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A Meta-analysis of Randomized Controlled Trials

Anastassios G. Pittas, MD; Richard D. Siegel, MD; Joseph Lau, MD

Arch Intern Med. 2004;164:2005-2011.

Background  Hyperglycemia is common in critically ill hospitalized patients, and it is associated with adverse outcomes, including increased mortality. The objective of this meta-analysis was to determine the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness.

Methods  An electronic search in the English-language articles of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles were performed. Randomized controlled trials that reported mortality data on critically ill hospitalized adult patients who were treated with insulin were selected. Data on patient demographics, hospital setting, intervention (formulation and dosage of insulin, delivery method, and duration of therapy), mortality outcomes, adverse events, and methodological quality were extracted.

Results  Thirty-five trials met the inclusion criteria. Combining data from all trials using a random-effects model showed that insulin therapy decreases short-term mortality by 15% (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses, insulin therapy decreased mortality in the surgical intensive care unit (RR, 0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71; 95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI, 0.58-0.90). A near-significant trend toward decreasing mortality was seen in patients with acute myocardial infarction who did not receive reperfusion therapy (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical intensive care unit were identified.

Conclusion  Insulin therapy initiated in the hospital in critically ill patients has a beneficial effect on short-term mortality in different clinical settings.

From the Divisions of Endocrinology, Diabetes and Metabolism (Drs Pittas and Siegel) and Clinical Care Research (Dr Lau), Tufts-New England Medical Center, Boston, Mass. The authors have no relevant financial interest in this article.

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