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Right arrow Minimally invasive surgery

Ann Thorac Surg 2005;80:2148-2153
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Renal Dysfunction in High-Risk Patients After On-Pump and Off-Pump Coronary Artery Bypass Surgery: A Propensity Score Analysis

Andrew Chukwuemeka, MD, FRCS a , Ashley Weisel, BS a , Manjula Maganti, MS a , A. Franka Nette, MD a , Duminda N. Wijeysundera, MD b , William S. Beattie, MD b , Michael A. Borger, MD, PhD a , *

a Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
b Department of Anesthesia, Toronto General Hospital, and University of Toronto, Toronto, Ontario, Canada

Accepted for publication June 7, 2005.

* Address correspondence to Dr Borger, Toronto General Hospital, 200 Elizabeth St, 4N-451, Toronto, Ontario, Canada, M5G 2C4 (Email: michael.borger{at}uhn.on.ca).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Cardiopulmonary bypass may be a causal factor in the development of renal impairment after cardiac surgery. When acute renal failure requiring dialysis occurs after cardiac surgery, it is associated with high mortality. We attempted to determine whether off-pump coronary artery bypass grafting surgery prevents postoperative renal dysfunction in patients at high risk for renal failure.

METHODS: Retrospective analysis identified 2,869 patients who had preexisting renal dysfunction (preoperative creatinine clearance less than 60 mL/min) and who underwent isolated coronary artery bypass grafting between 1995 and 2003. Patients who required preoperative dialysis were excluded. Propensity scores were computed to match off-pump coronary artery bypass surgery patients 3:1 with those who underwent conventional coronary artery bypass grafting surgery, and the independent predictors of postoperative renal dysfunction were determined.

RESULTS: Two thousand seven hundred eleven patients with preexisting renal dysfunction underwent conventional coronary artery bypass grafting surgery, and 158 patients underwent coronary artery bypass grafting surgery without cardiopulmonary bypass (off-pump coronary artery bypass grafting surgery group). The matched groups showed no differences in any of the preoperative or postoperative variables examined. Diabetes (odds ratio, 1.96; p = 0.01), peripheral vascular disease (odds ratio, 2.50; p < 0.001), and reduced preoperative creatinine clearance (odds ratio, 1.02; p = 0.02) were independent risk factors for the development of postoperative renal dysfunction. Off-pump coronary artery bypass grafting surgery was not associated with a decreased risk of renal dysfunction by univariate or multivariable analysis.

CONCLUSIONS: Off-pump coronary artery bypass grafting surgery did not reduce the risk of postoperative renal dysfunction in this large, unselected, sequential series of patients at high risk for renal failure after coronary artery bypass grafting surgery. Our results suggest that renal function should not be a deciding factor when determining whether or not a patient undergoes off-pump coronary artery bypass grafting surgery.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Acute renal failure requiring dialysis occurs in only 1% to 5% [1, 2] of cases after cardiac surgery, but is associated with a mortality rate of up to 60% [1]. The cause of acute renal failure after cardiac surgery is multifactorial, and may include the detrimental effect of cardiopulmonary bypass (CPB) on kidney function. Cardiopulmonary bypass–related renal dysfunction can be attributed to renal hypoperfusion, nonpulsatile flow, hypothermia, and stimulation of the inflammatory response during CPB [3, 4]. It has previously been suggested that myocardial revascularization by off-pump coronary artery bypass grafting surgery (OPCAB) can reduce the morbidity associated with coronary artery bypass grafting (CABG) when compared with on-pump, conventional CABG (CCAB) [5–9]. Off-pump CABG remains controversial, however, and several studies have failed to demonstrate a reduction in morbidity when compared with CCAB [10–13].

The effect of OPCAB on postoperative renal impairment has also been controversial. Although it has been reported that OPCAB may minimize renal injury in elective patients with normal and impaired preoperative renal function [14–17], other studies have failed to show such a benefit [18–21].

