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Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial

Cardiothoracic Center, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom

Received 27 August 2007; received in revised form 18 December 2007; accepted 20 December 2007.

^_* Corresponding author. Address: Department of Cardiothoracic Surgery, Harefield Hospital, Harefield UB9 6JH, United Kingdom. Tel.: +44 7951 033090; fax: +44 1895 828970. (Email: b.mahesh{at}rbht.nhs.uk).

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
Objective: Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction, diabetes and impaired left-ventricular function, and following complicated procedures involving prolonged cardiopulmonary bypass (CPB). The aim of this prospectively randomised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group. Methods: Patients with preoperative serum creatinine >130 µmol/l (1.4 mg/dl), left-ventricular ejection fraction <50%, congestive heart failure, diabetes, or procedures involving prolonged CPB were randomised to receive either saline at 2 ml/h (n = 21), or furosemide at 4 mg/h (n = 21). Infusion was commenced after induction of anaesthesia and continued for 12 h postoperatively. Renal dysfunction was defined as >50% increase in serum creatinine postoperatively, or >130 µmol/l (1.4 mg/dl), or requirement for haemodialysis, or all of these. In patients with preoperative serum creatinine >130 µmol/l, >50% increase over preoperative levels was used to define postoperative renal dysfunction. Results: Following cardiac surgery, patients receiving furosemide had a higher urine output (3.4 ± 1.2 ml/kg/h in furosemide group and 1.2 ± 0.5 ml/kg/h in placebo group; p < 0.001), higher postoperative fluid requirement (4631 ± 1359 ml in furosemide group and 3714 ± 807 ml in placebo group, p = 0.011), and lower urinary-creatinine (2 ± 1.3 µmol/l in furosemide group and 5.9 ± 2.5 µmol/l in placebo group p < 0.001). Both groups had significant increase in retinol binding protein/creatinine ratio (7.2 ± 6 to 3152 ± 1411 in furosemide group; 4.9 ± 2.1 to 2809 ± 1125 in placebo group; p < 0.001) and peak serum creatinine (98 ± 33 to 177 ± 123 µmol/l in furosemide group; 96 ± 20 to 143 ± 87 µmol/l in placebo group; p < 0.001), and a significant decrease in peak creatinine-clearance (64.3 ± 29.4 to 39.1 ± 16.6 ml/min in furosemide group; 65.5 ± 38.6 to 41.8 ± 17.8 ml/min in placebo group; p < 0.001) following cardiac surgery, implying significant renal injury following cardiac surgery. Peak creatinine levels (177 ± 123 µmol/l in furosemide group and 143 ± 87 µmol/l in placebo group; p = 0.35) and peak creatinine-clearance (39.1 ± 16.6 ml/min in furosemide group and 41.8 ± 17.8 ml/min in placebo group; p = 0.61) were similar in the two groups. Importantly, there was no difference in incidence of renal dysfunction between the furosemide group (9/21) and the control group (8/21) (relative risk 1.1, 95% confidence interval 0.6–2.2; p = 0.99). Conclusions: Our randomised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients. Although urinary output increased with furosemide, there was no decrease in renal injury, and no decrease in incidence of renal dysfunction.

Key Words: Furosemide • Retinol binding protein • Creatinine-clearance • Renal failure • High-risk cardiac surgery

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
Renal dysfunction is an important complication of cardiac surgery with an incidence from 0.1% to 39% [1–4]. Patients at high-risk of postoperative renal dysfunction include those with pre-existing renal dysfunction [5,6], diabetes [7], impaired left ventricular (LV) function [7], and those undergoing non-elective and/or complicated procedures involving prolonged cardiopulmonary bypass (CPB) or circulatory arrest [6].

Previously, trials of numerous pharmacological reno-protective regimes in the setting of cardiothoracic surgery have been conducted. The more important ones include dopamine [1,4,5,8–10], mannitol [9,11], dobutamine [1], and furosemide [8,9,11]. Most strategies including furosemide established a polyuric state, but were unable to improve renal function, or the requirement for dialysis or outcome. In other studies comparing potential reno-protective effects of dopamine, furosemide or placebo in patients with normal renal function, it was shown that dopamine was ineffective and furosemide may be damaging to renal function after cardiac surgery [8]. This is in contrast with another randomised study, which showed that early institution of mannitol, furosemide and dopamine infusion for 1–3 weeks reduced the incidence of dialysis dependence and expedited restoration of renal function in acute renal failure (ARF) following cardiac surgery [9]. Therefore in this study, it was not possible to ascribe the reno-protective effect to one particular agent.

