Hyperglycemia in critical illness – a controversy revisited

It is rare indeed for change in medical practice to be based on the evidence of a single clinical study. But that is exactly what happened in 2001 following publication of a study conducted at the intensive care unit of a hospital in Leuven, Belgium. 

Results of the now celebrated Leuven study indicated that hyperglycemia (raised blood glucose), a common finding among the acutely/critically ill, is not a benign adaptive response to critical illness as then supposed, but a potentially harmful phenomenon that demands treatment. 

The authors of the study demonstrated that administration of insulin to maintain blood glucose within normal limits resulted in a significant reduction in mortality among their intensive care study population. The clearly positive results of the study provoked enormous interest, and a policy of intensive insulin therapy aimed at normalization of blood glucose quickly became a standard of care in intensive care units around the world. 

As the authors of a recent review article reveal, the positive results of the Leuven study have never been replicated in many similarly designed studies. Indeed the largest and most comprehensive study to address the issue (the NICE-SUGAR trial) published in 2009 found that intensive insulin therapy was associated with increased rather than decreased mortality among intensive care patients. 

Taken together, Leuven and NICE-SUGAR study results nicely crystallize a 15-year controversy surrounding the treatment of hyperglycemia among the critically ill, that remains largely unresolved. That controversy is the focus of this review article, which details not only the Leuven and NICE-SUGAR trials but a number of other similar studies. 

Despite the now widespread skepticism surrounding the benefit of the Leuven protocol, there remains a research interest in defining the degree of hyperglycemia that warrants treatment and how, and to whom that treatment should be delivered. The authors of this review highlight three areas of current research relevant to the sought-for resolution of the controversy. 

They are: the extent and significance of hypoglycemia induced by insulin treatment among the critically ill; significance of glucose variability among critically ill patients; and the impact of pre-existing diabetes on the significance of hyperglycemia during unrelated critical illness. 

The authors describe current guidelines for the treatment of hyperglycemia among the critically ill, which are more permissive of hyperglycemia than the Leuven protocol, but imply that these will almost certainly be amended in the light of ongoing research. 

This review, which draws on 51 references, provides a concise and accessible account of current understanding of the significance and treatment of hyperglycemia among the critically ill.