Intermittent antegrade warm blood cardioplegia for CABG: extended interval of cardioplegia

Intermittent Antegrade Warm Blood Cardioplegia for CABG: Extended Interval of Cardioplegia Kenji Minatoya, MD, Hitoshi Okabayashi, MD, PhD, Ichiro Shimada, MD, Atsushi Tanabe, MD, Takeshi Nishina, MD, Koichiro Nandate, MD, and Mitsuru Kunihiro, MD Divisions of Cardiovascular Surgery and Anesthesiology, Kokura Memorial Hospital, Fukuoka, Japan

Background. Intermittent delivery of warm cardioplegia provides a bloodless surgical field, but it is clinically important to evaluate the periods of normothermic ischemia. The aims of this study are to compare intermittent antegrade warm blood cardioplegia (IAWBC) with intermittent antegrade cold blood cardioplegia (IACBC) groups in terms of myocardial protection, and also to evaluate whether the length of ischemic time in the IAWBC group has an effect on myocardial dysfunction. Methods. This study is based on a retrospective review of patients who underwent elective coronary artery bypass surgery: 162 consecutive patients with IAWBC and 107 consecutive patients with IACBC.

Results. The creatinine kinase peak was smaller in the IAWBC group compared with the IACBC group (p < 0.0001). The cardiac index after cardiopulmonary bypass was higher in the IAWBC group (p < 0.02), and the amount of inotropic support required to wean from cardiopulmonary bypass was less in the IAWBC group compared with the IACBC group (p < 0.0001). Conclusions. IAWBC with 30 minutes of ischemia provides to be clinically acceptable myocardial protection for coronary bypass surgery.

W

to use IAWBC, and we have gradually extended the average interruption of cardioplegia to 30 minutes. We report the comparison between IACBC and IAWBC, and our experience with the extended interval of IAWBC.

arm blood cardioplegia is now accepted as an alternative method of myocardial protection [1]. The continuous infusion of warm blood cardioplegia is the main stream of this concept [2, 3], because it conceptually provides a continuous protection of myocardium without ischemia. In practice, however, most surgeons have to discontinue the cardioplegia temporarily during the construction of the anastomosis. It is therefore clinically important to evaluate the safe period of normothermic ischemia. Some investigators have reported on intermittent antegrade warm blood cardioplegia (IAWBC) [4 – 8]. Lichtenstein and associates reported the limitation of intermittency using the concept of the longest single time off cardioplegia (LTOC) [7]. They found that a prolonged LTOC (more than 13 minutes) was a risk factor for adverse outcomes in their series. Calafiore and associates reported that 15 minutes of LTOC was chosen because they could perform even a difficult anastomosis during 15 minutes [8]. But Isomura and associates noted that it may be possible to prolong the ischemic time for IAWBC to 20 to 30 minutes without complications [9]. Calafiore and associates showed their experience with an ischemic interval of approximate 30 minutes [10]. We had used intermittent antegrade cold blood cardioplegia (IACBC), and the average interval time between cardioplegia was about 30 minutes. Since December 1995, we have started

Accepted for publication June 7, 1999. Address reprint requests to Dr Minatoya, Department of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-0873, Japan; e-mail: [email protected].

© 2000 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 2000;69:74 – 6) © 2000 by The Society of Thoracic Surgeons

Material and Methods Patient Population From December 1, 1995, to May 31, 1996 (18 months), 162 consecutive patients at our hospital underwent elective isolated coronary artery bypass surgery with IAWBC. The cases without cardiopulmonary bypass were excluded, as were the cases operated under ventricular fibrillation without cardioplegia. All patients signed a consent form approved by our hospital. Demographic data are summarized in Table 1. For comparison between the IAWBC and the IACBC groups, the data of the last 107 consecutive patients operated using IACBC were collected retrospectively. They had elective isolated coronary artery bypass grafting with IACBC from January 1, 1995, to November 30, 1995.

