The number of chronic dialysis patients in Japan is nearly 300,000, and 95% of them are treated with hemodialysis.1 Most dialysis clinics in Japan have mainly adopted the central dialysis fluid delivery system (CDDS) to provide constant treatment to many patients. In the CDDS, pure water is produced using a reverse osmosis (RO) device, and dialysis fluid for many patients is centrally prepared and subsequently distributed to dialysis console units for each patient for treatment. In this dialysis fluid preparation, A and B powders are dissolved and used, allowing dialysate preparation for many patients. However, in many other countries, pure water is prepared in the RO device and supplied to single-patient dialysis machines, where the dialysate is prepared for treatment (Figure 1, A and B). Manufacturers have released many original RO devices and dialysis fluid supply equipment, and many techniques have been developed for the CDDS. Nevertheless, no evaluation method has been determined; therefore, few reports on dialysate purification have been published. In response to this situation, the Japanese Society for Dialysis Therapy played a central role in establishing the Water Quality Control Standard based on the ISO standard.2 In the journal Blood Purification, Kawanishi et al.3 reported the characteristics of the CDDS and referred to the need to establish a validation protocol to ensure dialysate purification. Our clinic has also been using the CDDS for dialysis treatment since it was established, with a focus on dialysate purification. Recently, stricter water quality control and further dialysate purification have been required, taking on-line hemodiafiltration (HDF) into consideration, when prepared dialysate is used for infusion.4,5 In 2007, we introduced a new CDDS with an automatic hot water disinfection system to disinfect an RO device and a dialysis fluid supply equipment using the heat conduction effect. The new system has produced good results in dialysate purification since its introduction. However, it is necessary to verify the system in consideration of the 3 years that have passed since installation and in response to establishment of the dialysate purification guidelines.6–8
We describe how dialysate purification functioned for the 3 years since introduction of an automated hot water disinfection system that disinfects an RO device and a dialysis fluid supply equipment using the heat conduction effect.
In April 2007, we installed the “DCXnano201DP” RO device manufactured by Mitsubishi Rayon Co., Ltd (Tokyo, Japan), and the “NCS-V” multipatient dialysis fluid supply equipment, the “NPS-50A” automated A-powder dissolving equipment, and the “NPS-50B” automated B-powder dissolving equipment manufactured by Nipro Co., Ltd (Osaka, Japan). The disinfection cycle was as follows: disinfection with 350 ppm sodium hypochlorite (0.035%) every day when dialysis treatment was performed, 1,000 ppm (0.1%) acetic acid twice a week, and hot water once a week (Figure 2). Hot water disinfection was set to be performed in a fully automatic manner on Sundays. When the hot water temperature reached 90°C using the heating source of the RO device, electric signals were emitted and hot water flowed into the dialysis fluid supply equipment. During the actual hot water disinfection process, monitoring was performed using a thermistor. In addition, electric power consumption necessary for hot water disinfection was calculated and cost performance was evaluated. For the evaluation of dialysate purification, samples were obtained from 1) the end of the RO piping and 2) the end of the piping of the dialysis fluid supply equipment (dialysis fluid piping), and the endotoxin level and viable cell count were evaluated. For the measurement of endotoxin, a toxinometer ET-5500, manufactured by Wako Pure Chemical Industries, Ltd. (Osaka, Japan), was used. Toxinometer ET-5500 is a measuring equipment that detects endotoxin using Limulus polyphemus blood cells (amebocytes). The measurement sensitivity of the equipment depends on the reagent made from the Limulus polyphemus blood cells (amebocytes). The detection sensitivity of the equipment is 1.5 EU/L after a lapse of 5 minutes and 0.00361 EU/L on average after a lapse of 90 minutes. The sample volume was 200 µl. Considering adsorption by the container after sample collection, measurement was quickly performed using colorimetric time assay. The obtained gelation time was converted into the endotoxin level. Viable cells were counted using Reasoner’s 2A Agar culture and membrane filter methods. The sample volume for the Reasoner’s 2A Agar method was 1 ml. We used a membrane filter of 0.45 µm pore size. Because the membrane filter was a cartridge-type filter, samples (50 ml) were poured. Cells on Reasoner’s 2A Agar or membrane filters were cultured at room temperature (23°C) for 7 days. Measurement was performed monthly as has been strongly recommended since 2007 in Japan.
Our CDDS and Control Method
The old and new systems are shown in Figure 3 for comparison. The old system was characterized by flow in one direction from the RO device to the dialysis fluid supply equipment. Moreover, A and B concentrate piping were not disinfected.9 In the old system, the dialysis fluid supply equipment was disinfected with sodium hypochlorite daily and with acetic acid twice weekly. The new system is characterized by a heat source in the RO device, which allows hot water disinfection from the RO device to the dialysis fluid supply equipment, and the line to A- and B-powder dissolutions. Without changes in the chemical disinfection method for the old system, only hot water disinfection once weekly was added. In the hot water disinfection process, the heated RO water circulates in the RO piping and raises the temperature. The RO filter is heated as well. Finally, the RO tank is filled with hot water. The system remains in this state. At that time, the temperature of hot water in the RO device is 90°C or more. Signals are emitted from the dialysis fluid supply equipment, and hot water in the RO device flows into the dialysis fluid supply equipment, filling it. Although hot water in the RO device and the dialysis fluid supply equipment should be drained finally, we do not have piping that allows water drainage at temperatures from 80 to 90°C. Therefore, water must be cooled down to at least 60°C before being drained. As such, we developed a system mixing hot water with tap water, in which the temperature is controlled by a thermistor to ensure that the water cools down to 60°C or less before drainage.
