Cardiopulmonary Bypass, Coronary Artery Bypass, Coronary Artery Disease
Conditions
Keywords
Glutamine, Myocardial protection, Coronary artery bypass grafting, Cardiopulmonary bypass, Low ejection fraction, Myocardial injury
Brief summary
Coronary artery disease has the highest mortality rate worldwide and coronary artery bypass grafting (CABG) is the most common cardiac surgery performed in patients with coronary artery disease to revascularize the heart. Despite of improvement in operation techniques, cardioplegia, cardiopulmonary bypass (CPB), myocardial injury related to on-pump CABG is still prominent. In patient with low ejection fraction undergone on-pump CABG, myocardial injury is related to worse outcome and prognosis during peri-operative and post-operative period. On-pump CABG patients with low ejection fraction has increased (up to four times higher) post-operative in hospital mortality rate compared to patient with normal ejection fraction. Administration of intravenous glutamine had been documented in reducing myocardial damage during cardiac surgery and previous studies indicated that glutamine can protect against myocardial injury by various mechanism during ischemia and reperfusion. The purpose of this study to determine whether intravenous glutamine could prevent the decline of plasma glutamine level, reduce myocardial damage, improve hemodynamic profile, and reduce morbidity of on-pump CABG in patients with low ejection fraction.
Detailed description
The study was a double-blind randomized controlled trial to assess the role of glutamine as a myocardial protection during coronary artery bypass grafting under cardiopulmonary bypass in patients with left ventricle ejection fraction of 31-50%. This study was approved by Institutional Review Board of National Cardiovascular Center Harapan Kita and informed consent was obtained before randomization for patient eligible for this study. Allocation of participant to the treatment group was done by block randomization by staff who was not involved in the study. The intervention drug was prepared by pharmacist who also was not involved in the study. Glutamine solution was supplied as L-alanyl-L-glutamine dipeptide (Dipeptiven, 200 mg/mL, Fresenius Kabi, Bad Homburg, Germany) and was prepared to contain 0.5gr/kgbw glutamine diluted in NaCl 0.9% to a final volume of 500 mL. Placebo was supplied as 500 ml of NaCl 0.9%, prepared in similar fashion and packaging as glutamine solution. Principal investigator, care provider, outcome assessor, and participant were blinded to the assigned group until after the end of the study. Baseline participant characteristics were collected before the intervention included age, sex, body weight, body height, body mass index, and documented pre-operative left ventricle ejection fraction. Coronary artery bypass grafting and cardiopulmonary bypass was done in concordance to standard operating procedure in National Cardiovascular Center Harapan Kita, followed by transit time flow meter measurement to ensure quality of the graft. Modifying factor of the study, the investigators measured duration of surgery, duration of cardiopulmonary bypass, and duration of aortic cross clamp. The primary outcome of the study was plasma troponin I level. The investigators anticipated plasma troponin I level difference of 20% with standard deviation of 0.04 ng/mL, and for statistical power of 80% and level of significance of 0.05, the required sample size was 24.5 participants per group. As anticipation for participant drop out, the investigators planned to recruit a total of 60 participants.
Interventions
Intravenous infusion of 0.5 mg/kgbw L-alanyl-L-glutamine dipeptide diluted in normal saline to volume of 500 mL, started after induction of anesthesia for 24 hours.
DRUGPlacebo
Intravenous infusion of 500 mL normal saline, started after induction of anesthesia for 24 hours.
