U.S. patent application number 14/178861 was filed with the patent office on 2014-06-12 for double fiber bundle dialyzer.
This patent application is currently assigned to MIRIMEDICAL LLC. The applicant listed for this patent is MIRIMEDICAL LLC. Invention is credited to Gary MISHKIN.
Application Number | 20140158605 14/178861 |
Document ID | / |
Family ID | 41550984 |
Filed Date | 2014-06-12 |
United States Patent
Application |
20140158605 |
Kind Code |
A1 |
MISHKIN; Gary |
June 12, 2014 |
DOUBLE FIBER BUNDLE DIALYZER
Abstract
A dialyzer composed of: first and second dialyzation chambers,
and an intermediate chamber interposed between the first and second
dialyzation chambers. Each dialyzation chamber has opposed first
and second ends and contains a filter member that separates the
chamber into a blood compartment and a dialysate compartment. Each
of the compartments extends between first and second ends. Each of
the chambers has a respective one of a blood inlet or outlet and a
dialysate inlet or outlet arranged so that blood and dialysate flow
in counter-current to one another in both chambers. The
intermediate chamber is connected to form a dialysate-free blood
flow passage between the blood compartments.
Inventors: |
MISHKIN; Gary; (Potomac,
MD) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MIRIMEDICAL LLC |
Potomac |
MD |
US |
|
|
Assignee: |
MIRIMEDICAL LLC
Potomac
MD
|
Family ID: |
41550984 |
Appl. No.: |
14/178861 |
Filed: |
February 12, 2014 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
13054306 |
Jan 14, 2011 |
|
|
|
PCT/US2009/050494 |
Jul 14, 2009 |
|
|
|
14178861 |
|
|
|
|
61080769 |
Jul 15, 2008 |
|
|
|
Current U.S.
Class: |
210/321.72 |
Current CPC
Class: |
A61M 1/1633 20140204;
B01D 2319/02 20130101; B01D 2313/20 20130101; A61M 2205/3334
20130101; A61M 1/16 20130101; B01D 63/043 20130101; B01D 69/084
20130101; A61M 1/1601 20140204; A61M 1/3417 20140204 |
Class at
Publication: |
210/321.72 |
International
Class: |
A61M 1/16 20060101
A61M001/16 |
Goverment Interests
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] This invention was made with government support under
5R42DK64500 awarded by National Institutes of Health (NIH),
Bethesda, Md. The government has certain rights in the invention.
Claims
1. A dialyzer comprising: first and second dialyzation chambers,
and an intermediate chamber interposed between said first and
second dialyzation chambers, wherein, each of said dialyzation
chambers has opposed first and second ends; each of said
dialyzation chambers contains a filter member that separates said
dialyzation chamber into a blood compartment and a dialysate
compartment, each of said compartments extending between said first
and second ends; said filter member in said first dialyzation
chamber is made of a filter material for filtering out plasma water
from blood; said filter member in said second dialyzation chamber
is made of a filter material for passing dialysate from said
dialysate compartment to said blood compartment; said first
dialyzation chamber has, at said first end thereof, a blood inlet
communicating with said blood compartment and a dialysate outlet
communicating with said dialysate compartment; said second
dialyzation chamber has, at said first end thereof, a blood outlet
communicating with said blood compartment and a dialysate inlet
communicating with said dialysate compartment; said intermediate
chamber extends between said second end of said first dialyzation
chamber and said second end of said second dialyzation chamber and
communicates only with said blood compartments during operation of
said dialyzer to perform blood dialysis; said blood and dialysate
inlets and outlets are located to produce dialysate flows in
counter-current to blood flows in both of said dialyzation
chambers; and said first and second dialyzation chambers are
constructed to provide a dialysate flow path between said dialysate
compartments at said second ends of said chambers, said dialysate
flow path forming a constricted passage for dialysate that produces
a dialysate pressure drop between said second dialyzation chamber
and said first dialyzation chamber, wherein said constricted
passage is dimensioned such that, during operation of said
dialyzer, the dialysate pressure drop between said second
dialyzation chamber and said first dialyzation chamber causes
plasma water to be removed from blood in said blood compartment of
said first dialyzation chamber and causes dialysate to be filtered
from said dialysate compartment into said blood compartment of said
second dialyzation chamber.
2. The dialyzer of claim 1, wherein each said filter member is
composed of a fiber membrane bundle having a fiber membrane surface
area, and the fiber membrane surface area of said filter in said
first dialyzation chamber is different from the fiber membrane
surface area of said filter in said second dialyzation chamber.
3. The dialyzer of claim 2, wherein each said filter member has a
fiber membrane surface area of 0.9 m.sup.2 to 1.8 m.sup.2.
