Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the
Luregn J Schlapbach1,2, Kristen Gibbons1, Roberta Ridolfi1
1Child Health Research Centre, The University of Queensland, and Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.
Insights
This pilot study investigates metabolic resuscitation, a combination of hydrocortisone, ascorbic acid, and thiamine, for children with septic shock. It aims to assess feasibility and impact on organ dysfunction resolution in pediatric intensive care units.
Area of Science:
- Pediatric critical care medicine
- Intensive care research
- Sepsis management
Background:
- Septic shock is a leading cause of mortality in children.
- Limited therapeutic options exist for pediatric septic shock refractory to initial treatments.
- Hydrocortisone, ascorbic acid, and thiamine (HAT therapy) show potential for reducing sepsis-related organ dysfunction.
Purpose of the Study:
- To evaluate the feasibility of early, protocolized metabolic resuscitation in children with septic shock.
- To assess the impact of HAT therapy on the resolution of organ dysfunction.
- To determine the safety and potential mortality benefit of this intervention in a pediatric population.
Main Methods:
- Open-label, randomized-controlled pilot study in Australian and New Zealand PICUs.
- Sixty children (28 days to 18 years) with septic shock receiving inotropes randomized 1:1 to metabolic resuscitation or standard care.
- Metabolic resuscitation: hydrocortisone, ascorbic acid, and thiamine at specified doses and intervals.
Main Results:
- Primary outcomes: feasibility of the study protocol and survival free of organ dysfunction at 28 days.
- Secondary outcomes: neurodevelopment, quality of life, and functional status at 28 days and 6 months.
- Ancillary studies will investigate sepsis biomarkers through biobanking.
Conclusions:
- The RESPOND PICU study protocol is designed to provide critical data on metabolic resuscitation for pediatric septic shock.
- Findings will inform future larger randomized trials on HAT therapy in children.
- This research addresses a significant gap in evidence-based treatments for pediatric septic shock.
Abstract:
Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy ("metabolic resuscitation") in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.
