|
|
||||||||
Ann Thorac Surg 1999;68:493-498
© 1999 The Society of Thoracic Surgeons
a Bristol Heart Institute, Bristol Royal Infirmary, Bristol, United Kingdom
Address reprint requests to Dr Angelini, Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW United Kingdom
e-mail: g.d.angelini{at}bristol.ac.uk
| Abstract |
|---|
|
|
|---|
Methods. A prospective, randomized, controlled trial was performed in 50 patients (45 males, mean age 61 ± 3.7 years) undergoing elective coronary artery bypass grafting. Patients were randomly assigned to conventional revascularization with cardiopulmonary bypass (on pump) or beating heart revascularization (off pump). Glomerular and tubular function were assessed up to 48 hours postoperatively.
Results. There were no deaths, myocardial infarctions or acute renal failure in either group. Glomerular filtration as assessed by creatinine clearance and the urinary microalbumin/creatinine ratio was significantly worse in the on pump group (p < 0.0004 and 0.0083, respectively). Renal tubular function was also impaired in the on pump group as assessed by increased N-acetyl glucosaminidase activity (p < 0.0272).
Conclusions. These results suggest that off pump coronary revascularization offers a superior renal protection when compared with conventional coronary revascularization with cardiopulmonary bypass and cardioplegic arrest in first time coronary bypass patients.
| Introduction |
|---|
|
|
|---|
Recently, there has been a revival of interest in performing coronary artery bypass grafting on a beating heart [813], with early results suggesting better preservation of left ventricular contraction compared with conventional techniques in high-risk patients [9, 11]. There are, however, no data on the effects of beating heart operations on renal function from a prospective randomized study of patients who had elective operations.
| Patients and methods |
|---|
|
|
|---|
Anesthetic technique
Anesthetic technique was standardized for all patients and consisted of intravenous anesthesia with propofol infusion at 3 mg/kg per hour combined with remifentanyl infusion at 0.5 to 1 µg/kg per minute. Neuromuscular blockade was achieved by 0.1 to 0.15 mg/kg pancuronium bromide or vecuronium, and the lungs were ventilated to normocapnia with air and oxygen (45% to 50%) without positive end-expiratory pressure. In the on-pump group, metaraminol or phentolamine were used to maintain the systemic pressure between 50 to 60 mm Hg. In the off-pump group, mean arterial pressure of 60 mm Hg or higher was maintained with increments of metaraminol 0.5 to 1.0 mg or volume as dictated by the hemodynamic condition, in combination with esmolol to maintain a heart rate less than 70 beats per minute.
Heparin and protamine treatment
In the on-pump group, heparin was given at a dose of 300 IU/kg to achieve a target activated clotting time of 480 seconds or above before commencement of CPB. The activated clotting time was monitored during the bypass period (every 15 minutes), and an additional 3,000 IU of heparin were administered if required. In the off-pump group, heparin 100 IU/kg was administered before the start of the first anastomosis. The target activated clotting time in this group was 250 to 350 seconds. Protamine was used at the end of the operation to reverse the effect of heparin and return the activated clotting time to preoperative levels.
Surgical technique
Cardiopulmonary bypass was instituted using ascending aortic cannulation and a two-stage venous cannulation in the right atrium. A standard circuit was used, including a bard tubing set, which included a 40-µm filter, a Stockert roller pump (Sorin Biomedica, Midhurst, UK), and a hollow fiber membrane oxygenator (Monolyth; Sorin Biomedica, Midhurst, UK). The extracorporeal circuit was primed with 1,000 mL of Hartmanns solution, 500 mL of gelofusine, 0.5g/kg of mannitol, 7 mL of 10% calcium gluconate, and 60 mg of heparin. Nonpulsatile flow was used. The flow rate throughout bypass was 2.4 L/m2 per minute. Systemic temperature was kept between 34° and 36°C. Myocardial protection was achieved by using intermittent antegrade hyperkalemic warm blood cardioplegia as described by Calafiore and colleagues [14]. Once all distal anastomoses were completed, the aortic cross-clamp was removed and the proximal anastomosis performed with partial clamping. One surgeon completed all procedures.
