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Eur J Cardiothorac Surg 2004;26:1027-1031
© 2004 Elsevier Science NL

Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure

Department of Cardiothoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK

Received 29 February 2004; received in revised form 17 July 2004; accepted 23 July 2004.

^* Corresponding author. Tel.: +44-116-250-2687. (E-mail: mme3{at}le.ac.uk).

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Objective: The application and timing of hemofiltration (continuous veno-venous hemofiltration, CVVH) in patients with acute renal failure (ARF) post cardiac surgery has been called into question because of uncertain short-term outcome. The aim of the present study was to identify how the timing of introduction of hemofiltration affects the morbidity and mortality in patients with ARF after cardiac surgery. Methods: 1264 consecutive patients who underwent adult cardiac surgical procedures performed between January 2002 and January 2003 were audited. Out of these, case notes of 64 patients who required renal supportive intervention were reviewed. Statistical significance was accepted at a level of P<0.05. Results: Of the 64 (5%) patients, who developed ARF and required CVVH, there were 48 males and 16 females. Mean age was 70±6.8 years. The hospital mortality was 43% (12 patients) in Group-I and 22% (8) in Group-II (P<0.05), giving an overall 1.5% mortality associated with ARF. The mean time between the operation and the initiation of CVVH was 2.55±2.2 days in Group-I and 0.78±0.2 days in Group-II (P<0.001). The mean duration of CVVH was 4.57±11.4 days in Group-I and 4.61±2.0 days in Group-II (P=NS). Older age (P=0.013), elevated preoperative creatinine (P=0.002), postoperative pulmonary oedema (P=0.01), sepsis (P=0.001), multiple organ failure (P=0.031), hypotension (P=0.031) and preoperative renal failure (P<0.05) were the independent factors influencing the poor postoperative outcome and cardiac instability. Conclusion: Early and aggressive use of CVVH is associated with better than expected survival in severe ARF after cardiac operations.

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Acute renal failure (ARF) is a major postoperative complication in open-heart surgery and is associated with poor prognosis. The incidence of ARF varies between 1 and 15% with an observed mortality of 40–90% [1,2]. Lower frequency rate described may have been resulted from more conservative definition of ARF (dialysis requirement or creatinine level >5mg/dl) [3,4]. It is reported that even with standard intermittent haemodialysis treatment severe ARF still has high mortality rate [5]. Considering the extent of open-heart surgery worldwide and consequently the high number of patients with postoperative ARF, little attention had been paid in the past towards optimisation of the management of this complication.

More recently, continuous veno-venous hemofiltration (CVVH) has been introduced, which circumvent the hemodynamic instability associated with intermittent hemodialysis and its limited ability to control the state of the patients' volume [6]. One area that has been called into question is the application and particularly the timing of CVVH because of the perception this intervention has uncertain short-term outcome [7]. In addition, there is no algorithm to predict which patients will benefit most from such intensive therapy to use it rationally [8]. Bent and co-workers reported a mortality rate of 40% in ARF patients treated with CVVH (mean elapsed time between the operation and the initiation of CVVH of 2.38 days) [9]. Despite these developments and changed renal replacement therapy modalities, ARF after cardiac surgery still depicts high mortality. Hence, the aim of the study was to identify whether timing of CVVH has any significant effect on the outcome after cardiac surgery in patients with ARF.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
An audit of 1264 of consecutive patients who underwent adult cardiac surgical procedures conducted between January 2002 and January 2003 was performed. Out of these, there were 80 patients requiring renal supportive intervention. Sixteen of them were excluded from this group as they were already on chronic dialysis and remained on the dialysis postoperatively. The remaining 64 patients were analysed for demographics, preoperative risk factors, postoperative complications, treatment and outcome. Patients were divided into two groups. Group-I (n=28) received CVVH treatment when urea levels were 30mmol/l, creatinine levels were 250mmol/l or potassium levels exceeded 6.0mequiv./l despite glucose–insulin infusion, regardless of urine output (polyuria, oliguria and anuria). We described it as late hemofiltration. In Group-II (n=36) CVVH was started when urine output was less than 100ml within 8h consecutively after surgery despite furosemide infusion. We defined it as early hemofiltration. The levels of serum creatinine and potassium were not taken into account in Group-II. Respiratory complications were described as atelectasis, pneumonia, hemothorax or pneumothorax. Gastrointestinal complications were described as pancreatitis, pseudo-obstruction, bowel ischaemia or perforation and left ventricular failure (LVF) was described as pulmonary oedema.