The true place of furosemide, therefore, is undetermined. In contrast to dopamine trials [1,4,5,8–10], there is a lack of randomised studies on the use of a short-term loop-diuretic infusion as the sole renal protective agent in cardiac surgery, most studies utilising a combination of agents for renal protection.

The aim of our study was to evaluate the reno-protective effect of furosemide infusion alone when started prior to the onset of the surgical insult in high-risk cardiac surgical patients at risk of renal impairment.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
2.1 Sample size
In a placebo-controlled prospectively randomised double-blinded trial, 50 patients at risk of postoperative renal impairment were recruited. In a pilot observational study, we found the peak serum creatinine postoperatively after high-risk cardiac surgery (defined below) was 141 ± 37 µmol/l. To detect a 25% reduction in the serum creatinine, sample size was calculated to be approximately 18 patients per group, with statistical power of 80% and significance level of 5% ( = 0.05). Therefore, 25 patients were recruited in each group. Data analysis was performed at the end of the study. Research protocol was approved by the John Radcliffe Hospital ethics review board. Informed consent was obtained from all patients being recruited into this study.

2.2 Patient selection
Patients at higher risk of postoperative renal dysfunction were selected, based on the presence of one or more of following preoperative criteria: renal insufficiency (serum creatinine >130 µmol/l) [5,6,12], LV ejection fraction (LVEF) <50%, congestive heart failure, diabetes (requiring oral hypoglycemic agents and/or insulin), procedures involving prolonged CPB such as coronary artery bypass grafts with valvular surgery and redo cardiac surgery. Patients with end-stage dialysis-dependent renal failure were excluded. Patients were randomised to receive either infusion of 0.9% saline at 2 ml/h (control) or infusion of furosemide at 2 ml/h (4 mg/h) [8,13], commencing immediately after the induction of anaesthesia, and administered continuously by an infusion pump for 12 h postoperatively.

2.3 Preoperative data collection
Urine was collected from recruited patients for 12–24 h preoperatively (preop), and retinol binding protein (RBP) and creatinine levels in urine were measured. Serum creatinine was collected at the end of this collection period immediately prior to surgery. These were used to calculate preoperative creatinine-clearance.

2.4 Operative technique
In all patients, anaesthesia was induced with fentanyl (10–15 µg/kg), etomidate (10–20 mg), pancuronium (8 mg) and maintained with isoflurane when not on CPB and propofol (6 mg/kg) whilst on CPB. Duration of CPB, hourly urine output, and use of inotropes and intravenous fluids were documented. Arterial pressure was measured invasively and was maintained >60 mmHg (mean) at all times during the procedure.

CPB was achieved by standard ascending aortic and right atrial cannulation; bicaval cannulation was performed if access to mitral and/or tricuspid valve(s) was required. Non-pulsatile CPB was used to perfuse patients at rates of 2–2.8 l/min/m². Circuit was primed with crystalloid and haematocrit was maintained at >22%, supplemented with packed red blood cells as required; mannitol was not used. Alpha-stat method was used during CPB, PaCO₂ was maintained at 35–40 mmHg, and PaO₂ of 150–250 mmHg. Myocardial protection was achieved by intermittent cold crystalloid cardioplegia using St. Thomas’ solution or intermittent cold blood cardioplegia (standard Buckberg protocol).

2.5 Postoperative management
Patients were monitored in the cardiac intensive care unit (CICU). Trial infusion was continued for 12 h postoperatively. Urine output was recorded hourly and collected for 12 h postoperatively (postop). Central venous pressure was maintained between 8 and 14 mmHg by infusion of colloid solutions. Antifibrinolytic agents were not routinely used postoperatively. Patients were warmed, and following normalisation of arterial blood gases and correction of any base deficits, the patients were weaned off the ventilator and extubated according to standard protocols established on the CICU. Positive end expiratory pressure was maintained at 5 mmHg prior to extubation.

