"6. Dialysis Water Quality and Dialysatea. Rationale for Water Treatment in Hemodialysis
Hemodialysis, hemofiltration, and hemodiafiltration require special water-treatment processes to prevent adverse patient outcomes of dialysis therapy resulting from improper formulation of dialysate with water containing high levels of certain chemical or biological contaminants. The Association for the Advancement of Medical Instrumentation (AAMI) has established chemical and microbiologic standards for the water used to prepare dialysate, substitution fluid, or to reprocess hemodialyzers for renal replacement therapy.788–792 The AAMI standards address: a) equipment and processes used to purify water for the preparation of concentrates and dialysate and the reprocessing of dialyzers for multiple use and b) the devices used to store and distribute this water. Future revisions to these standards may include hemofiltration and hemodiafiltration.
Water treatment systems used in hemodialysis employ several physical and/or chemical processes either singly or in combination (Figure 6). These systems may be portable units or large systems that feed several rooms. In the United States, >97% of maintenance hemodialysis facilities use RO alone or in combination with deionization.793 Many acute-care facilities use portable hemodialysis machines with attached portable water treatment systems that use either deionization or RO. These machines were exempted from earlier versions of AAMI recommendations, but given current knowledge about toxic exposures to and inflammatory processes in patients new to dialysis, these machines should now come into compliance with current AAMI recommendations for hemodialysis water and dialysate quality.788, 789 Previous recommendations were based on the assumption that acute-care patients did not experience the same degree of adverse effects from short-term, cumulative exposures to either chemicals or microbiologic agents present in hemodialysis fluids compared with the effects encountered by patients during chronic, maintenance dialysis.788, 789 Additionally, JCAHO is reviewing inpatient practices and record-keeping for dialysis (acute and maintenance) for adherence to AAMI standards and recommended practices.
Neither the water used to prepare dialysate nor the dialysate itself needs to be sterile, but tap water can not be used without additional treatment. Infections caused by rapid-growing NTM (e.g., Mycobacterium chelonae and M. abscessus) present a potential risk to hemodialysis patients (especially those in hemodialyzer reuse programs) if disinfection procedures to inactivate mycobacteria in the water (low-level disinfection) and the hemodialyzers (high-level disinfection) are inadequate.31, 32, 633 Other factors associated with microbial contamination in dialysis systems could involve the water treatment system, the water and dialysate distribution systems, and the type of hemodialyzer.666, 667, 794–799 Understanding the various factors and their influence on contamination levels is the key to preventing high levels of microbial contamination in dialysis therapy.
In several studies, pyrogenic reactions were demonstrated to have been caused by lipopolysaccharide or endotoxin associated with gram-negative bacteria.794, 800–803 Early studies demonstrated that parenteral exposure to endotoxin at a concentration of 1 ng/kg body weight/hour was the threshold dose for producing pyrogenic reactions in humans, and that the relative potencies of endotoxin differ by bacterial species.804, 805 Gram-negative water bacteria (e.g., Pseudomonas spp.) have been shown to multiply rapidly in a variety of hospital-associated fluids that can be used as supply water for hemodialysis (e.g., distilled water, deionized water, RO water, and softened water) and in dialysate (a balanced salt solution made with this water).806 Several studies have demonstrated that the attack rates of pyrogenic reactions are directly associated with the number of bacteria in dialysate.666, 667, 807 These studies provided the rationale for setting the heterotrophic bacteria standards in the first AAMI hemodialysis guideline at <2,000 CFU/mL in dialysate and one log lower (<200 CFU/mL) for the water used to prepare dialysate.668, 788 If the level of bacterial contamination exceeded 200 CFU/mL in water, this level could be amplified in the system and effectively constitute a high inoculum for dialysate at the start of a dialysis treatment.807, 808 Pyrogenic reactions did not appear to occur when the level of contamination was below 2,000 CFU/mL in dialysate unless the source of the endotoxin was exogenous to the dialysis system (i.e., present in the community water supply). Endotoxins in a community water supply have been linked to the development of pyrogenic reactions among dialysis patients.794
