| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
Departments of Anesthesiology, and Cardiovascular Medicine and Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania
Address correspondence and reprint requests to Nanette Schwann, MD, Department of Anesthesiology, MS 310, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA 19102. Address e-mail to schwann{at}drexel.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
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.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
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.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
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.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
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).
|
|
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.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
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.
|
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.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  J. S. Ooi, M. R Abdul Rahman, S. A Shah, and M. Z Dimon Renal Outcome Following On- and Off-Pump Coronary Artery Bypass Graft Surgery Asian Cardiovasc Thorac Ann, December 1, 2008; 16(6): 468 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Massoudy, S. Wagner, M. Thielmann, U. Herold, E. Kottenberg-Assenmacher, G. Marggraf, A. Kribben, T. Philipp, H. Jakob, and S. Herget-Rosenthal Coronary artery bypass surgery and acute kidney injury--impact of the off-pump technique Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2853 - 2860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Rosner, D. Portilla, and M. D. Okusa Analytic Reviews: Cardiac Surgery as a Cause of Acute Kidney Injury: Pathogenesis and Potential Therapies J Intensive Care Med, January 1, 2008; 23(1): 3 - 18. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Di Mauro, M. Gagliardi, A. L. Iaco, M. Contini, A. Bivona, P. Bosco, S. Gallina, and A. M. Calafiore Does Off-Pump Coronary Surgery Reduce Postoperative Acute Renal Failure? The Importance of Preoperative Renal Function Ann. Thorac. Surg., November 1, 2007; 84(5): 1496 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Sajja, G. Mannam, R. M. Chakravarthi, S. Sompalli, S. K. Naidu, B. Somaraju, and R. R. Penumatsa Coronary artery bypass grafting with or without cardiopulmonary bypass in patients with preoperative non-dialysis dependent renal insufficiency: A randomized study J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 378 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rastan, J. I. Eckenstein, B. Hentschel, A. K. Funkat, J. F. Gummert, N. Doll, T. Walther, V. Falk, and F. W. Mohr Emergency Coronary Artery Bypass Graft Surgery for Acute Coronary Syndrome: Beating Heart Versus Conventional Cardioplegic Cardiac Arrest Strategies Circulation, July 4, 2006; 114(1_suppl): I-477 - I-485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Rosner and M. D. Okusa Acute Kidney Injury Associated with Cardiac Surgery Clin. J. Am. Soc. Nephrol., January 1, 2006; 1(1): 19 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. F. Fischer, B. Phillips-Bute, M. Swaminathan, C. Milano, and M. Stafford-Smith SymmetryTM Aortic Connector Devices and Acute Renal Injury: A Comparison of Renal Dysfunction After Three Different Aortocoronary Bypass Surgery Techniques Anesth. Analg., January 1, 2006; 102(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chukwuemeka, A. Weisel, M. Maganti, A. F. Nette, D. N. Wijeysundera, W. S. Beattie, and M. A. Borger Renal Dysfunction in High-Risk Patients After On-Pump and Off-Pump Coronary Artery Bypass Surgery: A Propensity Score Analysis Ann. Thorac. Surg., December 1, 2005; 80(6): 2148 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. McIlroy Failing to Reject the Null Hypothesis Does Not Mean that the Null Hypothesis Is True Anesth. Analg., June 1, 2005; 100(6): 1868 - 1869. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
