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CARDIOVASCULAR ANESTHESIA

Off-Pump Versus On-Pump Coronary Artery Bypass Surgery and Postoperative Renal Dysfunction

Cardiothoracic Division, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina

Address correspondence and reprint requests to Mark Stafford-Smith, FRCPC, Department of Anesthesia, Box 3094, Duke University Medical Center, Durham, NC 27710. Address e-mail to staff002{at}mc.duke.edu

	Abstract

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Renal dysfunction is a serious complication after coronary bypass surgery with cardiopulmonary bypass (CABG). Because duration of cardiopulmonary bypass (CPB) is associated with renal outcome, it has been proposed that avoidance of CPB with off-pump coronary bypass (OPCAB) may reduce perioperative renal insult. We therefore tested the hypothesis that OPCAB is associated with less postoperative renal dysfunction compared with CABG surgery. With IRB approval, we gathered data for 690 primary elective coronary bypass patients (OPCAB, 55; CABG, 635). Perioperative change in creatinine clearance (DCrCl) was calculated by using preoperative (CrPre) and peak postoperative (CrPost) serum creatinine values, and the Cockroft-Gault equation (DCrCl = CrPreCl - CrPostCl). Univariate and linear multivariate tests were used in this retrospective analysis; P < 0.05 was considered significant. Multivariate analysis did not identify OPCAB surgery as an independent predictor of DCrCl. However, previously reported associations of PreCrCl, age, and diabetes with DCrCl were confirmed. Power analysis demonstrated an 80% power to detect a 7.0 mL/min DCrCl difference between study groups. In this retrospective study, we could not confirm that OPCAB significantly reduces perioperative renal dysfunction compared with CABG surgery. Our findings suggest that reduction of renal risk alone should not be an indication for OPCAB over CABG surgery.

Implications: Retrospective analysis did not identify any significant difference in perioperative change in creatinine clearance after coronary revascularization with cardiopulmonary bypass compared with off-pump coronary surgery.

	Introduction

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Perioperative renal dysfunction is a significant complication of cardiac surgery, associated with major increases in morbidity, mortality, and cost. Acute renal insufficiency is reported to occur after 8% to 30% of cardiac operations performed with cardiopulmonary bypass (CPB) and is associated with mortality rates varying from 7% to 38% (1–5). When acute renal failure after CPB requires dialysis, as occurs in up to 2% of coronary bypass surgery patients, mortality rates exceed 60% (1–5). This is in marked contrast to the 1% to 2% mortality rate observed in patients whose cardiac operation is not complicated by acute renal impairment (1–5). Therefore, strategies that diminish or minimize renal insult after cardiac surgery are important because they may improve overall outcome.

Recently, we have demonstrated that duration of CPB is independently associated with the development of acute postoperative renal insufficiency and renal failure requiring dialysis (5). With the revival of interest in performing coronary artery bypass grafting (CABG) without CPB (6), there has been speculation that off-pump coronary artery bypass (OPCAB) may reduce perioperative renal insult (7). Studies examining early postoperative renal injury markers in small patient groups suggest that OPCAB is associated with less renal dysfunction than coronary artery bypass surgery with CPB (CABG) (8,9). However, these studies do not evaluate peak in-hospital postoperative renal impairment, a variable that has been associated with overall outcome after cardiac surgery in large patient groups (4,5). We therefore used estimated creatinine clearance, a validated measure of renal function in critically ill and postcardiac surgical patients (10,11), to test the hypothesis that OPCAB surgery is associated with a reduction in peak postoperative renal dysfunction compared with CABG with CPB.

	Methods

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After IRB approval, demographic, intraoperative, and renal data were obtained from the prospectively gathered Duke Cardiothoracic Surgery database for all primary elective OPCAB and CABG surgery patients between September 29, 1998, and June 14, 1999, a period including the first 55 OPCAB procedures performed at the study institution. OPCAB procedures included the administration of small-dose heparin, use of a myocardial stabilization device, and placement of a "sidebiter" clamp on the ascending aorta for attachment of proximal vein grafts. CABG procedures included large-dose heparin, hypothermic CPB (between 25° and 32°C nasopharyngeal temperature) using a Cobe CML membrane oxygenator^TM (Cobe Laboratories, Lakewood, CO), Sarns 7000 MDX pump^TM (Sarns Inc, Ann Arbor, MI), and a Pall SP 3840^TM (Pall Biomedical Products Co, Glencove, NY) 40-µm arterial line filter.

