Outcomes of pediatric fluid-refractory septic shock according to different vasoactive strategies: A systematic review and meta-analysis

ABSTRACT Background Hemodynamic support using vasoactive agents is a mainstay in the management of patients with pediatric Fluid-Refractory Septic Shock (FRSS). However, evidence supporting the appropriate choice of vasoactive agent is limited. This study aimed to perform a systematic review and meta-analysis on the effect of different first-line vasoactive strategies on mortality in pediatric FRSS. Methods MEDLINE, EMBASE, Scopus, CINAHL, Web of Science, the Cochrane Library, ClinicalTrials.gov, and the ISRCTN registry were searched up until December 2023. Randomized controlled trials and observational cohort studies reporting vasoactive agent-specific outcomes of children with FRSS were included. Mortality was assessed as primary outcome in studies on patients receiving dopamine, epinephrine, or norepinephrine as first-line. Random-effects meta-analyses were conducted. Prevalence ratio (PR) estimates were calculated between two drugs when was available in the same study. Findings Of the 26,284 identified articles, 13 were included, for a total of 997 children. Twelve studies included 748 patients receiving a single vasoactive agent. Of these, 361 received dopamine, 271 epinephrine, and 116 norepinephrine. Overall pooled mortality for patients receiving a single vasoactive was 12% (95% CI 6-21%) of which 11% (95% CI 3-36%) for patients receiving dopamine, 17% (95% CI 6-37%) for epinephrine, 7% (95% CI 1-48%) for norepinephrine. Four first-line dopamine (176 patients) and first-line epinephrine (142 patients): dopamine showed a tendency towards higher mortality (PR 1.38, 95% CI 0.81-2.38) and a significant higher need for mechanical ventilation (MV) (PR 1.12, 95% CI 1.02-1.22). Interpretation Among children with FRSS receiving a single vasoactive agent, norepinephrine was associated with the lowest mortality rate. Comparing dopamine and epinephrine, patients receiving epinephrine needed less MV and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population.