Surgical Technique There was no difference regarding the surgical technique except the temperature between the IAWBC and IACBC groups. IAWBC was used with normothermic cardiopulmonary bypass (CPB), and IACBC was used with hypothermic CPB. All operations were performed on CPB through a median sternotomy, using nonpulsatile pumps and membrane oxygenators. During CPB, the flow was maintained between 2.2 and 2.6 L/min/m2, the mean 0003-4975/00/$20.00 PII S0003-4975(99)01384-3

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MINATOYA ET AL EXTENDED INTERVAL OF WARM CARDIOPLEGIA

Table 1. Comparison Between Cold Cardioplegia and Warm Cardioplegia: Demographic Data

Age (years) CPB time (min) Ao X time (min) Average of lowest temperature No. of diseased vessel (1–3) No. of grafts No. of anastomosis Ao X ⫽ aortic cross-clamp;

Cold (n ⫽ 107)

Warm (n ⫽ 162)

p Value

64.7 ⫾ 7.9 113.8 ⫾ 25.8 74.6 ⫾ 21.6 27.4 ⫾ 0.86

65.0 ⫾ 8.4 89.8 ⫾ 24.3 64.9 ⫾ 17.4 36.7 ⫾ 0.36

0.71 ⬍ 0.0001 ⬍ 0.0001 ⬍ 0.0001

2.59 ⫾ 0.69

2.70 ⫾ 0.59

0.17

2.68 ⫾ 0.59 3.40 ⫾ 1.01

2.84 ⫾ 0.60 3.67 ⫾ 1.07

0.04 0.04

CPB ⫽ cardiopulmonary bypass.

perfusion pressure was maintained between 50 and 60 mm Hg, and the body temperature was actively maintained between 36°C and 37°C for patients in the IAWBC group. For patients in the IACBC group, the body temperature was maintained between 22°C and 25°C. Blood cardioplegia was prepared in a cardioplegic reservoir with a crystalloid additive and administered at 37°C for IAWBC and at 15°C for IACBC. The additive contained 20% mannitol, sodium bicarbonate, l-asparate, MgSO4, l-glutamate, and lidocaine (Table 2). After aortic cross-clamping, 10 mL/kg of antegrade blood cardioplegia was infused through the aortic root cannula at a flow rate of 250 to 300 mL/min. After the first dose, additional doses were reinfused around 30 minutes after completion of the anastomosis. The distal and proximal anastomoses were performed alternatively during a single aortic cross-clamp time. Therefore, after the construction of bypass grafts, the distribution of cardioplegia was improved beyond the stenosis of the coronary arteries. All patients were weaned off CPB with a small dose of dopamine and dobutamine routinely on anesthetic protocol in our hospital. If more inotropic support was required, noradrenaline or amrinone was used as a second choice.

Definitions and Data Collection Operative mortality was considered as death within 30 days of the operation. Perioperative myocardial infarction (PMI) was identified by the appearance of new Table 2. Blood Cardioplegia Components Component Blood 20% mannitol 8.4% sodium bicarbonate 2% lidocaine l-aspartate MgSO4 l-glutamate Potassium

Amount/Concentration 500 mL 40 mL 6 mL 0.3 mL 20 mM 1.6 mM 14 mM 20 mM

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Table 3. Comparison Between Cold Cardioplegia and Warm Cardioplegia: Results

Spontaneous rhythm (%) CKMB peak (%) CI on weaning (L/min/m2) Dopamine and dobutamine on weaning (␮g/kg/min) Needs of norepinephrine on weaning (%) Average interval of cardioplegia (min) CI ⫽ cardiac index;

Cold (n ⫽ 107)

Warm (n ⫽ 162)

77.6 6.1 ⫾ 3.4 3.73 ⫾ 0.69 7.8 ⫾ 2.2

85.8 0.08 4.5 ⫾ 2.2 ⬍ 0.0001 3.97 ⫾ 0.87 0.02 5.0 ⫾ 1.5 ⬍ 0.0001

p Value

15.0

10.5

0.28

25.4 ⫾ 4.0

31.9 ⫾ 5.2

⬍ 0.0001

CKMB ⫽ creatinine kinase.

electrocardiographic changes in the postoperative electrocardiogram or enzymatic criteria or both, as described by Calafiore and associates [8]. Samples for cardiac enzyme were collected at the following time intervals: at admission to the intensive care unit (ICU), 4, 8, 12, 16, and 24 hours after admission to ICU, and every 8 hours during the second and third postoperative days.

