U.S. patent application number 10/513693 was filed with the patent office on 2005-09-22 for last-chance quality check and/or air/pathogen filter for infusion systems.
Invention is credited to Brugger, James M., Burbank, Jeffrey H..
Application Number | 20050209547 10/513693 |
Document ID | / |
Family ID | 29739904 |
Filed Date | 2005-09-22 |
United States Patent
Application |
20050209547 |
Kind Code |
A1 |
Burbank, Jeffrey H. ; et
al. |
September 22, 2005 |
Last-chance quality check and/or air/pathogen filter for infusion
systems
Abstract
Blood treatment system and method for high rate hemofiltration
ensures against pyrogenic patient reaction by providing various
mechanisms for filtering replacement fluid to remove endotoxins and
other safety features including detecting incorrect fluid
administration.
Inventors: |
Burbank, Jeffrey H.;
(Boxford, MA) ; Brugger, James M.; (Newburyport,
MA) |
Correspondence
Address: |
PROSKAUER ROSE LLP
PATENT DEPARTMENT
1585 BROADWAY
NEW YORK
NY
10036-8299
US
|
Family ID: |
29739904 |
Appl. No.: |
10/513693 |
Filed: |
November 8, 2004 |
PCT Filed: |
June 5, 2003 |
PCT NO: |
PCT/US03/17743 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60386483 |
Jun 6, 2002 |
|
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|
60438567 |
Jan 7, 2003 |
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Current U.S.
Class: |
604/5.01 |
Current CPC
Class: |
A61L 2/0017 20130101;
A61M 1/3455 20130101; A61M 1/3458 20140204; A61M 2205/75 20130101;
A61M 1/1656 20130101; A61M 1/3465 20140204; A61M 1/1664 20140204;
A61M 1/1668 20140204; A61M 1/3462 20130101; A61M 1/1658 20130101;
B01D 61/32 20130101 |
Class at
Publication: |
604/005.01 |
International
Class: |
A61M 037/00 |
Claims
What is claimed is:
1. A method for performing hemofiltration, comprising the steps of:
providing at least one container of fluid that is
regulatory-cleared for infusion into patients; connecting said at
least one container to at least one filter effective to ensure a
concentration of endotoxins in said fluid passing therethrough is
below 0.03 EU/ml; administering to a patient a blood treatment
including a step of infusing said fluid into said patient after
filtering said fluid by means of said at least one filter.
2. A method as in claim 1, further comprising performing said
treatment within a regulatory regime in which a standard for
regulatory clearance is such that said fluid may contain more than
0.03 Eu/ml.
3. A method as in claim 1, wherein said step of administering
includes drawing said fluid from said at least one container and
passing it through said at least one filter, whereby said fluid is
filtered as it is consumed by said treatment.
4. A method as in claim 1, wherein said at least one filter is
located immediately upstream of a flow junction at which said fluid
is injected into a venous line returning blood into said
patient.
5. A method as in claim 1, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid
such as to deliver no more than 5 EU/hr per Kg of patient weight of
fluid upon filtration thereof at a defined rate of infusion into
said patient.
6. A method as in claim 1, wherein at least one container is at
least two containers and said at least one filter is at least one
filter for each of said containers, each said filtering being
connected inline in a respective flow line connected to each of
said at least two containers, whereby fluid from each container is
filtered by its own filter.
7. A method as in claim 1, wherein: said at least one filter is at
least two; said step of administering includes drawing said fluid
from said at least one container and passing it through at least
one of said at least two filters, whereby said fluid is filtered as
it is consumed by said treatment; and at least another of said at
least two filters is located upstream of a flow junction at which
said fluid is injected into a venous line returning blood into said
patient such that said fluid is double-filtered before entering
said patient's body.
8. A method as in claim 7, wherein said at least another of said at
least two filters is located immediately upstream of said flow
junction at which said fluid is injected into said venous line.
9. A method for performing hemofiltration, comprising the steps of:
providing at least one container of fluid that is
regulatory-cleared for a defined rate of infusion into patients;
connecting said at least one container to at least one filter
effective to reduce a concentration of endotoxins in said fluid to
a rate below that of said fluid in said container; administering to
a patient a blood treatment including a step of infusing said fluid
into said patient at said defined rate after filtering said fluid
by means of said at least one filter.
10. A method as in claim 9, further comprising performing said
treatment within a regulatory regime in which a standard for
regulatory clearance for said defined rate of infusion is such that
said fluid may contain more than 0.03 EU/ml.
11. A method as in claim 9, wherein said step of administering
includes drawing said fluid from said at least one container and
passing it through said at least one filter, whereby said fluid is
filtered as it is consumed by said treatment.
12. A method as in claim 9, wherein said at least one filter is
located immediately upstream of a flow junction at which said fluid
is injected into a venous line returning blood into said
patient.
13. A method as in claim 9, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
such as to deliver to a patient no more than 5 EU/hr per Kg. of
patient weight of fluid upon filtration thereof at said defined
rate of infusion.
14. A method as in claim 9, wherein at least one container is at
least two containers and said at least one filter is at least one
filter for each of said containers, each said filtering being
connected inline in a respective flow line connected to each of
said at least two containers, whereby fluid from each container is
filtered by its own filter.
15. A method as in claim 9, wherein: said at least one filter is at
least two; said step of administering includes drawing said fluid
from said at least one container and passing it through at least
one of said at least two filters, whereby said fluid is filtered as
it is consumed by said treatment; and at least another of said at
least two filters is located upstream of a flow junction at which
said fluid is injected into a venous line returning blood into said
patient such that said fluid is double-filtered before entering
said patient's body.
16. A method as in claim 15, wherein said at least another of said
at least two filters is located immediately upstream of said flow
junction at which said fluid is injected into said venous line.
17. A method as in claim 9, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
a rate below 0.03 EU/ml.
18. A method for performing hemofiltration, comprising the steps
of: providing at least one container of fluid for infusion into
patients; connecting said at least one container to at least one
filter effective to ensure a concentration of endotoxins in said
fluid passing therethrough is below both 0.03 EU/ml and such as to
deliver no more than 5 EU/hr per Kg of patient weight at a defined
rate of infusion into a patient; administering to a patient a blood
treatment including a step of infusing said fluid into said
patient.
19. A method as in claim 18, further comprising performing said
treatment within a regulatory regime in which a standard for
regulatory clearance for said defined rate of infusion is such that
said fluid may contain more than 0.03 EU/ml.
20. A method as in claim 18, wherein said step of administering
includes drawing said fluid from said at least one container and
passing it through said at least one filter, whereby said fluid is
filtered as it is consumed by said treatment.
21. A method as in claim 18, wherein said at least one filter is
located immediately upstream of a flow junction at which said fluid
is injected into a venous line returning blood into said
patient.