Postoperative parameters that were measured were: (i) day-1 serum creatinine (12 h postoperatively), (ii) urine output for 12 h, (iii) urinary retinol binding protein (RBP) and creatinine and from this, RBP/creatinine ratio (U-RBP/Cr), and (iv) daily creatinine until discharge from hospital. Samples were collected uniformly in all patients.

Preoperative and postoperative creatinine-clearances were calculated from serum and urine creatinine, and urine output, respectively, using the formula

Creatinine-clearance (ml/min) = urine output (ml/min) x urine creatinine/serum creatinine [8]

Peak creatinine-clearance (CC) was calculated from the peak creatinine (peak serum creatinine value until discharge from hospital), height and weight using the Cockcroft and Gault equation [14]. Urinary RBP was measured using Human RBP Nephelometric Kit (The Binding Site Ltd., Birmingham, UK) by immunonephelometry with the Dade-Behring BNII Analyser [15]. Urinary RBP [15,16] and RBP/creatinine [10] have been previously validated by several studies as accurate indicators of acute renal failure (ARF).

Renal dysfunction was defined as >50% increase in serum creatinine over preoperative levels, or >130 µmol/l (within 7-day period following cardiac surgery) or requirement for haemodialysis, or all of the above. In patients with preoperative serum creatinine >130 µmol/l, >50% increase over preoperative levels was used to define postoperative renal dysfunction. Serum creatinine >130 µmol/l was chosen to diagnose renal dysfunction, since previous studies demonstrated a 10-fold increase in mortality and higher incidence of ARF with similar levels of renal dysfunction [7,17]. Indications for haemodialysis included one or more of the following in the presence of oliguria (urine output <0.5 ml/kg/h for 3 h), pulmonary edema, acidosis (pH < 7.25), worsening base deficit (over –10 mmol/l), hyperkalaemia (>6 mmol/l), urea >30 mmol/l or creatinine>300 µmol/l [18].

Other formulae used to interpret the data include:

Change in U-RBP/Cr = (postop U-RBP/Cr – preop U-RBP/Cr)/preop U-RBP/Cr

Change in 12 h CC = (postop 12 h CC – preop 12 h CC)/preop 12 h CC

Change in peak CC = (postop peak CC – preop CC)/preop CC

2.6 Statistical analysis
Comparison between groups was performed using Student's 2-sample t-test for normally distributed continuous variables, and Mann–Whitney test for non-parametrically distributed continuous variables. Within a group, differences between preoperative and postoperative values of a continuous variable were analysed. If differences were normally distributed, paired t-test was used, the Null Hypothesis being the absence of a difference. If non-parametrically distributed, Wilcoxon signed-rank test was used. The chi-square test was used to compare nominal variables, using Fischer's exact test for small numbers (n 5) in any group. Differences were considered significant at p < 0.05. All statistics was performed using Statview-5.0.1 software package (SAS Institute Inc, Cary, NC).

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
Out of 50 patients, two patients opted out of the trial, three patients were excluded due to inadequate preoperative urine collection, and three others due to inadequate postoperative urine collection. Thus, 42 patients completed the trial with 21 in each group.

3.1 Preoperative parameters
The two groups were well matched in age, sex, body mass index, EuroScore, LVEF and preoperative serum creatinine (Table 1 ). Three patients in the furosemide group and four patients in the control group had serum creatinine >130 µmol/l (p = 0.99).

Four patients in the placebo group and five patients in the furosemide group required blood and blood products due to bleeding (p = 0.99). Out of these, two patients in the placebo group and three patients in the furosemide group required resternotomy for bleeding (p = 0.99). Two patients in the placebo group and four patients in the furosemide group (p = 0.66) required intra-aortic balloon counterpulsation (IABP) for homodynamic stability.

There were two deaths, due to stroke (day 12) and septicemia (day 7) in the placebo group, and one death due to myocardial infarction (day 5) in the furosemide group.