The method of exposure and stabilization used for the anastomosis was a combination of the technique previously described by our group [15] and a CTS retractor (Cardiothoracic Systems Inc, Cupertino, CA). The target vessel was then exposed and snared above the chosen point for anastomosis by using a 4-0 Prolene (Ethicon, Somerville, NJ) suture with a soft plastic snugger to prevent coronary injury. The coronary artery was then opened and the anastomosis performed. Visualization was enhanced using the surgical blower-humidifier (model SSVW-002; Surgical Site Visualization Wand, Research Medical Inc, Midvale, UT) with
-inch polyvinylchloride gas line and fluid administration set connected to a regulated gas source of medical air. An intracoronary shunt (Anastoflo Intravascular Shunt; Research Medical Inc, Midvale, UT) was used only in cases of relative electrocardiographic or hemodynamic instability and excessive bleeding during the anastomosis.
Biochemical markers
A selection of noninvasive markers was used to examine both glomerular and tubular function. Creatinine clearance is a well-established indicator of glomerular filtration rate [5] and can be determined by sampling both plasma and urinary creatinine content. Functional alterations were evaluated further by assessing the urinary levels of microalbumin-to-creatinine ratio as an index of glomerular damage. Although many enzymes are excreted into the urine by the kidney, many are unstable and are therefore unsuitable for use in clinical diagnosis [16]. N-acetyl-ß-glucosaminidase (NAG) is the most widely assayed urinary enzyme for the detection of renal damage because of its stability in urine, its relative molecular mass (M 130 000), which precludes filtration by the glomerulus and its presence in high activity in the tubular lysosomes. Increased NAG activity in urine therefore provides a marker of renal tubular damage [16].
Specimen collection
Urine was collected for creatinine clearance measurement during four intervals, including over a 3-hour period in the evening before the operation, during the entire period of the operation, and then 24 hourly until (and including) the second postoperative day. A blood sample was also taken at the beginning of each period for serum creatinine measurement. Furthermore, 10-mL aliquots of urine were collected at the same stages to assay NAG activity.
Laboratory methods
Blood was allowed to clot and centrifuged at 2,000 x g for 15 minutes; the serum was separated immediately, and analysis was performed on fresh serum. Serum and urine creatinine values were determined with a commercial reagent kit (HiCo Creatinine; Boehringer Mannheim GmbH Diagnostica, Lewes, UK). Creatinine clearance was determined by the standard formula: creatinine clearance (mL/minute) = [urine creatinine concentration (mg/mL) x urine volume (mL/min)]/plasma creatinine concentration (mg/mL). Serum creatinine level at the start of each period was used to determine the creatinine clearance during that period. Urine microalbumin levels (mg/L) were determined by immunoturbidimetry on the Cobas Mira (Koni Inst, Sweden) calibrated for albumin, an assay designed to quantify concentrations of urinary albumin less than 100 mg/L. N-acetyl-ß-glucosaminidase activity was measured as reported by Horak and associates [17].
Statistical analysis
Data are presented as mean ± standard deviation. Comparisons between preoperative variables were made using Fishers exact test. Repeated measures analysis of variance was used to assess differences over time between groups, and the Bonferroni test was used to assess differences within a group. Analyses were performed using Statview (SAS Institute Inc, Cary, NC)
| Results |
|---|
|
|
|---|
|
|
For creatinine clearance over time, the use of cardiopulmonary bypass had a significant effect (p = 0.0004). Creatinine clearance improved significantly in the on-pump group compared with the off-pump group from a mean of 88 ± 27 mL/minute preoperatively to 133 ± 45 mL/minute during the operative period (p < 0.0001). However, it then deteriorated during the first postoperative 24 to 48 hour period to 72 ± 24 mL/minute and 70 ± 24 mL/minute, respectively, which was significantly worse than the on-pump group (p < 0.0001) (Fig 1).
|
|
|
|
|
| Comment |
|---|
|
|
|---|
Operation on a beating heart is a relatively new surgical procedure and can be considered the best model of pulsatile perfusion, which also avoids the use of CPB and its side effects. In the present study we used beating heart operations in elective patients who needed myocardial revascularization (excluding patients with involvement of the distal branch of the circumflex artery) to clarify the impact of this procedure on renal function as part of a prospective randomized study. The exclusion criteria attempted to avoid exposing the two groups to concomitant renal risk factors.