22. A method as in claim 18, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
a rate such as to deliver to said patient no more than 5 EU/hr. per
Kg. of patient weight of fluid upon filtration thereof at said
defined rate of infusion into said patient.
23. A method as in claim 18, wherein at least one container is at
least two containers and said at least one filter is at least one
filter for each of said containers, each said filtering being
connected inline in a respective flow line connected to each of
said at least two containers, whereby fluid from each container is
filtered by its own filter.
24. A method as in claim 18, wherein: said at least one filter is
at least two; said step of administering includes drawing said
fluid from said at least one container and passing it through at
least one of said at least two filters, whereby said fluid is
filtered as it is consumed by said treatment; and at least another
of said at least two filters is located upstream of a flow junction
at which said fluid is injected into a venous line returning blood
into said patient such that said fluid is double-filtered before
entering said patient's body.
25. A method as in claim 24, wherein said at least another of said
at least two filters is located immediately upstream of said flow
junction at which said fluid is injected into said venous line.
26. A method as in claim 18, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
a rate below 0.03 EU/ml.
27. A method for performing hemofiltration, comprising the steps
of: filtering a replacement fluid to ensure against a presence of
endotoxins, in a filtered fluid resulting from said step of
filtering, at a concentration no higher than 0.03 EU/ml; drawing a
waste fluid from a patient; infusing said filtered fluid into said
patient; said step of filtering including filtering with a media
having a pore size that is ineffective to block endotoxins, but
made of a material that is effective to adsorb endotoxins.
28. A method as in claim 27, further comprising performing said
treatment within a regulatory regime in which a standard for
regulatory clearance for said defined rate of infusion is such that
said fluid may contain more than 0.03 EU/ml.
29. A method as in claim 27, wherein said step of administering
includes drawing said fluid from said at least one container and
passing it through said at least one filter, whereby said fluid is
filtered as it is consumed by said treatment.
30. A method as in claim 27, wherein said at least one filter is
located immediately upstream of a flow junction at which said fluid
is injected into a venous line returning blood into said
patient.
31. A method as in claim 27, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
a rate such as to deliver to said patient no more than 5 EU/hr per
Kg. of patient weight of fluid upon filtration thereof at said
defined rate of infusion into said patient.
32. A method as in claim 27, wherein at least one container is at
least two containers and said at least one filter is at least one
filter for each of said containers, each said filtering being
connected inline in a respective flow line connected to each of
said at least two containers, whereby fluid from each container is
filtered by its own filter.
33. A method as in claim 27, wherein: said at least one filter is
at least two; said step of administering includes drawing said
fluid from said at least one container and passing it through at
least one of said at least two filters, whereby said fluid is
filtered as it is consumed by said treatment; and at least another
of said at least two filters is located upstream of a flow junction
at which said fluid is injected into a venous line returning blood
into said patient such that said fluid is double-filtered before
entering said patient's body.
34. A method as in claim 33, wherein said at least another of said
at least two filters is located immediately upstream of said flow
junction at which said fluid is injected into said venous line.
35. A method as in claim 27, wherein said at least one filter is
effective to reduce a concentration of endotoxins in said fluid to
a rate below 0.03 EU/ml.
36. A device for performing hemofiltration, comprising: at least
one container of fluid for infusion into patients; connected to
said at least one container, at least one filter effective to
ensure a concentration of endotoxins in said fluid passing
therethrough is below both 0.03 EU/ml and such as to deliver no
more than 5 EU/hr per Kg of patient weight at a defined rate of
infusion into a patient; a hemofiltration system including at least
one pump for pumping blood from and back to said patient; a fluid
circuit for conveying said blood, said fluid circuit connecting an
outlet of said filter with a return flow of blood, whereby
replacement fluid having a low level of pyrogens in infused into
said patient.
37. A device as in claim 36, wherein said at least one filter is at
least two, each of which is incorporated in an inline configuration
in a respective arm of a manifold.
38. A device as in claim 36, wherein said at least one filter
includes a membrane of charged nylon.
39. A device as in claim 36, wherein said at least one filter
includes filter medium being such that an endotoxin load of a
filtrate thereof is obtained by a combination of mechanical
blocking due to small pore size and adsorption, whereby a pressure
drop of said medium is lower than would be required if the medium
relied on pore size alone to reduce the endotoxin load to said
concentration.
40. A disposable fluid circuit for infusion, comprising: a line for
receiving an infusible fluid; a pumping portion for engagement with
a peristaltic pump; an inline filter downstream of said pumping
portion and immediately prior to a connector to a patient access
configured to filter an infusate prior to contact with a patient
blood stream; said inline filter having properties to one of degass
and reduce a rate of endotoxins of said infusate.
41. A fluid circuit as in claim 40, wherein said fluid circuit
includes a blood filter or dialyzer and said inline filter is
located immediately upstream of a junction for diluting blood.
42. A fluid circuit as in claim 41, wherein said inline filter is
configured to reduce a rate of endotoxins to 3 EU/ml. or less.
43. A fluid circuit as in claim 40, further comprising a portion
for engagement with an air sensor downstream of said inline
filter.
44. A fluid circuit as in claim 43, wherein said inline filter is
configured to reduce a rate of endotoxins to 3 EU/ml. or less.
45. A fluid circuit as in claim 40, further comprising fluid
property detection sensor.
46. A fluid circuit as in claim 45, wherein said fluid property
detection device includes a conductivity detector.
47. A disposable fluid circuit for infusion, comprising: a line for
receiving an infusible fluid; a pumping portion for engagement with
a peristaltic pump; an inline sensor effective to detect a property
of an infusate prior to contact with a patient blood stream.
48. A fluid circuit as in claim 46, wherein said inline sensor
includes at least a portion of a conductivity cell.
49. A fluid circuit as in claim 47, wherein said inline sensor is
integrated within the housing of an inline filter that is arranged
to filter said infusate.
50. A disposable fluid circuit for renal replacement therapy and
connectable with a blood treatment machine, comprising: a blood
line connectable to a blood filter having properties appropriate
for treatment by hemofiltration or dialysis; said blood line having
arterial and venous portions connectable to a patient access; a
replacement fluid line connected to said venous portion of said
blood line for diluting blood; a connection for an inline component
in said replacement fluid line located immediately upstream of a
junction joining said replacement fluid line and said venous
portion; said inline component including at least one of an inline
filter effective to block pyrogens and/or air and a fluid property
sensor connectable to a controller or alarm.
51. A fluid circuit as in claim 50, wherein said inline component
includes a sterile filter permanently connected to said
connection.
52. A fluid circuit as in claim 51, wherein said inline component
includes an inline filter with media capable of reducing a rate of
endotoxins to less than 3 EU/ml.
53. A fluid circuit as in claim 52, wherein said inline filter is
permanently connected to said replacement fluid line.
