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National Kidney Foundation Report on Dialyzer Reuse
AMERICAN JOURNAL
~
The Official Journal of
..... The National Kidney Foundation
OF
KIDNEY DISEASES
VOL XI, NO 1, JANUARY 1988
A SPECIAL REPORT
National Kidney Foundation Report on Dialyzer Reuse (Approved by the National Kidney Foundation Executive Committee at its July 12, 1987 meeting) • Numerous organizations have presented their views previously on the reprocessing of hemodialyzers. These were well summarized by Easterling (Easterling, RE: Regulations and Standards, in Deane, Wineman, Bemis [eds]: Guide to Reprocessing of Hemodialyzers. Martlnus Nijhoff, 1986, pp 183-197). The publication of the Recommended Practice by the Association for the Advancement of Medical Instrumentation (AAMI) on the reprocessing of dialyzers, coupled with the announcement of the Federal Government to accept these as the basis for Regulations administered by HCFA (now published as "Standards for the Reuse of Hemodialyzer Filters and Other Dialysis Supplies," Federal Register, Oct. 2, 1987), prompted the President of The National Kidney Foundation, Dr Richard Glassock, to appoint a Task Force to formulate the Foundation's position on the above. The members of the Task Force were: Michael J. Fisher, Raymond Hakim, MD, Nathan W. Levin, MD, Chairperson, John M. Newmann, PhD, David A. Ogden, MD, and Vincent Pizziconi, PhD. After having reviewed the previous NKF report on the issue of dialyzer reuse (American Journal of Kidney Diseases 3:466, 1984), the Task Force resolved that the principles of patient consent to dialyzer reuse and right to refuse a reused dialyzer as presented in the report be reaffirmed. While accepting the AAMI Recommended Practice as the basis for its recommendations, the Task Force recognized that the concerns of some patients were not met by the document. In addition to a number of technical amendments that were proposed, the Task Force, acting in the interest of patients, felt that it was essential to add information concerning the potential advantages and disadvantages of reuse. It is recognized that to some the statements relating to patient participation are controversial. Many would argue that reuse of dialyzers should not be distinguished from other aspects of the dialysis treatment since it is generally felt that most decisions in relationship to dialysis should be made In the context of the relationship of individual patients and their physicians. However, it was felt that this Issue had become so emotional and had been so misrepresented by Informational media that it was essential to provide appropriate information and to facilitate the maximum cooperation between clinical care staff and patient. The current report is based on contemporary technology and analyses of patient outcomes; as these change, the NKF's review will continue and will give rise to further analysis. It is hoped that this Task Force Report, incorporating as it does the elements of the AAMI Recommended Practice, will increase the confidence of patients in those units where this has been lacking. Very likely, new questions will be raised with changes in technology and additional analyses of patient outcomes. New recommendations should continue to be made on the basis of factual information and with appropriate communication among all those concerned.
As
OF EARLY 1987, about 50% of hospitalbased and 80% to 90% of independent facilities reprocessed and reused dialyzers. i The Association for the Advancement of Medical Instrumentation (AAMD Recommended Practice, issued in final form in August 1986, represents a consensus of patients, industry, government representatives, physicians, and other health profes-
sionals. 2 The document was developed after substantial study of the problems of reprocessing dialyzers. In addition to individual physicians and manufacturer representatives who volunteered their services, the following organizations were represented: the Center for Devices and Radiological Health, the Centers for Disease Control, the American Society for Artificial Internal Organs,
American Journal of Kidney Diseases, Vol XI, No 1 (January), 1988: pp 1-6
2
AAMI, the American Nephrology Nurses Association, the National Association of Patients on Hemodialysis and Transplantation, the National Kidney Foundation, and the Health Industry Manufacturers Association. The National Kidney Foundation (NKF) Task Force on Dialyzer Reuse has reviewed the AAMI Recommended Practice for Reuse of Hemodialyzers and has concluded that this document, as modified herein, provides a satisfactory basis for the reprocessing of dialyzers and is largely compatible with the NKF's previously expressed views on this topic. 