralgias, stiff neck, and anorexia, occurring during the summer months. Even in endemic areas during the summer months, most patients with such symptoms do not have Lyme disease. When headache and stiff neck are the predominant symptoms, the principal diagnostic distinction to be made is between Lyme disease and the enteroviral diseases (and other causes of aseptic meningitis). The enteroviral diseases also have their peak incidence during the summer months; however, diarrhea, commonly associated with enteroviral infection, is not a feature of Lyme disease. Abdominal pain, anorexia, and nausea suggest hepatitis, sore throat, adenopathy, and fatigue suggest mononucleosis, and myalgias and arthralgias suggest connective tissue diseases. In many areas where Lyme disease is endemic, Ixodes ticks can be infected simultaneously with B. burgdorferi, Anaplasma phagocytophilum, and Babesia microti. Co-infection with more than one of these agents can occur.6 The rash of EM is characteristic of but not pathognomonic for Lyme disease. Some patients are not aware of having had such a rash and, in others, its appearance is atypical. An EM skin lesion is frequently misdiagnosed as a spider bite or community-acquired methicillin-resistant Staphylococcus aureus (MRSA) cellulitis, resulting in treatment with ineffective antibiotics. Other cutaneous entities in the differential diagnosis for EM include fungal infection, plant dermatitis, and fixed drug eruptions. Secondary lesions may be confused with the target lesions of erythema multiforme, which generally are smaller and nonexpanding. Erythema multiforme also may involve the mucous membranes, palms, and soles; EM does not. The presence of a malar rash in association with Lyme disease suggests systemic lupus erythematosus. Erythema nodosum generally causes more painful induration than EM and has a predilection for the extensor surfaces of the legs. Erythema marginatum of acute rheumatic fever also is in the differential diagnosis for EM; the Lyme disease rash differs in

comprising generally fewer, larger, less evanescent lesions that migrate more slowly. Atypical EM manifesting as a urticarial rash may suggest hepatitis B infection or serum sickness. Lyme disease should be considered in a patient with any atypical rash accompanied by a viral syndrome or meningitis-like illness, especially during the months of peak incidence. Acute rheumatic fever, coronary artery disease, or viral myocarditis may be suggested by the cardiac manifestations of Lyme disease. The carditis of Lyme disease, like the carditis of rheumatic fever, may follow pharyngitis and migratory polyarthritis. Erythema marginatum usually occurs with the onset of arthritis, in contrast with EM, which usually precedes the carditis. Although some patients with Lyme disease may satisfy the clinical aspects of the Jones criteria for acute rheumatic fever, they lack evidence of a preceding streptococcal infection; in addition, valvular involvement is not a prominent feature of Lyme carditis. The differential diagnosis of the neurologic manifestations caused by Lyme disease is extensive. Considerations include aseptic meningitis, herpes simplex encephalitis, Bell’s palsy of other causes, multiple sclerosis, Guillain-Barré syndrome, dementia, primary psychosis, cerebral vasculitis, and brain tumor. Neurologic symptoms often occur in the absence of any epidemiologic clues or preceding clinical symptoms suggestive of Lyme disease, making the diagnosis particularly challenging. Lyme arthritis may mimic other immune-mediated disorders. The arthritis of Lyme disease generally is asymmetric, oligoarticular, and episodic. In contrast to patients with rheumatoid arthritis, those with Lyme arthritis rarely have symmetric polyarthritis, morning stiffness, a positive result on rheumatoid factor assay, or subcutaneous nodules. Lyme arthritis commonly is mistaken for seronegative rheumatoid arthritis; however, Lyme arthritis is most similar to the spondyloarthropathies, particularly reactive arthritis. Lyme disease and reactive arthritis both commonly cause huge knee effusions but, in Lyme disease, absence of the extraarticular features of reactive arthritis (conjunctivitis, urethritis or cervicitis, balanitis, keratosis blennorrhagica) at the time of the arthritis helps distinguish it from reactive arthritis. In children, Lyme arthritis may mimic juvenile rheumatoid arthritis, but joint involvement in Lyme disease usually occurs in short intermittent attacks, and iridocyclitis typically is absent. Rheumatoid factor titers will be negative in juvenile rheumatoid arthritis and Lyme disease. The diseases resemble one another closely enough to have been confused at the time of the initial description of Lyme disease. Other diseases in the differential diagnosis for Lyme arthritis include acute gouty arthritis, septic arthritis, gonococcal arthritis, rheumatic fever, polymyalgia rheumatica, and temporomandibular joint syndrome.

Diagnostic Testing Results of routine laboratory studies are nonspecific, and such studies generally are not helpful in the diagnosis of Lyme disease. Abnormalities may include an elevated erythrocyte sedimentation rate, mild anemia, total white blood cell count in the normal range with a decreased absolute lymphocyte count, microhematuria, proteinuria, and increased alanine transferase level. Cultures of blood, tissue, and body fluids (including CSF and synovial fluid) for B. burgdorferi and direct visualization techniques are difficult to perform properly and have such a low yield that they are not clinically useful. Serologic testing is the most practical and useful means of confirming a clinical diagnosis of Lyme disease, but is not without limitations. Results of serologic tests should be interpreted cautiously within the clinical context, and such tests should be regarded only as adjuncts in the diagnostic process. Current serologic tests measure host antibody response (for IgG and IgM) to B. burgdorferi. Problems with the performance of these tests and

CHAPTER 126  Tickborne Illnesses

interpretation of their findings often result in diagnostic confusion. False-negative and, especially, false-positive results are common. The antibody response to B. burgdorferi develops slowly. The peak of IgM titers appears between 3 and 6 weeks after the onset of illness. Earlier in the course of the illness, IgM titers may be negative. IgM antibody usually returns to nondiagnostic levels 4 to 6 weeks after the peak, but elevations may persist. IgG antibody may be detectable 2 months after exposure and peaks at approximately 12 months. Early antibiotic therapy may blunt or even abolish the antibody response. A two-tier strategy is recommended for serologic testing—a sensitive enzyme-linked immunosorbent assay (ELISA) followed by a Western blot (immunoblot). Positive or equivocal ELISA results should be followed by a Western blot. If the ELISA is negative, no further testing is necessary. IgM and IgG immunoblots should be obtained if early disease is suspected. If late disease is suspected, IgG Western blot alone should be obtained. Criteria for positive Western immunoblotting (requiring the presence of bands at particular locations) have been adopted by the CDC. About one-third of patients with early localized Lyme disease (erythema migrans) are seropositive at the time of presentation by the two-tier method. Patients with skin lesions typical of EM do not require confirmatory serologic testing, and the rash itself is sufficient for the diagnosis to be made. If the cause of the rash is uncertain, acute and convalescent phase serologic testing may be considered, with the convalescent sample drawn 2 to 4 weeks after the acute sample. In contrast to early localized disease, most patients with early disseminated Lyme disease or late Lyme disease are seropositive. IgG (and occasionally IgM) antibody may persist for several years after adequate treatment and symptom resolution. Persistent seropositivity is not diagnostic of ongoing infection. Even an IgM response cannot be interpreted as a demonstration of recent infection or reinfection unless the appropriate clinical characteristics are present. IgG antibody that developed after natural infection does not always confer immunity against future infection by B. burgdorferi. Patients who are treated for EM may become reinfected; patients with Lyme arthritis, however, usually have high antibody titers to many spirochetal proteins and seem not to become reinfected.7 Thus, the expanded immune response of late disease appears to be protective against reinfection, at least in most patients, whereas the immature immune response of early disease does not.7 False-positive ELISA results are common. Serologic crossreactivity can occur between B. burgdorferi and other spirochetes, most notably Treponema pallidum. False-positive results for Lyme disease also can occur with relapsing fever, gingivitis, leptospirosis, enteroviral and other viral illnesses, rickettsial diseases, autoimmune diseases, malaria, and subacute bacterial endocarditis. In addition, it is estimated that up to 5% of the normal population will test positive for Lyme disease by ELISA. Bayes’ theorem states that if the pretest likelihood of the disease is low, the positive predictive value is low: a positive test result is more likely to be a false-positive result. For this reason, screening serologic tests are not indicated in the absence of objective clinical evidence of Lyme disease. Patients suspected of having acute Lyme neuroborreliosis should be evaluated with serologic tests and routine CSF examination. Paired serum and CSF samples should be obtained to evaluate for intrathecal production of antibody, although most patients with neuroborreliosis have positive results on serum serologic testing, thereby making additional laboratory confirmation with CSF serology unnecessary. The PCR assay has low sensitivity when performed on CSF and is not routinely recommended. However, the PCR assay is superior to culture for the detection of B. burgdorferi in synovial fluid and has a sensitivity of 73% and specificity of 99% in untreated Lyme arthritis.