4. The dialyzer of claim 1, wherein each said filter member is
composed of a fiber bundle having a coefficient of ultrafiltration
(Kuf) of 20-26 ml/h/(mmHg transmembrane pressure).
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] Applicant claims priority rights for Provisional Application
No. 61/080,769, filed on Jul. 15, 2008, the disclosure of which is
incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0003] The present invention relates to dialyzers, and particularly
single-unit dialyzers that can be used with all existing dialysis
equipment to provide dialytic therapies having increased
efficiency.
BRIEF SUMMARY OF THE INVENTION
[0004] A dialyzer according to the invention is composed of two
bundles of hollow fibers constituted by semi-permeable membranes,
preferably housed within a single casing that delimits, in effect,
two chambers. The dialyzer further includes an intermediate chamber
in which blood flows from one fiber bundle to the other so that the
blood coming from the first fiber bundle becomes intermixed and
thus homogenized. This dialyzer is arranged to be connected to a
standard dialysis machine via a blood inlet and outlet and a
dialysate inlet and outlet. No additional connections are
required.
BRIEF DESCRIPTION OF THE DRAWING
[0005] FIG. 1 is a simplified, elevational, pictorial view of one
preferred embodiment of a dialyzer according to the invention.
[0006] FIG. 2 is an elevational, cross-sectional view of the casing
according to a preferred embodiment of the invention.
[0007] FIG. 3 is an elevational, cross-sectional view of top header
caps of a dialyzer according to the invention.
[0008] FIG. 4 is an elevational, cross-sectional view of a bottom
header cap of a dialyzer according to the invention, viewed in the
direction of cross-section line 4-4 in FIG. 5.
[0009] FIG. 5 is a top plan view of the header cap of FIG. 4.
[0010] FIGS. 5A-5E are cross-sectional views viewed in the
direction of cross-section lines 5A-5A, 5B-5B, 5C-5C, 5D-5D and
5E-5E, respectively, in FIG. 5
DETAILED DESCRIPTION OF THE INVENTION
[0011] FIG. 1 shows one preferred embodiment of the invention,
which can be delineated as a double fiber bundle dialyzer. This
apparatus is composed, in effect, of an outer casing that delimits
two dialyzation chambers 2, 4 that may be disposed, effectively,
side by side. Each dialyzation chamber 2, 4 is closed off by a
respective part of the outer casing and manifolds 24, 26, 28, to be
described below. Each dialyzation chamber contains a filter member
in the form of a bundle 12, 14, respectively, of semi-permeable
hollow membrane fibers. Each fiber has the form of a small diameter
hollow tube. The outer casing parts have a common wall 20, the
common wall being provided, near the bottom of the outer casing,
with an opening 22 forming a constricted passage for dialysate.
[0012] Manifold 24 is provided with openings that place the upper
ends of the fibers of bundle 12 in communication with a blood
outlet compartment 30, while manifold 26 is provided with openings
that place the upper ends of the fibers of bundle 14 in
communication with a blood inlet compartment 34. Compartments 30
and 34 are delimited by header caps.
[0013] Manifold 28 is provided with openings that place the lower
ends of the fibers of bundles 12 and 14 in communication with an
intermediate chamber 38 in which blood flows from the fibers of
bundle 14 to the fibers of bundle 12 while blood from the various
fibers become intermixed so that the blood entering the fibers of
bundle 12 is of a more uniform composition. The component
delimiting chamber 38 may be a further header cap.
[0014] Manifolds 24, 26 and 28 close off the portions of each
chamber 2, 4 through which dialysate flows so that dialysate cannot
flow into chamber 38.
[0015] FIG. 2 is a cross-sectional view of one preferred embodiment
of the outer casing of a dialyzer according to the present
invention. This embodiment is composed essentially of two
circularly cylindrical tubes delimiting the dialyzation chambers 2,
4. Common wall 20 with opening 22 is provided at the lower end of
the outer casing. By way of example, opening 22 may have a circular
cross section with a diameter of the order of 1.4 mm and a
longitudinal axis that has a length of the order of 6.6 mm and is
inclined at an angle of the order of 60.degree.-85.degree. to the
longitudinal axis of each chamber 2, 4 and oriented to produce a
flow having a direction with a component parallel to the direction
of dialysate flow in chamber 4.
[0016] Also by way of example, the overall length of the outer
casing may be of the order of 28.6 cm and the distance between the
longitudinal axes of chambers 2 and 4 may be of the order of 5.2
cm.
[0017] The diameter of each chamber 2, 4 is of the order of 3.6 cm
at the center of the chamber. However, other diameter values can be
used. In general, the diameter of the chamber will be related to
the size of the fiber bundle. As a rule of thumb, the total area of
the fibers in a bundle, based on the outer diameters of all of the
fiber OD in one plane, should preferably be approximately 50-55% of
the cross-sectional area of the chamber in the same plane.
