Abstract
Introduction
The spectrum of renal injury following cardiopulmonary bypass (CPB) varies from sub-clinical injury to established renal failure requiring dialysis. Despite advances in anaesthetic techniques and in perioperative management of cardiac surgical patients, acute renal failure remains a frequent and serious complication of cardiac surgery. Its incidence varies depending on definition and affects 1-5% of all patients1-3. While it may often be regarded as a transient injury that recovers with conservative management in most patients, there is evidence supporting a significant increase in mortality and morbidity that accompanies perioperative renal dysfunction1-3. Severe acute renal failure (ARF) requiring dialysis after cardiac surgery is an independent risk factor for death 4 . In a multicenter observational study from the Veterans Affairs health system, Chertow and colleagues analyzed a large cohort of over 42,000 cardiac surgical patients. After adjusting for preoperative risk factors, as well as other postoperative morbidities that may influence mortality, the odds ratio for mortality associated with ARF requiring dialysis was 7.9 4 . In addition, mild preoperative renal dysfunction represents an independent predictor of in-hospital mortality, morbidity, and mid- and long-term survival5-7. Impairment of postoperative renal function is also associated with prolonged hospital stay and increased cost.
Over the last fifteen years, there has been a revival of interest in off-pump coronary artery bypass grafting (CABG). It is being used increasingly as an alternative to conventional CABG, aiming to reduce the mortality and morbidity associated with cardiopulmonary bypass. Following the introduction of new surgical techniques and technologies, about a fifth of CABG is now performed off-pump and the proportion is likely to increase 8 .
As most of the pathophysiological mechanisms resulting in postoperative renal injury are related to the use of CPB, it follows that a theoretical reduction in the incidence and severity of renal impairment may be achieved with the elimination of cardiopulmonary bypass. Only a few studies have evaluated the potential reno-protective effects of off-pump CABG in the presence of other confounding risk factors. The aim of this study is to determine whether off-pump CABG reduces the risk of postoperative renal injury.
Material and Methods
Patient Groups
All patients undergoing first-time CABG over a 3-year period (2002-2005) at a single institution (John Radcliffe Hospital, Oxford) were included in the study. There was a total of 1580 patients, of whom 1145 underwent on-pump and the remaining 435 underwent off-pump CABG. The selection of patients for either technique was dependent on the preference of the individual surgeons. The patient records were reviewed systematically and clinical data were prospectively collected.
Renal Function
Renal function was assessed by collecting serum creatinine values, obtained preoperatively and on days 1, 2 and 4 postoperatively. Creatinine clearance was used as the index of renal function as calculated using the Cockcroft and Gault formula 9 .
Cardiopulmonary Bypass
Following full anticoagulation with heparin, given at a dose of 300 IU/kg to maintain an activated clotting time of 400-600 seconds, CPB was instituted using an ascending aortic cannulation and a two-stage right atrial venous cannulation. A roller pump (Jostra HL 20, MAQUET Cardiopulmonary AG Hirrlingen Germany) and hollow-fibre membrane oxygenator (Affinity NT, Medtronic Inc., Medtronic International Trading Sàrl, Tolochenaz, Switzerland) were used. The extracorporeal circuit was primed with 1000 ml of Hartmann’s solution and 2500 IU heparin. CPB was maintained with non-pulsatile flow, with a flow rate of 2.4 l/m2/min at normothermia, with temperature allowed to drift to 34°C. Arterial line filtration was not used. Cardiotomy suction was used. Acid-base was managed with alpha-stat control. Myocardial protection was achieved with intermittent antegrade cold crystalloid cardioplegia. On completion of all distal anastomoses, the aortic cross-clamp was removed and the proximal anastomoses performed with partial aortic clamping.
Off-pump technique
All off-pump procedures were performed by a single surgeon (DPT). Complete anticoagulation with heparin was achieved as in the on-pump CABG group. Regional myocardial immobilisation was achieved with a suction stabilizer (Octopus, Medtronic Inc. or Guidant, Cardiothoracic Systems Inc., Indianapolis, IN, USA). The target coronary vessels were snared proximally with a silastic sling. An intracoronary shunt (Guidant Axius™) was only used when there was haemodynamic compromise during construction of the anastomosis (usually the distal right coronary artery). Increments of metaraminol and/or colloid were used as dictated by the haemodynamic condition. Visualization was enhanced by using a surgical blower-mister device (Medtronic Clearview®, Medtronic Inc.).
Statistical Analysis
Baseline data for the two groups are presented as mean and standard deviation or as proportions for categorical data. These are compared using t-tests or the Mann-Whitney U-test for non-normal data and Fisher’s exact tests for categorical data. Multiple regression analysis was used in order to adjust for known baseline preoperative confounding factors that include age, sex, diabetes and left ventricular function.