The purpose of the current study was to compare the incidence of postoperative renal dysfunction in a group of high-risk OPCAB and CCAB patients. High-risk OPCAB and CCAB patients were identified preoperatively using baseline creatinine clearance (CrCl), a significant predictor of adverse clinical outcomes [22–24]. The two groups of patients were matched with propensity scoring. We attempted to determine whether OPCAB surgery prevents postoperative renal dysfunction in patients at high risk for renal failure.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Study Population
A standard set of perioperative data was collected prospectively for all patients undergoing cardiac surgery at Toronto General Hospital, between 1995 and 2003. This information was entered into a database that has been described previously [25]. A total of 2,869 patients who had preexisting renal dysfunction (preoperative CrCl < 60 mL/min) and who underwent isolated CABG were identified. Patients requiring preoperative dialysis were excluded. In 2,711 patients, conventional CABG was performed (CCAB group), whereas 158 patients underwent CABG without cardiopulmonary bypass (OPCAB group). Patients underwent one of the two surgical techniques according to the preference and expertise of the operating surgeons.

Operative Technique
Standard anesthesia and surgical techniques, CPB, and myocardial protection techniques were used in the CCAB group. Cardiopulmonary bypass was instituted using ascending aortic cannulation and two-stage venous cannulation of the right atrium. It is our practice to maintain the perfusion pressure during CPB above 80 mm Hg in patients at risk of postoperative renal dysfunction. Under mild systemic hypothermia (34°C), cardiac arrest was induced and maintained using intermittent hyperkalemic cold blood cardioplegia. Proximal anastomoses were constructed before removal of the aortic cross-clamp.

In the OPCAB group, stabilization of the target vessel was achieved using suction devices, and exposure of the coronary vessels was facilitated by the use of deep pericardial sutures. The target vessel was exposed and snared proximally using 4-0 Prolene (Ethicon, Sommerville, NJ). An intracoronary shunt was not used routinely. Heparin (15,000 units intravenously) was administered before coronary exposure and was reversed at the end of the procedure with low-dose protamine (150 mg).

Definition of Renal Dysfunction
Creatinine clearance was calculated preoperatively for all patients using the Cockcroft and Gault formula [23]. In men, CrCl = [(140 – age) x weight x 1.2]/serum creatinine, and in women, CrCl = [(140 – age) x weight]/serum creatinine. Units for age, weight, and creatinine were years, kilograms, and micromoles per liter, respectively. Preoperative renal dysfunction was defined as CrCl less than 60 mL/min. We have previously demonstrated a fivefold increase in risk of postoperative dialysis in cardiac surgery patients with a preoperative CrCl less than 60 mL/min [22].

Creatinine clearance was calculated on the first, second, and third postoperative days. The maximum decrease in CrCl in the first 3 days postoperatively (CrCl72h) was also calculated, and the maximum percentage change in CrCl (%{Delta}CrCl72h) was subsequently determined: %{Delta}CrCl72h = ({Delta}CrCl72h/CrCl) x 100%. Postoperative renal dysfunction was defined as a decrease in CrCl72h of 25% or greater or a requirement for postoperative dialysis (continuous venovenous or intermittent hemodialysis). We have previously demonstrated that %{Delta}CrCl72h correlates well with postoperative dialysis, mortality, and prolonged intensive care unit stay [22]. In patients with preoperative renal dysfunction (CrCl < 60 mL/min), a %{Delta}CrCl72h of 25% or greater is associated with a sensitivity and specificity for predicting dialysis of approximately 90% [22].

Statistical Methods
The propensity score method [26] was used to provide an estimate of the probability of a patient undergoing OPCAB, as opposed to CCAB, given a set of preoperative risk factors. Propensity scores were computed after multivariable regression analysis. Patients who underwent OPCAB were matched 3:1 to those who had CCAB, on the basis of the propensity score. Thus, only patients with similar scores were compared in the final analysis. Such matching controls for potentially confounding variables, and minimizes the effect of selection bias in the allocation of patients to the two groups.

