U.S. patent number RE38,869 [Application Number 10/936,827] was granted by the patent office on 2005-11-08 for extracorporeal circuit for peripheral vein fluid removal.
This patent grant is currently assigned to CHF Solutions Inc.. Invention is credited to Steven Bernard, Mark Gelfand, Howard R. Levin, Hans-Dietrich Polaschegg.
United States Patent |
RE38,869 |
Polaschegg , et al. |
November 8, 2005 |
Extracorporeal circuit for peripheral vein fluid removal
Abstract
An extracorporeal blood circuit is disclosed for withdrawing,
filtering and returning blood from peripheral blood vessels. The
blood passage in the circuit extends through a withdrawal tube
connected to a catheter in a peripheral vein, a filter, one or more
pressure sensors and return tube also connected to a catheter in a
peripheral vein (which may or may not be the same vein as used for
the withdrawal tube). The blood passage is air free, and has smooth
passage walls which promoted continuous and uniform flow of the
blood through the circuit.
Inventors: |
Polaschegg; Hans-Dietrich
(Koestenberg, AT), Bernard; Steven (Andover, MN),
Levin; Howard R. (Teaneck, NJ), Gelfand; Mark (New York,
NY) |
Assignee: |
CHF Solutions Inc. (New York,
NY)
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Family
ID: |
24804040 |
Appl.
No.: |
10/936,827 |
Filed: |
September 9, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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660195 |
Sep 12, 2000 |
6887214 |
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618759 |
Jul 18, 2000 |
6890315 |
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Reissue of: |
698132 |
Oct 30, 2000 |
06533747 |
Mar 18, 2003 |
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Current U.S.
Class: |
604/6.09 |
Current CPC
Class: |
A61M
1/341 (20140204); A61M 1/3663 (20130101); A61M
1/3639 (20130101); A61M 1/3612 (20140204); A61M
1/361 (20140204); A61M 1/3653 (20130101); A61M
1/34 (20130101); A61M 2205/3334 (20130101); A61M
2205/12 (20130101); A61M 2205/3331 (20130101); A61M
2205/3393 (20130101) |
Current International
Class: |
A61M
1/34 (20060101); A61M 001/34 () |
Field of
Search: |
;604/6.09 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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29 44 062 |
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Sep 1976 |
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DE |
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WO 97/15228 |
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May 1997 |
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WO |
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Other References
Pierguiseppe Agostoni et al., "Sustained Improvement in Functional
Capacity After Removal of Body Fluid With Isolated Ultrafiltration
in Chronic Cardiac Insufficiency (etc.)", Mar. 1994, The American
Jounal of Medicine, vol. 96, pp. 191-199. .
Daniel Goldstein et al., "Venoarterial Strunting for the Treatment
of Right Sided Circulatory Failure After Left Ventricular Assist
Device Placement", ASAIO Journal 1997, pp. 171-176. .
Michael Berkoben et al., "Hemodialysis Vascular Acess", pp. 41-57.
.
James Cimino et al.,"Sample Venipuncture For Hemodialysis", The New
England Journal of Medicine, Sep. 20, 1962, pp. 608-609. .
Drukker et al., "Replacement of Renal Function Dialysis", pp.
334-379. .
Andrea Rimondini et al., "Hemofiltration as Short-Term Treatment
for Refractory Congestive Heart Failure", Jul. 1987, The American
Journal of Medicine, vol. 83, pp. 43-48. .
Strife, C.F. et al., "Experience With a Low Volume Ultrafiltration
Cell in Small Children", Clincal Nephrology 8:410-413 (1977). .
Lauer, A. et al., "Continuous Arteriovenous Hemofiltration in the
Critically Ill Patient, Clinical Use and Operational
Characteristics", Annals of Internal Medicine 99:455-460 (1983).
.
Verbanck, J. et al., "Pure Ultrafiltration by Repeated Puncture of
a Peripheral Arm-Vein as Treatment of Refractory Edema"(Case
Report), The International Journal of Artificial Organs, vol. 3,
No. 6 (1980) p. 342-343. .
Silverstein et al., "Treatment of Severe Fluid Overload by
Ultrafiltration", the New England Jounal of Medicine, vol. 291, No.
15, Oct. 10, 1974, pp. 747-751. .
Blake, P. et al., Refractory Congestive Heart Failure: Overview and
Application of Extracorporeal Ultrafiltration, Critical Care
Nephrology, Advances in Renal Replacement Therapy, vol. 3, No. 2
(Apr. 1966), pp. 166-173. .
Civati G. et al., "Haemofiltration Without Substitution Fluid",
Proc. EDTA-ERA, vol. 21 (1984), pp. 441-446. .
Jenkins, R.D. et al., "The Use of Continuous Arteriovenous
Hemofiltration With Hemodialysis in a Newborn", Draft #6, Personal
Communication, 1985 (6 pages). .
Jacobs, C. et al., "Continuous Arteriovenous Hemofiltration",
Replacement of Renal Function By Dialysis, 4.sup.th Ed., (1996) pp.
391-397. .
Gupta, B.B. et al., "High Shear Rate Hemofiltration: Influence of
Fiber Dimension and Shear Rates", Artificial Organs, International
Society for Artificial Organs, vol. 13(2) (1989), pp. 97-102. .
Donato, L. et al., "Treatment of End-Stage Congestive Heart Failure
by Extracorporeal Ultrafiltration", The American Journal of
Cardiology, vol. 59, (Feb. 1, 1987), pp. 379-380. .
L'Abbate, A. et al., "Ultrafiltration: A Rational Treatment for
Heart Failure", Cardiology 1989, 76:384-390. .
Chen, Y. et al., "Direct Peripheral Venopuncture: Another New
Choice of Temporary Vascular Access"(Case Report), Renal Failure,
22(3), 369-377 (2000). .
PRISMA.TM. M60 Set, "Instructions for Use", pp. 1-6 and 12,
(1998)..
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Primary Examiner: Michalsky; Gerald A.
Attorney, Agent or Firm: Nixon & Vanderhye, P.C.
Parent Case Text
This application is a continuation-in-part (CIP) application of
U.S. patent application Ser. No. 09/618,759, filed Jul. 18, 2000,
which is based on Provisional Application 60/206,232, filed May 23,
2000, and a CIP application of U.S. patent application Ser. No.
09/660,195, filed Sep. 12, 2000. These applications are
commonly-owned and incorporated by reference in their entirety.
Claims
What is claimed is:
1. An extracorporeal blood circuit comprising: a withdrawal tube
connectable at a first end to .[.a first peripheral blood vessel.].
.Iadd.a vascular system .Iaddend.of a mammalian patient; a filter
having a blood input connectable to a second end of the withdrawal
tube; a return tube having a first end connectable to an output of
the filter and a second end connectable to .[.a second peripheral
blood vessel.]. .Iadd.the vascular system.Iaddend.; a continuous
blood passage is formed in said withdrawal tube, filter and return
tube through which blood is withdrawn from the .[.first peripheral
blood vessel.]. .Iadd.vascular system.Iaddend., filtered and
returned to the .[.second blood vessel;.]. .Iadd.vascular system,
and.Iaddend. .[.wherein said continuous blood passage is air free
and.]. further wherein said filter has a concentration rise flow
volume of no greater than 15% of the total volume of the filter,
where the concentration flow volume is defined as a volume of flow
through the output of the filter during which a concentration of a
first fluid flowing through the filter output rises from a
concentration of 10% to a concentration of 90%.