In the first 12 h postoperatively, patients receiving furosemide had higher urine output (p < 0.001), leading to higher postoperative fluid requirement (p = 0.011), and lower levels of urine creatinine (p < 0.001) due to dilution by large urine volumes, compared to the control group. Both groups had a significant increase in RBP excretion and urinary RBP/creatinine (U-RBP/Cr) ratio following surgery (p < 0.001) (Table 5 ), reflecting impairment in proximal tubular reabsorption of these low molecular weight proteins possibly due the effects of prolonged cardiopulmonary bypass; however, there was no difference in postoperative U-RBP/Cr between the groups (p = 0.61). Both groups had significant increase in peak postoperative serum creatinine following cardiac surgery (p < 0.001); this was more in the furosemide group. In both groups there was no change in 12 h creatinine-clearance following surgery, but importantly, there was significant decrease in the peak postoperative creatinine-clearance following surgery (p < 0.001). Both the increase in peak postoperative serum creatinine and the decrease in peak postoperative creatinine-clearance occurred beyond the first 12 h, suggest a delay in occurrence of renal dysfunction as well as its recovery following complex high-risk cardiac surgery. Peak postoperative creatinine levels were higher (177 vs 143 µmol/l; p = 0.35), and peak postoperative creatinine-clearance were lower in furosemide group compared to the control group (39.1 vs 41.8 ml/min; p = 0.61), but not significant.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
Renal dysfunction is a well-recognised complication of high-risk cardiac surgery with an incidence of up to 39% [1–4]. The scale of this problem is likely to increase with the referral of elderly and high-risk cases for surgery [7]. The most sinister complication is ARF with an incidence of 1–15% [7,18]. In those requiring renal replacement therapy, there is a higher mortality ranging from 27% to 87.5% [7,9,17,18], and a higher risk of postoperative myocardial infarction, reoperation for bleeding, endocarditis and mediastinitis [7]. Even in those with mild to moderate renal dysfunction preceding cardiac surgery, there is a higher incidence of bleeding, cardiac and respiratory complications, and a higher mortality [12]. Aetiology of postoperative renal dysfunction is multifactorial and may include volume depletion, reduced renal perfusion, activation of inflammatory cascades during CPB, exposure to nephrotoxins (i.e. gentamicin), embolisation of atheromatous plaques during aortic manipulation and the systemic inflammatory response [2]. Factors associated with higher risk of renal dysfunction include increased age, preoperative renal dysfunction [6], left main coronary occlusion [7], active endocarditis, preoperative radio contrast agents, presence of peripheral/cerebrovascular arterial disease, previous stroke, diabetes, increased body weight, decreased LVEF, congestive heart failure, increased CPB time, deep hypothermic circulatory arrest, low urine output during CPB, and postoperative low cardiac output state and requirement for an intra-aortic balloon pump [3,6,7,9].

Furosemide is a loop-diuretic, which inhibits Na⁺/2Cl^–/K⁺ co-transport system in the luminal membrane of ascending limb of loop of Henle and thus promotes diuresis, and also promotes renal vasodilatation [8]. Clearly ineffective in established oliguric ARF [19], it was able to exert protective effects when given before a potential renal insult in experiments involving isolated perfused rat kidneys. In these experiments, it was shown that modification of transport activity in the thick ascending limb of Henle by furosemide reduced the severity of renal damage [20]. By reducing active NaCl transport, furosemide reduces oxygen requirement and may thus confer renal protection [8,20]. By augmenting tubular blood flow, furosemide decreases the concentration of nephrotoxins and prevents tubular obstruction.

In the past, clinical trials of furosemide as a renal rescue agent in established oliguric ARF have been generally disappointing. While furosemide established a polyuric state, it did not improve renal function, the requirement for dialysis or outcome [19,21]. Most studies performed in the past utilised a combination of agents including furosemide for renal protection; thus, there is a lack of randomised studies on the use of a short-term loop-diuretic infusion as the sole renal protective agent in cardiac surgery. Indeed in one study, furosemide had a detrimental effect on renal function after cardiac surgery. In this study, Lassnigg and associates [8] used dopamine at 2 µg/kg/min or furosemide at 0.5 µg/kg/min to confer renal protection in patients undergoing elective cardiac surgery. They found that continuous infusion of dopamine for renal protection was ineffective in preventing postoperative renal dysfunction. In contrast, continuous infusion of furosemide was detrimental to postoperative renal function [8]. The authors felt that this was a consequence of the activation of the sympathetic and the rennin–angiotensin systems by furosemide, which in turn led to an increase in peripheral vascular resistance, and thus a decrease in cardiac index and renal perfusion [8]. In another study, higher doses of furosemide were associated with renal dysfunction [22]. Other studies, however, reported a reno-protective effect with a combined continuous infusion of mannitol, furosemide and dopamine, in terms of restoration of urine output and renal function, and a reduction in dialysis dependence in ARF following cardiac surgery [9]. In this study, the authors showed that early commencement of infusion of mannitol, furosemide and dopamine was associated with earlier restoration of urine output and serum creatinine. However, in all instances the infusion was continued for a prolonged period of time of 1–3 weeks following commencement [9]. Furthermore, in this study, it appeared that the combined effect of the three agents conferred renal protection, and thus could not be ascribed to any one agent alone.

