Vasopressin in pediatric vasodilatory shock: a multicentred randomized controlled trial

Introduction

Vasopressin has been suggested as a useful vaso-active agent in the support of vasodilatory shock in adults; however, its effect in children is unclear. We hypothesized that low-dose vasopressin in this population, administered as an adjunctive vasoactive agent, would lead to more rapid reversal of vasodilatory shock when compared with placebo.

Methods

In this multicenter, double-blind trial, children with clinical evidence of vasodilatory shock were randomized to receive either low-dose vasopressin (0.0005 to 0.002 U/kg/min) or placebo in addition to open-label vasoactive agents. Vasoactive infusions were titrated according to established guidelines to maintain target mean arterial pressure and adequate perfusion. The primary outcome was the time to vasoactive-free hemodynamic stability. Secondary outcomes included mortality, organ-failure free days, length of stay, and adverse and serious adverse events.

Results

Sixty-five out 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 between the vasopressin and placebo groups in the time to vaso-active-free hemodynamic stability (49.7 vs. 47.1 hours, respectively, P = 0.85). There were 10 deaths (30%) in the vasopressin group and five deaths (15.6%) in the placebo group (relative risk = 1.94; 95% CI = 0.75 to 5.05, P = 0.24). There were no significant differences between the two groups with respect to organ-failure free days (22 vs. 25.5 days, P = 0.11), ventilator-free days (16.5 vs. 23 days, P = 0.15), length of pediatric critical care unit stay (8 vs. 8.5 days, P = 0.93), or the adverse and serious adverse event rate ratios (12.0%, 95% CI = -2.6 to 26.7, P = 0.15; and 3.2%, 95% CI = -13.7 to 7.8, P = 0.55, respectively).

Conclusion

In this multicenter, randomized, placebo-controlled trial in pediatric patients with vasodilatory shock, low-dose vasopressin did not demonstrate any beneficial effects but a concerning trend in mortality.