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Anesth Analg 2004;99:959-964 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000132978.32215.2C
Kenneth J. Tuman Section Editor |
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Abstract |
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In this prospective, observational trial, we determined whether off-pump coronary artery bypass (OPCAB) was associated with less postoperative renal dysfunction (RD) compared with coronary bypass surgery with cardiopulmonary bypass (CABG). All patients undergoing primary, isolated coronary surgery at our institution in the year 2000 participated. Data collected on each patient included demographics, preoperative risk factors for RD, perioperative events, and serum creatinine concentrations from date of admission until discharge or death. The criteria for RD was both a
50% increase from preoperative creatinine and an absolute postoperative creatinine 2.0 mg/dL (177 µM). Student’s t-test or the Fisher’s exact test was used to compare groups. Stepwise multiple logistic regression identified determinants of RD; P < 0.05 significant. The CABG group (n = 119) differed from the OPCAB group (n = 220) with respect to age (64 ± 13 versus 67 ± 10 yr, P = 0.0074) and number of distal grafts (median 4 versus 3, P = 0.0003). Type of operation did not associate with the presence of postoperative RD: 18 (8.2%) of 220 OPCAB patients versus 12 (10%) of 119 CABG patients (P = 0.55). Our data suggest that choice of operative technique (OPCAB versus CABG) is not associated with reduced renal morbidity. IMPLICATIONS: This prospective, observational trial suggests that patients who undergo complete coronary revascularization without cardiopulmonary bypass (off-pump) have similar incidences of postoperative creatinine increases when compared with patients undergoing traditional coronary artery bypass surgery with cardiopulmonary bypass.
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Introduction |
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Postoperative renal dysfunction (RD) is an independent predictor of negative outcome after coronary revascularization (1). Major predictors of postoperative RD include advanced age, preoperative RD, diabetes mellitus, congestive heart failure, prolonged cardiopulmonary bypass (CPB) time, and persistent low cardiac output states (2). Inadequate or nonpulsatile renal perfusion, macro- and microembolic loads to the renal vasculature, and the inflammatory response to CPB have been implicated as potential etiologic factors for the development of postoperative RD. The explicit contribution of these factors and the precise combination of underlying preoperative risk with mechanistic insult remain to be fully elucidated.
Off-pump coronary artery bypass (OPCAB) surgery eliminates several of the physiologic perturbations associated with CPB that have been implicated in the development of postoperative RD. OPCAB may therefore be the preferred technique for patients with multiple preoperative risk factors for RD. Early trials with small cohorts demonstrated a decreased incidence of RD in OPCAB versus coronary artery bypass with CPB (CABG) patients assessed by markers of renal filtration (3). Other small trials, however, contradicted these findings and found no differences in creatinine clearance between OPCAB and CABG groups (4). Because risk factors for perioperative RD in CABG are well known, patients identified preoperatively as high risk could be offered the technique by which the incidence of RD is minimized. In this prospective, observational trial of several hundred patients, we compared the incidence of RD in CABG and OPCAB patients undergoing complete revascularization using the difference of postoperative to preoperative creatinine as a marker of RD.
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Methods |
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After IRB approval, all consecutive patients undergoing primary, isolated, nonemergent coronary artery bypass surgery at our institution in the 2000 calendar year participated. Patient consent was not required by the IRB. Surgeons performed CABG or OPCAB at their discretion. Each OPCAB and CABG was performed with the goal of achieving complete surgical revascularization. OPCAB was performed by surgeons who initiated each coronary revascularization using the off-pump technique and whose combined intraoperative conversion rate to traditional CABG was <4%. Participating surgeons trained in and adopted the OPCAB technique well in advance of the study period, and were proficient in the technique.
Patient Data
Standard perioperative forms captured demographics, preoperative risk factors for RD, significant perioperative events, and creatinine levels from the date of admission until hospital discharge or death. Significant perioperative events included institution of intraaortic balloon counterpulsation; total CPB time >180 min; use of >4 µg/min epinephrine, the inotrope of choice at our institution; or any dose of epinephrine in combination with another inotrope.