[0018] The locations of manifolds 24, 26 and 28 are shown in broken
lines in FIG. 2.
[0019] FIG. 3 shows an example of top header caps delimiting
compartments 30 and 34.
[0020] FIGS. 4, 5 and 5A-5E show an example of the bottom header
cap delimiting compartment 38.
[0021] Some exemplary dimensions are shown in FIGS. 2, 4 and 5A-5E.
The bottom header cap is provided with a channel 60 designed to aid
blood flow from fiber bundle 14 to fiber bundle 12. The dimensions
of channel 60 are of the order of 10.5 mm wide and 5.3 mm high and
the radius of curvature of channel 60 is also 5.3 mm. Channel 60
extends essentially between the midpoints of the two halves of the
header cap. This provides a path for the blood to travel and mix
while minimizing the pressure drop where chamber 38 narrows between
fiber bundles. The top part is curved but the bottom forms a
semicircle or "D shape" with the flat top of the manifold.
[0022] The volumes enclosed by the fibers of bundles 12 and 14
define respective blood compartments in chambers 2 and 4, while the
volumes surrounding the fibers of bundles 12 and 14 define
respective dialysate compartments in chambers 2 and 4.
[0023] Manifolds 24, 26 and 28 constitute walls that close off the
upper ends of the dialysate compartments and manifold 28
constitutes a wall that close off the lower ends of the dialysate
compartments. The lower end of common wall 20 bounds a constricted
passage between the two dialysate compartments.
[0024] Compartment 34 is provided with an inlet passage 40 for the
delivery of blood into the apparatus, while compartment 30 has a
blood outlet 42 for removal of blood from the apparatus. In
addition, chamber 2 is provided with a dialysate inlet 44, while
chamber 4 is provided with a dialysate outlet 46.
[0025] During a dialysis procedure, fresh dialysate is introduced
through inlet 44 into the dialysate compartment in chamber 2, flows
through opening, or restricted passage, 22 near the bottom of
common wall 20 into the dialysate compartment in chamber 4, and
then out through outlet 46. At the same time, blood that is to be
dialyzed is introduced into chamber 34 via inlet 40, flows through
the fibers of bundle 14 into intermediate chamber 38, and then
flows through the fibers of bundle 12 to chamber 30 and finally
exits the apparatus through outlet 42.
[0026] In chamber 4, plasma water is removed from blood flowing
through the fibers of bundle 14 and is transferred into the
dialysate compartment in chamber 4 by being filtered across the
semipermeable membranes forming the walls of the fibers of bundle
14.
[0027] Upon exiting the blood compartment in chamber 4, the blood
enters and flows through intermediate chamber 38 and then into the
blood compartment in chamber 2. The function of intermediate
chamber 38 will be described below.
[0028] As the blood flows through the blood compartment in chamber
2, i.e., through the fibers of bundle 12, fresh dialysate is
filtered from the dialysate compartment, across the semipermeable
membranes forming the walls of the fibers of bundle 12 and into the
blood compartment of chamber 2 at a rate substantially equal to the
rate at which plasma water was filtered from the blood compartment
of chamber 4. The manner in which the filtration rates are
controlled will be described below.
[0029] Thus, ultrafiltration is performed in chamber 4, while
substitution fluid is introduced from fresh dialysate into the
blood compartment in chamber 2 via backfiltration. The dialyzer is
thus capable of achieving a high rate of ultrafiltration with the
introduction of substitution fluid by backfiltration that results
in an on-line Hemodiafiltration (HDF) treatment. HDF is a
hemodialysis modality that combines the use of dialysis fluid for
the diffusive removal of toxins with larger volumes of
ultrafiltration (compared to standard hemodialysis) to remove
middle weight molecules by convection.
[0030] Fresh dialysate fluid for this system may be generated using
existing methods and standard dialysis equipment. The dialysate
fluid enters the dialysate compartment in chamber 2 and flows in
counter-current with respect to the blood flow. This dialysate
fluid performs two functions: 1) it acts to set up a concentration
gradient relative to the blood compartment, thereby inducing
diffusion of solutes across the semi-permeable membranes from the
blood compartment to the dialysate compartment in chamber 2; and 2)
because of the relatively higher pressure of the incoming dialysate
compared to the blood compartment pressure, it produces a
backfiltration of dialysate into the blood compartment.
[0031] Upon exiting chamber 2, the dialysate fluid enters the
dialysate compartment in chamber 4, still flowing in
counter-current with respect to the blood flow in the respective
blood compartment. The dialysate flow rate increases as the
dialysate flows through the dialysate compartment in chamber 4, due
to filtration of plasma water from the blood compartment across the
semi-permeable membranes of the fibers of bundle 14.
