Moderate or severe hypoglycemia associated with mortality risk in the ICU

Moderate or severe hypoglycemia in the intensive care unit (ICU) was significantly associated with mortality, according to a new analysis of the NICE-SUGAR trial.

The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial randomly assigned intensive care patients to either intensive (mean blood glucose level, 115 mg/dL) or conventional (mean blood glucose level, 144 mg/dL) blood glucose control, and results were published in 2009. This new analysis provides more detail on the associations between intensive control and hypoglycemia and mortality found in the original study. The analysis appeared in the Sept. 20 New England Journal of Medicine.

Of the about 6,000 patients studied, 45% had moderate hypoglycemia, defined as a blood glucose level 41 to 70 mg/dL; 82% of them were in the intensive control group. Severe hypoglycemia (blood glucose level ≤40 mg/dL) occurred in 3.7% of patients (93% of them in the intensive group). Mortality was higher among the patients with severe hypoglycemia (35.4% mortality rate; adjusted hazard ratio [HR] for death, 2.10) and moderate hypoglycemia (28.5%; HR, 1.41) than in those with no hypoglycemia (23.5%; HR, 1). Patients also had an increased risk of dying if they had moderate hypoglycemia on more than one day or had severe hypoglycemia while not taking insulin.

Intensive glucose control leads to hypoglycemia, which in turn is associated with increased risk of death in critically ill patients, the researchers concluded. They noted the existence of a dose-response relationship but cautioned that the data cannot establish a causal relationship. However, a causal relationship would be “plausible,” according to the researchers, and is consistent with the finding that hypoglycemic patients were significantly more likely to die of distributive (vasodilated) shock.

It is also possible that the hypoglycemia was a marker rather than a cause of death, at least in some cases, such as the patients not taking insulin whose hypoglycemia likely resulted from underlying disease processes. Still, the authors concluded that critical care clinicians should work to avoid hyperglycemia and hypoglycemia in their patients, and follow current guidelines for a blood glucose target of 144 to 180 mg/dL. An accompanying editorial noted that the study showed the difficulty of implementing insulin protocols and accurately monitoring glucose. The editorialist expressed hope that new technologies for continuous glucose monitoring will help clarify the results of the NICE-SUGAR.