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Ann Thorac Surg 2005;79:1577-1583
© 2005 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Functional Renal Outcome in On-Pump and Off-Pump Coronary Revascularization: A Propensity-Based Analysis

^a Department of Cardiothoracic Surgery, St. Mary's Hospital, London, United Kingdom
^c Department of Surgical Oncology and Technology, St. Mary's Hospital, London, United Kingdom
^b Department of Cardiothoracic Surgery, Harefield Hospital, London, United Kingdom
^d Department of Cardiothoracic Surgery, Hammersmith Hospital, London, United Kingdom

Accepted for publication November 17, 2004.

^_* Address reprint requests to Dr Weerasinghe, Dept of Cardiothoracic Surgery, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK; (E-mail: a.weerasinghe{at}ic.ac.uk).

	Abstract

Top Abstract Introduction Material and Methods Results Comment References

 
BACKGROUND: Since the advent of off-pump coronary artery bypass grafting (OPCAB), comparisons have been made between it and on-pump coronary artery bypass grafting. Some observe a lesser incidence of acute renal failure requiring renal replacement therapy with OPCAB whereas others do not. The objective was to compare the occurrence of renal adverse outcome between on-pump coronary artery bypass grafting and OPCAB. Renal adverse outcome was defined as minor (20% increase in serum creatinine from preoperative) or major (composite end point of postoperative serum creatinine >200 µmol/L or postoperative mechanical renal support).

METHODS: The study was based on 2,041 patients with no known preoperative renal disease having first-time isolated coronary artery bypass grafting of multiple coronary arteries between January 2001 and November 2003, at St. Mary's Hospital, Harefield Hospital, and Hammersmith Hospital, in West London; 1,224 patients had on-pump coronary artery bypass grafting and 817 patients had OPCAB. Selection bias for surgical technique was addressed by calculating the propensity score for each patient and using it as an independent variable for adjustment in the multivariate analysis. Univariate and multivariate ordered logistic regressions were used to identify factors associated with renal adverse outcome ordered as none, minor, and major.

RESULTS: The number of grafts was 3.22 ± 0.82 for the on-pump coronary artery bypass grafting group and 3.35 ± 0.95 for the OPCAB group. On-pump coronary artery bypass grafting and increasing age were found to be the strongest independent predictors (p < 0.001) of renal adverse outcome. Other independent predictors included hypertension (p = 0.005), diabetes (p = 0.032), and preoperative serum creatinine (p = 0.001). A left ventricular ejection fraction of 0.30 to 0.49 (p = 0.099) and an ejection fraction of 0.50 or greater (p < 0.001) were associated with decreased risk compared with patients with an ejection fraction of less than 0.30. Interestingly, the use of non–left internal mammary arterial conduits significantly decreased the likelihood of renal adverse outcome (p = 0.034).

CONCLUSIONS: The results of this propensity-based study show that the OPCAB technique may reduce the risk for minor and major renal adverse outcome after coronary artery bypass grafting.

	Introduction

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Despite initial impressions that inflammatory responses initiated by the cardiopulmonary bypass circuit were responsible for differences observed between on-pump coronary artery bypass grafting (ONCAB) and off-pump coronary artery bypass (OPCAB), it is now apparent that the inflammatory response does not always differ greatly [1]. Both ONCAB and OPCAB surgery cause significant but similar changes in plasma and urinary cytokine homeostasis [2], but OPCAB has been shown to cause less complement activation [3]. From a physiologic perspective a major difference in cardiovascular physiology occurs between OPCAB and standard ONCAB techniques in that the OPCAB technique preserves an ejecting heart and hence pulsatile perfusion of the organs.

