Aggressive Control of Intraoperative Blood Glucose Concentration

INTRAOPERATIVE management of blood glucose concentration in patients with diabetes mellitus has traditionally focused on avoidance of profound hypoglycemia or hyperglycemia. In contrast, the relative importance of strict perioperative regulation of blood glucose within the normal range has received little emphasis, in large part because the benefits and risks of such a strategy have yet to be convincingly demonstrated in controlled clinical trials. In this issue of ANESTHESIOLOGY, Ouattara et al. provide compelling evidence indicating that tight control of intraoperative blood glucose positively affects patient outcome in diabetic patients after coronary artery bypass graft surgery. Using a multivariate analysis, the authors demonstrated that the risk of sustaining cardiovascular morbidity was increased more than sevenfold in patients with refractory hyperglycemia (defined as four consecutive determinations of blood glucose concentration exceeding 200 mg/dl despite insulin treatment) as compared with those in whom blood glucose concentration was more tightly controlled ( 150 mg/dl). The authors used a continuous infusion of insulin administered using a modified Portland protocol to treat blood glucose concentrations greater than 180 mg/ dl. The objective of treatment was to maintain the blood glucose concentration between 150 and 200 mg/dl intraoperatively and less than 140 mg/dl postoperatively in the intensive care unit (ICU). Thirty-six percent of the patients enrolled in the study required insulin treatment according to the authors’ criteria. Fifty percent of these patients had inadequate control of intraoperative blood glucose concentration. These findings were associated with an increased in-hospital mortality rate (11.4 vs. 2.4%) and a prolonged duration of stay ( 96 h) in the ICU (46 vs. 19%) as compared with patients in whom better control of blood glucose was achieved. The results of Ouattara et al. are quite provocative. A question that remains unanswered is whether hyperglycemia is truly a cause of increased cardiovascular morbidity and mortality or whether the correlation of hyperglycemia and cardiac complications is merely an epiphenomenon. Results from animal studies indicate that acute hyperglycemia alone, independent of chronicity, underlying diabetes, or alterations in plasma insulin concentration, adversely modulates endogenous and pharmacologically induced cardioprotective signal transduction pathways. Hyperglycemia increases myocardial infarct size, impairs endothelial function, adversely affects coronary microcirculatory regulation, and attenuates coronary collateral development in part by increasing the production of deleterious quantities of reactive oxygen species and blunting nitric oxide–dependent protective mechanisms. Several recent clinical trials also strongly suggest that aggressive control of blood glucose decreases overall and cardiac-related mortality in a variety of patient subpopulations. In an important prospective, randomized trial, Van den Berghe et al. demonstrated that intensive insulin therapy (target blood glucose concentration of 80–110 mg/dl) decreased in-hospital mortality by more than 30% in patients admitted to the ICU as compared with those who received insulin only if the blood glucose concentration exceeded 210 mg/dl. Sixty percent of the patients enrolled in this study had undergone cardiac surgery. Finney et al. demonstrated that hyperglycemia in excess of 145 mg/dl predicted an increase in mortality in ICU patients (primarily cardiac and thoracic surgical patients). Krinsley et al. reported similar findings in patients admitted to the ICU for a variety of medical conditions involving all organ systems. Interestingly, a multivariate statistical analysis identified administration of insulin as an independent predictor of death, whereas control of blood glucose concentration rather than the dose of insulin correlated with improvements in outcome. Taken together, these experimental and clinical findings suggested that insulin may activate prosurvival pathways in myocardium and, further, that control of blood glucose is likely to play an important role in protecting against ischemic injury. Interestingly, Quattara et al. showed that preoperative use of insulin was associated with increased postoperative risk, but preoperative insulin treatment did not demonstrate a statistically significant interaction with poor intraoperative glycemic control as an independent predictor of morbidity. This Editorial View accompanies the following article: Ouattara A, Lecomte P, Le Manach Y, Landi M, Jacqueminet S, Platonov I, Bonnet N, Riou B, Coriat P: Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients. ANESTHESIOLOGY 2005; 103:687–94.