Hybrid Dialysis Techniques in the Intensive Care Unit

Machinery

A fundamental feature of HT is the use of outpatient nephrology IHD machinery. Maintenance IHD programs are very common throughout the world, and hospitals that have such programs are in possession of all the technical elements necessary to an HT program. In some hospitals, there has been a clear mandate to adapt and share existing machinery between maintenance IHD and HT programs, thereby reducing the cost of program implementation and maintenance. In fact, one of the main motivating factors for nocturnal HT was the need to use the machinery in outpatient IHD facilities during the day. In other hospitals (particularly where ICU provides ARRT), machinery for HT is owned and maintained by the ICU as a separate ongoing concern, although it remains the same as (or technically very similar to) that used by nephrology services.

Almost any IHD machine can be used for HT. However, blood and dialysate flow rates (Q _B and Q _D , respectively) and treatment session duration are typically different from that of conventional IHD (see Table 159.1 ), and machines must be capable of being changed to any of these variations in a convenient fashion. The ideal HT machine therefore is versatile over a wide range of operating conditions and easy to use. Specifically, the following features should be considered in the choice of a machine for HT:

• Flexibility of Q _D from as low as 100 mL/min up to the dialysis flow rates used for conventional IHD

• Flexibility of treatment session length from as short as those used for conventional IHD up to continuous duration

• Clear interface between machine and staff conducting treatment

• Easy transition between IHD and HT modes

In the first descriptions of HT, dialysate for treatments was produced in batches and used in now-outdated batch dialysis machinery. In the modern practice of HT, only one such batch machine remains in common use, the GENIUS therapy system (Fresenius Medical Care, Bad Homburg, Germany). This machine is sold only in Europe at present. For this machine, dialysate is generated in the outpatient nephrology dialysis unit through the use of a separate machine called a “preparator” and stored in a 75- or 90-L tank within the machine. A single roller pump is used to move dialysate and blood (max Q _B 300 mL/min) through the extracorporeal circuit at a ratio of 1 : 1 to 1 : 2. This ratio is determined by the staff conducting treatment, who choose between lines that have different lumen widths for the segments in the roller pump that provide Q _B and Q _D . Fresh dialysate is pumped from the top of the dialysate storage tank, and spent dialysate is returned to the bottom. Despite the lack of a physical barrier between these fluids, there is little mixing within the tank. Separation is maintained by small but important differences in fluid density and temperature between fresh and spent dialysate. One HT session using the GENIUS machine can last up to 15 hours with a Q _D of 100 mL/min.

The GENIUS machine has several advantages over single-pass machines. Treatments can be performed in the ICU without the need for a water supply. It is very easy to set operating parameters via independent and simple controls, allowing unlimited combinations of Q _B , Q _D , and session duration. An argument has been made that dialysate sterility in this machine is superior to that in single-pass machines, although this contention has not been proven and is not likely. Disadvantages of the GENIUS machine are its weight (approx 165 kg) and its fixed clearance, which is due to the fixed aliquot of dialysate per treatment. Nevertheless, this machine is regarded by some opinion leaders as the best HT machine on the market.

Generally around the world, HT is performed using single-pass machines, whereby solutions for blood purification in HT are generated online from purified tap water and dialysate concentrate. Few of these machines are suited ideally for HT ( Table 159.2 ), and most have some limitations around the lowest Q _D and the longest HT session length that can be provided. With regard to Q _D , these limits do not impose any critical clinical limitation. A Q _D of 300 mL/min is perfectly satisfactory in most clinical circumstances, and there are often means to reduce effective Q _D without drastically modifying machine hardware. For instance, one group of researchers has used the Gambro AK200S Ultra machine (Gambro AB, Stockholm, Sweden) in hemofiltration mode; the replacement fluid is used as countercurrent dialysate within the dialyzer at 100 mL/min, the operational QD on the machine interface set to zero (E. Fiaccadori, personal communication, September 7, 2005; P. Van Malderen, personal communication, September 9, 2005). Another group has developed a simple shunt to be used with the Fresenius 4008H machine (Fresenius Medical Care), which allows a proportion of the dialysate to bypass the hemodialyzer. There are probably easier and simpler ways to reduce the effective Q _D from 300 mL/min to the equivalent of 100 mL/min, such as reducing hemodialyzer size and using co-current dialysate flow.

With regard to treatment session length, many machines in North America can perform treatments for 24 hours or even continuously (e.g., Fresenius 2008K, Fresenius Medical Care North America, Lexington, MA), but most in Europe and the Asia Pacific region can perform treatments for only 10 hours (e.g., Fresenius 4008S, Fresenius Medical Care). This difference is due to different regulatory environments between the continents. This trend is changing, and some of the newer European machines from major vendors have an option for 24-hour or continuous treatment (e.g., Fresenius 5008S, Fresenius Medical Care).

