Intensive versus Conventional Glucose Control in Critically Ill Patients
NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, et al
N Engl J Med. 2009;360:1283-1297. Epub 2009 Mar 24
At least since 2001, with the publication of the first major intensive insulin therapy article, there has been substantial and growing interest in glycemic control among critically ill patients. Although the initial results were only from a single-center unblinded study, many societies and evidence-based treatment guidelines rapidly adopted tight glycemic control as a best practice standard. Subsequent studies have raised questions with regard to both the safety and the efficacy of tight glycemic control in critically ill patients.[3-6] For these reasons, the Australia and New Zealand Intensive Care Society (ANZICS) set out to determine the role of glycemic control in critically ill patients. The NICE-SUGAR study was designed to identify critically ill patients within 24 hours who would require treatment in the intensive care unit for at least 3 days and then randomize them into 1 of 2 glucose control groups. The tight glycemic control group had a glucose target of 4.5-6 mmol/L (81-108 mg/dL), and the conventional group had a glucose target of less than 10 mmol/L (180 mg/dL). There were 6104 patients equally randomized from 42 hospitals over 4 years. Overall, patients in the tight glycemic control group were more likely to die within 90 days, with a relative risk of 1.14 (P = .02). Of importance, these results did not significantly differ between surgical and medical patients. Severe hypoglycemia (defined as blood glucose less than 2.2 mmol/L) was more common in the tight glycemic control group at 6.8% vs 0.5% (P < .001). There were no differences in morbidity or in other intermediate outcomes, such as the duration of stay in the intensive care unit.
The completion and reporting of the NICE-SUGAR study is a landmark event in critical care. Once again, ANZICS has shown the world how to effectively and efficiently complete a clinical trial that will determine clinical practice for years to come. This trial is particularly welcome because of the controversy surrounding tight glycemic control in critically ill patients. Studies over the past few years have raised serious questions about the safety of achieving tight glycemic control in critically ill patients, particularly as it relates to associated hypoglycemia. We now recognize that hypoglycemia carries substantial adverse consequences, which may outweigh any purported benefit related to lower glucose levels. With the publication of the NICE-SUGAR study, individual clinicians should change their practice, and institutions and societies should revise their practice guidelines as they relate to glucose control. In critically ill patients, the new standard should be to maintain blood glucose levels less than 10 mmol/L (180 mg/dL) and to avoid hypoglycemia whenever possible. One question remains unanswered: At what level of blood glucose do we begin to initiate control measures? The data are insufficient to support insulin use in all patients regardless of blood glucose because these patients would almost certainly require administration of substantial quantities of dextrose to counteract the effects of insulin. According to the NICE-SUGAR study, insulin therapy was not begun in the conventional group until glucose levels exceeded 10 mmol/L (180 mg/dL). For those patients with hyperglycemia, initiating insulin therapy when glucose levels exceed 10 mmol/L (180 mg/dL) is appropriate, and could be considered at lower levels (such as above 8.5 mmol/L) if hypoglycemia can be wholly prevented.
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