2. An extracorporeal blood circuit as in claim 1 wherein said
circuit has a perfusion volume interval of less than 30 percent of
a filling volume of the circuit for an increase of a concentration
of an output flow of the circuit from 10% concentration to 90%
concentration of an input flow.
3. The extracorporeal blood circuit as in claim 1 wherein a
concentration of blood flow at an output of the circuit is 90% of
an input concentration after perfusion through the filter, with
less than 110 percent of a filling volume of the circuit following
an increase of a concentration of flow into the withdrawal
tube.
4. A method for moving blood through an extracorporeal blood
circuit having a withdrawal tube connected to a .[.first blood
vessel.]. .Iadd.vascular system .Iaddend.of a mammalian patient, a
filter and a return tube connected to .[.a second blood vessel.].
.Iadd.the vascular system .Iaddend.and a pump acting on the
circuit, wherein the method comprises: withdrawing blood from the
.[.first blood vessel.]. .Iadd.vascular system .Iaddend.into the
withdrawal tube; moving blood through the circuit by action of the
pump; filtering the blood flowing through the filter from the
withdrawal tube, wherein the blood enters an inlet to the filter
and flows out of a blood output; returning blood flowing from the
blood output through the return tube to the .[.second blood
vessel.]. .Iadd.vascular system.Iaddend., and wherein said filter
has a concentration rise volume of no greater than 15% of a total
blood volume in the filter, where the concentration rise volume is
defined as a volume of flow from the output from the filter
occurring after an abrupt change at the inlet to the filter from a
first fluid to a second fluid and as a concentration of the second
fluid flowing through the output rises from 10% of fluid flowing
through the output to 90% of said fluid flowing through the
output.
5. A method for moving blood through an extracorporeal blood
circuit having a withdrawal tube connected to a .[.first blood
vessel.]. .Iadd.vascular system .Iaddend.of a mammalian patient, a
filter and a return tube connected to .[.a second blood vessel.].
.Iadd.vascular system .Iaddend.and a pump acting on the circuit,
wherein the method comprises: withdrawing blood from the .[.first
blood vessel.]. .Iadd.vascular system .Iaddend.into the withdrawal
tube; moving blood through the circuit by action of the pump;
filtering the blood flowing from the withdrawal tube and into the
filter, returning blood output from the filter through the return
tube to the .[.second blood vessel.]. .Iadd.vascular
system.Iaddend., and after abruptly switching an input flow to the
filter from a first fluid to a second fluid, measuring the output
flow from the filter to be no greater than 15% of a total blood
path volume of the filter as a concentration of the second fluid at
the outlet of the filter raises from a 10% concentration level to a
90% concentration level.
6. A method for moving blood through an extracorporeal blood
circuit having a withdrawal tube connected to a .[.first blood
vessel.]. .Iadd.vascular system .Iaddend.of a mammalian patient, a
filter and a return tube connected to .[.a second blood vessel.].
.Iadd.the vascular system .Iaddend.and a pump acting on the
circuit, wherein the method comprises: withdrawing blood from the
.[.first blood vessel.]. .Iadd.vascular system .Iaddend.into the
withdrawal tube; moving blood through the circuit by action of the
pump; filtering the blood flowing from the withdrawal tube and into
an inlet of the filter, returning blood output through a filter
output from the filter through the return tube to the .[.second
blood vessel.]. .Iadd.vascular system.Iaddend., and abruptly
switching an input flow to the inlet from a first fluid to a second
fluid such that a transition fluid volume flowing from the blood
outlet of the filter does not exceed 15% of a total volume of a
blood path in the filter, where the transition fluid volume is a
fluid having more that a concentration of at least 10% of the
second fluid and less than 90% of the second fluid.
7. A method as in claim 6 wherein the second fluid is blood.
8. A method as in claim 6 wherein the first fluid is of a
conductivity substantially different than a conductivity of the
second fluid.
9. A method for moving blood through an extracorporeal blood
circuit having a withdrawal tube connected to a .[.first blood
vessel.]. .Iadd.vascular system .Iaddend.of a mammalian patient, a
filter and a return tube connected to .[.a second blood vessel.].
.Iadd.vascular system .Iaddend.and a pump acting on the circuit,
wherein the method comprises: withdrawing blood from the .[.first
blood vessel.]. .Iadd.vascular system .Iaddend.into the withdrawal
tube; moving blood through the circuit by action of the pump;
filtering the blood flowing from the withdrawal tube and into an
inlet of the filter, wherein the filter has a blood path, and said
blood path has a total volume of blood in the filter; returning
blood output through a blood output from the filter through the
return tube to the .[.second blood vessel.]. .Iadd.vascular
system.Iaddend., abruptly switching an input fluid to the inlet of
the filter from a first fluid to a second fluid; detecting a
transition volume of mixed fluid flowing through the blood outlet,
wherein said transition volume does not exceed 15% of the total
volume of the blood path and wherein the transition volume is a
fluid mixture having at least 10% and no more than 90% of the first
fluid.
10. A method as in claim 9 wherein the second fluid is blood.
11. A method as in claim 9 wherein the first fluid is of a
conductivity substantially different than a conductivity of the
second fluid.
12. A method for moving blood through an extracorporeal blood
circuit having a withdrawal tube connected to a .[.first blood
vessel.]. .Iadd.vascular system .Iaddend.of a mammalian patient, a
filter and a return tube connected to a .[.second blood vessel.].
.Iadd.vascular system .Iaddend.and a pump acting on the circuit,
wherein the method comprises: withdrawing blood from the .[.first
blood vessel.]. .Iadd.vascular system .Iaddend.into the withdrawal
tube; moving blood through the circuit by action of the pump;
filtering the blood flowing from the withdrawal tube and into an
inlet of the filter, wherein the filter has a blood path, and said
blood path has a total volume of blood in the filter; returning
blood output through a blood output from the filter through the
return tube to the .[.second blood vessel.]. .Iadd.vascular
system.Iaddend., abruptly switching an input fluid to the inlet of
the filter from a first fluid to a second fluid, and a transition
flow period is no greater than a period during which 15% of the
total volume of the blood path of the filter flows through the
filter output, where the transition flow period starts when a fluid
mixture at the filter output has at least 10% concentration of the
second fluid and no more than 90% concentration of the first
fluid.
13. A method as in claim 12 wherein the second fluid is blood.
14. A method as in claim 12 wherein the first fluid is of a
conductivity substantially different than a conductivity of the
second fluid.
Description
FIELD OF INVENTION
This invention relates to methods and apparatus for treatment of
congestive heart failure (CHF) by removal of excessive fluids, such
as water. In particular, the invention relates to an extracorporeal
circuit with minimized blood residence time.
BACKGROUND OF THE INVENTION
Congestive Heart Failure (CHF) is the only form of heart disease
still increasing in frequency. According to the American Heart
Association, CHF is the "Disease of the Next Millennium". CHF is a
condition that occurs when the heart becomes damaged and reduces
blood flow to the organs of the body. If blood flow decreases
sufficiently, kidney function becomes impaired and results in fluid
retention, abnormal hormone secretion and increased constriction of
blood vessels. The fluid overload and associated clinical symptoms
resulting from these physiologic changes are the predominant cause
for excessive hospital admissions, terrible quality of life and
overwhelming costs to the health care system due to CHF.
