Written by Joshua Belfer
Spoon Feed
In children with septic shock, initial treatment with norepinephrine was associated with lower 30-day mortality compared to epinephrine, despite no difference in major adverse kidney events.
Why the first vasoactive choice still feels like a guess
Early choice of vasoactive agent in pediatric septic shock may impact mortality, making it crucial to know which medication offers the best outcomes. Although guidelines endorse both epinephrine and norepinephrine, no direct comparison in children with septic shock had been performed until now.
This single-center, retrospective cohort study used propensity score matching to compare outcomes of epinephrine versus norepinephrine as initial vasoactive therapy in pediatric septic shock without cardiac dysfunction. The primary outcome was major adverse kidney events at 30 days (MAKE30), while secondary outcomes included 30-day mortality. Among 231 encounters, there was no significant difference in major adverse kidney events at 30 days. However, after propensity score matching, 30-day mortality was higher with epinephrine compared to norepinephrine (3.7% vs. 0%; risk difference 3.7%, 95%CI 0.2%-7.2%). Findings suggest a potential mortality benefit with initial norepinephrine use. This single-center retrospective study may have limited generalizability, and despite propensity matching, unmeasured confounders could have influenced the observed differences in outcomes.
How will this change my practice?
There is no lack of studies on sepsis as we continue to explore optimal therapy in this critical entity, and this study focuses on the choice of first line vasopressors. While the results suggest lower mortality for those treated with norepinephrine, I’m not sure that this single center study with a relatively small sample size will push me to always reach for norepi before epi. What I take home is it may not be inappropriate to start with norepinephrine, but I need to see more evidence before I make this my standard practice.
Source
Epinephrine vs Norepinephrine as Initial Treatment in Children With Septic Shock. JAMA Netw Open. 2025 Apr 1;8(4):e254720. doi: 10.1001/jamanetworkopen.2025.4720. PMID: 40214988