Management Prompt treatment of early disease can shorten the duration of symptoms and prevent progression to later stages of disease. Most of the various manifestations of Lyme disease can be treated successfully with oral antibiotic therapy, with the exception of neurologic abnormalities, which usually require intravenous (IV) therapy. Treatment of Lyme disease is summarized in Table 126.3.

Early Disease Prompt antibiotic therapy is essential in early Lyme disease because it generally shortens the duration of the rash and associated symptoms and, more importantly, prevents later illness in most patients. Some patients with severe early disease, however, progress to later stages, despite appropriate antibiotic regimens. The drug of choice for men, nonpregnant and nonlactating women, and children older than 8 years is doxycycline, 100 mg bid for 3 weeks. An advantage of doxycycline is that it also is effective for the treatment of human granulocytic anaplasmosis, which is transmitted by the same tick that transmits Lyme disease. Pregnant or lactating women and children younger than 8 years should receive amoxicillin, 500 mg orally (20 to 40 mg/kg/day in three doses for children). Cefuroxime axetil has been shown to be as effective as doxycycline and may be used in children of any age, but cephalexin is ineffective in Lyme disease. Macrolide antibiotics are not recommended as first-line agents for therapy for early Lyme disease. They should be reserved for patients who cannot tolerate doxycycline, amoxicillin, and cefuroxime axetil. Macrolide regimens for adults include azithromycin, 500 mg orally daily for 7 to 10 days, erythromycin, 500 mg orally qid for 14 to 21 days, and clarithromycin, 500 mg orally bid for 14 to 21 days. A Jarisch-Herxheimer type of reaction may occur in the first 24 hours of antibiotic treatment, consisting of fever, chills, myalgias, headache, tachycardia, increased respiratory rate, and mild leukocytosis. Defervescence usually takes place within 12 to 24 hours. The pathogenesis of this reaction is controversial, but it probably is caused by the killing of spirochetes, with the release of pyrogens. The Jarisch-Herxheimer reaction occurs more commonly with penicillin and doxycycline than with erythromycin, probably because of their superior spirocheticidal activity.

Early Disseminated Infection Neurologic Disease.  For patients with relatively mild symptoms (eg, solitary facial nerve palsy with normal findings on CSF examination), doxycycline or amoxicillin can be used in the same dosage as for early disease, but the duration of therapy should be extended to 28 days. The use of prednisone for facial nerve palsy from Lyme disease has been suggested but is not currently recommended. Parenteral antibiotic therapy is required for patients with other objective neurologic abnormalities (eg, meningitis or encephalitis, peripheral neuropathies, cranial neuritis other than facial nerve palsy) or evidence of the spirochete in the CSF. Ceftriaxone, 2 g/ day IV for 14 days (75 to 100 mg/kg/day for pediatric patients), or penicillin G, 18 to 24 million units daily IV for 10 to 14 days, may be used. Ceftriaxone may be more effective than penicillin, and many experts recommend longer courses (eg, up to 4 weeks). In cases of penicillin or cephalosporin allergy, oral doxycycline may be used for 28 days. Cardiac Disease.  Patients with mild cardiac conduction system involvement (first-degree AV block with a PR interval < 0.30 second) and no other significant symptoms usually can be treated safely on an outpatient basis with oral doxycycline or

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TABLE 126.3 

Treatment of Lyme Disease SYNDROME AND MANIFESTATION Early Lyme disease

Neurologic disease • Facial nerve paralysis • Lyme meningitisc

Cardiac disease • Mildd • More severe

Arthritis

DRUG

ADULT DOSAGE

Doxycyclineb or Amoxicillin ALTERNATIVE Cefuroxime axetil or Erythromycin (less effective than doxycycline or amoxicillin)

100 mg PO bid for 21 days

PEDIATRIC DOSAGEa

250–500 mg PO tid for 21 days

25–40 mg/kg/day tid

500 mg PO bid for 21 days

250 mg bid

500 mg PO qid for 14–21 days

With an isolated deficit, oral regimens for early disease, used for at least 28 days, may suffice. For a deficit associated with other neurologic manifestations, intravenous therapy is warranted (see below). Ceftriaxone 2 g IV by single dose for 14– 8 days 75–100 mg/kg/day IV Penicillin G 20 million units daily in divided doses for 10–14 days 300,000 units/kg/day IV ALTERNATIVE Chloramphenicol 1 g IV qid for 10–21 days Doxycyclineb or Amoxicillin Ceftriaxone or Penicillin G ORAL Doxycyclineb or Amoxicillin PARENTERAL Ceftriaxone or Penicillin G

100 mg PO bid 250–500 mg PO tid 2 g IV daily by single dose for 14–21 days

25-50 mg/kg/day tid 75-100 mg/kg/day IV

20 million units daily in divided doses for 14–21 days

300,000 units/kg/day IV

100 mg PO bid for 30 days 500 mg PO tid for 30 days

50 mg/kg/day divided tid

2 g IV by single dose for 14–21 days

75–100 mg/kg/day IV

20 million units daily in divided doses for 14–21 days

300,000 units/kg/day IV

a

Pediatric dosage should not exceed adult dosage. Tetracycline, 250 to 500 mg PO qid, may be substituted for doxycycline. Neither doxycycline nor any other tetracycline should be used for children younger than 8 years or for pregnant or lactating women. c Regimens for radiculoneuropathy, peripheral neuropathy, and encephalitis are the same as those for meningitis. d Oral regimens are reserved for mild cardiac involvement (see text). Adapted from New drugs for allergic conjunctivitis. Med Lett Drugs Ther 42:39–40, 2000; and Wormser GP, Dattwyler RJ, Shapiro ED, et al: The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 43:1089–1134, 2006. b

amoxicillin for 21 to 30 days.8 Patients with higher degrees of AV block, including first-degree block with a PR interval of more than 0.30 second or evidence of global ventricular impairment, should be hospitalized for cardiac monitoring and treatment with parenteral antibiotics. Penicillin G, 18 to 24 million units IV in 4 divided doses, or ceftriaxone, 2 g daily for 21 days (50 to 80 mg/kg/day for children), may be used. The benefit of the adjuvant use of aspirin or prednisone in the treatment of Lyme carditis is uncertain. Temporary cardiac pacing may be necessary in patients who have severe heart block with hemodynamic instability. The block generally resolves completely with antibiotic treatment, so the recognition of Lyme carditis in young patients with unexplained heart block is critical for avoidance of unnecessary permanent pacemaker implantation.