54. A fluid circuit as in claim 53, wherein said inline filter
includes media capable of blocking gas bubbles.
55. A fluid circuit as in claim 54, further comprising a cartridge
for supporting said replacement fluid line, said blood line, and
said inline filter, said cartridge engaging with said blood
treatment machine to orient it with respect thereto.
56. A fluid circuit as in claim 55, wherein said inline filter is
operable in a selected orientation and said cartridge orients said
inline filter when said cartridge is engaged with said blood
treatment machine.
57. A fluid circuit as in claim 56, wherein said inline filter
includes media capable of reducing a rate of endotoxins to less
than 3 EU/ml.
58. A fluid circuit as in claim 54, further comprising a portion
for engagement with an air detector downstream of said inline
filter.
59. A fluid circuit as in claim 54, further comprising a cartridge
for supporting said replacement fluid line, said blood line, and
said inline filter, said cartridge engaging with said blood
treatment machine to orient it with respect thereto.
60. A fluid circuit as in claim 55, wherein said inline filter is
operable in a selected orientation and said cartridge orients said
inline filter when said cartridge is engaged with said blood
treatment machine.
61. A fluid circuit as in claim 50, wherein said blood treatment
machine is a hemofiltration machine.
62. A fluid circuit as in claim 61, wherein said inline component
includes an inline filter with media capable of reducing a rate of
endotoxins to less than 3 EU/ml.
63. A fluid circuit as in claim 50, wherein said blood line is
permanently connected to said blood filter.
64. A fluid circuit as in claim 50, further comprising a connection
connectable to a source of sterile replacement fluid and wherein
said inline component includes an inline filter with media capable
of reducing a rate of endotoxins to less than 3 EU/ml.
65. A device for batch preparation of replacement fluid
retrofittable to a blood treatment machine, comprising: a
disposable fluid circuit including a replacement fluid container
with a first input line having a connector for an inline sterile
filter and an inlet connectable to a source of replacement fluid to
be filtered by said sterile filter; a peristaltic pump actuator;
said first input line having a pumping portion engageable with said
peristaltic pump actuator; said replacement fluid container having
a first outlet connectable to a replacement fluid connector of a
blood treatment machine that consumes replacement fluid in
performing renal replacement therapy.
66. A device as in claim 65, further comprising an insulated
housing for supporting said replacement fluid container.
67. A device as in claim 66, further comprising a heater for
warming said replacement fluid container.
68. A device as in claim 67, further comprising a controller
configured to regulate a temperature of said replacement fluid
container.
69. A device as in claim 65, further comprising a control valve and
a controller configured to shut said control valve after a quantity
of replacement fluid is filtered by said filter.
70. A device as in claim 65, further comprising a heater to heat
filtered replacement fluid and a controller configured to control
said pump and said heater responsively to a scheduled treatment
time.
71. A device as in claim 65, wherein said controller is configured
to filter said replacement fluid at a time such that a batch of
replacement fluid is filtered, stored in said replacement fluid
container, and heated to a specified temperature immediately prior
to said scheduled treatment time.
72. A device as in claim 65, wherein said controller is configured
to filter said replacement fluid and maintain a temperature thereof
until a time for consumption by said blood treatment machine.
73. A tubing set for preparation of replacement fluid by sterile
filtering, comprising: a sterile replacement fluid container with
an inlet line connected to a filter and a connector for drawing
replacement fluid from a source; an outlet port for drawing
filtered replacement fluid from said replacement fluid container;
at least one recirculation port to flow sterile replacement fluid
in a recirculating flow through said replacement fluid container to
purge air from said outlet line, said recirculation port and a
connection between them provided by a blood treatment circuit.
74. A set as in claim 73, wherein said filter contains media
capable of reducing a rate of endotoxins to less than 3 EU/ml.
75. A set as in claim 73, wherein said outlet port is connected to
an outlet line having connector.
76. A set as in claim 73, wherein said at least one is at least two
ports.
Description
BACKGROUND OF THE INVENTION
[0001] During hemofiltration, hemodialysis, hemodiafiltration,
ultrafiltration, and other forms of renal replacement therapy,
blood is drawn from a patient, passed through a filter, and
returned to the patient. Depending on the type of treatment, fluids
and electrolytes are exchanged in the filter between a dialysate
and/or extracted from the blood by filtration. One effect may be a
net loss of fluid and electrolytes from the patient and/or
exhaustion of dialysate, with a concomitant need for its
replenishment, again depending on the type of treatment. To replace
fluid lost from the patient and keep the patient from dehydrating,
replacement fluid may be injected into the patient at a rate that
matches a rate of loss, with an adjustment for a desired net change
in the patient's fluid complement. To replace exhausted dialysate,
fresh dialysate is continuously circulated through the filter.
[0002] Presently methods to produce large volumes of dialysate from
tap water are known, but each requires complex water purification
and standardization equipment, since impurities and cleaning
additives such as chlorine vary greatly in tap water from
municipality to municipality and within a municipality over time.
(See Twardowski U.S. Pat. Nos. 6,146,536 and 6,132,616.) Moreover,
dialysate solution, whether prepared online or prepackaged, while
of the proper concentration for use as a replacement fluid, is not
directly infused into the patient's body. Instead, dialysate
flows-past a semipermeable membrane that permits ions and water to
be exchanged across the membrane until a balance between their
concentrations in blood and their concentrations in the dialysis is
achieved. This is effective to remove impurities from the blood and
to add missing electrolytes to the blood, but the volume of fluid
that is infused is not as great as with hemofiltration.
[0003] Conventionally, dialysate and/or replacement fluid is
supplied from either of two sources: batches of fluid, typically in
multiple bags, or a continuous sources of water that is
sterile-filtered and added to concentrated electrolytes to achieve
the required dilution level. Because replacement fluid is injected
directly into the patient, replacement fluid is required to be
sterile and is recommended to have limited levels of pyrogens,
particularly endotoxins, which are quantified in endotoxin units
(EU). The maximum amount of endotoxin allowed in a parenteral
product or medical device set by the US Food and Drug
Administration (FDA) and United States Pharmacopoeia (USP) for
drugs is 5.0 EU/Kg/hr, a rate taking into account the weight of the
patient (in Kg.) and the rate of infusion. Currently, however,
replacement fluid packaged such that it is regulated as a drug may
have an endotoxin load of up to 0.5 EU/ml. This would limit the
replacement fluid exchange rate for a 72 Kg. patient to less than
12 ml./min. To be safely infused, per these specifications, at
higher rates, the fluid must be further filtered of endotoxins.
Filtering to 0.03 EU/ml., a level that may be identified as
"ultrapure," allows an infusion rate of 200 ml./min., which may be
sufficient for high rate continuous hemofiltration therapy of the
type described in the following pending US patent applications each
of which is hereby incorporated by reference as fully set forth in
its entirety herein.
