How Long to Observe After Epinephrine for Anaphylaxis

Source: 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.Investigators from multiple institutions conducted a retrospective study to determine the incidence and timing of administration of multiple doses of epinephrine in children with anaphylaxis. A main goal of the study was to determine when it would be safe to discharge most patients from the emergency department (ED) after receiving treatment. Study participants were children 6 months to 17 years old who were treated at 31 EDs (30 in the US and 1 in Canada) for anaphylaxis between 2016 and 2019. Study patients were identified using ICD-10 codes; only those who received ≥1 dose of epinephrine were included. The medical records of participants were reviewed and demographic and clinical data abstracted. The time of administration of all doses of epinephrine were recorded, including those received prior to presentation to the ED. The presence of specific clinical findings was used to determine whether a participant strictly met criteria for a diagnosis of anaphylaxis. Patients were also characterized as having respiratory and/or cardiovascular involvement. The primary outcome was time from first to last epinephrine administration in a study child. Kaplan-Meier analysis was used to determine the time after the initial dose of epinephrine when the cumulative incidence of an additional dose was <2%, ie, the time at which it would be safe to discharge most children with anaphylaxis. The analysis was conducted for all patients, and those with respiratory or cardiovascular involvement, or neither.Data were analyzed on 5,641 children with a median age of 7.9 years. Among these patients, 4,956 (87.9%) met strict criteria for a diagnosis of anaphylaxis, and 2,562 (45.4%) received epinephrine before ED presentation. Repeat doses of epinephrine were administered to 263 (4.7%) study children after 2 hours from the initial dose, 109 (1.9%) after 4 hours, 64 (1.1%) after 6 hours, and 46 (0.8%) after 8 hours. Based on the Kaplan-Meier analysis, 115 minutes (95% confidence interval [CI], 105, 122) after the initial dose of epinephrine, the cumulative incidence of an additional dose was <2%, suggesting that 2 hours after the initial dose, 5,378 (95.3%) patients could have been safely discharged; 5,532 (98.1%) could be safely discharged after 4 hours. For the subgroup of 1,070 children without respiratory or cardiovascular involvement, the cumulative incidence of an additional dose of epinephrine was <2% at 105 minutes (95% CI, 54, 135). The threshold for a cumulative incidence <2% was 109 minutes (95% CI, 98, 118) for 4,076 patients with respiratory but not cardiovascular involvement and 161 minutes (95% CI, 125, 249) for 495 children with cardiovascular involvement.The authors conclude that a 2-hour observation period following an initial dose of epinephrine is probably safe for most children presenting to the ED with anaphylaxis.Dr Bechtel has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Anaphylaxis is a common reason for ED visits in children.1,2 From 2008 to 2016, there were more than 400,000 ED visits for anaphylaxis in the US, during which time visits tripled in children.3 Many children with anaphylaxis receive intramuscular epinephrine, and the optimal observation period to detect recurrence of symptoms is debatable. The current study results demonstrate that shorter, risk-stratified observation periods for children with anaphylaxis treated with epinephrine and emphasize the importance of reaction severity in determining safe discharge times.The current study has numerous strengths. First, data were collected from 5,641 children across 31 EDs in the US and Canada, making it one of the largest cohorts to evaluate anaphylaxis observation periods. Second, the study stratified patients based on reaction severity (eg, respiratory and cardiovascular involvement), allowing for tailored recommendations for observation periods. Third, Kaplan-Meier analyses were employed to identify observation thresholds and predictors of repeat epinephrine administration, providing detailed insights into the timing and risk factors. Fourth, the study focused on the timing of repeat epinephrine administration, a clinically relevant outcome that directly informs safe discharge practices.There were, however, minor limitations. The study was retrospective, with potential for data collection bias and loss to follow-up. Findings may not be generalizable to community EDs, as all patients were evaluated in children’s hospital EDs.Most children with anaphylaxis without cardiac involvement may be observed for 2 hours after receiving epinephrine in the ED, a shorter time duration than currently recommended.