Late Infection Arthritis.  In established Lyme arthritis, the response to antibiotic therapy may be delayed for several weeks or months. An oral regimen for 30 days, such as doxycycline, 100 mg orally bid,

or amoxicillin, 500 mg tid, usually are effective and, for reasons of cost and convenience, may be selected as first-line therapy given on an outpatient basis before parenteral antibiotic therapy is considered. Persistent or recurrent joint swelling after recommended courses of antibiotic therapy can be treated with another 4-week course of oral antibiotics or with a 2- to 4-week course of IV ceftriaxone. A small percentage of patients with Lyme arthritis, particularly those with HLA-DR4 specificity or antibody reactivity with OspA, may have persistent joint inflammation, despite treatment with oral or IV antibiotics. Such patients often do not respond to any antibiotic therapy and may require arthroscopic synovectomy. Neurologic Disease.  Patients with late neurologic disease affecting the central or peripheral nervous system should be treated with ceftriaxone (2 g once daily IV for 2 to 4 weeks). Alternative parenteral therapy may include cefotaxime (2 g IV tid) or penicillin G (18–24 million units IV daily, given in divided doses every 4 hours). Response to treatment is usually slow and may be incomplete.

CHAPTER 126  Tickborne Illnesses

Lyme Disease and Pregnancy

RELAPSING FEVER

Similar to the spirochetal agents of syphilis and relapsing fever, B. burgdorferi can be passed transplacentally. In rare cases, Lyme disease acquired during pregnancy may lead to infection of the fetus and possibly to stillbirth, but adverse effects on the fetus have not been documented conclusively. Counseling about the termination of a pregnancy because of maternal Lyme disease is unwarranted. Lyme disease contracted during pregnancy can be treated and cured. Treatment of pregnant patients can be identical to that of nonpregnant patients with the same disease manifestations, except that doxycycline should be avoided. Most women give birth to normal infants despite documented Lyme borreliosis during their pregnancies.

Relapsing fever is caused by bacteria of the Borrelia species, order Spirochaetales. Human Borrelia infections occur worldwide, and all are associated with arthropod vectors. The epidemic (louseborne) form of relapsing fever is caused solely by Borrelia recurrentis and is found mostly in Africa, where mortality rates can reach 70% with outbreaks. The endemic form, tickborne relapsing fever (TBRF), is caused by a group of closely related Borrelia species, their names derived from the species names of Ornithodoros tick vectors that carry them. The more common species in North America are Borrelia hermsii, Borrelia turicatae, and Borrelia parkeri. B. burgdorferi has been recognized as the causative agent of the third and most recently described borrelial disease, Lyme disease. TRIS is maintained in an animal reservoir consisting primarily of wild rodents, including squirrels, mice, rats, chipmunks, and rabbits. It is found predominantly at altitudes of 2000 to 7000 feet in coniferous forest habitats. The tick vectors are argasids (soft ticks) belonging to several species of the genus Ornithodoros, which routinely reside in the nests and burrows of their mammalian hosts. Ticks acquire the infection by feeding on a spirochetemic rodent. The borreliae remain viable in the ticks for several years and can be passed transovarially to the next generation; thus, the tick is a major reservoir and vector. These soft ticks feed for brief periods (15– 20 minutes), usually at night, and their painless bite generally is unnoticed by the sleeping victim. Transmission occurs by injection of infected saliva through the bite site or intact skin. Less common modes of transmission (eg, by way of venipuncture equipment in injection drug users) have been reported. In the United States, TBRF occurs primarily in the western Mountain and Pacific states, including Montana, Wyoming, Nevada, Colorado, California, and Washington. Between 1990 and 2011, the CDC received 504 reports of TBRF. The groups most commonly affected were males and people between the ages of 10 to 14 and 40 to 44 years. Of all reported cases, 70% were collectively from California, Washington, and Colorado. Most cases involved visitors to those states. Although TBRF is not nationally reportable, it was reported in 12 states in 2011.5 Persons who come into contact with infected ticks from wild rodents are at greatest risk. Outbreaks have been reported among groups of persons sleeping overnight in hunting cabins inhabited by wild rodents. In Texas, most cases were reported in the winter months among people who had been exploring caves.

Vaccination No vaccine against Lyme disease is currently available in the United States. The LYMErix vaccine (SmithKline Pharmaceuticals, Philadelphia), initially licensed in 1999, was withdrawn from the market in 2002. The vaccine, directed against the outer surface protein A of B. burgdorferi (OspA), was apparently safe and efficacious but required multiple and repeated doses for optimal protection. Ongoing questions about its safety and cost-effectiveness dampened demand for the vaccine. A history of vaccination with the previously licensed vaccine should not change the approach to management. Because protective immunity produced by the vaccine is short-lived, it is unlikely that previous vaccination will provide any residual protective effect. Vaccination may cause a persistently positive ELISA result but a negative Western blot result.

Prophylaxis and Asymptomatic Tick Bites Although previous expert consensus has recommended that persons bitten by deer ticks (I. scapularis) should not routinely receive antimicrobial chemoprophylaxis, this recommendation should be modified in accordance with the findings of a welldesigned trial in which a single 200-mg dose of doxycycline given within 72 hours after tick bite effectively prevented Lyme disease. A single 200-mg dose of doxycycline should be considered for adult patients and children 8 years of age and older (4 mg/kg, up to a maximum dose of 200 mg) when all the following criteria are met: (1) the tick is an adult or nymphal I. scapularis; (2) the tick has been attached for 36 hours or more, as indicated by certainty of the time of exposure or degree of engorgement; (3) prophylaxis can be started within 72 hours after tick removal; (4) the local rate of infection of these ticks with B. burgdorferi is 20% or greater; and (5) doxycycline is not contraindicated. Infection rates of 20% or greater of ticks with B. burgdorferi generally are reported from highly endemic areas such as New England, parts of the MidAtlantic region, and parts of Minnesota and Wisconsin. Most other areas of the United States do not have infection rates high enough to warrant prophylaxis. The efficacy of single-dose doxycycline in patients who present more than 72 hours after removal of a tick is unknown. In children, the dosing and efficacy of prophylactic treatment have not been evaluated. The effectiveness of doxycycline for the prevention of other infections transmitted by I. scapularis ticks (eg, babesiosis, human granulocytic anaplasmosis) is unknown and should not be assumed.9 Other antimicrobial agents effective for the treatment of Lyme disease (eg, amoxicillin) and even other regimens of doxycycline (eg, 100 mg bid) have unknown efficacy for Lyme disease prophylaxis. Anyone who has been bitten by a tick should be instructed to seek medical evaluation if symptoms of tick borne illness develop.

Clinical Features In TBRF, the initial febrile episode lasts 3 days. This is followed by an asymptomatic period of variable duration, usually approximately 7 days, during which patients generally feel better and may return to their usual daily activity levels under the assumption that they have recovered from another viral illness. Relapse then occurs, with symptoms that mimic those of the original illness. With TBRF, this cycle repeats itself three to five times. Each successive relapse usually is less severe. Relapse is caused by the spirochete’s unique ability to undergo antigenic variation within the body of the infected host. Each successive antigenic variation is cleared from the bloodstream by specific host antibodies, and a characteristic relapsing febrile course results. Clinical illness is manifested in two classic stages as each fever episode resolves. The first stage is called the chill phase (high fevers with reported temperatures of up to 106.7° F (41.5° C), mental status changes, tachycardia, and tachypnea), lasting approximately 30 minutes, followed by a flush phase (rapid temperature decrease, sweats, and hypotension), which can be confused with a Jarisch-Herxheimer reaction.6