In agreement with previous reports [5, 20], this study found a marked improvement in creatinine clearance, a reliable indicator of glomerular filtration rate, during CPB in the on-pump group. The off-pump group also showed a significant increase in this marker at the end of the operation. This improvement is probably made possible by the well documented ability of the kidney to increase its glomerular filtration capacity under a variety of conditions, so called renal functional reserve [21]. Nevertheless, at 24 and 48 hours postoperatively the creatinine clearance values decreased significantly in the on-pump group, reaching levels markedly lower than preoperative levels. Conversely, in the off-pump group the values returned to preoperative levels at both 24 and 48 hours postoperatively. Functional alteration of the glomerular and tubular parts of the nephron can be evaluated further by assessing microalbuminuria and NAG activity, respectively. When the normal tubular protein absorption mechanism is near saturation, a small increase in glomerular permeability results in a large increase in proteinuria. Therefore, concentrations of urinary albumin can be used reliably as an index of glomerular damage [5]. More recently, urinary NAG activity has emerged as the most widely assayed urinary enzyme for detection of renal damage because of its stability in urine, its relative molecular mass which precludes filtration by the glomerulus, and its presence in high activity in the tubular lysosomes. The marked increases in urinary albumin-to-creatinine ratio and NAG activity levels in the current study confirm the potential deleterious effect of the CPB on renal function. Furthermore, changes in these markers appeared to be significantly lower in the off-pump group, suggesting better functional preservation.
This study also showed a significantly higher requirement for vasoconstrictors in the on-pump group to keep the perfusion pressure at the predefined level during normothermic CPB compared with the need for vasoconstrictors to keep the mean blood pressure at a predefined level in the off-pump group. However, in previous reports that did not appear to have any effect on the degree of renal dysfunction or the impact on proteinuria [5, 22]. It is important that the above results were obtained despite the advantageous effect of hemodilution on blood viscosity and improved renal plasma flow secondary to pump priming [23] and the use of mannitol in the prime in the on-pump group. This is reported to maintain glomerular capillary pressure [24] and prevent tubular obstruction, protect against free radical induced injury to the renal brush border membrane, reduce ischemia-induced protein leakage across kidney vessel walls, and reduce plasma hydrogen peroxide free radicals [24].
The current study also showed a significantly higher blood loss and transfusion requirement in the on-pump group. Although this loss seems high, 28% of those patients were unstable and treated preoperatively with aspirin and low-molecular-weight heparin. Furthermore, these losses concur with other recently published data [25, 26]. Lung infections were defined as lung collapse and pyrexia requiring prolonged antibiotic therapy. Although the on-pump group had more infections, the difference was not significant. In conclusion, this study clearly showed that off-pump coronary revascularization is a safe surgical technique that provides better protection of renal function compared with conventional operations that use cardiopulmonary bypass and cardioplegic arrest.
