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Ann Thorac Surg 1997;63:1619-1624
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Evaluation of 7,000+ Patients With Two Different Routes of Cardioplegia

Minneapolis Heart Institute, Minneapolis, Minnesota

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. This study examined the efficacy and safety of retrograde cardioplegia in comparison with an antegrade/retrograde approach.

Methods. Between January 1, 1991, and December 31, 1995, 7,032 coronary artery bypass procedures, alone or in combination with valve replacement/repair, were performed using either retrograde cardioplegia (R) or an antegrade/retrograde (AR) approach. There were 4,224 patients in the R group and 2,808 in the AR group. These included elective, urgent, emergent/salvage, first operative, and redo cases.

Results. All preoperative, intraoperative, and postoperative variables listed in The Society of Thoracic Surgeons National Cardiac Surgery Database were used to compare the two groups using univariate analysis. The pump time was longer in the AR group, with fewer grafts per patient. The R group had higher predicted risk (3.2% versus 3.0%; p = 0.04), more postoperative atrial fibrillation (34% versus 31%; p = 0.006), and longer postoperative length of stay (8.8 versus 8.0 days; p < 0.001). Using The Society of Thoracic Surgeons National Cardiac Surgery Database predicted risk group model, a subgroup of 221 coronary artery bypass grafting patients in the retrograde (s-R) and 132 coronary artery bypass grafting patients in the antegrade/retrograde (s-AR) group fell into a greater incidence of predicted mortality group (10%). The s-R subgroup had more patients in New York Heart Association functional class IV. Univariate analysis revealed higher postoperative atrial fibrillation (51% versus 41%; p = 0.05) and longer postoperative length of stay (12.8 versus 10.8 days; p = 0.03) in the s-R subgroup versus the s-AR subgroup.

Conclusions. The results appear to favor neither approach. Preoperatively, both retrograde groups (R and s-R) had higher preoperative predicted risk, but operative mortality or complications were not significantly increased when compared with the AR and s-AR groups. Retrograde cardioplegia alone was shown to be effective in the R and s-R groups, but atrial fibrillation developed in more patients, which could have contributed to longer length of stay in these groups. Antegrade/retrograde cardioplegia offers good immediate outcome but the delivery method can be cumbersome and confusing during the adjustments of flow clamps for antegrade/retrograde delivery and may contribute to prolonged pump times. From this retrospective, nonrandomized review, it appears that retrograde cardioplegia alone provides as good myocardial protection and safety as an antegrade/retrograde approach in either the low-risk or high-risk patient.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 1624.

Retrograde cardioplegia could provide better myocardial protection despite the presence of coronary lesions [1–3]. The clinical use of retrograde cardioplegia still raises some concerns, including potentially inadequate preservation of the right ventricle and delay in arresting the heart with slow retrograde perfusion. The combined antegrade-retrograde approach may have some advantages over retrograde cardioplegia alone [4]. Therefore, at present, most surgeons are in favor of the combined approach [5, 6]. However, the antegrade/retrograde technique has some disadvantages. It requires another set of tubing in the operative field and other equipment for the perfusionist to be able to switch back and forth from one mode of perfusion to the other. Using this technique could be cumbersome, confusing, and more time-consuming while the aorta is cross-clamped and may not be cost-effective.

Our previous study has shown that the retrograde cardioplegia alone is simple and effective for protection of the myocardium [7]. There were concerns regarding the small sample size of this study and whether retrograde cardioplegia alone can be used in routine cases, including high-risk patients and all clinical situations such as emergent, urgent, elective, and reoperative cases.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Between January 1, 1991, and December 31, 1995, 7,032 coronary artery bypass procedures, either alone or combined with valve replacement or valve repair procedures using cardiopulmonary bypass and cardioplegia, were reviewed. These patients received either retrograde cardioplegia alone (R) or combined antegrade and retrograde (AR) cardioplegia for myocardial protection as per discretion of the surgeon. It is understood that in a retrospective study such as this, bias may be introduced unintentionally, such as surgeon-specific bias and patient referral bias. There were 4,224 patients in the R group and 2,808 in the AR group. The clinical profile, preoperative, intraoperative, and postoperative variables for groups R and AR, as suggested in The Society of Thoracic Surgeons (STS) National Cardiac Surgery Database (NCSD) are listed in Tables 1 through 3.