Sponsors
National Cardiovascular Center Harapan Kita Hospital Indonesia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with coronary heart disease indicated for elective coronary artery bypass grafting under cardiopulmonary bypass * Patients with left ventricle ejection fraction 31% -50% confirmed by echocardiography or radio nuclear study. * Patients age ≥18 years * Never had heart surgery before * Agree to participate in the study and signed informed consent
Exclusion criteria
* Emergency coronary artery grafting bypass * Having additional procedures other than coronary artery bypass grafting * History of myocardial infarction with onset less than 3 months * Patients with serum creatinine level more than 2 g/dL * Patients with ALT/AST levels more than 1.5 times the upper limit of normal value * Required to use intra-aortic balloon pump pre-operatively * History of stroke with onset less than 3 months * History of pre-operative atrial fibrillation * History of heart conduction problem and/or using a pacemaker * Patients with HIV * Contraindications to pulmonary artery catheter insertion Drop out Criteria * Experiencing stroke after surgery * Experiencing surgery related complication (haemorrhage) requiring re operation * Requiring continuous veno-venous hemofiltration or haemodialysis after surgery * Delayed sternal closure * Aortic cross clamp duration more than 120 minutes and/or cardiopulmonary bypass time more than 180 minutes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass | 24 hour after cardiopulmonary bypass | Plasma glutamine were measured using colorimetric tests in unit of µmol/L |
| Plasma Glutamine at Baseline | Before induction to anesthesia | Plasma glutamine were measured using colorimetric tests in unit of µmol/L |
| Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass | 24 hour after cardiopulmonary bypass | Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL |
| Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass | 48 hour after cardiopulmonary bypass | Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL |
| Plasma Troponin I at Baseline | Before induction to anesthesia | Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL |
| Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass | 5 minute after cardiopulmonary bypass | Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL |
| Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass | 6 hour after cardiopulmonary bypass | Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Index | Immediately after induction of anesthesia, 5 minute, 2 hour, 6 hour, 24 hour after cardiopulmonary bypass | Cardiac index were measured from pulmonary artery catheter using thermodilution method in unit of L/min/m\^2 |
| Plasma Lactate Before Induction to Anesthesia | Before induction to anesthesia | Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L |
| Plasma Lactate 6 Hours After Cardiopulmonary Bypass | 6 hours after cardiopulmonary bypass | Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L |
| Plasma Lactate 24 Hours After Cardiopulmonary Bypass | 24 hours after cardiopulmonary bypass | Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L |
| Plasma Lactate 48 Hours After Cardiopulmonary Bypass | 48 hours after cardiopulmonary bypass | Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L |
| Intensive Care Unit Length of Stay | 28 days (or until hospital discharge) | Intensive care unit length of stay were measured from length of time participant spent in intensive care unit in unit of hours |
| Vasoactive Inotropic Score | 28 days (or until hospital discharge) | Vasoactive inotropic score (VIS) were maximum vasoactive and inotropic dose required by participant after surgery measured by VIS=dopamine dose in mg/kgbw/min + dobutamine dose in mg/kgbw/min + 100 x epinephrine dose in mg/kgbw/min + 10 x milrinone dose in mcg/kgbw/min + 10.000 x vasopressin dose in units/kgbw/min + 100 x norepinephrine dose in mcg/kgbw/min. Higher scores means worse outcomes. VIS \>= 20 is considered as high VIS and is associated with poor outcomes. |
| Plasma Lactate 5 Minute After Cardiopulmonary Bypass | 5 minute after cardiopulmonary bypass | Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L |
| Intensive Care Unit Ventilation Time | 28 days (or until hospital discharge) | Intensive care unit ventilation time were measured from length of time participant was on ventilator in intensive care unit in minutes. |
| Right Atrial Appendage Alpha-ketoglutarate | 5 minute after cardiopulmonary bypass | Right atrial appendage alpha-ketoglutarate were measured from right atrial appendage tissue biopsy using colorimetric tests in unit of g/mol. |
| Right Atrial Appendage Myocardial Injury Score | 5 minute after cardiopulmonary bypass | Right atrial appendage myocardial injury score were measured from tissue section stained with hematoxylin-eosin and examined under by light microscopy in score of 0 (no change) to 3 (major changes with necrosis and diffuse inflammation). Higher scores mean worse outcome |
| Right Atrial Appendage Apoptosis Index | 5 minute after cardiopulmonary bypass | Right atrial appendage apoptosis index were measured from tissue section stained with in situ terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and examined under light microscopy in average number of apoptotic cells (positively stained) from 6 random fields per section |
| Anti Cardiac Troponin I Expression | 5 minute after cardiopulmonary bypass | Right atrial appendage anti cardiac troponin I expression were measured from tissue section stained with anti-cardiac troponin I antibody and examined under light microscopy in score of 0 (no change) to -3 (no area observed with anti-cardiac troponin I expression). Higher score mean better outcome |
| Ejection Fraction | Immediately after induction of anesthesia | Ejection fraction were measured by transesophageal echocardiography using Simpson method in percentage (%) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiopulmonary Bypass Time | Intraoperative | Total time measured the patient went under cardiopulmonary bypass. Measured in minutes. |
| Aortic Cross-clamping Time | Intraoperative | Total time the patient underwent aortic cross-clamping during the surgical procedure. Measured in minutes. |
| Coronary Graft | Intraoperative | Number of coronary arteries grafted during operation |
| Total Surgical Procedure Time | Intraoperative | Total time taken for the surgical procedure. Measured in minutes. |
Countries
Indonesia
Participant flow
Recruitment details
Participants were recruited based on inclusion criteria. This study was carried out at National Cardiovascular Center Harapan Kita. Written informed consent was obtained from all eligible patients. This study was conducted from January to October 2021.
