Study Finds Adrenaline Auto-Injectors Mostly Ineffective Against Fatal Anaphylaxis

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Adrenaline auto-injectors have little effect on fatal anaphylaxis rates, according to new findings, and the injectors’ lack of a sustained plasma adrenaline concentration suggests a need for alternatives for adrenaline infusion.^1,2

These findings represented the conclusion of new research published in Clinical & Experimental Allergy evaluating self-administered auto-injectors and their implementation among individuals with severe allergies resulting in anaphylaxis. The study was led by Marcus Sim, MD, from the National Heart and Lung Institute at Imperial College London.

Sim and colleagues noted that anaphylaxis, an acute systemic hypersensitivity reaction to various allergens, is typically associated with such conditions as nausea, breathing issues, and shock. They added that those who suffer from this condition are often prescribed adrenaline (epinephrine) autoinjectors like EpiPens.

“The experience of anaphylaxis, and ongoing risk of further episodes can have a significant impact on mental health and quality of life,” Sim et al. wrote. “In this article, we review the role of adrenaline in anaphylaxis management, and explore the effectiveness of (adrenaline auto-injectors) for preventing fatal outcome.”¹

Analysis Highlights

Autoinjectors were described by the investigators as having originally been developed in the 1960s for the American military, with rapid administration of intramuscular (IM) atropine being provided to individuals to counteract the impact of nerve agents. The EpiPen in the present day dominated the adrenaline auto-injector market up until US Food and Drug Administration (FDA) approvals led to the Adrenaclick and Auvi-Q also being widely marketed.

The research team pointed to parallels between the lack of randomized controlled trial evidence for the mortality reductions of auto-injectors and of parachutes, though they wrote that these situations differ. The team highlighted survival without a parachute is nearly impossible, yet anaphylaxis often resolves on its own without intervention.

Additionally, the investigators point to the general rarity of severe outcomes such as mortality or long-term neurodisability in anaphylaxis, adding that the mechanisms behind fatal situations are not well understood. The team highlighted that this causes difficulties in the establishment of surrogate markers for potentially deadly cases of anaphylaxis.

The evidence in support of adrenaline auto-injectors’ prevention of fatal anaphylaxis mainly comes from animal research, epidemiological data, and smaller human observational studies. Data was highlighted by the investigators suggesting that intravenous adrenaline infusions, commonly provided for patients at doses ranging from 0.05 - 0.5 μg/kg/min for 1–2 hours (or approximately 10 μg/kg total), are effective in physiological effect reversal in cases of anaphylaxis.

The research team also found that similar adrenaline levels, with a range between 100 - 500 pg/mL, can be successfully achieved through the use of intramuscular injection. However, the team noted that such levels are typically shown to be short-lived, adding that there is a general unpredictability of the pharmacokinetics and pharmacodynamics.

Notable Findings

Epidemiological data highlighted by the investigators indicated that the incidence of visits to emergency departments, anaphylaxis, and hospitalizations resulting from instances of anaphylaxis have risen during recent decades. This has been particularly true in cases of childhood food anaphylaxis.

Nevertheless, a notable finding reported by the research team is that the overall rate of fatal anaphylaxis has continued to be relatively stable. The team added that there is no clear evidence suggesting an association between the rise in prescriptions for auto-injectors and a reduction in fatal anaphylaxis.

The investigators added that the rates at which individuals carry and implement auto-injector devices remains low. All of these findings indicate that current adrenaline auto-injectors may have limited influence on cases of fatal anaphylaxis, and the team noted that this may be due to their inability to maintain adequate plasma adrenaline concentrations.

Lastly, the research team highlighted the fact that the effect of device prescriptions on quality of life appears to vary.

“Consistent with the findings from in vivo studies in humans, dogs and rats, the steady increase in (adrenaline auto-injectors) availability over the past 35 years has not been accompanied by an equivalent reduction in population rates of fatal anaphylaxis,” they wrote. “Thus, (adrenaline auto-injectors) may not be reliably effective for preventing fatal anaphylaxis.”

References

1. ^{Sim M, Sharma V, Boyle R, et al (2024). Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis. Clin Exp Allergy. https://doi.org/10.1111/cea.14565.}
2. ^{Can adrenaline auto-injectors prevent fatal anaphylaxis? EurekAlert! October 9, 2024. https://www.eurekalert.org/news-releases/1060201. Date accessed: October 9, 2024.}