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Ann Thorac Surg 2004;77:1250-1256
© 2004 The Society of Thoracic Surgeons
a Department of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany
Accepted for publication July 10, 2003.
* Address reprint requests to Dr Bucerius, University of Leipzig, Heart Center, Department of Cardiac Surgery, Strümpellstr. 39, Leipzig D-04289, Germany
e-mail: bucerj{at}medizin.uni-leipzig.de
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Abstract |
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METHODS: Prospective data on 9,631 patients receiving myocardial revascularization with (coronary artery bypass grafting [n = 8,870]) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting [n = 761]) between April 1996 and August 2001 were evaluated by univariate and multivariate logistic regression analysis.
RESULTS: Overall prevalence of postoperative continuous renal replacement therapy was 4.1% (coronary artery bypass grafting, 4.3%; off-pump coronary artery bypass grafting, 1.8%; p = 0.001). Thirty of 40 selected preoperative and intraoperative patient and treatment related variables had a high association with the requirement for postoperative renal replacement therapy; fifteen of these variables were independent predictors in the whole study population. Off-pump coronary artery bypass surgery was identified as having a significantly lower predictive value for postoperative continuous renal placement therapy. In the subgroup of patients undergoing off-pump coronary artery bypass grafting surgery, a second multivariate logistic regression model revealed preoperative cardiogenic shock, urgent operation, intraoperative low cardiac output, and high transfusion requirement as independent predictors for postoperative renal replacement therapy.
CONCLUSIONS: Patients with preoperative nondialysis dependent renal insufficiency are at a high risk for further decline in renal function requiring postoperative continuous renal replacement therapy. Off-pump coronary artery bypass surgery is associated with a lower prevalence of postoperative renal replacement therapy after coronary artery bypass grafting.
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Introduction |
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Contemporary practice of cardiac surgery encounters an increasing number of patients who are both older and afflicted with substantial additional risk factors as well as those requiring repeat cardiac surgery than previously. In parallel there are improvements in medical treatments such as off-pump coronary artery bypass grafting (OPCAB). Patients with certain concomitant diseases are at increased risk for a higher mortality and morbidity after cardiac surgery [5]. Care of these high-risk patients mandates the development of strategies to minimize the harmful effects of cardiac surgery and, in addition, cardiopulmonary bypass (CPB) with its undesirable effects that may contribute to an increased risk of postoperative patient's morbidity.
Prevalence of acute renal failure requiring renal replacement therapy after cardiac surgery has been previously reported to vary from 1.0% to 7.0% in patients undergoing cardiac surgery with CPB [3]. However, there is a lack of data regarding prevalence and predictors of this severe postoperative complication in patients undergoing coronary artery bypass grafting, especially on the beating heart. This increasingly used surgical technique may be beneficial with regard to prevalence of postoperative renal failure requiring continuous renal replacement therapy (CRRT) even in high-risk subgroups.
Aim of the present study was to systematically investigate the prevalence and possible predictors, as well as variables leading to acute renal failure requiring CRRT after coronary artery bypass grafting both with CPB and on the beating heart.
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Material and methods |
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Definition of postoperative CRRT
Postoperative CRRT was defined as any postoperative renal insufficiency requiring first time hemofiltration, dialysis or any other renal replacement therapy at our institution.
Oligo-anuria or serum urea levels greater than or equal to 160 mg/dL, or both, have been indications for CRRT. A sole elevation of the serum creatinine has not been an indication for CRRT in most cases. However, the majority of patients requiring CRRT fulfilled more than one of the previously mentioned criteria. Postoperative time period in the intensive care unit in which renal failure requiring CRRT was assessed lasted for 11.3 ± 9.4 days in the study population. Patients suffering from preoperative renal failure requiring acute or chronic CRRT have been excluded from this analysis.
Technique of CRRT
The technique of CRRT consisted of a double lumen catheter that was placed in the venous system. The blood flow rate was kept as high as possible.