[0032] Dialysate also flows around the fibers of each fiber bundle,
entering at one side of the respective dialysate chamber and
flowing diagonally across the chamber and around the membrane
fibers before exiting at the other side, and the other end, of the
respective chamber. This flow across, or around, both fiber bundles
may enhance fiber surface contact and diffusive removal of
substances.
[0033] Upon exiting the dialyzer, the spent or used dialysate is
transported back to the dialysis machine and to the drain in a
conventional manner.
[0034] The fibers of both bundles may be of the same material and
both bundles also have the purpose of diffusive removal of toxins.
It is also possible, at high protein concentrations in the blood,
that some backfiltration starts in fiber bundle 14.
[0035] The volumetric control of a dialysis machine ensures proper
ultrafiltration and controls the rates of filtration and
backfiltration. The fiber bundle involved in the backfiltration, in
chamber 2, acts as a final fluid quality filter and has been shown
to bring both bacteria and endotoxin to levels that approach
pharmaceutical grade fluids.
[0036] The advantage of this system is that small molecules such as
urea can be removed efficiently due to the appropriately large
surface area of the two fiber bundles, and midsized molecules are
removed efficiently due to the large filtration with
backfiltration, which is optimized with this double fiber bundle
configuration. No additional dialyzers, no final ultrafilters, no
additional pumps or external equipment and no external substitution
fluid are required.
[0037] The rate of filtration and backfiltration will be controlled
by the resultant pressures due to the blood and dialysate flow
rates. This is discussed in U.S. Pat. No. 6,406,631, issued Jun.
18, 2002, the disclosure of which is incorporated herein by
reference.
[0038] There are several advantages to the proposed double fiber
bundle dialyzer as compared with the prior art. First, the dialyzer
according to the invention can be given a large membrane surface
area that will result in improved urea and creatinine removal.
[0039] The largest dialyzer commercially available today has a
membrane surface area of 2.5 m.sup.2. Dialyzers employing known
ultrafiltration technology would exhibit a tendency to clot if
given a larger membrane surface area. In addition, if the
filtration rate is too high in known dialyzers, an alarm indicating
a reverse ultrafiltration error will be produced because the TMP
(transmembrane pressure=average blood side pressure-average
dialysate side pressure) becomes negative and implies fluid is
fluxed across the membrane from the dialysate into the blood. In
the past, when fluid quality was more questionable, this may have
been a problem. Various dialysis machines measure TMP in different
ways. Very few dialysis machines measure the blood in and blood out
as well as the dialysate in and dialysate out pressures to get a
true TMP. Most dialysis machines use the blood out and dialysate
out pressures and an offset to calculate the TMP.
[0040] However, the novel technology on which the present invention
is based makes possible a dialyzer having a membrane surface area
of 3.0 m.sup.2 or more. The double dialyzer configuration according
to the present invention resolves the clotting issue as discussed
herein, and also resolves the reverse ultrafiltration alarm problem
by decreasing the dialysate out pressure due to the restricted
passage between the dialysate compartments.
[0041] In addition, the rate of ultrafiltration and midsize
molecule removal will be greater in the dialyzer according to the
invention than in prior art systems having the same dialyzer area
and similar Kuf, Kuf being the coefficient of ultrafiltration for
the filter member, i.e., the rate of plasma water fluid flux across
the membrane, or fiber wall, per hour per mmHg of transmembrane
pressure (TMP). This is because the TMP is enhanced in the
invention dialyzer by the two dialyzation chamber design.
[0042] Further, the dialysate distribution and resultant clearance
will be better in dialyzers according to the invention, at least
when crimped fibers are used for the membranes. Specifically,
crimped fibers result in a more uniform dialysate flow throughout
the dialyzer. This results in improved clearance of small
molecules. Also, the provision of two separate dialysate
compartments communicating via the restricted passage, or orifice,
will help to redistribute the dialysate flows so any channeling,
even with straight fibers, will be all but eliminated in the second
dialysate compartment.
[0043] Moreover, the system according to the present invention is
constructed and operated to maintain the counter-current dialysate
flow throughout both bundles whereas at least one existing dialyzer
has a single chamber with counter-current flow in one stage that
contains a filter bundle and concurrent flow, i.e., blood and
dialysate flows in the same direction, in a second stage containing
another bundle, which greatly reduces the diffusion gradient. In
the operation of that dialyzer, it is necessary to add substitution
fluid directly into a space between the fiber bundles. If
substitution fluid is not added, this dialyzer clots very quickly.
The second stage will have a lower small molecule removal rate
since the concentration gradient is smaller.
