1. Greetings from CMC Vellore… To Christ be all glory !
Good morning to all teachers, colleagues and friends!

2. Re-use Dr. Suceena Alexander, MD, DM, FASN
Professor, Dept. of Nephrology
CMC Vellore

3. Dialyzer parts

4. Historical Perspective
1914- The first apparatus for hemodialysis in animals, made by Abel et al. at the beginning of 20th century, was cleaned with acid-pepsin to digest blood, dis- infected with thymol, and reused for up to 30 experiments for as long as 8 months!!
WHY?? saving time and labor!

5. Current perspective Most debatable aspects of hemodialysis
Banned by law in Japan
Most European countries do not Reuse dialyzers (except Portugal, Malta and East European countries)
FDA allowed in US
Reuse practiced in rest of the World
Reuse of certain other devices, tubings, and end caps is even more controversial

6. India
ISN Guideline Recommendation- Hollow fibre dialysers may be reprocessed in order to reduce the cost of the hemodialysis procedure. Prior to reprocessing the dialyzer should be checked for the manufacturers labeling it for single or multiple uses.
ISN Guideline Recommendation- The process has been associated with safe and effective dialysis provided the process is strictly adhered to and monitored

7. India
ISN Guideline Recommendation- Tubings, end caps, O rings and dialyser headers may be reused, however no tests of performance are available to monitor the process.
Venous and arterial transducer protectors SHOULD NOT be reused.

8. Dialyzers validated and Approved for reuse

9. Pre-processing of new dialyzers
NKF-K/DOQI guidelines recommend that each new dialyzer be pre-processed to obtain an accurate estimate of the FBV before first use.

10. Steps in dialyzer reprocessing.

11. Rinsing and reverse ultrafiltration
After dialysis- Blood returned with heparinized saline to the patient.
Removal of residual blood by reverse ultrafiltration with dialysate.
A pressurized rinse of both the blood and dialysate compartments. If there is a delay- the dialyzers refrigerated within 2 hours up to hrs.

12. Cleaning
Water- Prolonged rinse with reverse-osmosis water followed by reverse ultrafiltration
Bleach- Sodium hypochlorite (bleach) < 0.6% Increases albumin losses in high-flux dialyzers Increases ultrafiltration coefficient and causes overt membrane damage in cellulosic membranes
Other cleaning agents-
Hydrogen peroxide 3% or
Renalin: peracetic acid/hydrogen peroxide/acetic acid mixtures
Hydrogen peroxide – Should be available as solution. This is instilled in the dialysate
44  compartment of the dialyzer rather than the blood compartment.

13. Tests of dialyzer performance
Pressure test for leaks
manually or automated.
instilling pressurized air or nitrogen into the blood side of the dialyzer or by producing a vacuum in the dialysate side. 
also screens for defects in the dialyzer O-rings, potting compound, and end-caps.

14. Tests of dialyzer performance
Fiber bundle volume (FBV) or Total compartment Volume (TCV)
the total space within the blood compartment of hollow fiber hemodialyzer.
correlates closely with dialyzer surface area, a major determinant of solute clearance.
main criterion that allows a dialyzer to be reused.
reduction of 20% corresponds to 10% reduction in urea clearance, the maximum decrease acceptable for continued use.

15. Tests of dialyzer performance
In vitro dialyzer ultrafiltration coefficient (In vitro Kuf)
measured by determining the volume of water passing through the membrane at a given pressure and temperature.
a change in the KUf reflects changes in membrane resistance, as well as surface area
No clinical impact using machines with ultrafiltration control

16. Tests of dialyzer performance
Conductivity-based clearance
On-line determination of sodium or ionic clearance, is comparable to urea clearance
acceptable method of monitoring dialyzer performance
ISN Guideline Recommendation- Performance testing should be performed for all reused dialyzers.