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After a postbite incubation period of 4 to 18 days, during which time the host concentration of spirochetes increases, fever of abrupt onset occurs, often accompanied by shaking chills, headache, arthralgias, myalgias, nausea, and vomiting. On occasion, a pruritic eschar may be noted at the site of the tick bite, but this usually is absent by the onset of clinical symptoms. Consequently, the nonspecific nature of the clinical presentation often leads to misdiagnosis of the disease as a viral illness. The patient’s temperature is high, and generalized muscle weakness and lethargy are common. Hepatomegaly, splenomegaly, and jaundice are sometimes seen. Neurologic involvement is less common but can be manifested as delirium, nuchal rigidity, peripheral neuropathy, or pupillary abnormalities. Uveitis, iritis and other cranial neuropathies can present acutely or, rarely, as long-term sequelae. A macular or petechial rash, more apparent on the trunk than on the extremities, may be present. There is evidence that febrile illness caused by relapsing fever might cause Plasmodium vivax malaria relapse.10 Severe cases of TBRF resulting in acute respiratory distress syndrome (ARDS) in California and Nevada near the Lake Tahoe area and in the state of Washington prompted a comprehensive epidemiologic investigation of cases in those areas during a 10-year period. This study showed that ARDS may be more common than was previously suspected. Reported occurrence rates for Jarisch-Herxheimer reaction varied between 6% and 21%, 16% for hypoxia, 8% for elevated liver function test values, and 6% for ARDS; 46% of patients required hospitalization.1

Differential Diagnosis On initial presentation, the differential diagnosis is extensive; however, it narrows with the occurrence of relapse. A history of possible soft tick exposure together with recurrent fever should suggest the diagnosis. Other conditions that initially may be considered include malaria, typhus, dengue, yellow fever, Colorado tick fever, and tularemia. Careful examination of blood smears, together with clinical data and other laboratory tests, aid in making the correct diagnosis.

Diagnostic Testing The definitive diagnosis of relapsing fever depends on the demonstration of spirochetes in peripheral blood smears during a febrile episode. This is not a typical finding with other spirochetal diseases. In most cases, spirochetes are readily visible on a routine blood smear prepared with Wright or Giemsa stain. Thick or thin blood smears, such as those prepared for malaria evaluation, also are satisfactory. The organisms are seen within the plasma spaces between blood cells or may overlie the blood cells. Several organisms per high-power field typically are visible in smears from febrile patients with relapsing fever. Blood specimens for the smears should be obtained as the temperature curve swings up, and repeated samples may be required before a positive result is observed because sensitivity approaches only 70%. Spirochetes also may be visible in wet mounts with the use of phase contrast microscopy. Culture, although it is the most sensitive diagnostic method available, requires a special medium, does not yield rapid results, and therefore is not commonly performed. Genus-specific PCR testing has been used successfully and may be higher in sensitivity than serology or blood smear, especially in the acute phase of disease. Serologic testing is available through public and private health facilities but is not useful for immediate diagnosis. Nonspecific laboratory findings may include mildly increased bilirubin and liver function levels, thrombocytopenia, and an elevated erythrocyte sedimentation rate.6

Management Relapsing fever is effectively treated with tetracycline or erythromycin. Tetracycline should be avoided in children younger than 8 years and in pregnant women. Tetracycline or erythromycin should be given in an oral dose of 500 mg for 7 days; single-dose therapy is also effective. Other treatment regimens have been recommended, including doxycycline and chloramphenicol. Treatment with penicillin G has been associated with an increased rate of relapse. Success with ceftriaxone has been reported in a patient with relapsing fever who did not respond to penicillin. Prophylaxis with doxycycline for TBRF in exposed subjects in high-risk infested areas has been shown to be effective. As many as one-third of patients experience a JarischHerxheimer type of reaction during treatment with antibiotics. The reaction can be severe, especially with louseborne relapsing fever. This phenomenon may be related to release of high levels of cytokine intermediaries or endogenous opioids. Approximately 4 hours after antibiotic treatment, and coinciding with the clearance of spirochetes from the blood, the patient usually experiences an increase in temperature and severe rigors, accompanied by a drop in the leukocyte and platelet counts and onset of hypotension. Anticipation of this reaction is crucial because volume expansion with saline solution may be required to maintain the blood pressure; the reaction can be more threatening than the disease itself. Meptazinol, an opioid antagonist with agonist properties, has been proposed for use in treatment of this reaction. The prognosis is good for treated patients with relapsing fever; approximately 95% achieve complete recovery. Poor prognostic signs include the presence of jaundice, high spirochete counts in the blood, and hypotension. Transplacental transmission can occur in infected pregnant women. Perinatal death of the fetus or infant and spontaneous abortions occur in nearly 50% of cases in pregnant women. Death is rare in TBRF and is limited to infants and older adults.

TULAREMIA Tularemia was first characterized in 1837 by Soken, who described a febrile illness with generalized lymphadenopathy in people who had eaten infected rabbit meat. In 1912, McCoy first isolated Bacterium tularense, now known as Francisella tularensis, from rodents in Tulare County, California, giving rise to the name of the disease. Edward Francis, for whom the genus Francisella was later named, contributed much to the understanding of the bacteriology and epidemiology. Tularemia occurs worldwide and is endemic between 30 and 71 degrees north latitude. The incidence of tularemia is low. There were 247 reported cases of tularemia in the United States between 2004 and 2005, although it is not a notifiable disease in all states. Tularemia has been seen in every state but is most common in the southwest central region (Arkansas, Louisiana, Oklahoma, Texas, and Mississippi). Of reported cases, 56% have come collectively from Missouri, Oklahoma, South Dakota, and Arkansas. It is more common in men than in women. Persons at increased risk for infection include hunters, trappers, butchers, agricultural workers, campers, sheep herders, mink farmers, and laboratory workers. Ticks, lagomorphs (hares, rabbits), and rodents (mice, rats) are believed to be the most important sources of transmission to humans; however, the organism has been recovered from animals of more than 100 species. Significant epidemics have been linked to contact with a variety of them, including domestic cats.11 In 2002, a large number of commercially distributed prairie dogs from Texas died of tularemia. The ticks most commonly involved in transmission in the United States are the deer tick (I. scapularis), Lone Star tick (A. americanum), and dog tick (D. variabilis), all of which have been

CHAPTER 126  Tickborne Illnesses

associated with other tickborne illnesses. Whereas mosquitoes are major vectors in many European countries, horse fly and deer fly bites have been implicated in endemic situations in the United States. In 2007, an outbreak in Utah was associated with deer fly bites.12 Transmission to humans most commonly occurs through tick bites or handling of infected animals. It also can occur with ingestion of infected food or water, inhalation of dust or water aerosol, and insect bites. Nonimmune laboratory workers who work with F. tularensis can acquire the disease. Person to person transmission is rare. Tularemia has a bimodal prevalence in the United States; an increased incidence in May to August is associated with tickborne transmission, and a December to January peak is associated with hunting and skinning of infected mammals (primarily rabbits). F. tularensis has been found to coexist in reservoir populations harboring the agent responsible for Lyme disease. Eleven cases of pneumonic tularemia, found to be from aerosolization of contaminated vegetation clippings, were discovered in Martha’s Vineyard, Massachusetts. Outside the United States, tularemia has been confirmed in hundreds of cases in Kosovo through rodent contamination of food. Sweden has reported a high number of cases, usually associated with aquatic environments and mosquitoes.13 Tularemia is manifested in different ways, depending on the portal of entry of the organism. The primary route of infection by F. tularensis is through the skin. Entry can occur through hair follicles or small cuts and abrasions that may be contaminated by exposure to an infected animal; tick exposure can also introduce the bacteria. Because the bacterium has not been isolated from the salivary glands of ticks, it is thought that they transmit the organism through their feces. Scratching after a tick bite introduces the infected feces into the skin. Inhalation or ingestion of the organism or transmission through the conjunctivae also can cause infection. The incubation period is approximately 2 to 6 days, depending on the size of the inoculum. After penetration of the skin or epithelial membrane, the organism usually spreads to the regional lymph nodes. An erythematous tender papule develops at the primary infection site, followed by inflammation and skin ulceration. The regional nodes enlarge, necrose, and may rupture. The necrotic, purulent, painful lymph node is termed a bubo. In the ulceroglandular form of the infection, the organism may not spread farther than the regional lymph nodes. If the inoculum is sufficiently large or host defenses are inadequate, bacteremia ensues, with dissemination to phagocytic cells of the reticuloendothelial system. Pulmonary tularemia may result from inhalation of smallparticle aerosols containing F. tularensis or from hematogenous dissemination. Small areas of localized pneumonitis are most commonly seen, although chest radiographic findings are nonspecific; lobar consolidation or abscess formation is rare. Oculoglandular tularemia occurs when the conjunctiva becomes infected from contact with material from an ulcer or contaminated finger. Typhoidal tularemia follows the systemic spread of F. tularensis from the oropharynx and probably the gastrointestinal tract when a large inoculum is swallowed.

