The Hygienic Chain

How to optimize
dialysis fluid purity
Fluid Purity
a prerequisite to
quality dialysis treatment
Over the past three decades we have learned much about dialysis
fluid contaminants and how they affect patients. We have also
discovered new ways to enhance fluid purity by preventing the
development of biofilmcolonies of microorganisms in an HD
system that release toxins and resist standard disinfection.

Evidence exists that monocyte activation and cytokine production occur from
the transfer of bacterial by-products into the blood during HD treatment.
Consequently, the bacterial contamination of the dialysis fluid is a major factor
in HD bioincompatibility.

Further, a mounting body of scientific evidence suggests a causal relationship

between the microbial contamination of HD fluids and the signs of chronic
microinflammation seen in dialysis patients. The adverse effects related to
such inflammation are significant and costly.

As result, standards and practice guidelines on water and dialysis fluid purity
are revised. The American AAMI association introduces action levels for
bacteria and endotoxins in water for dialysis to assure that corrective actions
can be initiated before exceeding the maximum levels established by the
standard (RD52:2004). The European Best Practice Guidelines for Haemodialy-
sis, issued 2002 by ERA-EDTA, takes a further step by strongly recommending
the use of ultrapure fluid quality for all dialysis applications to minimize
inflammation (EBPG IV.1 and IV.4.3).

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The Hygienic Chain
a holistic approach to optimizing
dialysis fluid purity
Maintaining fluid purity means attending to the entire chain of components
and processes involved in HDfrom water treatment and concentrates to fluid
distribution and HD machines. We call this chain: The Hygienic Chain.

And like any chain, it is only as strong as its weakest link. This has never been
more true than in the prevention of biofilm. That is why Gambro has designed
an entire HD system to ensure optimal care while protecting your patients from
the hazards of biofilm every step of the way. From water treatment and tubing
to HD machines and concentrates, Gambro offers a fully integrated solution.

Water treatment and HD machines and

hot water flushing dry concentrates Tubing and inlets

We are pioneers in HD with decades of experience in water treatment and

fluid distribution systems specialized for HD units. In fact, we are the one
company that is able to provide every link in The Hygienic Chain. Whats
more, ours is the only system proven effective against biofilm because every
link is designed to resist microbial proliferation and is fully integrated from
RO unit to drain.

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Gambro Hygienic
Chain Products
The central component of the Gambro Hygienic Chain is the Gambro CWP
water treatment system. This system can integrate an effective hot water
flushing of the entire distribution loop. This way the entire pure water system
gets protection against biofilm formation.

The CWP system is perfectly matched by our HD machines and other products
like the BiCart cartridge, CleanCart cartridge, U 8000 S ultrafilter and
Clean-PEX tubing, recommended by Gambro. All designed to assure the
highest hygienic standard for the dialysis fluid.

Avoiding treatment-related
inflammation
Implementing The Hygienic Chain is an effective step for avoiding treatment-
related inflammation. As a result, the effectiveness of erythropoietin can
improve, morbidity may be mitigated and the need for advanced medical care
may be reduced.

In the pages that follow, we hope to provide insight and advice on how you
can strengthen every link of The Hygienic Chain to ensure optimal fluid quality
for your patients.

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How choosing the right
water treatment system can
help prevent biofilm
Water treatment and
hot water flushing

The first link in The Hygienic Chain is proper water treatment. Treatment
requirements vary according to the type of water available in each munici-
pality. Whats more, seasonal variations in water quality exist within each
municipality. So its important to contact your municipal waterworks for
information on water quality and seasonal variations in your area.

Typically, stages for water purification include pre-treatment, softener, and

reverse osmosis. While starting with a reliable water treatment system is
important, you should be mindful that most of the microbiological contami-
nants found in HD fluid are introduced further down the line, after the RO
unit. Purifying water only to have it contaminated downstream makes little
sense. Thats why part of your water treatment strategy should include a plan
for how to prevent subsequent contamination.

