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Ann Thorac Surg 2004;78:1604-1609
© 2004 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, The Cardiothoracic Centre Liverpool, Liverpool, United Kingdom
b Department of Research and Development, The Cardiothoracic Centre Liverpool, Liverpool, United Kingdom
Accepted for publication April 27, 2004.
* Address reprint requests to Dr Fabri, The Cardiothoracic Centre-Liverpool, Thomas Dr, Liverpool L14 3PE, UK
brian.fabri{at}ctc.nhs.uk
Presented at the Poster Session of the Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 2628, 2004.
| Abstract |
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METHODS: Between April 1997 and September 2002, 951 consecutive diabetic patients underwent isolated coronary artery bypass grafting. A total of 186 (19.6%) of these patients had off-pump coronary procedures. Multivariate logistic regression was used to assess the effect of off-pump coronary procedures on adverse in-hospital outcomes, while adjusting for patient and disease characteristics by constructing a propensity score from core patient characteristics. The propensity score was the probability of receiving off-pump coronary operation, with a C-statistic of 0.81, and was included along with the comparison variable in a multivariable analysis of outcome. All analysis was performed retrospectively.
RESULTS: Off-pump patients were more likely to be obese (p = 0.032), have left main stem stenosis (p = 0.034), and have undergone prior cardiac operation (p = 0.027). The off-pump group had fewer patients with three-vessel disease compared with the on-pump group. After risk adjusting with propensity score, off-pump patients had a significantly lower incidence of stroke (adjusted odds ratio 0.15; p = 0.039) and renal failure (adjusted odds ratio 0.38; p = 0.036). Off-pump patients also required less blood transfusion (p < 0.001) and had shorter lengths of stay (p < 0.001).
CONCLUSIONS: Off-pump coronary operation in diabetic patients significantly reduced postoperative morbidity and length of stay compared with on-pump coronary operation, although no in-hospital survival difference was noted between the two groups.
| Introduction |
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Off-pump CABG has now emerged as an established technique with particular benefits in various high-risk groups [11]. Ngaage [11], in his excellent review on off-pump CABG, documented evidence in the literature favoring the technique in high-risk groups such as individuals with recent acute myocardial infarction and impaired left ventricular function, preoperative renal impairment, chronic obstructive airways disease, and in elderly patients. Previous reports from our institution have shown that off-pump operation is associated with decreased neurologic events after CABG [12]. Other reported favorable outcomes include a reduced need for postoperative ventilatory support [13], less requirement for blood products [14], and a reduced length of hospital and intensive care unit (ICU) stay [15].
The goal of this study was to describe our experience with diabetic patients as a specific high-risk subgroup and analyze the role of off-pump techniques when compared with diabetic patients treated using conventional CABG in terms of mortality and postoperative morbidity.
| Material and Methods |
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A total of 186 (19.6%) diabetic patients underwent off-pump CABG, performed consecutively by 3 of the 7 surgeons at our institution. Any conversions to cardiopulmonary bypass (CPB) were classified as off-pump cases based on "intention-to-treat" analysis (2 cases were converted).
Data Collection
Preoperative definitions and data collection methods have been published previously [17]. Preoperative (Table 1) and postoperative (Table 2) data were collected prospectively during the patient's admission as part of routine clinical practice and entered into our cardiac surgery registry. Additional data on the use of CPB, number of grafts, and the amount of blood loss in the ICU were also collected.
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Statistical Analysis
Continuous variables are shown as median with 25th and 75th percentiles and categorical variables are shown as a percentage. Comparisons were made with Wilcoxon rank sum tests and
2 tests as appropriate. Standard statistical tests were used to calculate odds ratios (OR) with 95% confidence intervals (CI). The Parsonnet risk score and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) were derived to assess differences in patient case mix between off-pump and on-pump patients [19, 20]. Logistic regression was used to adjust in-hospital outcomes for differences in patient and disease characteristics (treatment selection bias) [21].
