Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol

Abstract

BackgroundThere is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum.Methods/DesignThe study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged ≤ 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective.Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management.Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI).A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs.DiscussionThe relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice.Trial RegistrationCurrent Controlled Trials ISRCTN61735247

Stress Hyperglycemia in Pediatric Critical Illness: The Intensive Care Unit Adds to the Stress!

“…The Control of Hyperglycemia in Pediatric Intensive Care trial in the United Kingdom aims to study the impact of TGC on numbers of days alive and freed of ventilator support at 30 days in 1500 critically ill children who are mechanically ventilated and on vasoactive infusions. 101 The Safe Pediatric Euglycemia in Cardiac Surgery study is examining the impact of TGC in reducing nosocomial infections and improving cardiac index at 24 hours following cardiac surgery using a continuous glucose monitoring system in 980 children.…”

Dilemmas in undertaking research in paediatric intensive care

“…Several investigators have therefore used surrogate outcome measures as the primary outcome. For example, the Safe Paediatric Euglycaemia after Cardiac Surgery (SPECS) study and CHiP investigators used healthcare-associated infections and ventilator-free days as primary outcome measures, respectively44 45; the Trial of Drotrecogin Alfa in Children (RESOLVE) study used a composite outcome measure called ‘composite time to complete organ failure resolution’46 and Transfusion Requirements in PICU (TRIPICU) study used new or progressive multiple-organ dysfunction syndrome 47. While this strategy may be valid and acceptable in some trials, widespread use of proxy short-term outcome measures is perhaps fraught with danger.…”

Multiple organ dysfunction syndrome associated with hyperglycemia in children requiring intensive care

“…5,6 There are two methods of insulin therapy for hyperglycemic patients due to organ dysfunctions; strict and standard therapy. 13,20 A previous study has showed a low incidence of hypoglycemia with the strict insulin therapy. 13 Therefore, we recommend the strict insulin therapy for hyperglycemia caused by MODS in children requiring intensive care.…”