Demographic variables gathered for each patient were chosen with reference to previously reported renal risk factors (4,5), including sex, age, weight, history of diabetes requiring medication, preoperative serum creatinine (CrPre), duration of CPB, preoperative left ventricular ejection fraction, number of vessels grafted, perioperative angiography with contrast dye, and use of an intraortic balloon pump (IABP) postoperatively. In addition, a Hannan Risk Score (12) was used for each patient as a marker of preoperative risk. Components of the Hannan score include age, sex, obesity, ejection fraction, previous myocardial infarction, chronic obstructive lung disease, dialysis, diabetes, history of failed angioplasty, history of previous IABP, previous cardiac surgery, unstable angina, cardiogenic shock, and congestive heart failure. Exclusion criteria were chronic dialysis and the presence of an IABP preoperatively.

Preoperative and daily in-hospital postoperative serum creatinine assessments per institutional routine were evaluated to identify preoperative and peak in-hospital postoperative values. CrPre was defined as the value recorded closest to surgery, but not within 24 h of the procedure. Peak serum creatinine (CrPost) was the highest of the daily in-hospital postoperative values. The Cockroft-Gault equation (13) was selected as the most consistently favored algorithm to calculate pre- and postoperative creatinine clearance (10,11,13–16).

For men:

For women:

Units are weight (kgs), age (yrs), serum Cr (mg/dL; 88.4 µmol/L = 1 mg/dL). Perioperative change in creatinine clearance (DCrCl) was calculated as the difference between these values (DCrCl = PreCrCl - PostCrCl).

Univariate comparisons of demographic variables between CABG and OPCAB groups were made by using Student’s t-tests. The association of OPCAB with DCrCl was then examined by using a linear regression multivariate analysis. Covariates considered for inclusion in the multivariate model were the following: age, sex, weight, duration of bypass, carotid bruit, number of grafts, ejection fraction, perioperative angiography with contrast dye, and history of hypertension, diabetes requiring medication, chronic angiotensin converting enzyme inhibitor use, chronic obstructive pulmonary disease, or congestive heart failure. These variables were entered into a backward selection model along with group (OPCAB or CABG) and PreCrCl. Significant variables were retained in the model. Because of the potential for nonnormal distribution of CrCl values and to assess generalizability and robustness of results, these analyses were then repeated on ranked data; P < 0.05 was considered significant.

	Results

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Demographic and renal data were collected for all OPCAB (n = 55) and CABG (n = 635) patients during the study. Demographic variables among the 690 patients were similar to those previously reported in large populations (4); data were presented as mean ± SD. Nineteen patients were excluded from the study (dialysis: 8, IABP: 11).

Univariate analysis demonstrated no significant differences between OPCAB and CABG patients with the exception of age (60.2 ± 12.9 vs 63.3 ± 10 yr; P = 0.04), number of grafts (1.72 ± 0.74 vs 3.10 ± 0.82; P = 0.0001), and perioperative angiography with contrast dye (25.0% vs 0.31%; P = 0.001) (Table 1). It should be noted that the first 14 OPCAB surgery patients received intraoperative angiography with contrast dye to assure graft patency as part of a planned introduction to this procedure. Mean CPB duration in the CABG group was 108.1 ± 65.6 min. Two patients in the OPCAB group converted to CPB (mean CPB 61 ± 86.3 min). For the purpose of analysis, these patients were included in the OPCAB group.