One possible method for removal of excessive fluid is mechanical
fluid removal employing an extracorporeal circuit with a
hemofilter. This method is especially useful if CHF is in its final
stage and drug treatment is no longer efficient. Extracorporeal
fluid removal is a common method used to treat acute renal disease.
Fluid removal treatments are usually combined with either
hemodialysis or hemofiltration to also remove solutes normally
excreted by the kidney. Currently the most advanced device for this
treatment is the PRISMA.TM. system from Gambro, which comprises an
air free extracorporeal circuit consisting of a blood tubing system
with integrated filter, a plurality of injection or sampling ports
and pressure measuring domes. Although attempts have been made to
construct a streamlined flow path, the blood flow passage in the
PRISMA.TM. system still had dead zones where fluid or blood
stagnates and resides for a prolonged time while blood is otherwise
flowing through the system. Zones of fluid stagnation are
especially found in the pressure measuring domes of the PRISMA.TM.
system.
Extracorporeal blood treatment usually requires anticoagulation of
blood. The reason for this is the activation of blood coagulation
by shear and by contact of blood to the surface of the
extracorporeal circuit. After activation of the clotting system, it
takes several minutes until a clot forms. If a fluid path contains
poorly perfused dead zones where blood stagnates for a longer
period, then blood clots will form at these sites and the clots
eventually will block the entire circuit. Other causes for the
enhanced formation of blood clots are blood-air interfaces and
obstructions in the fluid path, e.g., the commonly used "clot"
filters in drip chambers.
Typically, systemic anticoagulation is used such that
anticoagulants are not only in the blood in the extracorporeal
circuit, but also in the blood in the patient's circulation. This
use of anticoagulants increases the risk of bleeding by the patient
during and after treatment. Local anticoagulation or
anticoagulation free treatment has been reported, but is possible
only with additional equipment and monitoring.
The common blood accesses for acute treatment with extracorporeal
circuits are central venous catheters. The insertion and use of
central venous catheters are related to several risks that may
result in death or severe impairment. In particular, stenosis of
the central vessels after use of catheters, which has been well
documented, makes frequent insertion of central venous catheters
impossible.
The use of peripheral vein access has not been reported with
devices used for extracorporeal blood treatments, such as those
described above. Peripheral veins tend to collapse during the
withdrawal of blood by an extracorporeal blood circuit. The
collapse of a vein would cause the blood circuit to issue frequent
alarms that would require continuous observation by trained
personnel. Also, extracorporeal systems for the use with adults are
designed for blood flows not achievable with peripheral vein
access.
SUMMARY OF THE INVENTION
An extracorporeal circuit has been designed having an optimized
streamlined blood passage that is free of obstructions and dead
zones where blood can stagnate. The circuit components, e.g.,
pressure sensors, in the blood are free of obstructions and do not
cause blood to stagnate in the circuit or to undergo substantial
flow speed changes. The circuit can be used to treat CHF by
continuous filtration of blood using peripheral venous blood
access, and with minimal or no anticoagulation.
The extracorporeal circuit may be characterized by the normalized
residence volume method, derived from the residence time
measurements. The normalized volume parameter is used to
characterize the flow characteristics of an extracorporeal circuit
independently of the total fluid volume capacity of that circuit.
When using the 10% to 90% rise of the output function in the
normalized volume diagram, the optimized extracorporeal circuit
shows superior performance. The present extracorporeal circuit may
be applied to remove excess fluid from a CHF patient allow
treatment for up to eight hours using no or minimal
anticoagulation.
A practical means to overcome the barriers for the effective
treatment of CHF by mechanical fluid removal is described in U.S.
application Ser. No. 09/618,759, filed Jul. 18, 2000, entitled
"Method and Apparatus for Peripheral Vein Fluid Removal in Heart
Failure", U.S. application Ser. No. 09/660,195 filed Sep. 12, 2000,
entitled "Blood Pump Having Disposable Blood Passage Cartridge With
Integrated Pressure Sensors," both of which patent applications are
incorporated by reference.
SUMMARY OF THE DRAWINGS
A preferred embodiment of the invention, the setup for the
characterization of hydraulic components by the normalized
residence volume method as well as the results of such
characterization for an extracorporeal system as described by the
invention and for the extracorporeal circuit of the PRISMA device
are illustrated in the attached drawings.
FIGS. 1A and 1B illustrate the extracorporeal circuit of an
embodiment of the present invention.
FIG. 2 illustrates the flow diagram employed for the measurement of
the residence time function.
FIG. 3 is a graph showing the result of a residence time
measurement with conductivity sensors.
FIG. 4 is a graph showing the conversion of the graph 3 data from
the conductivity versus time domain into the concentration versus
volume domain.
FIG. 5 is a graph derived from the graph of FIG. 4 by the
normalization of the concentration axis with the maximum
concentration measured that is the concentration in carboy 302.
FIG. 6 is a graph derived from the graph of FIG. 5 by the
normalization of the volume axis with the volume of the test object
calculated from the graph of FIG. 5.
FIG. 7 is a graph derived from the graph of FIG. 6 by eliminating
the effect of the time course of the input
conductivity/concentration function. The input fraction is a step
function at zero normalized volume. The test object characterized
by this figure is the extracorporeal circuit described by this
invention.
FIG. 8 is a graph similar to the graph in FIG. 7. The test object
characterized by this graph is the extracorporeal circuit of the
PRISMA.TM.. FIG. 8 shows the normalized residence volume
calculation derived from a residence time measurement for the
extracorporeal circuit of the PRISMA.TM. device.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1A illustrates the treatment of a fluid overloaded patient
with a blood treatment system 100. Patient 101 can undergo
treatment while in bed or sitting in a chair. Patient can be
conscious or asleep. To initiate treatment two relatively standard
18G needles 102 and 103 are introduced into suitable peripheral
veins (on the same or different arms) for the withdrawal and return
of the blood. This procedure is no different from blood draw or IV
therapy. Needles and attached to tubing 104 and 105 and secured to
skin with attachments 106 and 107. The blood circuit that consists
of the blood filter 108, tubes, pressure sensors 109, 110 and 111
and the ultrafiltrate collection bag 112. The circuit is supplied
in one sterile package and is never reused. It is easy to mount on
the pump 113 and can be primed and prepared ready for operation
within minutes by one person.
During operation, the present invention requires minimal
intervention from user. User sets the maximum rate at which fluid
is to be removed from the patient using the control panel 114.
Ultrafiltrate is collected into a graduated one-liter collection
bag 112. When the bag is full, ultrafiltration stops until the bag
is emptied. Information to assist the user in priming, setup and
operation is displayed on the LCD display 115.
FIG. 1B illustrates the fluid path of an embodiment of the present
invention. The embodiment consists of a disposable extracorporeal
circuit for a treatment device comprising a peristaltic blood pump,
protective systems a display and a microprocessor control unit.
Blood is withdrawn from the patient through the withdrawal needle
assembly 201. Blood flow is controlled by a roller pump 204. The
withdrawal needle assembly is connected to the blood tubing 220 by
a pair of matching connectors 230, 232. Connector 230 is part of
the withdrawal needle assembly and connector 232 is a part of the
blood tubing 220. These connectors can either be an integral part
of the connected blood tubing or separate parts glued, welded or
mechanical fixated with the tubing.
