Ours is the 1st prospective, randomized, controlled study to demonstrate signiicantly better blood-glucose control in patients with diabetes by using CII after CABG. Patients treated with CII had a lower mean glucose level and were more likely to achieve the glycemic target than those treated with GGI.
The prevalence of diabetes mellitus in patients undergoing CABG ranges from 15% to 36.7%, with 2 series suggesting that the percentage has increased since 2000.4,6,9,12,13
The reasons for this increase are unclear. In our hospital, approximately half of the patients referred for CABG have a history of diabetes or are newly diagnosed. These patients often experience a more complicated postoperative course and have a higher incidence of postoperative death,4,6,12
sternal wound infection,6,12,14,15
and longer ICU stay.6,16
Associations between hyperglycemia and disordered fatty acid metabolism, and between hyperglycemia and compromised glycolysis in the myocardium, are also reported.17
The detrimental effect of free fatty acids on the ischemic myocardium has been reported to result from increased oxygen consumption, inhibited glucose utilization, decreased myocardial contractility, a predisposition to arrhythmias, and an increase in oxygen free radicals.18
Adequate glycemic control by administration of insulin implies improved glucose uptake by the myocardium, which should provide an energy supply that is more favorable for recovery from intraoperative myocardial ischemia. In addition, insulin stimulates pyruvate dehydrogenase activity and improves aerobic metabolism in postischemic myocardium.19,20
Clinically, perioperative hyperglycemia is associated with increased operative mortality rates,8
deep sternal infection,11
prolonged length of stay in the ICU, and greater consumption of hospital resources.21
The importance of glucose control on the 1st postoperative day has been reported previously. In a retrospective review conducted by McAlister and coworkers,10
an increase of 1 mmol/L (or 18 mg/dL) of glucose on the 1st postoperative day was associated with a 17% increase in the risk of adverse outcomes. Furnary and colleagues11
found a signiicant impact on the risk of postoperative deep sternal infection. Accordingly, reducing glucose levels on the 1st postoperative day may improve the outcomes of patients with diabetes undergoing CABG. In 2003, Furnary's group8
reported that insulin infusion signiicantly reduced mortality rates in these patients. The glucose levels on the day of surgery and the irst 2 days after CABG were signiicant independent predictors of operation-related death, further emphasizing the importance of glucose control in the immediate postoperative period.
With continuous infusion of insulin, we achieved faster achievement of adequate glucose control and a greater ability to maintain postoperative glucose levels near baseline values. Although our CII patients underwent glucose measurements more frequently and required more insulin than did our GGI patients, their overall consumption of hospital resources was not higher, because the closer monitoring of continuous infusions was likely offset by shortened lengths of stay in the ICU and the hospital.
The absence of significant differences in glucose levels in our 2 study groups after the 2nd postoperative day may have been related to an early return to oral feeding, which most patients began during the 1st or 2nd postoperative day. However, the actual food intake varied substantially among the patients, and we were unable to control for this variable. To prevent profound hypoglycemia between meals, we gave intermittent insulin injections instead of a continuous infusion once patients began eating. This limitation of our study appears to hold true for most other such studies, since most have been able to correlate unfavorable outcomes with hyperglycemia only on the 1st postoperative day.10,11
One limitation of our study was the small number of cases, which may explain why we were unable to show a benefit either in better survival or in a reduced incidence of sternal infections. Adverse outcomes and the length of ICU stay were similar in both groups. According to the incidence of death among our patients, an estimated 2,842 patients would be needed in each group to provide a P value of 0.05 with a 90% confidence interval. We did not deem it reasonable to enroll so many patients for study before applying the CII concept.
As a consequence of the study's not being blinded, 7 patients on the GGI protocol were dropped from the treatment protocol because of their physicians' concerns about their high blood-glucose levels. When our secondary goal of better glucose control was reached, we stopped the trial and began using the CII protocol routinely. Although our patients on the CII protocol experienced better control than did those in the GGI group, we were able to reach the target level in only about two thirds of the CII group. Van den Berghe and colleagues22
recommended that the goal of blood-glucose control for patients in the surgical ICU should be no higher than 110 mg/dL. Clearly, we were unable to achieve control that tight with our regimen. How-ever, only 13% of van den Berghe's patients had diabetes, and the researchers measured glucose only in the mornings—a practice insufficient to show that adequate glucose control was maintained in the patients. During the past several decades, Furnary's group8
adjusted the target glucose downward to a level of 100 to 150 mg/dL. They also expanded the application of continuous insulin infusion, initiating it in the operating room and continuing it until the morning of the 3rd postoperative day.8
We conclude that continuous insulin infusion provides better control of postoperative blood-glucose levels in patients with diabetes after CABG than does conventional intermittent injection of insulin. We recommend continuous infusion as the standard treatment for such patients.