LEUVEN, BELGIUM—It is well known that hyperglycemia and insulin resistance often develop in critically ill patients, even those with no history of diabetes. However, it has only recently become clear that failure to normalize their blood glucose levels may predispose them to complications, such as severe infection, polyneuropathy, multiple organ failure, and death.

That is what Belgian investigators learned when they prospectively studied 1,548 mechanically ventilated adults admitted to an intensive care unit (ICU) during a one-year period.[1] They also discovered that by keeping patients’ blood glucose levels in the normal range (80 to 110 mg/dL) with intensive insulin treatment, morbidity and mortality could be significantly reduced.

For example, ICU mortality was just 4.6% among patients who received intensive insulin treatment, but it was 8.0% among those given conventional therapy. Intensive treatment decreased in-hospital mortality by 34%, and it lowered the incidence of bloodstream infections, critical-illness polyneuropathy, and acute renal failure by 46%, 44%, and 41%, respectively. Intensive insulin treatment also significantly reduced the need for prolonged antibiotic therapy, the number of red-cell transfusions administered, and the duration of mechanical ventilation and ICU care.

“This treatment is a minor change in clinical practice with a major benefit,” lead investigator Greet Van den Berghe, MD, PhD, told PULMONARY REVIEWS. In fact, many ICUs around the world have switched to intensive insulin therapy based on this study, said Dr. Van den Berghe, a Professor of Intensive Care Medicine at the Catholic University of Leuven in Belgium.

MOST PATIENTS WERE SURGICAL PATIENTS

Because the ICU in the Belgian study is a surgical unit, the most common reason for admission was cardiac surgery. However, many patients were admitted for other reasons, including neurologic disease, respiratory insufficiency, and multiple trauma. Only 13% had a history of diabetes and 5% were receiving insulin at the time of ICU admission, when randomization to intensive or conventional insulin therapy occurred.

The 765 patients in the intensive treatment group were given insulin intravenously when their blood glucose level rose above 110 mg/dL; the maximum insulin dose was 50 IU/h. This group was switched to conventional treatment upon ICU discharge.

In the 783 patients given conventional treatment, insulin was administered only when the blood glucose level exceeded 215 mg/dL. The dose was then adjusted to maintain the glucose level between 180 and 200 mg/dL.

Virtually all of the patients in the intensive treatment group received insulin; the median daily dose was 71 IU. In contrast, only 39% of the conventionally treated patients were given insulin, at a median daily dose of 33 IU.

REDUCTION IN ORGAN–FAILURE DEATHS

The decreased ICU mortality associated with intensive insulin treatment was due to a lower fatality rate among the 451 patients who required more than five days in the ICU. In that subgroup, intensive therapy lowered mortality to 10.6%, versus 20.2% in those treated conventionally. The decreased in-hospital mortality among the patients given intensive therapy was largely due to a reduction in deaths from sepsis-related multiple organ failure.

A history of diabetes or hyperglycemia at the time of admission had no effect on mortality, the investigators found. Intensive insulin reduced the duration of ICU stay but not the overall length of hospital stay, they also noted.

Because virtually none of the patients admitted to their unit were excluded from the study, the results apply to all types of surgical ICU patients, said Dr. Van den Berghe. Whether they will also apply to medical ICU patients remains to be studied.

—Timothy Begany

Reference
1. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-1367.