Ultrafiltration for heart failure: How fast should we move?
Received 9 April 2008;
Article Outline
Extracorporeal ultrafiltration (UF) for fluid removal dates from the advent of dialysis therapy, and its technique was proposed by Silverstein et al1 in 1974 as a modification of the standard hemodialysis circuit. As early as 1979, its use was rapidly expanded to include management of patients with refractory congestive heart failure (HF).2 Although most studies reported favorable results in this setting, it was not until very recently that a greater interest was generated with the development of a portable UF device. This machine, recently approved by Food and Drug Administration for therapy in patients with fluid overload who failed diuretic therapy, is dedicated to isolated UF with very low blood flow (10-40 mL/min) suitable for peripherally inserted venous catheters. It is marketed for use by any physician who has received training in extracorporeal therapies, and its simple design avoids the necessity of an intensive care unit or dialysis facility.
Jaski et al3 were one of the first groups of investigators to use the portable device, and they concluded that rapid removal of fluid could be safely achieved. This was followed by similar favorable results reported from studies which either included a highly selected small number of patients or had no control groups.[4], [5] and [6] Finally, the results of the largest randomized controlled trial (Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure [UNLOAD]) in this field were published in 2007.7 This study used the device in an inpatient setting on a group of patients that met very specific criteria. Indeed, it took >1 year for 28 centers to recruit 200 patients despite HF being the single most frequent cause of hospitalization in patients aged >65 years in the US,8 with >1 million hospitalizations per year. In that prospective study, UF was compared with intravenous diuretics in stable patients who did not need any pressor agents. There was no advantage for UF in terms of dyspnea score even though these patients had a greater weight loss during the first 48 hours. Those who were ultrafiltered had, however, a lower rate of rehospitalization in the next 90 days. Although this investigation has shortcomings (which we have previously discussed9), it still has been considered the main body of evidence currently available in support of UF for decompensated HF.
Despite the paucity of rigorous clinical trials, the generally positive tone of these studies has resulted in an increasing number of cardiologists requesting nephrology consultations for UF in patients hospitalized for decompensated HF with different degrees of diuretic resistance. Parallel to this phenomenon, there has been an increasing interest in using UF in outpatient clinics or even in emergency department observation units.10 A few points seem noteworthy before any further expansion of this modality (inpatient, outpatient, or emergency department) can be considered.
First, one of the main hypothesized advantages of using UF in patients with HF has been to avoid the deleterious effects of aggressive diuresis on renal hemodynamics, in particular activation of the sympathetic nervous system and the renin-angiotensin-aldosterone axis. Indeed, it has previously been shown that a decline in renal function during fluid removal in HF is even a stronger predictor of mortality than the baseline creatinine level.11 Therefore, it is conceivable that the future role of UF may heavily depend on its impact on renal function and its proposed protective effects compared with diuretics.12 However, a substudy of the UNLOAD trial was recently published that specifically evaluated and compared renal blood flow and glomerular filtration rate between UF and diuretics.13 It failed to show any benefit for UF in preventing the decline in glomerular filtration rate or renal blood flow compared with diuretics.
The UF rate (UFR) plays an important role in the potential impact of UF on renal function. During extracorporeal UF, fluid removed from the intravascular sector is replenished from the extravascular compartment and this helps maintain hemodynamic stability. The rate of this shift (ie, plasma refill rate) depends on a number of factors including serum albumin level. It is known that many patients with HF, similar to other chronic disease states and wasting syndromes, have malnutrition-inflammation complex syndrome.14 Hence, the resultant low serum albumin levels could contribute to impaired plasma refill during UF, leading to intravascular volume contraction and renal dysfunction. The apparent discrepancies in the results of studies regarding the impact of UF on renal function can thus in part be attributable to the differences in the delicate balance between the UFR and plasma refill rate in each of the study populations. An appeal to using dialysis equipment and staff for fluid removal is that the nurses trained for UF therapy are already facile at making unanticipated changes in the UFR when there are indications of hypovolemia, hemoconcentration, or hypotension.
Second, there are currently no data available on the impact of UF on the long-term morbidity and mortality of patients with HF. The studies evaluating the efficacy and safety of UF have generally had a very short follow-up and were not designed to evaluate the morbidity and mortality.[4] and [7] The potential deleterious effects of contact between blood and extracorporeal circuits including filters and tubing are known to nephrologists.15 Although these devices are highly biocompatible, there is nevertheless a measurable degree of inflammatory reaction, with activation of various potentially deleterious cytokines.16 There is an obvious need for evaluation of long-term safety of this modality before its widespread use.