Blood tubing 220 that is typically 2 m (meters) long is connected
to a disposable pressure sensor 203. A suitable pressure sensor is
disclosed in U.S. application Ser. No. 09/660,195 filed Sep. 12,
2000. The opposite end of the pressure sensor 203 is further
connected to blood pump tubing 221 that is connected to the
disposable pressure sensor 205. Pressure sensor 205 is connected to
blood tubing 222 leading to and permanently connected to the inlet
of the blood side of the hemofilter 207.
The outlet of the blood side of the hemofilter is connected to
blood tubing 223 that is connected to one side of a disposable
pressure sensor 209. The other side of the disposable pressure 209
is connected to the blood tubing 224 that ends with the connector
233. Connector 231 is part of the blood return needle assembly. A
filtrate line 212 is connected to the filtrate outlet 211 of the
hemofilter 207 on one side and to the filtrate collection bag 215
on the other side. An ultrasonic air detector 206 with sensors in
contact with the outer surface of the blood tubing is included, but
does not interrupt the smooth flow path in the circuit.
The blood passage in the extracorporeal circuit is an obstruction
free smooth blood flow path throughout the circuit. There are no
dead zones and no blood--air interfaces in the blood passage. The
catheter needle assemblies 201, 210 are preferably designed such
that the interface between the needle with a typical inner diameter
of 1 mm is connected to the blood tubing with a typical inner
diameter of 3 mm by a cone with a smooth blood passage having a
cone angle of 100. Matching connectors 230, 232 and 231, 233
respectively are preferably designed such that the continuous blood
flow path with a typical inner diameter of 3 mm is not interrupted.
For convenience and for compatibility with existing systems,
Luer-lock connectors could be used at this point although these
connectors are not obstruction free.
Disposable pressure transducers are positioned in the flow path to
be obstruction free and have essentially the same diameter as the
blood tubing. To avoid kinking of the blood tubing leading from and
to the patient, blood tubing 220 and 209 is preferably made from a
harder tubing material than is the blood pump tubing 221. Blood
tubing 222 and 223 can be made from either the harder or the softer
variety of medical tubing material that is suitable for use in an
extracorporeal blood circuit.
The filter 207 provides a smooth flow path for the blood through
the filter passages. A membrane surface area of 0.1 m.sup.2 may be
used to provide sufficient fluid removal during operation of the
extracorporeal circuit. A smooth flow path is achieved by making
this filter long and thin, rather than short and thick as in the
PRISMA design. The filter may have an effective length of 22.5 cm
and a fiber bundle diameter of 1.2 cm.
A parameter for the characterization of the flow characteristic of
an extracorporeal circuit or of its components is the residence
time. This method of characterizing as extracorporeal has been
described, e.g., by Cooney D O, Infantolino W, Kane R. in
"Comparative Studies of Hemoperfusion Devices". For a passive
extracorporeal device, the total residence time of the blood in the
device should be minimized to reduce the potential for
clotting.
Pressure drop and flow uniformity tests may also be used to
characterize the blood flow through an extracorporeal circuit,
especially those that filter fluids and/or solutes from blood. See
Biomater Med Devices Artif Organs 1979;7:443-54. In this method the
device to be investigated is sequentially perfused with two fluids
with different properties. A step function is produced at the input
when the fluids are switched and the resulting function at the
output is recorded as a function of time. For an ideal flow, the
output function would be a step function as well. In an ideal
filter, all portions of the filter membrane are being perfused
uniformly. In an ideal filter, the blood is thickened (due to fluid
being removed by the filter) uniformly as it passes through the
capillaries of the filter. In a non-ideal filter, the slope of the
step-function deviates from the ideal slope because blood moves
faster in some capillaries than in others, and/or the blood is
thickened less in some capillaries than others. The blood becomes
more concentrated and has a higher viscosity in those filter
capillaries with slow perfusion, than in other capillaries that
have at least an average flow rate of blood. These non-uniformities
in the blood flowing through a filter can be indicated by the slope
of the step-function curve. Deviation from the ideal slope
indicates non-uniform thickening of the blood and non-uniform blood
viscosity. The deviation of the output function from a step
function can be used as a measure for the quality of the flow
design.
FIG. 2 shows a flow diagram of a test setup that can be employed to
determine the characterization of extracorporeal circuits or its
elements. Bag 301 is a carboy containing demineralized water with a
conductivity of typically 5 .mu.S/cm (microSiemens per cm).
Container 302 contains a salt solution (sodium chloride solution)
with a typical conductivity of 30 mS/cm. The container 301 is
connected through a conduit 303 with the valve 305. The container
302 is connected to the valve 306 through conduit 304. Valves 305
and 306 are connected with a T to conduit 308 leading to a gear
pump 310.
A gear pump 310 is connected to a first temperature compensated
conductivity sensor 314 by conduit 312. A test object 330, e.g., a
filter or blood path in an extracorporeal circuit, is connected to
the first conductivity sensor 314 on one side and the second
temperature compensated conductivity sensor 316 on the other side.
The outlet of the second conductivity sensor 316 is connected to a
mass flow meter 320 through conduit 318, and from the mass flow
meter 320 a conduit 326 leads to drain. The pressure drop of the
mass flow meter 320 is measured by pressure sensor 321 connected to
inlet and outlet of the mass flow meter 320 by lines 322 and 324
respectively. If the test object is a filter or if a filter is part
of the test object as shown in FIG. 2, the filtrate side is
connected to an air pump 340 through a conduit 342, from conduit
324 a pressure measuring line 344 leads to a pressure sensor
346.
An air pump 340 allows removal of fluid from the filtrate side of
the filter 330. Fluid in the blood passage side of the filter is
pushed through the membrane if the air pressure is higher than the
maximum fluid pressure on the fluid (blood) side of the membrane.
Because the membrane is hydrophilic, air cannot pass the membrane
as gas. Fluid, however, remains in the pores of the membrane. The
purpose of this fluid removal from the filtrate side is to avoid
any influence from the filtrate space. During the measurement,
sodium and chloride ions can diffuse freely through the membrane.
With a fluid filled filtrate space the measurement would include
the filtrate side that would lead to wrong conclusions about the
fluid distribution on the "blood" side.
Conductivity sensors 314, 316 and optionally pressure sensors 321
and 346 are connected to a computer for continuous recording of the
signals as function of time. To record the residence time, the
function valve 305 is opened and pump 310 operated at a prescribed
speed, e.g., 100 mL/min. A baseline value of .about.5 .mu.S/cm is
established, based on readings from conductivity sensors 314 and
316. Next, a continuous recording of the signals from conductivity
sensors 314 and 316 is started. Also, valve 305 is closed and valve
306 is opened. Fluid with a conductivity of .about.30 mS/cm flows
through the pump 310 to the conductivity sensor 314 causing an
increase of the signal as shown by signal tracing 404 in the graph
401 of FIG. 3. The conductivity sensor 316 at the outlet records a
similar but less steep signal after some delay in time depending on
the filling volume of the test object 330 and the flow speed of the
pump 310. The signal tracing of the conductivity sensor 316 is
shown as 406 in FIG. 3. In case the test object contains a filter
air pump 340 is employed to pressurize the filtrate side with air
at a pressure exceeding the maximum fluid pressure on the blood
side of the filter prior to the start of the measurement. This
forces all fluid from the filtrate side to the blood side limiting
the fluid volume to the fluid volume of the blood path and the
fluid volume trapped in the membrane pores.
