This study is, to our knowledge, the first multicenter, multinational study that estimated cost differences between CRRT and IRRT in critically ill patients. We examined cost differences across four different domains and found significant variability in clinical practice. These differences resulted in a wide range of potential cost differences, ranging from greater costs with CRRT to greater costs with IRRT. In most regions, fluid and extracorporeal circuit costs were the largest contributors to the greater cost of CRRT.
Physician and nursing practice varied significantly by region. In North and South America, nephrologists were primarily responsible for both CRRT and IRRT, although intensivists in Northern Europe and Asia played a more dominant role for both therapies. For CRRT, we found that in Northern Europe, Southern Europe, Asia, and Australia, primarily intensivists prescribed CRRT. Our results are consistent with those of Ronco et al
], who reported survey data from 345 participants who attended two international meetings, and found that 35% of centers had only nephrologists, 18%, only intensivists, and 36% had both prescribing CRRT.
We found that the cost of CRRT was usually greater than that of IRRT, but this was not always so. Results from previous single- or two-center studies showed wide variability in cost estimates. Manns et al
] reviewed charts from two tertiary ICUs in Canada and demonstrated that the cost of performing CRRT ranged between Can $3,486/week and Can $5,117/week, whereas the cost of performing IRRT was Can $1,342/week. In the same year, Vitale et al
] reported the data from a single center in Italy, and found that the daily cost of CRRT was €276.70, whereas the daily cost of 4 h of IRRT was €247.83. Finally, Rauf et al
] estimated that mean adjusted costs through to hospital discharge were $93,611 and $140,733 among IRRT-treated and CRRT-treated patients, respectively. In our study, we found a range of total cost differences between CRRT and IRRT, which included these prior estimates but also included scenarios in which no difference in cost existed between the modalities, as well as scenarios in which IRRT was actually more expensive compared with CRRT.
Although our analysis included four separate cost domains, we could not estimate secondary cost differences arising from differences in resource allocation as a result of the different therapies. For example, CRRT may limit patient mobility to a greater extent compared with IRRT. If this difference resulted in greater use of physical therapists, additional secondary costs would be associated with CRRT. Conversely, if the use of CRRT were associated with improved renal recovery, as suggested by some observational studies [21
], the added cost of continued renal support with IRRT would greatly increase cost differences in favor of CRRT. Available evidence from randomized trials has not demonstrated a survival benefit for CRRT when compared with IRRT [5
]. Similarly, these trials have not found consistent differences in the ICU or hospital length of stay when one modality is used instead of the other. However, such head-to-head comparisons between IRRT and CRRT do not reflect clinical practice in most of the world where each modality is used to meet specific clinical needs [6
]. Therefore, the portion of the RRT treatment that is considered to be discretionary between CRRT and IRRT may be limited. Nevertheless, it is important to note that cost differences between these modalities are determined largely by factors that can be modified.
For example, the cost of CRRT in our study was significantly influenced by the cost of fluids and therefore the rate of their use. When we limited effluent (replacement fluid plus dialysis) flow rate to 25 ml/min (~25 ml/kg/h), we could reduce fluid costs by ~43.3%. Given the results of the Acute Renal Failure Trials Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study [6
], which found no survival advantage by increasing effluent flow rates to 35 and 40 ml/kg/h, respectively, reducing fluid use by reducing effluent flow rates to 25 ml/kg/h would seem prudent - provided that this minimal dose can be ensured.
Surprisingly, nursing staffing was a significant cost component of IRRT, as shown in Figure . This finding reflects two underlying practices that were highly variable across centers. First, some centers increased ICU nurse staffing (decreased nursing ratios) when CRRT was provided. In these centers, labor costs were greater with CRRT. By contrast, for centers providing 1:1 nursing for all ICU patients or not changing staffing when providing CRRT, labor costs can be greater only when IRRT requires additional staff from the dialysis unit. Second, given that most ICUs (as opposed to dialysis units) do not group their patients on dialysis, the typical IRRT session is delivered by a dedicated dialysis nurse. Thus, labor costs will inevitably be greater for IRRT relative to CRRT in centers where ICU nurse staffing does not change when CRRT is provided and when IRRT is provided by a dedicated (single-patient) dialysis nurse.
Another source of costs differences between CRRT and IRRT came from the use of anticoagulation. In Japan, the cost of anticoagulation is an important part of the total cost of RRT: nearly 50% of RRT patients (42.03%) in Japan were treated with nafamostat mesylate, a synthetic serine protease inhibitor that inhibits coagulation and fibrinolysis [22
]. The cost of this drug is significantly greater than that of conventional heparin.
Our study had several limitations. First, it was not designed to estimate the fixed costs of RRT, such as the dialysis machine cost. Neither did we attempt to determine differences in physician billing, which varied depending on the health care system of each center and country.
Second, although we report a median cost difference between modalities among our centers, our primary goal was not to determine average costs. Instead, we intended to determine the range and variability of costs and their determinants. We believe that such information is more valuable to an individual practitioner or hospital, because local costs will vary but are likely to fall somewhere with the range we observed and are likely to be influenced by the same factors that we found in our study. Our median cost figure is undoubtedly a reflection of the composition of centers in our study, which may have been skewed toward those with a particular interest in AKI in the ICU. However, because we included a highly heterogeneous group of centers, the ranges of costs we report, as opposed to the point estimates, are likely to be highly generalizable.
Third, we had incomplete data on actual costs for certain domains and used regional references to estimate these costs. These regional references likely underestimate the variability between centers, particularly in some regions.
Finally, we accepted that a mixture of developed and developing countries exists in some regions such as in Asia. Furthermore, our categorization of countries by region was somewhat arbitrary, and wide differences may exist between practice patterns within each region. However, when the primary analysis is repeated after excluding the 44 patients from three centers in countries with arguably very different healthcare delivery systems (14 patients from Russia, six patients from China, and 24 patients from Indonesia), our results were not materially changed. We also realize that we may underestimate the cost of anticoagulation, because we do not include the cost of monitoring of anticoagulation such as ionized calcium, or aPTT/ACT. However, our intent was to provide an overall picture of the range of cost differences between IRRT and CRRT, rather than specifically to estimate costs in each region. Thus, the cost landscape we were able to illustrate provides the first international glimpse into this important area.