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 Heating unit RO unit

min 85C

90C

Regular hot water flushing of the entire fluid distribution system, including HD machines, can prevent biofilm.

Biofilm prevention by
proactive disinfection
Of particular concern is the development of biofilm in the system. Biofilm is
communities of microorganisms living under a protective slime matrix. They
form readily in aqueous environments, release toxins that contaminate dialysis
fluid, and, once established, are virtually impossible to remove.

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 Dialysis unit

Biofilm starts when bacteria encounter a solid surface. They form a temporary
bond to the surface and begin to multiply. Soon, they start developing a protective
polysaccharide slime coat that forms a permanent bond with the surface.

Once the slime layer is in place, the microbes are, in all practical senses,
impervious to both heat and chemical disinfection.

The only proven way to keep biofilm out of your HD system is to prevent it from
colonizing in the first place. That means eradicating all bacteria in the system
before they have the time to develop a protective slime layer. A random schedule
of disinfection is not sufficient; it should be performed on a regular basis without
fail. Further, the entire fluid path, all the way through the dialysis machines,
needs to be dealt with.

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Integrating reverse osmosis
and hot water flushing
The reverse osmosis unit should be well suited for to specialized needs of
the HD clinic. Its rejection of electrolytes as well as bacteria and bacterial
products should be highly effective and reliable. Beyond that, investing in a
reverse osmosis unit designed with an integrated hot water unit can protect
the entire fluid distribution system against biofilm formation.

Gambro has decades of experience designing and installing water systems

specifically for HD. This experience has helped us design a water system
that prevents the formation of biofilm and is simple to operate. The integrated
heat function by Gambro means that hot water can be regularly flushed
through the entire fluid path, all the way to and including the fluid pathways
inside HD machines. This makes the Gambro CWP system a complete and
highly effective tool to prevent microbial infestation.

Gambro has been developing water treatment systems tailored to the needs of HD clinics for over 30 years.
CWP 100 systems by Gambro are available with either single- or double-reverse osmosis, have a built-in hot water tank,
and are designed to perform daily unattended hot water flushing of the entire fluid distribution system.

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How choosing the right
HD machines and concentrates
can enhance fluid purity
HD machines and
dry concentrates

The next link in The Hygienic Chain is the HD machine. While most major
brands of HD machines would appear to perform HD equally well, their
hygienic performance can vary greatly. As a result, the machines themselves
can be a significant source of contamination.

Design elements like long flow paths, dead ends, complicated valves and
chamber systems all increase the risk of contamination. Thats because
bacteria, yeast, fungi and other microbes thrive in still fluid. Dead ends
cause stagnant fluid zones and are often difficult to reach with disinfectants.
The same can be said of areas where the flow rate is low. Complicated
valves allow microbes to hide and chamber systems can double as bacterial
incubators between treatments. The use of liquid bicarbonate concentrates
adds to this risk.

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HD machines designed for purity
Its easy to distinguish between an HD machine that is
designed for purity and one that is not. Open any Gambro
machine and compare it to other HD machines in your clinic.

Note the simplified flow path in the Gambro machine. This ensures an even
flow rate throughout the entire fluid path, giving microbes nowhere to hide
during heat or chemical disinfection. Youll also note that the Gambro
machine has no reservoirs where dialysis fluid can sit between treatments.

Microbe-friendly flow path design often results in biofilm inside the HD machine.
If that happens, one must rely on disinfection to kill the microbes or the dialysis
membrane to keep contaminants away from the patients blood stream. Unfor-
tunately, neither of these measures can provide adequate protection. The slime
which covers the microbes is extremely robust, able to withstand both heat and
chemicals. Whats more, many of the bacterial by-products released from the
biofilm are clearly small enough to pass freely through any dialysis membrane.

Many HD machines have complicated flow paths that favor microbial growth.
Note the numerous valves, low flow areas, and holding tanks where fluid can sit between treatments.

