Pharmacologic Management of Anaphylaxis


  • The consensus of experts is that, in general, treatment in order of importance is epinephrine, patient position, oxygen, intravenous fluids, nebulized therapy, vasopressors, antihistamines, corticosteroids, and other agents
  • The median times to cardiovascular and/or respiratory collapse during anaphylaxis are 10 min for iatrogenic events, 15 min for field insect stings, and 30 min for food

Protocol (Practice Parameter)

  • Remove exposure to trigger if possible (e.g. stop IV drug infusion)
  • Epinephrine, IM (anterior-lateral thigh); auto-injector or 1:1,000 solution (1 mg/mL)
    • Weight 10-25 Kg (22-55 lb): 0.15 mg epinephrine ("Junior") autoinjector
    • Weight >25 Kg (>55 lb): 0.3 mg epinephrine autoinjector
    • Exact dose by weight: Epinephrine 0.01 mg (or mL)/Kg per dose; maximum 0.3 mg (0.3 mL) per dose for children, maximum 0.5 mg (0.5 mL) per dose for adults
    • Note:
      • IM dose may need to be repeated every 5-15 minutes
      • The time to highest blood concentration (Cmax) is shorter when given IM in the lateral thigh (8 min) than when given either SC (34 min) or IM in the deltoid muscle of the arm
      • IV route may be considered if poorly responsive to IM, where there is inadequate time for emergency transport, or prolonged transport is required
        • Adolescent/adult: 1-15 mcg/minute
          • Infusion may be prepared by adding 1 mg (1 mL) of 1:1000 epinephrine to 250 mL of D5W to yield a concentration of 4.0 mcg/ml (1:250,000).
        • Child: 0.1 mcg/Kg/min
          • Infusion prepared by 0.6 X body weight (in Kg) = number of mg of epinephrine to be diluted to total 100 mL saline; then 1 mL/h delivers 0.1 mg/Kg/min
  • Place patient in recumbent position if tolerated, with the lower extremities elevated
  • Supplemental oxygen
  • IV fluid resuscitation if patient with orthostasis, hypotension, or incomplete response to IM epinephrine
    • Adult: 1-2 L of normal saline administered to adults at a rate of 5-10 ml/Kg in the first 5 minutes
    • Children: up to 30 mL/Kg in first hour
  • Albuterol
    • MDI: child: 4-8 puffs, adult 8 puffs
    • Nebulized solution 2.5 mg/3 mL every 20 minutes or continuously as needed
  • Vasopressors (other than epinephrine)
    • Dopamine
      • Adult: 2-20 mcg/kg/minute
        • Infusion prepared by 400 mg dopamine in 500 ml of D5W
      • Child: 2-20 mcg/kg/minute
        • Infusion prepared by 6 X body weight (in Kg) = number of mg of dopamine diluted to total 100 mL saline; then 1 mL/h delivers 1 mcg/kg/min
    • Glucagon IV for refractory hypotension; may reverse refractory bronchospasm and hypotension in patients on beta-blockers by activating adenyl cyclase directly and bypassing the beta-adrenergic receptor
      • Child: 20-30 mcg/Kg IV over 5 minutes (max 1 mg)
      • Adult: 1-5 mg over 5 minutes
      • Dose may be repeated or followed by infusion of 5-15 mcg/min titrated to clinical response
      • Protection of the airway is important since glucagon may cause emesis/aspiration in drowsy or obtunded patients. Placement in the lateral recumbent position may be sufficient airway protection.
  • Diphenhydramine
    • 1-2 mg/Kg per dose IV (slow infusion), IM, PO (oral liquid is more readily absorbed than tablets)
    • Maximum dose 50 mg
    • Alternative dosing may be with a less-sedating second generation antihistamine
  • Ranitidine
    • 1-2 mg/Kg per dose IV, IM, PO
    • Maximum dose 75-150 mg
    • If given IV, infuse over 10-15 minutes
  • Prednisone PO 1 mg/kg with a max dose of 60-80 mg or Methylprednisolone IV 1 mg/Kg with a max dose of 60-80 mg IV
  • If required:
    • Atropine for bradycardia, titrate to effect
  • Methylene blue 1% (1.5 mg/Kg in 100 mL of 5% dextrose IV over 20 minutes) has been reported as being effective in patients with anaphylaxis refractory to epinephrine
    • Controversial whether it should be reserved for patients with hypotension (as recommended by the practice parameter)


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Monitoring


Same day

  • Duration should be individualized according to the severity of the anaphylactic episode
  • Patients with moderate respiratory or cardiovascular compromise should be monitored for at least 4 hours and, if indicated, for 8-10 hours or longer, and patients with severe or protracted anaphylaxis might require monitoring and interventions for days

Next day

  • Biphasic anaphylaxis (recurrence of symptoms up to 72 hours [but usually 8-10 h] after initial symptoms) occurs in up to 23% of adults and up to 11% of children with anaphylaxis
    • Failing to treat initial symptoms with epinephrine increases risk for biphasic anaphylaxis
    • Other potential risk factors include concomitant asthma, low baseline peak expiratory flow, female gender, and the requirement for 2 doses of epinephrine to treat the initial systemic reaction



Discharge Care


  • Provide epinephrine auto-injector prescription (containing 2 doses) and injection instructions
  • Adjunctive treatment:
    • Diphenhydramine every 6 hours for 2-3 days; alternative dosing with a non-sedating second generation antihistamine
    • Ranitidine twice daily for 2-3 days
    • Prednisone daily for 2-3 days
  • Provide written action plan:
  • Medical identification jewelry (e.g. medic-alert bracelet) and/or wallet card
  • Follow-up with primary care physician
  • Consider referral to an allergist
    • Confirm anaphylaxis trigger(s) with allergy testing, usually waiting 3-4 weeks after anaphylaxis event
    • Provide avoidance education
    • Start desensitization or immunotherapy (if possible)



References