Critical Care Minutes

This week’s issue of NEJM features another in a long debated series of trials that investigates the benefits of  “tight” vs “conventional” glycemic control in the ICU.  Is this the one that finally gives us the answer? Let’s find out…

The NICE-SUGAR Study Investigators are a multinational, multicenter and multidisciplinary collaboration. The primary objective of this trial was to find the optimal glycemic level for critically ill patients. Patients expected to stay in the ICU for >3 days were enrolled within 24 hours of admission to the ICU. They were randomized to either recive INTENSIVE (81-108 mg/dl) or CONVENTIONAL (<180 mg/dl) therapy. The primary endpoint was 90 day mortality (any cause / after randomization).

After enrolling 6104 patients, 3054 received intensive rx and 3050 received conventional rx. Groups were relatively well matched at baseline.  The major difference in primary outcome was a RRR of ~ 9% in the conventional group (24.5% vs 27.5%). This corresponded to an odds ratio of 1.14 (95% CI 1.02-1.28),  p=0.02. There was no differernce in the treatment effect when looking at medical vs. surgical patients.  Of note, severe hypoglycemia (<40) occured ~13x more often in the intensive group (0.5% vs 6.8%    p<0.001). No other significant differences upon subgroup analysis or secondary outcomes were found.

 
So there you have it. Since the Van den Berghe et al. study was intially published in NEJM in 2001 the issue of glycemic control in the ICU has sparked a viscious debate. Early this century, the hospital administrators, the medicare/private payors and the “quality officers” jumped all over the concept of keeping the glucose tightly controlled. At the surface it certainly seemed to be a reasonable concept – keep the glucose load low and patients will do better! Interestingly, it was also easily marketable. The pharmaceutical and medical device industry was all over it! By the mid 2000s, there was a plethora of instant and fancy glucose measurement tools and database trackers that were developed and sold to the hospitals. In fact, by 2005, glycemic control became a measurement of quality of care in the ICU. BUT, now the paradigm is certainly shifting. More and more evidence has emerged recently that shows the exact opposite. Tight glycemic control may actually be doing harm to patients whilst providing no benefit at all. Incidence of severe hypoglycemia in these patients appears to be a major contributing factor. The process is labor intensive, costly and as the NICE-STUDY investigators show may actually be increasing risk of mortality in critically ill patients.

Until there is a safe way to test tight glucose control (with similar incidence of significant hypoglycemia) we should be no longer be testing this hypothesis. Until then maybe a more reasonable 120-180 mg/dl range might be safer to titrate therapy to. Even that, in my opinion, has not been shown to be beneficial to patients – just “seems to be the right thing to do.” Are we to base the care of the sickest patients in the hospital on a hunch??? There should be good evidence based medicine to support this or we should abandon the practice immediately.

So I ask, Do you believe the hype? Can we finally put this issue to rest …