High-Dose InsulinThe Effect of Insulin on Protein Metabolism After Cardiac Surgery

Background: The hyperinsulinemic-normoglycaemic clamp technique is a precise method of providing insulin and glucose while maintaining normoglycemia. High-dose insulin has profound effects on glucose and protein metabolism. It has been demonstrated in coronary artery bypass graft (CABG) surgery patients that high-dose insulin causes hypoaminoacidaemia. The investigators hypothesize that the reduction of plasma amino acids (AAs) levels as seen in patients undergoing CABG surgery and receiving high-dose insulin is a consequence of an inhibition of whole body proteolysis as assessed by L-\[1-13C\]leucine tracer kinetics.

Objective: The present study aims to investigate the effect of high-dose insulin therapy on whole body protein, glucose and end-organ metabolism in patients undergoing CABG surgery using stable isotope tracers \[6,6-2H2\]glucose, L-\[1-13C\]-leucine and L-\[2H5\]phenylalanine. The changes in the metabolic-endocrine milieu will also be evaluated by plasma concentrations of glucose, lactate, free fatty acids, prealbumin, albumin, fibrinogen, insulin, glucagon, and cortisol.

Methods: With the approval of local institution's ethical committee, 30 patients scheduled for elective will be enrolled. The patients will be divided randomly into two groups. The control group will receive a standard IV insulin protocol with the aim of keeping blood glucose < 10 mmol/L. The treatment group will be administered a high dose insulin infusion of 5 mU/kg/min coupled with a variable infusion of glucose to maintain normoglycemia (4-6 mmol/L). Insulin infusion will be continued until the end of the study period approximately 8 hours after surgery. L-\[1-13C\]leucine and \[6,6-2H2\]glucose kinetics will be used to assess changes in whole body protein and glucose kinetics. Hepatic albumin synthesis will be determined by using primed continuous infusion of L-\[2H5\]phenylalanine. The preoperative measurements will be performed on the morning before the surgery. Postoperative studies will be conducted two hours after arrival in the intensive care unit. Tracer kinetics between the two groups will be analyzed using ANOVA for repeated measurements.

Significance: High-dose-insulin results in a significant reduction in plasma AAs in cardiac surgery. This study should address if this drop in plasma AA levels is secondary to a decrease in breakdown, an increase in synthesis or both during high-dose insulin therapy in open heart surgery.