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Has Tight Glucose Control Come Full Circle?
By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.
Intensive insulin therapy in the ICU is a dynamic and controversial issue that has played out in the medical literature, at the bedside, and in the offices of policy makers over the last 8 years. Amid mounting evidence that hyperglycemia is harmful to critically ill patients, the initial report of Van den Berghe and colleagues of improved mortality with tight glucose control took the critical care world by storm,1 initiating a wave of ICU- and hospital-level policy changes and protocols as well as practice guidelines from several prestigious professional organizations and the Surviving Sepsis Campaign in support of intensive insulin therapy. That the Van den Berghe study was from a single institution, in surgical ICU patients monitored very closely and managed aggressively with mainly parenteral nutritional support, raising the possibility that perhaps not all patient populations or critical care management environments would derive the same benefits from intensive insulin therapy, was discussed at journal clubs and in editorials, but such therapy quickly became the standard of care for thousands of ICUs.
As nicely summarized by Dr. Akhtar, studies published since that initial report, extending intensive insulin therapy into wider populations of ICU patients, have been less positive, and the benefits of this therapy have become progressively less obvious. Publication of the NICE-SUGAR study, the largest clinical trial to date, which included medical, surgical, and mixed ICU patients, has increased the uncertainty, suggesting that intensive insulin therapy may actually be harmful.
The largest and most rigorous meta-analysis on this issue to date has just been published.2 This analysis by Griesdale and colleagues at several Canadian and U.S. institutions included results of the NICE-SUGAR study. In all, it included 13,567 patients in 26 randomized controlled trials of intensive insulin therapy. Among the trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI], 0.83-1.04). Among those that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI, 4.5-8.0) — a 6-fold increase in this complication. Stratification by type of ICU suggested a benefit in surgical ICU patients, whereas no such suggestion was found in medical or mixed ICU patients.
Griesdale et al conclude as follows: "[O]ur findings do not support the guidelines of organizations such as the American Diabetes Association, the American Association of Clinical Endocrinologists, and other organizations, including the Surviving Sepsis Campaign, that recommend intensive insulin therapy for all critically ill patients. Our meta-analysis incorporates the results of the largest trial to date. We are not aware of any ongoing trial of sufficient size to affect these results; thus, we suggest that policy makers reconsider recommendations promoting the use of intensive insulin therapy in all critically ill patients."
This most recent evaluation shows that a dogmatic approach to this issue is difficult to justify using currently available data. The authors emphasize that they "cannot exclude the possibility that some patients may benefit from intensive insulin therapy, although the characteristics of such patients remain to be clearly defined; as does the effect of different blood glucose algorithms, the method of measuring blood glucose, and the influence of nutritional strategies." In the meantime, Dr. Akhtar's recommendations seem to me to be sound advice.