Rosen & Barkin's 5-Minute Emergency Medicine Consult (644 page)

• Stabilize airway
  
• Vital signs
  
• IV access
  
• Fingerstick glucose
  
• Oxygen administration if needed
  

• Stabilize airway, establish IV access, continuous cardiac and temperature monitoring
  
• Conscientious avoidance of additional serotonergic agents while in-hospital (e.g., caution with ondansetron, fentanyl, linezolid, meperidine, dextromethorphan)
  
• Supportive care is cornerstone of treatment
  
  • Aggressive cooling measures particularly important if hyperthermia present
    
  • Fluid resuscitation
    

• Benzodiazepines are 1st-line medications:
  
  • Lorazepam, diazepam
    
• Aggressive cooling measures for hyperthermia:
  
  • Ice packs, cooling blanket, cool mists/fans
    
  • Hyperthermia derives from muscular rigidity and is not usually responsive to antipyretic medications
    
• Severe symptoms (e.g., uncontrollable hyperthermia) may necessitate intubation:
  
  • Paralytics may be required to control muscular rigidity and hyperthermia
    
• Cyproheptadine:
  
  • Nonspecific antihistamine with 5-HT2A antagonist activity may be considered for severe cases, but benefit has not been definitively established
    
  • Only PO available (must be crushed and given through oro- or nasogastric tube)
    
• Poison Control Center/Toxicology guidance (1-800-222-1222)
  

FOLLOW-UP

• All patients suspected to have serotonin toxicity, even mild-appearing cases, should be admitted for monitoring and treatment
  
• Severe symptoms including uncontrollable hypertension, altered mental status, cardiovascular instability, hyperthermia require ICU monitoring
  

• Discharge may be considered when all symptoms have resolved
  
• Careful evaluation of discharge medications and patient education is essential
  
• Poison Control Center guidance is recommended
  

Follow up with primary care after discharge

• Serotonin syndrome may be mild to severe in presentation; diagnosis in mild cases often elusive/missed
  
• Mental status changes, hyperthermia, muscular clonus in lower extremities are important findings
  
• Hyperthermia is due to muscular rigidity, should be aggressively controlled, and is not responsive to antipyretics
  
• Cyproheptadine has not been shown definitively to be beneficial but may be considered in severe cases
  
• Attentive supportive care and avoidance of serotonergic agents is the mainstay of care
  

• Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome.
  Am Fam Physician
  . 2010;81:1139–1142.
  
• Boyer EW, Shannon M. The Serotonin syndrome.
  N Engl J Med
  . 2005;352(11):1112–1120.
  
• Kant S, Liebelt E. Recognizing serotonin toxicity in the pediatric emergency department.
  Pediatr Emerg Care
  . 2012;28(8):817–824.
  
• Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: A review.
  Expert Opin Drug Saf
  . 2008;7(5):587–596.
  
• Torre LE, Menon R, Power BM. Prolonged serotonin toxicity with proserotonergic drugs in the intensive care unit.
  Crit Care Resusc.
  2009;11:272–275.
  

CODES

333.99 Other extrapyramidal diseases and abnormal movement disorders

BASICS

• Type III hypersensitivity reaction
  
• When a foreign protein or drug (the antigen) is injected, the body’s immune system responds by forming antibodies to the foreign material and subsequently forms complexes composed of the antigen, antibody, and complement.
  
• These complexes then deposit in tissue, inciting an inflammatory response:
  
  • C3a and C5a act as anaphylatoxins.
    
  • C5a is strongly chemotactic for neutrophils.
    
  • The neutrophils then infiltrate the vessel wall at the site of the immune complex deposition and release enzymes, such as collagenase and elastase, which damage vessel walls.
    
• Typically, symptoms arise 6–21 days after the primary exposure to the antigen.
  
• Symptoms can start 1–4 days after exposure if there has been an initial immunizing exposure.
  
• Symptoms typically last 1–2 wk before spontaneously resolving.
  

• Serum sickness:
  
  • Vaccines containing foreign protein or serum such as pneumococcal vaccine or rabies.
    
  • Antivenom and tetanus inoculations made with horse or sheep protein
    
  • Monoclonal antibodies
    
• Serum sickness–like reaction:
  
  • Caused by nonprotein drugs, mostly antibiotics:
    
    • Penicillins, amoxicillin
      
    • Cephalosporins (i.e., Cefaclor)
      
    • Sulfonamides (i.e., Bactrim)
      
    • Thiazides
      
    • Gold
      
    • Thiouracils
      
    • Hydantoins
      
    • Phenylbutazone
      
    • Aspirin
      
    • Streptomycin
      

DIAGNOSIS

Classic presentation is fever, rash, arthralgias, and lymphadenopathy.

• Fever
  
• Rash (urticarial, morbilliform, scarlantiniform)
  
• Arthralgias
  
• Myalgias
  
• Lymphadenopathy
  
• Facial and neck edema
  
• Chest pain
  
• Shortness of breath
  

• Fever
  
• Rash
  
• Lymphadenopathy
  
• Arthritis
  
• Edema
  
• Splenomegaly
  
• Peripheral neuritis
  
• Myocarditis/pericarditis
  
• Anaphylaxis
  

• History of a possible offending agent and time course of 6–21 days before onset of symptoms
  
• Physical exam revealing rash as well as joint, muscular, cardiac, neurologic, or renal insult from vasculitic type process
  

• Decreased complement levels
  
• CBC, possible eosinophilia
  
• Elevated ESR
  
• Hypergammaglobulinemia
  
• Urine with proteinuria or hematuria
  

Consider CXR.

Biopsy is the only means of definitive diagnosis.

• Vasculitides (e.g., polyarteritis nodosa, Goodpasture, Wegener)
  
• Rashes (e.g., erythema multiforme, toxic epidermal necrolysis)
  
• Immunologic (e.g., systematic lupus erythematosus, polymyositis, anaphylaxis)
  
• Infectious (e.g., tick-borne disease, Rocky Mountain spotted fever, mononucleosis)
  

TREATMENT

• ABC stabilization
  
• Anaphylaxis treatment as indicated.
  

ABCs if a severe systemic reaction is present

• Symptomatic relief until the disease spontaneously resolves in 1–13 wk
  
• Antihistamines
  
• Antipyretics
  
• NSAIDs
  
• Prednisone is controversial
  

• Acetaminophen: 325–650 mg PO/PR (peds: 10–15 mg/kg) q4–6h
  
• Diphenhydramine: 50–100 mg (peds: 5 mg/kg/d, div., max. dose 50 mg/dose or 300 mg/24h) q6–8h
  
• Hydroxyzine: 25–50 mg (peds: 0.5 mg/kg/dose) q6–8h
  
• Ibuprofen: 200–800 mg PO (peds >6 mo: 5–10 mg/kg) q6–8h
  
• Prednisone: 5–60 mg/d PO (peds: 0.5–2 mg/kg/d), 2-wk taper
  

FOLLOW-UP