Second Dose of Epinephrine for Anaphylaxis in the First Aid Setting: A Scoping Review

Anaphylaxis is a life-threatening hypersensitivity reaction where rapid, early administration of epinephrine (adrenaline) can be lifesaving in the first aid setting. There are instances where a single dose of epinephrine does not relieve symptoms and a second dose may be required to further mitigate symptoms and preserve life. We performed a scoping review as part of an update to a previously conducted International Liaison Committee on Resuscitation First Aid Task Force (ILCOR) review. PubMed and Embase were searched using the strategy from the 2015 ILCOR review (dates January 1, 2015 to October 22, 2019) and a review of the grey literature (all dates up to November 18, 2019) was performed to identify data on the requirement, use, and effectiveness of a second dose of epinephrine. Each search was rerun on June 26, 2020. We included all human studies of adults and children with an English abstract. Critical outcomes included resolution of symptoms, adverse effects, and complications of second dosing of epinephrine in the treatment of acute anaphylaxis. Included studies are presented descriptively. Our updated search identified 909 potential sources, 890 from the published literature and 19 from the grey literature. After full text review, two studies met our eligibility criteria (Campbell et al. and Akari et al.). For the outcome of resolution of symptoms, both studies found that two or more doses of epinephrine were required in 8% of 582 patients and 28% of 18 patients, respectively, with anaphylaxis requiring treatment with epinephrine. The other a priori outcomes were not reported. This scoping review identified limited evidence regarding the use of a second dose of epinephrine for anaphylaxis in the first aid setting, however, due to the potential benefit, it is reasonable to administer a second dose when symptoms of severe anaphylaxis fail to resolve following an initial dose. Given the potential mortality associated with anaphylaxis, further research is needed to better identify individuals who may benefit from a second dose of epinephrine.