Tight Glycemic Control With Intensive Insulin Therapy in PICU

• Reduction of inflammation [ Time Frame: during ICU stay to day 5 ] [ Designated as safety issue: No ]
• duration of dependency on intensive care (days in ICU) [ Time Frame: time in ICU ] [ Designated as safety issue: No ]

• Duration mechanical ventilation [ Time Frame: during time in ICU ] [ Designated as safety issue: No ]
• Organ failure/need for organ support [ Time Frame: during time in ICU ] [ Designated as safety issue: No ]
• mortality (safety endpoint) [ Time Frame: during time in ICU ] [ Designated as safety issue: Yes ]
• long-term follow-up study : focus on neurocognitive development (ethical approval granted) [ Time Frame: 3 years (+/- 6 months) after randomization ] [ Designated as safety issue: Yes ]

• Stay in ICU
• Duration mechanical ventilation
• Organ failure

In a previous study, the investigators showed that tight blood glucose control with insulin during intensive care reduced morbidity and mortality in adult intensive care patients. Whether this intervention also improves prognosis of pediatric intensive care patients remains unknown. The current prospective, randomized, controlled study will asses the impact of intensive insulin therapy on outcome of patients in a pediatric intensive care unit. On admission patients will be randomly assigned to either strict normalization of blood glucose according age adjusted values or the conventional approach, in which insulin infusion is initiated only when blood glucose exceeds 215 mg/dl to maintain blood glucose levels between 180-200 mg/dl.

Study type: Interventional study

Study design: single centre, prospective, randomized, active control, parallel assignment, efficacy study

• Drug: intensive insulin therapy (Actrapid IV to normoglycemia)
  intensive insulin therapy (Actrapid IV in continuous infusion to age-dependent normoglycemia)
  Other Name: Actrapid IV to normoglycemia
• Drug: conventional insulin therapy (Actrapid IV only for excessive hyperglycemia)
  conventional insulin therapy (Actrapid IV in continuous infusion only to treat blood glucose levels exceeding 220 mg/dl)
  Other Name: Actrapid IV only for excessive hyperglycemia

• Active Comparator: A
  conventional insulin therapy (using Actrapid IV)
  Intervention: Drug: conventional insulin therapy (Actrapid IV only for excessive hyperglycemia)
• Experimental: B
  intensive insulin therapy (using actrapid IV)
  Intervention: Drug: intensive insulin therapy (Actrapid IV to normoglycemia)

• van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67.
• Mesotten D, Gielen M, Sterken C, Claessens K, Hermans G, Vlasselaers D, Lemiere J, Lagae L, Gewillig M, Eyskens B, Vanhorebeek I, Wouters PJ, Van den Berghe G. Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA. 2012 Oct 24;308(16):1641-50.
• Gielen M, Mesotten D, Wouters PJ, Desmet L, Vlasselaers D, Vanhorebeek I, Langouche L, Van den Berghe G. Effect of tight glucose control with insulin on the thyroid axis of critically ill children and its relation with outcome. J Clin Endocrinol Metab. 2012 Oct;97(10):3569-76. doi: 10.1210/jc.2012-2240. Epub 2012 Aug 7.
• Gielen M, Mesotten D, Brugts M, Coopmans W, Van Herck E, Vanhorebeek I, Baxter R, Lamberts S, Janssen JA, Van den Berghe G. Effect of intensive insulin therapy on the somatotropic axis of critically ill children. J Clin Endocrinol Metab. 2011 Aug;96(8):2558-66. Epub 2011 Jun 1.
• Vlasselaers D, Mesotten D, Langouche L, Vanhorebeek I, van den Heuvel I, Milants I, Wouters P, Wouters P, Meyns B, Bjerre M, Hansen TK, Van den Berghe G. Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery. Ann Thorac Surg. 2010 Jul;90(1):22-9.

Inclusion Criteria:

• Children admitted to the pediatric intensive care unit and anticipated to require intensive care for at least 24 hours

Exclusion Criteria:

• Expected stay < 24 hours
• Therapy restriction upon admission
• No informed consent
• Other study enrollment