[0004] Ser. No. 08/800,881, filed Feb. 14, 1997 for Hemofiltration
System;
[0005] Ser. No. 09/451,238 for Nov. 29, 1999 for Systems and
Methods for Performing Frequent Hemofiltration;
[0006] Ser. No. 09/512,929, filed Feb. 25, 2000 for Fluid
Replacement systems & Methods for Use in Hemofiltration;
[0007] Ser. No. 09/513,564, filed Feb. 25, 2000 for Systems and
Methods for Detecting Air in an Arterial Blood Line of a Blood
Processing Circuit;
[0008] 60/438,567, filed Jan. 30, 2003 for Preparing Replacement
Fluid by Means of Batch Filtration Prior to Treatment;
[0009] Ser. No. 09/513,910, filed Feb. 25, 2000 for Systems and
Methods that Maintain Sterile Extracorporeal Processing
Conditions;
[0010] Ser. No. 09/513,911, filed Feb. 25, 2000 for Synchronized
Volumetric Fluid Balancing Systems and Methods;
[0011] Ser. No. 09/513,915, filed Feb. 25, 2000 for Systems and
Methods for Controlling Blood Flow & Waste Fluid Removal During
Hemofiltration;
[0012] Ser. No. 09/862,207, filed May 21, 2001 for Methods, Systems
and Kits for the Extracorporeal Processing of Blood;
[0013] Ser. No. 09/865,905, filed May 24, 2001 for Fluid Processing
Systems and Methods Using Extracorporeal Fluid Flow Panels Oriented
Within a Cartridge;
[0014] Ser. No. 09/894,236, filed Jun. 27, 2001 for Hemofiltration
System;
[0015] Ser. No. 09/900,362, filed Jul. 7, 2001 for Method and
Apparatus for Leak Detection in a Fluid Line (Disconnect
Sensor--Reverse Lines to Use Air Sensor on Arterial Line
(Leak));
[0016] Ser. No. 09/905,246, filed Jul. 12, 2001 for Devices and
Methods for Sterile Filtering;
[0017] Ser. No. 09/907,872, filed Jul. 17, 2001 for Hermetic Flow
Selector Valve;
[0018] 60/324,437 filed Sep. 24, 2001 for Device and Method for
Enhancing Performance of Membranes.
[0019] Ser. No. 10/040,659, filed Jan. 7, 2002 for Blood Treatment
Replacement Fluid Using Infusible Fluids in Combination;
[0020] 60/346,458 filed Jan. 7, 2002 for Hemofiltration Filter with
High Membrane Utilization Effectiveness; and
[0021] 60/346,403 filed Jan. 7, 2002 for Hemofiltration System
Method of Use and Associated Control System.
[0022] In many instances, blood treatment therapies may require a
large quantity of sterile fluid. A typical way to provide the large
quantity of replacement fluid is to provide multiple bags of
replacement fluid, dialysate, or infusate. The connection of these
bags of fluid to an extracorporeal blood circuit creates a risk of
touch contamination resulting in the introduction of contaminants
into the fluids. Contamination may occur, for example, at the point
where bags of fluid are accessed ("spiked") or at other times
during preparation for infusion such as when the patient is
accessed.
[0023] Attempts to render dialysate suitable for use as a
replacement fluid in hemofiltration and hemodiafiltration have
focused on continuous sterilization processes that require a
separate dialysate filtration/purification apparatus that must be
periodically purged and verified to provide sufficient constant
flow of sterile replacement fluid required for hemofiltration. (See
Chavallet U.S. Pat. Nos. 6,039,877 and 5,702,597.) Such devices are
necessarily complicated and require separate pumping systems for
the sterilization process. In addition, the rate of supply of
dialysate for such systems is very high, requiring an expensive
filter to be used. The same high-rate problem exists for the
generation of replacement fluid for hemofiltration, and therefore
also requires an expensive filter.
[0024] There is a need for improved mechanisms for providing safe
economic replacement fluid for use in various blood therapies.
SUMMARY OF THE INVENTION
[0025] In the present invention, sterile, and preferably
substantially non-pyrogenic (e.g., including endotoxin-free)
replacement fluid or dialysate may be generated in batch form by
filtering. According to various embodiments of inventions
disclosed,
[0026] 1. raw fluid is passed through a filter prior to treatment
to prepare a batch of infusible replacement fluid;
[0027] 2. raw fluid is passed by gravity feed during treatment
through filters attached to infusion lines from each of one or more
batch containers;
[0028] 3. raw or prefiltered fluid according to either or both of
the previous methods is passed through a last-chance filter
immediately prior to injection into the patient.
[0029] Preferably, the filter has a pore size and quality effective
to block endotoxins such that the replacement ultimately infused
that is substantially less than 5 EU/Kg./hr (based on the rate of
treatment), the limit set by the USP for parenteral drugs and no
more than 0.5 EU/ml. Preferably the filter provides this degree of
filtration with minimal pressure drop, for example by means of a
relatively large pore size (e.g., 02. Micron) in combination with a
charged nylon membrane which attracts endotoxins and helps to
ensure against their passage. Filters are available with smaller
pore sizes and may be used rather than relying on adsorption as
with the nylon membrane example. For example pores sizes of 0.005
micron and somewhat larger will block most endotoxins. But small
pore size implies high pressure drop and generates inefficiencies
for production.
[0030] The raw (source) replacement fluid may be industry standard
quantities of pyrogens and labeled as suitable for injection, the
inventive method providing a higher degree of purity than is
currently allowed for infusible fluids regulated either as medical
devices or drugs.
[0031] The batch filtration process may be permitted to take any
length of time because the rate of flow of raw replacement fluid
(or components thereof) through the filter is completely
independent of the rate of consumption by the renal therapy.
Because the filters used for such filtering tend to be expensive,
it may be desirable for such a batch process to employ a small
pyrogen filter for such filtration. Such a filter can have a flow
capacity that is much lower than that required for real-time
filtering of the replacement fluid (or components). Alternatively,
the fluid may be passed under pressure for a suitably supported
membrane or strong membrane material adequate to permit real-time
filtration as discussed elsewhere in the present specification. In
addition to preparation of low pyrogen (preferably at least with
low levels of endotoxins) fluid from sterile or non-sterile and/or
pyrogen-purified fluid, embodiments of inventions disclosed may be
used to ensure against touch contamination.
