Tight glucose control among ICU patients significantly raised the risk of death within 90 days, compared with conventional glucose control, Dr. Simon Finfer reported at the International Symposium on Intensive Care and Emergency Medicine in Brussels.
In a large international, randomized clinical trial, a blood glucose target of less than 180 mg/dL resulted in lower mortality than a target of 81–108 mg/dL. “On the basis of these results, we do not recommend use of the lower target in critically ill adults,” Dr. Finfer said.
Hyperglycemia is common in acutely ill patients. Intensive glucose control for ICU patients has been recommended by many professional organizations “on the assumption that treatment aimed at normoglycemia will benefit patients,” said Dr. Finfer of the George Institute for International Health, Sydney.
However, some clinicians are reluctant to attempt tight glucose control because the risks—primarily the higher incidence of severe hypoglycemia—may outweigh the benefits.
Several studies have yielded conflicting results. Dr. Finfer and his associates undertook the Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial to determine whether tight glucose control reduces mortality at 90 days.
The study involved 6,104 medical and surgical patients admitted to ICUs in 38 academic tertiary care hospitals and 4 community hospitals in Australia, New Zealand, and North America. Of the 6,030 subjects for whom study data were available, 3,014 were randomized to receive conventional glucose control (with a target of 180 mg/dL or less), and 3,016 to receive tight glucose control (with a target of 81–108 mg/dL) with intravenous insulin infusions. The mean duration of study treatment was 4 days.
Ninety-day mortality was 24.9% with conventional glucose control and 27.5% with tight glucose control, a significant difference. “This represents a number needed to harm of 38,” Dr. Finfer said (N. Engl. J. Med. 2009;360:1283–97).
Median survival time was shorter in the tight-control than in the conventional-control group.
Tight glucose control did not improve mortality in certain subgroups of patients who might be expected to benefit from more stringent control. Mortality was similar between surgical patients and medical patients, between patients with or without diabetes, between those with or without severe sepsis, and between those with high or low Acute Physiology and Chronic Health Evaluation (APACHE) scores.
Severe hypoglycemia, defined as a blood glucose level of 40 mg/dL or less, occurred in 206 (6.8%) of the tight-control group, compared with 15 (0.5%) of the conventional-control group. There were 272 episodes of severe hypoglycemia in patients under tight glucose control, compared with 16 episodes in those under conventional glucose control.
There were no significant differences between the two groups in ICU or hospital lengths of stay, the number of single or multiple organ failures that developed, the number of days on mechanical ventilation or on renal replacement therapy, or the rates of positive blood cultures and red-cell transfusions.
“Our findings suggest that a goal of normoglycemia for glucose control does not necessarily benefit critically ill patients and may be harmful,” Dr. Finfer said. “Whether the harm we observed resulted from the reduced blood glucose level, increased administration of insulin, occurrence of hypoglycemia, methodologic factors specific to our trial, or other factors is unclear.”
According to a joint statement released by the American Diabetes Association and the American Association of Clinical Endocrinologists, this study “should not lead to an abandonment of the concept of good glucose management in the hospital setting,” and should not “swing the pendulum of glucose control too far in the other direction,” leading to complacency about uncontrolled hyperglycemia. “Until more information is available, it seems reasonable for clinicians to treat critical care patients with the less intensive—yet good—glucose control strategies used in the conventional arm of the NICE-SUGAR trial.”
Clinicians “are now left in something of a quandary,” because many hospitals have already adopted “the automatic and seamless use of insulin infusion in patients in the ICU,” Dr. Silvio E. Inzucchi and Dr. Mark D. Siegel of Yale University, New Haven, Conn., wrote in an editorial (N. Engl. J. Med. 2009;360:1346–8).
“We would caution against any overreaction to the NICE-SUGAR findings,” they said.
“It would be a disservice to our critically ill patients to infer from the NICE-SUGAR data that neglectful glycemic control involving haphazard therapeutic approaches (e.g., use of insulin ‘sliding scales’)—all too common a decade ago—is again acceptable practice in our ICUs,” Dr. Inzucchi and Dr. Siegel said.
Dr. Finfer reported receiving reimbursement for travel to present research results at scientific meetings from Eli Lilly & Co., Cardinal Health Inc., and CSL Bioplasma Ltd., as well as reimbursement for serving on steering committees for studies sponsored by Eli Lilly and Eisai Inc. Dr. Inzucchi reported receiving research funding from Eli Lilly.
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