What First-line Vasoactives Are Associated with Improved Outcomes in Pediatric Septic Shock?

Background: Globally, more than 3 million children per year die from sepsis. Vasoactives are a mainstay of supportive therapy for patients with septic shock, however there is no consensus about which vasoactives should be used first in these children. Several studies have been done to understand current vasoactive usage and outcomes in pediatric septic shock. These studies show significant clinical practice variation and highlight the need for more research in this area to lead to improvements in pediatric sepsis treatment. Improved understanding of how certain vasoactives affect outcomes can lead to practice changes and improvement that ultimately may improve care for millions of children yearly.

Objectives: Compare outcomes associated with the choice of first-line vasoactive in children with septic shock in a multicenter dataset.

Design/Methods: We analyzed an NIH-funded dataset of 5,739 children with septic shock from 13 U.S. PICUs, all treated with vasoactives within 24 hours. Using a target trial emulation, we compared norepinephrine vs. epinephrine, epinephrine vs. dopamine, and norepinephrine vs. dopamine. Outcomes included in-hospital mortality, MODS at 1 week, need for a second vasoactive, and 6-hour vasoactive infusion score (VIS). We used propensity score matching (PSM0 and inverse probability treatment weighting (IPTW) to mimic a randomized control trial and to adjust for confounding (PRISM III, malignancy, age, biennial admission, site). All analyses were performed in R.

Results: When comparing norepinephrine to epinephrine (Table 2), norepinephrine was associated with a lower rate of mortality, lower rates of MODS at 1 week, and lower VIS score at 6 hours. The results of epinephrine versus dopamine (Table 3) demonstrated that dopamine was associated with lower mortality, lower rates of MODS at 1 week; however, epinephrine was associated with less need for a second vasoactive. When comparing norepinephrine versus dopamine (Table 4), it was found that norepinephrine was associated with less need for a second vasoactive and a lower VIS score at 6 hours.

Conclusions: In this comparative analysis using PSM and IPTW, norepinephrine was consistently associated with more favorable outcomes. It was linked to lower mortality and MODS at 1 week when compared to epinephrine, and less need for a second vasoactive and lower VIS score at 6 hours when compared to dopamine. These findings suggest that norepinephrine may offer clinical benefits over both epinephrine and dopamine as a first-line vasoactive in pediatric septic shock.