Key Points 
Question Is there an association between the first vasoactive agent administered and outcomes in children with septic shock without known cardiac dysfunction?
Findings In this retrospective cohort study of 231 encounters using propensity matching, there was no difference in the primary outcome, major adverse kidney events by 30 days, between patients receiving epinephrine vs norepinephrine, but epinephrine was associated with greater 30-day mortality.
Meaning These findings suggest that outcomes were different for patients treated with epinephrine vs norepinephrine as the initial agent, supporting the need for prospective, confirmatory studies.
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.