3 These modifications deal specifically with the issues of consent and the right to refuse or substitute a dialyzer, which the Task Force felt needed emphasis and clarification. In addition, some technical issues have been clarified. The document also supplements the proposed Health Care Financing Administration (HCFA) rule4 providing standards for the reuse of hemodialyzer filters and other dialyzer supplies. The rule proposes adoption of the AAMI guidelines on hemodialyzer reuse and adds requirements detailing procedures governing the use of chemical germicides, including staff exposure to these, and adds a requirement for surveillance of patient reactions to bacteria. The proposed rule also adds standards concerning the reuse of dialyzer caps and forbids the reuse of transducer filters, and requires ESRD facilities to have written policies and procedures with respect to reuse to ensure that patients are fully informed regarding the reuse of dialyzers. Although the Department of Health and Human Services believes that the majority of reusing facilities already meet the standards specified in their proposed regulations, this procedure remains an issue of concern for patients and providers. Patients are uneasy concerning the rare reports of severe accidents and deaths in reuse dialysis facilities, and that they are asked to use reprocessed dialyzers in situations in which alternative providers of dialysis (who did not insist that their patients use reprocessed dialyzers) are not available within a reasonably close geographic area. Patients not only wish to be assured of a safe and effective dialysis treatment, they want some choice in the matter of reuse. Given the commitment of the NKF to patient services and promotion of excellence in the treatment of end-stage renal disease, this report attempts to deal with the issues raised since the publication of the NKF Revised
NATIONAL KIDNEY FOUNDATION
Standards for Reuse. 3 This report in no way contradicts the previous NKF reuse standards, but complements them in conjunction with private and public developments in dialyzer reuse since 1984. TECHNICAL ISSUES· Requirement for Treated Water for Rinsing Dialyzers (MMI Sections 9.22,9.412, A9.2, A9.4)
Despite published evidence that trace metals that may be found in untreated water (including silver, lead, iron, mercury, calcium, copper, zinc, and aluminum) may be taken up by blood constituents from dialysis membranes, there is little clinical evidence of a deleterious effect of untreated water in regard to these contaminants. However, the Task Force recommends that treated water, preferably reverse osmosis (R/O)-generated water provided by a functional RO system that is routinely disinfected, be used in all reuse procedures. This would be expected to significantly decrease the potential for bacteriologic trace elements and other extraneous materials found to exist in water used for reprocessing to bind to synthetic membranes or accumulate in the dialyzer, posing unnecessary risks. Performance Testing of the Reprocessed Dialyzer Alternatives (MMI Section 9.3)
The AAMI document requires that only the clearance of small molecules be validated. Extensive experience has demonstrated the safety of either monitoring urea clearance or using an appropriate indirect test for urea clearance, eg, fiber bundle volume, in setting the appropriate cutoff point for reuse of hollow-fiber dialyzers. Determination of ultrafiltration rate (UFR), an alternative indirect test method, improves the ability to achieve desired weight loss and, if measured prior to each reuse, can serve as a check of quality control. Blood Tubing Set Reuse
Blood tubing set reuse is practiced increasingly and is used in approximately 18% of US dialysis units. 1 At present, however, the Task Force does not have sufficient scientific information to endorse or proscribe the practice of blood tubing set *When appropriate, the relevant sections of the AAMI document are cited.
3
SPECIAL REPORT
reuse. More information is being generated in this area and the AAMI is presently writing a technical information report regarding this procedure, since conclusions should be based on objective statistically significant studies concerning the safety and effectiveness of the procedure. Membrane Integrity (AAMI Section 9.2.3)
In addition to cleaning agents, disinfectants or sterilants (when used in recommended concentrations and for recommended periods) should not affect the integrity of dialyzer membranes, since this could be a possible cause of endotoxemia, bacteremia, and blood leak. Attention should be given to the variable degree of sensitivity of synthetic and cellulosic membranes to substances such as sodium hypochlorite or other substances releasing or containing chlorine. The use of these substances has been associated with structural damage to cellulose-based membranes. When such substances are used, the structural integrity of the membranes should be confirmed by appropriate testing. Appearance of the Reprocessed Dialyzer (AAMI Section 9.5)
The cosmetic appearance of the dialyzer should be satisfactory, ie, water clear or blue (when FDC blue is used as a formaldehyde marker), and be free of gray or brown color prior to reuse. Only a few (up to five) dark clotted fibers are acceptable. Method to Guarantee the Presence of Formaldehyde
A small amount (2 mg/L) of FDC blue dye is added to a stock solution of formaldehyde of welldefined concentration. The presence of a light blue coloring in each dialyzer prior to preparation for use will be a visual test for the presence of this disinfecting agent. Concentration of Formaldehyde
Recent experience suggests that formaldehyde concentration of 4% at 20°C is effectively equalled and, in some cases, improved in its di"sinfecting potency by 1 % concentration at 37°C (both for a period of 24 hours). 5 As a result of this technique, the rinsing period, until the formaldehyde reaches an acceptable concentration before initiating dialysis, is shortened substantially and the body burden of formaldehyde is decreased.
