Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts

About 5 to 10% of patients admitted to the ICU develop acute kidney injury (AKI) requiring renal replacement therapy (RRT) [1]. AKI is an independent risk factor for mortality [1‐3] and independently associated with the development of end-stage renal disease [4, 5]. AKI is therefore not only one of the most important complications, but also one of the most cost-intensive interventions in ICU patients.

Recent randomized clinical trials showed no survival benefit or improved renal recovery in critically ill patients with AKI depending on the RRT, that is continuous RRT (CRRT) vs. intermittent renal replacement therapy (IRRT) [6‐8], or the delivered dose of RRT [9‐11]. More recently, newer hybrid techniques such as sustained low efficiency dialysis using a single-pass batch dialysis system (SLED-BD) which combines several advantages of both CRRT and IRRT have been introduced into clinical practice [12, 13]. However, only small randomized controlled trials are available that compare SLED-BD with CRRT methods. Therefore, our study aimed to investigate survival, hemodynamic stability, practicability and costs in critically ill patients with AKI treated with either SLED-BD or continuous veno-venous hemofiltration (CVVH).

In this prospective randomized study, we compared CVVH with a targeted dose of 35 ml/kg per h with SLED-BD for the treatment of AKI in ICU. In line with other reports on patients with sepsis and multi-organ failure, we found high 90-day mortality, and no differences in mortality at any time (for ICU-, in-hospital, or long-term mortality) [1, 7, 8].

Recent data demonstrate that neither the technique of RRT [7, 8] nor the dose of RRT [9‐11] had an impact on patient survival. In the light of the markedly higher costs of CRRT, it was therefore suggested that, in the absence of a survival benefit of CRRT, intermittent hemodialysis (IHD) should be the preferred treatment modality for AKI in critically ill patients [20]. In the meantime, the newer hybrid technique, SLED, which combines the hemodynamic stability of CRRT with a more favorably priced dialysis technique, has been introduced as a new cost-effective approach to the treatment of AKI in the ICU [13, 21, 22]. The hemodynamic stability of this approach was demonstrated in the first prospective smaller investigations [12, 21]. This study is, to the best of our knowledge, the first larger randomized study comparing SLED-BD with CVVH. As demonstrated, blood pressure was well maintained and even tended to be higher after treatment in the SLED group compared to CVVH, although the net UF and the use of vasopressors were not significantly different with either therapy. The decreased temperature of the non-heated dialysate during SLED-BD might have accounted for this; and in fact, the decrease in body temperature after treatment in the SLED-BD patient cohort was greater than in the CVVH treated cohort. However, the maintained hemodynamic stability in the SLED treated group may also be the result of the extended duration of the SLED treatment prescribed by the ICU physician in charge. Primarily SLED was prescribed to deliver a treatment time of 12 hours; however, the actual delivered treatment time was prolonged by the ICU physician to 14.9 hours. In contrast, the actual treatment time in the CVVH cohort was reduced but was still significantly higher than the treatment time for SLED. Although the average treatment time seems rather low, we assume that the actual delivered treatment time for CVVH in this study reflects clinical practice, at least in surgical units, where treatment is often interrupted due to bleeding complications, operative revisions or consecutive investigations. In addition, one has to consider, that we evaluated the treatment time from 12 pm to 12 pm, which means that if a treatment starts in the afternoon of the first day at 6 pm, the first session was documented as a 6 h treatment (from start until midnight). This applies also for the last treatment. When we excluded the incomplete first and last CVVH treatments, the mean duration of treatment was 19.9 ± 3.64 hours. Although, this is in line with current practice [10], this emphasizes that the method of time evaluation of treatment is of great importance and should be given. It is of interest that in almost all studies on CRRT, the prescribed and delivered doses are mentioned, but the treatment time per day and the time of interruption of treatment are not [7‐9, 23]. This is of importance, as some studies demonstrate that the time of interruption of CRRT might be relevant [11].

Our data illustrate that SLED treatment was adapted by the intensivists to a CRRT modality. In the face of newer hybrid techniques the classical differentiation in CRRT (mostly performed by CVVH with convective elimination of solutes) and IRRT (hemodialysis with diffusive elimination of solutes) may become obsolete. One has to keep in mind that adapting the treatment time of a dialysis device to a CRRT modality, resulted not only in a higher solute clearance but might lead to a potentially dangerous underdosing of, for example, anti-infective agents [24].

Another aspect, apart from the actual delivered treatment time, is that it still remains a matter of debate when to start, but also when to stop RRT, and this discussion is ongoing. It might be considered that the start of RRT in our study was too early (or too late), however, even today, criteria for starting and ending RRT remain arbitrary in many respects.

A potentially complicating factor is the more intensified anticoagulation for CRRT due to the longer treatment time required to prevent clotting of the extracorporeal circuit. In fact, earlier reports have demonstrated a significantly lower need for anticoagulation in SLED-treated patients [12, 21, 25]. However, the total amount of heparin administered in our study was slightly, but not statistically significantly lower in patients treated with SLED. This clearly overcomes the prejudice that CRRT per se requires a more intensified anticoagulation; the need for anticoagulation seems rather a consequence of the treatment time than a consequence of the treatment modality used. We do not believe that a slightly but insignificantly increased amount of heparin infused in CVVH patients in this study resulted in a higher quantity of transfused red packed cells. We may eventually only speculate as to whether small but insignificant differences in volume balance might be causative for the observed differences in blood transfusions or in the number of days of mechanical ventilation. On the other hand, the longer duration of mechanical ventilation might be responsible for the slight difference observed in the time for recovery of kidney function [26].

Costs for medical devices and treatment are of increasing importance. CVVH treatment in general consumes greater health care resources than dialysis techniques [20]. We evaluated the modality-associated costs of SLED, taking the acquisition costs for the dialysis facility into account, and compared them with CVVH for ICU patients with AKI, based on the average purchase price, number of membranes used, personnel costs and the reimbursement by the German DRG system. SLED was associated with a reduction in cost for providing RRT. In addition, a further cost reduction for the SLED modality was achieved in our department by substituting the specific AKI membrane by a conventional high-flux membrane. The costs for RRT (treatment and nursing costs) differed by about €220 per ICU patient. In fact, the difference would be much higher using conventional high-flux membranes rather than the specific AKI membranes used in our study. The difference was about €1,300 per patient. Further cost savings may be achieved by the use of a newer biocompatible low-flux membrane, which has almost equivalent efficacy to high-flux membranes at lower costs [27, 28], or by the substitution of heparin anticoagulation by using regional citrate anticoagulation protocols [29]. Though a large number of membranes were used this is in line with other studies [9]. During cost calculations, one has also to consider that the hospital reimbursement by the German DRG system is markedly higher for CVVH compared to dialysis devices. Taking the lower direct costs of SLED and the higher reimbursement for CVVH into account, our data demonstrate that CVVH remains still more expensive than SLED without superior patient outcome, at least in this small patient cohort of surgical ICU patients. Therefore, using a SLED-BD system in AKI patients in ICU has distinct advantages with regard not only to cost effectiveness, but also patency and practicability.

Newer hybrid SLED techniques using a single-pass batch system demonstrated similar patient outcomes and hemodynamic properties compared to CVVH but were associated with a more favorable price. In the light of limited health care resources, SLED offers an attractive alternative for treatment of AKI in ICU patients.