[0032] Treatment by hemofiltration requires the extraction from
patients of a large volume of fluid compared to hemodialysis,
although both perform similar functions. In hemodialysis, fluid and
electrolytes cross a filter membrane into and out of the blood of
the patient in response to a difference in concentration of
electrolytes. Some net quantity of fluid may be taken from the
patient if there is an excess in the patient's blood and some net
quantity of replacement fluid may be infused directly if there is a
paucity in the patient's blood. In hemofiltration, fluid is drawn
out of the patient continuously and replaced with
electrolytically-proper fluid. As a result, the quantity of fluid
infused in the patient tends to be much greater than with
hemodialysis and, coincidentally, most other types of infusion
therapies including parental infusion therapies. In addition, new
hemofiltration therapies have been developed which permit very fast
continuous treatment, which may involve the infusion of replacement
fluid at a very high rate. The risk of adverse reactions due to the
infusion of pyrogens into patients increases with the dose and the
period of time over which the infusion takes place. As a
consequence, the allowed concentration of pyrogens in replacement
fluid for hemofiltration should be substantially lower than for
other treatments, for example for hemodialysis or other infusion
therapies.
[0033] While low pyrogen levels may be achieved using sterilization
and filtration techniques that are known, there are also a number
of practical matters that are well to combine in addressing the
problem of pyrogen infusion in hemofiltration. For example, even
when highly purified replacement fluid is used for replacement
fluid, touch-contamination can cancel any benefit of starting with
a highly purified fluid.
[0034] In disclosed embodiments of blood treatments systems,
including hemofiltration systems generally as well as high
flow-rate hemofiltration systems particularly, the low pyrogen
concentrations may be achieved by one or more features,
including:
[0035] 1. batch filtration of raw replacement fluid at the site of
use and in a manner that minimizes risk of touch-contamination or
other sources of recontamination;
[0036] 2. filtration of raw replacement fluid at the site of use at
the rate of consumption in real time during treatment, preferably
with a filter located close to the point of injection so as to
minimize the risk of downstream contamination;
[0037] 3. filtration using filters that permit the passage of no
more than 0.03 endotoxin units per ml.; and
[0038] 4. filtration using filters using a combination of
adsorption and blocking mechanisms to provide an optimal balance
between pressure drop across the filter media and the need to block
pyrogen particles, preferably with a charged nylon membrane, which
attracts endotoxins thereby helping to block them and having an
approximately 0.2 micron pore size.
[0039] Generally replacement fluid is heated before being infused
into a patient. This is often accomplished by passing the fluid
through a heater with enough heating capacity to heat the fluid as
it is being infused. The capacity of the heater must be matched to
the mass flow of the fluid and the temperature rise required. In a
batch preparation process, where a batch of fluid is prepared over
a substantial period before use, a small heater may heat the
replacement fluid over a long period of time. Insulation may be
provided to prevent heat loss. An insulating outer container for
the source replacement fluid may be provided. For example, the
container may be an insulated box with room for one or more large
disposable sterile bags of the type normally used for infusible
fluids.
[0040] The preparation of warm replacement fluid may be automated
by a control process that permits a user to set up the fluids and
other materials well in advance of a scheduled treatment. The
process would ensure that the replacement fluid is treated to
remove pyrogens and heated to the proper temperature when the
treatment is to begin. The automation process may be permit the
user to select how far in advance of the treatment the preparation
should be performed. This may be useful, for example, where a
particular source of replacement fluid has proved to release more
than a usual quantity of dissolved gases upon heating. Heating the
replacement fluid and permitting it to settle for a time before it
is used may allow gases to come out of solution and settle at the
top of the batch vessel or vessels. The automation process may be
incorporated in the control functions of renal therapy machine.
[0041] The invention or inventions will be described in connection
with certain preferred embodiments, with reference to the following
illustrative figures so that it may be more fully understood. With
reference to the figures, it is stressed that the particulars shown
are by way of example and for purposes of illustrative discussion
of the preferred embodiments of the present invention or inventions
only, and are presented in the cause of providing what is believed
to be the most useful and readily understood description of the
principles and conceptual aspects of the invention or inventions.
In this regard, no attempt is made to show structural details of
the invention in more detail than is necessary for a fundamental
understanding of the invention or inventions, the description taken
with the drawings making apparent to those skilled in the art how
the several forms of the invention or inventions may be embodied in
practice.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] FIG. 1 is a schematic illustration of a standalone/retrofit
apparatus system for batch filtration of a sterile,
endotoxin-purified, or pyrogen-purified replacement fluid.
[0043] FIG. 2 is a flow chart illustrating an exemplary control
procedure applicable to various embodiments of the invention
including those of FIGS. 1 and 3.
[0044] FIG. 3 is a schematic illustration of a blood treatment
machine with an attached subsystem for batch preparation of
infusible replacement fluid.
[0045] FIGS. 4A and 4B are illustrations of fluid filters that may
be use in various embodiments of the invention.
[0046] FIG. 5 illustrates an exemplary blood-treatment system with
a filter used to filter gas, pyrogens, endotoxins, or pyrogens from
replacement fluid during treatment.
[0047] FIGS. 6-8 illustrate a blood treatment machine and cartridge
providing various supporting mechanical features for the embodiment
of FIG. 5 and further embodiments, including one in which a quality
of replacement fluid is sensed before infusion.
[0048] FIG. 9 illustrates a disposable fluid circuit kit which may
support various embodiments of the invention.
[0049] FIG. 10 illustrates a set up for priming a blood treatment
process, which components of the invention may be used to
support.
[0050] FIG. 11 illustrates a portion of a blood treatment machine
that allows a pump used as part of the blood treatment to also be
used to control the filtering of fluid to provide a batch of
infusible replacement fluid.
[0051] FIG. 12 illustrates a patient undergoing treatment.
[0052] FIGS. 13 and 14 illustrate embodiments of a filtering
manifold for filtering of infusible fluids.
DETAILED DESCRIPTION
[0053] Referring to FIG. 1, a filter 160 filters fluid from a
source of fluid 150 to generate a batch of infusible replacement
fluid 130. The filter 160 may be, and preferably is, a microporous
filter that blocks pyrogens and allows the passage of dissolved
electrolytes and water. The latter may provide an infusible fluid
free of all pyrogens, however, in practice, the pyrogen
concentration must be reduced, but not necessarily eliminated since
total elimination is not practical. The most common type of pyrogen
is endotoxins, which may be present even in sterilized fluids.
[0054] In hemofiltration, a large quantity of fluid is drawn from
the patient and replaced with replacement fluid. Compared to
dialysis, the quantity actually removed and replaced with
replacement fluid tends to be high. As a consequence, it is
desirable to provide replacement fluid that has a lower
concentration of pyrogens than may be allowed in other infusible
fluids and what may cross the membrane of a dialysis system. Thus,
a filter effective to reduce endotoxins to levels at least as low
as 0.03 endotoxin units per ml. should be provided for the filter
160.
