Findings challenge common practice regarding glucose control for critically ill patients

August 26, 2008

An analysis of randomized trials indicates that for critically ill adults, tight glucose control is not associated with a significantly reduced risk of death in the hospital, but is associated with an increased risk of hypoglycemia, calling into question the recommendation by many professional societies for tight glucose control for these patients, according to an article in the August 27 issue of JAMA.

In 2001, a randomized controlled trial (van den Berghe et al) showed that tight glucose control for critically ill surgical patients reduced hospital mortality by one-third. "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," the authors write. Numerous organizations, including the American Diabetes Association and the American Association of Clinical Endocrinologists now recommend tight glucose control in all critically ill adults. "These recommendations have led to worldwide adoption of tight glucose control in a variety of intensive care unit (ICU) settings." But some subsequent trials of tight glucose control in certain ICU settings have failed to show the mortality benefit, and have indicated an increased risk for hypoglycemia (abnormally low blood sugar level).

Renda Soylemez Wiener, M.D., M.P.H., of the Department of Veterans Affairs Medical Center, White River Junction, Vt., and Dartmouth Medical School, Hanover, N.H., and colleagues conducted a meta-analysis of 29 randomized controlled trials, examining the risks and benefits of tight glucose control (glucose goal less than 150 mg/dL) as compared with usual care in critically ill adults. The meta-analysis included data for 8,432 patients.

The researchers found that among these trials, there was no significant difference in hospital mortality between tight glucose control and usual care strategies (21.6 percent vs. 23.3 percent) and no significant difference in hospital mortality when stratified by surgical, medical, and medical-surgical ICU setting. Tight glucose control was not associated with a significantly decreased risk for new need for dialysis (11.2 percent vs. 12.1 percent), but was associated with a significantly decreased risk of septicemia (10.9 percent vs. 13.4 percent; generalized illness due to bacteria in the bloodstream). The risk of hypoglycemia was increased about 5-fold (13.7 percent vs. 2.5 percent).

"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," the authors write.

(JAMA. 2008;300[8]:933-944. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Tight Glycemic Control in Critically Ill Adults

In an accompanying editorial, Simon Finfer, M.B.B.S., F.J.F.I.C.M., of The George Institute for International Health, and Anthony Delaney, M.B.B.S., F.J.F.I.C.M., of the Royal North Shore Hospital, Sydney, Australia, comment on the results of the meta-analysis.

"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."

"... 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."

(JAMA. 2008;300[8]:963-965. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other affiliations, financial disclosures, funding and support, etc.
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