From their inception, Gambro HD machines have been designed to resist microbes and enhance fluid purity.
Note that Gambro machines can be drained and have no reservoirs where dialysis fluid can sit between treatments.

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Dry bicarbonate cartridges
easy, safe and hygienic
Liquid bicarbonate concentrate is an excellent growth medium for bacteria.
The introduction of even a single microbe into the liquid can result in
explosive bacterial growth. And the more steps involved in delivering the
bicarbonate concentrate to the machine, the higher the risk of contamination.
In fact, in systems using a central supply of liquid bicarbonate concentrate,
contamination cannot be avoided.

The simple answer is the use of a dry bicarbonate powder cartridge.

Hermetically sealed and ready for on-line preparation as needed, there is
no chance for contamination to occur between preparation and use. The
BiCart cartridge by Gambro is one such dry bicarbonate powder cartridge.
Gambro was the first to offer this hygienic milestone and today over 200
million BiCart cartridges have been used around the globe, making it the
worlds most widely used dry bicarbonate.

The BiCart cartridge enables easy safe and

hygienic preparation of dialysis fluid. Today
the BiCart cartridge is an essential part of
both The Hygienic Chain concept and Gambros
BiCart Select package that also includes
SelectCart dry sodium chloride and SelectBag
minor electrolytes.

Automatic cleaning &

disinfection
Further in the pursuit of purity, citric acid and sodium carbonate powders are
used to decalcify and clean the machines fluid paths. Since liquid citric acid
provides an excellent growth medium for microbes, the CleanCart C cartridge
ensures that this fluid is prepared by the machine as needed, with no time for
contamination. Just press the disinfection button and place the cartridge in the
holder. The machine takes care of the rest, initiating heat disinfection in combi-
nation with a decalcification or cleaning.

Ease of disinfection is a factor that is often overlooked with regard to

fluid purity. Simply put, the easier and/or less time consuming
it is to disinfect, the more regularly it is likely to
be done.

With that in mind, Gambro has designed

an HD system that disinfects the entire fluid
pathfrom water treatment to HD machine
to drainautomatically, every day, during The CleanCart concept provides easy, safe and
non-dialysis hours. effective disinfections and cleaning.

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Ultrafiltration
of dialysis fluid
Ultrafilters may also be used to strengthen The Hygienic Chain. Inserting a U 8000
S ultrafilter in the dialysis fluid line significantly reduces levels of bacterial
derivatives in the fluid. More ultrafilters are required to prepare on-line substitution
fluid for HDF or HF. To assure sterile equivalent and non-pyrogenic fluid in all
cases, the ULTRA system by Gambro uses a set-up of three ultrafilters. The first
one is to assure that ultrapure water feeds the machines interiora requirement
for all on-line systems. The second one prepares ultrapure dialysis fluid. The last
one, a sterile single-use ultrafilter inserted in the infusion line, is the essential last
safety barrier which makes it possible to achieve sterile substitution fluid (sterile
equipment is necessary in order to produce sterile fluid).

UF
A
conc
High quality
concentrates

RO Ultrafilter 3
U 2000
Ultrafilter 1
U 8000 S

Ultrafilter 2
U 8000 S

The ULTRA system by Gambro, with its set-up of ultrafilters, provides ultrapure dialysis fluid and non-pyrogenic substitution fluid for HDF or HF.

Extra purity and security

While the ULTRA system is highly efficient at removing contaminants from the
dialysis fluid, prudence would suggest that every precaution be taken to keep
contaminants from entering the fluid system in the first place. A secure hygienic
chain adds an extra measure of purity and security to the ULTRA system. In
addition, ensuring cleaner fluid from the start prolongs the life of the ultrafilters
and reduces the need for elaborate maintenance programs.