[0055] The result of the filtration process is the sterilization
and cleansing of endotoxins and particulate pyrogens in the raw
fluid from the source of fluid 150. The source of fluid 150 may be
a container 196 of fluid approved for injection or non-sterile
replacement fluid. It may also be one or more containers of
constituents which, when combined, form a proper replacement fluid
(not shown) or a continuous source such as a tap water that is
combined or has been combined with electrolyte concentrate (not
shown). The starting fluid may be a function of the type of filter
160 used. For example, when processing fluid with a relatively
large concentration of particulate pyrogens, for example bacteria,
it is desirable to use a very large filter to ensure that its
filtering performance is not compromised. In a preferred
embodiment, a small replacement filter is used (since they tend to
be costly) and the source fluid is fluid that has already been
filtered to achieve low levels of pyrogens.
[0056] One or more conduit elements form a line 120 to convey the
source fluid 150 through the filter 160 and into a batch container
147. The latter may be any type of sterile, preferably disposable
container, for example, a large IV bag. It may also include a
number of such containers appropriately interconnected to permit
flow into and out of them in the fashion of container 147.
[0057] Included in the conveyance from source fluid 150 to
infusible replacement fluid 130 may be a pump 190, such as a
peristaltic pump. The pressure at an outlet of the filter 160 may
be sensed by a pressure sensor 162 and the pump 190 controlled by a
controller 170 to insure a predefined transmembrane pressure (TMP)
threshold of the filter 160 is not breached. The TMP may be
maintained at a maximum safe level to maximize throughput. Note
that complexity may be avoided if the source fluid 150 is arranged
such as to maintain a desired TMP at the filter 160 without the
need of a pump 190 or pressure sensor 162. For example, the source
fluid 150 may be provided by a batch container elevated at a
certain height to provide a desired head. Note that a control valve
165 or a speed of the pump 190 may be used to regulate the flow
rate to maintain desired TMP limits.
[0058] A control/shutoff valve 180 may provide the controller 170
the ability to stop the flow of fluid through the filter 160 once a
desired volume is reached. A heater 185 may be provided to warm the
filtered replacement fluid 130 to prepare it for use. An insulated
container 145 may be used to reduce heat loss so that heater 185
can be a relatively low power type. The heater 185 may be
controlled by the controller 170 to ensure the replacement fluid
130 is at a desired temperature when required to be used.
Alternatively the heater 185 can be controlled by an independent
device actuated by, for example, a pressure sensor (for example as
shown at 186 in FIG. 1) triggered by the flow of fluid into the
batch container 147, a timer (not shown) settable to trigger based
on a predefined treatment time, or some other means. Preferably, in
either case, a temperature regulator (e.g., a temperature sensor
183 combined with logic in controller 170) regulates power to the
heater to ensure a required temperature is maintained and not
exceeded. The temperature sensor 183 may be used to sense the
quantity of filtered replacement fluid by the rate of detected
temperature increase versus heater output. The temperature sensor
183, heater 185, and filtered replacement fluid 130 can be modeled
in any desired fashion. For example one may neglect all but the
thermal mass of the RF, assume perfect heat transfer (including
assuming the RF fluid to be isothermal). Then, the mass is given by
the product of the temperature change, the thermal capacitance of
the fluid, and the heat output rate of the heater. More complex
theoretical or empirical algorithms would be a simple matter to
derive and implement, for example the temperature variation can be
fitted to the transient exponential that governs for instantaneous
uniform heating from a plane source as the heater is started,
taking temperature data points before substantial convection
starts. The mass may also be determined by means of a contact-type
pressure sensor 186 (e.g., strain gage attached to a bendable plate
and calibrated against mass). Once the mass of fluid is calculated
to be below a certain level, the controller 170 may be programmed
to respond in accord with the assumption the filtered replacement
fluid is exhausted. Equivalently, the controller 170 may simply
respond to some predefined rate of temperature rise of the
temperature sensor 183.
[0059] When the temperature of the filtered replacement fluid 130
is raised, dissolved gas may come out of solution. This may cause
bubbles to accumulate inside the replacement fluid container 147,
which is undesirable because of the risk of infusing bubbles into
the patient's bloodstream. To help ameliorate that problem, a
vibrator or ultrasonic transducer 184 may be provided to cause
bubbles to coalesce and rise to a top of the container 147. As a
result, bubble-free replacement fluid may be drawn through the
outlet 148.
[0060] A connector 195 may be provided for connecting the source
fluid to the line 120. The connector may be a luer, spike, threaded
adapter, or any other suitable type. Although the various controls
indicated above are shown to be controlled an automatic controller
170, each may be controlled also by manual mechanisms.
[0061] The FIG. 1 embodiment allows replacement fluid to be
prepared in batch for later use. Thus, the rate of filtration of
replacement fluid need not match the requirements of the treatment
process or preparatory steps such as priming. As a result, a low
capacity filter may be used for the filter 160. For example,
typically only a small quantity of expensive media is required to
make a small-capacity filter and as such, the cost of a low
capacity filter can be much smaller than a high capacity filter.
Also, other features found in high capacity filters, such as a
large ratio of media surface to volume of the filter module are
achievable only by means of folding or forming media into shapes
that can be difficult to manufacture, such as tubes. Thus, savings
can be achieved in simplification of the configuration of the
filter as well. Relatively small filters with simple planar media
held in plastic casings are available and suitable for this
purpose.
[0062] The configuration of FIG. 1 may be retrofitted for use with
an existing treatment system. For this purpose, the outlet 148 may
be provided with any required connection adapter. A user interface
175 for entering data into the controller 170 may be provided as
well.
[0063] Referring now also to FIG. 2, a control algorithm for
controlling the heater 185, pump 190, valves 165/180, etc. begins
with the a setting of a time for treatment S10, for example by
entering a time into the controller 170 via a user interface (UI)
175. The time can be entered manually or automatically by means of,
for example, a data signal from a remote source via a switched or
network circuit. The time for treatment may be obtained from a
treatment calendar entered into the controller 170, which also may
be obtained from a remote source. In the present simple algorithm,
first and second time intervals T1 and T2 are defined representing
the interval required for filtration of RF and the interval
required for heating of RF, respectively. These values may be
obtained from any of the above means (e.g., local manual or remote
entry via UI/interface 175) or from data encoded on one of the
consumables involved in the process. For example, the filter 160,
the RF fluid container 147, the source fluid 150 container(s), or
any other consumable may be provided with one or more bar-codes,
RFID tags, or other suitable encoding device. Such devices may
provide values for T1 and T2, tables of values that depend upon
other factors, or other data from which T1 and T2 may be
derived.
