Intensive vs conventional blood glucose control in critically ill patients

Abstract

Hyperglycemia is common during critical illness and has been identified as a modifiable risk factor for increased morbidity and mortality in critically ill patients. Data from selected clinical trials suggest that intensive insulin therapy (IIT) and tight glycemic control (TGC) achieve a clinical benefit when targeting blood glucose (BG) in the range of 4.4– 6.1 mmol L. However, reports of recently conducted randomized trials have shown conflicting results. Consequently, the NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) trial was designed as a pragmatic multi-national multi-centre randomized ‘‘effectiveness’’ trial to evaluate the impact of IIT to achieve TGC on 90-day all cause mortality and several secondary morbidity outcomes. The NICESUGAR trial aimed to resolve existing concerns about the applicability of IIT to achieve TGC in critical illness. This article considers the NICE-SUGAR trial and discusses its key findings in the context of the published literature. As the optimum target range for blood glucose (BG) in critically ill patients remains unclear, the objective of this study was to evaluate whether intensive glucose control in critical illness is associated with improved clinical outcomes. The design was a multi-national multi-centre randomized controlled trial. The setting involved 42 participating intensive care units (ICUs) across Australia, New Zealand, Canada, and the United States. Critically ill adult subjects met the eligibility requirements if, within 24 hr after admission to an ICU, they were expected to require treatment in the ICU for three or more consecutive days. Subjects were randomized to receive either intensive glucose control with a target blood glucose range of 4.5–6.0 mmol L or conventional glucose control with a target blood glucose range of 10.0 mmol L or less. The primary endpoint was allcause mortality 90 days after randomization. Of the 6,104 subjects who were randomized, 3,054 patients were randomized to undergo intensive glucose control and 3,050 patients received conventional glucose management. Data with regard to the primary outcome at day 90 were available for over 98% of the subjects evaluated. The two groups had similar characteristics at baseline. The authors reported that 829 patients (27.5%) in the intensive-control group and 751 (24.9%) patients in the conventional-control group died (odds ratio [OR] for intensive control, 1.14; 95% confidence intervals [CI], 1.02–1.28; P = 0.02). The treatment effect was similar when comparing operative (surgical) patients and non-operative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P = 0.10). Severe hypoglycemia, defined as a blood glucose level \2.2 mmol L was reported in 206 (6.8%) of patients in the intensive-control group and 15 (0.5%) of patients in the conventional-control group (P 0.001). The groups were found to be similar regarding the median S. M. Bagshaw, MD (&) M. J. Jacka, MD University of Alberta, Edmonton, Canada e-mail: bagshaw@ualberta.ca