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Insulin Therapy and In-Hospital Mortality in Critically Ill Patients: Systematic Review and Meta-analysis of Randomized Controlled Trials

Anastassios G. Pittas, MD^*, Richard D. Siegel, MD^* and Joseph Lau, MD

From the ^* Division of Endocrinology, Diabetes and Metabolism and Institute for Clinical Research and Health Policy Studies, Tufts–New England Medical Center, Boston, Massachusetts

Correspondence: Anastassios G. Pittas, MD, Division of Endocrinology, Diabetes and Metabolism, Tufts–New England Medical Center, 750 Washington Street, #268, Boston, MA 02111. Electronic mail may be sent to apittas{at}tufts-nemc.org.

Background: Hyperglycemia is common in critically ill hospitalized patients and has been associated with adverse outcomes, including increased mortality. In this review, we examine the effect of insulin therapy on mortality in critically ill patients. Methods: We updated our previous systematic review and meta-analysis to include recently published trials that report data on the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness. We also include a short primer on the methods of systematic reviews and meta-analyses, outlining the specific steps and challenges of this methodology. We performed an electronic search in the English language of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles for randomized controlled trials that reported mortality data on critically ill hospitalized adult patients treated with insulin (regardless of method of administration). Results: We identified 38 relevant studies that entered the analysis. We found that therapy with insulin in adult patients hospitalized for a critical illness, other than hyperglycemic crises, may decrease mortality in certain groups of patients. The beneficial effect of insulin was evident in the surgical intensive care unit (relative risk [RR], 0.58; confidence interval [CI], 0.22–0.62) and in patients with diabetes (RR, 0.76; CI, 0.62–0.92). There was a trend toward benefit in patients with acute myocardial infarction (RR, 0.89; CI, 0.76–1.03). Targeting euglycemia appears to be the main determinant of the benefit of insulin therapy (RR, 0.73; CI, 0.57–0.94). Conclusions: Insulin therapy in adult patients hospitalized for a critical illness, other than hyperglycemic crises, may decrease mortality in certain groups of patients.

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