Initially, cold crystalloid cardioplegia was used and delivered as soon as the aortic cross-clamp was applied. Moderate systemic hypothermia (28° to 30°C) and topical hypothermia with cold saline solution were used in patients between 1991 and 1993. In the AR approach, an initial antegrade bolus of 500 to 700 mL of cardioplegic solution was used followed by an intermittent retrograde dose of 200 mL every 20 minutes during aortic cross-clamping. The same approach was carried out in group R except a larger bolus of 800 to 1,000 mL was given directly into the coronary sinus during a 2- to 3-minute period while coronary sinus pressure was maintained at less than 60 mm Hg. No additional doses of cardioplegia were given through the vein grafts after completion of the distal anastomoses in either group. The details of transatrial coronary sinus cardioplegia delivery have been described elsewhere [6]. In 1994, tepid heart surgery and blood cardioplegia were introduced in our practice; topical hypothermia is used rarely, core temperature is allowed to drift to 32° to 34°C without cooling, and body temperature is increased to at least 35°C before separation from the cardiopulmonary bypass.

Fifty-one percent of the patients in both groups had hemodynamic measurements obtained just before initiation of cardiopulmonary bypass and repeated approximately 6 hours after return from the operating room when hemodynamic instability was corrected. Arterial blood pressure, heart rate, central venous pressure, pulmonary artery pressure, and pulmonary capillary wedge pressures were recorded. Cardiac output determinations were made with an American Edwards Laboratories Swan-Ganz catheter and computer (Santa Ana, CA).

The cardiac index, stroke volume, systemic vascular resistance, pulmonary vascular resistance, right ventricular stroke work index, and left ventricular stroke work index were derived. Postoperative hemodynamic measurements were obtained in only 37% of patients in group AR and 33% of patients in group R after reaching a fixed preload pulmonary wedge pressure of 15 mm Hg. An electrocardiogram and serum enzyme levels were obtained on arrival in the intensive care unit and on a daily basis for 3 days.

Statistical Analysis System software (version 6.09 for Microsoft Windows NIT; SAS Institute, Carey, NC) was used for all analyses. All tests were performed univariately to detect association between cardioplegia technique (antegrade/retrograde versus retrograde) and the preoperative, intraoperative, and postoperative data. To determine univariate associations between cardioplegia technique and discrete patient characteristics, Pearson's ² or Fischer's exact test were used when appropriate. For the continuous data, t tests were used to show associations between characteristics and cardioplegia technique.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Preoperative, intraoperative, and postoperative risk variables and complications listed in the STS NCSD were used to compare these two groups of patients using univariate analysis. The R group had higher preoperative predicted risk (3.2% versus 3.0%; p = 0.04), but otherwise, these two groups of patients were similar with respect to age, associated medical problems, angiographic extent of coronary artery disease, and mean preoperative ejection fraction (see Table 1). The mean core temperature was 30°C in the AR group and 31.5°C in the R group. The pump time was longer in the AR group (126 versus 107 minutes; p = 0.001), with patients requiring fewer grafts/patient (3.12 versus 3.24; p = 0.0001) (see Table 2). There was no statistical difference in the number of patients needing inotropic agents (50.9% versus 49.3%; p = 0.18) coming off cardiopulmonary bypass or in the need for permanent pacemaker implantation (2.3% versus 1.9%; p = 0.3) before discharge. There were no differences in the incidence of postoperative renal or pulmonary complications, in the peak level of the myocardial specific isoenzyme of creatine kinase, or in the incidence of postoperative myocardial infarction. There was a higher incidence of postoperative atrial fibrillation (31% versus 34%; p = 0.006) and longer (8.02 versus 8.98 days; p < 0.0001) postoperative length of stay (see Table 3). Otherwise, there were no significant differences in postoperative complications or death (3.2% versus 3.9%; p = 0.09).

Studies using a pulmonary catheter to record and compute the hemodynamic variables showed that there was a difference in cardiac index (2.7 versus 2.6 L•min^-1•m^-2; p = 0.007), but not in the left ventricular stroke work index (26.9 ± 6 versus 25.0 ± 10 g-m/m^2; p > 0.05) or right ventricular stroke work index (8.5 ± 3 versus 8.4 ± 2 g-m/m^2; p >0.05) at a fixed preload of 15 mm Hg (mean right atrial pressure, 11 ± 3 mm Hg; mean pulmonary artery pressure, 24 ± 5.5 mm Hg; and mean aortic pressure, 70 ± 18 mm Hg).

