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Simon J. Finney, MBChB, MRCP; Cornelia Zekveld, BSc; Andi Elia, BSc; Timothy W. Evans, MD, DSc, FRCP

JAMA. 2003;290:2041-2047.

Context  Hyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear.

Objective  To determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients.

Design, Setting, and Patients  Single-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine.

Main Outcome Measures  The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death.

Results  Of 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four–hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartile range, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase), suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level.

Conclusions  Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.

Author Affiliations: Adult Intensive Care Unit (Drs Finney and Evans), Department of Occupational and Environmental Medicine (Ms Zekveld), and Department of Biomedical Engineering (Ms Elia), Royal Brompton Hospital, London, England.

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