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Comparative Study
. 2025 Apr 1;8(4):e254720.
doi: 10.1001/jamanetworkopen.2025.4720.

Epinephrine vs Norepinephrine as Initial Treatment in Children With Septic Shock

Matthew A Eisenberg  1   2   3 , Nathan Georgette  1   2   3 , Alexandra H Baker  1   2   3 , Gregory P Priebe  4   5   6 , Michael C Monuteaux  1   2   3
Affiliations
Comparative Study

Epinephrine vs Norepinephrine as Initial Treatment in Children With Septic Shock

Matthew A Eisenberg et al. JAMA Netw Open. .

Abstract

Importance: There is no consensus and wide practice variation in the choice of initial vasoactive agent in children with septic shock.

Objective: To determine whether receipt of epinephrine compared with norepinephrine as the first vasoactive medication administered is associated with improved outcomes among children with septic shock without known cardiac dysfunction.

Design, setting, and participants: This single-center, retrospective cohort study used propensity score matching to examine encounters in which a patient was diagnosed with septic shock and required a vasoactive infusion within 24 hours of ED arrival at a freestanding quaternary care children's hospital. Participants included patients aged 1 month to 18 years who presented to the ED and were diagnosed with septic shock without known cardiac dysfunction and began an epinephrine or norepinephrine infusion within 24 hours of ED arrival between June 1, 2017, and December 31, 2023. Data were analyzed from March 1 to December 31, 2024.

Exposure: Epinephrine vs norepinephrine as the first vasoactive medication received.

Main outcomes and measures: The primary outcome was major adverse kidney events by 30 days (MAKE30). Secondary outcomes were 30-day in-hospital mortality, 3-day mortality, need for kidney replacement therapy or persistent kidney dysfunction, endotracheal intubation, mechanical ventilation days, extracorporeal membrane oxygenation, and hospital and intensive care unit length of stay. Primary and secondary outcomes were assessed with the χ2 test of proportions for binary variables and Wilcoxon rank sum test for continuous variables.

Results: Among 231 included encounters, the median (IQR) age was 11.4 (5.6-15.4) years, 126 were female (54.6%), and 142 had a medical history that predisposed them to sepsis (61.5%). Most (147 [63.6%]) initially received an epinephrine infusion and 84 (36.4%) received norepinephrine. In the epinephrine group, 9 of 147 (6.1%) met the outcome of MAKE30 and 6 of 147 (4.1%) died within 30 days. In the norepinephrine group, 3 of 84 (3.6%) met MAKE30 and there were no deaths. After inverse probability of treatment weighting, there were no significant differences in the primary outcome, MAKE30. With 2:1 propensity matching, epinephrine was associated with greater 30-day mortality compared with norepinephrine (3.7% vs 0%; risk difference: 3.7%; 95% CI, 0.2%-7.2%).

Conclusions and relevance: In this study, those receiving epinephrine had greater 30-day mortality but no difference in MAKE30. Prospective, confirmatory studies are needed to determine if norepinephrine should be the first-line vasoactive agent in pediatric septic shock.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Patient Selection Flowsheet
CICU indicates cardiac intensive care unit; ED, emergency department; IM, intramuscular.
See this image and copyright information in PMC

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