2.1. Statistical analysis
Data were expressed as means±SD. Statistical analysis was performed using the SPSS software, version 9.05 (SPSS, Inc., Chicago, IL). Mann–Whitney U-test and chi-squared test were used for statistical analysis and P<0.05 was considered as statistically significant.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Out of 1264 patients there were 956 (76%) males and 308 (24%) females. Mean age was 64.9±9 years. The surgical procedures performed were: coronary artery bypass grafts (CABG) 667 (52.7%), CABG+valve repair or replacement 153 (12.1%), valve alone 341 (27%), valve+others 42 (4.2%) and surgery involving thoracic aorta 61 (4.8%). Sixty-four (5%) patients developed ARF and required CVVH.

Clinical and demographic characteristics of ARF patients are described in Table 1. There was no significant difference observed in mean cardiopulmonary bypass time (CPB), mean cross-clamp time, required inotropic support, incidence of intra-aortic balloon pump treatment between Group-I and Group-II (P=NS). The mean time between the operation and the initiation of CVVH was 2.55±2.2 days in Group-I and 0.78±0.2 days in Group-II (P<0.001) though there was no significant difference with regards to mean duration of CVVH between the two groups (Table 2). There was a significant difference observed in pre and post CVVH urea (26.8±21.7 vs 11.6±3.8mmol/l in Group-I and 23.9±12.4 vs 9.9±5.7mmol/l in Group-II; P<0.05 in both cases) and creatinine (380±170.3 vs 173.8±76µmol/l in Group-I and 328±123 vs 174.9±43.9µmol/l in Group-II; P<0.05 in both cases).

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
According to the literature, development of ARF in the intensive care setting has adverse prognostic significance and itself increases risk of death [2,10]. Some of the factors that contribute to renal failure in the postoperative period are advanced age, pre-existing renal insufficiency, preoperative left ventricular dysfunction, low cardiac output in the peri-operative period and duration of CPB and aortic cross clamp time [2,11]. In fact, patients with severe ARF requiring renal replacement therapy, usually continue to deteriorate and require more intensive ICU care [12]. Many of these patients have multi-organ failure, require assisted ventilation, intra-aortic balloon counterpulsation, the continuous administration of inotropic drugs, and at times the use of extracorporeal life support. In these patients, mortality has remained high despite the use of renal replacement therapy.

There are several potential explanations for such a high morbidity and mortality in this group of patients. Transient endotoxemia in patients undergoing surgery involving CPB has been widely recognised to be a major stimulus for the development of systemic inflammatory response syndrome (SIRS) [13]. This endotoxemia associated with cardiac surgery is thought to be dominantly influenced by the use of CPB [14,15]. However, the pathogenesis involved in this phenomenon is not entirely clear. Studies have also shown that haemodynamic changes during different stages of the operation; in other words, decrease in cardiac output might likely lead to a reduction of vital organs perfusion [16]. Moreover, Pinhu and colleagues postulated that mechanical ventilation also induces pulmonary production of inflammatory mediators [17], which exacerbate further postoperative tissue injury. Whether or not, multiple organ failure is the result of the poor balance in proinflammatory and anti-inflammatory cytokine production in these conditions has not been proven.

