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Ann Thorac Surg 1995;59:1141-1149
© 1995 The Society of Thoracic Surgeons
Divisions of Cardiovascular and Thoracic Surgery, Anesthesia, Intensive Care, Cardiology, and Biostatistics, University Hospital of Mont-Godinne (Catholic University of Louvain), Yvoir, Belgium
Accepted for publication January 24, 1995.
| Abstract |
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| Introduction |
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Besides the fact that the perioperative features of unstable angina need to be better understood, two main components of the surgical technique deserve further clarification: the extended use of arterial conduits and the myocardial protection techniques. Indeed, the techniques of myocardial protection seem to matter very much when dealing with cases of unstable angina [1, 8, 9]. Second, although arterial grafts have rarely been used in the setting of unstable angina [10, 11], it was suggested recently that the use of internal thoracic arteries (ITA) as grafts could be associated with a better hospital outcome than that associated with the use of venous conduits alone [1214].
The study described here was undertaken to analyze the factors associated with a poor hospital outcome, using as a primary end point postoperative mortality or the need for an intraaortic balloon pump (IABP). The influence on hospital survival of various techniques of myocardial protection and of an increased use of arterial conduits was evaluated specifically.
| Patients and Methods |
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Between January 1986 and February 1993, 474 patients undergoing aortocoronary bypass for unstable angina at our institution were included in the study. Sixty-eight patients required emergency myocardial revascularization within 24 hours of catheterization. The remaining 406 patients were referred for surgical treatment during the same hospitalization. Patients undergoing valvular replacement or ventricular septum closure were excluded from this study. Also excluded from consideration were patients requiring an emergency operation for the management of complications from percutaneous transluminal coronary angioplasty. However, patients suffering unstable angina after recent myocardial infarction were included. During the study period, an upward trend (p < 0.0001) was seen in the percentage of patients requiring an operation for unstable angina (from 17.4% in 1986 to 36.2% in 1992).
Diabetes was considered to be present if the patient was being treated with oral medications or insulin. Obesity was defined as weight 15% or more than that expected according to height. Hypertensive patients were included if the patient had a history of high blood pressure, if the blood pressure frequently exceeded 140/90 mm Hg, or if the patient was taking antihypertensive medications. Renal dysfunction was defined by a preoperative serum creatinine concentration of 2.0 mg/ 100 mL or more.
Braunwald's classification [15] was used to separate patients into meaningful subgroups. This grouping focuses on three aspects of angina: (1) the severity of the clinical manifestations (from class I to III); (2) the clinical circumstances in which unstable angina occurs (class A, secondary unstable angina; class B, primary unstable angina; class C, postinfarction unstable angina [within 2 weeks from the onset of myocardial infarction]); and (3) the intensity of treatment (1, minimal therapy; 2, oral therapy; 3, maximally tolerated doses of antiischemic drugs, including intravenously administered nitroglycerin).
The coronary scoring system described by Leaman and colleagues [16] was applied to assess the extent of underlying coronary artery disease. Briefly, this system is based on the severity of the luminal diameter narrowing (taking into account a luminal diameter reduction of more than 70%) and is weighted according to the usual flow to the left ventricle in each coronary vessel. The resultant number indicates the overall severity of the obstructive coronary artery disease.
A perioperative myocardial infarction was defined as the appearance of a new Q wave on the electrocardiogram or a concentration of creatine kinasemyocardial band of at least 10%, or both findings. Hospital mortality was defined as death occurring either while the patient was in the hospital or, if the patient was discharged from the hospital, within 30 days of the operation.
