New findings published in the August 27 issue of JAMA call into question the tight glucose control that many professional societies recommend for critically ill adults. Researchers performed a meta-analysis and found that tight glucose control is not associated with a significant reduction in risk of death in the hospital, but it is linked to an increased risk of hypoglycemia (lower than normal glucose sugar levels).
A randomized controlled trial published in 2001 by van den Berghe et al found a 33% reduction in risk of hospital mortality for critically ill surgical patients who practiced tight glucose control. “Because few interventions in critically ill adult patients reduce mortality to this extent, the results of this trial were enthusiastically received and rapidly incorporated into guidelines,” write Renda Soylemez Wiener, M.D., M.P.H., (Department of Veterans Affairs Medical Center, White River Junction, Vt., and Dartmouth Medical School, Hanover, N.H.) and colleagues.
Further, tight glucose control in all critically ill patients is a recommendation of highly respected organization such as the American Diabetes Association and the American Association of Clinical Endocrinologists. “These recommendations have led to worldwide adoption of tight glucose control in a variety of intensive care unit (ICU) settings,” according to Wiener. However, there are some trials of tight glucose control in certain intensive care unit (ICU) settings that have not resulted in mortality benefit but have resulted in an increased risk for hypoglycemia.
In the meta-analysis, Wiener and colleagues studied 29 randomized controlled trials with 8,432 patients that compared risks and benefits of usual care in critically ill adults with tight glucose control (glucose goal of less than 150 mg/dL).
One finding was that between tight glucose control and usual care strategies, there was no significant difference in hospital mortality – 21.6% to 23.3%, respectively. The researchers also noted no significant differences in hospital mortality when individually analyzing surgical, medical, and medical-surgical ICU settings. While tight glucose control resulted in a risk of new need for dialysis by 11.2%, the rate for usual care was 12.1% – not a significant difference. However, tight glucose control was associated with a significantly decreased risk of septicemia, a generalized illness due to bacteria in the bloodstream (10.9% to 13.4%, respectively). Additionally, the risk of hypoglycemia under tight glucose control was about 5 times higher than under usual care (13.7% to 2.5%).
The authors conclude that, “Given the overall findings of this meta-analysis, it seems appropriate that the guidelines recommending tight glucose control in all critically ill patients should be re-evaluated until the results of larger, more definitive clinical trials are available.”
Simon Finfer, M.B.B.S., F.J.F.I.C.M. (The George Institute for International Health) and Anthony Delaney, M.B.B.S., F.J.F.I.C.M. (Royal North Shore Hospital, Sydney, Australia) write in an accompanying comment that:
“Possible explanations for the discordant results of the study by van den Berghe et al and the meta-analysis by Wiener et al are that the meta-analysis is flawed, the studies that form the basis of the meta-analysis are flawed or inherently different, or the findings of the study by van den Berghe et al occurred due to random chance or as a result of another unique factor interacting with tight glycemic control.”
They add: “Those investigating tight glycemic control should take a step back and address the fundamental questions of defining quality standards for tight glycemic control, finding affordable methods of frequent and highly accurate measurement of blood glucose in the ICU, and conduct multicenter efficacy studies to determine if tighter glycemic control can reduce mortality under optimal conditions. If tighter glycemic control can be proven effective in optimal conditions, determining how to make that benefit available to millions of critically ill patients in both developed and resource-poor countries around the world would be a truly worthwhile challenge. There is no simple or clear answer to the complex problem of glycemic control in critically ill adults; at present, targeting tight glycemic control cannot be said to be either right or wrong.”
Benefits and Risks of Tight Glucose Control in Critically Ill Adults: A Meta-analysis
Renda Soylemez Wiener; Daniel C. Wiener; Robin J. Larson
JAMA (2008). 300[8]: pp. 933-944.
Written by: Peter M Crosta