Testing for Residual Disinfectant (AAMI Sections 10.3, 10.4.1, 10.4.3)
Every dialyzer should be tested just before initiation of dialysis for the residual concentration of disinfectant, not only a sample, as suggested in the AAMI document. A variety of tests are available of which the most widely used for formaldehyde is the modified Schiff reagent. To achieve a residual concentration test for 3 mg/L or less, as now required in some states, a test of greater sensitivity may be required. Maximal Residual Germicidal Concentrations (AAMI Section 10.4.1)
While the AAMI document recommends that the residual concentration of formaldehyde in the dialyzer not be greater than 5 mg/L, it does not establish maximum residual levels for germicides other than formaldehyde. It is difficult to establish maximum residual levels for the relatively new (for dialysis) disinfecting agents developed or introduced on the market. It is suggested that maximal residual concentrations should be determined from safety data following their approval by the Environmental Protection Agency and/or the Federal Drug Administration. Disinfecting agents in use at present include: formaldehyde, gluteraldehyde, Nephrex® (activated gluteraldehyde), Renalin® (peracetic acid), Warexin®, and Amuchina®. Note on the Body Burden of Formaldehyde
Formaldehyde has been reported to be present in normal individuals as a product of normal metabolism in a serum concentration of 2.6 ± 0.14 mg/ L. 6 Although formaldehyde concentrations in renal failure have not been reported, they may not differ from those reported in normal individuals, since metabolism of formaldehyde results in carbon dioxide or water. 7 As stated previously, allowable concentrations of formaldehyde in reprocessed dialyzers should not exceed 3 to 5 mg/L prior to initiation of dialysis. Since the volume of these dialyzers is small, the total amount of formaldehyde that patients may receive is less than 10 mg. 8 If this is distributed in total body water, making no allowances for concurrent metabolism and excretion, the plasma concentration of formaldehyde in patients should only increase by 0.3 mg/L, a relatively insignificant increase in body burden. Furthermore, other studies have shown that any excess formaldehyde is ex-
4
NATIONAL KIDNEY FOUNDATION
creted by the lungs after metabolism. 7 Lower initial concentrations of formaldehyde used to disinfect the dialyzer should result in lower residual amounts of formaldehyde (as when 1 % formaldehyde is used), when using equivalent rinsing methodology. Acquired Immunodeficiency Syndrome and Reuse
According to recommendations of the Centers for Disease Control, standard blood and body fluid precautions and disinfection and sterilization strategies routinely practiced in dialysis centers are adequate to prevent the transmission of human immunodeficiency virus (HIV). Since the practice of reuse of dialyzers used by patients with detected HIV antibodies has not been well studied for its safety, the NKF urges caution with respect to the reprocessing and reuse of dialyzers for such patients. Environmental Exposure
The NKF endorses staff exposure limits as promulgated by the Occupational Safety and Health Administration (Table 1).
adverse reports concerning dialyzer reprocessing appear to be the result of inappropriate methodology. The only established parenteral toxicity of formaldehyde in humans at low exposure level is the development of anti-N antibodies. These are observed when formaldehyde levels in dialyzers are more than 10 mg/L. When residual formaldehyde levels are less than 5 mg/L, anti-N antibodies were not present. However, more research is needed in this area. More than 65% to 70% of dialysis patients are treated with reprocessed dialyzers, and this technique has been used safely and efficiently for more than 20 years. From one point of view, reuse is a medically accepted part of the dialytic technique for which no specific informed consent is needed. However, since patients justifiably require complete information, the NKF policy is that the reuse procedure must be presented separately from a general "Informed Consent for Dialysis." This is in keeping with the previous NKF Revised Standards. If patients at a center do not sign a consent form to reuse, they are entitled to a new dialyzer at that center for each hemodialysis treatment.
INFORMED CONSENT Rationale
Example of a Consent Form
Potential hazards exist with both new and reprocessed dialyzers. On the basis of published reports concerning dialyzer reprocessing, when the latter has been performed utilizing acceptable standards, both mortality and morbidity appear to be less in units reprocessing dialyzers than in those that do not. A recent paper9 showed a lower risk of death in units that had been reprocessing dialyzers for 5 years or more than in those that did not reuse dialyzers or had less experience. Several reports have also indicated clearly that reuse of cuprophane or cellulose dialyzers is associated with decreased symptoms,IO compared to dialysis with new cuprophane or cellulosis dialyzers. ll ,12 All
Principles
Table 1. Formaldehyde
Gluteraldehyde Gluteraldehyde phenol Peracetic acid Chlorine dioxide Hydrogen peroxide Chlorine
1. I understand that my dialyzer may be used multiple times in my treatment and I will reuse only my own dialyzer. 2. I understand that these dialyzers can be reused safely, according to strict procedures and standards that this facility follows and that are and will be reviewed by State and Federal gov~rnment authorities. These standards include tests for how the dialyzers will function, and include a requirement that the concentration of the disinfecting or sterilizing agent left in the dialyzer will be as low as is necessary to insure safety from any adverse effect caused by the residual germicide.
