Objective: Hyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressiveglycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear. The objective was to determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients. Methods: This was a 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. 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 under‐went 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 to 3.7) days and 6 (inter‐quartile range, 4.5 to 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 to 1.04] at a prevailing glucose level of 111 to 144 mg/dL [6.1 to 8.0 mmol/L] for a 1‐IU/day 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 to 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 appears to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.

Both low minimum and high maximum levels of arterial carboxyhemoglobin were associated with increased intensive care mortality. Although the heme oxygenase system is protective, excessive induction may be deleterious. This suggests that there may be an optimal range for heme oxygenase-1 induction.

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