The Effect of Insulin on Protein Metabolism After Cardiac Surgery
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
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.
Phase:
N/A
Details
Lead Sponsor:
McGill University Health Center McGill University Health Centre/Research Institute of the McGill University Health Centre