Even Mild or Moderate Hypoglycemia Linked to Mortality in Critically Ill Patients

Laurie Barclay, MD

March 25, 2010

March 25, 2010 — Even mild or moderate hypoglycemia is linked to mortality in critically ill patients, according to the results of a study reported in the March issue of Mayo Clinic Proceedings.

"Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death," said second author Rinaldo Bellomo, MD, from Austin Health in Heidelberg, Victoria, Australia, in a news release.

The goal of the study was to evaluate whether there is an independent association between mild or moderate hypoglycemia in critically ill patients and an increased risk for mortality.

From January 1, 2000, to October 14, 2004, a total of 4946 patients were admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia. The investigators examined the independent association between hypoglycemia, defined as a glucose concentration of less than 81 mg/dL, and outcome in 1109 of these patients who had at least 1 episode of hypoglycemia.

Hospital mortality rate was 36.6% in these 1109 patients vs 19.7% in the 3837 nonhypoglycemic control patients (P < .001). Unadjusted mortality rate was greater in patients with a minimum blood glucose concentration between 72 and 81 mg/dL vs control patients (25.9% vs 19.7%; unadjusted odds ratio [OR], 1.42; 95% confidence interval [CI], 1.12 - 1.80; P = .004.)

"This risk of death persisted after correction for other risk factors, suggesting that hypoglycemia may independently contribute to this increased risk," Dr. Bellomo said.

Increasing severity of hypoglycemia was associated with significantly increased mortality rate (P < .001). After adjustment for insulin treatment, hypoglycemia was independently associated with an increased risk for death, cardiovascular death, and death from infectious disease.

"Our results suggest that any tolerance of mild to moderate hypoglycemia by intensive care clinicians may be undesirable," Dr. Bellomo said. "In this regard, newer technologies such as continuous glucose monitoring in the ICU setting might help avoid hypoglycemia or identify it earlier."

Limitations of this study include retrospective design, creating the potential for systematic error and bias; observational design, preventing determination of causality; and setting at only 2 centers, limiting generalizability.

"In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality," the study authors write. "Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death."

In an accompanying editorial, James S. Krinsley, MD, from Stamford Hospital in Stamford, Connecticut, and Mark T. Keegan, MD, from Mayo Clinic in Rochester, Minnesota, note that the development and clinical implementation of continuous or near-continuous glucose monitoring devices and "closed-loop" glycemic control systems may be helpful.

"With the use of these new technologies, coupled with algorithm-driven treatment protocols, the rate of hypoglycaemia should plummet; moreover, studies can be completed to prospectively evaluate the potential benefit in targeting a reduction in glycemic variability as an additional therapeutic goal," Drs. Krinsley and Keegan write. "Until then, we think that the study by Egi et al confirms the deleterious effect of hypoglycemia, especially severe hypoglycemia, in critically ill patients; highlights the complexity of this clinical problem; and reinforces the principle that clinicians practicing glycemic control must do so safely."

This study was supported by a grant from the Austin Hospital Intensive Care Trust Fund.

Mayo Clin Proc. 2010;85:215-216, 217-224. Abstract

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