Renal function in patients undergoing cardiopulmonary bypass for open cardiac surgical procedures

Irshad Ahmad1, *Mubasher Ahmad Bhat 2, Abdul Wahid Bhat3, Mohamad Ommid4, Tanveera Gani5, Gousia Nisa5 Assistant Professor1, Senior Resident2, Lecturer4 Department of Anaesthesiology and Critical care, Assistant Professor3 Department of Blood Transfusion and Immunohematology, Sher-i-Kashmir Institute of Medical Sciences and Medical College, Srinagar, India. Assistant Surgeon5, Department of Health Services, Jammu and Kashmir, India.


Introduction
Cardiopulmonary bypass (CPB) allows perfusion of the patient's vital organs while oxygenating blood and removing carbon dioxide permitting surgical exposure of heart and great vessels.Most cardiac procedures use full cardiopulmonary bypass, in which blood is drained from right side of heart and returned to systemic circulation through the aorta.The cardiopulmonary bypass circuit performs functions of both heart and lungs 1 .Renal dysfunction following CPB is a frequent complication of open heart surgery.Acute renal failure (ARF) requiring dialysis occurs in approximately 1.5% of patients following cardiac surgery and remains a cause of major morbidity and mortality 2 .Impairment of renal function (plasma creatinine levels greater than 1.5 mg/dl but less than 5 mg/dl) occurs after 30% of cardiac operations performed with CPB and is associated with a mortality rate of 7-38 % 3 .When acute renal failure after CPB is severe enough to require dialysis morality reaches 70-100 % 4 .This is in marked contrast to the 1-2% mortality rate observed in patients whose cardiac operation is not complicated by acute renal failure 4 .
The negative effect of CPB on renal function may be due to several factors including non pulsatile blood flow, inadequate renal perfusion and free plasma haemoglobin 5,6,7,8 .
The aetiology of renal insufficiency following cardiac surgery is poorly understood but it is believed that ischaemic injury of the kidney resulting from inadequate perfusion is a major factor, although renal injury by exotoxins (e.g.antibiotics, anaesthetic agents, contrast media, diuretics etc.) and endotoxins (e.g.myoglobin) may also be involved 9 .Cardiopulmonary bypass utilizing non-pulsatile flow produces alteration in vasomotor tone with initial vasodilatation and subsequent vasoconstriction.This vasomotor response to bypass ultimately produces renal arteriolar vasoconstriction with resultant reduction in renal and cortical blood flow and potential development of renal tubular necrosis.Angiotensin II levels are reported to be higher during nonpulsatile CPB.These elevations in angiotensin II could contribute to renal vasoconstriction 8 .Among other factors, CPB is incriminated in pathogenesis of renal failure since such intraoperative factors such as prolonged duration of cardiopulmonary bypass, haemoglobinemia, hypotension, oliguria and low output syndromes have been shown to correlate with development of renal failure 10,11,12 .This prospective study was undertaken to study renal function in patients undergoing cardiopulmonary bypass for open cardiac procedures.

Methods
This study was conducted in department of anaesthesiology and critical care over a two year period.After approval from the institutional ethical committee and informed consent, 65 patients of either sex in the age group of 10 -50 years scheduled to undergo various cardiac procedures were enrolled in the study.Inclusion criteria were represented by normal preoperative levels of serum creatinine, blood urea nitrogen (BUN), blood glucose levels, urine analysis, 24 hour urinary protein < 200 mg, and normal 24 hour creatinine clearance.Patients with any degree of renal impairment and those with diabetes mellitus were excluded from this study.After pre-operative evaluation patients underwent elective cardiac surgical procedures with CPB.Induction of anaesthesia with propofol 3mg/kg, atracurium 0.5 mg/kg and morphine 100µg/kg was followed by maintenance with nitrous oxide 66% in oxygen and intermittent halothane 0. After completion of procedure patients were transferred to surgical intensive care unit for postoperative management and monitoring.Patients were managed with or without ventilatory or inotropic support depending on their clinical condition.Patients were shifted to cardiovascular and thoracic surgery ward as soon as their clinical condition permitted.Blood urea nitrogen, serum creatinine, 24 hour creatinine clearance was performed on day one and day seven of postoperative period.Statistical analysis was performed on SSPS version 11.3, statistical software for social sciences, Chicago, U.S.A for windows and included students paired t-test and ANOVA.A p value <0.05 was considered significant.For serum creatinine and 24 hour creatinine clearence values, while comparing preoperative with postoperative day 7 and postoperative day 1 with postoperative day 7, a statistically significant difference was observed in MVR, AVR and ASD repair patients.(Figure 2 and 3).