Results
Of the 1580 patients included in the study, 435 (28%) underwent off-pump CABG. The two groups were similar with respect to age, gender and diabetes (Table 1). Of the total number of patients, 274 (17%) were female and a similar proportion were diabetics.
Clinical characteristics and demographics of the patient population.
DM: diabetes mellitus; LVF: left ventricular function; SD: standard deviation.
Multivariate analysis demonstrated significantly lower creatinine clearance postoperatively in patients with diabetes (P<0.001), advanced age (P<0.001) and impaired preoperative left ventricular function (P=0.04). Patients undergoing on-pump surgery had significantly lower postoperative creatinine clearance compared to the off-pump CABG group (P=0.01) (Figure 1). The latter effect remained consistent after adjusting for potential confounding factors (age, diabetes, gender, LV function and preoperative creatinine clearance) in the multivariate analysis model (Table 2).
Figure showing creatinine clearance comparing patients undergoing on-pump to off-pump CABG surgery.
Multiple regression analysis.
DM: diabetes mellitus; LVF: left ventricular function.
All analyses were adjusted for baseline creatinine clearance
A –ve value in the results indicates better renal function (higher creatinine clearance)
Discussion
This study demonstrated a significant reduction in perioperative renal injury with off-pump CABG, as measured using creatinine clearance. In addition to avoidance of CPB, advanced age, diabetes and impaired left ventricular function were associated with significantly worse renal outcome.
The pathophysiology of renal injury is multifactorial and is related to perioperative renal hypoperfusion and the presence of endogenous and exogenous nephrotoxins and microembolisation9-19. As most of the pathophysiological mechanisms resulting in postoperative renal injury are related to the use of CPB, it follows that a theoretical reduction in the incidence and severity of renal impairment may be achieved with the elimination of extracorporeal circulation, especially in high-risk patients20,21.
The current evidence for off-pump surgery in reducing postoperative renal injury is conflicting. A randomised study by Ascione and colleagues 10 demonstrated a significant reno-protective effect of off-pump surgery whereas Tang and associates demonstrated no significant differences despite a trend of less injury in the off-pump group 22 . In a small observational study, Loef and colleagues demonstrated a significant reduction in transient renal injury with off-pump CABG 15 . We, similarly, reported that avoidance of cardiopulmonary bypass may reduce renal injury, as assessed using Cystatin C, particularly in higher risk patients 14 . The above studies, however, only included relatively low-risk patients and it has been argued that the benefits of off-pump surgery may only be evident in those at higher perioperative risk. In a propensity-based study of over 2000 patients, Weerasinghe and colleagues reported that off-pump surgery may reduce the risk for minor and major renal adverse outcome 23 . With regards to the conduct of CPB, Tang showed that leukodepletion may offer some renal protection in low-risk patients during CABG 22 . Additionally, with regards to the flow characteristics during extracorporeal circulation, Kocakulak et al. reported superior renal protection with pulsatile flow in high-risk patients 24 . In a prospective randomised comparison of two hundred unselected patients undergoing off-pump versus conventional CABG, Puskas and colleagues reported no difference in the postoperative incidence of renal failure between the two groups 17 . Several large observational studies that included high-risk patients have reported a significant reduction in the frequency of renal failure in patients undergoing off-pump CABG9,11,12,16,25. Di Mauro studied renal outcomes in over 2600 patients undergoing CABG, of whom 160 patients had preoperative renal impairment 26 . Acute renal failure occurred in 2.9% of the off-pump patients and 7.9% of those undergoing conventional CABG. This is consistent with results from the meta-analysis by Reston and colleagues 18 .
The results available to date would indicate that renal outcomes are at least as safe with off-pump surgery as with on-pump surgery. Selected groups, including ours, have reported significant benefits with the off-pump technique. Further large randomised trials, targeting higher risk patients are warranted before firm conclusions can be made.
There are several limitations to this study. It is relatively small and was conducted retrospectively. However, the data was prospectively collected on all the patients as part of the routine database entry for all cardiac surgical patients at that institution. Creatinine clearance was estimated from serum creatinine values using the Cockcroft and Gault formula. It has to be appreciated that while serum creatinine is the most commonly used parameter for the assessment of renal function, it has a relatively low sensitivity and its assay may be influenced by several confounding factors. In addition, as this was not a prospective randomised trial, the selection of patients for on-pump or off-pump surgery was left to the discretion of the individual surgeons.
In conclusion, this study suggests that off-pump CABG is associated with a reduction in renal injury as assessed using creatinine clearance.
Footnotes
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of Interest Statement
None Declared.