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

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, and 7% (95% CI 1%-48%) for norepinephrine. Four first-line dopamine (176 patients) and first-line epinephrine (142 patients): dopamine showed a tendency toward higher mortality (PR 1.38, 95% CI 0.81-2.38) and a significant higher need for mechanical ventilation (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 mechanical ventilation and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population.