Timing of Repeat Epinephrine in Pediatric Anaphylaxis: How Long Should We Observe?

Introduction Observation periods after epinephrine treatment for pediatric anaphylaxis vary widely across emergency departments. While prolonged stays are often intended to catch biphasic reactions, they can also lead to unnecessary admissions and extended ED length of stay. This multicenter retrospective study aims to provide evidence-based guidance by determining when the risk of repeat epinephrine administration becomes acceptably low. What Did They Do? Researchers conducted a retrospective cohort study across 30 US and 1 Canadian pediatric emergency departments, analyzing data from 5641 children (ages 6 months to 17 years) treated with epinephrine for an acute allergic reaction between 2016 and 2019. The primary outcome was the time from first to last epinephrine dose, whether given before arrival, in the ED, or during hospitalization. The investigators used Kaplan-Meier analyses and a semiparametric cure model to identify the observation threshold after which the cumulative incidence of repeat epinephrine was less than 2 percent. Patients were stratified by initial severity: No respiratory or cardiovascular involvement Respiratory involvement only Cardiovascular involvement Key Findings Overall 4.7 percent of children received repeat epinephrine after 2 hours 1.9 percent after 4 hours. Cumulative Incidence of Repeat Epinephrine by Time Threshold for <2 percent risk of repeat epinephrine Discharge safety 95.3 percent of the cohort could have been safely discharged at 2 hours 98.1 percent could have been safely discharged at 4 hours Predictors of repeat epinephrine included: Severe respiratory or cardiovascular symptoms History of severe anaphylaxis Prehospital epinephrine ED steroid administration Why Does This Matter? This is the largest study to date addressing the optimal observation period after epinephrine in children with anaphylaxis. By linking observation time to a quantifiable clinical risk threshold, the findings offer an evidence-based approach to streamline care. These results could support ED protocols that prioritize risk-stratified observation, reduce variability in practice, limit unnecessary admissions, and improve patient and caregiver experience without compromising safety. Bottom Line A 2-hour observation period after epinephrine is likely sufficient for most pediatric patients with anaphylaxis who do not have cardiovascular involvement. For those with cardiovascular symptoms, a 4-hour window is likely appropriate. Risk of repeat epinephrine drops significantly beyond those time points, suggesting diminishing returns with longer observation. Shared decision-making, access to epinephrine autoinjectors, and allergist follow-up remain essential. References Dribin TE, Sampson HA, Zhang Y, et al. Timing of repeat epinephrine to inform paediatric anaphylaxis observation periods: a retrospective cohort study. Lancet Child Adolesc Health. 2025;9(7):484-496. doi:10.1016/S2352-4642(25)00139-7