Transcript Dialysis Fluid Purity Best Practice Guidelines (and real life)

Dialysis Fluid Purity
Best Practice Guidelines
(and real life)
Elizabeth Lindley
St James’s University Hospital and Leeds General Infirmary
Leeds, UK
European and National Guidelines
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ERA-EDTA
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European Best Practice Guidelines for Haemodialysis Part 1
Section 4: Dialysis Fluid Purity
Nephrol Dial Transplant (2002) 17 Suppl 7: 45-62
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EDTNA/ERCA
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Technical Guidelines for the Control and monitoring of
microbiological contamination in water for dialysis
EDTNA/ERCA Journal 2002; 28(3), 107-115
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UK Renal Association
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Guidelines 3rd Edition
Chapter 3: Haemodialysis (Draft, March 2002)
DGN Guidelines (draft edition)
‘ERA’ guidelines
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Drafted by Prof Bernard Canaud with input
from the panel of experts in haemodialysis
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Evidence-based where possible, otherwise
expert opinion
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The panel also covered when to refer patients and
start dialysis, adequacy, biocompatibility, anticoagulation, infection control and vascular disease.
Fresenius helped with extensive literature search
Circulated to the National Associations for
comment and approval
‘EDTNA’ guidelines
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The EDTNA guidelines were developed after a
survey of renal units in 14 countries showed the
majority of units aimed to meet the EP limits for
bacteria and endotoxin contamination
BUT……
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40% had no policy for routine disinfection of the water
distribution pipework
Only 50% were regularly testing the dialysis water for
endotoxin
Most units were checking bacteria levels routinely, but
often with unsuitable culturing conditions
EDTNA technical members requested guidelines
‘EDTNA’ guidelines
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Drafted by a Project Group with help from
Rolf Nystrand (Consultant Microbiologist)
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Input from an panel of interested people from renal
units, industry and the regulatory bodies, and from
contributors to the Journal Club
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Evidence-based where possible,
otherwise expert opinion or good practice
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Approved by the European Society for
Artificial Organs and ERA-EDTA
National guidelines
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UK Renal Association Guidelines were
drafted by two doctors and a scientist
and posted on the internet for feedback
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DGN guidelines were drafted by a group
of nephrologists with input from
chemists, microbiologists, technicians
and expertise from the water supplier
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This sounds like a good multidisciplinary
approach
In-house quality assurance policies
ERA
guidelines
Local knowledge
and
COMMON
SENSE!
EDTNA
guidelines
National
guidelines
Do the guidelines
agree with each other?
What do they
recommend?
Chemical quality - chlorine
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Maximum allowed level:
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ERA
“Meet European Pharmacopoeia”
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Ammonium not included in list. EP includes test for heavy metals
Chemical quality - chlorine
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Maximum allowed level:
Meet EP (Total chlorine < 0.1 ppm)
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ERA
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EDTNA Total chlorine < 0.1 ppm*
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DGN
Total chlorine < 0.1 ppm
Frequency of testing:
Daily
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ERA
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EDTNA Daily* (longer intervals if justified)
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DGN
According to local circumstances
* Guidelines on carbon adsorption, to be published soon
Other daily tests
ERA Guideline IV.3.1
recommends daily checks
of Ca and Mg (Hardness) &
Na (conductivity)
Leeds local policy on ‘daily’ checks
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Conductivity is monitored continuously
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Alarms should be checked regularly
Chlorine and hardness would only be checked
daily in exceptional circumstances
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Weekly monitoring for hardness (when brine tanks
are filled) has been perfectly adequate
Weekly (where carbon filters are installed) or
monthly monitoring for chlorine is justified
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We have a history of relatively low chlorine levels (0.05 to
0.30 ppm) and a close relationship with our water supplier
Other chemical contaminants
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Contaminants that should be checked:
As minimum, specified in EP
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ERA
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EDTNA Will probably recommend EP
plus any ‘local problems’
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DGN
12 point list
EP = 2000
The Nitrate Problem
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Limit for tap water 50 ppm
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Typical rejection by RO = 85 to 95%
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Will reduce high nitrate tap water to about 5 ppm
To achieve 0.05 ppm would require a triple RO
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EP requires 2 ppm as NO3
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AAMI requires 2 ppm as N ( 9 ppm as NO3)
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US experts say this has not led to any problems
Is the EP evidence based……
Highly purified water
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(Question from Roelf Smit) Is
highly purified water
with conductivity below 1.1 µS/cm really
required for HDF?
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(My opinion, not EDTNA) Meeting
this strict
requirement on conductivity would be very
expensive and it seems to be unnecessary.
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Conductivity is mainly due to Na (especially if water
has been softened
About 137 mmol/l of Na will be added to the water
I would invest in keeping the
distribution system free from bacteria
(which are absolutely forbidden in HDF
substitution fluid), rather than water
that is free from sodium
Testing for chemical contaminants
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Frequency of testing (after validation):
Six-monthly (quarterly in Appendix)
Monthly tests for aluminium
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ERA
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EDTNA Will probably recommend 6 to 12 monthly
More frequent for Al? Local decision
Data from the RUDIAL Test Service
provided by ALcontrol Labs for about 54
Euros per location. (The labs send us
the 5 sample bottles required for each
location every 6 months)
Sampling water for microbiological tests
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Frequency of testing:
At least monthly (after validation)
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ERA
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EDTNA At least monthly (after validation)
Where to sample:
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Incoming (tap) water
Entrance to dialysis machines
EDTNA At points in treated water loop with
highest bacterial load
ERA
Testing substitution fluid could be a problem.