	Discussion

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OPCAB surgery is an approach to myocardial revascularization that eliminates the need for extracorporeal circulation; reports of equivalent surgical outcomes to CABG have stimulated interest in the potential for improved myocardial, neurologic, and renal outcome with avoidance of CPB (17–20). The results of two small studies with inconclusive findings have led to speculation that OPCAB may reduce postoperative renal insult. In a prospective, randomized trial of 50 patients, Ascione et al. (9) demonstrated a slightly greater decrease in 24-hour postoperative creatinine clearance with CPB compared with OPCAB. However, there was no significant difference between pre- and postoperative renal function in either study group. In a second prospective study of 24 patients, Loef et al. (8) demonstrated a marginally greater increase in markers of glomerular and tubular damage (i.e., N-acetylglucosaminidase, fractional excretion of sodium, and microalbuminuria) after on-pump versus off-pump surgery. Similarly, these differences were not statistically significant. It is important to note that neither study evaluated maximum postoperative impairment of renal filtration function, a variable that has been associated with overall outcome after cardiac surgery (4,5). The findings of our study therefore do not conflict with these reports; however, we conclude from our data that if a difference in renal outcome exists between OPCAB and CABG procedures, it is small and may not be significant.

The pathophysiology of renal dysfunction after CPB continues to be the focus of much clinical and basic science research. Several studies have demonstrated a relationship between postoperative renal dysfunction and the duration of CPB (4,5). Thus, it would seem logical that OPCAB surgery, by avoiding this renal risk, would improve outcome for patients with preoperative renal insufficiency. However, the avoidance of CPB by using current OPCAB techniques may introduce new factors that pose a comparable risk of renal insult. Conditions unique to the OPCAB procedure that may contribute to renal dysfunction include routine intraoperative use of vasoactive drugs, disturbances related to cardiac distortion (i.e., hypotension, low cardiac output), perioperative angiography with contrast dye, and intraoperative normothermia. These factors may confound analysis of reduced renal function related to the presence or absence of CPB. Perioperative imaging with contrast dye administration occurred in 14 of the 55 OPCAB patients. Because contrast dye is a nephrotoxin in other settings (21), this intervention may be expected to influence renal outcome. However, we found that this variable was not an independent predictor in our multivariate analysis. In addition, a univariate comparison of OPCAB patients that did and did not receive perioperative coronary artery imaging demonstrated no difference in postoperative reduction in creatinine clearance (-16.8 vs -16.7 mL/min, respectively; P = 0.98).

The use of retrospective data for our study presents some analytical limitations. Anesthesia was managed per the attending anesthesiologist’s preference; use of drugs with renal effects (e.g., IV dopamine, furosemide) was not regulated; however, 50 g of 20% mannitol solution was routinely added to the CPB circuit priming solution. Another limitation of this study is the restricted conclusions regarding the overall integrity of the kidney that can be drawn from a single study, such as creatinine clearance. Creatinine clearance is an adequate test of renal filtration function, but does not address the numerous other homeostatic roles of the kidney, including production and release of several enzymes and hormones, regulation of osmolality, electrolyte and acid/base status, and excretion of metabolic endproducts and toxins. In addition, the study population represents the first 55 OPCAB patients at the study institution; although graft patency results were of sufficient quality to obviate the need for intraoperative angiography after the first 14 patients, a period of learning through the introduction of the OPCAB procedure is common (22) and may have influenced renal outcome. Also, the selection process for OPCAB versus CABG surgery candidates (i.e., only patients with suitable coronary artery lesions were offered OPCAB) may have introduced bias not accounted for in the multivariate analysis; however, the results of the Hannan score for each group demonstrate a similar level of preoperative risk between the two groups (see Table 1). Finally, the size of our study population provides an 80% confidence that an 8% difference in PostCrCl values would be demonstrated. It is possible that a smaller difference in renal insult between groups would not be detected by our study. The clinical significance of small differences in renal insult in this setting is not well understood. Therefore, the data we report suggesting that OPCAB surgery does not offer major reduction in renal risk should be confirmed with a large, prospective, controlled trial that examines both renal function and overall outcome.

In summary, our study suggests that OPCAB surgery does not confer major protection from postoperative renal impairment compared with CABG surgery with CPB. Although there is continued interest in developing strategies that minimize renal insult, these data suggest that the reduction of renal risk alone should not be used as an indication for OPCAB over CABG surgery.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999