First-line vasopressor therapy in neonates with fluid-refractory septic shock: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION

Neonates with fluid-refractory septic shock require prompt vasopressor support, including dopamine, epinephrine, and norepinephrine; however, the optimal first-line treatment remains unclear. This meta-analysis assessed the first-line vasopressors for shock reversal and clinical outcomes.

METHODS

A comprehensive search of the PubMed, Scopus, Ovid, and CINAHL databases was performed from inception to April 2026. We included randomized controlled trials evaluating first-line vasopressor therapy in neonates (<28 days old) with fluid-refractory septic shock, comparing epinephrine and norepinephrine with dopamine. The primary outcomes were early shock reversal and all-cause mortality, with secondary outcomes including the need for additional vasoactive agents and changes in hemodynamic responses. Analyses were performed using Review Manager (RevMan) version 5.4 software.

RESULTS

Four RCTs were included. Compared with dopamine, epinephrine or norepinephrine showed no significant difference in shock reversal within 1h (RR = 1.07; 95% CI = 0.84-1.36; P = 0.57; I2 = 39%) or mortality (RR = 0.95; 95% CI = 0.80-1.13; P = 0.58; I2 = 0%). Subgroup analyses showed no significant differences for norepinephrine (RR = 0.97; 95% CI = 0.66-1.44; P = 0.90; I2 = 73%) or epinephrine (RR = 1.16; 95% CI = 0.86-1.56; P = 0.32; I2 = 0%), with no difference between subgroups (P = 0.48). Secondary outcomes including the requirement of additional vasoactive agent, mean arterial pressure were not different.

CONCLUSION

No substantial changes were observed in the vasoactive therapies used in neonates with fluid-refractory septic shock. Nonetheless, owing to the limited number of trials and considerable clinical heterogeneity within the studies, these results should not be construed as definitive equivalency between treatments. Additional high-quality neonatal-specific research with standardized criteria is essential to determine the most appropriate first-line treatment.