Whether endotoxin actually crosses the dialyzer membrane is controversial. Several investigators have shown that bacteria growing in dialysate-generated products that could cross the dialyzer membrane.809 810 Gram-negative bacteria growing in dialysate have produced endotoxins that in turn stimulated the production of anti-endotoxin antibodies in hemodialysis patients;801, 811 these data suggest that bacterial endotoxins, although large molecules, cross dialyzer membranes either intact or as fragments. The use of the very permeable membranes known as high-flux membranes (which allow large molecules [e.g., â2 microglobulin] to traverse the membrane) increases the potential for passage of endotoxins into the blood path. Several studies support this contention. In one such study, an increase in plasma endotoxin concentrations during dialysis was observed when patients were dialyzed against dialysate containing 103–104 CFU/mL Pseudomonas spp.812 In vitro studies using both radiolabeled lipopolysaccharide and biologic assays have demonstrated that biologically active substances derived from bacteria found in dialysate can cross a variety of dialyzer membranes.802, 813–816 Patients treated with high-flux membranes have had higher levels of anti-endotoxin antibodies than subjects or patients treated with conventional membranes.817 Finally, since 1989, 19%–22% of dialysis centers have reported pyrogenic reactions in the absence of septicemia.818, 819
Investigations of adverse outcomes among patients using reprocessed dialyzers have demonstrated a greater risk for developing pyrogenic reactions when the water used to reprocess these devices contained >6 ng/mL endotoxin and >104 CFU/mL bacteria.820 In addition to the variability in endotoxin assays, host factors also are involved in determining whether a patient will mount a response to endotoxin.803 Outbreak investigations of pyrogenic reactions and bacteremias associated with hemodialyzer reuse have demonstrated that pyrogenic reactions are prevented once the endotoxin level in the water used to reprocess the dialyzers is returned to below the AAMI standard level.821
Reuse of dialyzers and use of bicarbonate dialysate, high-flux dialyzer membranes, or high-flux dialysis may increase the potential for pyrogenic reactions if the water in the dialysis setting does not meet standards.796–798 Although investigators have been unable to demonstrate endotoxin transfer across dialyzer membranes,803, 822, 823 the preponderance of reports now supports the ability of endotoxin to transfer across at least some high-flux membranes under some operating conditions. In addition to the acute risk of pyrogenic reactions, indirect evidence in increasingly demonstrating that chronic exposure to low amounts of endotoxin may play a role in some of the long-term complications of hemodialysis therapy. Patients treated with ultrafiltered dialysate for 5–6 months have demonstrated a decrease in serum â2 microglobulin concentrations and a decrease in markers of an inflammatory response.824–826 In studies of longer duration, use of microbiologically ultrapure dialysate has been associated with a decreased incidence of â2 microglobulin-associated amyloidosis.827, 828
Although patient benefit likely is associated with the use of ultrapure dialysate, no consensus has been reached regarding the potential adoption of this as standard in the United States. Debate continues regarding the bacterial and endotoxin limits for dialysate. As advances in water treatment and hemodialysis processes occur, efforts are underway to move improved technology from the manufacturer out into the user community. Cost-benefit studies, however, have not been done, and substantially increased costs to implement newer water treatment modalities are anticipated.
