Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation - NICE-SUGAR
The goal of the trial was to evaluate a strategy of intensive glucose control compared with conventional control in critically ill patients.
Intensive glucose control would be more effective in reducing mortality.
Patients Enrolled: 6,104
Mean Follow Up: 90 days
Mean Patient Age: 60 years
- Patients admitted to the ICU and expected to be there for at least 3 days
- Patients have or are expected to have an arterial catheter for blood draws in place
- Age <18
- Imminent death
- Diabetic ketoacidosis or hyperosmolar state
- Patients who are expected to be eating on the day following admission
- Patients who previously suffered from hypoglycemia without full neurological recovery or patients who have a high risk for hypoglycemia
- Inability to provide informed consent
- Patient has already been in the ICU for 24 hours prior to consideration of enrollment in the study
- All-cause mortality at 90 days
- Survival time
- Cause-specific death
- Duration of mechanical ventilation
- Duration of renal-replacement therapy
- Duration in the ICU
- Duration in the hospital
- All-cause mortality at 28 days
- Place of death
- Incidence of new organ failure
- Positive blood culture
- Blood transfusion
Patients admitted to the intensive care unit (ICU) were randomized to intensive glucose control (81-108 mg/dl; n = 3,054) versus conventional glucose control (<180 mg/dl; n = 3,050). In all patients, insulin was given intravenously and nutrition was given enterally.
Overall, 6,104 patients were randomized. There was no difference in baseline characteristics between the groups. The mean age was 60 years, 37% were women, body mass index was 28 kg/m2, 20% had diabetes, mechanical ventilation was used in 94%, renal-replacement therapy was used in 6%, sepsis was present in 22%, trauma was present in 14%, and APACHE II score ≥25 was present in 31%.
The incidence of the primary outcome, all-cause mortality at 90 days, occurred in 27.5% in the intensive group versus 24.9% of the conventional control group (p = 0.02). There was no difference in the primary outcome according to surgical or medical patients. Mortality at 28 days was 22.3% versus 20.8% (p = 0.17), respectively. The cause of death was cardiovascular shock in 20.3% versus 18.6%, other cardiovascular cause in 21.4% versus 17.2%, neurologic in 21.7% versus 25.8%, respiratory in 23.0% versus 23.6%, and other in 13.6% versus 14.8%, respectively for intensive versus conventional control.
Severe hypoglycemia occurred in 6.8% versus 0.5% (p
Among patients admitted to the ICU, intensive glucose control was not beneficial and in fact increased mortality at 90 days. This strategy increased mortality by an absolute 2.6%, which corresponded to a number needed to harm of only 38 patients. Severe hypoglycemia was more common in the intensive control group.
Previous studies have shown mixed results comparing these treatment strategies; however, the present trial had high statistical power with one of the longest follow-up periods. Only one-fifth of the study participants had a previous diagnosis of diabetes. It is unknown if low glucose levels, administration of insulin, or periodic severe hypoglycemia accounted for the harm with intensive glucose control. Unless a future study definitively disputes these findings or finds a subgroup of patients who benefits, the use of intensive glucose control in ICU patients should likely be discouraged.
The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.
Keywords: Insulin, Intensive Care Units, Follow-Up Studies, Sepsis, Respiration, Artificial, Critical Care, Dissent and Disputes, Hypoglycemia, Glucose, Cause of Death, Body Mass Index, APACHE, Critical Illness, Diabetes Mellitus
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