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Ann Thorac Surg 2001;71:832-837
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery

^a Department of Intensive Care, Austin & Repatriation Medical Centre, Heidelberg, Melbourne, Victoria, Australia
^b Department of Anaesthesia, Austin & Repatriation Medical Centre, Heidelberg, Melbourne, Victoria, Australia
^c Department of Cardiothoracic Surgery, Austin & Repatriation Medical Centre, Heidelberg, Melbourne, Victoria, Australia

Accepted for publication June 27, 2000.

Address reprint requests to Dr Bellomo, Intensive Care Unit, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
e-mail: rb{at}austin.unimelb.edu.au

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH.

Methods. Medical record analysis with collection of demographic, clinical, and outcome information was used.

Results. Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively).

Conclusions. Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Severe acute renal failure (ARF) (defined as renal failure requiring renal replacement therapy) is a major complication of cardiac surgery and is associated with a very high mortality (60% to 100%) when treated with standard intermittent hemodialysis [1, 2]. More recently, continuous renal replacement techniques have been introduced, which circumvent the hemodynamic instability associated with intermittent hemodialysis and its limited ability to control the patient’s volume state [3]. One such form of continuous renal replacement therapy is continuous venovenous hemofiltration (CVVH) [4]. The early and intensive application of this therapy has the potential to substantially facilitate the care of patients with severe ARF after cardiac operation [5].

However, its application has been called into question because of the perception that CVVH is costly, resource intensive, and ultimately still unable to improve the short-term outcome of these patients [6]. In addition, there is a need to predict which patients will benefit from such intensive therapy to use it more rationally [7, 8]. Thus, outcome prediction and choice and effect of renal replacement therapy after cardiac operation remain poorly defined and yet important issues in the postoperative management of patients undergoing cardiac operations.

Accordingly, we conducted this study to address two questions: (1) whether the early and intensive use of CVVH resulted in a better than predicted outcome, and (2) whether a simple and yet accurate model could be developed to predict the outcome of these patients before renal replacement therapy was applied.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Patients treated with CVVH for severe ARF after cardiac operation were identified using a prospectively collected intensive care unit database. The medical records of these patients were obtained and data were retrospectively recorded with focus on demographic features, surgical characteristics, hemodynamic and clinical features at the time of initiation of CVVH, duration of intensive care unit (ICU) stay, survival to ICU discharge, and survival to hospital discharge. Such information was collected to achieve the following goals: (1) perform meaningful comparisons with recent series of similar patients; (2) calculate a predicted risk of death using a recently validated formula [7]; and (3) develop a simple and yet reasonably accurate outcome prediction model specific to these patients.

The technique of CVVH consists of a double lumen catheter (Fig 1) that is used to pump blood through a module (AK 10, Gambro, Lund, Sweden) containing pressure alarms and an air bubble trap. The blood flow rate is kept at 200 to 250 mL/m. Ultrafiltration is pump controlled at 2 L/h. Replacement fluid is administered prefilter at a dynamically adjusted rate chosen to achieve the desired fluid therapy goals for any time period. Polyacrylonitrile filters (AN69, Hospal, Lyon, France) are used in all patients. Anticoagulation of the circuit is carried out according to clinical judgment and circuit duration. In this study, some patients received no anticoagulation, others received only low-dose (300 to 500 IU/h) prefilter heparin therapy, and others received either full heparinization or regional heparinization (prefilter heparin at 1,000 or 1,500 IU/h and postfilter protamine at 10 or 15 mg/h). A diagram of the circuit is presented in Figure 2.

View larger version (15K): [in this window] [in a new window]   Fig 1. Illustration of the external and internal appearance of a double lumen catheter used for continuous venovenous hemofiltration vascular access.

View larger version (16K): [in this window] [in a new window]   Fig 2. Schematic representation of a continuous venovenous hemofiltration circuit as applied in this study. (IV = intravenous; UF = ultrafiltrate.)

Two predictive models were then developed. The first model was obtained using multivariate linear regression analysis (Microsoft Excel 97 SR-1; Microsoft, Seattle, WA), whereas the second used a back propagation, feed-forward neural network (Neurosolutions 1998; Neuro Dimension, Gainesville, FL). Both models were developed using the whole data set of 65 patients, and then tested on the same 65 patients. In addition, the data set was randomly divided into two sets: one set of 35 patients (a training set) and a second set of 30 patients (a test set), to develop a second set of models that could be tested on a new set of patients.