Definition of RD
The analysis excluded patients with preoperative serum creatinine (Cr-Pre) values 2.0 mg/dL (177 µM), those on hemodialysis, and patients whose OPCAB converted to CPB. The analysis also excluded patients with "unstable" preoperative creatinine (presumed to have evolving renal injury secondary to contrast dye or other preoperative causes) as defined by a >25% increase in serum creatinine concentration from hospital admission to the morning of surgery. The criteria for RD required both a 50% increase from Cr-Pre and an absolute postoperative creatinine 2 mg/dL (177 µM). Creatinine measured within 24 h before surgery constituted the patient’s baseline Cr-Pre. Serum creatinine measurements occurred daily after surgery until date of discharge.
Operative Technique
OPCAB.
OPCAB was performed using either the CTS(Cardio Thoracic Systems, Inc., Cupertino, CA) or Octopus 2 (Medtronic, Minneapolis, MN) myocardial stabilization devices via a median sternotomy incision. After mediastinal entry, deep pericardial sutures were placed to lift the myocardial apex and facilitate exposure to the posterior and lateral aspects of the myocardium. Each distal anastomosis was approached with a stabilize-wait, occlude-wait sequence. This sequence allowed for diagnosis of hemodynamic aberrations and timely intervention. When hemodynamic instability occurred, the operating team attributed it to either myocardial displacement, iatrogenic vessel occlusion, or both. Instability associated with myocardial displacement was almost always amenable to repositioning without sacrificing visualization or field stability. After achieving hemodynamic stability in the revascularization position, the surgeon applied a tourniquet to occlude proximal coronary artery inflow. After arteriotomy, intracoronary shunt insertion provided target vessel hemostasis and perfusion of the distal myocardial bed. Immediate adverse hemodynamic responses to vessel occlusion prompted aggressive pharmacologic support. In rare cases of severe and sustained instability, conversion to CPB occurred. In almost all cases, the left anterior descending artery was bypassed with the left internal mammary artery first, in effort to provide protection to the large amount of the left ventricle that is supplied by this vessel.
CABG.
Extracorporeal circulation was established with aortic cannulation and either single or double cannulation of the right atrium, depending on the surgeon’s preference. Moderate hypothermia (25°–28°C) was used in all cases. Flows were maintained at 1.8–2.2 L/min/m2. Mean arterial blood pressure was kept in a range of 50–70 mm Hg. Antegrade and/or retrograde cold blood cardioplegia was used to induce cardiac arrest, which was maintained by serial administration of additional aliquots at 15-min intervals. The left internal thoracic artery was routinely used to bypass the left anterior descending coronary artery. Other bypasses were constructed using the right internal thoracic artery, a radial artery, or segments of saphenous vein. Distal anastomoses were constructed first. Proximal anastomoses were constructed during the rewarming period using a partial occlusion clamp on the ascending aorta. After decannulation, heparin was reversed. Patients were transferred to the cardiothoracic intensive care unit on no routine infusions except as indicated for hemodynamic support.
Hemodynamic Management
Hemodynamic goals differed between the two groups. For OPCAB patients, patients first received IV fluids, then 
-adrenergic agonists, then mixed and ß agonists to increase systolic blood pressure (SBP) to 140–160 mm Hg before each myocardial manipulation. Phenylephrine and norepinephrine also maintained SBP at 120 mm Hg when necessary during the completion of each distal anastomosis. When these drugs alone failed to support SBP during distal graft completion, epinephrine augmented collateral flow and supported cardiac index at l.5 L/min/m2. Both CABG and OPCAB patients received inotropic support as needed to maintain cardiac index 2.0 L/min/m2 after completion of revascularization.
Fluid management differed between groups. OPCAB patients received liberal intravascular fluid administration (crystalloid or 5% albumin) until completion of the last distal anastomosis. Specifically, before the first elevation of the myocardium for the placement of the deep pericardial sutures, OPCAB patients received IV hydration to improve the cardiac output as determined by thermodilution. Volume administration was restricted prebypass in patients in the CABG group unless hydration was indicated by SBP <100 mm Hg with low filling pressures or anemia, and/or presence of ST segment changes. All patients in both groups were monitored with a pulmonary artery catheter. Transesophageal echocardiography was used in <2% of all cases.
