Myocardial Protection With Multiport Antegrade Cold Blood Cardioplegia

Coronary Artery Bypass Surgery Clinical Trial

— MACBC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02303704
• Other study ID #: multanic
• Status: Completed
• Phase: Phase 2
• Start date: April 2013
• Est. completion date: August 2014

Study information

• Verified date: February 2021
• Source: Chaudhry Pervaiz Elahi Institute of Cardiology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 448
• Est. completion date: August 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Bypass Surgery

Intervention

Procedure:
• multiport 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
• Aortic root antegrade cardioplegia
only cold blood cardioplegia was used for myocardial protection without hotshot.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chaudhry Pervaiz Elahi Institute of Cardiology

References & Publications (22)

Allen BS, Winkelmann JW, Hanafy H, Hartz RS, Bolling KS, Ham J, Feinstein S. Retrograde cardioplegia does not adequately perfuse the right ventricle. J Thorac Cardiovasc Surg. 1995 Jun;109(6):1116-24; discussion 1124-6. — View Citation

Ardehali A, Gates RN, Laks H, Drinkwater DC Jr, Rudis E, Sorensen TJ, Chang P, Aharon A. The regional capillary distribution of retrograde blood cardioplegia in explanted human hearts. J Thorac Cardiovasc Surg. 1995 May;109(5):935-9; discussion 939-40. — View Citation

Carrier M, Grégoire J, Khalil A, Thai P, Latour JG, Pelletier LC. Myocardial distribution of retrograde cardioplegic solution assessed by myocardial thallium 201 uptake. J Thorac Cardiovasc Surg. 1994 Dec;108(6):1115-8. — View Citation

Goldman BS, Ovil Y, Mycyk T. A technique for selective graft perfusion during aortocoronary bypass. J Card Surg. 1987 Dec;2(4):495-8. — View Citation

Goncu MT, Sezen M, Toktas F, Ari H, Gunes M, Tiryakioglu O, Yavuz S. Effect of antegrade graft cardioplegia combined with passive graft perfusion in on-pump coronary artery bypass grafting. J Int Med Res. 2010 Jul-Aug;38(4):1333-42. — View Citation

Gürsoy M, Bakuy V, Hatemi AC. Delivering Cardioplegia Beyond Totally Occluded Native Coronary Arteries Through the Saphenous Bypass Vein Graft: Is It Really a Protective Technique? Kosuyolu Kalp Derg. 2012;15:100 -104

Guyton RA, Thourani VH, Puskas JD, Shanewise JS, Steele MA, Palmer-Steele CL, Vinten-Johansen J. Perfusion-assisted direct coronary artery bypass: selective graft perfusion in off-pump cases. Ann Thorac Surg. 2000 Jan;69(1):171-5. — View Citation

Hatemi AC, Ulusoy RfE, Gürsoy M, Tongut A. Myocardial Protection with Simultaneous Antegrade/Vein Graft Cardioplegia Compared to Antegrade Cardioplegia Alone in Elective Coronary Artery Bypass Grafting Patients. Balkan Medical Journal. 2011

Lu F, Ji BY, Liu JP, Liu MZ, Wang GY, Hu SS. Passive graft perfusion in off-pump coronary artery bypass grafting. Chin Med J (Engl). 2007 Feb 5;120(3):192-6. — View Citation

Mack MJ, Brown PP, Kugelmass AD, Battaglia SL, Tarkington LG, Simon AW, Culler SD, Becker ER. Current status and outcomes of coronary revascularization 1999 to 2002: 148,396 surgical and percutaneous procedures. Ann Thorac Surg. 2004 Mar;77(3):761-6; discussion 766-8. — View Citation

Onem G, Sacar M, Baltalarli A, Ozcan AV, Gurses E, Sungurtekin H. Comparison of simultaneous antegrade/vein graft cardioplegia with antegrade cardioplegia for myocardial protection. Adv Ther. 2006 Nov-Dec;23(6):869-77. — View Citation

