Intensive versus Conventional Glucose Control in Critically Ill Patients

Background:  Currently, no guidelines exist which provide guidance for target blood glucose ranges in critically ill patients.

Objective:  The purpose of this study was to determine whether intensive or conventional glucose control in critically ill patients reduces mortality at 90 days.

Methods:  This study was a stratified randomized, open-label, parallel-group, controlled trial which used an intent-to-treat analysis.  Medical and surgical patients were enrolled from the Intensive Care Units of 42 different hospitals in New Zealand, Australia, and Canada, and followed for 90 days.  Inclusion criteria were an expected stay of 3 days in the ICU, and placement of an arterial line as part of routine ICU management.  Exclusion criteria were age less than 18 years, imminent death, and admission for diabetic ketoacidosis or hyperosmolar state.  Also, patients expected to be eating before the end of the day following the day of admission to the ICU, those who have previously suffered hypoglycemia without documentation of full neurological recovery, those considered to be at abnormally high risk for hypoglycemia, previous study enrollees, patients who could not provide informed consent, or patients that have been in the study ICU or another ICU for 24 hours or more for the admission were excluded from the study. 6104 patients underwent randomization.  3054 were assigned to the intensive control group, and 3050 were assigned to the conventional control group.  Blood glucose control was achieved with IV infusion of insulin.  Treatment was guided by a standardized treatment algorithm.  Intensive and conventional control groups had glucose goals of 81 to 108 mg/dL and less than 180 mg/dL, respectively.  A power of 90% was targeted.  The primary outcome measure analyzed death from any cause within 90 days of randomization.  Secondary outcome measures analyzed survival time during first 90 days, cause-specific death, duration of mechanical ventilation, renal-replacement therapy, and stays in the ICU and hospital. 

Results:  The analysis included data for 6030 patients.  The intensive control group had 829 (27.5%) patients die compared to 751 (24.9%) patients in the conventional control group, a 2.6% difference (95% CI, 0.4 to 4.8, p<0.05).  The odds ratio for death in the intensive control group was 1.14 (95% CI, 1.02 to 1.28, p=0.02).  Median survival time was lower in the intensive control group; hazard ratio of 1.11 (95% CI, 1.01 to 1.23, p=0.03).  Other secondary outcome measures were not significantly different.  Severe hypoglycemia was significantly more common with intensive glucose control, and mean blood glucose values differed significantly between the two groups.  The author’s concluded that intensive glucose control increased the absolute risk of death at 90 days by 2.6%, representing a number needed to harm of 38, and they do not recommend using the lower target range in critically ill adults.

Strengths:  A high power, extended follow-up period, standardized algorithmic treatment, and a predefined statistical analysis plan act as positive study assets.

Weaknesses:  The use of subjective criteria, expected length of ICU stay, as inclusion criteria acted as a limitation in this study. Also, the unblinding of clinical staff and a failure for the intensive control group to reach an average blood glucose target within the set range pose additional limitations within the study.  Furthermore, the number of people receiving parenteral and enteral nutrition in each group was not reported.

Conclusion:  Intensive glucose control in critically ill patients demonstrated a significant increase in mortality when compared to conventional glucose control.  The study set forth with a very clear and specific primary outcome in mind.  This outcome, patient mortality, was analyzed appropriately, and secondary outcome measures were used beneficially to supplement the study’s findings.  Due to a lack of current guidelines and the outcome of this study, blood glucose ranges in the critically ill should not aim to reach targets between 80 and 108 mg/dL.  Blood glucose levels in these patients should target the conventional goals of less than 180 mg/dL.  Further study may be necessary to evaluate glucose control in trauma patients and those receiving corticosteroids.

NICE-SUGAR Study Investigators, Finfer S, et al.  Intensive versus conventional glucose control in critically ill patients.  New England Journal of Medicine.  2009;360(13):1283-95.

Bradley Evans
PharmD. Candidate