Different types of hemofiltration and dialysis machines like Fresenius Multifiltrate, ADM/ABM 08 (Fresenius Medical Care, Bad Homburg, Germany) or Hospal Prisma (Hospal Medizintechnik GmbH, Planegg-Martinsried, Germany) were used. Replacement fluid was administered pre-filter at a dynamically adjusted rate chosen to achieve the desired fluid therapy goals for any time period.
Systemic anticoagulation was carried out according to the standard anticoagulation protocol adapted to the performed surgical intervention and the circuit duration [1].
Data collection
Perioperative data were recorded prospectively using an online database system as previously described (Medwork database software (Lenz + Partner GmbH, Germany) [6]. All variables analyzed were entered prospectively to accomplish a complete and valid data set for each patient. The validity of the data was routinely ensured by using this information for generating text documents, thus resulting in a meticulous confirmation of the entered data by the user. Preoperative and intraoperative risk factors included in a univariate analysis and consecutively in a stepwise logistic regression model are listed in the Appendix.
Statistical analysis
Continuous variables are expressed as mean ± standard deviation, categorical data as proportions. Continuous variables between patients with and without postoperative CRRT were compared using the student's unpaired t test for variables, which were normally distributed or used the Mann Whitney U test for continuous variables without normal distribution. Categorical variables were compared by using 
2 analysis. Univariate analysis of risk factors was performed by a calculating odds ratio (OR) with a 95% confidence interval. Variables with a p value of less than 0.05 were consecutively examined to a multivariate logistic regression model to assess the independent impact of the risk factors on postoperative CRRT. A stepwise procedure (the backward Wald test) was used. A p value less than 0.05 was used to enter and eliminate variables [7]. To identify potential risk factors for postoperative CRRT in the subgroup of patients undergoing OPCAB surgery, a second multivariate logistic regression model was performed with those preoperative and intraoperative risk factors in the Appendix marked with an asterisk. The design of this second multivariate regression analysis was the same as that previously stated. All statistical analyses were performed using the SPSS statistical package 9.0 (SPSS Corp, Chicago, IL).
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Results |
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2.0 mg/dL or urea treated medically without renal replacement therapy, or both; see Appendix), prevalence of postoperative CRRT was higher in those undergoing CABG surgery as compared with those in the OPCAB group reaching close to statistical significance (p = 0.055) (Fig 1). Patients requiring postoperative CRRT had a significantly lower left ventricular ejection fraction (42.1% ± 23.7 vs 53.6% ± 20.3; p < 0.0001) as patients without this postoperative complication. Furthermore, patients with postoperative CRRT suffered significantly more often from impaired preoperative New York Heart Association functional classification ( 3 [90.6% vs 78.9%; p < 0.0001]) and from impaired CCS-classification (3 [50.4% vs 36.1%; p < 0.0001]). However, no statistically significant differences with regard to patient's age have been found between patients with and without postoperative CRRT (65.4 years ± 13.4 vs 65.3 years ± 9.1; p = 0.838). Number of bypass grafts was significantly lower in patients with postoperative renal replacement therapy (2.0 grafts ± 1.1 vs 2.5 grafts ± 0.9; p < 0.0001), and 75.1% of those patients were male.
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Comment |
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In the current series comprised of more than 9,000 adult patients undergoing coronary artery bypass grafting using CPB or OPCAB technique, several preoperative and intraoperative risk factors significantly associated with CRRT-dependent postoperative renal failure have been identified.
As reported in other series, a significant relationship has been found between the severity of the underlying cardiac disease and renal replacement therapy requiring renal failure. This association was revealed by a significant odds ratios of CCS greater than or equal to 3 (OR, 1.41), cardiogenic shock (OR, 3.28), and preoperative myocardial infarction (OR, 1.31) with all of them frequently resulting in the need for urgent operation (OR, 2.36), and postoperative CRRT-dependent renal failure [9, 12]. In addition, indication for repeat coronary artery bypass grafting has been significantly associated with postoperative CRRT in this series (OR, 1.95) as recently reported, probably due to severe underlying coronary artery disease [12, 13].