[0044] Furthermore, in prior art systems substitution fluid
requires a separate filter for the fluid generated on-line and a
separate pump to control infusion, making the system more
complicated and expensive to run than a dialyzer according to the
invention.
[0045] Specifically, dialyzers according to the invention are
intended to be connected to standard dialysis machines that are
already in dialysis clinics to perform an HDF treatment. To perform
any of the other HDF treatments, prior art machines require a
specialized structure that has extra sensors to measure the amount
of filtration, separate pumps to return the substitution fluid and
extra filters since they reinfuse the substitution fluid either
directly into the blood line or into the header of the dialyzer.
For example, these other systems will need to calculate the volume
going into the system (blood and dialysate) and the volume coming
out (blood and dialysate). The system needs to calculate the rates
of filtration and then must add the proper amount of substitution
fluid to the system to balance the fluid removed. So the equipment
is complicated by balances or fluid control units that measure the
fluid exchanged. This also requires a pump to infuse the
substitution fluid directly into the blood line. Our system uses
the existing fluid balancing system in the current machines. The
fluid balancing system can be a diaphragm pump such as in the
Frensius machines or flow meter controlled system such as in the
Gambro machines.
[0046] An advantage of the present invention is that the double
fiber bundle dialyzer can be used with any known dialysis machine
with volumetric control to perform an HDF treatment without needing
to set up additional infusion lines, filters and/or pumps or
units.
[0047] Improved midsize molecule clearance is achieved in a
dialyzer according to the invention by increasing filtration and
backfiltration. More specifically, midsize molecules are removed
more effectively by filtration (convection removal) and dialyzers
according to the invention enhance convective removal by the action
of the restricted dialysate passage 22 and by using the proper
membranes.
[0048] Furthermore, a dialyzer according to the invention can be
used in existing dialysis machines without the need for additional
hardware or modifications.
[0049] For example, a dialyzer according to the invention can be
used with known dialysis machines, such as a standard Fresenius
machine, on which a dialyzer according to the invention was tested,
in place of a conventional dialyzer, using the exact same set-up as
for a standard dialysis treatment, including standard blood lines.
The dialyzer according to the invention will automatically enhance
the filtration and back filtration based on its design. Nearly all
current dialysis machines have a place for an ultrafilter. This is
a filter that filters the dialysate fluid prior to reaching the
dialyzer. It is a component of a dialysis machine, possibly not
needed in systems according to the present invention. An
ultrafilter is usually a hollow fiber filter similar to a standard
dialyzer, but is designed to have the fluid diffuse across the
fibers (filtration) and then flow to the dialyzer. All machines
marketed within the past 5 years or more have a built in
ultrafilter (also called an endotoxin filter).
[0050] The double fiber bundle dialyzer according to the invention
differs from the prior art (e.g., U.S. Pat. No. 5,700,372) in
several ways. One important difference is that in the system
according to the invention, blood passes through and exits the
fibers of bundle 14, then enters a large space, i. e., intermediate
chamber 38, where the blood exiting all of the fibers of bundle 14
is mixed together before entering the fibers of bundle 12. No
filtration, or back filtration, or substitution of fluid occurs in
intermediate chamber 38; only blood flows through intermediate
chamber 38.
[0051] Chamber 38 performs an important function that serves to
eliminate, or at least minimize, the adverse effects of a common
problem in dialysis known as "channeling". Channeling can occur on
the dialysate side or the blood side of the fibers. Channeling on
the blood side is when blood flows through different fibers at
different rates. In the fibers in which a relatively fast flow
occurs, the fibers see more blood than do the fibers in which a
slower blood flow occurs, although ultrafiltration occurs from all
of the fibers. In the fibers experiencing slow blood flow, while
plasma water is being removed by ultrafiltration (raising the
hematocrit: the proportion of blood volume that is occupied by red
blood cells), the blood will tend to clot and the fibers will
become blocked. This results in more flow through the other fibers
and a reduction in the active filter surface area, i.e., the filter
surface area participating in the filtering of toxins. A reduction
in the active filter surface area of the dialyzer will reduce the
efficiency of the dialyzer and the treatment. At the same time, the
reduction in the active filter surface area causes a higher
pressure at blood inlet 40, which in turn causes more
ultrafiltration in the remaining fibers. This higher
ultrafiltration will lead to more clotting.
[0052] Since systems according to the invention have two smaller
bundles of fibers separated by intermediate chamber 38, as the
blood goes through the fibers of bundle 14 it becomes more
concentrated (because of ultrafiltration). However, all of the
blood exiting the fibers of bundle 14 enters the common
intermediate chamber 38 and mixes together. This will include the
blood that flowed slowly through one or more fibers and the blood
that flowed faster through other fibers. The blood entering the
fibers of bundle 12 will, therefore, be more homogenous. The
pressure of the blood entering the fibers of bundle 12 will also be
the same at all of the fiber walls, leading to a more consistent
backfiltration and reconstitution of the blood returning to the
body at nearly the same hematocrit at which it was pumped out of
the body.
