Choice of Initial Pressor in Pediatric Septic Shock

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Septic shock remains a leading cause of pediatric mortality, but the choice of first-line vasoactive agent has long been debated. Dr Newton, a PGY-3, discusses this single-center retrospective cohort study comparing epinephrine and norepinephrine as initial infusions in children with septic shock. While the primary kidney outcome (MAKE30) showed no difference, epinephrine was linked to higher 30-day mortality in propensity-matched analysis. The findings are hypothesis-generating and highlight the need for prospective pediatric trials.

THE PODCAST

Eisenberg MA, Georgette N, Baker AH, Priebe GP, Monuteaux MC. Epinephrine vs Norepinephrine as Initial Treatment in Children With Septic Shock. JAMA Netw Open. 2025;8(4):e254720.

A SUMMARY

Background
Septic shock remains a major cause of pediatric morbidity and mortality. After fluids, the optimal first-line vasoactive agent is debated. Pediatric guidelines have allowed both epinephrine and norepinephrine, while adult guidelines favor norepinephrine. Until now, no direct comparative data existed in children.

The Study
Investigators at Boston Children’s Hospital performed a retrospective cohort study of ED encounters from 2017–2023 to compare outcomes in children started on epinephrine vs. norepinephrine as their first vasoactive infusion.

  • Population: Children 1 month–18 years with community-acquired septic shock who received IV antibiotics and a vasoactive infusion within 24h of ED arrival.

  • Exclusions: Anaphylaxis, known/suspected cardiac dysfunction, cardiac ICU admissions, pre-transfer vasoactive use.

  • Primary Outcome: MAKE30 (major adverse kidney events within 30 days).

  • Secondary Outcomes: 30-day mortality, additional vasoactive use, ICU length of stay, new organ dysfunction.

Results

  • Cohort: 231 encounters (147 epinephrine, 84 norepinephrine). Median age ~11 years.

  • MAKE30: 6.1% epinephrine vs. 3.6% norepinephrine (not statistically significant after adjustment).

  • 30-Day Mortality: 4.1% epinephrine vs. 0% norepinephrine.

    • No mortality difference with inverse probability weighting (IPTW).

    • In 2:1 propensity-matched analysis, epinephrine was associated with higher 30-day mortality (RD 3.7%, 95% CI 0.2–7.2%).

  • Other Findings: Epinephrine patients were more likely to require additional vasoactives (47.6% vs. 17.9%). No tachyarrhythmias requiring treatment occurred in either group.

Discussion
This study found no difference in the primary kidney outcome, but a signal for higher 30-day mortality with epinephrine in matched analyses. Interpretation is limited by retrospective design, potential confounding (e.g., clinician preference, illness severity), and low event rates. The biologic rationale for harm with epinephrine remains uncertain, though its β-adrenergic effects may worsen metabolic or cardiac stress.

Limitations
Single-center, retrospective design with modest sample size and rare outcome events. Baseline differences in patient severity and location of infusion initiation (ED vs ICU) may bias results. Vasoactive dose and duration were not captured, and analysis only considered the first agent.

Implications
This is the first direct pediatric comparison of epinephrine vs. norepinephrine for septic shock. Findings suggest norepinephrine may have a mortality advantage, but results are hypothesis-generating and require confirmation in prospective randomized trials. Clinicians may consider norepinephrine preferentially in the absence of suspected cardiac dysfunction, but guideline-level changes await stronger evidence.

AUTHORSHIP

Written by: Sophia Newton, MD, PGY-3 University of Cincinnati Department of Emergency Medicine

Editing, Posting, and Audio Editing by Anita Goel, MD Adjunct Associate Professor, University of Cincinnati Department of Emergency Medicine.

Cite as: Newton, S., Goel, A. Choice of Initial Pressor in Pediatric Septic Shock. TamingtheSRU.com. www.tamingthesru.com/blog/journal-club-pressors-in-pediatric-septic-shock. 10/1/2025.