Figure 4, A and B shows the endotoxin level at the end of the RO piping and the dialysis fluid piping, respectively, before and after system introduction. No viable bacteria were found after the system introduction. We also checked the inflow to each dialysis console and did not find viable bacteria. Endotoxin level often showed abnormal values before introduction of the hot water disinfection system, but values were lower than measurement sensitivity after introduction at either end of the dialysis fluid piping, the RO piping, and the consoles. Such conditions were maintained even after 3 years had passed. In addition, the ultrapure dialysate standard addressed in the last updated Dialysate Purification Guidelines6,7 was satisfied. From this, it can be said that the system can produce ultrapure dialysate satisfying the current ISO requirements. The results of monitoring using a thermistor in the hot water disinfection process are shown in Figure 5. Water is heated to 90°C or more in the tank of the RO device containing a heat source and flows into the dialysis fluid supply equipment from the RO device. The maximum temperature in the tank of the dialysis fluid supply equipment is 86.3°C. Monitoring in this study also showed a maximum temperature of 83.1°C and maintenance of temperatures ≥80°C for approximately 17 minutes or more. With regard to cost performance, the electricity consumption/hot water disinfection was 35 KW, and the charge for electricity was approximately 130 yen in Japan.
In Japan, the CDDS has been mainly used for hemodialysis systems, but the standards for the CDDS are not clear. In reality, each dialysis clinic disinfected the system based on its own internal standard. In recent years, various related studies have been performed in Japan. Dialysate purification was defined as the goal of system design, along with its management methods to prepare dialysis water/fluid that was free from chemical or biologic contaminants and that could be safely used for hemodialysis therapy. Recommended standards assuring the safety of hemodialysis therapy and showing minimal compliance items have been evaluated as the Japanese guidelines. Recently, the on-line HDF system has also been actively used, and standards for the direct entry of dialysis fluid into the body are required.
Until approximately 20 years ago, the CDDS was disinfected using hot water in many clinics in Japan. At that time, the purification standards were not clear, and it was quite costly and required great effort to control the hot water. Although it could be successful for purification, its drawbacks led to its replacement by convenient chemical disinfection. Using the old system of our hospital, because cleaning after disinfection was manually performed, the procedure tended to be complicated, there was concern about residual chlorine, and safety was not assured. (Indeed, problems caused by residual chlorine have been reported, and exercising caution with regard to chemical disinfection has also been stated as a safety measure.) In addition, there were dead spaces that could not be disinfected, such as the space from the RO device to the dialysis fluid supply equipment and the powder solution line, which were considered to be major factors for unstable endotoxin levels. On the other hand, as hot water is effective against all microbes except bacterial spores,9,10 it may be an advantage that hot water disinfection using heat conduction is free from risk of solution residue and can thoroughly disinfect dead spaces where biologic film is likely to be created.11 In the new automated hot water disinfection system, the maximum temperature in the tank at the time of hot water inflow from the RO device to the dialysis fluid supply equipment is 86.3°C. Monitoring in this study also showed that the maximum temperature in the tank at the time of inflow into the dialysis fluid supply equipment was 83.1°C, and temperatures ≥80°C were maintained for approximately 17 minutes. These findings fulfilled the hot water disinfection and sterilization conditions (80°C, 10 minutes)10 for medical devices according to the Guidelines for Disinfection and Sterilization in Japan, suggesting adequate hot water disinfection effects. Therefore, in the entire process, the RO device and the dialysis fluid supply equipment operate together in a fully automatic manner, problems caused by high-temperature drainage can be avoided using the terminal thermistor by mixing drainage water with tap water, and accurate and safe hot water disinfection can be performed. Dead spaces that could not be disinfected were markedly reduced, which might have greatly contributed to dialysate purification. Although we wished to evaluate biofilm formation, pipes were not collected in this study because of the possible development of contamination caused by their cutting. The endotoxin level and viable cells below measurement sensitivity and the maintenance of this condition for 3 years suggest the usefulness of this disinfection method for dialysate purification.
After the introduction of the new system, there were no major problems leading to suspension of dialysis. Hot water disinfection was sometimes suspended because of thermistor deterioration or an error in programming the cleaning program, but these problems were solved by increasing inspection items, and subsequently, the system operated properly without problems. Stable operation of the system has been maintained without any emergency action, which is a major advantage.
With regard to cost performance, electricity consumption was small, and the charge for electricity was approximately 130 yen per hot water disinfection. In conventional chemical disinfection, when the control of the endotoxin level was poor, expensive chemical disinfectants were sometimes used. However, during the previous 3 year period, no specific disinfectant was used. Therefore, the cost of dialysate purification involving hot water disinfection is low using this system.
Dialysate purification was maintained even after introduction of an automated hot water disinfection system and it helped the CDDS to supply the dialysate in a stable manner. Therefore, the system can be very useful in terms of both cost and safety, and ensures dialysis treatment for multiple patients.
The authors extend their sincere gratitude to all the staff members of the Division of Artificial Kidney, Saitama Medical Center, Saitama Medical University, for the introduction of the new system and their cooperation in relation to this study.
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