Inpatient glucose control: How intensive is too intensive?

In 2001, Van den Berghe et al reported a 42% relative decrease in mortality in the surgical ICU when blood glucose was controlled to between 80 mg/dL and 110 mg/dL. However, in a subsequent study, they did not find reduction in mortality in the medical ICU, except for those patients requiring more than three days of intensive care. Other studies have not definitively confirmed the benefits of aggressive inpatient control. Some had excessively high rates of hypoglycemia.

The results of these studies raised many questions: what is optimal glucose range for inpatients? Is hyperglycemia a cause of mortality, or is it only a marker of severe illness? How can potential benefits of aggressive glycemic control be balanced with risks of hypoglycemia?

Nevertheless, work groups were organized and consensus statements were written. Professional organizations advocated for aggressive inpatient glycemic control. Many centers reevaluated their standard practice. New protocols for inpatient glucose control were developed.

More recently, however, some have begun to question how tightly blood glucose should be controlled.

The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study raises further questions. In this multicenter study, 6,104 ICU patients were randomized to more intensive (81 mg/dL to 108 mg/dL) or conventional (<180 mg/dL) glucose control. Individuals in the more intensively treated group were 14% more likely to die compared with the conventional control group. Not surprisingly, there was a greater risk of severe hypoglycemia in the more intensively treated group compared with the conventional control group (6.8% vs. 0.5%). There was no difference in length of stay in the ICU or the hospital and no difference for other outcomes, such as days on mechanical ventilation or need for dialysis. The reasons for these results are unclear.

Many have voiced concerns about the pendulum swinging back the other way. The American Diabetes Association and the American Association of Clinical Endocrinologists issued a joint statement advising caution when interpreting NICE-SUGAR and applying the results to practice. They stated that the results of this study should not result in abandonment of the goal of excellent inpatient glycemic control. Full recommendations are to be released later this spring.

As clinicians we must balance doing what we think is best with the potential for causing harm. The results of NICE-SUGAR raise many questions. Perhaps we have been overly aggressive in pursuing glycemic targets? Perhaps there are factors beyond glycemic control contributing to risk not yet elucidated? No one is advising that we return to the days of sliding scales or ignoring blood glucose completely. We need to be cautious in how we react to the results of this study.

I remember a surgeon asking me once years ago when I was a medical student: “What is the enemy of good?” Not sure what he was looking for, I hesitated and he answered, “The enemy of good is perfect.”

Maybe that applies to inpatient glycemic control as well? Only time and research will tell.