Many vendors are selling or developing machines that switch easily and instantaneously between IHD and HT modes (so-called universal platforms). Fresenius Medical Care undoubtedly has taken the lead in this regard, having developed the two or three leading machines in terms of ease of operation—the Fresenius 2008K (US), 4008S ARrT Plus (Asia Pacific), and 5008S (Europe). All of these machines allow selection of CRRT or HT from their startup screens and enable easy changes of operating parameters.

Water Quality

Fluids for blood purification in HT usually are generated online from purified tap water and dialysate concentrate. In contrast are those used in CRRT, which are pharmacy-made or commercially purchased and delivered to the point of service, for batch and single-pass machinery. A growing concern is the possibility of exposure to bacterial contaminants—and specifically endotoxin—from these fluids. Such exposure may arise during direct infusion of online replacement fluid and also from backfiltration via dialysate into the patient. It therefore generally is accepted that water quality for online fluids should conform to the same standards that are used in the outpatient nephrology IHD setting.

The critical question, however, is whether water purity for ARRT actually should be higher than this standard. In the absence of any definitive clinical trial data, many opinion leaders opt for dialysate sterilization using ultrafilters in the dialysate pathway, especially if high-flux membranes are being used. These ultrafilters remove bacteria and endotoxin by virtue of a pore size of about 0.22 µm and specific adsorptive properties. This decision is based on observational evidence or surrogate end points. A counterargument has been made that bacterial contaminants are removed sufficiently by the dialyzer during backfiltration by most common membranes and that dialysate sterilization is unnecessary. Clearly, a definitive trial is needed urgently to determine optimal clinical practice.

There is less debate about water quality for online replacement fluid for hemodiafiltration. This fluid is a fraction of dialysate that is infused directly into the extracorporeal circuit either before or after the diafilter. The ionic composition of replacement fluid does not differ from that of dialysate. Such fluid should be sterile (no growth, endotoxin concentration < 0.03 endotoxin units). This is achieved by passing water and/or dialysate through two (Fresenius) or three (Gambro) ultrafilters before being infused. This process has been shown to yield a fluid that is at least as sterile as commercially available fluids. The U.S. Food and Drug Administration has not approved such a process, and a similar situation exists in some European countries. In these countries, online replacement fluid preparation is not used in patients, and hemodiafiltration during HT is performed using pharmacy-made or commercially purchased fluids or, more commonly, normal saline.

Hemodialyzers

Hemodialyzers used for HT can be the same as those used for conventional IHD and intermittent hemodiafiltration (IHDF). Hemodialyzer membranes can be low-flux or high-flux. High-flux membranes contain large pores that theoretically allow for greater permeability of larger putative uremic toxins. There are no comparisons of low-flux and high-flux membranes in HT; the only available data pertain to comparisons involving conventional IHDF or high-flux IHD versus low-flux IHD. In studies of ARRT in the ICU population, the more permeable membranes demonstrate no clinical or laboratory advantages over the less porous ones. This negative result may be biased by residual confounding in these studies from unrecognized back-transport of potentially harmful waterborne molecules (see previous discussion). Alternatively, the negative results may be true, resulting from the low mass removal of larger solutes (in absolute terms) afforded by these modalities. For instance, low-flux IHD clears about 3 mL/min of β ₂ -microglobulin from blood water during the course of treatment, high-flux IHD clears only about 35 mL/min, and even IHDF clears only about 50 to 150 mL/min, depending on the hemofiltration (Q _F ) rate. Given the short duration over which these modalities are applied, a meaningful clinical effect seems unlikely. In contrast, the longer duration for HT makes a clinical effect seem more plausible, although it remains to be proven.

The effect of membrane biocompatibility on outcomes (when present) is consistently beneficial, although the data overall are conflicting. Notwithstanding, such membranes now can be obtained cheaply, and because cost has been eliminated as a deciding factor, it is recommended that all patients be treated with these membranes.

Online hemodiafiltration is being used increasingly during HT. The rationale for this technique is predicated on a survival benefit conferred by combined convection and diffusion that is not conferred by diffusion alone. This assumption has some support in the literature but is not proven. Hemofiltration rates reported during convective HT vary from 17 to 100 mL/min. Higher convection leads to increased clearance of middle-sized and larger uremic solutes, which can amount to more than 50% of the small solute clearance. Moreover, other features of online hemodiafiltration, such as thermal energy transfer, also may affect clinical outcomes. Several groups of investigators have demonstrated the logistic feasibility of convective HT. However, further studies still are needed to compare outcomes of this modality and diffusive HT. These studies should explore not only the relationship between removal of middle-sized and larger uremic solutes and clinical outcomes but also the role of thermal energy transfer and other features of convective ARRT in general.

Hemodialyzer size is probably not critical. Two groups have reported experience with moving from a larger to smaller hemodialyzers for HT, for the purposes of reducing extracorporeal circuit clotting. Neither group has reported any deterioration in solute control or clearance. The relationship between hemodialyzer urea mass-transfer area coefficient (K _O A), Q _D , and Q _B is not predictable during HT because of a mismatch between dialysate and blood flows resulting from incomplete fiber bundle penetration at low flows that creates a shunt within the dialyzer. Further studies on this important area are needed before a recommendation can be made.