The role of insulin therapy in critically ill patients.

Protracted critically ill patients have a seriously deranged metabolism, characterized by severe hyperglycemia, a disturbed serum lipid profile, and protein hypercatabolism. The severity of stress-induced hyperglycemia and insulin resistance in critically ill patients reflect the risk of death. A large, prospective, randomized, controlled study showed that maintaining normoglycemia with intensive insulin therapy reduces morbidity and mortality of surgical intensive care patients. These results were recently confirmed by two studies: one randomized controlled study of surgical intensive care patients and a prospective observational study of a heterogeneous patient population admitted to a mixed medical/surgical intensive care unit. The clinical benefits of intensive insulin therapy appear to be related both to prevention of glucose toxicity and to other direct insulin actions that are independent of glycemic control. Prevention of the toxic effects of high circulating glucose levels protected the ultrastructure and function of hepatocyte mitochondria. Benefits of the non-glycemic effects of insulin included partial correction of the deranged serum lipid profile and possibly counteraction of the catabolic state. In addition to its metabolic effects, intensive insulin therapy also prevented excessive inflammation and improved immune function.