Hypoglycemia was associated with increased mortality in ICU patients regardless of glucose control strategy

A post hoc analysis of the NICE-SUGAR trial that included about 6,000 ICU patients compared intensive glucose control (targeting blood glucose levels of 81 to 108 mg/dL) and conventional glucose control (targeting levels ≤180 mg/dL). Intensive glucose control caused more moderate and severe hypoglycemia than conventional control. Hypoglycemia was associated with increased risk for 90-day mortality in the intensive and control groups.

The study was published by New England Journal of Medicine on Sept. 20. The following commentary by Todd W. Rice, MD, MSc, was published in the ACP Journal Club section of the Jan. 15 Annals of Internal Medicine.

Evidence of a direct association between iatrogenic hypoglycemia and mortality in critical illness, as shown in the NICE-SUGAR study, reinforces concerns about interventions to achieve tight glucose control. Findings from a seminal trial showing improved ICU survival with intensive insulin therapy have been refuted by more recent systematic reviews. It is likely that both severe hyperglycemia and hypoglycemia adversely affect ICU survival. A recent study of intensive insulin therapy in patients with sepsis was stopped early when the data monitoring committee observed increased hypoglycemia, with no measurable survival effect.

Historically, hypoglycemia in the ICU was perceived to be a marker of illness severity rather than a direct cause of mortality. The post hoc analysis of the NICE-SUGAR study supports both explanations. The association between hypoglycemia and mortality in the absence of insulin therapy suggests that hypoglycemia is a marker for sicker patients with a higher risk for death. However, the same association among patients receiving insulin therapy for hyperglycemia supports a causal link in this group. Mortality increased with the severity of hypoglycemia and also with an increasing number of hypoglycemic events.

These data show a complicated relation between hypoglycemia and mortality in critically ill patients. At the present time, a reasonable approach for treating critically ill patients with hyperglycemia is to use a moderate glucose control treatment algorithm, targeting 144 to 180 mg/dL, to minimize severe hyperglycemia and avoid iatrogenic hypoglycemia.