FIG. 3 includes a diagram 401 that is mathematically converted into
the diagram 411 shown by FIG. 4 by the following steps:
Conductivity 402 is converted into concentration 412 by employing a
five order power function derived from tables published in the CRC
handbook of chemistry and physics 65.sup.th edition for sodium
chloride. The time axis 403 is converted into a volume axis 413 by
multiplying the time increments between the discrete points of
measurement with the corresponding flow values and summation. The
results are the input sensor function 414 and the output sensor
function 416 in the concentration versus volume domain.
FIG. 5 shows a diagram 421 mathematically derived from the graph
411 of FIG. 4 by normalizing the concentration axis 412 with the
maximum concentration measured. This concentration is equal to the
concentration in carboy 302 within the errors of measurement. The
result is a graph in the normalized concentration 422 versus volume
423 domain with 424 being the input function and 426 being the
output function.
FIG. 6 shows a diagram mathematically derived from the graph 421 of
FIG. 5 by normalizing the volume scale 423 with the calculated
volume of the test object. The volume of the test object is
calculated from the graph 421 of FIG. 5 by subtracting the integral
under tracing 424 from the integral under tracing 426 over the
volume interval shown in the graph of FIG. 5. The result is the
graph 431 in the normalized concentration 432 versus normalized
volume 433 domain with 434 being the input function and 436 being
the output function.
FIG. 7 shows the result of the final step of the derivation in
graph 440. The delay time and non-ideal step function of the input
signal 434 is removed by subtracting the normalized volume between
start and tracing 434 for discrete values of the normalized
concentration from the corresponding normalized volume of the
tracing 436 by employing a lookup table. The lookup table is
constructed in 1% intervals of the normalized concentration. This
procedure results in the tracing 445 of graph 441 showing the
output function for an extracorporeal circuit as described by the
invention for an ideal step function at normalized volume 0 at the
input.
FIG. 8 shows the result of the measurement and derivation
equivalent to the steps described for FIGS. 3 to 7 but for the
extracorporeal circuit of the PRISMA. The graph 451 (where the
normalized concentration 452 is the vertical axis and the
normalized volume 453 is the horizontal axis) shows the tracing 454
in the normalized volume 453 versus normalized concentration 452
domain. The described data has been recorded employing the program
LabView (National Instruments). The recorded data has been imported
into SigmaPlot 5.0 (SPSS, Inc.) and the mathematical conversions
described above were done with the transform program written for
SigmaPlot shown in the appendix.
Comparing graphs 441 and 451 allow for a comparison of
extracorporeal circuits independent of the absolute volume and the
blood flow. For the quantitation of the 10% to 90% interval is used
as shown in the following table:
Data from FIG. 7 Data from FIG. 8 Relative volume (Invention)
(PRISMA) 10% 0.87 0.78 50% 1.01 1.00 90% 1.02 1.22 90%-10% 0.15
0.44
The 10% to 90% rise time is more than twice as large for the PRISMA
compared to the optimized extracorporeal circuit according to the
invention. The volume calculated for the two systems was 37.09 mL
for the system according to the invention and 105.38 for the
PRISMA. As mentioned above, this volume includes the fluid trapped
in the porous structure of the microporous fibers of the filters.
This volume is larger than the volume measured by blowing out fluid
with air. Normalization of the data as described above nevertheless
allows the direct comparison of the flow properties independent of
the absolute size and volume of the system.
From graphs 441 (FIG. 7) or 451 (FIG. 8) and the volumes the
residence time can easily be calculated. For the extracorporeal
circuit according to the disclosed embodiment of the invention the
volume is .about.37 mL. r 128 sec a factor of 3.5 large. For a flow
of 60 mL/min typical for peripheral flow, the resulting residence
time for the 90% concentration point (1.12) is 1.12*37/60=0.69 min
or .about.41 sec. For the same flow the 90% residence time for the
PRISMA is 1.22*105/60=2.13 min or 128 sec a factor of 3.5
larger.
In an exemplary embodiment, FIGS. 1A and 1B illustrate the
operation and fluid path of the blood treatment system 100 of a
microprocessor controlled console and a disposable kit. Disposable
kit is bonded (with the exception of needles) and is supplied
sterile.
Blood is withdrawn from the patient through the 18 Gage or similar
withdrawal needle 102. The needle 102 is inserted into a suitable
peripheral vein in the patient's arm. Blood flow is controlled by
the roller pump 113. Before entering the pump blood passes through
approximately two meters of plastic tubing 104. Tubing is made out
of medical PVC of the kind used for IV lines and has internal
diameter (ID) of 3 mm. Pump 113 is rotated by a DC motor under
microprocessor control. The pump segment (compressed by the
rollers) of the tubing has the same ID as the rest of the blood
circuit. The system is designed so that approximately 1 mL of blood
is pumped per each full rotation of the pump, e.g. pump speed of 60
RPM corresponds to 60 mL/min.
The disposable withdrawal pressure sensor 109 is a part of the
blood circuit. Pressure sensor 109 is a flow-through type commonly
used for blood pressure measurement. There are no bubble trap or
separation diaphragms in the sensor design, which reduce the
accuracy. Pressure sensor is designed to measure negative (suction)
pressure down to -400 mmHg. All pressure measurements in the fluid
extraction system are referenced to atmospheric. The withdrawal
pressure signal is used by the microprocessor control system to
maintain the blood flow from the vein. Typically, a peripheral vein
can continuously supply 60-100 mL/min of blood. This assumption is
supported by the clinical experience with plasma apheresis
machines.
In some cases, blood flow can be temporarily impeded by the
collapse of the vein caused by the patient motion. In other cases
the vein of the patient may not be sufficient to supply the maximum
desired flow of 60 mL/min. The software in the present invention
microprocessor is designed to control the withdrawal of blood to
prevent or recover from the collapse of the vein and reestablish
the blood flow based on the signal from the withdrawal pressure
sensor.
The same pressure signal from the sensor 109 is used to detect the
disconnect of the withdrawal bloodline 104 from the needle 102.
This condition is detected by the abrupt decrease of the withdrawal
pressure generated by the pump. The resistance of the 18 Gage
needle, which is 4 cm long with an approximately 0.8 mm ID at a
flow rate corresponding to a 60 mmHg, pressure drop is on the order
of the 100 mmHg. The resistance of 2 meters of blood tubing with a
3.5 mm ID at the same flow rate is on the order of 20 mmHg. This
enables automatic reliable detection of the line disconnection. The
occlusion of the withdrawal bloodline is detected in the similar
fashion. The occlusion can be caused by the collapse of the vein or
by the kinked blood tube. Occlusion results in a rapid decrease
(more negative) of the pump suction pressure that is detected by
the microprocessor. In response to this condition, the
microprocessor stops the pump and alarms the user.
A double roller pump 113 may be used to pump blood. As the pump 113
rotates, rollers compress the segment of PVC tubing and generate
flow. Pump is adjusted to be fully occlusive until the pressure
limit is reached. The rollers are spring loaded to limit the
maximum positive and negative pressure generated by pump head. This
feature is not normally used to limit pressure in the circuit and
is only included as a secondary safety precaution.
A direct drive stepper motor rotates the rollers, and the speed of
the motor is determined by the controller microprocessor. The RPM
of the pump 113 is used as a feedback signal by the controller to
determine the blood flow. Normal operational blood flow in the
present invention is between 40 and 60 mL/min. This minimum rate of
blood flow is needed to generate Trans Membrane Pressure (TMP)
needed for ultrafiltration and to prevent stagnation and clotting
of blood in filter 207.