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Tubing: a critical link in
The Hygienic Chain
Tubing and inlets

If the water treatment system and HD machines are adequately equipped to

prevent contamination, there is only one source left. That is, the tubing that
runs throughout the clinic connecting all the machines to their fluid source.
This crucial link in The Hygienic Chain is perhaps the most important
because it is so often found to be the source of contamination due to the
growth of biofilm.

Of particular concern are the machines fluid inlet and the line that connects
it to the central loop. These are the missing links in many hygienic chains.
That is because neither the loops nor the machines disinfection routine
include these areas. Such an omission leaves the entire system vulnerable to
microbial contamination.

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Preventive maintenance
The effectiveness of all other purity precautions is seriously reduced if the tubing
is home to thriving communities of bacteria and other microorganisms that are
found in biofilm. Sometimes this film can be observed with the naked eye as a
creamy yellowish deposit coating the inner surfaces of fluid pipes. Since these
microorganisms are securely fastened to the walls of the tubing, they are not
floating in the fluid and therefore will not be revealed by CFU counts of the fluid.
Nonetheless, they serve as a reservoir of toxins that are constantly leached into
the system. While biofilm is virtually impossible to remove, it can be prevented
from establishing a presence. Prevention with daily prophylactic disinfection is the
only known answer. That is, daily circulation of hot water through the entire fluid
circuit in your clinic. Its not difficult. In fact, the Gambro system can perform this
daily routine automatically during non-dialysis periods.

Gambros automatic hot water flushing program

Biofilm poses a real threat to
tubing. Here the tubing has not
beeen regularly flushed with
hot water. Within two years
biofilm is clearly evident.
stops biofilm before it starts. Here, Gambros
prophylactic hot water flushing of the tubing
results in a surface that is as clean two years
later as the day it was installed.

Often overlooked, tubing can be the critical weak link in

many hygienic chains. Gambros PEX tubing resists heat,
is flexible, tough, and chemically inert.

Tubing
The choice of tubing is important. There are many requirements placed on HD
system tubing. It should be tough, flexible, heat resistant, chemically inert, and
have a smooth inner surface. Meeting all these requirements, our PEX tubing is
ideally suited for the specialized demands of the HD clinic. Its tough yet easily
bendable and can be installed in long sections without joints. This is important
because joints favor the growth of biofilm. All in all, PEX tubing offers an advan-
tage over any other type of tubing, including electro-polished stainless steel.

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A final word
Fluid purity is a topic of increasing importance in HD treatment. With this brochure
we hope to promote an approach we call The Hygienic Chain concept. Our aim is
to demonstrate the importance of fluid purity and explain how we achieve it. As
part of that message, I would like to express Gambros dedication to The Hygienic
Chain concept as a way to better serve you and your patients.

The Hygienic Chain concept has been a guiding principle in Gambros product
design for decades. It is reflected in a string of Gambro innovations like hygienic
fluid path design in our HD machines, on-line heat disinfection, on-line prepara-
tion of bicarbonate from dry powder, and on-line preparation of HF/HDF infusion
fluidall Gambro firsts. It is also reflected in our product range, which provides a
complete hygienic chain solution. Gambro can provide every link in the hygienic
chain from water treatment to ultrafilters.

If you are considering replacing your water treatment system, now is the time to
make your clinics hygienic chain even stronger. I hope that the ideas presented in
the booklet will help you and your patients to teach the highest quality dialysis
treatment available.

Ingrid Ledebo, Ph.D.

Director Scientific Affairs
Gambro Research & Development

Contact Gambro
If you are planning to update an existing clinic, call Gambro to see how we can
work with your current equipment to maximize fluid quality and minimize the risk
posed by biofilm. If you are planning a new HD clinic, we recommend that you
consider establishing a fully integrated hygienic chain from the start. Your Gambro
representative would be happy to consult with you.

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 HCEN1156_4 2009.12. Gambro Lundia AB
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passionately committed to promoting life by advancing products,
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PO Box 10101
SE-22010 Lund
Sweden
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