[0064] The controller 170 waits until it is time to start the flow
of raw RF fluid from source fluid 150 toward container 147 by
comparing a current time (indicated by a clock internal to the
controller 170, which is not shown) to a difference between a
scheduled treatment time and T1, which represents the lead time
(ahead of the scheduled treatment) required for the filtering
process. A loop through step S20 is exited to step S30 when the
clock reaches the treatment time minus T1. At step S30, the flow of
source fluid 150 through the filter 160 is initiated. If the pump
190 is present, it may be started and regulated according to a
specified TMP. The latter may be provided to the controller 170
manually or automatically through UI/interface 175. Automatic entry
may be by way of a data store such as bar-code or RFID attached to
the filter, for example which may be read when the filter 160 is
installed in a chassis with a corresponding reader device (not
shown). Note, as mentioned above, the source fluid may be sterile
and the filtration process provided as a guarantee against
contamination, for example by accidental touching.
[0065] Once the flow of source fluid 150 is initiated, the
controller waits for the required time for applying power to the
heater 185. The delay and the initiation are controlled by step S40
which is exited to step S50 only when the treatment time minus the
predefined interval T2 is reached. Note that the delay may also be
zero. As mentioned above, alternatively, the heater may be
triggered by detecting fluid such as by means of a sensor 186 of
FIG. 1 (not shown) triggered by the presence of filtered
replacement fluid 130 in the container 147. The sensor 186 may be
any of a variety of types, such as an ultrasonic sensor,
capacitance sensor, mass sensor, optical sensor, etc.
[0066] Once the heater is started, the controller 170 may wait for
the source fluid to be exhausted at step S60. Step S60 exits to
step S70 when the source fluid is determined to be exhausted. The
latter may be detected by integrating the flow rate to measure the
total volume (the rate may be determined by the pumping rate, for
example, or by a flow meter (not shown)). The exhaustion of the
source fluid 150 may also be indicated by a quantity indicator
(e.g., a level indicator) in the filtered replacement fluid
container 147 or an intermediate container supplied through a drip
chamber, for example. Alternatively, the exhaustion of the source
fluid 150, if supplied from a fixed-volume container, may be
indicated by a sensor such as an ultrasonic sensor, capacitance
sensor, mass sensor, optical sensor, a scale, etc. Yet another
alternative is to sense gas or a precipitous rise in negative
pressure (sensed by a pressure sensor which is not shown) at the
pump 190 inlet. At step S70, the line 120 may be clamped by
actuating shutoff/control valve 180. Additionally, if appropriate,
the pump 190 may be deactivated at the point where the exhaustion
of the source fluid 150 is detected at step S70.
[0067] According to an embodiment, as the fluid is pumped, the TMP
of the filter, as indicated by pressure sensors 162, may be
monitored. If the TMP is determined by the controller 170 to be, at
any point, below a predetermined nominal value or to have changed
precipitously during filtration, the controller 170 may trigger an
alarm or take some other action to insure that the resulting
replacement fluid is handled appropriately. For example, a back-up
filter could be added during treatment as discussed with respect to
FIG. 5. The TMP results could trigger an alarm at any point during
filtration or could be assessed and reported at step S70, before
treatment would begin.
[0068] The controller 170 pauses again at step S80 to wait for the
sterile fluid to be exhausted. This may be indicated by a signal
from the treatment machine (e.g., received via UI/interface 175) or
by direct measurement by a sensor, such as an ultrasonic sensor,
capacitance sensor, mass sensor, optical sensor, a scale, etc. As
mentioned above, the controller 170, or the heater 185 itself, may
be provided with a threshold temperature-rise rate that indicates
the mass of fluid in the replacement fluid container 147 has fallen
below a minimum level. The loop of step S80 is exited to step S90
where power to the heater 185 is terminated.
[0069] Note that all the functionality of the controller 170 may be
provided, via a control interface, by a controller (not shown)
internal to a treatment machine. For example, the apparatus of FIG.
1 could be provided as an optional module for such a treatment
machine rather than a retrofit module.
[0070] Referring now to FIG. 3, a combination blood treatment
system and filtered replacement fluid device 310 has a replacement
fluid preparation subsystem 305 configured substantially as the
device of FIG. 1. A filter 260 filters fluid from a source of fluid
250 to generate a batch of filtered replacement fluid 230 as in the
embodiment of FIG. 1. Again, the source of fluid 150 may be a
container of purified or unpurified replacement fluid, one or more
containers of constituents which, when combined, form a proper
replacement fluid and any of the latter may include a continuous
source such as a water tap. A line 320 conveys the source fluid 250
through the filter 260 and into a batch container 247, which may be
any type of sterile, preferably disposable container, for example,
a large IV bag. It may also include a number of such containers
appropriately interconnected to permit flow into and out of them in
the fashion of container 247.
[0071] Again, a pump 290 may be provided and pressure at an outlet
of the filter 260 may be sensed by a pressure sensor 262. The pump
290 may be controlled by a controller 270 to insure a maximum safe
TMP to maximize throughput. Again, the pump 290 is not required and
the source fluid 250 may be arranged such as to maintain a desired
TMP at the filter 260 without the need of the pump 290 or pressure
sensor 262 by elevation. A control valve 265 or a speed of the pump
290 may be used to regulate the flow rate to maintain desired TMP
limits.
[0072] A control/shutoff valve 280 may provide the controller 270
the ability to stop the flow of fluid through the filter 260 once a
desired volume is reached. A heater 285 may be provided to warm the
filtered replacement fluid 230 to prepare it for use. An insulated
container 245 may be used and the heater controlled using a
temperature sensor 283 as discussed with respect to the FIG. 1
embodiment. Bubbles may be controlled, as discussed above, by means
of a vibration or ultrasonic transducer 284 and remaining fluid by
means of pressure sensor 286.
[0073] A connector 295 may be provided for connecting the source
fluid to the line 320. The connector may be a luer, spike, threaded
adapter, or any other suitable type. Although the various controls
indicated above are shown to be controlled an automatic controller
270, each may be controlled also by manual mechanisms. Other
aspects of the control mechanisms for the embodiment of FIG. 3 may
be provided as discussed with respect to FIGS. 1 and 2.
[0074] The benefits of the FIG. 3 embodiment are similar to those
of the FIG. 1 embodiment in that it allows replacement fluid over a
time period that is not driven by the speed of supply to the
treatment process. As a result, a low capacity filter may be used
for the filter 260 with the attendant benefits identified above.
Note that the UI/interface 275 and controller 270 are shared in the
present embodiment by the treatment machine. Thus, any information
required for control of both the treatment and preparation of
filtered replacement fluid 230 would not need to be communicated to
a separate controller such as controller 270. Note also that the
communications among the illustrated components is provided by a
channel 202 which may be wire harness, separate wires, a bus, a
wireless channel or any suitable communications/power transmission
device.
[0075] In the embodiment of FIG. 3, a predicted quantity of
replacement fluid may be filtered and stored for use during
treatment. If, however, for some reason, more is required, the
treatment machine controller 270 could be configured to identify
that situation and control the subsystem 305 components to provide
it. Many blood treatment process employ a filter 220 to filter
blood and into which replacement fluid is supplied to a patient
225. More details on preferred embodiments of the treatment machine
are discussed below.