Treatment selection bias was controlled for by constructing a propensity score [22]. The propensity score was the probability that a patient would receive off-pump coronary operation, and was constructed from the variables (age, sex, body mass index, ejection fraction, extent of disease, left main stem stenosis, urgency of operation, prior cardiac operation, respiratory disease, renal dysfunction, peripheral vascular disease, and insulin-dependent diabetes) recommended by the American Heart Association and the American College of Cardiology guidelines for risk-adjusting outcomes after CABG [8] and the EuroSCORE. The C-statistic for this model was 0.81 [23]. Once the propensity score is constructed for each patient, the score can be used three ways for comparisons: matching, stratification, and multivariable adjustment. Because of the small sample size available, we decided to use multivariable adjustment because matching would have reduced the study size even further and stratification can be difficult to interpret. The propensity score was then included along with the comparison variable (off-pump or on-pump) in multivariable analyses of outcome producing adjusted OR with 95% CI as shown in Table 3. The propensity score adjusts for the treatment selection bias, which is evident in Table 1, between one group and the other (eg, extent of disease, left main stem stenosis, and prior cardiac operation). Using a propensity score as the sole means for adjusting outcomes was preferable due to the low number of events in our study and provides better adjustment for those factors driving treatment selection; the overall effect is more complete risk adjustment [22]. In all cases p < 0.05 was considered significant. All statistical analysis was performed retrospectively with SAS 8.2 (SAS Institute, Cary, NC).
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| Results |
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The median number of grafts used in the off-pump patients was three (25th and 75th percentiles: 3 to 3) compared with a median of four grafts (25th and 75th percentiles: 3 to 4) for the on-pump patients (p < 0.001).
Crude Outcomes
Off-pump patients were more likely to have a shorter postoperative length of stay (median 7 days; 25th and 75th percentiles: 6 to 9) compared with on-pump patients (median 8 days; 25th and 75th percentiles: 7 to 11; p < 0.001). This significant finding remained the same when examining the proportion of patients staying longer than 7 days after the operation (Table 2).
Table 2 shows that off-pump patients were also less likely to require red blood cell transfusion (p < 0.001) and to stay longer than 3 days in the ICU (p = 0.004). Off-pump patients were less likely to have postoperative stroke; however, this difference failed to reach statistical significance (0.5% versus 3.0%; p = 0.051).No association was noted between avoiding CPB and in-hospital mortality, renal failure, sternal wound infection, reexploration for bleeding, and perioperative myocardial infarction in the univariate analysis (Table 2).
Risk-Adjusted Outcomes
Table 3 shows postoperative data adjusted for the propensity score. After adjusting for the propensity score, the incidence of postoperative stroke was significantly lower in patients receiving off-pump coronary operation (adjusted OR 0.15; 95% CI 0.02 to 0.96; p = 0.039).
Postoperative renal failure was also significantly lower in the off-pump group (adjusted OR 0.38; 95% CI 0.16 to 0.94; p = 0.036). After removing 43 patients who had preoperative mild or severe renal dysfunction (defined as patients with preoperative creatinine > 130 mmol/L or on dialysis support), 175 off-pump patients and 733 on-pump patients were still available for further analysis. Among these patients we noted a trend toward less postoperative renal failure when avoiding CPB (adjusted OR 0.37; 95% CI 0.13 to 1.08; p = 0.069; data not shown). After risk adjustment, off-pump patients still had significantly shorter lengths of ICU and postoperative hospital stay and required less blood transfusion.
| Comment |
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Risk factor management of patients with coronary artery disease is undergoing a conceptual change. Factors like glucose intolerance, hypertension, and hypercholesterolemia are now treated as part of a single metabolic syndrome with considerable overlap and cross-influence. The term metabolic syndrome has been defined by the Adult Treatment Panel III of the National Cholesterol Education Program [4] as the presence of three of the following five variables: abdominal adiposity, fasting hyperglycemia, low high-density lipoprotein concentration, high triglyceride levels, and hypertension. By this definition, even patients without overt diabetes are recommended to be treated for insulin resistance and risk factor modification to decrease the probability of the development of coronary artery disease and type II diabetes.
From a cardiac surgical point of view, it is important to consider type II diabetes not as a single comorbidity but as one end point of a metabolic syndrome and hence a far more advanced stage in this systemic illness than previously considered. Patients with type I diabetes behave differently in terms of disease development and have a high risk of coronary artery disease and arteriosclerosis usually further complicated by a relatively silent presentation. In general, patients with diabetes have higher risk of arteriosclerosis, impaired fibrinolysis, stroke, and renal impairment than individuals without diabetes. Coronary artery disease contributes up to 80% of the excess mortality among patients with type II diabetes.
In this study, we showed that diabetic patients undergoing off-pump CABG had a significantly reduced incidence of cerebrovascular events and renal dysfunction in the immediate postoperative period when compared with diabetic patients undergoing conventional on-pump CABG. Other advantages include a reduction in the need for blood transfusion and shorter ICU and postoperative lengths of stay.