Anesthesia and Surgical Procedure
A peripheral line and an arterial line were placed with the patient under local anesthesia. General anesthesia was achieved with fentanyl citrate (25 µg/kg) and pancuronium bromide (Pavulon; Organon, West Orange, NJ) (0.1 mg/kg). A Swan-Ganz thermodilution catheter was introduced percutaneously through the internal jugular vein. Cardiac output was measured with a cardiac output computer (Hellige, Freiburg im Breisgau, Germany). The results were rendered as a mean of three consecutive recordings. The aorta was cannulated in the standard fashion. Ascending aorta venting was performed through a catheter with a Y connector to the cardioplegic line. Cardiac drainage was realized through the atrial appendage using a No. 34 two-stage cavoatrial catheter (USCI Division of C.R. Bard, Billerica, MA). The cardiopulmonary bypass system was primed mainly with crystalloids and occasionally with banked blood to maintain a hematocrit value above 20%. The extracorporeal circulation was performed with a heart-lung machine (model 10-00-00; Stöckert Instrumente, Munich, Germany) using a membrane oxygenator. All distal anastomoses were done during a single interval of aortic cross-clamping; the aortic anastomoses were done during tangential aortic cross-clamping, while the heart was kept in the empty beating state. Moderate hemodilution (hematocrit, 20% to 25%) and systemic hypothermia (25° to 28°C) were maintained during cardiopulmonary bypass. Multidose cold nonoxygenated crystalloid cardioplegia was administered antegradely in 375 patients and retrogradely in 99 patients. Cold blood cardioplegia was introduced into use at our institution in December 1989 and its use was favored in the severe cases (117 patients). This method has been described elsewhere [17]. Briefly, the cardioplegic delivery system consists of disposable tubing to deliver blood and crystalloid cardioplegia at a 4:1 ratio (HE 100 heat exchanger; American Bentley Hospital Supply, Irvine, CA). The tubing was attached to a coronary cardioplegic adapter containing four limbs that allows simultaneous distribution of the cardioplegic solution into the aorta and the vein grafts (CDS-004; Research Medical, Midvale, UT). Thus, in the present study, blood cardioplegia was administered antegradely. The composition of the solution was as follows: Na, 138.9 ± 0.9 mEq/L; K, 8.5 ± 0.5 mEq/L; Ca, 7.0 ± 0.2 mEq/L; and HCO3, 19.3 ± 0.3 mEq/L. The following conditions were maintained in the blood cardioplegia: osmolarity, 305.2 ± 2.0 mOsm/L; pH, 7.34 ± 0.01; hemoglobin, 6.1 ± 0.4 g/100 mL; hematocrit, 0.17 ± 0.01; oxygen partial pressure, 248.3 ± 31.6 mm Hg; and carbon dioxide partial pressure, 33.1 ± 1.0 mm Hg. The temperature of the perfusate was 8.0° ± 0.3°C and the temperature of the septum was maintained at 11.1° ± 0.7°C. After each distal anastomosis the solution was infused through a roller pump into the aortic root at a rate of 250 mL/min over 2 minutes.
At five defined points, the cardiac index, left ventricular stroke work index, right ventricular stroke work index, systemic vascular resistance, and pulmonary vascular resistance were evaluated. The five defined points were before aortic cannulation (pericardial incision), at the end of operation after reversal of the heparin effects and before sternal closure, and at the arrival of the patient in the intensive care unit, 4 hours later, and 12 hours later.
Data Analysis
Perioperative data were collected and entered prospectively into the cardiovascular surgery clinical research database by the surgeon in charge of the patient. Values are presented as the mean ± the standard error of the mean. Two-way analysis of variance with repeated measurements was used for comparisons between groups at specific points in time. Values of p were obtained for the overall group effect, overall time effect, and grouptime interaction. Other clinical data were compared by the two-sample t test,
2 test, or Fisher's exact test when appropriate. Linear tests of trend over surgical year category were done using the test proposed by Cochran. One-way analysis of variance was performed to analyze the effect of one qualitative factor on one response variable. Between-group differences were then compared by Scheffé's test. Multivariate analysis of the prediction of adverse outcome was performed by logistic regression, with backward selection of variables using the Wald test at the 0.05 level. Cardiopulmonary bypass time was deleted from the multivariate analysis because it correlated strongly with the cross-clamp time. Because logistic regression analysis requires that all variables be present for each patient, we could not include factors that were frequently missing. For example, ejection fraction, which was usually available for patients in stable conditions, was often not determined in patients in an unstable condition because of the increased risk associated with left ventricular angiography in such circumstances. Therefore we used the dichotomous variable reduced ventricular function if the left ventricular ejection fraction was shown to be less than 0.40 by angiographic or isotopic means, or if left ventricular contractility appeared to be severely reduced at the time of direct surgical examination. Statistical analysis was performed with use of the SPSS (SPSS, Chicago, IL) and Datasim (Desktop Press, Lewiston, ME) software packages.
| Results |
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The breakdown of patients into subgroups of unstable angina classified according to the Braunwald groupings is given in Table 1
. A history of remote myocardial infarction was present in 180 patients (38.0%), whereas recent preoperative myocardial infarction (within 6 weeks of operation) had occurred in 120 patients (25.3%). Recent myocardial infarction was transmural in 24 patients and fibrinolysis was attempted in 69. Coronary operation was performed 14 days on average after a recent myocardial infarction. Ninety-six patients (20.3%) were treated for acute coronary insufficiency in the intensive care unit. Twelve patients (2.5%) experienced at least one episode of ventricular fibrillation and 24 patients (5.1%) were in cardiogenic shock. Twenty-seven patients (5.7%) required an IABP to achieve anginal relief (19 patients) or hemodynamic stabilization (8 patients) before urgent revascularization.