Since the advent of OPCAB, comparisons have been made between ONCAB and OPCAB in studies [4, 5] investigating morbidity and mortality. Meta-analysis of the literature has shown that off-pump surgery may result in improved short-term and midterm outcomes [6]. Differences in the renal impact between ONCAB and OPCAB have also been studied specifically focusing on various aspects of postoperative renal outcome [7–9]. Biochemical evidence of damage to both glomerular and renal tubular elements of the kidneys has been studied with conflicting results. In work done by Ascione and colleagues [7], glomerular filtration was significantly worse with ONCAB than with OPCAB. In contrast, Tang and associates [8] observed no difference in glomerular or tubular function between OPCAB and ONCAB techniques. In a study of multiple morbidity outcomes by Meharwal and coworkers [4], no difference in the requirement for dialysis between ONCAB and OPCAB was detected. In contrast, in a further study by Ascione and associates [9] looking at multiple morbidity outcomes, OPCAB reduced the likelihood of acute renal failure in patients with preoperative nondialysis-dependent renal insufficiency. A number of other studies have noted a lower incidence of renal failure requiring dialysis with OPCAB, but the mean number of bypass grafts in the OPCAB patients was consistently and significantly lower than in the ONCAB patients, reducing the impact of these results [5, 10, 11]. Thus, there was a need for a comparative study that compared ONCAB with OPCAB in patients having multivessel OPCAB, with better matched numbers of coronary grafts between the two techniques being compared.

In the present study we compare a specific renal outcome in patients having multivessel ONCAB, with patients having multivessel OPCAB, to facilitate evaluation of the role of cardiopulmonary bypass on the occurrence of renal adverse outcome (RAO). The specific objective of the study was to compare the occurrence of renal dysfunction between ONCAB and OPCAB, in first-time coronary artery bypass grafting in nondialysis-dependent patients. We evaluated the influence of cardiopulmonary bypass on the following:

1 The likelihood of being associated with minor RAO defined as at least a 20% increase in serum creatinine from the preoperative value with an absolute postoperative serum creatinine of 200 µmol/L or less and not requiring postoperative mechanical renal support.

2 The likelihood of being associated with major RAO defined as the occurrence of a composite end point of a postoperative serum creatinine of greater than 200 µmol/L or postoperative renal dysfunction requiring mechanical renal support.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment References

 
This study is based on patients who underwent coronary artery bypass grafting between January 2001 and November 2003, at St. Mary's Hospital, Harefield Hospital, and the Hammersmith Hospital, all of which are teaching hospitals affiliated with Imperial College, University of London, and situated in West London. Use of patient data were approved by the local research ethics committee. As the outcome of interest was the occurrence of RAO, patients already receiving dialysis were excluded from the study. Serum creatinine was used as a continuous variable to assess preoperative renal function. Patients having surgery within the same admission as referral were classed as having nonelective surgery. Only patients with multivessel disease undergoing first-time revascularization of more than one target coronary artery were included in the study. Initially 2,121 patients operated on within the specified time frame were identified for the study. Because the intraoperative and perioperative management protocols for managing patients with a preoperative serum creatinine greater than 200 µmol/L differed among the three institutions, these patients (n = 80) were excluded to improve homogeneity in the study population, resulting in a final study cohort of 2,041 patients who had no known preoperative renal disease. Of the 2,041 patients, 1,224 (59.97%) had ONCAB and the remaining 817 (40.03%) had OPCAB surgery. Mechanical renal support was used if renal failure was associated with volume overload, persistent hyperkalemia, or persistent acidosis.

Analysis of the study patients was planned on the basis of intention to treat. The selection of the patients for either surgical technique (whether ONCAB or OPCAB) was made by the individual surgeons, and the decision was completely based on their preference at the time of the operation.

Surgical Technique
ON-PUMP TECHNIQUE HAMMERSMITH HOSPITAL
On-pump surgery was performed using aortocaval cannulation, a Stockert roller pump (Stockert Instrumentee, Munich, Germany), and a Bard (C. R. Bard, Inc, Murray Hill, NJ) or Quadrox hollow-fiber membrane oxygenator (Jostra Medizintechnik AG, Hirrlingen, Germany). The mean blood pressure during cardiopulmonary bypass was maintained at 50 to 60 mm Hg using pulsatile flow with a pulse pressure of 20 mm Hg and flow of 2.4 L · min^–1 · m^–2. Proximal anastomoses were performed with a side-biting aortic clamp. The activated clotting time was maintained at 500 seconds during cardiopulmonary bypass, and moderate hypothermia was achieved. A cell-saving device and cardiotomy suction were used.

ON-PUMP TECHNIQUE HAREFIELD AND ST. MARY'S HOSPITALS
Cardiopulmonary bypass was instituted with aortocaval cannulation. Standard bypass management included membrane oxygenators, arterial line filters, and nonpulsatile flow of 2.4 L · min^–1 · m^–2 with a mean arterial blood pressure 50 to 60 mm Hg. Myocardial protection was achieved mainly by intermittent antegrade cold-blood cardioplegia (4:1 blood to crystalloid ratio). Retrograde blood cardioplegia was used occasionally in addition, particularly if there was left main stem disease with tight right coronary artery stenosis, which might cause inadequate delivery of the cardioplegia to the targeted myocardium and consequently incomplete myocardial protection. Temperature management was again achieved with moderate hypothermia. A cell-saving device and cardiotomy suction were used.