OSHA Exposure Limits
3 mg/L 5 mg/L
Time weighted average Maximum exposure ceiling (1 part/million proposed)
None developed Individual standards of recommendation should apply None developed Time weighted average 100 mg/L Time weighted average 1 mg/L Maximum exposure ceiling 1 mg/L
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SPECIAL REPORT
3. I understand that the reuse of dialyzers has important medical advantages to many patients in terms of improved tolerance and fewer side effects and/or lessening of potentially adverse changes in my blood chemistry. Reuse of dialyzers using the cuprophane or cellulose membranes is associated with significant medical benefits in some patients. Many studies have shown that the interaction of blood with these membranes for the first time, as in a new dialyzer, leads to an intense response that is typical of an inflammatory reaction. These reactions are lessened when such dialyzers are reprocessed and reused. Some patients experience major adverse effects with new dialyzers, such as chest pain, shortness of breath, and back pain that are also significantly less with reused dialyzers. More recently it has been shown that rates of hospitalization are lower and patient survival is better in patients treated in units that have long-term experience reusing dialyzers. 4. I understand that reuse is done partly to reduce the cost of dialysis. With respect to the use of high efficiency (or high flux) biocompatible dialyzers, reprocessing in some instances may allow more patients to be dialyzed and more services to be provided. 5. Finally, there is early evidence that the use of certain synthetic membranes (eg, polysufone, polyacrylonitrile, polymethalomethacrylate) in dialyzers is associated with fewer reactions and a lower incidence of joint problems from which patients dialyzed for many years with conventional membranes suffer. These dialyzers are significantly more expensive than cellulose or cuprophane dialyzers and reuse is required for their use to be economically practical. Right of Substitution
1. I understand that I am free to change my mind to reuse and to have a new dialyzer at any time. I understand that this decision may alter other aspects of my dialysis care, including the machine I am treated with, the dialyzer I am treated with, the flow rates of dialysate and blood, the duration of my dialysis treatment, and perhaps other details of my dialysis prescription. 2. I understand that my doctor will provide me adequate dialysis care in any decision to alter my dialysis prescription. I understand that my decision to reuse or not to reuse will in no way influence my right to dialyze at the facility of my choice. I
may agree to transfer to another dialysis facility where reprocessing and reuse is not a standard method of operation. In that case, my physician, with my approval, will transfer to another physician information in my record and will ensure that continuity of care is provided. I understand that I may elect not to make the transfer if the conditions for the transfer and the circumstances are not suitable for me. I am then entitled to remain in my present facility and receive a new dialyzer for each treatment with possible modifications of the treatment as described above. The following information should be available for providers and patients. Hazards of a New Dialyzer
The risks and hazards of the new dialyzer include 1. The possible routine infusion into the bloodstream and body of small particles that are residual from the manufacturing process. It is not obvious at this time if this has any clinical significance. 2. Routine infusion during dialysis into the bloodstream and body of chemical substances that wash out of the plastics used to manufacture the dialyzer. It is not obvious at this time if this has any clinical significance. 3. Routine infusion during dialysis into the bloodstream and body of a chemical substance (eg, ethylene oxide) used to sterilize the dialyzers with possible formation of antibodies to the substance. Very rarely these may be associated with an allergic (anaphylactic) reaction with marked difficulty in breathing, chest pain, and shock. 4. A basic incompatibility of the dialyzer membrane and my blood may result in changes in white cells and a number of other chemical changes in my bloodstream. These reactions are much more common with cellulose and cuprophane than with newer synthetic membranes such as polysulfone, polyacrylonitrile, or polymethylmethacrylate. Hazards of a Reprocessed Dialyzer
1. The risks and hazards of the use of a reprocessed dialyzer include a lesser exposure to each of the hazards that are described above for new dialyzers; however, if significant concentrations of bleach are used in the reprocessing of dialyzers made of cellulose, this can return the dialyzer to its original state (since the buildup of biocompatible
6
NATIONAL KIDNEY FOUNDATION
blood products on the dialyzer membrane is removed with bleach). In addition, bleach may, in some circumstances, cause deterioration of the integrity of the membrane. 2. The infusion into the bloodstream and body of some blood proteins altered by the cleaning and disinfecting processes employed. No clinical disadvantages of this are known. 3. The routine infusion into the bloodstream and body of the residuals of the disinfecting agent used to treat my reprocessed dialyzer. I understand that by using appropriate standards, the chance of hazards from this is very small. 4. A small chance of inadequate disinfection of
the dialyzer with attendant risk of mild, severe, or even fatal clinical infection. 5. A decrease of the clearance and ultrafiltration efficiency of the dialyzer compared to a new dialyzer, should the hollow-fiber bundle volume of the dialyzer not be 80% of its original volume. This should not occur if proper procedures are followed. Significant increases in ultrafiltration due to membrane deterioration may also pose a risk. 6. Possible increase in heparin dosage to prevent clotting of the reused dialyzer; however, studies have not borne out that an increase in heparin dosage is necessary with reprocessed dialyzers. 13