Pump pressure sensor 205 is incorporated into the post-pump segment
of the blood tubing connecting pump 204 to the blood inlet line 104
coupled to the filter 207. Like other pressure sensors in the
present invention, it is a flow through device that does not create
a blood-air interface and does not disturb the blood flow. The pump
pressure signal is used by the microprocessor to determine TMP used
to calculate the ultrafiltration rate. It is also used to detect
abnormal conditions in the circuit such as occlusion or
unacceptable clotting of the filter and disconnection of the blood
line between the pump 204 and the filter 207.
On its way from the pump 204 to the filter 207, blood passes
through the air detector 206. The air detector 206 is of ultrasonic
type and can detect air in amounts exceeding approximately 50
microliters. The detector 206 uses technology based on the
difference of the speed of sound in liquid and in gaseous media. If
an air bubble is detected, the pump 204 is stopped almost
instantaneously (within few milliseconds). The bubble detector
output signal is hard wired into the motor control logic and the
pump 204 is stopped independently of the microprocessor control if
a bubble is detected.
Air can only enter the present invention circuit from the pre-pump
(negative pressure) segment of the blood circuit 202. All the rest
of the circuit downstream of the pump 204 is always pressurized.
For this reason, the bubble detector is placed before the
filter.
Blood pressure in the post pump, pre-filter segment of the circuit
is determined by the patient's venous pressure, the resistance to
flow generated by the return needle 210, resistance of hollow
fibers in the filter assembly 207 and the resistance of
interconnecting tubing 224. At blood flows of 40 to 60 mL/min the
pump pressure is in the 300 to 500 mmHg range depending on the
blood flow, condition of the filter, blood viscosity and the
condition in the patient's vein.
The filter 207 is a main component of the present invention. Inside
the filter 207 the ultrafiltration occurs. Whole blood enters the
bundle of hollow fibers from the connector on the top of the cap of
the filter canister. There are approximately 700 hollow fibers in
the bundle, and each fiber is a filter. Blood flows through a
channel approximately 0.2 mm in diameter in each fiber. The walls
of the channel are made of a porous material. The pores are
permeable to water and small solutes but impermeable to red blood
cells, proteins and other blood components that are larger than
50,000-60,000 Daltons. Blood flow in fibers is tangential to the
surface of the filter membrane. The shear rate resulting from the
blood velocity is high enough such that the pores in the membrane
are protected from fouling by particles, allowing the filtrate to
permeate the fiber wall. Filtrate (ultrafiltrate) leaves the fiber
bundle and is collected in space between the inner wall of the
canister and outer walls of the fibers.
The geometry of the filter is optimized to prevent clotting and
fouling of the membrane. The active area of the filter membrane is
approximately 0.1 m.sup.2. The permeability KUF of the membrane is
30 to 33 mL/hour/m.sup.2 /mmHg. These parameters allow the desired
ultrafiltration rate of approximately 500 mL/min at the TMP of 150
to 250 mmHg that is generated by the resistance to flow. The
effective filter length is 22.5 cm and the diameter of the filter
fiber bundle is 1.2 cm. This results in the shear rate of 1,200 to
1,800 sec.sup.-1 at the blood flow rate of 40 to 60 mL/min.
The TMP is the present invention is defined predominantly by the
resistance of the return needle 210 and the resistance of the
filter bundle inside the filter 207. The properties of the filter
207 and the needle 210 are selected to assure the desired TMP of
150 to 250 mmHg at blood flow of 40-60 mL/min where blood has
hematocrit of 35 to 50% at 37.degree. C.
The quantitative clinical goal was formulated for the apparatus
being developed in terms of fluid removal. Applicants' research
established that for the fluid removal device to be clinically
useful it should remove water at the rate of 100 to 500 mL/hour.
Lower rates of fluid removal are only required in hemodynamically
unstable patients that are treated in the ICU and are not the
targeted patient population. Fluid removal rates higher than 500
mL/hour (theoretically as high as 1,000 mL/hour) may be practical
in some patients but are expected to be too high risk in the
majority. It is only advisable to remove water from blood at the
rate at which fluid can be recruited from tissue. Higher rates may
lead to hypotension.
Blood hematocrit (volume fraction of red blood cells) in CHF
patients is expected to be in the range of 30 to 40% of the total
blood volume. It is possible to condense the filtered blood to the
hematocrit range of 50% to 60% and still be able to return blood
through a standard needle. Therefore, extraction of approximately
20% to 30% of volume from blood as water is possible. Assuming this
extraction rate, the amount of blood removed from a peripheral vein
is less than 2% of the total cardiac output. In addition, at this
extraction rate, the potential ultrafiltrate flow may be as much as
1 L/hour. Alternatively, a lower extraction rate, e.g., 0.1
liter/hour, may be selected. At the blood flow rate of 60 mL/min
applicants successfully extracted up to 12 mL/min (or 720 mL/hour)
of ultrafiltrate in the laboratory using the filter described in
this invention. Therefore, it is possible to consistently extract
the required 500 mL/hour of water from the blood flow withdrawn and
returned into a peripheral vein.
Applicants established that the much higher blood flows that are
used in adults by all existing renal replacement therapy machines
and particularly by machines for acute CVVH treatment of CHF
patients are necessitated by the filter designed to remove solute
and more specifically by the relatively high surface area of the
filter. This large surface area is needed for solute removal. If
the goal of treatment was to remove water only, high blood flow
will still be needed to reduce the time of exposure of blood to the
synthetic membrane and to prevent clotting.
Another important consideration that forces the designers of CVVH
machines to use high blood flow and consequentially the central
venous access is the need to maintain substantially high wall shear
rate of blood flowing inside the filter capillaries (hollow
fibers). Flow of blood inside a fiber is laminar. Shear rate at the
wall can be calculated using the simple Equation 1:
Q is blood volumetric mass flow rate and "d" is the internal
diameter of the capillary.
The ultrafiltration rate is influenced by membrane fouling which is
an equilibrium of wall shear rate and ultrafiltration rate per unit
surface area. With the increasing surface area the wall shear rate
will decrease unless the blood flow is increased to compensate. It
becomes apparent from literature that the wall shear rate should be
1,000 sec.sup.-1 or higher to achieve sufficient filtrate flux at
high hematocrit. It is also known from literature that the high
shear rate in excess of 2,500 sec.sup.-1 is undesirable since it
can cause hemolysis and damage to red blood cells. At the same
time, it is apparent that the surface area and size of the filter
should be minimized. Biocompatibility is inversely proportional to
the surface area exposed to blood. The likelihood of clotting
increases with residence time proportional to the filling volume.
Also, cost of a smaller filter is lower.
To minimize the cost of the filter, the use of
commercially-available fibers with optimized biocompatibility and
consistent filtration properties is desired. Suitable filter fiber
is available, for example, from Minntech Inc. in Minnesota. Each
fiber has internal diameter of 0.2 mm. Pores in the fiber walls are
optimized to retain solutes of greater than 50,000 Daltons. The
permeability of this fiber is 33 mL/hour/m.sup.2 /mmHg. If a
membrane with total surface area of only 0.1 m.sup.2 is constructed
from this fiber, the resulting theoretical ultrafiltration rate
will be 330 mL/hour at TMP of 100 mmHg and 660 mL/hour at TMP of
200 mmHg. These numbers are consistent with the objective of the
design.