OFF-PUMP TECHNIQUE
Off-pump surgery was performed with proximal occlusion of the target coronary vessel with a silicone elastomer sling and the use of epicardial stabilizing devices and apical suction devices (Octopus 3 or 4, Medronic Inc, Minneapolis, MN; Starfish, Medronic Inc; or the Guidant Vortex Vacuum Assist, Cupertino, CA). Intracoronary shunts were not used routinely during the distal anastomoses. Systolic arterial pressures were maintained at a minimum of 70 mm Hg during distal anastomoses using venous volume regulation, rate control, inotropic agents, or vasoconstrictors. Proximal anastomoses were performed with a side-biting aortic clamp, with systemic pressures that were dictated by individual surgeon preference. The target activated clotting time during surgery was 300 seconds. Normothermia was maintained by using warm intravenous fluids, a heating mattress, and a humidified airway, in addition to maintaining a warm operating theater. Cell-saving devices and cardiotomy suction were used, and a perfusionist with primed bypass circuit was available for all OPCAB cases.

Statistical Methods
Data were expressed as mean ± standard deviation. Numerical variables were compared using the Student's t test or the Mann-Whitney U test as appropriate. Categorical variables were compared using Fisher's exact test or the ² test as appropriate, and p values of 0.05 or less were considered significant. All tests were two-sided. Preoperative serum creatinine was included in the analysis as a continuous variable.

The statistical analysis included three parts: (1) A multivariate logistic regression model was developed to calculate the propensity score by setting the use of OPCAB or ONCAB as the binary dependent variable (OPCAB = 0, ONCAB = 1). (2) Univariate ordered logistic regression analysis was performed to identify significant predictors of RAO. The ordinal dependent variable for the ordered regression was defined as following: none = 0, minor adverse renal outcome = 1, major adverse renal outcome = 2. (3) Those variables identified to have a p value of 0.25 or less in the univariate analysis were considered as candidates for the multivariable analysis, which was performed in a stepwise fashion to identify independent predictors of RAO.

The propensity score was used for statistical analysis as previously practiced and recommended both by the present authors and others [12–14]. Variables included in the propensity scoring (Table 1) were age, sex, hypertension, diabetes, hypercholesterolemia, previous myocardial infarction, ejection fraction, preoperative serum creatinine, priority, total number of grafts, the use of the left internal mammary artery, and the use of non–left internal mammary, arterial grafts. The multifactorial logistic regression analysis provided a propensity score for the likelihood of an ONCAB technique for each patient. The propensity score was subsequently regressed as an independent covariate in the multifactorial ordered logistic regression model, using all relevant observations. This technique offers advantages versus the conventional propensity matching, which limits the number of observations used in the final analysis. In this way the statistical analysis addressed confounding (patient selection) by use of a propensity score, and heterogeneity (risk factors) by multivariable risk factor analysis.

	Results

Top Abstract Introduction Material and Methods Results Comment References

 
The study consisted of 1,505 men and 536 women. The mean age was 64.64 ± 9.22 years for the ONCAB group and 64.34 ± 9.89 years for the OPCAB group. The left internal mammary artery was used as a conduit in 1,203 of 1,224 ONCAB patients and 780 of 817 OPCAB patients. The mean number of grafts was 3.22 ± 0.82 for ONCAB patients and 3.35 ± 0.95 for OPCAB patients. The patient demographic characteristics for the study groups are presented in Table 2. Conversion from OPCAB to ONCAB occurred in 19 patients, and 3 of them had a postoperative serum creatinine greater than 200 µmol/L and 1 required renal replacement therapy.

View larger version (17K): [in this window] [in a new window]   Fig 1. Prediction curves displaying the probability of minor and major renal adverse outcomes. (CPB = cardiopulmonary bypass; OPCAB = off-pump coronary artery bypass grafting.)