Using the STS NCSD predicted risk group model, 132 patients in the s-AR subgroup and 221 patients in the s-R subgroup fell into the higher predicted mortality risk group (10%). Univariate analysis between these two subgroups revealed the following differences: more patients in the s-R subgroup were in New York Heart Association functional class IV and receiving intravenous nitroglycerin up to the time of the operation (30% versus 21%; p = 0.05). Patients in the s-R subgroup had lower mean ejection fraction (0.29 versus 0.36; p = 0.003) (see Table 4). Pump time was greater (136 versus 104 minutes; p = 0.0001) in the s-AR subgroup despite fewer grafts/patient (3.13 versus 3.36; p = 0.04) (see Table 5). The postoperative incidence of atrial fibrillation was higher in the s-R subgroup (51% versus 41%; p = 0.05) and possibly contributed to a longer postoperative length of stay (12.8 versus 10.8 days; p = 0.03) (see Table 6). Except for these, there again was no significant difference in postoperative complications. The operative mortality (30 days) was 11% for the s-AR subgroup and 13% for the s-R subgroup (p = 0.4). Hemodynamic study in these two subgroups showed no difference in cardiac index (2.34 versus 2.23 L•min^-1•m^-2; p = 0.4) and similar left and right ventricular stroke work indices.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The principle of retrograde cardioplegia relies on the fact that the unobstructed coronary venous system can serve as a delivery conduit for the homogeneous distribution of cardioplegic solution. One of the advantages of this technique is that cardioplegic solution is distributed through a transmural network of veins directly to the cardiac microstructure, independent of flow-limiting lesions [8]. Because of concerns over the speed of cardiac arrest and the consistency of myocardial preservation during isolated retrograde cardioplegia, some investigators [4–6] have advocated combining the antegrade and retrograde approach.

Generally, retrograde administration takes a longer time to deliver a similar volume of cardioplegic solution because of lower flow rates and pressures used to prevent myocardial edema and coronary sinus injury. Therefore, both initial cardiac arrest and subsequent myocardial protection may require more time with retrograde than with antegrade delivery. Neither our results nor the work of other investigators [9, 10] suggest that the differential rate of myocardial preservation and cooling has any clinically detectable adverse effects on postoperative outcome. Nevertheless, the delay in cardiac arrest may be circumvented by administering the first dose of cardioplegic solution through the aortic root [11].

One potential limitation of coronary sinus cardioplegia is inadequate right ventricular preservation. This concern has been raised on the basis of canine studies [12, 13] that suggest that retrograde delivery does not consistently cool the right ventricle. However, Partington and coworkers [11] found that retrograde perfusate may shunt directly to the right-sided heart chambers and that the thebesian-sinusoidal drainage of the cold retrograde effluent causes right ventricular hypothermia and sufficient right-sided myocardial protection. Moreover, intracavitary cooling of the right ventricle can aid in right ventricular preservation [4, 10, 12]. Using radionuclide angiocardiography, Menasché and associates [14] have shown that right ventricular function is adequately preserved after coronary sinus cardioplegia during aortic valve replacement. Similar observations have been made by others [9, 10, 15] in patients undergoing coronary bypass operations.

We and other investigators [7, 16] have examined the safety and effectiveness of retrograde cardioplegia in coronary artery bypass grafting and have concluded that it provides more even cooling of the myocardium, less need for postoperative inotropic support and temporary pacing [7, 17, 18], better preservation of myocardial cellular structures [19], improved left ventricular diastolic compliance after aortic valve replacement [10], and less depression of ventricular contractility [20]. Partington's group [4, 11] evaluated retrograde cardioplegia in canine models and found it superior to antegrade delivery in its maintenance of preferential subendocardial flow to muscle in jeopardy of ischemia while producing excellent left ventricular septal cooling. Noyez and colleagues [21] evaluated patients who underwent myocardial revascularization and found that when the left anterior descending artery was occluded, retrograde delivery was superior to combined delivery. However, Noyez and colleagues were unable to demonstrate better preservation of left ventricular myocardial function when the left anterior descending artery occlusion was not considered independently. Most important, both groups of patients had an excellent clinical outcome without distinction.

