A Randomized Controlled Trial of Corticosteroids in Pediatric Septic Shock: A Pilot Feasibility Study

Abstract

Objective: To determine the feasibility of conducting a randomized controlled trial of corticosteroids in pediatric septic shock.

Design: Randomized, double-blind, placebo controlled trial.

Setting: Seven tertiary level PICUs in Canada.

Patients: Children newborn to 17 years old inclusive with suspected septic shock.

Intervention: Administration of IV hydrocortisone versus placebo until hemodynamic stability is achieved or for a maximum of 7 days.

Measurements and main results: One hundred seventy-four patients were potentially eligible of whom 101 patients met eligibility criteria. Fifty-seven patients were randomized, and 49 patients (23 and 26 patients in the hydrocortisone and placebo groups, respectively) were included in the final analysis. The mean time from screening to randomization was 2.4 ± 2.1 hours and from screening to first dose of study drug was 3.8 ± 2.6 hours. Forty-two percent of potentially eligible patients (73/174) received corticosteroids prior to randomization: 38.5% (67/174) were already on corticosteroids for shock at the time of screening, and in 3.4% (6/174), the treating physician wished to administer corticosteroids. Six of 49 randomized patients (12.2%) received open-label steroids, three in each of the hydrocortisone and placebo groups. Time on vasopressors, days on mechanical ventilation, PICU and hospital length of stay, and the rate of adverse events were not statistically different between the two groups.

Conclusions: This study suggests that a large randomized controlled trial on early use of corticosteroids in pediatric septic shock is potentially feasible. However, the frequent use of empiric corticosteroids in otherwise eligible patients remains a significant challenge. Knowledge translation activities, targeted recruitment, and alternative study designs are possible strategies to mitigate this challenge.

Figures

Figure 1

CONSORT diagram.

Figure 2

Kaplan-Meier curves for corticosteroids vs placebo in septic shock. a) Adjusted for PRISM, mechanical ventilation, pre-existing conditions. b) Adjusted for PRISM, mechanical ventilation, pre-existing conditions. c) Adjusted for PRISM, antibiotics, lactate, fluid resuscitation volume. d) Adjusted for PRISM.