| Acknowledgments |
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
C. H. Moller, L. Penninga, J. Wetterslev, D. A. Steinbruchel, and C. Gluud Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass surgery: systematic review with meta-analyses and trial sequential analyses Eur. Heart J., July 15, 2008; (2008) ehn335v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Briffa Off pump coronary artery bypass: a passing fad or ready for prime time? Eur. Heart J., June 1, 2008; 29(11): 1346 - 1349. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. G Raja and G. D Dreyfus Current Status of Off-pump Coronary Artery Bypass Surgery Asian Cardiovasc Thorac Ann, April 1, 2008; 16(2): 164 - 178. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Masoumi, M. R Saidi, F. Rostami, H. Sepahi, and D. Roushani Off-Pump Coronary Artery Bypass Grafting in Left Ventricular Dysfunction Asian Cardiovasc Thorac Ann, February 1, 2008; 16(1): 16 - 20. [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] |
||||
![]() |
J. W. Hammon Extracorporeal Circulation: The Response of Humoral and Cellular Elements of Blood to Extracorporeal Circulation Card. Surg. Adult, January 1, 2008; 3(2008): 370 - 389. [Full Text] |
||||
![]() |
T. M. Dewey and M. J. Mack Myocardial Revascularization without Cardiopulmonary Bypass Card. Surg. Adult, January 1, 2008; 3(2008): 633 - 654. [Full Text] |
||||
![]() |
V. Falk and F. W. Mohr Minimally Invasive Myocardial Revascularization Card. Surg. Adult, January 1, 2008; 3(2008): 697 - 710. [Full Text] |
||||
![]() |
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] |
||||
![]() |
E. L. Hannan, C. Wu, C. R. Smith, R. S.D. Higgins, R. E. Carlson, A. T. Culliford, J. P. Gold, and R. H. Jones Off-Pump Versus On-Pump Coronary Artery Bypass Graft Surgery: Differences in Short-Term Outcomes and in Long-Term Mortality and Need for Subsequent Revascularization Circulation, September 4, 2007; 116(10): 1145 - 1152. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Mizutani, A. Matsuura, K. Miyahara, T. Eda, A. Kawamura, T. Yoshioka, and K. Yoshida On-Pump Beating-Heart Coronary Artery Bypass: A Propensity Matched Analysis Ann. Thorac. Surg., April 1, 2007; 83(4): 1368 - 1373. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Liangos, M. C. Perianayagam, V. S. Vaidya, W. K. Han, R. Wald, H. Tighiouart, R. W. MacKinnon, L. Li, V. S. Balakrishnan, B. J.G. Pereira, et al. Urinary N-Acetyl-beta-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure J. Am. Soc. Nephrol., March 1, 2007; 18(3): 904 - 912. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Natarajan, S. Samadian, and S. Clark Coronary artery bypass surgery in elderly people Postgrad. Med. J., March 1, 2007; 83(977): 154 - 158. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Allen, W. T. McBride, T. J. McMurray, A. S. Phillips, S. P. Penugonda, G. Campalani, I. S. Young, and M. A. Armstrong Cell Salvage Alters the Systemic Inflammatory Response After Off-Pump Coronary Artery Bypass Grafting Surgery Ann. Thorac. Surg., February 1, 2007; 83(2): 578 - 585. [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. Sedrakyan, A. W. Wu, A. Parashar, E. B. Bass, and T. Treasure Off-Pump Surgery Is Associated With Reduced Occurrence of Stroke and Other Morbidity as Compared With Traditional Coronary Artery Bypass Grafting: A Meta-Analysis of Systematically Reviewed Trials * Supplemental Appendix I Stroke, November 1, 2006; 37(11): 2759 - 2769. [Full Text] [PDF] |
||||
![]() |
J. DeSimone and P. Sergeant Off-pump myocardial revascularization MMCTS, October 9, 2006; 2006(1009): 539. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Stamou Reply to the Editor J. Thorac. Cardiovasc. Surg., July 1, 2006; 132(1): 212 - 212. [Full Text] [PDF] |
||||
![]() |
Y. Abu-Omar and C. Ratnatunga Cardiopulmonary Bypass and Renal Injury Perfusion, July 1, 2006; 21(4): 209 - 213. [Abstract] [PDF] |
||||
![]() |
