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Glycemic Control, Mortality, and Hypoglycemia in Critically Ill Patients: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Yamada T, Shojima N, Noma H, et al. Intensive Care Med. 2017;43:1-15.
Study Question: What are the mortality rates and frequency of hypoglycemic events associated with various types of glucose control strategies for the critically ill who receive insulin therapy?
Study Description: This systematic review and meta-analysis identified PubMed, Cochrane Library, and Web of Science randomized control trials (RCT) that compared different glycemic control strategies using insulin in critically ill patients with hyperglycemia. Studies were included if the RCT compared various insulin regimens in adult critically ill patients with hyperglycemia and reported outcomes of interest. The primary efficacy outcome assessed was short-term mortality defined as ICU, hospital, 28-day, 90-day, or 6-month mortality. The primary safety outcome was hypoglycemia (blood glucose < 3.3 mmol/L), with severe hypoglycemia defined as blood glucose < 2.2 mmol/L. Patients were stratified into four groups: tight control (4.4 to < 6.1 mmol/L), moderate control (6.1 to < 7.8 mmol/L), mild control (7.8 to < 10.0 mmol/L), and very mild control (10.0 to < 12.2 mmol/L).
Results: Thirty-six RCTs were identified which included 17,996 patients. There was no statistical difference in the primary efficacy outcome between very mild control and tight control (RR 0.94, 95% CI 0.83-1.07, p = 0.36), mild control (RR 0.88, 95% CI 0.73-1.06, p = 0.18), or moderate control (RR 1.1, 95% CI 0.66-1.84, p = 0.72). Severe hypoglycemia was more common than tight control compared to very mild control (RR 5.49, 95% CI 3.22-9.38, p < 0.001) or mild control (RR 4.47, 95% CI 2.5-8.03, p < 0.001).
Conclusions: Tight glycemic control did not confer mortality benefit and was associated with increased hypoglycemic events.
Perspective: The American Diabetes Association recommends critically ill patients maintain blood glucose values between 140 mg/dL to 180 mg/dL (Grade A). This meta-analysis reflects the current practice of critical care clinicians today and previous works in the literature such as the NICE-SUGAR trial and the Leuven II from Van den Berghe et al (2006). While tighter control may have been shown to have some benefit in ICU length of stay and duration of mechanical ventilation, its benefits do not outweigh the risks reflected in hypoglycemia rates.