Ordinal and nominal data were compared using the {chi}2 test or Fisher's exact test when appropriate. Continuous variables were compared with the unpaired Student's t test or the Kruskal-Wallis test when appropriate. Univariate analysis of preoperative risk factors for the development of postoperative renal dysfunction was performed, and an odds ratio (OR) was calculated. Variables with a p value of less than 0.25 were examined in a multivariable logistic regression model to assess the independent impact of those risk factors on postoperative renal dysfunction (ie, %{Delta}CrCl72h of 25% or greater, or dialysis). A stepwise procedure (backward Wald elimination test) was used, and a p value of less than 0.05 used to enter and eliminate variables.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Univariate comparisons of baseline preoperative characteristics before propensity score matching are shown in Tables 1 and 2. Go Patients in the OPCAB group were more likely to be 65 years of age or younger (24.0% versus 16.6%, p = 0.02), although the mean ages of the two groups did not differ significantly. Off-pump CABG patients were more likely to have peripheral vascular disease and less extensive coronary artery disease than the CCAB patients. The two groups were similar for all other variables, including preoperative creatinine and CrCl.


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  		Table 1. Ordinal and Nominal Preoperative Data for All Conventional and Off-Pump Coronary Artery Bypass Grafting Surgery Patients
 

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  		Table 2. Interval Preoperative Data for All Conventional and Off-Pump Coronary Artery Bypass Grafting Surgery Patients
 
Comparisons for OPCAB and propensity-matched CCAB patients are displayed in Tables 3 and 4. Go The matched groups showed no differences in any of the preoperative variables examined. Postoperative outcomes are shown in Table 5. None of the differences in postoperative outcomes between the groups reached statistical significance.


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  		Table 3. Ordinal and Nominal Preoperative Data for Conventional and Off-Pump Coronary Artery Bypass Grafting Surgery Patients Entering Final Analysis
 

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  		Table 4. Interval Preoperative Data for Conventional and Off-Pump Coronary Artery Bypass Grafting Surgery Patients Entering Final Analysis
 

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  		Table 5. Postoperative Outcome Data for Conventional and Off-Pump Coronary Artery Bypass Grafting Surgery Patients Entering Final Analysis
 
Multivariable logistic regression was performed to determine the independent predictors of postoperative renal dysfunction (%{Delta}CrCl72h of 25% or greater, or postoperative dialysis). Diabetes, peripheral vascular disease, and a reduced preoperative CrCl were risk factors for the development of renal dysfunction (Table 6).


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  		Table 6. Independent Predictors of Postoperative Renal Dysfunction in Patients Entering Final Analysis
 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
The current study examined a large, unselected, sequential series of patients at high risk of developing renal dysfunction after CABG. As such, it is representative of the patient population likely to present to a large teaching hospital, particularly as the risk profile of patients presenting for revascularization continues to increase. Moderate, transient impairment of renal function (serum creatinine between 130 and 440 µmol/L) may occur in almost one third of patients undergoing CPB, and this transient deterioration in renal function is associated with a mortality rate between 7% and 38% [27]. The benchmark study of Chertow and colleagues [23] reported a mortality of 63% at 30 days when dialysis is required to treat renal failure after cardiac surgery. More recent work confirms this high mortality [28], and mortality rates as high as 100% have been reported [29].

Previous attempts to prevent post-CPB renal dysfunction have centered on attempts to control patients' hemodynamics and hydration, optimization of perfusion pressure during CPB, and use of drugs such as mannitol, furosemide, and dopamine [30–32]. None of these interventions has been shown to reduce postoperative renal dysfunction. The advent of OPCAB has allowed surgeons to take a different approach to the problem of postoperative morbidity. Off-pump CABG has obviated the need for CPB in many cases and has been reported to reduce postoperative morbidity and mortality, particularly in high-risk patients [33, 34], despite the almost inevitable periods of hypotension and diminished cardiac output that occur during displacement of the heart. The literature, however, contains many conflicting reports on the results of OPCAB surgery [35]. There is also a lack of reliable data comparing outcomes of OPCAB in high-risk patients [36]. Mild preoperative renal dysfunction has, however, recently been shown to be an independent predictor of long-term cardiac mortality after CABG [37].