In animal models, studies [22, 23] comparing antegrade delivery of cardioplegic solution with retrograde delivery have demonstrated that, when the left anterior descending artery is occluded, there are improvements in tissue acidosis, fewer wall motion abnormalities, less myocardial necrosis, and better myocardial cooling with retrograde delivery systems. A similar study design was used by Misare and colleagues [24], who evaluated warm blood cardioplegia in swine and found improvements in global and ischemic-zone systolic function with retrograde delivery systems.

Although retrograde delivery of cardioplegic solution, used alone or in combination with antegrade delivery, has been demonstrated to be an effective and safe technique for myocardial preservation, its clinical importance has not been well demonstrated. In the previous small study, the immediate clinical outcome did not appear to be affected by the route of cardioplegia administration used in patients undergoing first-time myocardial revascularization [7].

The present study was not prospectively randomized and lacks sophisticated hemodynamic and statistical evaluations, but all patients were operated on consecutively and included all operative categories: elective, urgent, emergent/salvage, redo, and all risk groups. Patients were registered in the STS NCSDB and complied with the set definitions, allowing us to compare two groups of patients using univariate analysis. Also, the available preoperative predicted risk group model of the STS NCSDB enabled us to identify high risk (predicted operative mortality 10% and higher) for patients undergoing only coronary artery bypass grafting and use univariate analysis to identify the differences between these two higher risk groups. The observed lower ejection fraction in the s-R group should not cause clinical differences in spite of statistical significance. Also, some of the preoperative variables (history of cerebrovascular accident, redo status, intraaortic balloon, and nitroglycerin drips) may or may not play a role in the clinical outcome. Thermodilution data suggest that both routes of cardioplegia resulted in nearly identical postoperative left and right ventricular dynamic function, confirming that retrograde cardioplegia alone did not compromise right ventricular function as originally anticipated.

When the high-risk group of patients was analyzed, the s-R group had more patients in New York Heart Association functional class IV, had a lower ejection fraction, and required nitroglycerin drips more frequently preoperatively. The pump time was significantly longer in the AR group in spite of fewer number of grafts per patient. Postoperative creatine kinase-MB levels were higher in the s-R group but without any greater incidence of perioperative myocardial infarction. The number of patients in whom atrial fibrillation developed was also higher in group R. The occurrence of atrial fibrillation after operation is one of our major concerns, because it not only created an uncomfortable and annoying situation for the patients but also resulted in a potential increase in length of stay. Since 1993 after our clinical pathway had been implemented, ß-blockers have been used in most of the patients beginning on the evening of the operation, resulting in some decline in the incidence of postoperative atrial fibrillation. The causes of atrial fibrillation and the mechanism of its development after cardiopulmonary bypass are beyond the scope of this discussion.

In summary, good clinical results can be obtained in all patients who undergo routine coronary artery bypass grafting with or without valve replacement/repair using either retrograde cardioplegia alone or an antegrade/retrograde approach combined, regardless of the clinical status or severity index. The results appear to favor neither approach. In the retrograde groups, patients had higher predicted operative mortality, and the s-R subgroup had more patients in New York Heart Association functional class IV. Both R and s-R patients went through the operation without significant operative mortality or complications when compared with the antegrade groups. Retrograde cardioplegia alone has been shown to be effective for myocardial protection, but postoperative atrial fibrillation developed in more patients in this group, potentially leading to a longer length of hospital stay. The antegrade/retrograde approach offers a good immediate outcome, but this method could be cumbersome and confusing during the adjustments of the flow clamps for antegrade and retrograde delivery and could be the reason for prolonged pump time. From this study, it appears that retrograde cardioplegia alone provides as good myocardial protection and safety as the antegrade/retrograde approach in either routine or high-risk patients. However, this study is unable to conclude that either approach provides superior myocardial protection and safety to another, and a prospective, randomized study is encouraged for more conclusive results.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We thank Patricia Janey, RN, for her research efforts. It was her dedication and commitment that helped to make this project a success.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presented at the Forty-third Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 7–9, 1996.

Address reprint requests to Dr Arom, 920 E 28th St, Minneapolis, MN 55407.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Menasché P, Kucharski K, Mundler O, et al. Adequate preservation of right ventricular function after coronary sinus cardioplegia: a clinical study. Circulation 1989;80(Suppl 5):19–24.
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kit V. Arom Robert W. Emery Rebecca J. Petersen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arom, K. V. Articles by Bero, J. W. Search for Related Content PubMed PubMed Citation Articles by Arom, K. V. Articles by Bero, J. W.