By Anthony J. Brown, MD

NEW YORK (Reuters Health) - For patients in pediatric intensive care units (PICU), insulin infusion therapy aimed at achieving normal fasting blood glucose levels may improve survival and reduce the PICU stay, new research suggests.

"The novelty and challenge lies in the fact that normal (fasting) levels of blood glucose in young children are lower than in adults and thus it is quite challenging to titrate the insulin infusion to these lower ranges," senior author Dr. Greet Van den Berghe told Reuters Health. "However, our studies indicated that getting to these lower targets is crucial to get any benefit."

Hyperglycemia (high blood sugar) is a common finding in PICU patients and it has been linked to adverse clinical outcomes, Van den Berghe, from Catholic University Leuven, Belgium, and colleagues explain. Whether these infants' outcomes could be improved by normalizing the blood glucose level, however, was unclear.

As reported in The Lancet, the researchers evaluated 700 patients who were randomly assigned to receive insulin infusions to normalize their blood glucose levels or only enough to keep glucose levels below 11.9 mmol/L.

The main outcome measures were the length of stay in the PICU and inflammation, as assessed by C-reactive protein levels, a biologic marker of inflammation.

As expected, the average blood glucose levels were significantly lower in the intensive insulin group than in controls. Hypoglycemia, or low blood glucose, was also significantly more common in the intensive insulin group. On day 5 of treatment, the inflammatory response was also lower in the intensive insulin group.

On average, intensive insulin patients had a shorter PICU stay than did controls: 5.51 vs. 6.15 days. The number of patients with an extended PICU stay, defined as a day or longer than the average, was 132 (38 percent) in the intensive insulin group compared with 165 (47 percent) in the control group.

Although not a primary outcome measure, the mortality rate in the intensive insulin therapy group was half that of the control group: 3 percent vs. 6 percent.

"We did not expect a mortality benefit," Van den Berghe said. The study was designed to detect differences in illness and length of PICU stay. "To find, besides a morbidity benefit, also a similar reduction in the risk of death as previously observed in our adult studies was thus quite striking," Van den Berghe said.

Because the study "was performed in one center only, the results do not necessarily apply to other centers," Van den Berghe stressed. "Experienced nurses are needed to perform this intervention safely, and thus further studies are needed before the results can be extrapolated to other centers."

SOURCE: The Lancet, January 27, 2009.

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