P. S. Lingaas, P. K. Hol, R. Lundblad, K. A. Rein, L. Mathisen, H.-J. Smith, R. Andersen, E. Thaulow, T. I. Tonnesen, J. L. Svennevig, et al. Clinical and Radiologic Outcome of Off-Pump Coronary Surgery at 12 Months Follow-Up: A Prospective Randomized Trial Ann. Thorac. Surg., June 1, 2006; 81(6): 2089 - 2095. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Brown, R. S. Poston, J. S. Gammie, M. G. Cardarelli, K. Schwartz, J. A. H. Sikora, S. Yi, R. N. Pierson III, and B. P. Griffith Off-Pump Versus On-Pump Coronary Artery Bypass Grafting in Consecutive Patients: Decision-Making Algorithm and Outcomes Ann. Thorac. Surg., February 1, 2006; 81(2): 555 - 561. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Izumi, K. Magishi, N. Ishikawa, and F. Kimura On-Pump Beating-Heart Coronary Artery Bypass Grafting for Acute Myocardial Infarction Ann. Thorac. Surg., February 1, 2006; 81(2): 573 - 576. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. B. Gerritsen, W.-J. P. van Boven, D. S. Boss, F. J. Haas, E. P. van Dongen, and L. P. Aarts Malondialdehyde in plasma, a biomarker of global oxidative stress during mini-CABG compared to on- and off-pump CABG surgery: a pilot study Interactive CardioVascular and Thoracic Surgery, February 1, 2006; 5(1): 27 - 31. [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] |
||||
![]() |
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] |
||||
![]() |
S. G Raja and G. D Dreyfus Modulation of Systemic Inflammatory Response after Cardiac Surgery Asian Cardiovasc Thorac Ann, December 1, 2005; 13(4): 382 - 395. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Holzmann, S. Ahnve, N. Hammar, L. Jorgensen, K. Klerdal, K. Pehrsson, and T. Ivert Creatinine clearance and risk of early mortality in patients undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 746 - 746. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.J. Murphy, C.S. Rogers, W.B. Lansdowne, I. Channon, H. Alwair, A. Cohen, M. Caputo, and G.D. Angelini Safety, efficacy, and cost of intraoperative cell salvage and autotransfusion after off-pump coronary artery bypass surgery: A randomized trial J. Thorac. Cardiovasc. Surg., July 1, 2005; 130(1): 20 - 28. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Dixon, J. Santamaria, and D. Campbell Coagulation Activation and Organ Dysfunction Following Cardiac Surgery Chest, July 1, 2005; 128(1): 229 - 236. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. D.L. Keenan, Y. Abu-Omar, and D. P. Taggart Bypassing the Pump: Changing Practices in Coronary Artery Surgery Chest, July 1, 2005; 128(1): 363 - 369. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Asimakopoulos, A. P. Karagounis, O. Valencia, N. Alexander, M. Howlader, M. A. Sarsam, and V. Chandrasekaran Renal Function After Cardiac Surgery Off- Versus On-Pump Coronary Artery Bypass: Analysis Using the Cockroft-Gault Formula for Estimating Creatinine Clearance Ann. Thorac. Surg., June 1, 2005; 79(6): 2024 - 2031. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Abu-Omar, S. Mussa, M. J. Naik, N. MacCarthy, S. Standing, and D. P. Taggart Evaluation of Cystatin C as a marker of renal injury following on-pump and off-pump coronary surgery Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 893 - 898. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Weerasinghe, T. Athanasiou, S. Al-Ruzzeh, R. Casula, P. P. Tekkis, M. Amrani, P. Punjabi, K. Taylor, R. Stanbridge, and B. Glenville Functional Renal Outcome in On-Pump and Off-Pump Coronary Revascularization: A Propensity-Based Analysis Ann. Thorac. Surg., May 1, 2005; 79(5): 1577 - 1583. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Bainbridge, J. Martin, and D. Cheng Off Pump Coronary Artery Bypass Graft Surgery Versus Conventional Coronary Artery Bypass Graft Surgery: A Systematic Review of the Literature Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2005; 9(1): 105 - 111. [Abstract] [PDF] |
||||
![]() |
G. W. Staton, W. H. Williams, E. M. Mahoney, J. Hu, H. Chu, P. G. Duke, and J. D. Puskas Pulmonary Outcomes of Off-Pump vs On-Pump Coronary Artery Bypass Surgery in a Randomized Trial Chest, March 1, 2005; 127(3): 892 - 901. |