Variables were eliminated in a stepwise manner from the regression model if they did not increase performance (measured by the R² value and the receive operating characteristic [ROC] value).

The four remaining variables left the simplest model that did not significantly affect performance (ie, difference in R² value was < 0.02 and ROC < 0.01 when compared with a model that incorporated all variables). For the basis of comparison, the neural network was developed using the same four variables as the statistical model. Continuous variables were converted to binary variables by graphing and arbitrary selection of the best cut-off point. This was performed for the purpose of simplicity of the model.

The four final variables were hypotension, repeat operation, base deficit (< -2), and Glasgow coma score (< 11).

Discrimination of the two models, and the Liano score, was tested using the ROC curve method, using the Wilcoxon statistic to generate standard errors and confidence intervals.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Cardiac operation was performed on 3,154 patients during the 5-year period. Sixty-five patients (2.1%) developed severe ARF. Their demographic and clinical characteristics are presented in Table 1.

Using Liano’s predictive model, the mean predicted risk of death for this group of patients was 66% (95% CI 60% to 72%). However, the ICU mortality was 36.9% and the actual in-hospital mortality was 40% (95% CI 28% to 52%). This difference was significant (p = 0.003). The standardized mortality ratio (actual/predicted mortality) was 0.61 (95% CI 0.38 to 0.84).

Using readily available clinical and biochemical variables univariate analysis was performed to identify which factors were most clearly associated with poor outcome (Table 2). Subsequent multivariate regression analysis allowed for the development of a simple predictive equation to calculate the risk of death (ROD) in a given patient: .

View larger version (13K): [in this window] [in a new window]   Fig 3. Visual comparison of the receive operating characteristic (ROC) achieved with the three different predictive models in the entire population of acute renal failure patients. (Closed diamond = Liano model; open triangle = regression model; X = neural network.)

	Comment

Top Abstract Introduction Material and methods Results Comment References

In fact, patients with mild to moderate ARF are usually responsive to medical therapy and eventually remit spontaneously. Those with severe ARF (ARF requiring renal replacement therapy), however, are different. They usually continue to deteriorate, require ICU care, and need acute artificial renal support [12]. Many of these patients have multiorgan failure, require mechanical ventilation, intraaortic balloon counterpulsation, the continuous administration of inotropic/vasopressor drugs, and, at times, the use of extracorporeal life support. In these patients, even in this decade, mortality has remained high (> 60%) despite the aggressive use of intermittent hemodialysis [12].

There are several potential explanations for such a high mortality. Case mix has changed over time to include older and sicker patients [9]. Irreversible postoperative cardiogenic shock may develop, and dialysis is more aggressive applied. All of the above explanations may account for the persistently high mortality rate associated with severe ARF after cardiac operations. However, in our opinion, an additional explanation may lie in the choice, timing, and intensity of renal support.

Early case series from large North American academic centers the 1970s used intermittent hemodialysis and reported a 100% mortality [9]. Although a recent report shows a mortality of 63% [12] using standard hemodialysis, fluid control and the removal of uremic toxins may be suboptimal in critically ill patients when this technique is used [13] and bioincompatible membranes may aggravate inflammation [14]. Furthermore, intermittent hemodialysis causes serious hemodynamic instability [14]. Because of the limitations of intermittent hemodialysis in hemodynamically compromised patients, continuous renal replacement therapies have been developed [13].

Continuous renal replacement techniques offer continuous and steady fluid removal and uremic toxin clearance. Their intensity can be easily titrated to prevent or rapidly treat volume overload. Continuous removal of waste products also ensures the minimization of the adverse immunologic and proinflammatory effects of uremia. Myocardial depressant factors may be removed [15], myocardial performance improved [7], and nutrition optimized [16].

Given the physiologic advantages of continuous renal replacement techniques, it may appear surprising that several clinical studies have so far failed to demonstrate evidence of a survival advantage [17–19]. There are, in our opinion, some potential explanations for such failure. First, CVVH has often been applied too late in the postoperative course [17], leading to prolonged and poorly controlled uremia, restricted nutrition, and volume overload. Second, CVVH has often been of limited intensity leading to inferior uremic control with its attendant sequelae [20, 21].