Anticoagulation
OPCAB patients weighing 
70 kg received 7500 U of heparin initially; those weighing >70 kg received 10,000 U. Additional doses were administered as needed each half-hour to maintain the activated clotting time (ACT) at least 300 s. CABG patients received sufficient heparin to maintain an ACT >450 s before and during CPB. Both groups received protamine to return the ACT to baseline values. 
-Aminocaproic acid was routinely used in the CABG but no patient received the drug in the OPCAB group. At least 50% of OPCAB patients received crushed clopidogrel via orogastric tube in the immediate postoperative period, whereas none of the CABG patients did. Some patients in both groups received doses of clopidogrel preoperatively followed by postoperative oral administration. Diltiazem infusions for 24 h accompanied all revascularizations using a radial artery conduit, regardless of treatment group (CABG or OPCAB).
Anesthetic Drugs
Anesthetic administration of anxiolytics, narcotics, and muscle relaxants was similar in both groups. No patient in either group received regional anesthesia. Intraoperative temperature management differed between groups. Bladder temperature in the CABG group was allowed to "drift" before institution of CPB. Although temperature management on bypass varied according to surgeon, all patients separated from CPB at bladder temperatures between 34.0° and 36.0°C. The OPCAB group had the operating room ambient temperature at least 22°C and a forced air warming blanket adjusted to maintain bladder temperature at 35°C. All patients received warmed blood products.
Mean ± SD summarize measurements, unless otherwise specified. Student’s t-test or the Fisher’s exact test was used to compare groups. Stepwise multiple logistic regression identified determinants of RD; P < 0.05 significant. SAS release 8.1 statistical software (SAS Institute Inc., Cary, NC) was used for all statistical analyses.
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Results |
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Three-hundred-sixty-six patients were evaluated for the analysis. Of those, 27 patients were excluded because of Cr-Pre values
2.0 mg/dL (177 µM) (n = 8), preoperative hemodialysis (n = 1), conversion to CPB (n = 13), and "unstable" preoperative creatinine values suggestive of evolving preoperative renal injury (n = 5). Of the remaining 339 patients, the CABG group comprised 119 patients and the OPCAB group 220 patients. Table 1 displays the demographic data of these two observational cohorts. The CABG group differed from the OPCAB group with respect to age and number of distal grafts (Table 1). CPB time was 105 ± 35 min. Type of operation did not associate with the presence of postoperative RD as defined in Methods: 18 (8.2%) of 220 OPCAB patients versus 12 (10%) of 119 CABG patients (P = 0.55).
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Table 2 presents the variables entered into the logistic regression for potential association with postoperative RD. Only age (P = 0.011, odds ratio 1.05/yr) and number of distal grafts (P = 0.037, odds ratio 1.5/graft), but not type of operation, associated independently with postoperative RD. Patients undergoing CABG with CPB more often arrived at the intensive care unit receiving inotropic support compared with those having OPCAB (37 of 199 versus 16 of 220 patients, P < 0.0001); however, inotrope use after operation did not associate with RD.
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The stepwise logistic regression c statistic (0.678) suggests valid results of the analysis. The data from 21 patients were not used in the multiple logistic regression model because of missing values. Two of these excluded patients (9.5%) developed RD. Of the 318 patients remaining in the analysis, 28 (8.8%) developed RD postoperatively.
