Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis

Sim, M., Sharma, V., Li, K., Gowland, M., Garcez, T., Shilladay, C., Pumphrey, R., Patel, N., Turner, P. and Boyle, R. (2024), Clin Exp Allergy. https://doi.org/10.1111/cea.14565

ABSTRACT

Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human in vivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1–2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100–500 pg/mL.

However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.

Graphical Abstract

During 35 years of increasing Adrenaline Autoinjector prescribing, there has been no obvious reduction in numbers of fatal anaphylaxis cases. Animal and human studies suggest intravenous adrenaline infusion, with appropriate fluid resuscitation, prevents fatal anaphylaxis. Current Adrenaline Autoinjectors may have little impact on rates of fatal anaphylaxis due to a lack of sustained and sufficient plasma adrenaline concentration.

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