Statistical Methods Data were analyzed using the Statview statistical software package (SAS Institute Inc, Cary, NC). Continuous variables are summarized as mean ⫾ standard deviation. Categorical variables are summarized as the absolute frequencies or as a percentage. Between-group comparisons were performed with the ␹2 test. A p value less than 0.05 was considered significant.

Results There was one hospital death in the IACBC group and two hospital deaths in IAWBC group. Table 3 shows the results comparing the IAWBC group with the IACBC group. Although the number of grafts and number of anastomoses were greater in the IAWBC group ( p ⬍ 0.04), the CPB time is shorter in the IAWBC group ( p ⬍ 0.0001). It is because no time is wasted by the need to rewarm. The creatine kinase (CKMB) peak was smaller in the IAWBC group ( p ⬍ 0.0001). The cardiac index was higher in the IAWBC group ( p ⬍ 0.02), and the doses of dopamine and dobutamine on weaning from CPB were less in the IAWBC group ( p ⬍ 0.0001). It was unusual to see hyperkalemia postoperatively, even though we used only high-potassium (20 mEq) cardioplegia. Average interval of cardioplegia was 31.9 ⫾ 5.2 minutes in IAWBC group and 25.4 ⫾ 4.0 minutes in the IACBC group.

Comment The continuous infusion of cardioplegia without ischemic time might be the ideal myocardial protection, assuming the risk of reperfusion damage and ischemia is avoided [3]. Several reports have shown that even short periods of interruption of warm cardioplegia may result in irrevers-

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ible cell damage and permanent regional ventricular dysfunction [11, 12]. But, Mezzetti and associates reported that after about 1 hour of ischemia in hearts protected with IAWBC, blood samples taken simultaneously from the radial artery and coronary sinus did not show release of CK and reduced glutathione 1 and 20 minutes after aortic declamping [13]. Tian and associates also found in their experimental study using pigs that, in the normal heart, IAWBC may provide as much myocardial protection as does antegrade continuous warm cardioplegia [14]. Ali and Kinley reported that intermittent warm blood cardioplegia is as safe as cold blood cardioplegia when the clamp time is less than 90 minutes, but that extra precautions are needed with longer times [5]. Landymore and associates described preserved functional recovery after multidose warm blood cardioplegia and suggest that repetitive episodes of ischemia may condition the myocardium, thus preventing injury during prolonged aortic cross-clamping [15]. There were 13 patients in our IAWBC group who had cross-clamp time over 90 minutes, with the longest cross-clamp time being 137 minutes. Despite the long cross-clamp time, all these patients made an uneventful recovery. Lichtenstein and associates noted that their data suggested that the longest single ischemic interval is more important than the cumulative ischemic time. They demonstrated that short periods of normothermic ischemia would be as well tolerated with warm blood cardioplegia as they are with cold blood cardioplegia, whereas extended intervals may be associated with an increased frequency of adverse outcomes [7]. The postoperative CKMB in our hospital is relatively high compared with the data reported for other institutes. Calafiore and associates reported a peak CKMB of 38 ⫾ 38 in the IAWBC group and 51 ⫾ 30 in the IACBC group [8]. This discrepancy may be due partly to the laboratory difference but also to the influence of longer ischemic time. Our data demonstrated that the peak CKMB in the IAWBC group is significantly lower than the IACBC group. Our rate of perioperative myocardial infarction (PMI) is consistent with those reported by other centers. The difference of cardioplegic solution should be mentioned. Calafiore and associates used dexistrose, THAM (trihydroxymethylaminomethane), K⫹, Ca2⫹, and Mg2⫹ as the additive, whereas Lichtenstein and associates [7] used dexistrose, THAM, K⫹, Mg2⫹, and CPD-adenine as the additive. Our crystalloid additive is more complicated than theirs. As Calafiore and associates reported, there are some possible reasons that the value of CKMB might be elevated, such as the dissection of the muscle and the harvesting of the internal thoracic arteries. We did not have instances of spontaneous beating or ventricular fibrillation during aortic cross-clamp, despite the elongation of LTOC. Even though the concentration of potassium was 20 mEq for every infusion, we did not have difficulties in hyperkalemia postoperatively. Christakis and associates pointed out in their article that for nearly one-third of the patients with normothermic cardioplegia, the concentration of potassium had to be increased to completely arrest electrical activity, and in a