REFERENCES 1. Favero M, Centers for Disease Control: Personal communication 2. Association for the Advancement of Medical Instrumentation: Recommended Practice for Reuse of Hemodialyzers, Arlington, VA, 1986 3. NKF revised standards for reuse of hemodialyzers. Am J Kidney Dis 3:466-468, 1984 4. Federal Register, vol 52, no 116, June 17, 1987 5. Hakim R, Freiderich R, Lowrie EG: Formaldehyde kinetics and bacteriology in dialyzers. Kidney Int 28:936-943, 1985 6. Heck H, et al: Formaldehyde (CHzO) concentrations in the blood of humans and Fischer-344 rats exposed to CHzO under controlled conditions. JAm Ind Hyg Assoc 46:1-3, 1985 7. Neely WB: The metabolic fate of formaldehyde-I'C in-
tra-peritoneally administered to the rat. Biochem Pharmacol 13: 1137-1142, 1964 8. Gotch FA, Keene ML: Formaldehyde kinetics in reused dialyzers. Trans Am Soc Artif Intern Organs 24:396-401, 1982 9. Held P, Pauly MY, Diamond L: Survival analysis of patients undergoing dialysis. JAMA 257:645-650, 1987 10. Robson MD, Charoentanich R, Kant KS, et al: Effect of first and subsequent use of hemodialyzers on patient well-being. Am J NephroI6:101-106, 1986 11. Kant LS, Pollak VE, Cathey M, et al: Multiple use of dialyzers; safety and efficacy. Kidney Int 19:728-738, 1984 12. Bok DV, Pascual L, Levin Nw, et al: Effect of multiple use of dialyzers on intradialytic symptoms. Proc Dial Transplant Forum 10:92-104, 1980 13. Lowrie EG: Personal communication
~
The Official Journal of
..... The National Kidney Foundation
OF
KIDNEY DISEASES
VOL XI, NO 1, JANUARY 1988
A SPECIAL REPORT
National Kidney Foundation Report on Dialyzer Reuse (Approved by the National Kidney Foundation Executive Committee at its July 12, 1987 meeting) • Numerous organizations have presented their views previously on the reprocessing of hemodialyzers. These were well summarized by Easterling (Easterling, RE: Regulations and Standards, in Deane, Wineman, Bemis [eds]: Guide to Reprocessing of Hemodialyzers. Martlnus Nijhoff, 1986, pp 183-197). The publication of the Recommended Practice by the Association for the Advancement of Medical Instrumentation (AAMI) on the reprocessing of dialyzers, coupled with the announcement of the Federal Government to accept these as the basis for Regulations administered by HCFA (now published as "Standards for the Reuse of Hemodialyzer Filters and Other Dialysis Supplies," Federal Register, Oct. 2, 1987), prompted the President of The National Kidney Foundation, Dr Richard Glassock, to appoint a Task Force to formulate the Foundation's position on the above. The members of the Task Force were: Michael J. Fisher, Raymond Hakim, MD, Nathan W. Levin, MD, Chairperson, John M. Newmann, PhD, David A. Ogden, MD, and Vincent Pizziconi, PhD. After having reviewed the previous NKF report on the issue of dialyzer reuse (American Journal of Kidney Diseases 3:466, 1984), the Task Force resolved that the principles of patient consent to dialyzer reuse and right to refuse a reused dialyzer as presented in the report be reaffirmed. While accepting the AAMI Recommended Practice as the basis for its recommendations, the Task Force recognized that the concerns of some patients were not met by the document. In addition to a number of technical amendments that were proposed, the Task Force, acting in the interest of patients, felt that it was essential to add information concerning the potential advantages and disadvantages of reuse. It is recognized that to some the statements relating to patient participation are controversial. Many would argue that reuse of dialyzers should not be distinguished from other aspects of the dialysis treatment since it is generally felt that most decisions in relationship to dialysis should be made In the context of the relationship of individual patients and their physicians. However, it was felt that this Issue had become so emotional and had been so misrepresented by Informational media that it was essential to provide appropriate information and to facilitate the maximum cooperation between clinical care staff and patient. The current report is based on contemporary technology and analyses of patient outcomes; as these change, the NKF's review will continue and will give rise to further analysis. It is hoped that this Task Force Report, incorporating as it does the elements of the AAMI Recommended Practice, will increase the confidence of patients in those units where this has been lacking. Very likely, new questions will be raised with changes in technology and additional analyses of patient outcomes. New recommendations should continue to be made on the basis of factual information and with appropriate communication among all those concerned.
As
OF EARLY 1987, about 50% of hospitalbased and 80% to 90% of independent facilities reprocessed and reused dialyzers. i The Association for the Advancement of Medical Instrumentation (AAMD Recommended Practice, issued in final form in August 1986, represents a consensus of patients, industry, government representatives, physicians, and other health profes-
sionals. 2 The document was developed after substantial study of the problems of reprocessing dialyzers. In addition to individual physicians and manufacturer representatives who volunteered their services, the following organizations were represented: the Center for Devices and Radiological Health, the Centers for Disease Control, the American Society for Artificial Internal Organs,
American Journal of Kidney Diseases, Vol XI, No 1 (January), 1988: pp 1-6
2