Clinical Features Presentations Tularemia has six clinical presentations, depending on whether disease is localized to an entry site and its regional lymph nodes— ulceroglandular, glandular, oculoglandular, and oropharyngeal forms—or is more invasive and generalized—typhoidal and pulmonary forms. Ulceroglandular Tularemia.  This accounts for approximately 80% of cases. Typically, a skin lesion on an extremity at

the site of primary inoculation begins as an erythematous papule, which then ulcerates 2 to 3 days later. The ulcer is slow to heal and often is still present when the subsequent regional lymphadenopathy and fever develop. The distribution of the regional adenopathy reflects the primary entry site; patients with tickborne tularemia usually have inguinal or femoral adenopathy, whereas those who acquire rabbit-associated tularemia have axillary or epitrochlear nodal involvement. Generalized lymphadenopathy also may be seen. On occasion, nodes suppurate and drain. Glandular Tularemia.  This is the second most common form. It is characterized by the development of lymphadenopathy (usually cervical) without an associated skin ulcer. Oculoglandular Tularemia.  This is seen in less than 2% of cases. It is characterized by unilateral conjunctivitis, with regional adenopathy involving preauricular lymph nodes. Oropharyngeal Tularemia.  This is manifested as severe exudative pharyngitis, with associated cervical lymphadenitis. It has been known to cause acute glaucoma. Typhoidal Tularemia.  This is a systemic form of the disease in which no obvious entry site can be found; it occurs in approximately 10% of cases. Only 10 to 50 organisms are required to induce disease; incubation time is 2 to 10 days. Symptoms and signs may include fever, chills, constipation or diarrhea, abdominal pain, and weight loss. A 30% to 60% case fatality rate is associated with untreated typhoidal tularemia.14 Pulmonary Tularemia.  This has symptoms similar to those of other bacterial pneumonias—fever and chills, cough (usually nonproductive), substernal burning, dyspnea, malaise, and prostration. It may result from direct inhalation of aerosolized organisms or bacteremic spread from another site.

Other Considerations Uncommon complications of tularemia include pericarditis, meningitis, endocarditis, peritonitis, appendicitis, perisplenitis, and osteomyelitis. Guillain-Barré syndrome associated with tularemia also has been reported. Tularemia is one of the most widely studied diseases with respect to potential biologic warfare. The United States developed an aerosolized form in the 1950s, and the Japanese allegedly contaminated prisoners with the disease in the 1930s. It was removed from the national list of notifiable diseases in 1995 but then was reinstated in view of the heightened biologic weapons threat. It is classified by the CDC as one of the six category A critical biologic diseases.8 An aerosolized form of the bacterium would be the most likely delivery mechanism used in biologic warfare. With the release of aerosolized particles, disease would be manifested clinically as acute fever, progressive pneumonia, pleuritis, and hilar lymphadenopathy, beginning as early as 3 to 5 days after delivery. The mortality rate for untreated tularemia in general ranges from 5% to 30%, but the rate for the pulmonary form can reach 60%.15 With appropriate antibiotic treatment, death is rare (mortality rate < 1%). Only approximately 55% of emergency departments (EDs) have been adequately educated on the recognition of and preparedness for tularemia.

Diagnostic Testing The diagnosis of tularemia is based on clinical findings and serologic testing. Antibody titers begin to rise approximately 7 to 10 days after exposure and peak in 3 to 4 weeks. In a patient with a clinical presentation suggesting tularemia, an antibody titer of

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1 : 160 or higher in a single specimen is diagnostic. Confirmatory evidence is provided by a fourfold or greater rise in titer in a second sample obtained 2 weeks later. Unfortunately, titers of IgG and IgM can continue to be high for up to 10 years, and cellmediated immunity can be maintained for up to 25 years. Rapid testing with PCR assay is available,9 and point of care analysis using an immunochromatographic approach has proven useful in testing water sources. As for most infectious organisms, culture is the gold standard for diagnosis; however, aspiration of affected lymph nodes for culture is not routinely recommended because of the associated risk to laboratory personnel. If tularemia is suspected, the laboratory should be alerted so that appropriate precautions can be taken in specimen handling and enriched culture medium can be used.

Management Isolation of patients with tularemia is not required. Streptomycin is the drug of choice for the treatment of all forms of tularemia, but is not widely available. When given intramuscularly in a dose of 30 to 40 mg/kg/day bid, streptomycin usually produces symptomatic improvement and resolution of fever in 1 to 2 days. After the third treatment day, half of the dose is given for a total course of 7 to 14 days. With this regimen, relapses are unusual. Gentamicin is effective for treatment, especially in children (3 to 5 mg/kg/day for 10 to 14 days), and is more readily available.16 Tetracycline and chloramphenicol are also effective; however, the risk of relapse is greater than that associated with the aminoglycosides. Imipenem-cilastatin, an antibiotic without nephrotoxicity, has been used successfully to treat pulmonary tularemia in a patient with acute renal failure. Ceftriaxone is not effective against F. tularensis infections. Prophylaxis for possible exposure requires doxycycline, 100 mg bid for 14 days. Doxycycline or ciprofloxacin prophylaxis is recommended for a large biologic attack. Ulcers and tender lymph nodes usually heal within 7 to 10 days; however, enlarged nodes occasionally develop into fluctuant sterile buboes, requiring incision and drainage after completion of the course of antibiotics. The unique ability of F. tularensis to attenuate host inflammatory responses has been emerging as a basis for research investigating the use of immunomodulatory agents or antibodies for adjunctive treatment.17 There continues to be no approved vaccine for tularemia. Because of recent interest in biologic warfare, however, research on tularemia vaccines has resurged.18

ROCKY MOUNTAIN SPOTTED FEVER Rocky Mountain spotted fever (RMSF) is an acute, febrile, systemic tickborne illness caused by Rickettsia rickettsii. The genus Rickettsia is divided into the spotted fever group and typhus group. R. rickettsii is considered the typical representative of the spotted fever group. Twenty-six species now exist.19 RMSF is found in North, South, and Central America and is a nationally reportable disease. All cases are to be registered with the respective state department. As of 2010, reported cases of RMSF are categorized in the broader name of spotted fever rickettsiosis (Box 126.1).20 The number of reported cases in the United States more than tripled between 2000 and 2007, especially in suburban areas.21 The increase during this period was thought to be due to more widespread use of ELISA. Use of the assay has also resulted in a significantly lower case fatality rate, which could be related to the high cross-reactivity of serologic tests with more benign rickettsioses. Higher awareness and more aggressive empirical treatment of RMSF might also have contributed to the decreased fatality rate. The number of reported spotted fever cases in the United States rose 9% in 2010, which included all spotted fever rickettsioses, not just RMSF, in accordance with the

