Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation - NICE-SUGAR
Description:
The goal of the trial was to evaluate a strategy of intensive glucose control compared with conventional control in critically ill patients.
Hypothesis:
Intensive glucose control would be more effective in reducing mortality.
Study Design
- Randomized
- Parallel
Patients Enrolled: 6,104
Mean Follow Up: 90 days
Mean Patient Age: 60 years
Female: 37%
Patient Populations:
- 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
Exclusions:
- 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
Primary Endpoints:
- All-cause mortality at 90 days
Secondary Endpoints:
- 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
Drug/Procedures Used:
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.
Principal Findings:
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
Interpretation:
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.
References:
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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