Epinephrine and its Use in Anaphylaxis: Current Issues

Keith J. Simons; F. Estelle R. Simons


Curr Opin Allergy Clin Immunol. 2010;10(4):354-361. 

In This Article

Evidence Base for Epinephrine Use in Anaphylaxis

No randomized controlled trials that meet optimal standards have been published for any medication used in the treatment of acute anaphylaxis; however, the evidence base for epinephrine injection in anaphylaxis is stronger than the evidence base for use of H1-antihistamines, H2-antihistamines, or glucocorticoids in the initial treatment of this disease.[26•,27,28] Recommendations for prompt epinephrine injection are based on a century of clinical use [1] and on fatality studies,[17,29–31] epidemiologic studies,[9,10] and prospective studies.[12–15,32,33] The latter include both dramatic observational nonrandomized uncontrolled studies in patients actually experiencing anaphylaxis at the time of the investigation[32,33] and randomized controlled studies in patients not experiencing anaphylaxis at the time of the investigation.[12–15] In vitro studies relevant to anaphylaxis[1,12,34] and studies in animal models of anaphylaxis[1,12,35] have also been performed.

Delayed injection of epinephrine is potentially associated with fatal anaphylaxis.[17,29–31] In a study of 164 patients with fatal anaphylaxis, the median time from initial symptom to cardiorespiratory arrest was 5 min in iatrogenic anaphylaxis, 15 min in venom-triggered anaphylaxis, and 30 min in food-triggered anaphylaxis.[17] In this and other fatality studies, a small percentage of patients died despite receiving an injection of epinephrine before they experienced cardiac arrest. The body weight and, therefore, the adequacy of the epinephrine dose on a mg/kg basis were either not known or not reported in these patients. For many of them, the precise time elapsed from the first symptom to epinephrine injection, and whether the injection was administered correctly were also not known or not reported.[17,29–31]

Delayed injection of epinephrine might be one of several factors contributing to biphasic anaphylaxis, defined as symptom recurrence 1–72 h (usually within 8 h) after resolution of the initial symptoms, without ongoing or further exposure to the anaphylaxis trigger.[8•,36•,37•]


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