17. Disinfection/sterilization
High-level disinfection differs from sterilization as it may not destroy spores.
Current standards require- high-level disinfection

18. Disinfection/sterilization
Germicides
Chemicals:
Renalin- Peracetic acid/hydrogen peroxide/acetic acid mixtures
minimum contact time of 12 hours
Formaldehyde (vapour and liquid):
4% at room temperature for 24 hours
1% at 400C for 24 hours
Glutaraldehyde (Diacide) 2%
Renalin or Puresteril offers the advantage of qualifying as a sterilant with the limitations mentioned above. 

19. Disinfection/sterilization
Germicides
Non-chemicals
Heated water at 1050C (Kaufman, 1992)
Heated 1.5% citric acid at 950C (Levin et al., 1995)
Renalin or Puresteril offers the advantage of qualifying as a sterilant with the limitations mentioned above. 

20. Disinfection/sterilization
Documenting the presence of germicide
Formaldehyde: FD&C blue dye no. 1- light blue color indicates that formaldehyde is present. 
Renalin: Potassium iodide or starch testing strips 

21. Disinfection/sterilization
Germicide removal
Automated or manual
Flushing of the blood compartment, followed by flushing of the dialysate compartment
Air removed from the arterial line before flushing
Dialyzer rotated at intervals during flushing
Blood circuit checked for residual germicide Eg. modified Schiff reagent for formaldehyde
Starch iodide paper for peracetic acid and sodium hypochlorite
Removal (by diffusion) of formaldehyde and peroxide/acetic acid mixtures can be accomplished by circulating saline through the blood compartment while coursing dialysate at usual temperatures through the dialysate compartment in a single-pass fashion for 15 minutes

22. Disinfection/sterilization
Heat sterilization
Reverse-osmosis water is instilled, and the dialyzers are heated in a 1050C convection oven for 20 hours
1.5% citric acid solution allows for heating at 950C for 20 hours 
Polysulfone is the only membrane that is heat resistant for clinical use
Potting compounds must meet certain design specifications
Absence of color change with litmus or pH papers for citric acid ensures removal

23. Disinfection/sterilization
ISN Guideline Recommendation- Chemical disinfectant reprocessing is the usual method, Polysulfone dialyzers may be processed by heat.
Final inspection
Dialyzers should not be used if they have an abnormal appearance (e.g., brownish or blackish discoloration, clots in the header, bands of clotted fibers).

24. Disinfection/sterilization
Cleaning and disinfecting agents:- Preferably be available online
Overhead tanks- 25 to 50 litres capacity
Refilled with fresh solutions every week, after cleaning.
All tanks and piping for sodium hypochlorite should be composed of medical grade PVC, and those for formaldehyde glutaraldehyde and peracetic acid should be composed of 316SS.

25. Automated Reuse Machines
Early Dialyzer Reuse Machines (1974–1976)
The first machine for automatic dialyzer reuse was designed by De Palma et al. in Encino, CA, in 1974.
Second-Generation Reuse Machines (1977–1983)
Several companies designed automated equipment.
In the late 1970s and early 1980s at least six reuse machines were commercially available.

26. Automated versus manual systems
Advantages of automated system:
Process multiple dialyzers simultaneously
Cleansing cycles- highly reproducible
Quality control tests- FBV, KUF, and pressure holding are built in.
Dialyzer labels automatically printed.
Computerized analysis of records
ISN Guideline Recommendation- Where possible automated reprocessing should be used, however for cost reasons manual reprocessing only may be feasible.

27. Advantages and disadvantages of dialyzer reuse
widespread use of costlier dialyzes:  High-efficiency dialyzers, high-flux synthetic dialyzers
Reduced exposure to residual industrial chemicals used in the manufacture of new dialyzers: residual amounts of ethylene oxide, perfluorocarbons.
Reduced “First use syndrome”: cellulosic (Cuprophan) dialyzers

28. Advantages and disadvantages of dialyzer reuse
Enhanced dialyzer biocompatibility/reduced immune system activation (with unsubstituted cellulose membranes and when bleach is not used)
ISN Guideline Recommendation- There is no improvement in biocompatibility of reprocessed dialysers made of synthetic material.
Reduction in TREATMENT COST
With unsubstituted cellulose dialyzers, reuse lessens the degree of membrane-induced activation of complement and the resulting transient leukopenia. This may be the result of protein coating of the membrane during its first clinical use. The benefit disappears if bleach is used in the reprocessing method because bleach acts to remove or alter the protein coat from the membrane. Nonreused cellulosic dialyzers can cause chronic suppression of several aspects of the immune system.