In the past, serum creatinine has been used as an indicator of renal injury, but this is relatively insensitive because of the presence of a large renal functional reserve [23]. Creatinine-clearance is thus considered to be a more accurate indicator of renal injury [4,22]. An even more accurate and sensitive method of detecting tubular injury depends on the ability of the proximal convoluted tubular (PCT) cells to reabsorb low molecular weight (LMW) proteins, such as retinol binding protein (RBP) [16,24,25]. PCTs are characteristically injured early in acute tubular necrosis (ATN), and urinary RBP levels have been shown to have a greater sensitivity in detection of PCT injury and ATN/ARF following cardiac surgery [25], and indeed, in predicting the need for renal replacement therapy, and an unfavourable outcome [10,15,16,24,25].

Ho and Sheridan [13] examined the effectiveness of furosemide in their meta-analysis of nine studies, three of which were used to prevent ARF, and six to treat ARF. Most of the studies used furosemide at 1–2.5 mg/h to prevent ARF, and 600–3400 mg/day in established ARF. There was no improvement in in-hospital mortality, requirement for haemodialysis, or proportion of patients with persistent oliguria. High-dose furosemide used in established ARF was associated with an increased risk of temporary deafness and tinnitus, and an increase in hospital stay. While it has been argued that furosemide may convert oliguric ARF into a polyuric state, they felt that responders to furosemide might represent those with less-severe ARF. They concluded that furosemide was ineffective in the prevention or treatment of ARF in adults [13].

In our double-blinded randomised trial, we found that patients receiving furosemide had higher urine output during the period of administration of the drug leading to a higher postoperative fluid requirement, compared to the control group. This also led to lower levels of urine creatinine and RBP due to dilution by large urine volumes, compared to control. Overall, both groups had a significant increase in urinary-RBP/creatinine ratio following surgery. The early 12 h postoperative serum creatinine levels were not significantly elevated; however, both groups had a significant delayed increase in peak serum creatinine following cardiac surgery. Importantly, there was also a significant decrease in the peak postoperative creatinine-clearance following surgery. Creatinine levels and peak creatinine-clearance were similar in the furosemide group and control group. These findings suggest a delay in appearance of renal dysfunction as well as in the recovery of renal function following complex cardiac surgery, since these changes were not manifest in the first 12 h postoperatively, but appeared after 48–72 h. Therefore, any therapeutic interventions aimed at addressing this problem might have to be continued for longer than 12 h postoperatively.

Overall incidence of renal dysfunction was high in our series of patients undergoing high-risk cardiac surgery, though we could not find any particular attributing factor. The majority of these patients, however, did not require dialysis; the requirement for haemodialysis was low at 2.5%. We found no difference in the incidence of renal dysfunction between furosemide and control groups, but this may be a reflection of the small sample size, since our study did indicate a trend to higher peak postoperative serum creatinine levels and lower peak postoperative creatinine-clearance in patients receiving furosemide. However, in the absence of statistical significance, this can be attributed to chance only.