Among patients with preoperative renal insufficiency (1.5 mg/dL Cr-Pre < 2 mg/dL), operative technique also did not impact on the incidence of postoperative RD (
2 = 2.27, P = 0.132). One OPCAB patient required postoperative hemodialysis versus no CPB patients. In-hospital mortality for the patients who developed postoperative RD was 10% versus 2.3% in the non-RD group (P = 0.017). Table 3 displays serum creatinine data for the patients with RD.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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These data fail to demonstrate that the OPCAB approach conferred renal protection compared with coronary revascularization with CPB. The potential reduction of renal risk and its association with morbidity and mortality may have a significant role in the choice of operative technique. This analysis supports that in a moderate-risk population, complete coronary revascularization via OPCAB is not associated with improved renal outcome as defined by a clinically relevant marker of RD. Similarly, no benefit accrued in a group of patients with mild preoperative renal insufficiency.
Occult perioperative renal ischemia is postulated to be a major contributing factor to the development of postoperative RD. The association between markers of compromised renal perfusion and adverse renal outcome has been well demonstrated in the literature and in clinical practice (5–7). RD may manifest as a result of several interrelated phenomena that result in an imbalance of the medullary oxygen supply demand relationship. This asymptomatic "renal angina" may be elicited during the course of CABG and other major surgical procedures. Off-pump revascularization, which potentially eliminates some of these phenomena, might have a salutary effect on postoperative renal outcome. Several small trials have demonstrated a change in surrogate markers of RD such as creatinine clearance, fractional excretion of sodium, microalbuminuria, and N-acetyl glucosaminidase activity in OPCAB versus CABG patients (3,8). The current investigation did not examine surrogate markers but rather focused on increases in postoperative serum creatinine concentration of at least 50% more than baseline levels and an absolute value of at least 2.0 mg/dL. This definition of RD has correlated well with adverse postoperative outcome in 2 major analyses of 9498 and 2222 patients, respectively (1,2). We confirm the clinical relevance of this definition of RD and report a more than fourfold increase (2.3% versus 10%, P = 0.017) in the mortality for those patients developing RD. Using this definition, however, the present study did not reveal a benefit of OPCAB over CABG with respect to postoperative renal function.
An observational study by Ascione et al. (9) of patients with preoperative renal insufficiency (preoperative creatinine >1.7 mg/dL) demonstrated a statistically significant increase in isolated 12-hour postoperative serum creatinine in 3250 on-pump patients when compared with 51 OPCAB patients. The reasons those results differ from the current results may include differences in the Cr-Pre, the small OPCAB cohort studied by Ascione et al., and potential differences in European and United States populations. Results of the current study deserve particular attention despite the observational design because of the cohort size, because all patients received complete revascularization by surgeons proficient with the OPCAB technique, and because the population studied is representative of a United States cohort at a tertiary care center.
Another small study suggests that the anecdotal perception that OPCAB is renoprotective may be inaccurate. In a randomized trial of 40 low-risk patients, Tang et al. (10) found similar increases in microalbumin and retinol binding protein, sensitive indicators of renal tubular injury and glomerular dysfunction, after both OPCAB and CABG. Although none of these randomized low-risk patients developed postoperative creatinine abnormalities, the similar increase in the surrogate markers of renal injury suggests equal susceptibility in both groups should a "threshold" for injury be crossed. Data in the current study confirm the results of Tang et al. (10) and suggest that avoidance of CPB does not reduce renal morbidity for patients with normal preoperative renal function or for those with mild preoperative renal insufficiency. The current results also confirm the previously demonstrated increased mortality associated with RD (10% versus 2.3%) (10–13).
Table 4 categorizes some specific etiologies implicated in the development of postoperative RD and their postulated prevalence during the two operative bypass revascularization techniques. Although OPCAB, by avoiding nonpulsatile flow, may cause less inflammation and a smaller embolic load, the technique often features major hemodynamic swings, periods of low cardiac output, and liberal use of vasoconstrictors. These factors may mitigate any benefits of avoiding CPB. Despite the differences in fluid and hemodynamic management inherent with the two techniques, RD occurred with similar frequency, and inotrope use did not independently predict RD. Similar rates of RD with OPCAB and CABG implicate hemodynamically induced renal ischemia as the etiology of postoperative RD, whether from low cardiac output (OPCAB) or lack of pulsatile perfusion (CABG), rather than the CPB-only associated factors of inflammation, hyperthermia during aggressive rewarming (perfusate >37°C), and renal macroemboli. Alternatively, each technique may cause RD by its unique mechanism, with resultant similar aggregate rates.
