• Dirk Vlasselaers, Ilse Milants, Lars Desmet, Pieter J Wouters, Ilse Vanhorebeek, Ingeborg van den Heuvel, Dieter Mesotten, Michael P Casaer, Geert Meyfroidt, Catherine Ingels, Jan Muller, Sophie Van Cromphaut, Miet Schetz, and Greet Van den Berghe.
• Department of Intensive Care Medicine (Paediatric Intensive Care Unit), Catholic University Leuven, Leuven, Belgium.
• Lancet. 2009 Feb 14;373(9663):547-56.

BackgroundCritically ill infants and children often develop hyperglycaemia, which is associated with adverse outcome; however, whether lowering blood glucose concentrations to age-adjusted normal fasting values improves outcome is unknown. We investigated the effect of targeting age-adjusted normoglycaemia with insulin infusion in critically ill infants and children on outcome.MethodsIn a prospective, randomised controlled study, we enrolled 700 critically ill patients, 317 infants (aged <1 year) and 383 children (aged >or=1 year), who were admitted to the paediatric intensive care unit (PICU) of the University Hospital of Leuven, Belgium. Patients were randomly assigned by blinded envelopes to target blood glucose concentrations of 2.8-4.4 mmol/L in infants and 3.9-5.6 mmol/L in children with insulin infusion throughout PICU stay (intensive group [n=349]), or to insulin infusion only to prevent blood glucose from exceeding 11.9 mmol/L (conventional group [n=351]). Patients and laboratory staff were blinded to treatment allocation. Primary endpoints were duration of PICU stay and inflammation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00214916.FindingsMean blood glucose concentrations were lower in the intensive group than in the conventional group (infants: 4.8 [SD 1.2] mmol/L vs 6.4 [1.2] mmol/L, p<0.0001; children: 5.3 [1.1] mmol/L vs 8.2 [3.3] mmol/L, p<0.0001). Hypoglycaemia (defined as blood glucose median) stay in PICU was 132 (38%) in the intensive group versus 165 (47%) in the conventional group (p=0.013). Nine (3%) patients died in the intensively treated group versus 20 (6%) in the conventional group (p=0.038).InterpretationTargeting of blood glucose concentrations to age-adjusted normal fasting concentrations improved short-term outcome of patients in PICU. The effect on long-term survival, morbidity, and neurocognitive development needs to be investigated.FundingResearch Foundation (Belgium); Research Fund of the University of Leuven (Belgium) and the EU Information Society Technologies Integrated project "CLINICIP"; and Institute for Science and Technology (Belgium).

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