Ann Thorac Surg 2000;69:74 – 6

large number of patients, there was a low systemic vascular resistance that required the administration of vasoconstrictors [16]. We required definitely smaller amount of inotropes with IAWBC compared with the cases with IACBC. The technique of every 15-minute interval of cardioplegia is somewhat cumbersome and inconvinient. We think that IAWBC with an intermittency of less than 15 minutes or continuous warm blood cardioplegia theoretically provides better myocardial protection than IAWBC with extended intermittency, but IAWBC with 30-minute intermittency provides clinically acceptable myocardial protection for CABG. We are indebted to James Kuo, MD, for his assistance in preparing the manuscript, and Masahiro Ishibashi, MT, and Kenji Taninobu, MT, for their assistance in collecting the data.

References 1. Mauney MC, Kron IL. The physiologic basis of warm cardioplegia. Ann Thorac Surg 1995;60:819–23. 2. Lichtenstein SV, Ashe K, El-Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1990;101:269–74. 3. Salerno TA, Houick JP, Barrozo CAM, et al. Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac Surg 1991;51:245–7. 4. Isomura T, Hisatomi K, Sato T, Hayashida N, Ohishi K. Interrupted warm blood cardioplegia for coronary artery bypass grafting. Eur J Cardiothorac Surg 1995;9:133– 8. 5. Ali IM, Kinley CE. The safety of intermittent warm blood cardioplegia. Eur J Cardiothorac Surg 1994;8:554– 6. 6. Pelletier LC, Carrier M, Leclerc Y, Cartier R, Wesolowska E, Charles S. Intermittent antegrade warm versus cold blood cardioplegia: a prospective, randomized study. Ann Thorac Surg 1994;58:41–9. 7. Lichtenstein SV, Naylor D, Feindel CM, et al. Intermittent warm blood cardioplegia. Circulation 1995;92(Suppl II):341– 6. 8. Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995; 59:398 – 402. 9. Isomura T, Hisatomi K, Satoh T, Hayashida N. Letter to the editor. Eur J Cardiothorac Surg 1996;10:480. 10. Calafiore AM, Teodori G, Bosco G, et al. Intermittent antegrade warm blood cardioplegia in aortic valve replacement. J Card Surg 1996;11:348–54. 11. Matsuura H, Lazar HL, Yang XM, Rivers S, Treanor P, Shemin RJ. Detrimental effects of interrupting warm blood cardioplegia during coronary revascularization. J Thorac Cardiovasc Surg 1993;106:357– 61. 12. Misare BD, Krukenkamp IB, Lazer ZP, Levitsky S. Recovery of postischemic contractile function is depressed by antegrade warm cardioplegia. J Thorac Cardiovasc Surg 1993; 105:37– 44. 13. Mezzetti A, Calafiore AM, Lapenna D, et al. Intermittent antegrade warm carioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium. J Thorac Cardiovasc Surg 1995;109:787–95. 14. Tian G, Xiang B, Butler KW, et al. A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia. J Thorac Cardiovasc Surg 1995;109:1155– 63. 15. Landymore RW, Marble AE, Fris J. Effect of intermittent delivery of warm blood cardioplegia on myocardial recovery. Ann Thorac Surg 1994;57:1267–72. 16. Christakis GT, Koch JP, Deemar KA, et al. A randomized study of the systemic effects of warm heart surgery. Ann Thorac Surg 1992;54:449–59.