Reducing glycemic variability in intensive care unit patients: a new therapeutic target?

Abstract

Acute hyperglycemia is common in critically ill patients. Strict control of blood glucose (BG) concentration has been considered important because hyperglycemia is associated independently with increased intensive care unit mortality. After intensive insulin therapy was reported to reduce mortality in selected surgical critically ill patients, lowering of BG levels was recommended as a means of improving patient outcomes. However, a large multicenter multination study has found that intensive insulin therapy increased mortality significantly. A difference in variability of BG control may be one possible explanation why the effect of intensive insulin therapy varied from beneficial to harmful. Several studies have confirmed significant associations between variability of BG levels and patient outcomes. Decreasing the variability of the BG concentration may be an important dimension of glucose management. If reducing swings in the BG concentration is a major biologic mechanism behind the putative benefits of glucose control, it may not be necessary to pursue lower glucose levels with their attendant risk of hypoglycemia.

Figure 1.

Graphic representation of glycemic control with a high mean glucose level and high variability (left) and with a high mean glucose level and low variability (right).

Figure 2.

Relationship between mortality and variability of BG control in critically ill patients. The SD of BG control during the ICU stay was used as a marker of variability of BG control. GluSD; SD of BG concentration.

Figure 3.

Time course of the predictive ability of average and SD of BG. Odds ratios (expressed with 95% confidential interval) for glucose indices indicate the risk change of ICU mortality per 1-mmol change in each index. For example, average of BG on 7 days from admission means average of entire glucose measurements during 7 days from admission. As time in the ICU increased, so did the ability of glucose control indices to predict the outcome.

Figure 4.

Example of closed-loop glycemic control using the STG-22™ system (Nikkiso, Tokyo, Japan) in a postcardiac surgery patient (body weight: 70 kg, male). The patient developed postoperative acute hyperglycemia (12.4 mmol/liter) on admission to the ICU. Blood glucose monitoring using the STG-22 was performed continuously every 12 seconds by a dual lumen catheter blood sampling technique. The target BG level was 8 mmol/liter. The BG level of the patient was controlled by adjusted insulin infusion (gray bar) and glucose infusion (black bar). Once he achieved the target glucose level (8 mmol/liter), his SD of glycemia as a surrogate of glycemic variability was very small at 0.06 mmol/liter.