29. Advantages and disadvantages of dialyzer reuse
Exposure of patient and personnel to chemicals
Formaldehyde:
Anti-N antibodies
Acute formaldehyde reactions
Itching
Bacterial/endotoxin contamination of dialyzer
water used to rinse and clean the dialyzers and to prepare the germicides
Anaphylactoid reactions with Renalin and ACE inhibitors
Reuse of dialyzers with oxidizing agents, such as peracetic acid/hydrogen peroxide/acetic acid, can produce a strong negative charge on the protein-coated membrane and thereby activate factor XII, kininogen, kallikrein, and, subsequently, bradykinin. ACE inhibitor–induced inhibition of bradykinin degradation may potentiate the reaction.

30. Advantages and disadvantages of dialyzer reuse
Loss of dialyzer mass transfer (clearance) and ultrafiltration capacity
FBV at least 80%
Ensure adequate heparin anticoagulation
Bicarbonate dialysate containing a small amount of citrate is beneficial.
residual dialyzer formaldehyde levels are high and have been associated with hemolysis and with early transplant failure.
 Immediate burning at the fistula site may indicate that formaldehyde has been improperly removed from the dialyzer
itching during dialysis has improved after switching from formaldehyde to alternative disinfecting agents.
inadvertent spillage of blood at the time that the dialyzer is reprocessed poses the theoretical risk of exposure of both staff and other patient

31. Advantages and disadvantages of dialyzer reuse
Transmission of an infectious agent from one dialyzer to another during the reprocessing procedure
Loss of β2-microglobulin clearance
High-flux dialyzer when resued with Renalin and without bleach
residual dialyzer formaldehyde levels are high and have been associated with hemolysis and with early transplant failure.
 Immediate burning at the fistula site may indicate that formaldehyde has been improperly removed from the dialyzer
itching during dialysis has improved after switching from formaldehyde to alternative disinfecting agents.
inadvertent spillage of blood at the time that the dialyzer is reprocessed poses the theoretical risk of exposure of both staff and other patient

32. Noneconomic Difference Between Dialyzer Reuse and Single Use

33. Headers and the O rings
The headers and the O rings- placed in glutaraldehyde while the dialyzer is being reprocessed.
Improper placement of the O ring or failure to replace- results in blood leak 

34. Reuse of Tubings No literature supports the reuse of blood tubings
Washed free of blood by treated water and then with a 1.6% solution of sodium hypochlorite.
Again rinsed with water and then connected to a supply of 4% formaldehyde.
No objective tests of performance are available for blood tubings.

35. Quality assurance/ Audits
Documentation of all aspects of present and past reuse of a patient's individual dialyzers
Each patient's dialyzer is individually labeled with a unique identifier
A log is also kept of the weekly test results of the disinfectant stock
Percentage of the program's reused dialyzers are cultured weekly for bacteria and checked for proper disinfectant concentration.
24-hour temperature-recording devices
Preventive maintenance program

36. Quality assurance/ Audits
ISN Guideline Recommendation- The process of reusing dialyzers should be monitored for efficacy and safety.
This is the duty of the attending nephrologist
ISN Guideline Recommendation- The spKt/V with new and reused dialyzers should be monitored at least once a month.

37. Personnel and physical plant considerations
Use of protective eyewear and clothing is stressed.
Current (1990) maximum allowable time-weighted average (TWA) exposure for formaldehyde is 1 ppm and for short-term exposure is 3 ppm.
Maximum exposure limits for hydrogen peroxide is 1 ppm TWA and for glutaraldehyde is 0.2 ppm.
There are no current exposure limits for peracetic acid.

