Tight Glucose Control in Critically Ill Adults May Not Improve All Outcomes

A recent study sheds new light on the standard hospital practice of glucose control. The study indicates that for critically ill patients, striving to keep blood glucose at normal levels doesn’t significantly reduce risk of death in the hospital, and actually increases the risk of low blood sugar.

"The American Diabetes Association and Surviving Sepsis Campaign recommend tight glucose control in critically ill patients based largely on 1 trial that shows decreased mortality in a surgical intensive care unit," write Renda Soylemez Wiener, MD, MPH, from Dartmouth Medical School in Hanover, New Hampshire, and colleagues. "Because similar studies report conflicting results and tight glucose control can cause dangerous hypoglycemia, the data underlying this recommendation should be critically evaluated."

The goal of this meta-analysis was to assess the benefits and risks for tight glucose control vs usual care in critically ill adult patients. The reviewers searched for studies in  which adult patients in the intensive care unit (ICU) were randomly assigned to tight glucose control vs usual glucose control.

Of 1358 identified studies, 34 randomized trials met criteria for inclusion; of these, 23 were full publications, 9 were abstracts, and 2 were unpublished studies.

Using a prespecified protocol and standardized scale, 2 reviewers independently extracted data and evaluated the methodologic quality of the included trials. Study investigators were contacted for missing details, and random-effects and fixed-effects models were used to estimate relative risks (RRs).

The 29 randomized controlled trials used for the meta-analysis enrolled a total of 8432 patients. Overall hospital mortality rate was not significantly different with tight glucose control vs usual care. When stratified by glucose target, the analysis still showed no significant difference in mortality rates with very tight glucose control(≤ 110 mg/dL) moderately tight glucose control (< 150 mg/dL)

Although tight glucose control was not linked to a significantly decreased risk for a new need for dialysis, it was associated with a significantly decreased risk for septicemia and a significantly increased risk for hypoglycemia (glucose levels ≤ 40 mg/dL)

"In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia," the study authors write. "When stratified by ICU setting, the significant association with reduced risk of septicemia was limited to trials conducted in the surgical ICU. 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 reevaluated until the results of larger, more definitive clinical trials are available."

In an accompanying editorial, Simon Finfer, MBBS, FJFICM, and Anthony Delaney, MBBS, FJFICM, from the University of Sydney and Royal North Shore Hospital in Australia, note the need to define quality standards for tight glycemic control, to find affordable methods of frequent and highly accurate measurement of blood glucose in the ICU, and to conduct multicenter efficacy studies to determine if tighter glycemic control can reduce mortality rates under optimal conditions.
"If tighter glycemic control (80 – 110 mg/dL) 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," Drs. Finfer and Delaney write. "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."

Practice Pearls:

• Tight glucose control vs usual glucose control in critically ill patients is not associated with a reduction in hospital mortality rates or the need for new dialysis.
• Tight glucose control vs usual glucose control in critically ill patients is associated with reduced septicemia in critically ill patients in surgical ICUs and an increased risk for hypoglycemia.

JAMA. 2008;300:933-944, 963-965.

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