Pre-assignment details
Sixty patients with a left ventricle EF of 31-50% who underwent on-pump CABG were included in this study and randomized to treatment. Two patients were dropped out in this study
Participants by arm
| Arm | Count |
|---|---|
| Glutamine Intravenous L-alanyl-L-glutamine 0.5 mg/kgbw
L-alanyl-L-glutamine dipeptide: Intravenous infusion of 0.5 mg/kgbw L-alanyl-L-glutamine dipeptide diluted in normal saline to volume of 500 mL, started after induction of anesthesia for 24 hours. | 29 |
| Control Intravenous NaCl 0.9%
Placebo: Intravenous infusion of 500 mL normal saline, started after induction of anesthesia for 24 hours. | 29 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Meet drop out criteria | 1 | 1 |
Baseline characteristics
| Characteristic | Control | Total | Glutamine |
|---|---|---|---|
| Age, Continuous | 61.31 years STANDARD_DEVIATION 6.48 | 60.76 years STANDARD_DEVIATION 6.85 | 60.21 years STANDARD_DEVIATION 7.29 |
| Body Mass Index | 26.47 kg/m^2 STANDARD_DEVIATION 2.85 | 26.36 kg/m^2 STANDARD_DEVIATION 2.67 | 26.25 kg/m^2 STANDARD_DEVIATION 2.53 |
| Pre-op Ejection Fraction | 44.00 percent | 43.00 percent | 41.44 percent |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 28 Participants | 54 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass
Plasma glutamine were measured using colorimetric tests in unit of µmol/L
Time frame: 24 hour after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass | 935.42 μmol/L | Standard Deviation 319.1 |
| Control | Plasma Glutamine at 24 Hour After Cardiopulmonary Bypass | 634.79 μmol/L | Standard Deviation 243.89 |
p-value: 0.001Unpaired T-Test
Primary
Plasma Glutamine at Baseline
Plasma glutamine were measured using colorimetric tests in unit of µmol/L
Time frame: Before induction to anesthesia
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Glutamine at Baseline | 555.09 μmol/L | Standard Deviation 198.16 |
| Control | Plasma Glutamine at Baseline | 632.24 μmol/L | Standard Deviation 266.36 |
p-value: 0.216Unpaired T-Test
Primary
Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass
Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
Time frame: 24 hour after cardiopulmonary bypass
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass | 3.08 ng/mL |
| Control | Plasma Troponin I at 24 Hour After Cardiopulmonary Bypass | 3.77 ng/mL |
p-value: 0.038Wilcoxon (Mann-Whitney)
Primary
Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass
Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
Time frame: 48 hour after cardiopulmonary bypass
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass | 1.66 ng/mL |
| Control | Plasma Troponin I at 48 Hour After Cardiopulmonary Bypass | 1.75 ng/mL |
p-value: 0.423Wilcoxon (Mann-Whitney)
Primary
Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass
Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass | 1.72 ng/mL | Standard Deviation 0.98 |
| Control | Plasma Troponin I at 5 Minute After Cardiopulmonary Bypass | 1.68 ng/mL | Standard Deviation 1.1 |
p-value: 0.883Unpaired T-Test
Primary
Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass
Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
Time frame: 6 hour after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass | 3.43 ng/mL | Standard Deviation 1.51 |
| Control | Plasma Troponin I at 6 Hour After Cardiopulmonary Bypass | 4.41 ng/mL | Standard Deviation 1.89 |
p-value: 0.034Unpaired T-Test
Primary
Plasma Troponin I at Baseline
Plasma troponin I were measured using enzyme immunoassay (ELISA) in unit of ng/mL
Time frame: Before induction to anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Plasma Troponin I at Baseline | 0.42 ng/mL |
| Control | Plasma Troponin I at Baseline | 0.17 ng/mL |
p-value: 0.993Wilcoxon (Mann-Whitney)
Secondary
Anti Cardiac Troponin I Expression
Right atrial appendage anti cardiac troponin I expression were measured from tissue section stained with anti-cardiac troponin I antibody and examined under light microscopy in score of 0 (no change) to -3 (no area observed with anti-cardiac troponin I expression). Higher score mean better outcome
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Anti Cardiac Troponin I Expression | -0.33 score on a scale |
| Control | Anti Cardiac Troponin I Expression | -0.83 score on a scale |
p-value: 0.031Wilcoxon (Mann-Whitney)
Secondary
Cardiac Index
Cardiac index were measured from pulmonary artery catheter using thermodilution method in unit of L/min/m\^2
Time frame: Immediately after induction of anesthesia, 5 minute, 2 hour, 6 hour, 24 hour after cardiopulmonary bypass
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glutamine | Cardiac Index | Immediately after induction of anesthesia | 2.00 L/min/m^2 | Standard Deviation 0.58 |
| Glutamine | Cardiac Index | 2 hours after cardiopulmonary bypass | 2.45 L/min/m^2 | Standard Deviation 0.55 |
| Glutamine | Cardiac Index | 6 hours after cardiopulmonary bypass | 2.54 L/min/m^2 | Standard Deviation 0.45 |