[0053] To summarize, intermediate chamber space 38 in the double
fiber bundle system according to the invention acts to mix the
blood while no filtration, or back filtration, or substitution of
fluid is occurring so that the blood entering the fibers of bundle
12 is homogenous and at nearly the same pressure from one fiber to
another.
[0054] An exemplary preferred embodiment of the invention may have
the following specific parameters:
[0055] Dimensions of each fiber: ID=180-200 .mu.m; wall
thickness=filter member 35-50 .mu.m; OD=250-300 .mu.m; length=28
cm.+-.3 cm;
[0056] Effective surface area of each fiber bundle=1.5 m.sup.2;
[0057] Number of fibers in each chamber, i. e., in each
bundle=approximately 9500 fibers +/-500 fibers, the exact number
depending on the diameter and length of the fibers.
[0058] The pore size for toxin removal should be selected to
produce as sharp a drop as possible in the elimination rate of
molecules at 65,000 or 66,000 Daltons (the universal mass unit or
atomic mass unit). Little or no molecular weight substances above
65,000 or 66,000 Daltons should be removed. This will minimize
protein losses during treatment.
[0059] One nonlimiting example of the membrane material of the
fibers in bundles 12 and 14 would be a product marketed by Asahi
Kasei Kuraray Medical Co., Ltd. under the trade names REXBRANE and
Polysulfone APS, a polysulfone membrane with a hydrophilic gel
layer.
[0060] The fibers should be crimped to enhance dialysate flow. This
crimping gives the fibers a form that follows a sinuous path along
their length, which is the form of the REXBRANE fibers.
[0061] Each fiber bundle may have a KuF (Coefficient of
Ultrafiltration) of 20-26 ml/h/(mmHg TMP), TMP can be calculated as
the average pressure on the blood side of the membrane minus the
average pressure on the dialysate side of the membrane. TMP is
mostly determined by the hydrostatic pressure of the blood flow on
the blood side of the membrane (favoring flux from the blood side
to the dialysate side), the opposite pressure of the dialysate
fluid on the dialysate side of the membrane (favoring dialysate
fluid flux to the blood side) as well as the opposite pressure
associated with the oncotic pressures (which is a form of osmotic
pressure exerted by proteins in blood plasma that normally tends to
pull water into the circulatory system) of the blood proteins
(favoring fluid flux from the dialysate side to the blood side). As
more fluid flows across a membrane from the blood side to the
dialysate side, the oncotic pressures increase as the protein
concentration increases due to less plasma water and a relatively
higher protein concentration.
[0062] The true calculation of Kuf, therefore, can vary as a
function of the protein concentrations, dialysate flows, and blood
flows. The Kuf range given above was consistent for the specific
embodiment tested using the Fresenius 2008 series dialysis machine
and the blood and dialysate flows tested blood flow=350-550 ml/min
and dialysate flow=800 ml/min). When the dialysate flow (Qd) is
reduced to 500 ml/min, there is a drop in TMP (machine measured) of
close to 100 mmHg. This is due to the increase in average dialysate
side pressures. The incoming dialysate pressures are nearly the
same at 800 and 500 ml/min dialysate flows, the pressures being
approximately 200 mmHg.+-.dependent on blood flow.
[0063] The pressure drop between the inlet and outlet of the
dialysate compartment in chamber 2 is slight due to the presence of
the constricted passage between the dialysate compartments. The
pressure drop across the constricted passage is lower with a 500
ml/min flow rate since the flow is lower. This yields a higher
average pressure in the dialysate compartment of chamber 4 for a
500 ml/min dialysate flow than for an 800 ml/min flow. The higher
pressure on the dialysate side of chamber 4 yields a drop in
TMP.
[0064] Also, the conventional volumetric controller (not shown) of
the dialysis machine to which the dialyzer is connected, which
makes sure that the dialysate volume entering via inlet 44 is the
same as the volume that leaves via outlet 46, can apply a slight
negative pressure at outlet 46, thereby pulling fluid from the
blood side to make the incoming and outgoing volumes the same.
Additional fluid removal is normally programmed into the dialysis
machine in order to remove the excess fluid a patient consumes
between treatments. This excess fluid removal is controlled by a
separate pump in all dialysis machines and works in conjunction
with the present invention.
[0065] The Kuf (coefficient of ultrafiltration) is calculated for
the fibers of bundle 14 only using human blood reconstituted with
saline and bovine albumin at a concentration of .about.6 g/dL (this
also effects the measured Kuf. If it was measured with saline, the
Kuf would be calculated to be much higher due to the lower
viscosity and lack of blood proteins, i.e. albumin).