BOX 126.1 

Diagnostic Criteria for Spotted Fever Rickettsiosis (Rickettsia spp.) • Clinical criteria • Any reported fever and one or more of the following: rash, eschar, headache, myalgia, anemia, thrombocytopenia, or hepatic transaminase level elevation • Laboratory-confirmed • Serologic evidence of a fourfold change in immunoglobulin G (IgG)–specific antibody titer reactive with Rickettsia rickettsii or other spotted fever group antigen by indirect immunofluorescence assay (IFA) between paired serum specimens (one taken in the first week of illness and a second 2 to 4 weeks later) or • Detection of R. rickettsii or other spotted fever group DNA in a clinical specimen via amplification of a specific target by PCR assay, or • Demonstration of spotted fever group antigen in a biopsy or autopsy specimen by immunohistochemistry (IHC), or • Isolation of R. rickettsii or other spotted fever group Rickettsia from a clinical specimen in cell culture • Laboratory-supportive • Has serologic evidence of elevated IgG or immunoglobulin M (IgM) antibody reactive with R. rickettsii or other spotted fever group antigen by IFA, enzyme-linked immunosorbent assay (ELISA),a dot ELISA, or latex agglutination • Exposure • Exposure is defined as having been in a potential tick habitat within the 14 days preceding the onset of symptoms. The patient’s occupation should be recorded if relevant to exposure. A history of a tick bite is not required. • Case classification • Suspected: A case with laboratory evidence of past or present infection but no clinical information available (eg, laboratory report) • Probable: A clinically compatible case (meets clinical evidence criteria) that has supportive laboratory results • Confirmed: A clinically compatible case (meets clinical evidence criteria) that is laboratory-confirmed From Centers for Disease Control and Prevention, National Notifiable Diseases Surveillance System: Spotted fever rickettsiosis (Rickettsia spp.) 2010 case definition. www.cdc.gov/NNDSS/script/ casedef.aspx?CondYrID=853&DatePub=2010-01-01. a NOTE: Current commercially available ELISA tests are not quantitative, cannot be used to evaluate changes in antibody titer, and hence are not useful for serologic confirmation. IgM tests are not strongly supported for use in the serodiagnosis of acute disease because the response might not be specific for the agent (resulting in false-positives) and the IgM response might be persistent. Complement fixation (CF) tests and older test methods are neither readily available nor commonly used. CDC uses in-house IFA IgG testing (cutoff ≥ 1:64), preferring simultaneous testing of paired specimens, and does not use IgM results for routine diagnostic testing.

surveillance changes mentioned.22 Another rare rickettsiosis that emerged in North America in 2004 was caused by Rickettsia parkeri, transmitted through the Gulf Coast tick, Amblyomma maculatum. It is distinguished from RMSF by sometimes causing eschars or a vesicular rash. RMSF ranges in clinical severity from mild or even subclinical illness to a fulminant disease, with vascular collapse and death within several days of onset. It is the only rickettsiosis still associated with significant mortality, causing approximately 40 deaths in the United States each year, with a mortality rate ranging from 3% to 5%, despite appropriate treatment. Before tetracycline and chloramphenicol were available, death occurred in as many as 30% of cases in the 1930s. The highest mortality rates occur in patients between the ages 5 and 9 years or older than 70

CHAPTER 126  Tickborne Illnesses

years, among Native Americans, and among immunosuppressed patients. In the South Atlantic United States, mortality reaches 9% in patients older than 70 years.23 The median time between onset of illness and death is 9.5 days, whereas death occurs in hospitalized patients in a median time of 3 days.14 The recorded history of RMSF suggests that the disease was present at least before the European settlement of western North America among inhabitants of wooded Rocky Mountain regions. Early terms used to name the disease included tick fever and black measles. In 1899, RMSF was described as “an acute, endemic, noncontagious but probably infectious, febrile disease, characterized by a continuous moderately high fever, severe arthritic and muscle pains, and a profuse petechial or purpuric eruption in the skin, appearing first on the ankles, wrists, and forehead, but rapidly spreading to all parts of the body.”24 In 1906, the causative organism, R. rickettsii, was identified by Howard T. Ricketts, who also described the importance of the tick vector in transmission to humans. Although RMSF was first described in Montana and Idaho, it is now relatively rare in the Rocky Mountain states. Endemic in all 48 contiguous states except Maine, the disease continues to be most prevalent in the southeastern United States. RMSF has been reported in Canada, Central America, Mexico, and South America but never outside the Western Hemisphere. In 1987, four cases of RMSF were reported among residents of the Bronx in New York City; none of the affected persons had recently traveled to an area known for endemic disease, raising the possibility that other urban foci of RMSF may exist. RMSF also tends to be focally endemic, with clustering of cases within a larger endemic area that may correspond to islands of infected ticks. These areas, ecologically distinct from surrounding areas, may be ideally suited to ticks; they usually consist of wild open fields, deciduous forests with thick ground cover and poor water drainage, or uncultivated areas. Geographic clusters of severe disease have been reported.25 In areas with frequent occurrence of RMSF (Oklahoma, North and South Carolina, Tennessee, Pennsylvania, Missouri, Arkansas), an infectivity rate of 2% to 15% of the tick population has been reported. North Carolina and Oklahoma carry the highest incidence rates (35% of all cases) for RMSF. R. rickettsii organisms are obligate intracellular bacteria with tropism for human endothelial cells. They often occur in pairs and possess a cell wall similar in structure and chemical composition to that of gram-negative bacteria. R. rickettsii contain RNA and DNA and, in contrast with other rickettsial organisms, can invade the nucleus as well as the cytoplasm. The American dog tick, Dermacentor variabilis, and the Rocky Mountain wood tick, Dermacentor andersoni, have been the vectors responsible for human RMSF cases in the United States to date. However, the common brown dog tick, Rhipicephalus sanguineus, has emerged as a third vector. R. sanguineus has been the main RMSF vector in Mexico and Central America. Amblyomma imitator, in the genus of the Lone Star tick, has been implicated as yet another vector because R. rickettsii has been found in its eggs.26 Ticks feed on virtually any available warm-blooded animal and human; the occurrence of R. rickettsii in the United States does not depend on the presence of any given order of mammal. Domestic dogs infected with R. rickettsii can demonstrate clinical illness similar to that seen in humans. Although dogs do not play an important role in the amplification cycle of RMSF, they can serve as a conduit for infected ticks, carrying them into close contact with pet owners. Dogs may serve as sentinels for RMSF in humans. A high prevalence of rickettsial antibodies in stray dogs in Arizona was thought to be a major factor in the 70 cases and 8 deaths from RMSF reported there between 2003 and 2008.27 It has been speculated that the reason Native Americans have a

fourfold greater incidence and case fatality rate than other ethnic groups is a result of their more frequent exposure to free-roaming dogs.28 The deadliest spotted fever, Brazilian spotted fever, is also caused by R. rickettsia. The capybara, a common mammal in Brazil, appears to be the main reservoir through the vector tick Amblyomma cajennense.29 Communication between physicians and veterinarians is important when cases of zoonotic diseases are detected. Humans serve only as accidental participants in the cycle of infection. A retrospective study has revealed that none of 10 recipients of blood products found to be from donors with confirmed or probable RMSF contracted the disease.13

Pathophysiology After introduction of R. rickettsii into the host by the tick vector, the organisms invade and multiply in the vascular endothelial cells. They then enter deeper areas of the vessel walls and infect vascular smooth muscle. Rickettsial organisms move from cell to cell by actin-based motility. Damage to endothelial cells not only exposes subendothelium but also releases tissue plasminogen activator and von Willebrand factor, thereby causing microhemorrhage, microthrombus formation, and increased vascular permeability. In addition, antibody forms, with antigen activating the complement system (type III immune response), and a cellular response is recruited. These widespread vascular lesions form the basis for most of the clinical features associated with RMSF. Hypotension, edema, and increased extravascular fluid space result from the increased small-vessel permeability. The early rash results from the vasculitis and associated changes in permeability; later petechial and hemorrhagic lesions are secondary to the vasculitis and thrombocytopenia. Microinfarcts and focal lesions develop in various organs, including the brain, heart, lungs, kidneys, adrenal glands, liver, and spleen. Rickettsial encephalitis and diffuse microinfarcts are usual features of central nervous system involvement. An interstitial pneumonitis caused by direct lung invasion by the organism may occur, and ARDS can ensue. Acute renal failure and hypovolemic shock, the primary causes of death, can occur as early as the second week of illness.