The effect of diabetes mellitus (OR, 1.38) on postoperative renal failure may be the result of renal parenchymal disease, such as glomerulonephritis or glomerulosclerosis. Furthermore, renal artery stenosis in diabetic patients may further compromise renal function. As previously stated, inadequate perfusion pressure during CPB and postoperative ICU periods may even elevate this risk [3, 9, 14]. In this context, it was not surprising that peripheral vascular disease (OR, 1.62) as a systemic disease frequently affecting both renal arteries was significantly associated with postoperative CRRT in this series as well [12].
Higher patient's age is one of the most reported preoperative risk factors for postoperative renal failure requiring CRRT [9, 12, 15, 16]. This finding was confirmed in this series as age of 80 years or older (OR, 1.99) and has been found to be significantly associated with postoperative renal failure.
It was not surprising that preoperative nondialysis dependent renal dysfunction predicts a further decline in renal function leading to postoperative mechanical renal support as reported by several previous series (OR, 2.44) [3, 8, 9, 12, 14–16]. This may be due to renal parenchymal disorders being more susceptible to have postoperative renal failure develop after cardiac surgery. Renal cord ischemia may be a result of an intraoperative drop in renal perfusion pressure during onset of CPB or during mechanical lifting of the heart in OPCAB surgery. Renal failure in those predisposed patients is further depressed even during postoperative periods [9].
Intraoperative low cardiac output (OR, 2.8) leading to impaired perfusion pressure frequently after intraaortic balloon pump or assisted device support, or both (OR, 1.88 and 3.23, respectively) was significantly associated with postoperative CRRT in this series. This association has been reported by several previous studies [8, 13, 17]. It is obvious that the named devices are inserted in order to assist in the maintenance of cardiac output in unstable patients undergoing cardiac surgery. The use of both devices may also be associated with the development of postoperative renal failure if insertion of the cannulas or the balloon leads to limb ischemia and rhabdomyolysis [18]. Intraoperative hemofiltration (OR, 2.25) and prolonged perfusion time (OR, 2.62) are both variables inalienably associated with the use of cardiopulmonary bypass and have been shown as significant predictors of postoperative renal failure [13, 16, 19]. Both of them may indicate nonphysiological conditions leading to an impaired renal function during the intraoperative as well as the postoperative period. Need for intraoperative hemofiltration seems to be a marker for an existing preoperative renal insufficiency, a significant risk factor itself as previously mentioned. Intraoperative transfusion of a significant amount of red blood cells (1000 mL; OR, 1.86) most likely indicates unstable intraoperative conditions leading to an impaired renal function.
Off-pump coronary artery bypass surgery was the only independent predictor significantly associated with a lower prevalence of postoperative CRRT requiring renal failure (OR, 0.55). In several previous studies, lower prevalence of postoperative complications (eg, cerebral deficits [stroke or postoperative delirium] or renal insufficiency), and a lower mortality rate have been documented for patients undergoing beating heart surgery as compared with patients undergoing conventional CABG [20–24]. Furthermore, in a series comprising more than 3,000 consecutive patients, Ascione and associates [25] demonstrated higher postoperative serum creatinine and urea levels in patients with preoperative nondialysis-dependent renal insufficiency undergoing on-pump CABG with a significant difference at 12 hours postoperatively as compared with those undergoing OPCAB surgery. In addition, in a further study they reported a significantly impaired renal tubular function as assessed by increased N-acetyl glucosaminidase activity in the CABG group [26]. Loef and associates [27] found significantly less changes in microalbuminuria, free hemoglobin, fractional excretion of sodium, and free water clearance as well as N-acetyl-ß-D glucosaminidase as a marker for tubular function and damage, respectively, in patients undergoing OPCAB as compared with CABG patients. They conclude that off-pump coronary surgery attenuates renal injury after surgical myocardial revascularization. Hayashida and associates [28] found a significantly less increase in creatinine levels and a greater creatinine clearance in OPCAB patients as compared with the CABG group. Postoperative recovery of free water clearance was more prompt in the OPCAB group. In contrast to these findings, in a recent study by Gamoso and associates [15] including 690 patients, no significant reduction of perioperative renal dysfunction in OPCAB patients could been found.