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The current trial suffers from its observational, nonrandomized design, and use of a single, relatively nonspecific measure of renal function, i.e., serum creatinine concentration. However, a previous analysis of 3991 patients at another institution demonstrated that both peak serum creatinine concentration after surgery and the fractional change perioperatively, the indices used by the current study, independently associated with major morbidity and mortality after coronary artery surgery.1 The differences in cohorts for age and number of distal grafts detected in this trial, although minor, might reflect a surgical selection bias. Despite the overall comparability of the two cohorts, other subtle differences in the groups may have gone undetected and influenced the choice of technique and outcome. A prospective, randomized trial with greater technical standardization is needed to determine whether OPCAB attenuates the incidence of end organ dysfunction, whether renal or neurologic.
Unfortunately, clinicians continue to resist randomly assigning patients to OPCAB or CABG, on the ethical grounds of providing optimum patient care. Until such time when sufficient randomized trials appear, observational cohorts such as the current report, of varying cohort sizes, must suffice to provide incremental evidence comparing the two approaches.
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Footnotes |
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1 Stafford Smith M, Redden D, Newman M, Phillips-Bute B. Association of postoperative peak and fractional serum creatinine change with post-CABG mortality [abstract]. Anesthesiology 2000;93:A-240.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Chertow GM, Lazarus JM, Christiansen CL, et al. Preoperative renal risk stratification. Circulation 1997; 95: 878–84.
[Abstract/Free Full Text] - Mangano CM, Diamondstone LS, Ramsay JG, et al. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. Ann Intern Med 1998; 128: 194–203.
[Abstract/Free Full Text] - Ascione R, Lloyd CT, Underwood MJ, et al. On-pump versus off-pump coronary revascularization: evaluation of renal function. Ann Thorac Surg 1999; 68: 493–8.
[Abstract/Free Full Text] - Gamoso MG, Phillips-Bute B, Landolfo KP, et al. Off-pump versus on-pump coronary artery bypass surgery and postoperative renal dysfunction. Anesth Analg 2000; 91: 1080–4.
[Abstract/Free Full Text] - Slogoff S, Reul GJ, Keats AS, et al. Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 1990; 50: 911–8.[Abstract]
- Zanardo G, Michielon P, Paccagnella A, et al. Acute renal failure in the patient undergoing cardiac operations: prevalence, mortality rate and main risk factors. J Thorac Cardiovasc Surg 1994; 107: 1489–95.
[Abstract/Free Full Text] - Myers BD, Moran SM. Hemodynamically mediated acute renal failure. N Engl J Med 1986; 314: 97–105.[Web of Science][Medline]
- Loef BG, Epma AH, Navis G, et al. Off-pump coronary revascularization attenuates transient renal damage compared with on-pump coronary revascularization. Chest 2002; 121: 1190–4.
[Abstract/Free Full Text] - Ascione R, Nason G, Al-Ruzzeh S, et al. Coronary revascularization with or without cardiopulmonary bypass in patients with preoperative nondialysis-dependent renal insufficiency. Ann Thorac Surg 2001; 72: 2020–5.
[Abstract/Free Full Text] - Tang AT, Knott J, Nanson J, et al. A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. Eur J Cardiothorac Surg 2002; 22: 118–23.
[Abstract/Free Full Text] - Chertow GM, Levy EM, Hammermeister KE, et al. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998; 104: 343–8.[Web of Science][Medline]
- Anderson RJ, O’Brien M, MaWhinney S, et al. Renal failure predisposed to adverse outcome after coronary artery bypass surgery. Kidney Int 1999; 55: 1057–62.[Web of Science][Medline]
- Forescue EB, Bates DW, Chertow GM. Predicting acute renal failure after coronary bypass surgery: cross-validation of two risk-stratification algorithms. Kidney Int 2000; 57: 2594–602.[Web of Science][Medline]
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