AAMI, the American Nephrology Nurses Association, the National Association of Patients on Hemodialysis and Transplantation, the National Kidney Foundation, and the Health Industry Manufacturers Association. The National Kidney Foundation (NKF) Task Force on Dialyzer Reuse has reviewed the AAMI Recommended Practice for Reuse of Hemodialyzers and has concluded that this document, as modified herein, provides a satisfactory basis for the reprocessing of dialyzers and is largely compatible with the NKF's previously expressed views on this topic. 3 These modifications deal specifically with the issues of consent and the right to refuse or substitute a dialyzer, which the Task Force felt needed emphasis and clarification. In addition, some technical issues have been clarified. The document also supplements the proposed Health Care Financing Administration (HCFA) rule4 providing standards for the reuse of hemodialyzer filters and other dialyzer supplies. The rule proposes adoption of the AAMI guidelines on hemodialyzer reuse and adds requirements detailing procedures governing the use of chemical germicides, including staff exposure to these, and adds a requirement for surveillance of patient reactions to bacteria. The proposed rule also adds standards concerning the reuse of dialyzer caps and forbids the reuse of transducer filters, and requires ESRD facilities to have written policies and procedures with respect to reuse to ensure that patients are fully informed regarding the reuse of dialyzers. Although the Department of Health and Human Services believes that the majority of reusing facilities already meet the standards specified in their proposed regulations, this procedure remains an issue of concern for patients and providers. Patients are uneasy concerning the rare reports of severe accidents and deaths in reuse dialysis facilities, and that they are asked to use reprocessed dialyzers in situations in which alternative providers of dialysis (who did not insist that their patients use reprocessed dialyzers) are not available within a reasonably close geographic area. Patients not only wish to be assured of a safe and effective dialysis treatment, they want some choice in the matter of reuse. Given the commitment of the NKF to patient services and promotion of excellence in the treatment of end-stage renal disease, this report attempts to deal with the issues raised since the publication of the NKF Revised
NATIONAL KIDNEY FOUNDATION
Standards for Reuse. 3 This report in no way contradicts the previous NKF reuse standards, but complements them in conjunction with private and public developments in dialyzer reuse since 1984. TECHNICAL ISSUES· Requirement for Treated Water for Rinsing Dialyzers (MMI Sections 9.22,9.412, A9.2, A9.4)
Despite published evidence that trace metals that may be found in untreated water (including silver, lead, iron, mercury, calcium, copper, zinc, and aluminum) may be taken up by blood constituents from dialysis membranes, there is little clinical evidence of a deleterious effect of untreated water in regard to these contaminants. However, the Task Force recommends that treated water, preferably reverse osmosis (R/O)-generated water provided by a functional RO system that is routinely disinfected, be used in all reuse procedures. This would be expected to significantly decrease the potential for bacteriologic trace elements and other extraneous materials found to exist in water used for reprocessing to bind to synthetic membranes or accumulate in the dialyzer, posing unnecessary risks. Performance Testing of the Reprocessed Dialyzer Alternatives (MMI Section 9.3)
The AAMI document requires that only the clearance of small molecules be validated. Extensive experience has demonstrated the safety of either monitoring urea clearance or using an appropriate indirect test for urea clearance, eg, fiber bundle volume, in setting the appropriate cutoff point for reuse of hollow-fiber dialyzers. Determination of ultrafiltration rate (UFR), an alternative indirect test method, improves the ability to achieve desired weight loss and, if measured prior to each reuse, can serve as a check of quality control. Blood Tubing Set Reuse
Blood tubing set reuse is practiced increasingly and is used in approximately 18% of US dialysis units. 1 At present, however, the Task Force does not have sufficient scientific information to endorse or proscribe the practice of blood tubing set *When appropriate, the relevant sections of the AAMI document are cited.
3
SPECIAL REPORT
reuse. More information is being generated in this area and the AAMI is presently writing a technical information report regarding this procedure, since conclusions should be based on objective statistically significant studies concerning the safety and effectiveness of the procedure. Membrane Integrity (AAMI Section 9.2.3)
In addition to cleaning agents, disinfectants or sterilants (when used in recommended concentrations and for recommended periods) should not affect the integrity of dialyzer membranes, since this could be a possible cause of endotoxemia, bacteremia, and blood leak. Attention should be given to the variable degree of sensitivity of synthetic and cellulosic membranes to substances such as sodium hypochlorite or other substances releasing or containing chlorine. The use of these substances has been associated with structural damage to cellulose-based membranes. When such substances are used, the structural integrity of the membranes should be confirmed by appropriate testing. Appearance of the Reprocessed Dialyzer (AAMI Section 9.5)
The cosmetic appearance of the dialyzer should be satisfactory, ie, water clear or blue (when FDC blue is used as a formaldehyde marker), and be free of gray or brown color prior to reuse. Only a few (up to five) dark clotted fibers are acceptable. Method to Guarantee the Presence of Formaldehyde
A small amount (2 mg/L) of FDC blue dye is added to a stock solution of formaldehyde of welldefined concentration. The presence of a light blue coloring in each dialyzer prior to preparation for use will be a visual test for the presence of this disinfecting agent. Concentration of Formaldehyde
Recent experience suggests that formaldehyde concentration of 4% at 20°C is effectively equalled and, in some cases, improved in its di"sinfecting potency by 1 % concentration at 37°C (both for a period of 24 hours). 5 As a result of this technique, the rinsing period, until the formaldehyde reaches an acceptable concentration before initiating dialysis, is shortened substantially and the body burden of formaldehyde is decreased.