Avoiding CPB is beneficial even in patients with an existing preoperative renal insufficiency undergoing CABG as confirmed in this study (Fig 1) [25]. This benefit may be due to the avoidance of nonpulsatile flow, renal hypoperfusion, hypothermia, and prolonged duration of CPB for all of them thought to have adverse effects on renal function in patients undergoing off-pump coronary artery bypass grafting.
When narrowing the analysis to the subgroup of patients receiving OPCAB surgery, the logistic regression model revealed preoperative cardiogenic shock (OR, 3.93) and urgent operation (OR, 9.8) as well as intraoperative low cardiac output (OR, 9.85) and high transfusion requirement (OR, 36.18) as independent predictors for postoperative renal failure requiring renal replacement therapy. As discussed in context with the risk factors for postoperative renal failure in the whole study population, all of these four predictors indicate an impaired preoperative or intraoperative cardiac function or unstable intraoperative conditions potentially leading to postoperative renal failure with the subsequent need for CRRT. It is obvious that this severe cardiac impairment can not be overcome totally by avoiding cardiopulmonary bypass in OPCAB surgery. Interestingly, patients with concomitant diseases or risk factors seem to benefit from the beating heart approach as all of the independent risk factors identified (except those previously named) in the whole study population did not show a significant association with postoperative renal failure requiring CRRT in the analyzed subgroup of patients undergoing OPCAB surgery.
In this series, preoperative patient characteristics revealed significant differences regarding age, New York Heart Association functional class, prevalence of preoperative nondialysis dependent renal failure, and number of coronary bypass grafts between both surgical groups. This reflects that initially only selected patients received OPCAB surgery. The possibility of selection bias (as for all nonrandomized studies) is the main limitation of the current study. However, it is important to note that the OPCAB group did not have the lowest prevalence of all independent predictors for postoperative CRRT as shown in Table 3. Furthermore, prevalence of impaired CCS classification was significantly higher in the OPCAB group, and prevalence of preoperative nondialysis dependent renal failure being one major independent risk factor for postoperative CRRT failed to be statistically significant between both groups. In addition, multivariable logistic regression analysis revealed that OPCAB surgery was associated with lower risk of postoperative renal replacement therapy, even after accounting for other risk factors. In addition, prevalence of postoperative CRRT was lower in patients with preoperative renal disease undergoing OPCAB surgery reaching close to statistical significance. Therefore we conclude that OPCAB surgery with avoidance of CPB seems to be associated with a significantly lower risk for postoperative renal failure requiring CRRT.
In this series of patients after coronary artery bypass surgery either with cardiopulmonary bypass or on the beating heart, several preoperative and intraoperative patient or treatment variables have been shown to be significantly associated with postoperative CRRT. Understanding and analysis of the multivariate regressions presented in this study, possibly leading to a preoperative scoring-system estimating the risk of postoperative renal failure and subsequent continuous renal replacement therapy should allow the identification of high-risk subsets of patients undergoing coronary artery bypass graft surgery. This may lead to preoperative and intraoperative interventions, such as OPCAB surgery, to reduce severe postoperative renal failure.
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Appendix |
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aVariables included in the logistic regression analysis to identify risk factors for postoperative renal failure requiring CRRT in the subgroup of patients undergoing OPCAB surgery (n = 761).
CABG = coronary artery bypass grafting; CCS = Canadian Cardiovascular Society angina classification; CPB = cardiopulmonary bypass; CRRT = continuous renal replacement therapy; ECMO = extracorporal membrane oxygenation; IABP = intra-aortic ballon pump; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association heart failure association; OPCAB = off-pump coronary artery bypass grafting; OR = Odds ratio; postop = postoperative; PTCA = percutaneous trans coronary angioplasty; RBC = red blood cells.
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= total study population; 
= patients with preoperative renal disease. (CABG = conventional coronary artery bypass grafting; OPCAB = off-pump coronary artery bypass grafting.)
30%a (Assessed by angiography or 2D echocardiography)