Applied nutritional investigationPerioperative tight glucose control with hyperinsulinemic-normoglycemic clamp technique in cardiac surgery
Introduction
Major surgical tissue trauma is associated with alterations in carbohydrate metabolism, including increased glucose production and impaired glucose utilization, resulting in hyperglycemia [1], [2]. During cardiac surgery this disturbance of glucose homeostasis is striking, with blood glucose levels frequently exceeding 10 mmol/L in non-diabetic and 15 mmol/L in diabetic patients [3], [4]. Moderately increased circulating blood glucose concentrations are independent risk factors for death, cardiovascular, respiratory, infectious, and renal complications [5], [6], [7], [8], [9], [10], [11].
Although tight glucose control has been demonstrated to improve outcomes in critically ill patients, mostly after cardiac surgery [12], there is only observational evidence to suggest that maintenance of perioperative normoglycemia is beneficial [13], [14]. This lack of evidence may be due to the fact that previous attempts to maintain glucose homeostasis, during and immediately after cardiac surgery, failed, leading to the commonly held belief that normoglycemia is unattainable [4], [15]. The only randomized-controlled trial on the effect of rigorous intraoperative glycemic control found no risk reduction in cardiac surgery [16]. This investigation was limited by the fact that normoglycemia was not achieved. Similarly, other protocols in the critical care setting were unable to achieve their glycemic targets [16], [17], [18]. Recently, two large European trials had to be terminated prematurely due to an unacceptably high incidence of severe hypoglycemia (blood glucose <2.2 mmol/L) [17], [18]. The consequences of severe hypoglycemia may offset the benefits of controlling blood glucose levels. It appears that tight glucose control cannot be achieved by occasional measurement of blood glucose, which is followed by reactive adjustments of insulin infusion, the so-called insulin sliding scale.
In 2004 we introduced the GIN concept in cardiac surgery, i.e., perioperative glucose and insulin administration while maintaining normoglycemia, applying the principle of the hyperinsulinemic-normoglycemic clamp technique; using a fixed pre-emptive infusion of insulin together with glucose infused at a variable rate titrated to maintain the blood glucose from 3.5 to 6.1 mmol/L, we established and preserved normoglycemia during aortocoronary bypass surgery in a small number of diabetic and non-diabetic patients [3]. As opposed to conventional traditional insulin sliding scales, which dictate changes in the amount of insulin to be administered, this strategy modifies the rate of glucose infusion rather than changing the insulin infusion, which is kept constant.
The aim of the present study was to evaluate the efficacy and safety of GIN administered perioperatively, i.e., during surgery and the first 24 h after surgery, in larger cohort of patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB).
Section snippets
Materials and methods
This study was conducted according to the Declaration of Helsinki. With approval from the McGill University Health Center research ethics board we approached and received written consent from patients scheduled for elective coronary artery bypass grafting, valve procedure, or a combination of both. The inclusion criteria were patients 18 to 90 y of age and the ability to give written informed consent. Patients scheduled for off-pump coronary artery bypass grafting, or with anticipated deep
Results
A total of 70 non-diabetic and 40 diabetic patients were enrolled. There were no significant differences in the characteristics of the two study groups, with the exception of preoperative glycosylated hemoglobin values, which were higher in diabetic patients (Table 1). Among diabetics, 9 patients were on insulin treatment, 23 were taking oral hypoglycemic agents, and 8 were treated by diet only.
A total of 3880 blood glucose measurements (average 35 per patient) were recorded: 1415 during
Discussion
The clinical relevance of strict glycemic control during surgery and critical care is still a matter of debate. Although the results of the Leuven trial in 2001 showed a better outcome with maintenance of normoglycemia in surgical ICU patients [12], other investigators failed to show clinical benefits. Furthermore, recent meta-analyses do not support the widespread adoption of tight glycemic control. In addition to its well-known effects on glucose homeostasis, insulin has a broad spectrum of
Acknowledgments
The authors thank Ann Wright for reviewing the manuscript.
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Dr. Sato is supported by a grant from the Research Institute of Yamanashi University, Japan. Drs. Carvalho and Lattermann are supported by grants from the Research Institute of the McGill University Health Center, Montreal, Canada. Dr. Schricker is receiving funds from the Canadian Institutes of Health Research, Ottawa, Canada.