Clinical Features Children from 5 to 9 years of age are the most common victims of RMSF. Two-thirds of all cases are in children younger than 15 years. More than 90% present with a fever and rash. A history of tick bite or presence in possible tick-infested areas is elicited in 60% to 70% of all patients with RMSF, although only 49% of the pediatric population reports a bite. The incubation period ranges from 2 to 14 days, with a mean of 7 days. A short incubation period may indicate a more serious infection. Factors that bring higher risk of death include delayed onset of rash, glucose-6phosphate dehydrogenase deficiency, hepatomegaly, neurologic deficits, renal insufficiency, increased period between symptoms and antibiotic treatment, and lack of tick bite history. Onset of symptoms usually is generally abrupt but may be gradual in approximately one-third of patients. Early symptoms are nonspecific and similar to those of many acute infectious diseases, making early diagnosis difficult. Typical patients experience sudden onset of fever, severe headache, myalgias, prostration, nausea, and vomiting. Tenderness may be noted in large muscle groups (Table 126.4). As many as 80% of patients may have gastrointestinal symptoms secondary to myositis of the abdominal wall. Fever (temperature usually > 102° F [39° C]) is nearly always present during the first 2 to 3 days of illness and may precede other signs by 1 week or more. On occasion, the onset of illness is mild, with lethargy, headache, anorexia, and low-grade

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TABLE 126.4 

Symptoms and Signs of Rocky Mountain Spotted Fevera FREQUENCY DURING ILLNESS (%) SYMPTOM OR SIGN

Any Time

First 3 Days

Fever (temperature of 37.8° –38.9°  C [100°–102°  F])

99

73

Headache, mild to moderate

91

71

Fever (≥102°  F [38.9°  C])

90

63

Any rash

88

49

Myalgia, mild to moderate

83

57

Rash, maculopapular

82

46

Rash, palms and soles

74

28

Triad of fever, rash, history of tick exposure

67

3

Nausea and vomiting

60

38

Headache, severe

57

40

Abdominal pain

52

30

Rash, petechial and hemorrhagic

49

13

Myalgia, severe

47

25

Conjunctivitis

30

13

Lymphadenopathy

27

13

Stupor

26

6

Diarrhea

19

9

Edema

18

3

Ataxia

18

7

Meningismus

18

5

a

In 262 patients. From Helmick CG, Bernard KW, D’Angelo LJ: Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis 150:480–488, 1984.

fever; these patients may remain ambulatory. Although the triad of fever, rash, and tick exposure traditionally was seen in only approximately 3% to 18% of cases, more recent data have shown that it is found in up to 45% of children with the disease. An extreme complication of RMSF is gangrene, which probably is induced by small-vessel occlusion.

Cutaneous Manifestations Vasculitis secondary to rickettsial invasion of vascular endothelial cells causes the rash commonly associated with RMSF; however, the rash reportedly is absent in 4% to 16% of laboratory-confirmed cases, referred to as Rocky Mountain spotless fever. In addition, the rash may go unnoticed in dark-skinned patients. It usually appears on the third to fifth febrile day but can emerge as early as the second and as late as the sixth day. The initial lesions generally are restricted to the ankles and wrists, spreading to the palms and soles. The rash then spreads centripetally to the forearms, arms, legs, thighs, and trunk. The face can be involved, although it is usually spared. Despite the common belief that the palms and soles are critical for diagnosis, they are not consistently involved; rash on the palms and soles is reported in approximately 50% of cases. Involvement of the scrotum or vulva can be an evasive clue

for RMSF. The rash of RMSF typically begins as 1- to 5-mm blanchable pink to bright red discrete macules that may be pruritic (see Fig. 126.7). At this initial stage, the lesions fade when pressure is applied and are not palpable. A warm compress applied to the area enhances the rash. After 6 to 12 hours, the rash spreads centripetally. After 2 to 3 days, the rash becomes maculopapular and changes to a deeper red; at this stage, skin changes can be appreciated on light palpation. By approximately the fourth day, the rash becomes petechial and no longer fades with applied pressure. Applying tourniquets for several minutes or taking the blood pressure may cause additional petechiae to form distal to the site of occlusion (Rumpel-Leede phenomenon). The lesions occasionally coalesce to form large ecchymotic areas that may slough and form indolent ulcers (Fig. 126.8). Prompt institution of specific therapy can cause the initial nonfixed lesions to disappear rapidly, unlike the later fixed lesions. Patients who have had the typical rash may exhibit brownish discolorations at the site during the convalescent period.

Cardiopulmonary Manifestations Echocardiographic evidence of decreased left ventricular contractility secondary to myocarditis is commonly seen and often is detectable even before clinical signs of RMSF appear. Clinical manifestations of left ventricular dysfunction are uncommon, however, and hypotension and pulmonary edema, when present, usually have noncardiogenic causes. Chest radiographs may demonstrate cardiac enlargement. Electrocardiographic changes include low-voltage, nonspecific ST-T changes, first-degree AV block, dysrhythmias (eg, sinus and nodal tachycardia, paroxysmal atrial tachycardia, atrial fibrillation), and left ventricular hypertrophy. Most cardiac abnormalities are transient, but persistent echocardiographic changes have been described. Decreased systolic function, elevated serum cardiac markers, no finding of vascular lesions, and a fourfold rise in antibody titers are consistent with myocarditis from RMSF. Interstitial pneumonitis and increased pulmonary capillary permeability may result from infection of the pulmonary capillaries with rickettsiae. Nonproductive cough and dyspnea secondary to pneumonitis are sometimes seen on presentation. Chest radiographic abnormalities are identified in approximately 25% of patients. These abnormalities include interstitial infiltrates, patchy alveolar infiltrates, pleural effusions, and cardiomegaly with pulmonary edema. Pulmonary consolidation is rare. In severe cases, progression to noncardiogenic pulmonary edema and ARDS may occur.

Neurologic Manifestations Neurologic manifestations of RMSF range from mild headache and lethargy to seizures and coma. Acute disseminated encephalomyelitis has been described. Headache, generally severe, is common, occurring in 50% to 90% of cases. Meningismus is present in 16% to 29% of patients. The CSF may be normal or show a slight protein elevation and pleocytosis of lymphocytes and polymorphonuclear cells (usually 8 to 35 cells/mL). The CSF glucose level and opening pressure usually are normal. Resolution of eosinophilic meningitis during RMSF after appropriate antibiotic treatment has been reported. Less than 40% of patients have a positive CSF finding. Cerebral thrombovasculitis may cause focal neurologic deficits, which usually are transient. Seizures can occur, especially during the acute phase of the illness. Generalized cerebral dysfunction ranging from lethargy to coma can occur secondary to systemic toxicity (eg, fever, hypotension, hyponatremia) or vasculitic lesions involving the central nervous system. Coma is a late finding in patients with severe disease and is seen in less than 10%

CHAPTER 126  Tickborne Illnesses

B

A

Fig. 126.8.  A, Exanthem of Rocky Mountain spotted fever. B, Exanthem of Rocky Mountain spotted fever, close-up view. (From McGinley-Smith DE, Tsao SS: Dermatoses from ticks. J Am Acad Dermatol 49:363–392, 2003.)

of cases. Some reports have described patients who remain alert but are amnesic for their illness after recovery. Other reported neurologic manifestations include transient deafness, tremor, rigidity, athetoid movements, paralysis, ataxia, opisthotonos, aphasia, and blindness. In general, neurologic signs abate without residual deficits, and permanent neurologic deficits are rare. Behavioral disturbances and learning disabilities have been reported after recovery from RMSF-associated coma in children.