Testing for Residual Disinfectant (AAMI Sections 10.3, 10.4.1, 10.4.3)
Every dialyzer should be tested just before initiation of dialysis for the residual concentration of disinfectant, not only a sample, as suggested in the AAMI document. A variety of tests are available of which the most widely used for formaldehyde is the modified Schiff reagent. To achieve a residual concentration test for 3 mg/L or less, as now required in some states, a test of greater sensitivity may be required. Maximal Residual Germicidal Concentrations (AAMI Section 10.4.1)
While the AAMI document recommends that the residual concentration of formaldehyde in the dialyzer not be greater than 5 mg/L, it does not establish maximum residual levels for germicides other than formaldehyde. It is difficult to establish maximum residual levels for the relatively new (for dialysis) disinfecting agents developed or introduced on the market. It is suggested that maximal residual concentrations should be determined from safety data following their approval by the Environmental Protection Agency and/or the Federal Drug Administration. Disinfecting agents in use at present include: formaldehyde, gluteraldehyde, Nephrex® (activated gluteraldehyde), Renalin® (peracetic acid), Warexin®, and Amuchina®. Note on the Body Burden of Formaldehyde
Formaldehyde has been reported to be present in normal individuals as a product of normal metabolism in a serum concentration of 2.6 ± 0.14 mg/ L. 6 Although formaldehyde concentrations in renal failure have not been reported, they may not differ from those reported in normal individuals, since metabolism of formaldehyde results in carbon dioxide or water. 7 As stated previously, allowable concentrations of formaldehyde in reprocessed dialyzers should not exceed 3 to 5 mg/L prior to initiation of dialysis. Since the volume of these dialyzers is small, the total amount of formaldehyde that patients may receive is less than 10 mg. 8 If this is distributed in total body water, making no allowances for concurrent metabolism and excretion, the plasma concentration of formaldehyde in patients should only increase by 0.3 mg/L, a relatively insignificant increase in body burden. Furthermore, other studies have shown that any excess formaldehyde is ex-
4
NATIONAL KIDNEY FOUNDATION
creted by the lungs after metabolism. 7 Lower initial concentrations of formaldehyde used to disinfect the dialyzer should result in lower residual amounts of formaldehyde (as when 1 % formaldehyde is used), when using equivalent rinsing methodology. Acquired Immunodeficiency Syndrome and Reuse
According to recommendations of the Centers for Disease Control, standard blood and body fluid precautions and disinfection and sterilization strategies routinely practiced in dialysis centers are adequate to prevent the transmission of human immunodeficiency virus (HIV). Since the practice of reuse of dialyzers used by patients with detected HIV antibodies has not been well studied for its safety, the NKF urges caution with respect to the reprocessing and reuse of dialyzers for such patients. Environmental Exposure
The NKF endorses staff exposure limits as promulgated by the Occupational Safety and Health Administration (Table 1).
adverse reports concerning dialyzer reprocessing appear to be the result of inappropriate methodology. The only established parenteral toxicity of formaldehyde in humans at low exposure level is the development of anti-N antibodies. These are observed when formaldehyde levels in dialyzers are more than 10 mg/L. When residual formaldehyde levels are less than 5 mg/L, anti-N antibodies were not present. However, more research is needed in this area. More than 65% to 70% of dialysis patients are treated with reprocessed dialyzers, and this technique has been used safely and efficiently for more than 20 years. From one point of view, reuse is a medically accepted part of the dialytic technique for which no specific informed consent is needed. However, since patients justifiably require complete information, the NKF policy is that the reuse procedure must be presented separately from a general "Informed Consent for Dialysis." This is in keeping with the previous NKF Revised Standards. If patients at a center do not sign a consent form to reuse, they are entitled to a new dialyzer at that center for each hemodialysis treatment.
INFORMED CONSENT Rationale
Example of a Consent Form
Potential hazards exist with both new and reprocessed dialyzers. On the basis of published reports concerning dialyzer reprocessing, when the latter has been performed utilizing acceptable standards, both mortality and morbidity appear to be less in units reprocessing dialyzers than in those that do not. A recent paper9 showed a lower risk of death in units that had been reprocessing dialyzers for 5 years or more than in those that did not reuse dialyzers or had less experience. Several reports have also indicated clearly that reuse of cuprophane or cellulose dialyzers is associated with decreased symptoms,IO compared to dialysis with new cuprophane or cellulosis dialyzers. ll ,12 All
Principles
Table 1. Formaldehyde
Gluteraldehyde Gluteraldehyde phenol Peracetic acid Chlorine dioxide Hydrogen peroxide Chlorine
1. I understand that my dialyzer may be used multiple times in my treatment and I will reuse only my own dialyzer. 2. I understand that these dialyzers can be reused safely, according to strict procedures and standards that this facility follows and that are and will be reviewed by State and Federal gov~rnment authorities. These standards include tests for how the dialyzers will function, and include a requirement that the concentration of the disinfecting or sterilizing agent left in the dialyzer will be as low as is necessary to insure safety from any adverse effect caused by the residual germicide.
