Rationale: Vasopressin has been proposed as a potent vasoactive agent in the treatment of vasodilatory shock in adults and children. The objective of this trial was to evaluate the efficacy and safety of vasopressin as an adjunctive agent in pediatric vasodilatory shock.
Methods: In this multicenter, double-blind trial, children with vasodilatory shock were randomized to receive low-dose vasopressin (0.0005-0.002 U/kg/min) or placebo in addition to open-label vasoactive agents. Vasoactive infusions were titrated to clinical endpoints of adequate perfusion. The primary outcome was time to vasoactive-free hemodynamic stability. Secondary outcomes included mortality, organ-failure-free days, length of critical care unit stay, and adverse events.
Measurements and main results: Sixty-five of 69 children (94%) who were randomized received the study drug (33 vasopressin, 32 placebo) and were included in the analysis. There was no significant difference in the primary outcome between the vasopressin and placebo groups (49.7 vs. 47.1 hours; P = 0.85). There were 10 deaths (30%) in the vasopressin group and five (15.6%) in the placebo group (relative risk, 1.94; 95% confidence interval, 0.75-5.05; P = 0.24). There were no significant differences with respect to organ failure-free days (22 vs. 25.5 days; P = 0.11), ventilator-free days (16.5 23 days; P = 0.15), length of stay (8 vs. 8.5 days; P = 0.93), or adverse event rate ratios (12.0%; 95% confidence interval, -2.6 to 26.7; P = 0.15).
Conclusions: Low-dose vasopressin did not demonstrate any beneficial effects in this pediatric trial. Although not statistically significant, there was a concerning trend toward increased mortality. Clinical trial registered with www.controlled-trials.com (ISRCTN11597444).