Third, one of the major proposed advantages of the UF device compared to traditional dialysis machines has been its ability to use peripheral venous access rather than a need for central venous catheters. It is noteworthy, however, that after its approval by the Food and Drug Administration, it later received marketing clearance both for use of central venous access and dual-lumen extended length catheters. Whereas some studies with a limited number of patients (eg, 9 cases) have exclusively used peripheral venous catheters,6 others (eg, UNLOAD trial) failed to report the number of patients who actually needed placement of a central venous access. Patients with HF generally tend to have compromised peripheral blood vessels owing to their advanced age, poor cardiac output, and fluid overload. The frequency for needing indwelling vascular access is of paramount importance because of their related complications, such as catheter-associated infections. There is a concern that the more frequent and chronic use of this modality in the future could increase the need for more durable blood access. Another concern with regard to practical aspects of UF would be the need for anticoagulation, similar to other extracorporeal therapies. The fact that the blood flow rate with newer machines is significantly lower than traditional dialysis therapy makes it impractical to use this modality without anticoagulation. As UF therapies are usually much longer than typical (ie, 4 hour) dialysis sessions, the prolonged anticoagulation would lead to an increased risk of bleeding complications.
Fourth, the portable UF device is intended for use by any physician who has received training in extracorporeal therapies and does not require the presence of trained dialysis nurses for its operation. Although these new sophisticated technologies are very simple to use, we believe that their efficacy and safety would be optimized by a fully trained staff; microprocessors and automation cannot be considered a “replacement” for nurses with years of clinical insights from direct patient care. We have previously discussed several serious potential complications of UF, which are similar to those associated with other extracorporeal therapies.15 In particular, there are problems that can arise from overzealous fluid removal rates (eg, hypotension and acute renal failure) and from those associated with any blood-pumped extracorporeal therapy (eg, air embolus, blood leaks, or hemolysis). These complications as well as their management strategies should ideally be incorporated in the training of the staff and physicians who intend to deliver such therapies.
Fifth, before a potential expansion of indications for this modality, it is crucial first to carefully evaluate its cost-effectiveness in the inpatient setting, where it was initially tested. Although it has been hypothesized that the impact of UF on reducing the rate of hospitalization might be financially advantageous in the long-term,7 it is currently one of the most costly modalities used for the management of HF, especially with regard to disposable supplies (eg, hemofilter). At the present time, it is unclear whether these costs would be offset by shorter length of hospitalization or shifting the care of these patients outside the intensive care units. As there would be a cost from training staff new to extracorporeal therapies (as discussed above), each facility would need to determine whether it would be financially more advantageous to use already existing resources, such as on-site dialysis nurses. In the absence of definitive randomized control trials supportive of improved clinical outcomes with UF, it has been argued that these UF therapies still have an important role in the care of patients with HF by virtue of potentially decreasing the hospital length of stay.7 Shorter admissions are attractive from the patient's perspective, lower the risk of hospital-acquired complications, and would likely appeal to the facility. Indeed, in that so many patients have their admissions paid on a fixed diagnosis-related group basis, hospitals are highly motivated for early discharge. Shortened lengths of stays could yield attractive returns on investments that would eventually permit purchase of these UF devices, the expensive disposable supplies, and hiring or training of additional staff. We anticipate that as data accumulate demonstrating a shortened length of stay, there will be more market forces and facility acceptance of proposals to expand inpatient UF services. The factors affecting the returns on investments for patients in the emergency departments, outpatient clinics, or admitted in the observation status would need to be explored and would likely vary widely between insurance carriers.
In conclusion, we believe that UF undoubtedly has the potential for greatly changing the traditional therapeutic approach to patients with proven refractory HF, and that the newer techniques and devices are certainly intended to facilitate this phenomenon. However, judicious and evidence-based use of this therapeutic modality, similar to any new therapy, is warranted. Considering the aforementioned points as well as the shortcomings of the trials that have been the scientific basis to support the increasing use of UF in patients with decompensated HF, a number of critical questions (eg, long-term safety) are still unanswered. Nevertheless, there has been an increasing interest in rapidly expanding the use of UF to the outpatient setting (eg, aquaphresis clinics) and even to the emergency department observation units, a concept encouraged by the manufacturing company of the portable UF device.17 Based on the currently available data, clinicians should judiciously use this therapy only in patients who fit within the narrow spectrum of settings (ie, inpatient) and strict criteria used in the published trials, thereby avoiding unjustified expansion of the modality's implementation or indications pending future more robust studies (current guidelines regarding the use of UF for patients with HF are summarized in Table I).
Current guidelines for the use of UF in the management of HF
| Expert group | Comment |
|---|---|
| American College of Cardiology/American Heart Association18 | If the degree of renal dysfunction is severe or if the edema becomes resistant to treatment, ultrafiltration or hemofiltration may be needed to achieve adequate control of fluid retention. This can produce meaningful clinical benefits and may restore responsiveness to conventional doses of loop diuretics. |
| Canadian Cardiovascular Society19 | In highly selected patients, intermittent slow continuous venovenous ultrafiltration may be considered. This should be performed in consultation with a nephrologist or a specialist physician who has experience using ultrafiltration in a setting of close inpatient observation. |
| European Society of Cardiology20 | In chronic heart failure, ultrafiltration can resolve pulmonary edema and overhydration in case of refractoriness to pharmacological therapies. In most patients with severe disease the relief is temporary. In acute heart failure, ultrafiltration or dialysis can be considered if other strategies are ineffective. |
References
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The authors have no potential conflicts of interest to declare with respect to this paper.
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