title: Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study.
abstract: BACKGROUND
  Critically 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Mean 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 <or=2.2 mmol/L) occurred in 87 (25%) patients in the intensive group (p<0.0001) versus five (1%) patients in the conventional group; hypoglycaemia defined as blood glucose less than 1.7 mmol/L arose in 17 (5%) patients versus three (1%) (p=0.001). Duration of PICU stay was shortest in the intensively treated group (5.51 days [95% CI 4.65-6.37] vs 6.15 days [5.25-7.05], p=0.017). The inflammatory response was attenuated at day 5, as indicated by lower C-reactive protein in the intensive group compared with baseline (-9.75 mg/L [95% CI -19.93 to 0.43] vs 8.97 mg/L [-0.9 to 18.84], p=0.007). The number of patients with extended (>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).
  
  
  CONCLUSIONS
  Targeting 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.
  
  
  BACKGROUND
  Research 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).
authors.affiliation: Department of Intensive Care Medicine (Paediatric Intensive Care Unit), Catholic University Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vlasselaers
authors.forename: Ilse
authors.initials: I
authors.lastname: Milants
authors.forename: Lars
authors.initials: L
authors.lastname: Desmet
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van den Heuvel
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.forename: Michael P
authors.initials: MP
authors.lastname: Casaer
authors.forename: Geert
authors.initials: G
authors.lastname: Meyfroidt
authors.forename: Catherine
authors.initials: C
authors.lastname: Ingels
authors.forename: Jan
authors.initials: J
authors.lastname: Muller
authors.forename: Sophie
authors.initials: S
authors.lastname: Van Cromphaut
authors.forename: Miet
authors.initials: M
authors.lastname: Schetz
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D000293:Adolescent; D001530:Belgium; D001786:Blood Glucose / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003422:Critical Care / Q000379:methods*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D015278:Intensive Care Units, Pediatric; D007902:Length of Stay; D008297:Male; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin