Objectives: Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range.
Design: Multi-center randomized clinical trial.
Setting: Pediatric ICUs at 35 academic hospitals.
Patients: Children aged 2weeks to 17years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients.
Interventions: Patients receive intravenous insulin titrated to either 80-110mg/dL (4.4-6.1mmol/L) or 150-180mg/dL (8.3-10.0mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk.
Measurements and main results: The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test.
Conclusions: This trial tests whether hyperglycemic critically ill children randomized to 80-110mg/dL benefit more than those randomized to 150-180mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control.
Trial registration: ClinicalTrials.gov NCT01565941.
Keywords: Insulin therapy; Pediatric critical care; Randomized clinical trial; Stress hyperglycemia.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.