Continuous renal replacement techniques offer continuous and steady fluid removal and uremic toxin clearance. Their intensity can easily be titrated to prevent or treat volume overload rapidly. CVVH is useful in right heart failure because it reduces preload and may be therefore particularly useful in patients with valvular heart disease. A series of studies revealed that hemofiltration improves heart and lung functions in patients with ARF and cardiac shock after heart surgery. This can reduce the need of inotropic support, which also contributes to the patients' survival [11,18]. This method provides better control of fluid status, improves uremia, and also ultrafiltrates toxic proteins such as myocardial depressant factors. CVVH also helps in improving the ventricular function by restoring the myocardial water content (MWC) within normal limits. Schaff et al. reported that MWC which normally ranges from 78% under normal conditions can increase to more than 82% in pathologic states [19]. A similar range was reported subsequently in experimental studies of CPB which demonstrated that a variety of injuries were associated with increase in MWC and LV mass and with a decrease in LV compliance [20]. Oedema and increased chamber stiffness also were described following ischaemic arrest and reperfusion. These observations set the stage for the study of the oedema related changes in geometry and wall volume.

However, in-hospital mortality remained at a high percentage despite these innovative techniques. Hospital mortality rate was reported to be as high as 52.3% in a study by Alarabi [21], 80% by Baudouin [20], and 40% by Bent [9]. The lowest mortality rate was reported by Bent and coworkers [9]. They advocated early and aggressive CVVH after cardiac surgery, but apparently, they waited for the development of full-blown renal failure findings and then aggressively performed CVVH. Recognition of renal failure after cardiac surgery may take time when classical recognition parameters are used and new parameters for early recognition of renal failure after cardiac surgery may help in avoiding this high mortality. We performed CVVH when urine output was less than 100ml in 8h for Group-II patients. Renal failure could easily be recognized with these criteria and renal replacement therapy could be started as soon as possible after cardiac surgery. Of course, these criteria cannot be applied to polyuric renal failure after heart surgery, which was not developed in the case of our Group-II patients.

Given the physiologic advantages of continuous renal replacement technique, it may appear surprising that several clinical studies have so far failed to demonstrate evidence of a survival advantage [20]. There are in our opinion some potential explanations for such failure. CVVH has often been applied too late in the postoperative course [20] leading to prolong and poorly controlled uraemia, restricted nutrition and volume overload [22]. In light of this, we hypothesised that earlier (practically within first postoperative day) CVVH would lead to a better than predicted outcome which is supported by Bent and coworkers [9]. More over, Sirivella and coworkers showed the use of infusion of mannitol, furosemide and dopamine in ARF patients post cardiac surgery to be useful [23], however, they failed to demonstrate its usefulness in patients (post cardiac surgery) with low cardiac output syndrome. Our analysis demonstrated that use of CVVH in the early postoperative period is associated with improvement in low cardiac output syndrome.

In this investigation we demonstrated that in a single institution, both the incidence and survival from ARF after CPB have improved on the initiation of CVVH at an early stage. Being a retrospective audit study, there were several potential limitations that should be considered when interpreting the results of this study. It is not possible to identify a single factor responsible for the apparent deterioration in the outcome in those patients with considerably late onset of CVVH. As with most advances in critical care medicine, it seems to be a sequence of events most probably influencing the survival rate rather than isolated phenomena. Although this study was limited by a relatively small number of ARF patients, it was not intended to investigate a standardised optimisation strategy following the results of a previous study [24], which demonstrated that survivors tended to be started on haemofiltration earlier than non-survivors. This seems to confirm our results and suggests initiating CVVH earlier than later before any significant metabolic and physiological derangements occur.

We conclude that post-cardiotomy patients who develop ARF after CPB have a poor prognosis if CVVH is initiated late. Current criteria for CVVH initiation are not sensitive enough and creatinine levels are not relevant in decision making in such patients. Therefore, it is advisable the sooner the ARF after cardiac surgery is recognised and CVVH is initiated the greater the chances of improved cardiac output and survival probably through removal of SIRS toxins and control of MWC.

	Acknowledgments

 
The authors gratefully acknowledge the assistance of Mrs Karren Jack, Audit Planning and Performance Manager and Ms Toni Hall, Renal Nurse Specialist in Cardiac surgery at the Glenfiled Hospital, Leicester.

	Footnotes

 
Presented at the Therapeutic Filtration and Extracorporeal Circulation Conference, Hammersmith Hospital, London, UK, July 18, 2003.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 

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