38. Personnel and physical plant considerations
Comprehensive training course required
ISN Guideline Recommendation- Operators concerned with the actual reprocessing procedure should wear appropriate protective gear for all reprocessing procedures.
This should include waterproof apron, goggles or spectacles.

39. Reuse for Viro positive patients
The risk of transmission of hepatitis B is approximately 30% after a mucosal exposure, around 3% for Hepatitis C and 0.3% for HIV.
ISN Guideline Recommendation- Separate Reprocessing areas should be utilized for dialyzers of patients who are infected with Hepatitis C.

40. Reuse for Viro positive patients
Dialyzers of patients with Hepatitis B infection should not be reprocessed.
Reprocessing of dialyzers of patients infected with HIV not associated with increased risks of transmission.
The areas utilized for reprocessing should be equipped with a hood and preferably with an exhaust fan.
Sinks should have a depth of at least 45 cm with a drainage mesh at a depth of around 20 cm to prevent the dialyzer and tubing resting in the effluent.

41. Reuse water Reuse water be treated by reverse osmosis
Bacterial colony count of <200 cfu/mL
Endotoxin concentration <2 endotoxin units/mL
The reverse osmosis system should be disinfected monthly
High-flux treatment- ideally, sterile, pyrogen-free water 
(determined by limulus amebocyte lysate assay)

42. Reuse water The water line pressure- 1.3 kg/cm2 (20 psi),
Washing area- 2 outlets or a T connection.
2 different fittings on the water line- a standard tubing to clean the blood compartment and a Hansen connector for backwashing the dialysate compartment.
Fittings should be of 316 SS, or medical grade PVC only.
(determined by limulus amebocyte lysate assay)

43. Patient monitoring
Patient's treatment and course is the primary validation of dialyzer performance: post dialysis weight, pre dialysis plasma urea, urea kinetic modeling, online clearance
ISN Guideline Recommendation- Rigors, fever and hypotension on dialysis should be investigated keeping in mind infection caused by failure of the reprocessing technique, and hemolysis caused by the chemical disinfectants.

44. Patient monitoring
ISN Guideline Recommendation- In case of rigors, fever and hypotension or a visible change in the color of the blood in the tubing, the dialysis should be stopped. Blood should not be returned to the patient.
Samples should be sent for culture, LDH, and smear examination.

45. Patient monitoring
The dialyzer should be rinsed with sterile normal saline and the effluent tested for
1. Residual disinfectants
2. Cultured on TSA and R2A at 25oC and 37oC.
3. Endotoxin by Gel clot LAL assay.

46. Responsibilities of Personnel concerned with reusing dialyzers
Returning blood Reuse process – Dialysis technician or dialysis nurse.
Fixing protocol and decision to use dialyzer singly or multiple times. – Nephrologist in charge of Unit.
Adherence to reprocessing protocol - Dialysis technician or dialysis nurse.
Documentation of tests of performance – Dialysis technician /dialysis nurse.

47. Responsibilities of Personnel concerned with reusing dialyzers
Decision to discard dialyzer - Dialysis technician or dialysis nurse as per protocol, Nephrologist in charge in case of protocol deviation.
Verification of identity by label on dialyzer prior to starting dialysis - Dialysis technician or dialysis nurse AND concerned patient.

48. Responsibilities of Personnel concerned with reusing dialyzers
Monitoring of adequacy and safety of the reuse procedure - Nephrologist in charge of Unit.
Maintaining of records relevant to the reuse procedure – Senior technician or Sister in charge of the Unit.
Informed consent- for Reuse of medical devices

49. Bibliography
Twardowski Dialyzer Reuse—Part I: Historical Perspective. Semin in Nephrol.
Handbook of dialysis. 4th edition. Daugirdas
Handbook of dialysis therapy. 4th edition. Nissesson
Indian Society of Nephrology Hemodialsis Unit Guidelines

50. Thank you