DISCUSSION
The development of acute kidney injury (AKI) after adult cardiac surgery is associated with increased morbidity and mortality 13 .The morbidity was 7.69% due to postoperative oliguric acute renal failure and the overall mortality was 6.1% in our study.
The development of acute postoperative renal insufficiency after cardiac operations has been attributed to cardiopulmonary bypass as a result of haemodynamic factors or toxic insults on the kidneys or both 4 .
In our study procedures involved ranged from congenital defects to valve replacements.Commonest procedure performed was mitral valve replacement (MVR) followed by ASD repair.
In our results the patient with maximal total cardiopulmonary bypass (CPB) time (160 minutes) had a normal postoperative course.Patients who had postoperative deranged kidney function tests had total CPB times lower than some of the patients who had a normal postoperative course.This is in accordance with the study by Mancini E et al 14  later release it.So, on long perfusions tubular cells may become less functional in extracting PAH inspite of full blood flow.Safe duration of total CPB is thought to be closer to three hours in general 16 .It has been suggested more specifically that postoperative renal dysfunction is due to renal afferent arteriolar vasoconstriction during CPB.Although in terms of renal blood flow there are no really gross differences between pulsatile and non-pulsatile CPB 6,17 .
In our study there was no correlation between aortic cross clamp time (ACCT) and postoperative renal dysfunction.Minimum ACCT was 18 minutes for ASD repair and maximum ACCT was 83 minutes for DVR.Patients who had postoperative deranged kidney function had ACCT lower than some of those patients who had a normal postoperative course.Estimate of safe ACCT during CPB is not valid due to differing vulnerabilities between patients 1 .The morbidity of 7.69% due to postoperative oliguric acute renal failure (ARF) and the overall mortality of 6.1% in our study are significantly lower than a study done by Gailiunas P Jr et al 3 .In our study ARF requiring dialysis occurred in 100% of patients and there was mortality of 80% which is in agreement with the study by Hieberman L et al 4 .However, the patients in our study were in age group of 10-50 years and had normal pre-operative renal function tests.It is still controversial whether age is important in predisposing to ARF though a reduced functional capacity of kidneys is documented in older patients 18 .
Blood urea nitrogen, serum creatinine and 24hour creatinine clearance were utilised as indicators of renal function.For patients who underwent MVR (n=24) comparison of BUN on postoperative day 7 with BUN postoperative day1 showed statistically significant difference.For patients who underwent ASD repair, there was a decrease in BUN on postoperative day 1 with respect to pre-operative values and the difference was statistically significant.This lower BUN on postoperative day 1 is possibly because of atrial natriuretic peptide (ANP) release during manipulation of atria 19 .When considering patients who underwent DVR (n=9) and AVR (n=8), 2 patients with DVR and one patient with AVR had very high BUN on postoperative day 7 with respect to pre-operative values leading to higher standard deviation (± 19.22 in case of DVR and ± 15.98 in case of AVR).Hence statistical significance was not observed.
A decrease in serum creatinine was found on postoperative day 1 with respect to pre-operative values in patients undergoing various surgical procedures except in case of AVR patients.In MVR, ASD repair and AVR patients, a statistically significant difference was found between serum creatinine (pre-operative, postoperative day 1 and postoperative day 7).Patients who underwent DVR (n=9, 2 patients of DVR) had very high serum creatinine on postoperative day 7 with respect to postoperative day 1 and pre-operative values leading to higher standard deviation (± 1.40).Hence statistical significance was not observed.
There was an increase in 24hour creatinine clearance on postoperative day 1 in comparison with pre-operative values for patients undergoing various surgical procedures except for DVR and LAM excision.In MVR and ASD repair a statistically significant difference was found between 24hour creatinine clearance (preoperative, postoperative day 1 and postoperative day 7).Patients who underwent DVR (n=9) and AVR(n=8), 2 patients of DVR and one patient of AVR had significant decrease in 24hour creatinine clearance on postoperative day 7 with respect to pre-operative values leading to higher standard deviation(±35.81 in case of DVR and ±25.94 in case of AVR).Hence statistical significant difference could not be achieved.The results in our study are in agreement with the study by Mancini E et al 14 .
The intraoperative urinary output has been taken into consideration only in a minority of the studies on ARF after cardiac operation.Abel and colleagues 11 registered a lower diuresis before CPB in patients with postoperative renal impairment, whereas urinary output during and after CPB was not different.Slogoff and associates 20 evaluated the incidence of oliguria during CPB, and Crown and associates 21 considered the total intraoperative diuresis.Both studies failed to demonstrate any statistical correlation with postoperative renal outcome.In our study all patients who underwent CPB for open cardiac surgical procedures received diuretic treatment with furosemide during CPB and patients who underwent valvular replacements received additional mannitol during CPB, thereby proving that intraoperative diuresis has no correlation with postoperative renal outcome.
In the study by Parolari A et al 23 ARF occurred in 8.9% patients with pre-operative normal renal function tests.In contrast in our study postoperative oliguric ARF occurred in 7.69%.This difference may be because of the large sample size in the study by Parolari A et al 13 .In our study all patients with ARF received dialysis, overall mortality in our study was 6.1% and mortality in patients requiring dialysis was 80%.

CONCLUSION
The prevention of acute renal failure in the cardiovascular surgical patients appears to be still the major challenge.Despite the use of physical and pharmacological adjuncts for its prevention and monitoring of haemodynamic variables, the incidence of postoperative renal failure has not decreased in patients who had normal pre-operative renal status.Optimisation of cardiac performance post cardiopulmonary bypass seems to be the most important observed factor in the prevention of postoperative renal dysfunction in patients requiring total cardiopulmonary bypass.
which revealed that CPB time did not predict acute renal failure during cardiac surgery.Moghissi and co-workers confirmed flow after two hours of CPB possibly causing renal dysfunction which was in contradiction to our study 7 .The reason of contradiction with Moghissi K et al study is likely to be by the use of Para amino Hippuric acid (PAH) clearance technique used for that study as the kidneys may store PAH and creatinine Post operative day 1 Serum creatinine Pre operative Serum creatinine Post operative day 7

Table 3 :
Showing aortic cross clamp time (in minutes) in relation to various surgical procedures Mean ± SD = Mean Standard Deviation

Table 4 :
Showing percentage of patients with renal dysfunction (deranged KFT's) in relation to surgical procedures.