| Glutamine | Cardiac Index | 5 minutes after cardiopulmonary bypass | 3.15 L/min/m^2 | Standard Deviation 0.57 |
| Glutamine | Cardiac Index | 24 hours after cardiopulmonary bypass | 2.68 L/min/m^2 | Standard Deviation 0.35 |
| Control | Cardiac Index | 24 hours after cardiopulmonary bypass | 2.47 L/min/m^2 | Standard Deviation 0.41 |
| Control | Cardiac Index | 5 minutes after cardiopulmonary bypass | 3.03 L/min/m^2 | Standard Deviation 0.38 |
| Control | Cardiac Index | 2 hours after cardiopulmonary bypass | 2.36 L/min/m^2 | Standard Deviation 0.56 |
| Control | Cardiac Index | 6 hours after cardiopulmonary bypass | 2.27 L/min/m^2 | Standard Deviation 0.4 |
| Control | Cardiac Index | Immediately after induction of anesthesia | 1.87 L/min/m^2 | Standard Deviation 0.35 |
Comparison: After induction to anesthesiap-value: 0.33Unpaired T-Test
Comparison: 5 minutes after cardiopulmonary bypassp-value: 0.352Unpaired T-Test
Comparison: 2 hours after cardiopulmonary bypassp-value: 0.544Unpaired T-Test
Comparison: 6 hours after cardiopulmonary bypassp-value: 0.022Unpaired T-Test
Comparison: 24 hour after cardiopulmonary bypassp-value: 0.038Unpaired T-Test
Secondary
Ejection Fraction
Ejection fraction were measured by transesophageal echocardiography using Simpson method in percentage (%)
Time frame: 5 minutes after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Ejection Fraction | 46.17 percentage | Standard Deviation 5.15 |
| Control | Ejection Fraction | 45.55 percentage | Standard Deviation 5.03 |
p-value: 0.645Unpaired T-Test
Secondary
Ejection Fraction
Ejection fraction were measured by transesophageal echocardiography using Simpson method in percentage (%)
Time frame: Immediately after induction of anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Ejection Fraction | 41.40 percentage |
| Control | Ejection Fraction | 41.60 percentage |
p-value: 0.549Wilcoxon (Mann-Whitney)
Secondary
Intensive Care Unit Length of Stay
Intensive care unit length of stay were measured from length of time participant spent in intensive care unit in unit of hours
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Intensive Care Unit Length of Stay | 20.00 hours |
| Control | Intensive Care Unit Length of Stay | 20.00 hours |
p-value: 0.862Wilcoxon (Mann-Whitney)
Secondary
Intensive Care Unit Ventilation Time
Intensive care unit ventilation time were measured from length of time participant was on ventilator in intensive care unit in minutes.
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Intensive Care Unit Ventilation Time | 652.82 minutes | Standard Deviation 195.09 |
| Control | Intensive Care Unit Ventilation Time | 656.82 minutes | Standard Deviation 277.07 |
p-value: 0.95Unpaired T-Test
Secondary
Plasma Lactate 24 Hours After Cardiopulmonary Bypass
Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
Time frame: 24 hours after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Lactate 24 Hours After Cardiopulmonary Bypass | 2.08 mmol/L | Standard Deviation 0.67 |
| Control | Plasma Lactate 24 Hours After Cardiopulmonary Bypass | 2.46 mmol/L | Standard Deviation 0.69 |
p-value: 0.044Unpaired T-Test
Secondary
Plasma Lactate 48 Hours After Cardiopulmonary Bypass
Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
Time frame: 48 hours after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Lactate 48 Hours After Cardiopulmonary Bypass | 2.13 mmol/L | Standard Deviation 0.63 |
| Control | Plasma Lactate 48 Hours After Cardiopulmonary Bypass | 2.28 mmol/L | Standard Deviation 0.61 |
p-value: 0.349Unpaired T-Test
Secondary
Plasma Lactate 5 Minute After Cardiopulmonary Bypass
Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Plasma Lactate 5 Minute After Cardiopulmonary Bypass | 2.02 mmol/L | Standard Deviation 0.53 |
| Control | Plasma Lactate 5 Minute After Cardiopulmonary Bypass | 2.08 mmol/L | Standard Deviation 0.62 |
p-value: 0.72Unpaired T-Test
Secondary
Plasma Lactate 6 Hours After Cardiopulmonary Bypass
Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
Time frame: 6 hours after cardiopulmonary bypass
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Plasma Lactate 6 Hours After Cardiopulmonary Bypass | 5.30 mmol/L |
| Control | Plasma Lactate 6 Hours After Cardiopulmonary Bypass | 5.70 mmol/L |
p-value: 0.042Wilcoxon (Mann-Whitney)
Secondary
Plasma Lactate Before Induction to Anesthesia
Plasma lactate were measured using enzymatic method by blood gas analyser machine in unit of mmol/L
Time frame: Before induction to anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Plasma Lactate Before Induction to Anesthesia | 1.40 mmol/L |
| Control | Plasma Lactate Before Induction to Anesthesia | 1.30 mmol/L |
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Right Atrial Appendage Alpha-ketoglutarate
Right atrial appendage alpha-ketoglutarate were measured from right atrial appendage tissue biopsy using colorimetric tests in unit of g/mol.
