The Anabolic Effect Of Perioperative Nutrition With Insulin In Patients Undergoing CABG
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Study type: Interventional

Summary: 
      This study evaluates whether providing a nutritional intervention in the form of insulin,
      sugar and protein during and after open-heart surgery will increase the body's protein stores
      and maintain a normal level of blood sugar. The primary outcome will be Whole body protein
      balance which will be assessed by isotope tracer kinetics. Protein balance will be calculated
      as protein synthesis minus protein breakdown with positive values indicating anabolism and
      negative values catabolism. The preoperative measurements will be performed on the morning
      before the operation. Postoperative studies will be conducted two hours after surgery in the
      intensive care unit. Patients will be followed for 12 hours after surgery.
    

Detailed description: 
      Open heart surgery is associated with a catabolic response which is characterized by
      hyperglycemia and whole body protein loss. Results of a previous study demonstrated that a
      reduction in whole-body protein breakdown and synthesis in patients receiving insulin and
      isocaloric amounts of glucose (hyperinsulinemic-normoglycemic clamp, HNC) after coronary
      artery bypass graft (CABG) surgery. Because protein oxidation did not change and the
      circulating concentrations of amino acids decreased (hypoaminoacidemia) in the presence of
      insulin therapy whole-body protein balance remained negative, ie patients were still
      catabolic. The investigators hypothesize that this lack of anabolic effect is due to the
      absence of anabolic substrate supply (amino acids). The primary objective of this study is to
      test the hypothesis that insulin administered as part of a hyperinsulinemic-normoglycemic
      clamp during and immediately after CABG:

        1. Will induce whole-body positive protein balance if supplemented with intravenous amino
           acids (AA) in amounts to preserve normal AA plasma concentrations (isoaminoacidemia),
           and

        2. Will further enhance whole-body protein balance if combined with the infusion of AA in
           amounts to increase AA plasma concentrations to supra-normal levels (hyperaminoacidemia)
           The primary outcome, whole body protein balance, will be measured 2 hours after surgery
           in the intensive care unit. Secondary objectives include (1) measure hepatic albumin
           synthesis and (2) assess changes in the metabolic-endocrine milieu.

      Methods: 30 patients scheduled for elective CABG surgery requiring cardiopulmonary bypass
      will be enrolled. Consenting patients will be divided randomly into 3 groups. Patients in
      group 1 will receive HNC from the beginning of surgery until the end of the eight-hour study
      period after surgery. No amino acids will be given. Patients in group 2 will receive HNC and
      AA (Travasol Baxter, Deerfield IL) during and after surgery in an amount equivalent to 20% of
      the patient's energy expenditure (EE) as measured before surgery to maintain
      isoaminoacidemia. Patients in group 3 will receive HNC and Travasol iduring and after surgery
      in an amount equivalent to 35% of the patient's EE to promote hyperaminoacidemia. HNC will
      consist of an insulin infusion of 5 mU/kg/min coupled with a variable infusion of glucose
      (dextrose 20%) to maintain normoglycemia (4-6 mmol/L). Whole body protein balance will be
      assessed by L-[1-13C]leucine tracer kinetics. Protein balance will be calculated as protein
      synthesis minus leucine rate of appearance (Ra) with positive values indicating anabolism and
      negative values catabolism. Whole body glucose metabolism will be assessed by stable isotope
      tracers [6,6-2H2]glucose. 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 operation. Postoperative studies will be conducted 2 hours after
      surgery in the intensive care unit. Patients will be followed for 12 hours after surgery.
      Whole body leucine kinetics between the two groups will be analyzed using ANOVA for repeated
      measurements. Statistical significance will be set as P<0.05. All p-values will be presented
      are 2-tailed.

      Tracer kinetics:

      Whole body leucine and glucose metabolism measurements were made under postabsorptive
      conditions on the day before surgery and, postoperatively, in the intensive care unit. Plasma
      kinetics of glucose and leucine, i.e. the glucose and leucine rate of appearance (Ra),
      leucine oxidation and non-oxidative leucine disposal, were determined by a primed constant
      infusion of tracer quantities of L-[1-13C]leucine and [6,6-2H2]glucose. Blood and expired air
      samples were collected, before the infusion, to analyze baseline enrichments. Priming doses
      of NaH13CO3 (1 µmol/kg, po), L-[1-13C]leucine (4 µmol/kg, iv) and [6,6-2H2]glucose (22
      µmol/kg, iv), were administered followed by the infusion of L-[1-13C]leucine (0.06
      µmol.kg-1.min-1) and [6,6-2H2]glucose (0.44 µmol.kg-1.min-1). For the determination of 13CO2
      isotope enrichments four expired breath samples were taken after 150, 160, 170 and 180
      minutes of isotope infusion.

      Whole body leucine and glucose kinetics were calculated by the conventional isotope dilution
      technique using a two-pool random model during steady state conditions. At isotopic steady
      state the Ra of unlabeled substrate in plasma is derived from the plasma isotope enrichment,
      expressed as MPE, according to the following equation: Ra = I.(MPEinf/MPEpl - 1), where I is
      the infusion rate of the tracer, MPEinf is the enrichment of the tracer in the infusate and
      MPEpl is the tracer enrichment in plasma. The final MPE values represent the mean of all the
      MPE measurements during each isotopic plateau. Isotopic steady state conditions were regarded
      as valid when the CV of the MPE values at isotopic plateau was <5%.

      At isotopic steady state leucine flux (Q) is quantified by the following formula: Q = S+O =
      B+I, where S is the rate of synthesis of protein from leucine, O is the rate of oxidation, B
      is protein breakdown and I is the dietary intake. Furthermore Q is equal to Ra (Ra = B+I) and
      the rate of disappearance (Rd; Rd = S+O). When tracer studies are done in fasting states,
      leucine flux equals B. The rate of protein synthesis is calculated by subtracting leucine
      oxidation from leucine flux (S = Q-O). Protein balance is calculated as protein synthesis
      minus leucine Ra with positive values indicating anabolism and negative values catabolism.
      Plasma [1-13C]α-KIC is used to calculate the flux and oxidation of leucine. The α-KIC is
      formed intracellularly from leucine and is released into the systemic circulation. It
      reflects the intracellular precursor pool enrichment more accurately than plasma leucine
      itself.
    

Intervention name(s): Amino acids
Intervention type(s): Dietary Supplement
Intervention description(s): AA (Travasol Baxter, Deerfield IL) during and after surgery in an amount equivalent to 20% and 35% of the patient's energy expenditure (EE)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Catabolic response; Amino Acids; Insulin