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.
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.
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.
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.