To reconcile AAMI documents with current International Organization for Standardization (ISO) format, AAMI has determined that its hemodialysis standards will be discussed in the following our installments: RD 5 for hemodialysis equipment, RD 62 for product water quality, RD 47 for dialyzer reprocessing, and RD 52 for dialysate quality. The Renal Diseases and Dialysis Committee of AAMI is expected to finalize and promulgated the dialysate standard pertinent to the user community (RD 52), adopting by reference the bacterial and endotoxin limits in product water as currently outlined in the AAMI standard that applies to systems manufacturers (RD 62). At present, the user community should continue to observe water quality and dialysate standards as outlined in AAMI RD 5 (Hemodialysis Systems, 1992) and AAMI RD 47 (Reuse of Hemodialyzers, 1993) until the new RD 52 standard
becomes available (Table 18).789,
The current AAMI standard directed at systems manufacturers (RD 62 [Water Treatment Equipment for Hemodialysis Applications, 2001]) now specifies that all product water used to prepare dialysate or to reprocess dialyzers for multiple use should contain <2 endotoxin units per milliliter (EU/mL).792 A level of 2 EU/mL was chosen as the upper limit for endotoxin because this level is easily achieved with contemporary water treatment systems using RO and/or ultrafiltration. CDC has advocated monthly endotoxin testing along with microbiologic assays of water, because endotoxin activity may not correspond to the total heterotrophic plate counts.829 Additionally, the current AAMI standard RD 62 for manufacturers includes action levels for product water. Because 48 hours can elapse between the time of sampling water for microbial contamination and the time when results are received, and because bacterial proliferation can be rapid, action levels for microbial counts and endotoxin concentrations are reported as 50 CFU/mL and 1 EU/mL, respectively, in this revision of the standard.792 These recommendations will allow users to initiate corrective action before levels exceed the maximum levels established by the standard.
In hemodialysis, the net movement of water is from the blood to the dialysate, although within the dialyzer, local movement of water from the dialysate to the blood through the phenomenon of backfiltration may occur, particularly in dialyzers with highly permeable membranes.830 In contrast, hemofiltration and hemodiaflltration feature infusion of large volumes of electrolyte solution (20–70 L) into the blood. Increasingly, this electrolyte solution is being prepared on-line from water and concentrate. Because of the large volumes of fluid infused, AAMI considered the necessity of setting more stringent requirements for water to be used in this application, but this organization has not yet established these because of lack of expert consensus and insufficient experience with on-line therapies in the United States. On-line hemofiltration and hemodiafiltration systems use sequential ultrafiltration as the final step in the preparation of infusion fluid. Several experts from AAMI concur that these point-of-use ultrafiltration systems should be capable of further reducing the bacteria and endotoxin burden of solutions prepared from water meeting the requirements of the AAMI standard to a safe level for infusion.
b. Microbial Control Strategies
The strategy for controlling massive accumulations of gram-negative water bacteria and NTM in dialysis systems primarily involves preventing their growth through proper disinfection of watertreatment systems and hemodialysis machines. Gram-negative water bacteria, their associated lipopolysaccharides (bacterial endotoxins), and NTM ultimately come from the community water supply, and levels of these bacteria can be amplified depending on the water treatment system, dialysate distribution system, type of dialysis machine, and method of disinfection (Table 19).634, 794, 831 Control strategies are designed to reduce levels of microbial contamination in water and dialysis fluid to relatively low levels but not to completely eradicate it.
Two components of hemodialysis water distribution systems – pipes (particularly those made of polyvinyl chloride [PVC]) and storage tanks – can serve as reservoirs of microbial contamination. Hemodialysis systems frequently use pipes that are wider and longer than are needed to handle the required flow, which slows the fluid velocity and increases both the total fluid volume and the wetted surface area of the system. Gram-negative bacteria in fluids remaining in pipes overnight multiply rapidly and colonize the wet surfaces, producing bacterial populations and endotoxin quantities in proportion to the volume and surface area. Such colonization results in formation of protective biofilm that is difficult to remove and protects the bacteria from disinfection.832 Routine (i.e., monthly), lowlevel disinfection of the pipes can help to control bacterial contamination of the distribution system. Additional measures to protect pipes from contaminations include a) situating all outlet taps at equal elevation and at the highest point of the system so that the disinfectant cannot drain from pipes by gravity before adequate contact time has elapsed and b) eliminating rough joints, dead-end pipes, and unused branches and taps that can trap fluid and serve as reservoirs of bacteria capable of continuously inoculating the entire volume of the system.800 Maintain a flow velocity of 3–5 ft/sec.