In the light of the above considerations, we hypothesized that earlier and more intensive CVVH would lead to a better than predicted outcome. To test this hypothesis we analyzed the results of such a policy in our cardiothoracic ICU during the past 5 years. The outcomes achieved are consistent with our hypothesis.

It is possible that we achieved encouraging results simply because our patients were only moderately ill. Our findings, however, suggest the opposite with many requiring intraaortic balloon pump, prolonged mechanical ventilation, and the administration of inotropic or vasopressor drugs. Yet, in-hospital mortality was only 40%, the lowest reported in the literature so far. For example, Alarabi and colleagues [22] reported an overall mortality of 52.3% in patients with severe ARF after cardiac operation treated with continuous arteriovenous hemodialysis and continuous hemofiltration. Their patients appeared similar to our group in illness severity and age, but the intensity of treatment was much less. A French study by Levy and associates [19], of 16 patients who had undergone operation with cardiopulmonary bypass, reported a mortality rate of 87.5% despite the use of CVVH. These investigators treated patients similar to ours in illness severity; however, they only achieved ultrafiltration rates of 0.5 to 1 L/h, half of that applied to our patients. No information on the timing of treatment is provided.

Baudouin and colleagues [17] reported a more than 80% mortality in similar patients. In this series, however, CVVH was initiated much later (> 8 days postoperatively) and delay in initiating CVVH identified patients more likely to die. Furthermore, the ultrafiltration rate was also approximately 50% of that achieved in our patients. Finally, Tsang and colleagues [6] recently reported 48 cardiac patients treated with either continuous arteriovenous hemodialysis/hemofiltration or CVVH. Their patients were younger than our group and appeared to have a similar degree of illness severity. However, once again, the intensity of filtration was approximately 50% of that used in our patients. The duration of ICU stay was longer than in our cohort and in-hospital mortality was 52%. No information was available on the timing of intervention.

To further test our hypothesis, we compared the outcome of our patients to that predicted using a previously validated, ARF-specific predictive model [7]. The results suggest a reduction in mortality from 66% to 40%. The predictive model might not operate accurately in this very specific group of patients and only a randomized controlled trial could address this question with full scientific methodology. However, this model performed well in our patients (discussed later) and the difference is striking and highly significant. The difficulties associated with conducting a randomized controlled trial of sufficient power and quality have been previously highlighted [23].

The second aim of our study was to develop a specific predictive model that could be applied before hemofiltration to decide whether its use was warranted. We found that the following risk factors were important predictors of outcome: sustained hypotension, use of intraaortic balloon pump for hemodynamic support, neurologic dysfunction, metabolic acidosis, reoperation, and the need for prolonged mechanical ventilation. Multivariate logistic regression analysis further narrowed the significant prognostic variables to hypotension, second cardiac operation (reoperation), the presence of a base deficit, and neurologic dysfunction as reflected by the Glasgow coma scale at the time of starting CVVH.

Increasing the ability to predict patient outcome can assist clinicians to select patients most likely to benefit from CVVH. Several attempts have been made to develop ARF-specific prognostic tools. Among such scores, Liano’s is the one best sustained by statistical evidence. It was derived from a community-based ARF database. Thus, it may not strictly apply to the critically ill patient who has undergone a cardiac operation. We, therefore, used readily available clinical data to develop a predictive scoring system for this selected group of patients and compared its performance to that of Liano’s equation. Although Liano’s score yielded a ROC value of 0.86, the ROC values in our regression models ranged from 0.89 to 0.92, depending on the developmental approach. In addition, a neural network analysis model was associated with a higher ROC value ranging from 0.9 to 0.98. Clearly it is possible to predict outcome with reasonable accuracy either using our predictive equation or neural network software. We believe such information can assist clinicians in making difficult therapeutic decisions and allocating resources wisely.

In conclusion, we report the largest series of patients with severe ARF after cardiac operation treated with CVVH. Early and intensive application of CVVH was associated with a better than predicted outcome, which is the best reported so far in the literature. These results are encouraging and support our approach. Furthermore, we have developed a simple predictive equation to estimate mortality before the start of CVVH. We have also shown that, using neural network software, an accurate prognosis can be achieved. We believe these findings have significant clinical implications.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): George Matalanis Jai Raman Alexander Rosalion Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bent, P. Articles by Buxton, B. F. Search for Related Content PubMed PubMed Citation Articles by Bent, P. Articles by Buxton, B. F. Related Collections Extracorporeal circulation