0.5 mg Epinephrine Dose Reduces Need for Additional Anaphylaxis Treatment

New research found that significantly fewer patients receiving an initial 0.5 mg intramuscular epinephrine for anaphylaxis required additional intervention compared to those who received 0.3 mg.1

“These findings support the World Allergy Organization weight-based recommendation for adult patients experiencing anaphylaxis,” wrote study investigator Caroline A. Jackson, PharmD, from the department of pharmaceutical services at Vanderbilt University Hospital, and colleagues.

The World Allergy Organization recommends intramuscular epinephrine 0.01 mg/kg, with a maximum dose of 0.5 mg, for individuals experiencing anaphylaxis.2 The dose of 0.3 mg is the most common despite increased risks of poor outcomes in adults who weigh over 110 lbs.1

In this retrospective study, investigators aimed to investigate the incidence of patients requiring additional intervention after initial epinephrine dosing to treat anaphylaxis.1 The study defined escalating care as an additional dose of intramuscular epinephrine, epinephrine infusion initiation, or intubation 6 hours after the initial dose.

The study also compared adverse events between dosages, which was the secondary outcome. Other secondary outcomes include the efficacy of the individual additional treatments, the resolution of symptoms, and the length of stay in the emergency department (ED).

Safety outcomes included peak change in heart rate and systolic blood pressure > 200 mmHg, ischemic changes noted on EKG, and atrial or ventricular arrhythmia, all within 6 hours of epinephrine administration. Investigators also measured elevated troponin (≥ 0.04 ng/mL) within 12 hours of epinephrine administration.

The study included 338 patients aged ≥ 18 years (mean age, 44 years; range, 29 – 57) who received intramuscular epinephrine 0.3 (n = 254) or 0.5 mg (n = 84) for anaphylaxis from 2018 to 2024 at Vanderbilt University Hospital. The sample had 61% females and a median weight of 82 mg (IQR, 71 – 98). Most patients were at the hospital for anaphylaxis (73%), while 27% of participants were already in the ED or admitted to the hospital at the time of the patients’ initial anaphylaxis symptoms, which included urticaria (78%), shortness of breath (57%), facial or mouth swelling (38%), nausea and/or vomiting (23%).1

The most common additional treatment after initial epinephrine was another epinephrine dose (23%), followed by an epinephrine infusion (6%) and intubation (2%).1

Investigators found the incidence of escalating care was significantly greater in the 0.3 mg group compared to the 0.5 mg group (29.5% vs 7.1%; P <.001). They found similar findings when comparing the incidences of an additional intramuscular dose (28% vs 6%; P <.001) and infusion initiation (7.7% vs 1.2%; P =.034), both of which were significantly greater in the 0.3 mg group. A multivariable logistic regression confirmed that an initial dose of 0.5 mg epinephrine was independently associated with a lower incidence of requiring additional treatment.1

The analysis also found that the 0.5 mg group had a longer time from first epinephrine dose to additional treatment (29 minutes [IQR, 16.5 – 39.3] vs 26 minutes [IQR, 9.5 – 78.4]), though this lacked significance (P =.928).

Compared to the 0.3 mg group, more participants in the 0.5 mg group had a resolution of symptoms after the first epinephrine dose (95.2% vs 72.4%; P <.001) and fewer required hospital admission (14.5% vs 28.7%; P =.010). The 0.5 mg group also had a shorter ED length of stay (4.1 [IQR, 2.8 – 5.4] vs 5.0 [IQR, 3.9 – 6.9; P <.001).1

The study observed no major difference between groups for the outcomes of peak increase in heart rate, systolic blood pressure > 200 mmHg, ischemic changes on EKG, and atrial or ventricular arrhythmia within 6 hours of initial epinephrine or elevated troponin within 12 hours of initial epinephrine. Since many patients did not have documented safety data, investigators noted that it was difficult to interpret these findings.1

“Larger, prospective studies are needed to confirm the use of an initial IM epinephrine dose of 0.5 mg leads to less escalation of care and to determine the impact of the two doses on safety outcomes in patients with anaphylaxis,” investigators wrote.1 “Our study provides justification for following the recommended guideline dosing of epinephrine in the treatment of anaphylaxis.”

References

1. Jackson CA, Dillon RC, Fleenor LM, Pauw EK, O'Keefe MM. Retrospective comparison between 0.3 mg and 0.5 mg dosing of intramuscular epinephrine for anaphylaxis. Am J Emerg Med. Published online October 10, 2025. doi:10.1016/j.ajem.2025.10.020

2. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472. Published 2020 Oct 30. doi:10.1016/j.waojou.2020.100472