A storage tank in the distribution system greatly increases the volume of fluid and surface area available and can serve as a niche for water bacteria. Storage tanks are therefore not recommended for use in dialysis systems unless they are frequently drained and adequately disinfected, including scrubbing the sides of the tank to remove bacterial biofilm. An ultrafilter should be used distal to the storage tank.808, 833
Microbiologic sampling of dialysis fluids is recommended because gram-negative bacteria can proliferate rapidly in water and dialysate in hemodialysis systems; high levels of these organisms place patients at risk for pyrogenic reactions or health-care–associated infection.667, 668, 808
Health-care facilities are advised to sample dialysis fluids at least monthly using standard microbiologic assay methods for waterborne microorganisms.788, 793, 799, 834–836 Product water used to prepare dialysate and to reprocess hemodialyzers for reuse on the same patient should also be tested for bacterial endotoxin on a monthly basis.792, 829, 837 (See Appendix C for information about water sampling methods for dialysis.)
Cross-contamination of dialysis machines and inadequate disinfection measures can facilitate the spread of waterborne organisms to patients. Steps should be taken to ensure that dialysis equipment is performing correctly and that all connectors, lines, and other components are specific for the equipment, in good repair, and properly in place. A recent outbreak of gram-negative bacteremias among dialysis patients was attributed to faulty valves in a drain port of the machine that allowed backflow of saline used to flush the dialyzer before patient use.838, 839 This backflow contaminated the drain priming connectors, which contaminated the blood lines and exposed the patients to high concentrations of gram-negative bacteria. Environmental infection control in dialysis settings also includes low-level disinfection of housekeeping surfaces and spot decontamination of spills of blood (see Environmental Services in Part I of this guideline for further information).
c. Infection-Control Issues in Peritoneal Dialysis
Peritoneal dialysis (PD), most commonly administered as continuous ambulatory peritoneal dialysis (CAPD) and continual cycling peritoneal dialysis (CCPD), is the third most common treatment for endstage renal disease (ESRD) in the United States, accounting for 12% of all dialysis patients.840 Peritonitis is the primary complication of CAPD, with coagulase-negative staphylococci the most clinically significant causative organisms.841 Other organisms that have been found to produce peritonitis include Staphylococcus aureus, Mycobacterium fortuitum, M. mucogenicum, Stenotrophomonas maltophilia, Burkholderia cepacia, Corynebacterium jeikeium, Candida spp., and other fungi.842–850 Substantial morbidity is associated with peritoneal dialysis infections. Removal of peritoneal dialysis catheters usually is required for treatment of peritonitis caused by fungi, NTM, or other bacteria that are not cleared within the first several days of effective antimicrobial treatment. Furthermore, recurrent episodes of peritonitis may lead to fibrosis and loss of the dialysis membrane.
Many reported episodes of peritonitis are associated with exit-site or tunneled catheter infections. Risk factors for the development of peritonitis in PD patients include a) under dialysis, b) immune suppression, c) prolonged antimicrobial treatment, d) patient age [more infections occur in younger patients and older hospitalized patients], e) length of hospital stay, and f) hypoalbuminemia.844, 851, 852 Concern has been raised about infection risk associated with the use of automated cyclers in both inpatient and outpatient settings; however, studies suggest that PD patients who use automated cyclers have much lower infection rates.853 One study noted that a closed-drainage system reduced the incidence of system-related peritonitis among intermittent peritoneal dialysis (IPD) patients from 3.6 to 1.5 cases/100 patient days.854 The association of peritonitis with management of spent dialysate fluids requires additional study. Therefore, ensuring that the tip of the waste line is not submerged beneath the water level in a toilet or in a drain is prudent."
Several pages have references to dialysis units: pages 20, 28, 37-39, 41, 46, and 57.
Disclaimer: This draft document is intended for public comment only. Healthcare personnel should not modify practices or policies based on these preliminary recommendations.
This guideline has been developed for practitioners who provide care for patients and who are responsible for monitoring and preventing infections in healthcare settings, including hemodialysis units. This guideline is intended to replace the section in Guideline for Handwashing and Hospital Environmental Control, 1985, that dealt with sterilization and disinfection.
Public comments on the new guidelines and recommendations should be submitted before June 14.
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