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Right Atrial Appendage Alpha-ketoglutarate | 674.93 g/mol | Standard Deviation 333.49 |
| Control | Right Atrial Appendage Alpha-ketoglutarate | 507.32 g/mol | Standard Deviation 280.79 |
p-value: 0.043Unpaired T-Test
Secondary
Right Atrial Appendage Apoptosis Index
Right atrial appendage apoptosis index were measured from tissue section stained with in situ terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and examined under light microscopy in average number of apoptotic cells (positively stained) from 6 random fields per section
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Right Atrial Appendage Apoptosis Index | 5.00 cell |
| Control | Right Atrial Appendage Apoptosis Index | 6.17 cell |
p-value: 0.975Wilcoxon (Mann-Whitney)
Secondary
Right Atrial Appendage Myocardial Injury Score
Right atrial appendage myocardial injury score were measured from tissue section stained with hematoxylin-eosin and examined under by light microscopy in score of 0 (no change) to 3 (major changes with necrosis and diffuse inflammation). Higher scores mean worse outcome
Time frame: 5 minute after cardiopulmonary bypass
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Right Atrial Appendage Myocardial Injury Score | 1.30 score on a scale | Standard Deviation 0.24 |
| Control | Right Atrial Appendage Myocardial Injury Score | 1.48 score on a scale | Standard Deviation 0.26 |
p-value: 0.011Unpaired T-Test
Secondary
Vasoactive Inotropic Score
Vasoactive inotropic score (VIS) were maximum vasoactive and inotropic dose required by participant after surgery measured by VIS=dopamine dose in mg/kgbw/min + dobutamine dose in mg/kgbw/min + 100 x epinephrine dose in mg/kgbw/min + 10 x milrinone dose in mcg/kgbw/min + 10.000 x vasopressin dose in units/kgbw/min + 100 x norepinephrine dose in mcg/kgbw/min. Higher scores means worse outcomes. VIS \>= 20 is considered as high VIS and is associated with poor outcomes.
Time frame: 28 days (or until hospital discharge)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Vasoactive Inotropic Score | 5.00 score on a scale |
| Control | Vasoactive Inotropic Score | 5.00 score on a scale |
p-value: 0.075Wilcoxon (Mann-Whitney)
Other Pre-specified
Aortic Cross-clamping Time
Total time the patient underwent aortic cross-clamping during the surgical procedure. Measured in minutes.
Time frame: Intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Aortic Cross-clamping Time | 44.38 minutes | Standard Deviation 9.07 |
| Control | Aortic Cross-clamping Time | 43.86 minutes | Standard Deviation 14.81 |
Other Pre-specified
Cardiopulmonary Bypass Time
Total time measured the patient went under cardiopulmonary bypass. Measured in minutes.
Time frame: Intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Cardiopulmonary Bypass Time | 87.00 minutes |
| Control | Cardiopulmonary Bypass Time | 78.00 minutes |
Other Pre-specified
Coronary Graft
Number of coronary arteries grafted during operation
Time frame: Intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glutamine | Coronary Graft | 3.00 grafts |
| Control | Coronary Graft | 3.00 grafts |
Other Pre-specified
Total Surgical Procedure Time
Total time taken for the surgical procedure. Measured in minutes.
Time frame: Intraoperative
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glutamine | Total Surgical Procedure Time | 225.79 minutes | Standard Deviation 45.6 |
| Control | Total Surgical Procedure Time | 214.48 minutes | Standard Deviation 50.13 |