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Myocardial Protection With Multiport Antegrade Cold Blood Cardioplegia

Myocardial Protection With Multiport Antegrade Cold Blood Cardioplegia and Continuous Controlled Warm Shot Through Vein Grafts During Proximal Ends Anastomosis in Conventional CABG

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02303704
Acronym
MACBC
Enrollment
448
Registered
2014-12-01
Start date
2013-04-30
Completion date
2014-08-31
Last updated
2021-02-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Bypass Surgery

Keywords

Multiperfusion set, Myocardial protection, Coronary Artery Bypass Grafting

Brief summary

In spite improvements in methods of myocardial protection, peri-operative myocardial damage is still the commonest cause of early morbidity and mortality after technically successful CABG Surgery. What is the optimum method of myocardial protection is still debatable. The investigators conducted this study to see effects of multiport antegrade cold blood cardioplegia on myocardial protection, along with continuous controlled warm blood perfusion through veins graft during proximal ends anastomosis in conventional CABG surgery in patients having multi-vessel disease.

Detailed description

A prospective randomized controlled study was conducted between April-2013 and June-2014, in the Department of Cardiac Surgery, Chaudary Pervaiz Elahi Institute of cardiology (CPEIC) Multan, Pakistan. The CPEIC is a tertiary cardiac care center and is presently performing over 600 coronary artery bypass surgery annually. The study was conducted in strict compliance of the rules established by the revised Helsinki convention and had approval from the ethical committee of the institute. Patients undergoing isolated conventional CABG were included in the study except; The redo CABG, those who required 2 or less than 2 grafts, patients who had major postoperative neurological complications like stroke, 2nd arterial graft along with LIMA, patients who need CABG within a week of STEMI or NSTEMI and Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis. The patients were randomized into two groups by using draw randomization technique. The investigators made 112 sets, each set containing four patients. The staff nurse on duty was requested to pick up the two folded papers from four containing hidden identity of the patients. The patients chosen by draw were included in the study group, others in the control group. Group I: Patients who received multiport antegrade cardioplegia and continuous controlled warm blood perfusion through vein grafts (Study Group) and Group II: Patients who underwent routine conventional CABG with antegrade aortic root cardioplegia without warm blood perfusion (Control Group). All operations were carried out by two consultant surgeons at the investigators institution, who are certified cardiac surgeons with sufficient experience. Patients were premedicated with oral dose of 3mg bromazepam the night before surgery. Anaesthesia was induced with intra-venous morphine (0.1mg/kg), midazolam (0.05-0.1 mg /kg), and propofol (1.0-2.5 mg/kg titrated according to the response. They were given atracuronium (1mg/kg) before endotracheal intubation. The anaesthesia was maintained with sevoflorane/isoflurane. In all patients the standard cardiopulmonary bypass (CPB) was established with an ascending aortic arterial cannula and a two stage single venous cannula in the right atrium. The CPB circuit was primed with crystalloid Ringer's solution. Heparin was administered in a dose of 400 U/Kg. The body temperature was lowered to 30-32°C. The local cooling was achieved with ice cold saline. Cold blood cardioplegia was used in each group. The first dose of cardioplegia was 10-15 ml/kg and further doses were given as 5-7ml/kg repeated after each graft or after 20 minutes. Cold blood cardioplegia was given by using cardioplegia delivery system including heat exchanger in both groups. A cardioplegia delivery cannula with a separate vent line (DLP Medtronic, Grand Rapids, MI, USA) was inserted into the ascending aorta. The pump flow rate was kept between 2.0 and 2.4 L/min/m2 to maintain a mean arterial pressure of 55 - 70 mmHg. In both groups, myocardial protection was achieved by an initial antegrade infusion of cold (4 °C) blood cardioplegic potassium solution followed by intermittent antegrade cold blood cardioplegia at the completion of each distal anastomosis via a cardioplegia delivery cannula from the aortic root. Whereas in Group I, a multiple perfusion set was used to deliver cardioplegia simultaneously in aortic root and vein grafts. After the distal anastomosis of each vein graft had been completed, the proximal ends were connected to the free branch of the multi- perfusion set. In this way, simultaneous intermittent antegrade graft cardioplegia was administered in addition to aortic root cardioplegia (named as multiport antegrade cardioplegia). LIMA and great saphenous vein were used as conduits. LIMA was anastomosed to LAD and other coronary vessels received greater saphenous vein grafts as conduits. Just before the removal of the aortic cross-clamp, warm blood shot (normo-kalemic) was started through multi-perfusion set attached to cardioplegia cannula in the aortic root and vein grafts in Group I. As contraction of heart started the multiport limb attached to cardioplegia cannula was off and cross clamp was removed .The warm perfusion through the vein grafts was continued at controlled pressures of about 50-70 mmHg, flow rate of 10-30ml/min/graft and temperature of 35-37 oC. Proximal anastmosis was performed in both groups using partial occluding clamp. The necessity of inotropic support and the choice of inotropic drugs to be administered during weaning from cardiopulmonary bypass (CPB) were determined by a cardiac anaesthetist team, who were blinded and independent with respect to the study. The CK-MB levels were determined at five points of time i.e. before operation, immediately after shifting to ICU, at 12, 24 hours and 36 hours after shifting of patient to ICU. The reagent used for determining the serum CK-MB levels was the product of Merck (Merck, France) and the designated reference value for detection of myocardial damage were \>25 units/liter for CK-MB. 448 patient characteristics were prospectively entered in the investigators electronic database (CASCADE DATABASES, Lahore, Pakistan). The study specific data not included in the database were separately entered in a Microsoft Excel spreadsheet (MS Excel, version 2007, Microsoft Co USA). The statistical analysis was carried out using SPSS (SPSS version 20, SPSS Inc, Chicago, IL). The preoperative, operative and postoperative characteristics were summarized using means and standard deviation for the numeric variables. The groups were compared using Student's t-test for numeric variables and Chi-square test for categorical variables. The significance of differences between the groups was expressed as p-value and a value of \<0.05 was considered significant.