In this observational, retrospective study, we examined whether postoperative renal dysfunction is reduced when CABG is performed off-pump in patients with preexisting renal impairment. We focused on these high-risk patients because of their significant risk of postoperative renal failure. The change in CrCl after surgery was analyzed as a surrogate measure of renal dysfunction because we have previously demonstrated its significant correlation with postoperative dialysis, mortality, and prolonged intensive care unit stay [22].

The current study is the largest to date comparing OPCAB and CCAB specifically in patients at high risk for renal failure. Our results suggest that when compared with conventional CABG, OPCAB patients do not have a reduced risk of postoperative renal dysfunction. These findings support those of Gamoso and colleagues [20], who found no significant reduction in perioperative renal dysfunction in OPCAB patients when compared with conventional CABG patients. Seargent and colleagues [18] were also unable to demonstrate a reduced requirement for hemofiltration or dialysis in a retrospective study of more than 1,500 OPCAB patients. That study, however, excluded patients with significant preoperative renal impairment. Zamvar [21] also reported no renal protective effect of OPCAB, although the sample size in that study was small. Such negative results are not unexpected in view of the number of prospective randomized studies of OPCAB that have failed to report major, clinically important outcome differences [5, 7, 9]. The principal difference between those and the current study is that these patients were at significant risk of postoperative renal failure and constitute a subgroup of patients undergoing surgical revascularization who may have been expected to benefit from the avoidance of CPB. Our study addresses the problem of a lack of reliable data comparing outcomes of OPCAB in high-risk patients, and goes part of the way toward determining whether OPCAB is "a step forward, backward, or sideways" [36].

We propensity-matched CCAB and OPCAB patients in a 3:1 ratio to account for baseline population differences. Multivariable logistic regression demonstrated that diabetes, peripheral vascular disease, and reduced preoperative CrCl were independent predictors of postoperative renal dysfunction. Reduced CrCl before surgery predisposes patients to renal dysfunction after surgery, and has been reported as an important risk factor in several other studies [22–24]. The effect of diabetes on postoperative renal dysfunction is likely to be the result of associated renal parenchymal disease, or renal artery stenosis, both of which are more frequent in diabetic subjects. Peripheral vascular disease can similarly cause renal parenchymal disease and renal artery stenosis.

Study Limitations
The principal limitations of this study lie in the fact that it is retrospective, observational, and limited to a single institution. However, all data were entered into the database prospectively as part of routine patient management. In addition, propensity score matching resulted in comparable risk profiles for the two groups of patients. The relatively low incidence of postoperative renal dysfunction makes it unlikely that adequately powered randomized studies will be performed in the foreseeable future. We therefore think that our results are the best available evidence at this time. A further limitation of this study is that OPCAB surgery was not performed by all of the surgeons. It is therefore not possible to separate treatment differences from differences among surgeons. Outcomes for conventional CABG were, however, similar for all surgeons during the period of the study.

Conclusions
To conclude, we were unable to demonstrate any advantage of OPCAB over conventional CABG on postoperative renal dysfunction. This study supports the findings of a recent meta-analysis of 37 randomized trials of OPCAB versus conventional CABG, which reported that patients undergoing OPCAB do not have a reduced incidence of postoperative renal dysfunction [38]. Mild preoperative renal dysfunction is an independent predictor of adverse outcomes in both the short-term [39] and long-term after CABG [37].

Our results are important because the patients studied all had preoperative renal dysfunction and were all at increased risk of further postoperative renal impairment. Proponents of OPCAB have previously stated that such patients receive a benefit from avoiding CPB, without much supportive evidence. Our results suggest that renal function should not be a deciding factor when determining whether or not a patient undergoes OPCAB surgery.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
DNW is supported in part by the Canadian Institutes for Health Research.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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Ann. Thorac. Surg., December 1, 2005; 80(6): 2153 - 2154.
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