Recently, the concept that stress hyperglycaemia in critically ill patients is an adaptive, beneficial response has been challenged. Two large randomised studies in adult intensive care unit (ICU) patients demonstrated that maintenance of normoglycaemia with intensive insulin therapy substantially prevents morbidity and reduces mortality. Since then, questions have been raised about efficacy and safety with regard to the potential harm of brief hypoglycaemic episodes and high-dose insulin administration. These issues will be addressed in relation to the available evidence. Also, the first randomised study in the paediatric ICU has been finalised (ClinicalTrials.gov NCT00214916). All available studies that have adequately targeted true “normoglycaemia” consistently showed that what can be expected from intensive insulin therapy in the ICU is an absolute 3% reduction in mortality and prevention of morbidity (secondary organ damage) in an intention-to-treat analysis. This number forms the basis for determining the sample size of repeat studies.
Blood glucose control to strict normoglycaemia appears crucial to obtain clinical benefit. The risk of hypoglycaemia increases with insulin therapy, but it remains unclear whether this is truly harmful in the setting of critical care. Hyperglycaemia on the other hand has been shown to cause toxicity in several cell types that take up glucose passively, independent of insulin, including hepatocytes, alveolar cells, endothelial cells, neurons and immune cells. The prevention of glucose toxicity to the mitochondrial compartment in such cells appears important. In addition, insulin may exert direct effects as long as hyperglycaemia is avoided. Such insulin effects include partial correction of dyslipidaemia and prevention of excessive inflammation.