2-Hour Emergency Department Observation Safe After Epinephrine

A new study suggested that a 2-hour observation after receiving epinephrine at an emergency department for an acute allergic reaction may be safe for most children.1

"A 4-[hour] observation period might be enough for patients with cardiovascular involvement who appear well,” wrote study investigator Timothy E. Dribin, MD, from the division of emergency medicine at Cincinnati Children's Hospital Medical Center, and colleagues.1

At the emergency department, children with anaphylaxis receive at least one dose of epinephrine and then are observed for recurrent anaphylaxis or ongoing symptoms. Observations can last variable durations before discharge is deemed safe. Investigators sought to determine an optimal observation duration for children receiving epinephrine for anaphylaxis.

In this multicenter, retrospective cohort study across 30 emergency departments in the United States and Canada, investigators aimed to estimate the incidence and timing of repeat epinephrine to identify the observation threshold where the cumulative incidence fell below 2% for each additional monitoring hour. The primary outcome was the time from first to last administration of epinephrine. For patients receiving intravenous infusions, this interval was defined from the start to the discontinuation of the infusion.

Dribin and colleagues collected data on demographics, medical history, and emergency department revisits within 72 hours of discharge via electronic medical records. They evaluated the cumulative incidence of repeat epinephrine using Kaplan-Meier analyses, comparing time to last dose by initial reaction severity and stratified by respiratory and cardiovascular involvement.1

The sample included 5641 children aged 6 months to 17 years (mean, 7.9 years; 56.1% males) who visited an emergency department with an acute allergic reaction. Children either received intramuscular, subcutaneous, or intravenous epinephrine before or during the emergency department visit between 2016 and 2019. The study excluded patients who had no documentation of symptoms before heading to the emergency department, were transferred from outside healthcare facilities, had medication-related adverse events in the emergency department, or had comorbidities requiring personalized management.1

Among the participants, 78% identified as non-Hispanic, and 22% identified as Hispanic. In total, 263 (4.7%) patients received a second epinephrine dose 2 hours after the first one, 109 (1.9%) received repeat epinephrine after 4 hours, 61 (1.1%) after 6 hours, and 46 (0.8%) after 8 hours.1

The study found that the observation period when the increase in cumulative incidence of repeat ephedrine was less than 2% was 115 minutes, or 1 hour and 55 minutes (95% confidence interval [CI], 105 – 122). Moreover, the observation time when repeat epinephrine had a cumulative incidence below 2% was 105 minutes (95% CI, 54 – 135) for patients without respiratory or cardiovascular involvement (n = 1070), 109 minutes (95% CI, 98 – 118) for patients with respiratory but no cardiovascular involvement (n = 4076), and 161 minutes (95% CI, 125 – 249) for patients with cardiovascular involvement (495).1

The findings indicate that 95.3% of patients could safety discharge 2 hours after receiving their first epinephrine dose, and 98.1% could safely discharge after 4 hours.

1 in 7 children with anaphylaxis experience a biphasic reaction

A study published earlier this year found approximately 1 in 7 children with anaphylaxis experience a biphasic reaction after receiving an intramuscular injection of ephedrine.2

When patients were treated with intramuscular epinephrine and corticosteroid—either dexamethasone, methylprednisolone, prednisolone, or prednisone—all biphasic reactions occurred within the 0 – 4-hour interval after treatment initiation. No child required an extra dose of epinephrine during the 4 – 48 hours after treatment initiation (95% CI, 0 – 1.3%; P ≤ .001). Furthermore, no child returned to the emergency department with persistent anaphylaxis symptoms within 48 hours of discharge.2

“The [intramuscular epinephrine] effect is rapid in onset, lasting briefly… whereas [corticosteroid] has clinical onset approximately > 4 hours following administration, lasting beyond 24 hours,” wrote study investigator William Bonadio, MD, from Mount Sinai Morningside Medical Center, and colleagues.2 “It is likely that after four hours the [intramuscular epinephrine] effect wanes, and any ongoing anti-allergy effect is likely due to [corticosteroid]. Within this context, we found the rate of [biphasic reaction] requiring repeat [intramuscular epinephrine] administration was significantly lower 4 - 48 hours vs 0 - 4 hours after initiating therapy.”

References

1. 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

2. Derman, C. Biphasic Anaphylaxis in Children: Study Finds 1 in 7 Cases Occur After Epinephrine. HCPLive. February 12, 2025. https://www.hcplive.com/view/biphasic-anaphylaxis-in-children-study-finds-1-in-7-cases-occur-after-epinephrine. Accessed August 18, 2025.