Written by Clay Smith
For anaphylaxis in adults ≥50kg, 0.5mg vs. 0.3mg IM epinephrine is strongly associated with a reduction in escalation of care (repeat epi, epi drip, or intubation).
So weird that a dose circa 1918 needs to be reconsidered…
Epinephrine auto-injectors come with standard 0.3mg doses (0.15mg for pediatrics). But why 0.3mg? The recommended dose is 0.01mg/kg, max 0.5mg. Most adults weigh more than 50kg. Might a 0.5mg dose be better?
This retrospective, single-center study found that among 338 adult patient (254 received 0.3mg; 84 received 0.5mg), escalation of care (repeat IM epi, epi drip, or intubation) was far more common in the 0.3mg cohort: 30% vs. 7%, p < 0.001. This composite outcome was driven by repeat epinephrine dosing (28% vs 6%), followed by epi drip (7.8% vs 1.2%), then intubation (2.8% vs 0%) in the 0.3mg vs. 0.5mg cohorts, respectively. The 0.5mg cohort was slightly heavier, but this was not statistically significant: 81.8 kg vs. 86.2, p = 0.302. Safety variables such as troponin were often not documented; therefore, this study cannot conclusively address them. Heart rate increased 9.5 beats/minute in the 0.5mg group. Using multivariate logistic regression, a 0.5mg dose of epinephrine was independently associated with a marked reduction in escalation of care: OR 0.17 (95%CI 0.07–0.41, p<0.001).
In my own unadjusted calculations, I found RR 0.24 (95%CI 0.11-0.54) for escalation of care. Assuming this association is true, this would be a NNT = 5. As always, retrospective studies may be confounded. That said, I work in this hospital system, and it seems there are some of us that go up to 0.5mg and some that rigidly start with 0.3mg, somewhat arbitrarily.
How will this change my practice?
I personally don’t see a downside to weight-based, appropriate, guideline-concordant dosing of epinephrine. We should not be chained to a 0.3mg dose just because a pharmacology textbook from 1918 recommended it––that’s nuts (oh wait… hope you’re not allergic to nuts). If your patient is ≥50kg, go with the 0.5mg dose.
Source
Retrospective comparison between 0.3 mg and 0.5 mg dosing of intramuscular epinephrine for anaphylaxis. Am J Emerg Med. 2025 Oct 10;99:270-275. doi: 10.1016/j.ajem.2025.10.020. Epub ahead of print. PMID: 41106150.