Differential Diagnosis Delayed diagnosis or misdiagnosis is the principal reason for the historically significant mortality associated with RMSF. Clinical diagnosis is difficult, especially early in the course of the illness, because of its nonspecific presentation. For avoidable deaths to be prevented, a diagnosis of RMSF should be considered in any patient with an unexplained febrile illness, with or without a rash and headache, even in the absence of a history of tick bite or travel to an area known to be endemic for the disease. The emergency clinician should remember to ask routinely about recent tick bites, especially when assessing children with unexplained febrile illness, because parents do not always spontaneously provide this important information. An atypical presentation or manifestation of RMSF also should be considered during the differential diagnosis, including the following: (1) absence of a rash (Rocky Mountain spotless fever) or late appearance of a rash (Fig. 126.9); (2) predominant gastrointestinal features or abdominal pain suggestive of an acute condition in the abdomen; (3) cough and pulmonary congestion suggestive of pneumonitis; and (4) meningismus suggestive of viral meningitis.30 A presumptive diagnosis is advised, with the initiation of specific therapy, well before specific confirmatory laboratory values are available. A wide variety of other infections with similar exanthems can be confused with RMSF.31 The most common include meningococcal infection, measles (rubeola) and atypical measles, gonococcemia, infectious mononucleosis, toxic shock syndrome, and enteroviral infections. Less common diseases include dengue

Fig. 126.9.  Late appearance of the rash of Rocky Mountain spotted fever on the lower extremity. (Courtesy Dr. Theodore Woodward.)

fever, leptospirosis, murine typhus, and epidemic typhus. R. parkeri rickettsiosis should be considered.

Diagnostic Testing Most immediately available laboratory tests provide little help in the diagnosis of RMSF. Early in the course of the illness, the

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diagnosis is based primarily on clinical evidence, so epidemiologic features should be correlated with clinical signs and symptoms. The initial presentation of RMSF is similar to that of many acute febrile infectious diseases, and almost invariably a therapeutic decision must be made on clinical grounds alone, without the luxury of confirmatory laboratory evidence. Abnormalities such as thrombocytopenia, hyponatremia, and acute renal failure may be detected by routine laboratory tests, but they are nonspecific and unhelpful diagnostically. Up to 30% of patients present with anemia. A definitive diagnosis of RMSF requires positive results on one or more of several tests—serologic study, skin biopsy, or direct isolation and identification of the organism (see Box 126.1).

Skin Biopsy Identification by immunofluorescent assay (IFA) and immunoperoxidase staining of R. rickettsii in biopsy specimens of the rash from patients with suspected RMSF are the best rapid diagnostic tests currently available. In experienced laboratories, the diagnosis of RMSF can be confirmed as soon as 4 hours after the specimen is obtained. The organisms can be detected as early as day 3 of clinical illness and as late as day 10. Unfortunately, this technique can be used only when a rash is visible for accurate localization of the biopsy site. Biopsy specimens generally are obtained with a 3-mm punch in the center of the skin lesion. Immunofluorescent demonstration of rickettsiae in frozen sections of skin biopsy specimens has a sensitivity of 70%. Results of immunohistochemical staining of tissues at autopsy were positive in all fatal cases in one study, whereas IFA results were negative in most cases. Failure to obtain a biopsy specimen of a rickettsial cutaneous lesion or failure to obtain sections through its center is associated with false-negative results. Treatment with antirickettsial drugs for 24 hours does not appreciably alter the sensitivity of the test; however, after 48 hours, rickettsiae are substantially reduced in number.

species. Real-time PCR assays that can be completed in 1 hour and are 100% specific for RMSF have been developed but are not readily available.32

Isolation of Organism For most pathogenic infections, the standard diagnostic criterion is isolation and identification of the causative organism from the patient’s blood or tissues. This is seldom attempted in rickettsioses, however, because the isolation procedures are time-consuming, expensive, and hazardous to laboratory personnel. In addition, primary isolation of rickettsiae by inoculation in the yolk sac of a chick embryo usually fails because of the small number of organisms in the patient’s blood.

Management Treatment of RMSF consists of antibiotic therapy, supportive care, and possibly administration of steroids. An understanding of the underlying pathophysiologic changes and appreciation of the systemic complications that can occur in the patient afflicted with RMSF are necessary for the formulation of a balanced therapeutic regimen. The course of the disease can be complicated by circulatory collapse, coma, renal failure, and electrolyte imbalances. Although these complications are often absent in the mildly ill patient, for whom antibiotic therapy alone usually suffices, they should be anticipated in the seriously ill patient, especially if the patient is first seen late in the disease course. The most important factor contributing to the persistent case fatality rate of 5% is delayed administration of specific antibiotic therapy. Without appropriate treatment, the fatality rate rises to 25%. For a select group of early-stage, mildly ill patients, outpatient therapy with oral antibiotics can be successful if the patient is reliable and close follow-up observation is arranged. More severely ill patients in whom the diagnosis is uncertain should be hospitalized for the administration of IV antibiotics.

Serologic Studies

Supportive Care

Rickettsial infection can be confirmed by demonstration of an antibody rise in paired sera. Even with the most sensitive serologic tests, however, elevations in antibody titers do not occur until approximately 5 to 7 days after the onset of initial symptoms. Accordingly, serodiagnosis is retrospective. It is achieved by comparing acute serum, which typically yields negative findings, with convalescent serum, which yields positive results for antibodies. The indirect IFA generally is considered to be the reference standard for RMSF diagnosis and is the test currently used by the CDC and most state public health laboratories. It has a high specificity and sensitivity (94%). IFA can be used to detect IgG or IgM antibodies. An RMSF latex agglutination test that reportedly gives a turnaround result in less than 24 hours is available in selected laboratories.13 A prior study has shown a 12% seroprevalence, with antibody titers of 1 : 64 or higher, in the pediatric population in the southeastern and south central regions of the United States. Accordingly, clinical correlation with titers in these regions is critical. Convalescent-stage blood samples are best obtained 2 to 3 weeks after the onset of clinical illness. Antibiotic therapy does not affect the time of appearance of antibodies or their ultimate titer if this treatment is begun several days after the onset of illness. However, if antibiotic therapy is initiated earlier in the course of the illness, the rise in titers can be delayed for 4 weeks or more. Under these circumstances, antibody titers should be tested again at 4 to 6 weeks after the onset of illness. Nested PCR testing with a turnaround time between 1 and 2 days has been used but is not specific for individual rickettsial

Major complications of RMSF, such as shock, congestive heart failure, disseminated intravascular coagulation, and ARDS, should be anticipated and standard supportive measures instituted when appropriate. Circulatory collapse is common in patients with severe illness and is a major contributor to morbidity and mortality in RMSF. Hypotension unresponsive to fluid administration may require the use of vasopressors, such as dopamine. In the critically ill patient with widespread vasculitis, however, a delicate balance exists between maintenance of effective circulating volume and excessive leakage of fluids into the tissues, including the lungs and brain. Under these circumstances, the excessive administration of IV fluids can be catastrophic. Isolation of the patient is unnecessary unless the diagnosis is still uncertain and other highly communicable illnesses, such as meningococcemia and measles, have not been excluded.

Antibiotics Antibiotic therapy is most effective when initiated during the early stages of disease, coincident with the initial appearance of the rash. Although data from randomized clinical trials about antibiotic selection for RMSF are lacking, doxycycline is still widely regarded as the therapeutic agent of choice for most patients, including children.33 Chloramphenicol should be considered only for patients in whom tetracyclines have caused significant adverse events and for pregnant women, except those who are near term. The recommended doses of doxycycline and chloramphenicol are summarized in Table 126.5.

CHAPTER 126  Tickborne Illnesses

TABLE 126.5 

Antibiotic Therapy for Rocky Mountain Spotted Fevera PATIENT

DOXYCYCLINEb (ORAL OR IV)

CHLORAMPHENICOLc (ORAL OR IV)

Adult

100 mg bid; consider initial loading dose of 200 mg IV for seriously ill patients

50–75 mg/kg/day, divided q6h

Child (