“Sterile” = <1 cfu/1000 litres
A good, practical test procedure is required
(e.g. Using an in-line filter during a normal HDF session)
Sampling water for microbiological tests
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Sample ports:
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Flame sterilised taps
EDTNA Specialised ports, flame sterilised
or alcohol disinfected taps
ERA
All guidelines prefer
immediate testing
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Sample storage:
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Time not specified, 3 to 6°C
EDTNA Up to 6 hrs at <10°C (not frozen)
Longer if in validated conditions
ERA
Bacteria levels in water
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Maximum level (for conventional dialysis):
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<100 cfu/ml (but aim for ultrapure)
EDTNA <100 cfu/ml (but aim for ultrapure)
DGN
also <100 cfu/ml
ERA
Test methods:
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TGEA or R2A, 20 to 22°C, 7 days
EDTNA TGEA or R2A, 20 to 22°C, 7 days
DGN
TGEA or R2A, 17 to 23°C, 5-7 days
ERA
Endotoxin levels in water
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Maximum level (for conventional dialysis):
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<0.25 IU/ml (but aim for ultrapure)
EDTNA <0.25 IU/ml (but aim for ultrapure)
DGN
also <0.25 IU/ml
<0.03 IU/ml for on-line HDF
ERA
Test methods:
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LAL assay
EDTNA LAL assay or other validated technique
ERA
Aside - why I like to check endotoxin
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Pyocyanin produced
by P. aeruginosa in a
dialysis fluid sample.
This pigment makes
pus in infected wounds
go blue or green.
Bacteria in the distribution system, will
be producing waste products that that
can pass through a dialyser membrane
(e.g. pyocyanin - see caption).
We don’t test for waste products, only
for actively reproducing bacteria and
endotoxin.
Something could happen to stop the
bacteria reproducing (e.g. UV
irradiation) but for gram-negative
bacterial endotoxin will still be there
Maintenance
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Changes of resins, carbon and filter
Periodic according to manufacturer’s
recommendations and microbiology
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ERA
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EDTNA (Carbon) according to manufacturer’s
recommendations and microbiology
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Disinfection of RO(s) and distribution system:
At least once a month
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ERA
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EDTNA At intervals based on microbiology,
default = at least once a month
But water is not the final product….
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What do the guidelines say about dialysis fluid?
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ERA:
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EDTNA:
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Use same sampling, storage & testing procedures as water
Meet EP guidelines (ambiguous for standard dialysis)
Perform ‘micro-biological’ check-up of all machines monthly
Take samples from in-line ports or the dialyser outlet
Use the same culturing technique (and limits) as for water
Modify disinfection protocols if endotoxin levels > water
Check a representative sample of machines each month
DGN:
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Use same limits for dialysis fluid as for purified water
Testing dialysis fluid in real life
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For my centre, to meet the ERA requirement
would mean sampling and testing over 160
machines each month
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This would cost over 30000 Euros per year
What would the benefit be?
Our current policy is to test a sample of
machines in each location so that every machine
is tested on a 6 monthly or annual basis
Minimising the cost of tests (1)
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Bacteria
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Accredited tests in labs are costly - negotiate a ‘low
resolution’ or ‘indicative’ test with simplified counting
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Actual count up to 50
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Nearest 10 from 50 to 200
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>200
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>2000
Develop an in-house test procedure
In-house bacteria tests
Incubate in a secure
cupboard. I have an old
laboratory incubator the temperature
controller doesn’t work
but it’s okay for culturing
at room temperature
In-house testing - bacteria
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Problems
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A good relationship with microbiology is essential
Health and safety assessment required
Advantages
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Cheap (~60 cents per sample)
Quick (no booking or sample forms)
Plates can be checked easily
No chasing up of results
You can incubate for 14 days (for moulds)
You get to see the colonies
Moulds on a plate incubated for 14 days
The value of dilution
Minimising the cost of tests (1)
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Endotoxin
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External labs are expensive - negotiate a special
price for many samples with only one or two positive
controls
In-house gel-clot tests are time consuming and costly
when multiple dilutions are required - form a local
group and lease an automated analyser
Kinetic LAL test kit leased jointly by the
renal units in West Yorkshire. I do
routine tests on the first and third
Tuesday of each month. This works
out at about 11 Euros per sample
You need to be able to make
the calibration standards and
to pipette out small volumes
accurately
Kinetic analyser
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Problems
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Space required for kit
Training required for staff
Advantages
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Compared to in-house gel-clot tests
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Cheaper and quicker for large number of tests
No water bath, no careful timing
Compared to external lab
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Cheaper for large number of tests
No chasing up of results
Unexpected results can be checked immediately
Conclusions
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The Best Practice Guidelines are in reasonable
agreement
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Especially for microbiological testing
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Local practice must depend on local conditions
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Invest in high quality equipment not a more
expensive monitoring programme!
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EDTNA guidelines include advice on system design