To calculate the KUF of the filter, the permeability of fiber is
multiplied by the surface area of the membrane. Therefore KUF
filter=33.times.0.1=3.3 mL/hour/mmHg.
It is known from literature that the blood flow is not equal
between the fibers in the filter bundle. Blood flow and
consequentially the wall shear rate tends to be lower in the fibers
closer to the periphery and higher in the central ones.
Accordingly, blood residence time is longer in peripheral fibers.
It is known from the practice of dialysis that the peripheral
fibers tend to clot first.
To reduce the extracorporeal blood volume and the time that blood
resides outside of the body it is desired to use blood lines that
have internal diameter as small as practical without creating
excessive resistance to flow. For our application, an internal
diameter of around 3.0 mm is well suited. When blood exits the
tubing and flows into the fiber bundle the diameter of the channel
through which blood flows increases substantially. This creates
turbulence and stagnant zones at the entrance into the bundle.
These factors increase the probability of lotting.
It is therefore beneficial to design a filter that has a minimal
but still practical diameter of the fiber bundle. This is achieved
by reducing the number of fibers and increasing the length of the
bundle. This approach is limited by two constraints. Resistance of
the bundle to flow increases in proportion to the bundle length.
Also, long filters substantially in access of 20-25 cm are
difficult to manufacture and cumbersome to use.
Applicants chose to use a maximum length of the filter that is
practical from the manufacturing standpoint. The resulting working
length of the bundle is 22 cm (centimeters). To ensure the required
surface area of the membrane, approximately 620 to 720 fibers of
this length are need to be bundled in parallel. Assuming the fiber
density of approximately 630 capillaries per cm.sup.2 the diameter
of the bundle is 1.2 cm. Such filter can be easily manufactured
using existing methods and equipment. At the blood flow of 40 to 60
mL/min and blood hematocrit of approximately 40%, the resistance of
this filter to blood flow is on the order of 100 to 200 mmHg. This
pressure level is acceptable for the design of a circuit with a
standard peristaltic pump and an 18 to 20 Gage (internal diameter
of 0.8-1.0 mm) return needle.
Applicants overcame the perceived impossibility of clinical
peripheral vein ultrafiltration that limited the use of mechanical
fluid removal in CHF patients outside of the ICU environment.
Applicants did this by drastically reducing the filter membrane
surface area compared to common dialysis or CVVH filters to
maintain high shear rate and low blood residence time.
Specifically, a filter with the membrane surface of less than 0.2
m.sup.2 and preferably 0.05 to 0.15 m.sup.2 can remove the desired
100 to 700 mL/hour of water from the extracorporeal blood flow of
less than 100 mL/min or more specifically of 40 to 60 mL/min with
an average blood cell residence time outside the body of less than
2 minutes, and may be less than 1 minute. Although the filter is
made of high permeability fiber due to the small surface area the
KUF of the filter is less than 5 mL/hour/mmHg or preferably 2 to 4
mL/hour/mmHg. Typical filters used in adult patients have KUF of 30
to 50 mL/hour/mmHg. The much lower KUF gives the present invention
device design an advantage of inherently safer operation. Food and
Drug Administration (FDA) classifies all filters with KUF greater
than 8 mL/hour/mmHg as "high permeability dialyzers". According to
current FDA safety standards these devices have to be labeled for
use only with ultrafiltration controllers that are independent of
TMP based ultrafiltrate rate calculation. A small error of TMP
measurement or a deviation of membrane permeability from the
specification can result in substantial over or under filtration.
The use of a low KUF filter enables, if desired, the present
invention to avoid using a cumbersome and expensive ultrafiltration
controller that typically involves a scale balance and an
ultrafiltration pump.
A filter that is relatively long and narrow may optimize the blood
flow inside the filter, maintain the desired wall shear rate and
minimize membrane fouling and filter clotting. A filter with a
fiber bundle that is approximately 20 cm long and 1.5 cm in
diameter is particularly well suited for the application and is
practical for manufacturing.
Filters for ultrafiltration of blood with small surface area of
less than 0.2 m.sup.2 are known. Example of such filter is
Miniflow.TM. 10 from Hospal. Miniflow has surface area of 0.042
m.sup.2 and KUF of 0.87 mL/hour/mmHg. All such filters without
exception are used for hemofiltration therapy in neonatal patients
and infants. The clinically used amount of blood flow through these
filters is within the range that we targeted or 10 to 60 mL/min.
Nevertheless, this amount of flow--if expressed as a fraction of
the cardiac output for infants--is the same as the blood flow used
in adult hemofiltration. Consequently, these infant filters are
used with the central and not peripheral venous access.
To minimize clotting and fouling of the membrane it is desired to
maintain substantially high blood flow through the filter even if
the desired ultrafiltration rate is low. In traditional machines
for renal replacement therapy it is typically achieved by reducing
the TMP. Flow of ultrafiltrate is actively controlled by the roller
pump in the ultrafiltrate removal line between the filter and the
ultrafiltrate collection bag. When the pump is slowed down
ultrafiltrate flow is retarded, pressure gradient across the
membrane is reduced and ultrafiltration is slowed to the desired
level. Alternatively, if the pump RPM is increased, the flow of
ultrafiltrate is accelerated. Negative pressure can be developed by
the pump to actively suck the ultrafiltrate across the membrane.
For reasons of safety and simplicity, it was desired to have a
machine that can reduce the ultrafiltration rate at the user
command without an ultrafiltrate pump. For our preferred embodiment
we used the duty cycle controlled ultrafiltration. A simple pinch
valve is placed in the ultrafiltrate line. When the valve is
closed, pressure across the membrane quickly equilibrates, and no
ultrafiltration occurs. When the valve is opened, ultrafiltration
occurs at the rate determined by the TMP and the KUF of the
membrane. This rate can be calculated by the controller. Valve is
cycled approximately every minute. The fraction of the cycle during
which the valve remains opened determines the average rate at which
fluid is removed.
Since the system embodying the present invention does not employ an
ultrafiltrate pump that can create sub-atmospheric pressure on the
ultrafiltrate side of the membrane, a simple and reliable method of
controlling the total amount of fluid removed in one treatment
iteration is possible. The ultrafiltrate is collected into a sealed
bag that is connected by a tube to the ultrafiltrate collection
chamber of the filter casing. During the treatment the bag is
gradually filled up with fluid. It is desired to have a bag that
has a relatively small volume and specifically volume of 0.5 to 1.5
liters. When the bag is full and its walls are fully distended, the
pressure in the bag will start to rise until it is equal to the
average pressure of blood inside the filter capillaries. Although
some circulation of fluid is still possible in and out of fibers
the net loss of fluid is zero. Until a nurse empties the bag, no
removal of fluid is possible.
Pressure sensors are used in the blood circuit to alarm the
disconnection and occlusion of blood lines. The pre- and
post-filter pressure signals are also used to calculate TMP and
ultrafiltration rate. Two types of pressure measurement devices are
typically used in machines for renal replacement therapy.
Machines such as BP11 from Baxter use disposable air filled
separation or drip chambers that are connected to permanently
installed pressure sensors that are the part of the machine. This
design introduces potentially hazardous air into the circuit. Air
can cause embolism and accelerated clotting. Also, this type of
measurement is affected by gravity.