OSHA Exposure Limits
3 mg/L 5 mg/L
Time weighted average Maximum exposure ceiling (1 part/million proposed)
None developed Individual standards of recommendation should apply None developed Time weighted average 100 mg/L Time weighted average 1 mg/L Maximum exposure ceiling 1 mg/L
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SPECIAL REPORT
3. I understand that the reuse of dialyzers has important medical advantages to many patients in terms of improved tolerance and fewer side effects and/or lessening of potentially adverse changes in my blood chemistry. Reuse of dialyzers using the cuprophane or cellulose membranes is associated with significant medical benefits in some patients. Many studies have shown that the interaction of blood with these membranes for the first time, as in a new dialyzer, leads to an intense response that is typical of an inflammatory reaction. These reactions are lessened when such dialyzers are reprocessed and reused. Some patients experience major adverse effects with new dialyzers, such as chest pain, shortness of breath, and back pain that are also significantly less with reused dialyzers. More recently it has been shown that rates of hospitalization are lower and patient survival is better in patients treated in units that have long-term experience reusing dialyzers. 4. I understand that reuse is done partly to reduce the cost of dialysis. With respect to the use of high efficiency (or high flux) biocompatible dialyzers, reprocessing in some instances may allow more patients to be dialyzed and more services to be provided. 5. Finally, there is early evidence that the use of certain synthetic membranes (eg, polysufone, polyacrylonitrile, polymethalomethacrylate) in dialyzers is associated with fewer reactions and a lower incidence of joint problems from which patients dialyzed for many years with conventional membranes suffer. These dialyzers are significantly more expensive than cellulose or cuprophane dialyzers and reuse is required for their use to be economically practical. Right of Substitution
1. I understand that I am free to change my mind to reuse and to have a new dialyzer at any time. I understand that this decision may alter other aspects of my dialysis care, including the machine I am treated with, the dialyzer I am treated with, the flow rates of dialysate and blood, the duration of my dialysis treatment, and perhaps other details of my dialysis prescription. 2. I understand that my doctor will provide me adequate dialysis care in any decision to alter my dialysis prescription. I understand that my decision to reuse or not to reuse will in no way influence my right to dialyze at the facility of my choice. I
may agree to transfer to another dialysis facility where reprocessing and reuse is not a standard method of operation. In that case, my physician, with my approval, will transfer to another physician information in my record and will ensure that continuity of care is provided. I understand that I may elect not to make the transfer if the conditions for the transfer and the circumstances are not suitable for me. I am then entitled to remain in my present facility and receive a new dialyzer for each treatment with possible modifications of the treatment as described above. The following information should be available for providers and patients. Hazards of a New Dialyzer
The risks and hazards of the new dialyzer include 1. The possible routine infusion into the bloodstream and body of small particles that are residual from the manufacturing process. It is not obvious at this time if this has any clinical significance. 2. Routine infusion during dialysis into the bloodstream and body of chemical substances that wash out of the plastics used to manufacture the dialyzer. It is not obvious at this time if this has any clinical significance. 3. Routine infusion during dialysis into the bloodstream and body of a chemical substance (eg, ethylene oxide) used to sterilize the dialyzers with possible formation of antibodies to the substance. Very rarely these may be associated with an allergic (anaphylactic) reaction with marked difficulty in breathing, chest pain, and shock. 4. A basic incompatibility of the dialyzer membrane and my blood may result in changes in white cells and a number of other chemical changes in my bloodstream. These reactions are much more common with cellulose and cuprophane than with newer synthetic membranes such as polysulfone, polyacrylonitrile, or polymethylmethacrylate. Hazards of a Reprocessed Dialyzer
1. The risks and hazards of the use of a reprocessed dialyzer include a lesser exposure to each of the hazards that are described above for new dialyzers; however, if significant concentrations of bleach are used in the reprocessing of dialyzers made of cellulose, this can return the dialyzer to its original state (since the buildup of biocompatible
6
NATIONAL KIDNEY FOUNDATION
blood products on the dialyzer membrane is removed with bleach). In addition, bleach may, in some circumstances, cause deterioration of the integrity of the membrane. 2. The infusion into the bloodstream and body of some blood proteins altered by the cleaning and disinfecting processes employed. No clinical disadvantages of this are known. 3. The routine infusion into the bloodstream and body of the residuals of the disinfecting agent used to treat my reprocessed dialyzer. I understand that by using appropriate standards, the chance of hazards from this is very small. 4. A small chance of inadequate disinfection of
the dialyzer with attendant risk of mild, severe, or even fatal clinical infection. 5. A decrease of the clearance and ultrafiltration efficiency of the dialyzer compared to a new dialyzer, should the hollow-fiber bundle volume of the dialyzer not be 80% of its original volume. This should not occur if proper procedures are followed. Significant increases in ultrafiltration due to membrane deterioration may also pose a risk. 6. Possible increase in heparin dosage to prevent clotting of the reused dialyzer; however, studies have not borne out that an increase in heparin dosage is necessary with reprocessed dialyzers. 13
REFERENCES 1. Favero M, Centers for Disease Control: Personal communication 2. Association for the Advancement of Medical Instrumentation: Recommended Practice for Reuse of Hemodialyzers, Arlington, VA, 1986 3. NKF revised standards for reuse of hemodialyzers. Am J Kidney Dis 3:466-468, 1984 4. Federal Register, vol 52, no 116, June 17, 1987 5. Hakim R, Freiderich R, Lowrie EG: Formaldehyde kinetics and bacteriology in dialyzers. Kidney Int 28:936-943, 1985 6. Heck H, et al: Formaldehyde (CHzO) concentrations in the blood of humans and Fischer-344 rats exposed to CHzO under controlled conditions. JAm Ind Hyg Assoc 46:1-3, 1985 7. Neely WB: The metabolic fate of formaldehyde-I'C in-
tra-peritoneally administered to the rat. Biochem Pharmacol 13: 1137-1142, 1964 8. Gotch FA, Keene ML: Formaldehyde kinetics in reused dialyzers. Trans Am Soc Artif Intern Organs 24:396-401, 1982 9. Held P, Pauly MY, Diamond L: Survival analysis of patients undergoing dialysis. JAMA 257:645-650, 1987 10. Robson MD, Charoentanich R, Kant KS, et al: Effect of first and subsequent use of hemodialyzers on patient well-being. Am J NephroI6:101-106, 1986 11. Kant LS, Pollak VE, Cathey M, et al: Multiple use of dialyzers; safety and efficacy. Kidney Int 19:728-738, 1984 12. Bok DV, Pascual L, Levin Nw, et al: Effect of multiple use of dialyzers on intradialytic symptoms. Proc Dial Transplant Forum 10:92-104, 1980 13. Lowrie EG: Personal communication