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Patients undergoing exclusive saphenous vein grafting, or single or bilateral internal thoracic arterial grafting were compared with regard to their operative risk factors (Table 2
). Those having no arterial grafting were clearly at greater risk by virtue of the severity of their angina class, their coronary score, the finding of a reduced ejection fraction, the need for an IABP preoperatively, and transfer from the intensive care unit. Likewise, there were considerable differences in the risk characteristics associated with the two myocardial protection techniques (Table 3
). Indeed patients undergoing cardiopulmonary bypass under cold blood cardioplegia were significantly older, more frequently needed intravenously administered nitrates, had more diffuse coronary artery disease, and had a lower ejection fraction.
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| Comment |
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The focus of the present work was to identify the factors predictive of adverse major outcomes characterized by ventricular failure requiring insertion of an IABP or complicated by hospital death. Indeed, the combination of hospital mortality and the need for an IABP as a dependent variable leaves no room for subjectivity, and is strongly associated with a severe low-output syndrome.
The duration of aortic cross-clamping was the principal predictive factor, which partly corroborates the findings of Naunheim and associates [3] who demonstrated that the cross-clamp time was a predictor of hospital death and low-output syndrome in univariate analysis, but not in multivariate analysis. The fact that the global ischemic time remains the most important intraoperative variable in predicting a major adverse outcome raises the question of the adequacy of myocardial protection techniques. Patients with unstable angina represent the most extreme challenge in terms of intraoperative myocardial protection. Cold blood cardioplegia reduced the morbidity and mortality in patients undergoing urgent coronary artery bypass grafting for unstable angina, as was demonstrated by Teoh [1] and Christakis [9] and their associates. In a group of patients undergoing emergency surgical procedures for acute coronary occlusion, Beyersdorf and colleagues [19] showed that improved techniques of myocardial protection, including warm blood cardioplegic induction, multidose cold blood cardioplegia for maintenance, and controlled reperfusion, resulted in a decrease in the overall mortality despite an increased number of risk factors [19]. In our series, cold blood cardioplegia was administered predominantly to high-risk patients. Furthermore, techniques of warm induction and warm reperfusion, which have been shown to be advantageous in patients at high risk [19], were not used in these patients. Given the aforementioned limitations, analysis failed to show that the myocardial protection techniques had any influence on outcome in the overall group of patients. Nevertheless, some improved techniques of myocardial protection not currently in general use may be effective in further reducing morbidity and mortality in patients with unstable angina undergoing coronary artery bypass grafting, and are currently being investigated. These include continuous cold blood retrograde coronary sinus perfusion and warm reperfusion.
Hemodynamic data obtained from patients undergoing coronary artery bypass grafting for the treatment of unstable angina are not available. In our study, only the left ventricular stroke work index and pulmonary vascular resistance differed significantly among the groups. Interestingly these hemodynamic changes existed before the start of cardiopulmonary bypass. The more frequent preoperative occurrence of compromised left ventricular function and cardiogenic shock in the poor outcome group, as demonstrated by univariate analysis, probably explains these observations. Moreover, Leung and associates [20] demonstrated by continuous transesophageal echocardiographic monitoring that up to 20% of such patients have episodes of wall motion abnormalities indicating myocardial ischemia during the prebypass period.
The suitability of the ITA conduit for use in emergency situations is not uniformly accepted. Indeed, concerns about early reperfusion and adequacy of flow have rendered ITA an unacceptable choice for revascularization in the minds of many surgeons. Therefore, according to previous publications, arterial grafts have rarely been used in the setting of unstable angina [10, 11]. Conversely, it was demonstrated recently that ITA conduits were associated with a significant improvement in operative mortality compared with the operative mortality observed for the use of venous conduits alone [14, 21]. In patients undergoing emergency coronary artery bypass grafting, use of the ITA was not associated with an increase in complications [22], and it was even shown that nonuse of the ITA was among the predictors of operative mortality [12] and low-cardiac output [13]. Our findings confirm that the use of a single or bilateral ITA is not associated, as an independent risk factor, with an increased incidence of a major adverse outcome. However, despite the fact that the results of univariate analysis suggest that a ``protective'' effect was conferred by single ITA bypass grafts (Appendix 1), this is not confirmed by multivariate analysis. Indeed, when preoperative risk factors are correlated with the technique of revascularization (see Table 2
), the resultant distribution shows the saphenous vein group to be adversely affected. We admit that an apparent ``superiority'' of arterial grafting from the standpoint of short-term survival may be explained by the surgeon selecting a less complex procedure for the worst cases in an attempt to shorten the aortic cross-clamp time and reduce the operative mortality.
Thus, during the study period we observed a gradual reduction in the need for an IABP, which contrasted with a constant operative mortality rate. The aortic cross-clamp time was the main determinant of postoperative outcome, which implies that the techniques of myocardial protection currently used need to be improved. More importantly, the increased use of arterial grafts was not found to have an adverse effect on early outcome.
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| Footnotes |
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| References |
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