Onorati F, De Feo M, Mastroroberto P, Cristodoro L, Pezzo F, Renzulli A, Cotrufo M. Determinants and prognosis of myocardial damage after coronary artery bypass grafting. Ann Thorac Surg. 2005 Mar;79(3):837-45. — View Citation

Onorati F, Renzulli A, De Feo M, Santarpino G, Gregorio R, Biondi A, Cerasuolo F, Cotrufo M. Does antegrade blood cardioplegia alone provide adequate myocardial protection in patients with left main stem disease? J Thorac Cardiovasc Surg. 2003 Nov;126(5):1345-51. — View Citation

Panos AL, Ali IS, Birnbaum PL, Barrozo CA, al-Nowaiser O, Salerno TA. Coronary sinus injuries during retrograde continuous normothermic blood cardioplegia. Ann Thorac Surg. 1992 Dec;54(6):1137-8. Review. — View Citation

Radmehr H, Soleimani A, Tatari H, Salehi M. Does combined antegrade-retrograde cardioplegia have any superiority over antegrade cardioplegia? Heart Lung Circ. 2008 Dec;17(6):475-7. doi: 10.1016/j.hlc.2008.04.009. Epub 2008 Jul 26. — View Citation

Sabzi F, Zokaei A. Factors predicting coronary sinus rupture following cannula insertion for retrograde cardioplegia. Clin Med Insights Cardiol. 2012;6:1-6. doi: 10.4137/CMC.S7861. Epub 2011 Dec 6. — View Citation

Sanjay OP, Srikrishna SV, Prashanth P, Kajrekar P, Vincent V. Antegrade versus antegrade with retrograde delivery of cardioplegic solution in myocardial revascularisation. A clinical study in patients with triple vessel coronary artery disease. Ann Card Anaesth. 2003 Jul;6(2):143-8. — View Citation

Soltesz EG, Laurence RG, De Grand AM, Cohn LH, Mihaljevic T, Frangioni JV. Image-guided quantification of cardioplegia delivery during cardiac surgery. Heart Surg Forum. 2007;10(5):E381-6. — View Citation

Steuer J, Hörte LG, Lindahl B, Ståhle E. Impact of perioperative myocardial injury on early and long-term outcome after coronary artery bypass grafting. Eur Heart J. 2002 Aug;23(15):1219-27. — View Citation

Teoh KH, Christakis GT, Weisel RD, Fremes SE, Mickle DA, Romaschin AD, Harding RS, Ivanov J, Madonik MM, Ross IM, et al. Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia. J Thorac Cardiovasc Surg. 1986 Jun;91(6):888-95. — View Citation

Tian G, Xiang B, Dai G, Sun J, Lindsay WG, Deslauriers R. Simultaneous antegrade/retrograde cardioplegia protects myocardium distal to a coronary occlusion: a study in isolated pig hearts. Magn Reson Med. 2001 Oct;46(4):773-80. — View Citation

Vassiliades TA Jr, Nielsen JL, Lonquist JL. Coronary perfusion methods during off-pump coronary artery bypass: results of a randomized clinical trial. Ann Thorac Surg. 2002 Oct;74(4):S1383-9. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-op CK-MB Levels	CK-MB is a marker of Myocardial Damage.	36 hours after surgery.
Secondary	Pharmacologic Inotropic Support (Adrenaline)	The need, dose and duration of adrenaline infusion to maintain hemodynamic stability after surgery were noted.	Upto 1 week after sugery
Secondary	Pharmacological Inotropic Support (Nor-adrenaline)	The need, dose and duration of Nor-adrenaline infusion to maintain hemodynamic stability after surgery.	Upto 1 week after sugery
Secondary	Pharamacological Inotropic Support (Dobutamine)	The Need, Dose and duration of Dobutamine to maintain hemodynamic stability after surgery.	Upto 1 week after sugery
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.	24 hours before surgery and upto 1 week of surgical procedure.
Secondary	Operative Mortality	Deaths due to surgical complication during or after surgery.	Within 30 days after surgical Procedure