There are some limitations to our study. One is the small number of patients in each group. But the results of our study revealed marginally higher serum creatinine and lower creatinine-clearance in furosemide group, and thus the sample size required to detect a significant difference between the groups would have be very large. However, despite being underpowered, this study still conveys an important message that postoperative furosemide infusion following cardiac surgery is not only not useful, but maybe potentially nephrotoxic, as reflected by a trend to higher peak serum creatinine levels and lower peak postoperative creatinine-clearance in patients receiving furosemide, compared to control receiving saline. Another limitation is the choice of marker of renal tubular injury. However, based on available reports we felt that measurement of urinary creatinine, urinary and calculated creatinine-clearances, RBP and urinary-RBP/creatinine ratios would provide a reliable and sensitive indication of deterioration in renal function [10,15,16]. A third limitation could be the low dose of furosemide used. However, the meta-analysis by Ho and Sheridan [13] has shown that higher doses of furosemide only led to ototoxicity and did not alter renal dysfunction. A fourth limitation could be early termination of the infusion, since results from this study suggest a delay in the appearance of renal dysfunction following surgery. This would need to be addressed by another randomised trial, wherein larger doses of furosemide could be continued for longer durations.

Thus, our randomised double-blinded placebo-controlled study failed to demonstrate any convincing benefit of furosemide infusion administration postoperatively to high-risk cardiac surgical patients, and therefore we cannot recommend routine infusion of low-dose furosemide to high-risk cardiac surgical patients. Although urinary output did increase with furosemide, all markers of renal dysfunction did not differ significantly from the control group, nor did the incidence of renal failure requiring renal replacement therapy. More importantly, peak postoperative serum creatinine levels were higher and peak postoperative creatinine-clearance were lower in patients receiving furosemide compared to the control group receiving saline, and though not statistically significant, they may indicate a trend to potentially deleterious short-term nephrotoxic effects of postoperative furosemide infusion following high-risk cardiac surgery.

	Appendix A

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 
Conference discussion

Dr M. Dahm (Mainz, Germany): I have three remarks or questions. The first one concerns methodology. As you pointed out, the determination of creatinine has some limitations especially when you use the Cockcroft formula which has certain limitations in cases of mild and moderate renal insufficiency instead of the collection of urine. Therefore, I don’t understand why you changed your methodology after this 12-h period postoperatively.

The second question concerns the inclusion criteria or the groups of patients that were followed. Mainly you looked at three groups of patients, those that entered the operation with pre-existing renal failure or renal dysfunction, a second group that had factors predisposing for the development of renal dysfunction, and the third group was a mixture of these two.

So were these three groups equally distributed into the study group and the placebo group or was there a difference? And did you analyse your data looking at these three groups separately?

The third question and remark concerns preload. Preload is a very important factor for the development of renal dysfunction. As mentioned in your manuscript, you measured and kept central venous pressure between 8 and 14. As you showed clearly, there was much more urine output in the group of patients that received furosemide, but this loss of volume was only partially replaced by infusions as seen in Table 3 of your manuscript.

So one could get the impression that these two groups were not comparable concerning volume load or preload. Could you elucidate on that and tell us about the use of vasopressors in the two study groups?

Dr Mahesh: The first question I agree with the implication that the value of serum creatinine is limited and the significant proportion of the renal function has to be lost before the serum creatinine is elevated. We have tried to address that by measuring urinary retinol-binding protein, and we found that there was a significant increase in the excretion of retinol-binding protein postoperatively.

However, looking at the literature in the past, we did not find any cutoff values of retinol-binding protein which we could use to define an impairment of renal function. And, therefore, we did not use this particular modality as a criterion to define renal failure. And we stuck to the existing guidelines which talk about serum creatinine and creatinine-clearances.

Now, I’m trying to address the second question which talks about the three or four different criteria that we used for our inclusion criteria. These were equally distributed between the two groups of patients, but because the number of patients in each group was only 21 per group, it would be very difficult to analyse each of these criteria separately and come up with any solid conclusions because the numbers would then be about four or five in each subgroup and then it will be very difficult to draw any conclusions due to small numbers in each group.

So we looked at the literature in the past, and we found that these were somewhat important issues that were associated with renal dysfunction, and we thought of addressing these subgroups of patients by furosemide administration.

Regarding the third question about the preload, we did ensure that the two groups of patients would have adequate maintenance of preload. We ensured that the CVP was maintained between 8 and 14 by regular administration of fluids.

Dr Dahm: But just keeping the central venous pressure isn’t so –

Dr Veit (Chair): I’m sorry. We have to stop the discussion now because of time.

	Acknowledgments

 
The authors thank the patients for participating in the study, and the nurses on the CICU for helping with the study.

	Footnotes

 
Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.

Sources of funding: John Radcliffe Hospital Research Committee.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A References

 

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