[0066] In chamber 2, the dialysate compartment pressure drop with
Qd=800 ml/min (dialyzer with incoming dialysate from the associated
machine and provided with the restricted passage beneath common
wall 20 as well as back filtration)=about 15 mmHg (this is a slight
pressure drop due to the constricted passage at the outlet of the
dialysate compartment in chamber 2).
[0067] In chamber 4, the pressure drop across the dialysate
compartment with Qd=800 ml/min (with a large filtration volume from
blood to dialysate side, the machine volume controller can cause a
negative pressure at the outlet 46)=about 55 mmHg, with or without
negative pressure at outlet 46, downstream of the restricted
passage to outlet 46 (dialysate flows in counter-current to blood
flow).
[0068] Constricted passage 22 in common wall 20 between the
dialysate compartments in chambers 2 and 4 should preferably
provide a pressure drop of .about.100 mmHg with a Qd=800 ml/min, or
a 50 mmHg drop with Qd=500 ml/min.
[0069] The total dialysate pressure drop between inlet 44 and
outlet 46 should be about 170 mmHg. There is some variability
dependent on blood flow, rate of filtration with backfiltration and
access needle size used or catheter type (which effects venous
pressure of returning blood at outlet 42).
[0070] The blood side pressure drop is dependent on blood flow and
the size of the venous needle used to return the blood to the
patient's body (using a smaller venous needle will result in a
higher pressure leaving chamber 2), but can be approximated, for
chamber 4, as a pressure drop, between chambers 34 and 38, of 40%
of the pressure entering the dialyzer fibers (header pressure,
chamber 34). For example, if the incoming pressure is 402 mmHg and
the outgoing is 240 mmHg this is a difference of 162 mmHg, or 40%
(=162/402), and approximately a 65% pressure drop of the pressure
in chamber 38 to the exit chamber 30 (pressure drop across Chamber
2). The pressure drop in Chamber 2 will vary dependent on blood
flow, a higher blood flow resulting in a higher pressure drop. In
the operation of a dialyzer according to the invention, a pressure
drop of 75% at blood flows of 550 ml/min and a pressure drop of 62%
at blood flows of 350 ml/min were measured.
[0071] The double dialyzer according to the invention has two
separate bundles of fibers for filtration, with fiber bundle
headers at the ends of the chambers. Manifolds 24, 26 and 28 may be
constituted by potting compound bodies. U.S. Pat. No. 4,227,295
(Bodnar) and U.S. Pat. No. 5,700,372 (Takesawa), the disclosures of
which are incorporated herein by reference, describe common methods
to manufacture dialyzers using the potting compound to form
manifolds. This method can be used in the fabrication of a dialyzer
according to the present invention. The fibers enter and exit
through these bodies so that the blood encounters some resistance
upon entering the fibers and the resistance at the entry to each
fiber bundle aids filtration.
[0072] The potting compound is used to separate the internal
pathways presented by the fibers from the dialysate compartments.
This is done by inserting the fiber bundles into the dialyzer
casing. Thus, a lower end header cap will be provided. The potting
compound bodies are formed in place before the top and bottom
header caps are put in place. To form the potting compound bodies,
a special cap is clamped on each end of the casing and potting
compound (polyurethane material) is injected into the special caps
and around the fibers. The chambers are usually spun in order to
distribute the potting compound so as to reliably form seals
between the dialysate side and blood side of each chamber. Since
blood flowing out of the fibers of bundle 14 will flow through
chamber 38 and into the fibers of bundle 12, potting compound seals
will be formed around the fiber ends that will extend into chamber
38, as well as around the fiber ends that will extend into
compartments 30 and 34, after which the fiber bundle ends
projecting from the potting compound bodies may be sliced off. The
header caps may then be assembled to the ends of the casing.
[0073] Two separate dialysate compartments are provided in order to
be able to provide the flow constriction 22 therebetween to control
the rates of filtration and backfiltration. In fact, the flow
constriction between dialysate compartments, near the bottom of
wall 20, is a key component of the double dialyzer according to the
invention. If the flow constriction yields too low of a pressure
drop, the machine will alarm for low TMP because the average
dialysate pressure will be too low for the amount of filtration the
system produces. If the pressure drop across the flow constriction
is too high (too small of a passage cross section), the dialyzer
could clot as the TMP of fiber bundle 14 in chamber 4 increases
(because of very low dialysate pressures), causing additional
ultrafiltration of plasma water and hemoconcentrating the blood in
chamber 4. By having two separate bundles of fibers for blood and
dialysate, it becomes possible to maintain a counter-current flow
between dialysate and blood through the entire double dialyzer
system, maximizing diffusive removal of blood toxins.