	Comment

Top Abstract Introduction Material and Methods Results Comment References

Both biochemical and physiologic factors may potentially contribute to the observed renoprotective effect of OPCAB. Expression of neutrophil CD11b and its mobilization in response to in vitro stimulation does not differ between OPCAB and ONCAB [3], but a more rapid (C5a and C5b-9) and more profound (C5b-9) expression of complement activation occurs with ONCAB than with OPCAB. The primary renal effect of complement in the setting of ischemia–reperfusion appears to be on the tubular epithelial cells rather than on the vascular endothelium, and mainly results from the formation of C5b-9 on the renal tubules [15]. This intriguing information from the literature may shed light on why a larger proportion of patients in the ONCAB group with postoperative serum creatinine of greater than 200 µmol/L met the electrolyte and acid-base criteria (tubular functions) for mechanical renal support than in the OPCAB group. Thus, decreased complement activation may possibly contribute toward the improved functional RAO observed with OPCAB in this study.

Another factor potentially contributing toward the superior functional renal outcome with OPCAB is that higher mean arterial pressures are usually maintained during off-pump surgery and may have a renoprotective effect. In the methodology, we mention that systolic arterial pressures were maintained at a minimum of 70 mm Hg during distal anastomoses when performing OPCAB. This minimum was applicable only when performing some of the anastomoses in the circumflex territory. At most times, both when grafting the circumflex and other territories, systolic pressures were maintained at around or above 100 mm Hg. In a significant percentage of our practice, we use suction devices such as the Starfish (Medronic Inc) or the Guidant Vortex Vacuum Assist to position the heart (especially when grafting the circumflex territory), to ensure that higher systemic pressures are maintained when stabilizers are used to facilitate suturing. The influence of arterial blood pressure and systemic blood flow on renal function has been studied previously in the setting of hypothermic cardiopulmonary bypass, and both renal blood flow and urine flow were positively related to primarily systemic blood pressure. In a comparable manner, the beneficial effect on functional renal outcome seen with OPCAB may be a reflection of the maintenance of higher systemic blood pressures during OPCAB [16].

The design of the study allowed us to revisit the debate on the influence of pulsatility of renal perfusion on renal outcome. When nonpulsatile ONCAB and pulsatile ONCAB were compared with OPCAB in the unifactorial ordered logistic regression analysis, it was observed that the use of nonpulsatile flow was more strongly associated with an increased likelihood of functional RAO than the use of pulsatile flow. This difference was no longer significant in the multifactorial ordered logistic regression analysis. The issue of pulsatility is complex, and it appears to be more important for renal function under hypotensive conditions than if normal flow or perfusion pressures are maintained [17].

An interesting observation that arose out of the multifactorial ordered regression analysis was that the use of arterial conduits other than the left internal mammary artery was associated with a decreased likelihood of RAO after coronary artery bypass grafting. It may well be that this is a reflection of a bias in selecting patients with absence of extracardiac arteriopathy for using non–left internal mammary, arterial conduits. Hence, these patients are less likely to have covert arteriopathy affecting their renal vasculature. We did not have information on the occurrence of peripheral vascular disease and appreciate that this is a limitation of our study. Other limitations of the study are that it is not a prospective randomized trial, and also that the adjustment with propensity scoring was limited by available variables, which underlines the fact that selection bias could not be completely eliminated. Although the study adjusted for patient-related and procedure-related factors, it was not possible to accommodate for surgeon-related variables such as how individual expertise may have played some role in the incidence of postoperative RAO. In contrast to these limitations, a distinct positive feature of the study that we hope will increase its impact is that the number of coronary grafts performed in the OPCAB group was actually greater than in the ONCAB group, potentially making the observed results clinically more robust.

The results of this propensity-based study show that the OPCAB technique may reduce the risk for minor and major RAO after coronary artery bypass grafting. We hope this study has contributed toward better understanding the differences in functional renal outcome between OPCAB and ONCAB surgery for coronary revascularization.

	References

Top Abstract Introduction Material and Methods Results Comment References

 

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This Article Abstract Full Text (PDF) 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): Arjuna Weerasinghe Sharif Al-Ruzzeh Roberto Casula Mohammed Amrani Prakash Punjabi Kenneth Taylor Rex Stanbridge Brian Glenville Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weerasinghe, A. Articles by Glenville, B. Search for Related Content PubMed PubMed Citation Articles by Weerasinghe, A. Articles by Glenville, B. Related Collections Minimally invasive surgery