Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial

Abstract

Objectives: In children with septic shock, guidelines recommend resuscitation with 40-60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock.; Design: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days.; Setting: Four pediatric Emergency Departments in Queensland, Australia.; Patients: Children between 28 days and 18 years old with septic shock.; Interventions: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23).; Measurements and Main Results: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9-12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12-26 min) in the intervention group, and 49 minutes (IQR, 29-63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0-10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6-28.6 mL/kg) in the standard group (difference, -20.0; 95% CI, -28.0 to -12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26-27 d) versus 26 days (IQR, 25-27 d). There were no adverse events reported associated with the intervention.; Conclusions: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.; Competing Interests: Drs. George’s, Long’s, and Schlapbach’s institutions received funding from Gold Coast Hospital Foundation. Drs. George’s, Long’s, and Schlapbach’s institutions received funding from the Emergency Medicine Foundation, Queensland. Drs. Long’s and Schlapbach’s institutions received funding from Financial Markets for Children Australia and a Children’s Health Queensland Study, Education and Research Trust Account grant. Dr. Lister’s institution received funding from the Hospital Foundation Charity. Dr. Schlapbach received funding from the National Health and Medical Research Council Practitioner Fellowship and the Children’s Hospital Foundation, Australia. The remaining authors have disclosed that they do not have any potential conflicts of interest. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)