Several studies have identified CPB as an independent predictor of impaired cognitive brain function and adverse neurovascular events after CABG [12, 2428]. We have shown previously that CPB, older age at operation, and a history of peripheral vascular disease are significant predictors for postoperative stroke [12]. Newman and associates [25] in their prospective study concluded that diabetes along with age, previous cerebrovascular accident, history of peripheral vascular disease, redo CABG, and unstable angina were independent significant predictors of postoperative neurologic complications. Notably, in this report all the above risk factors were found significantly more often in the off-pump patients who were therefore at higher risk of postoperative neurologic events.
Good evidence in the literature suggests that off-pump operation provides some renal protection [2931]. Ascione and associates published two papers on renal outcomeone a randomized control trial involving 50 patients assigned to either off-pump or conventional on-pump CABG [29] and the other a retrospective study comparing both surgical techniques in patients with preoperative nondialysis-dependent renal dysfunction [30]. Both reports demonstrated a protective effect with off-pump CABG when compared with the on-pump technique. A recent study by Stallwood and colleagues [31] at our own institution also showed the benefits of off-pump operation with respect to renal failure, with patients being treated with CPB being 2.6 times more likely to develop the complication.
Renal dysfunction after CABG is multifactorial and usually attributed to use and duration of CPB, nonpulsatile flow, hypothermia, perioperative cardiovascular compromise, and toxic and free radical injury to the kidney. Off-pump operation eliminates CPB, nonpulsatile flow, and hypothermia. Toxic (tumor necrosis factor-alpha, interleukins, etc) and free radical release are a result of the systemic inflammatory response to CPB. Studies have also shown CPB is associated with levels of activated complement factors, interleukin 6 and 8, tumor necrosis factor-alpha, elastase, and markers of endothelial injury [30].
Diabetes as a systemic illness with a huge inflammatory component can be presumed to have a significant derangement after CPB. Nevertheless, this experience shows that the renal protection offered by avoiding CPB also extends to diabetic patients.
Our literature search identified only one report assessing off-pump or on-pump coronary grafting in diabetic patients. Magee and colleagues [32] concluded that although no survival advantage was noted for diabetic patients undergoing off-pump CABG, they had a significantly decreased incidence of prolonged ventilation, blood product usage, atrial fibrillation, and renal failure requiring dialysis. We have similarly shown decreased blood product usage and renal failure. Ventilation time was also shorter in the off-pump group, just failing to reach statistical significance. The main criticism of Magee's study is that it involved 22 different surgeons with different selection criteria, in different institutions over a 5-year period. We have a far smaller but comparable group, with only 7 surgeons from one institution, therefore minimizing any bias accrued by institutional differences.
It is important to note that the need for blood transfusion is a relatively subjective outcome and interpretation can depend in large part on protocols for blood conservation and anticoagulation. A more robust outcome would be the amount of blood loss in the ICU; in our study such blood loss was significantly lower in the off-pump group compared with the on-pump group (590 mL versus 670 mL; p = 0.005).
Some limitations, which may affect the conclusions drawn from this study, must be noted. First, this study was observational and by its retrospective nature could not account for the unknown variables affecting the outcomes that were not correlated strongly with the variables used in the risk adjustment. Second, the study period was long, slightly more than 5 years, with most patients on CPB being from the early part of the study period, whereas most patients in the off-pump group were from the later part of the study period. Also, the off-pump patients included patients undergoing operation during the "learning curve" for the surgeons, perhaps indicating a degree of selection bias. Perhaps one of the most important limitations was inextricable confounding [22] caused by the off-pump procedures being performed completely by 3 of the 7 surgeons. Even after careful application of multivariate logistic regression analysis and propensity scores, distinguishing between surgeon and treatment differences remains difficult.
Another limitation was the fact that we have not examined long-term outcomes. The incidence of adverse events is important but has to be evaluated in relation to other outcomes such as freedom from angina and the need for repeat revascularization. These outcomes will be of interest as follow-up accrues.
We conclude that off-pump CABG in diabetic patients is as safe as conventional on-pump operation in terms of early survival. When compared with CABG with CPB, off-pump operation in this group of high-risk patients significantly decreases the incidence of postoperative stroke, renal impairment/failure, and the need for blood transfusion, resulting also in reduced ICU and hospital lengths of stay.
| Acknowledgments |
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| References |
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