For many of us, the challenge in anaphylaxis isn’t when to give epinephrine (oftentimes, it’s pretty clear, but my personal rule of thumb: when in doubt, give it!), but rather what to do after the epi. Did it work? Great, now how long should I watch them? Worked a little bit, do I need to give more? Should I do steroids?
The first dose of epinephrine is only the beginning. Here are three decisions that come next.
1. A two-hour observation period after epi seems to be safe for most
The PEM CRC conducted a 31-center retrospective cohort study examining the timing of repeat epinephrine in pediatric anaphylaxis. Among 5641 children, only 4.7% received a second dose of epi after 2 hours following the initial dose, and only 1.9% after 4 hours. After stratifying the cohort based on severity, it was found that patients with no cardiovascular involvement were at low risk of receiving epi beyond 2 hours after the initial dose. Applying this to their cohort, the authors suggested that their findings could potentially support discharge after two hours for more than 95% of patients.
How is this being applied? CHOP’s Clinical Pathway has already incorporated this research, advising that if symptoms resolve after the first dose of epi (rash excluded), the patient can be discharged after 2 hours. For those who require 2 doses of epinephrine for symptom resolution, a four-hour observation period is recommended, with discharge if they remain well. If you need 3 or more doses? Admission it is.
What will I be doing? I’ve already started incorporating a two-hour observation period for most patients with anaphylaxis. For those children with more severe symptoms (even if they improve quickly after epi) or any other concerning features (i.e. delayed epinephrine administration, unknown trigger, parental concern), I will use my judgment and sometimes stretch the observation period out. For those parents who have been used to sitting in the ED for several hours as their fully recovered child waits out a four-hour obs period, I have found that they have been especially appreciative of this change.
2. Adjunctive medications? Maybe…
Sure, I’m biased, but the CHOP Clinical Pathway does a good job summarizing the utility of adjunctive medications:
- Antihistamines (H1) relieve symptoms such as hives and itching, but do not relieve severe symptoms.
- The addition of an H2 antihistamine may provide more symptomatic relief for pruritus and abdominal symptoms. They are not indicated for discharge care.
- For children who respond well to epinephrine, the addition of steroids is not necessary unless there are persistent respiratory symptoms. A 2020 systematic review failed to document a decrease in biphasic reactions with steroid use.
What is my practice? I consider use based on presentation. For those kids who received an EpiPen at home or from EMS and whose symptoms have resolved, I will typically recommend cetirizine for several days. For patients presenting in anaphylaxis, I will always prioritize the epinephrine, but then will typically give cetirizine (H1) and famotidine (H2), especially if they have GI symptoms. Steroids? For severe anaphylaxis (hemodynamic instability, need for multiple doses of epinephrine), I have to admit – I do tend to give steroids. I know, I know, the evidence doesn’t show improvement, but practically speaking we do give steroids to help taper inflammatory response in other conditions, so could there be some role in severe anaphylaxis? Is that controversial?
Do you use steroids in anaphylaxis? Comment below!
3. No needle, no problem – here comes neffy
Delayed administration of epinephrine is associated with more severe anaphylaxis and worse outcomes. Why don’t people give epi? There are several reasons, but one documented barrier is fear of the needle. For those who have never done it before, sticking your child with a needle can be pretty scary.
In 2024, the FDA approved neffy, the first commercially available epinephrine nasal spray. IN epinephrine provides a needle-free and much simpler option to administer this lifesaving medication. While there has not been a large trial yet, the evidence suggests that neffy may be an effective alternative that can help shift the paradigm of pediatric anaphylaxis treatment. A few of the studies so far (there’s not a ton):
- 2025, Phase 3 open-label study: 15 children, all of whom improved (1 needed IM epi for a biphasic reaction 2.5+ hours later), median symptom-resolution time was 16 minutes.
- 2023, adult study analyzing 4 randomized crossover phase 1 trials: neffy produced lower peak plasma epinephrine concentrations but a rapid systolic blood pressure response that was comparable to or greater than that observed with injected epinephrine.
- 2025, survey study looking at real-world data: In a survey of 375 healthcare professionals reporting on 680 patients treated with intranasal epinephrine, 603 patients (88.7%) were effectively treated with a single dose – a rate similar to that reported with injectable epinephrine.
The Bottom Line
While it may be a little longer until we have enough strong evidence to replace intramuscular epinephrine in our day-to-day practice in the ER, I think intranasal epi is a game changer in pre-hospital anaphylaxis management. Parents will almost certainly be more comfortable administering medication into their child’s nose than injecting it with a needle. Earlier epinephrine administration is associated with better outcomes, making PEM clinicians, parents, and, most importantly, our patients safer and happier.
Dr. Joshua Belfer, MD, is a Pediatric Emergency Medicine physician at the Children’s Hospital of Philadelphia, and is the Founder and Editor-in-Chief of HipPEMcrates. He can be reached at HipPEMcrates@gmail.com.