Interventions

PROCEDUREmultiport antegrade cardioplegia

Cold blood cardioplegia was used for myocardial protection and just before the removal of the aortic cross-clamp, warm blood shot (normo-kalemic) was started through multi-perfusion set attached to cardioplegia cannula in the aortic root and vein grafts.As contraction of heart started the multiport limb attached to cardioplegia cannula was off and cross clamp was removed .The warm perfusion through the vein grafts was continued at controlled pressures of about 50-70 mmHg, flow rate of 10-30ml/min/graft and temperature of 35-37 oC

PROCEDUREAortic root antegrade cardioplegia

only cold blood cardioplegia was used for myocardial protection without hotshot.

Sponsors

Chaudhry Pervaiz Elahi Institute of Cardiology
Lead SponsorOTHER_GOV

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE

Eligibility

Sex/Gender
ALL
Healthy volunteers
No

Inclusion criteria

* All patients undergoing isolated conventional CABG were included in the study

Exclusion criteria

The redo CABG surgery. Those who required 2 or less than 2 grafts. Patients who had major postoperative neurological complications like stroke. 2nd arterial graft along with LIMA. Patients who need CABG within a week of STEMI or NSTEMI. Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis

Design outcomes

Primary

MeasureTime frameDescription
Post-op CK-MB Levels36 hours after surgery.CK-MB is a marker of Myocardial Damage.

Secondary

MeasureTime frameDescription
Pharmacologic Inotropic Support (Adrenaline)Upto 1 week after sugeryThe need, dose and duration of adrenaline infusion to maintain hemodynamic stability after surgery were noted.
Pharmacological Inotropic Support (Nor-adrenaline)Upto 1 week after sugeryThe need, dose and duration of Nor-adrenaline infusion to maintain hemodynamic stability after surgery.
Pharamacological Inotropic Support (Dobutamine)Upto 1 week after sugeryThe Need, Dose and duration of Dobutamine to maintain hemodynamic stability after surgery.
Intra-aortic Balloon Pump Counter-pulsation (IABPC) Support24 hours before surgery and upto 1 week of surgical procedure.The need of IABPC (mechanical support) before surgery or during weaning from Cardiopulmonary bypass and in ICU to assist in maintaining hemodynamics of the patient.
Operative MortalityWithin 30 days after surgical ProcedureDeaths due to surgical complication during or after surgery.

Participant flow

Participants by arm

ArmCount
Multiport Antegrade Cardioplegia
Patients who received multiport antegrade cardioplegia and continuous controlled warm blood perfusion through vein grafts
215
Aortic Root Antegrade Cardioplegia
Patients who underwent routine conventional CABG with antegrade aortic root cardioplegia without warm blood perfusion
219
Total434

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyProtocol Violation59

Baseline characteristics

CharacteristicMultiport Antegrade CardioplegiaAortic Root Antegrade CardioplegiaTotal
Age, Continuous54.97 years
STANDARD_DEVIATION 8.44
53.62 years
STANDARD_DEVIATION 9.6
54.29 years
STANDARD_DEVIATION 9.06
Sex: Female, Male
Female
29 Participants27 Participants56 Participants
Sex: Female, Male
Male
186 Participants192 Participants378 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 2150 / 219
serious
Total, serious adverse events
0 / 2150 / 219

Outcome results

Primary

Post-op CK-MB Levels

CK-MB is a marker of Myocardial Damage.