[0074] The parameters presented herin have been found to produce
good results. However, variations are possible within the framework
of the invention. For example, the membrane fibers can have a
smaller ID, and/or thinner walls, and/or smaller or larger fiber
membrane surface areas (e.g., 0.9 to 1.8 m.sup.2 for each bundle).
It is possible to have a difference in area between the two fiber
bundles. This could be, for example 1.3 m.sup.2 for bundle 12 and
1.5 m2 for bundle 14, although this may make manufacturing more
difficult. Unequal surface areas may also have to be balanced by
possibly changing the filtration capability of the fiber bundles.
If a fiber bundle having a smaller surface area were provided in
one chamber, this may need to be compensated with a higher
filtration capability in order to provide the correct filtration
and backfiltration. If the inner diameter of each fiber were made
smaller, the result would be an increase in pressure drop and an
increase in filtration. There are numerous possible
configurations.
[0075] Other variations, such as lower Kuf of the fiber bundles
with higher pressure drops of the inter-dialysate chamber
constriction are also possible, as well as higher Kuf and lower
pressure drops. However, such variations should be within a small
range to reach the optimal 25% of blood flow filtration. For
example, a Kuf of 10 with a blood flow of 500 ml/min would require
a TMP of 750 mmHg; however the limit for TMPs for the membranes is
usually around 500 mmHg or they could break. Similarly, a Kuf of 30
requires a maximum TMP of 250 mmHg; however at a 500 ml/min blood
flow rate, the minimum TMP achievable is about 300 mmHg. The TMP
referred to is the actual measured TMP at the inlet and outlet of
both blood side and dialysate side, not the machine calculated
TMP.
[0076] The constricted passage 22 in wall 20 is important because
if there were no constriction, the pressure at dialysate outlet 46
would be substantially equal to the pressure at dialysate inlet 44,
so that there would be less filtration with backfiltration.
Therefore, clearance of middle weight toxins would be reduced and
there would also be problems with the dialysis machine because the
dialysate pressure at outlet 46 would be higher than if the
constricted passage was present. This higher pressure at outlet 46
will result in a reverse TMP alarm.
[0077] Also, a double fiber bundle with similar parameters but
smaller total membrane surface areas (0.3 to 0.9 m.sup.2 for each
bundle) can be used to provide a hemodiafiltration treatment at
lower blood flows (200 ml/min) and lower dialysate flows (100-500
ml/min). The constricted passage between dialysate compartments
will still be required in order to drop the average of the
dialysate side pressures to allow the double fiber bundle dialyzer
system to run on standard equipment.
[0078] Distribution rings, or dialysate diverters, commonly used in
this art, may also be provided near the inlet and outlet of
dialysate ports 44 and 46, below manifolds 24 and 26, and at the
bottom of the chambers, above manifold 28, to aid in distribution
of the dialysate around the fibers. Examples of such diverters are
disclosed in U.S. Pat. Nos. 4,396,510; 5,084,244; and 6,623,638,
the disclosures of which are incorporated herein by reference.
[0079] The casing shown in FIG. 2 is provided with diverters 52,
53, 54 and 55, which may be integral parts of the casing. Dialysate
entering via inlet 44 flows around diverter 52 and upwardly over
the upper edge of diverter 52 before entering the dialysate
compartment in chamber 2. Similarly, dialysate exiting from passage
22 will flow around diverter 55 and then under the lower edge of
diverter 55 before entering the dialysate compartment in chamber 4.
Diverters 53 and 54 are also used to aid in dialysate flow
distribution by forcing the fluid to flow from the center of the
dialyzer over the diverter to the periphery where dialysate will
flow through restricted passage via diverter 53 and to port 46 via
diverter 54. Since channeling commonly occurs along the walls of
the chambers, the diverters force the dialysate away from the walls
to the center where the fibers are located.
[0080] This present invention may also be used with the specialized
dialysis machines capable of delivering HDF treatments. The use of
pre-dilution HDF (fluid infused before entering the dialyzer) using
the present invention as the dialyzer will deliver a rate of
filtration equal to or greater than the amount of filtration of
which a standard HDF dialyzer in the same pre-dilution modality is
capable.
[0081] While the description above refers to particular embodiments
of the present invention, it will be understood that many
modifications may be made without departing from the spirit
thereof. The accompanying claims are intended to cover such
modifications as would fall within the true scope and spirit of the
present invention.
[0082] The presently disclosed embodiments are therefore to be
considered in all respects as illustrative and not restrictive, the
scope of the invention being indicated by the appended claims,
rather than the foregoing description, and all changes which come
within the meaning and range of equivalency of the claims are
therefore intended to be embraced therein.
* * * * *