Machines such as Prisma from Gambro use flexible silicone
diaphragms to transmit blood pressure to sensors once again mounted
on the apparatus itself. This method overcomes the deficiencies of
drip chambers. Separation diaphragms are subject to error when the
travel of a diaphragm is restricted. This necessitated a
complicated diaphragm positioning system if the system is used for
a substantial duration of time. Also, a substantial area of a
diaphragm (typically 2-3 cm in diameter) is required to ensure
reliable transmission of pressure. At a low blood flow it is likely
that a stagnant zone will form inside the diaphragm chamber that
will eventually lead to clotting.
The present invention utilizes flow through disposable pressure
sensors. This sensors are a part of the disposable blood circuit.
They do not disturb the laminar blood flow inside the blood line
since the internal diameter of the sensor element is the same as of
the blood tubing (3 mm). The sensing element is less than 2 mm in
diameter and is embedded flush in the wall of the sensor housing.
The housing is bonded flush with the internal wall of the blood
line tube to form a continuous channel. Although similar disposable
blood pressure sensors (such as ones made by Merit Medical of Utah)
are used widely for invasive blood pressure measurement this design
has never been previously used in an apparatus for fluid
removal.
The present invention is intended to provide safe, controlled fluid
removal in patients with fluid overload for up to 8 to 24 hours.
These patients all suffer from decompensated chronic CHF and are
admitted or on the verge of admission to a hospital. Regardless of
the exact nature of their disease theses patients present at the
hospital with a number of symptoms that manifest fluid overload and
result in difficulty of breathing and pulmonary edema require
immediate treatment. These patients are typically 5 to 20 kg over
their dry weight and, if treated with diuretics, can tolerate fluid
removal rates of up to 0.5 L/hour for until symptoms are
relieved.
The intended use of the present invention is to assist in the
initial removal of 2 to 4 liters of fluid that should result in the
relief of symptoms and much improved responsiveness to medication.
The present invention can be performed by a physician or nurse
trained in the use of the device. Treatment can be performed in the
setting of a monitored hospital floor, outpatient clinic or
Emergency Room. The present invention is prescribed by a
cardiologist. The main idea behind the present invention is to
remove excess water from the patient's blood using a well-accepted
ultrafiltration technique at the same rate at which the surplus
fluid can be recruited from the tissue.
The intended use of the present invention is slow continuous
removal of fluid by ultrafiltration of blood. Excessive removal of
fluid can lead to hypotension and serious risks to health. If the
fluid is removed from vascular space too fast, it is equally
dangerous and can lead to hypotension. The principle method of
treatment with the present invention is to remove fluid at a rate
that allows vascular blood volume to be replenished with water that
has accumulated in the interstitial space as a result of the
patient's condition. Patients that should be treated by the present
invention are typically 10 to 20 kg over their dry weight due to
this excess water.
Potential excessive water loss or gain is a recognized hazard
associated with RRT. Modern CRRT machines used in SCUF or CVVH mode
can potentially remove and replace tens of liters of fluid from
patient in a space of several hours. As a result, even a small
error in fluid balance can result in severe risks to a patient. To
prevent this from happening accurate ultrafiltration controllers
are used that are based on continuous measurement of the weight of
extracted and infused fluids. Ultrafiltration rate is adjusted
accordingly by controlling the speed of an ultrafiltration pump
that can apply negative or positive pressure to the ultrafiltration
side of the filter membrane.
In the case of the present invention, fluid gain is not a risk. The
present invention is designed for fluid removal only. To prevent
excessive removal of fluid from the patient, the present invention
relies on a number of inherently safe features and materials
properties rather than the ultrafiltrate pump controller.
Ultrafiltrate rate (UF) is a function of TMP, Permeability of the
membrane and the membrane surface. Membrane surface is a constant
and in the case of the present invention is 0.1 m.sup.2.
Permeability of a filter membrane, is expressed as ml of
ultrafiltrate per hour per unit of the membrane surface area.
Permeability of the present invention filter membrane is 30 to 33
mL/hour/m.sup.2 /mmHg. The resulting KUF of the filter is 3
mL/hr/mmHg. KUF of a filter can decrease during the operation owing
to the fouling of the membrane but can not increase unless the
membrane is broken. Equation 2 takes into account the affects of
oncotic pressure on the ultrafiltration rate. The KUF of the
membrane is determined using animal blood at standard conditions
such as hematocrit of 27%, temperature of 37.degree. C. and
appropriate concentration of protein and electrolytes. Although
these conditions do not perfectly reflect clinical conditions in
all patients it is a useful engineering approximation.
In the present invention, TMP is a function of blood flow and the
resistance of circuit elements downstream, including the filter.
TPM can be calculated in real time by the microprocessor using
equation 3 from the readings of pressure transducers.
Where Pp is the pump (pre filter) pressure, Pr is the return (post
filter) pressure and Pg is a pressure generated by the weight of
the column of ultrafiltrate. Given the unadjustable design of the
ultrafiltrate circuit, Pg is a constant. For the 20 cm level
difference between the filter and the level of fluid in the bag Pg
is 17 mmHg.
Substitution of the calculated TMP into Equation 2 gives a
reasonable estimate of the ultrafiltration rate.
During the use of the present invention the operator sets the
maximum allowed rate of ultrafiltration in mL/hour. Values between
100 and 500 mL/hour are allowed. The present invention
microprocessor establishes the rate of withdrawal of blood in the
range of 40 to 60 mL/min. This flow rate is determined by the
quality of access. It is advantageous to establish and maintain
blood flow constant.
Based on the pressure sensor readings the TMP is calculated. This
allows the calculation of ultrafiltrate rate for known KUF of the
filter.
If the ultrafiltration rate is higher than desired it is reduced
using a solenoid ultrafiltrate pinch valve attached to the filtrate
line 211. When the valve is closed the pressure inside the
ultrafiltrate compartment of the filter 6 rises rapidly until it is
equal to the pressure in the blood compartment (fibers). When the
system is in equilibrium, no ultrafiltration occurs. The pinch
valve is cycled approximately once per minute. The duty cycle
(ratio of open to closed state) is calculated ratiometrically from
the actual and desired ultrafiltration rate.
Blood exiting the filter 207 through the connector on the bottom of
the filter casing is continuously returned to the patient through
the return needle 210. Blood flow leaving the filter is the same as
the blood flow entering the filter if the ultrafiltrate clamp 213
is closed. If the clamp 213 is open ultrafiltration occurs and the
blood is continuously fractured into the ultrafiltrate and more
concentrated blood. The hematocrit and the volume of returned blood
was determined by the ultrafiltration fraction, which is the
volumetric fraction of the ultrafiltrate relative to the volume of
whole blood entering the filter.
Blood return circuit pressure sensor 209 serves several functions.
The return pressure is used in the TMP calculation that is in turn
used to calculate input data for the control of the ultrafiltration
rate. It is also used to detect a disconnected or occluded circuit.
Excessive pressure signals the occlusion that can be caused by a
kinked tube or a clotted needle. Since the resistance of the needle
210 is much higher than the resistance of the infusion blood line
224, disconnection of the needle from the tubing is easy to detect
from an adapt drop of the return pressure.
While the invention has been described in connection with what is
presently considered to be the most practical and preferred
embodiment, it is to be understood that the invention is not to be
limited to the disclosed embodiment, but on the contrary, is
intended to cover various modifications and equivalent arrangements
included within the spirit and scope of the appended claims.
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