Time frame: 36 hours after surgery.

Population: All patients in whom Peak CKMB levels were noted within 24 hours after surgery

ArmMeasureValue (MEAN)Dispersion
Multiport Antegrade CardioplegiaPost-op CK-MB Levels71.70 IU/LStandard Deviation 41.5
Aortic Root Antegrade CardioplegiaPost-op CK-MB Levels92.66 IU/LStandard Deviation 88.1
Comparison: Null hypothesis was there is no significant difference between the means of two groupsp-value: <0.05t-test, 2 sided
Secondary

Intra-aortic Balloon Pump Counter-pulsation (IABPC) Support

The need of IABPC (mechanical support) before surgery or during weaning from Cardiopulmonary bypass and in ICU to assist in maintaining hemodynamics of the patient.

Time frame: 24 hours before surgery and upto 1 week of surgical procedure.

Population: All patients who underwent surgery and for whom IABP support was required.

ArmMeasureValue (NUMBER)
Multiport Antegrade CardioplegiaIntra-aortic Balloon Pump Counter-pulsation (IABPC) Support4 participants
Aortic Root Antegrade CardioplegiaIntra-aortic Balloon Pump Counter-pulsation (IABPC) Support14 participants
Comparison: Null Hypothesis:The proportion of IABP use is same between the two groupsp-value: <0.05Chi-squared
Secondary

Operative Mortality

Deaths due to surgical complication during or after surgery.

Time frame: Within 30 days after surgical Procedure

Population: all patients who underwent surgery and monitored for death due to surgical complication.

ArmMeasureValue (NUMBER)
Multiport Antegrade CardioplegiaOperative Mortality1 participants
Aortic Root Antegrade CardioplegiaOperative Mortality9 participants
Comparison: Null Hypothesis: Operative mortality ratio is same in both groupsp-value: <0.05Fisher Exact
Secondary

Pharamacological Inotropic Support (Dobutamine)

The Need, Dose and duration of Dobutamine to maintain hemodynamic stability after surgery.

Time frame: Upto 1 week after sugery

Population: All patients in whom Dobutamine was used to wean off the patients from Cardiopulmonary Bypass.

ArmMeasureValue (MEAN)Dispersion
Multiport Antegrade CardioplegiaPharamacological Inotropic Support (Dobutamine)3.41 ug/kg/minStandard Deviation 1.7
Aortic Root Antegrade CardioplegiaPharamacological Inotropic Support (Dobutamine)4.20 ug/kg/minStandard Deviation 2.24
p-value: <0.05t-test, 2 sided
Secondary

Pharmacological Inotropic Support (Nor-adrenaline)

The need, dose and duration of Nor-adrenaline infusion to maintain hemodynamic stability after surgery.

Time frame: Upto 1 week after sugery

Population: All patients in whom Nor-adrenaline was used to wean off the patients from Cardiopulmonary Bypass.

ArmMeasureValue (MEAN)Dispersion
Multiport Antegrade CardioplegiaPharmacological Inotropic Support (Nor-adrenaline)0.035 ug/kg/minStandard Deviation 0.016
Aortic Root Antegrade CardioplegiaPharmacological Inotropic Support (Nor-adrenaline)0.089 ug/kg/minStandard Deviation 0.5
Comparison: Null Hypothesis: The dose of nor-adrenaline on weaning from CPB is same for Group I and II.p-value: <0.05t-test, 2 sided
Secondary

Pharmacologic Inotropic Support (Adrenaline)

The need, dose and duration of adrenaline infusion to maintain hemodynamic stability after surgery were noted.

Time frame: Upto 1 week after sugery

Population: All patients in whom Adrenaline was used to wean off the patients from Cardiopulmonary Bypass.

ArmMeasureValue (MEAN)Dispersion
Multiport Antegrade CardioplegiaPharmacologic Inotropic Support (Adrenaline)0.047 ug/kg/minStandard Deviation 0.018
Aortic Root Antegrade CardioplegiaPharmacologic Inotropic Support (Adrenaline)0.064 ug/kg/minStandard Deviation 0.82
p-value: <0.05t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026