[0076] In either of the above embodiments, the rate of flow of
fluid during preparation of the batch of replacement fluid may be
substantially less than the rate of consumption during treatment.
In an exemplary embodiment of an application for hemofiltration,
the amount of replacement fluid consumed is between 9 and 18 l. and
the rate of consumption is approximately 200 ml./min. For daily
treatment, a higher quantity of fluid is required. Also, the media
used for sterile filtration may be any suitable media that insures
the quality of the replacement fluid is as desired. In the
embodiments discussed above, it was assumed that the end sought was
preparation of filtered replacement fluid employed microfiltration
to prevent the passage of pyrogens including endotoxins and any
other pyrogens. However, the invention could be used with other
types of filtration or treatment processes to produce a batch of
fluid consumed by a medical treatment process, for example,
dialysate for hemodialysis treatment. The benefits accrue in
particular when the time scale of preparation may be longer than
the time scale of consumption. Moreover, the benefits are more
appreciable when some sort of energy-consuming process is required,
such as heating, before consumption. Here, not only is the time
scale of preparation compatible with a small inexpensive filter,
but the long time scale permits heating of the replacement fluid
over a long interval. To support this benefit, the batch container
may be insulated to minimize heat loss so a small heater will be
adequate. Also, the preferred application for the present invention
is in the context of hemofiltration because the quantity of fluid
required for such treatment is relatively small.
[0077] Note that other motivations for filtering the fluid, in
addition to or as an alternative to sterilization of a non-sterile
fluid, is (1) removal of air bubbles and/or (2) as a safety net for
ensuring against accidental contamination. If bubble removal is the
only concern, a drip chamber may be used instead of a filter. For
removing bubbles, the filter preferably is of a type that permits
the passage of fluid, but which blocks the passage of bubbles, for
example due to its media pore size and the surface tension of the
fluid.
[0078] Referring now to FIG. 4A, a preferred type of filter 400 for
some of the present embodiments has an inlet port 415 providing an
inlet channel 410 communicating with an inlet chamber 440. An
outlet leading port 405 provides an outlet channel 420
communicating with an outlet chamber 445. A piece of filter media
425 separates the inlet and outlet chambers 440 and 445. The fluid
to be sterilized enters the inlet chamber 440, is sterilized by
passing through the filter media 425, and exits via the outlet
chamber 445. A gas relief gasket 428 allows gas accumulating in the
inlet chamber 440 to be released to the ambient atmosphere.
Internal supports and structural details are not shown in the
illustration for clarity, but a practical embodiment of the filter
of FIG. 4 may have ribs for strength and internal supports for the
media 425 and gasket 428 so that the filter 400 may be capable of
tolerating a substantial TMP.
[0079] An integrated contact sensor 412 may be incorporated in the
filter to sense the quality of the fluid such as its salinity. The
illustration shows a pair of conductive contacts which, as will be
understood by those of skill in the art, may be connected to a
conductivity measuring device to generate a signal. Note that the
sensor 412 could also include a non-contact type sensor such as an
induction type device.
[0080] The gas relief gasket 428 may be of a porous hydrophobic
material such as PTFE. Air bubbles trapped in the inlet chamber 440
can coalesce in the inlet chamber 440 and exit via the gas relief
gasket 428. It may be, depending on the type of gas relief gasket
428 used, that a substantial TMP will be required to eliminate
air.
[0081] An alternative to the gas relief gasket 428 is a gas relief
valve 426 as shown in FIG. 4B. Since the inlet chamber 440 is
connected to the non-sterile side of the filtration system, there
is little risk of contamination if microbes were to enter through a
mechanical device such as the gas relief valve 426. The latter is
illustrated figuratively and allows only gas to escape. Other
features of the embodiment of FIG. 4B are labeled with the same
numerals as features of the embodiment of FIG. 4A where they serve
substantially identical functions and, thus, their descriptions are
not repeated here.
[0082] Referring now to FIG. 5, the filters of FIGS. 4A and 4B may
be used for filtration of replacement fluid in the embodiment of
FIG. 5 as discussed presently. Replacement fluid 360, which may or
may not be sterile, is supplied to a hemofiltration machine 490. A
replacement fluid pump 350 pumps the replacement fluid into a
balancing mechanism 330 which meters the replacement fluid before
it is introduced, via a junction 485, into the venous (return) line
480 and ultimately into the blood stream of a patient 225. Note
that a common alternative configuration dilutes the arterial blood
at 480B before it enters the filter 395. Waste fluid is drawn
through a waste line 470 from a filter 395 and pumped via a waste
pump 365 through the fluid balancing mechanism 330. The fluid
balancing mechanism 330 meters the replacement fluid to match the
rate of withdrawal of waste fluid so that the patient's fluid
balance is maintained during treatment. Actually, the rate of
withdrawal of waste fluid may be greater than the rate of metering
of replacement fluid by pumping waste fluid through a bypass pump
called an ultrafiltration pump 339. The latter sends some of the
waste fluid directly to a waste fluid sump 380, thereby bypassing
the fluid balancing-mechanism 330. The fluid balancing mechanism is
depicted figuratively and may operate in accord with any suitable
control device. Preferably it meters replacement fluid on an
equal-volume or equal-mass basis. A preferred mechanism is
described in U.S. patent application Ser. No. 09/513,911, filed
Feb. 25, 2000, entitled: "Synchronized Volumetric Fluid Balancing
Systems and Methods," which is hereby incorporated by reference as
if fully set forth in its entirety herein. Various sensors and line
clamps, indicated figuratively at 335, 355, 320, 385, and 390, may
be provided to control flow and ensure safe operation.
[0083] A filter 337, is provided in the replacement fluid line 338
just upstream of the junction 485. The filter 337 may serve as a
last chance safety net for ensuring that replacement fluid is
sterile and/or that all bubbles are removed before flowing into the
venous line 480. To ensure that air is not infused into the
patient's body, an air sensor 390 is often provided in
hemofiltration systems, but detection of air normally triggers an
alarm, automatic shutdown, and skilled intervention to restart the
hemofiltration treatment. Obviously, this is undesirable so the
system should, as effectively as possible, insure that air or other
gas is not injected into the venous line 480 without requiring
interruption.
[0084] Although the embodiment of FIG. 5 includes a hemofiltration
machine, other types of treatment processes may be provided a
last-chance filter similar to filter 337 and air sensor 390. For
example, hemodiafiltration, hemodialysis, or other treatments may
require the infusion of replacement fluid and thereby benefit from
a filter such as filter 337. Preferably, the filter 337 is
substantially as in the embodiment of FIG. 4A. Thus, the filter 337
removes both air and pyrogens.
[0085] Instead of employing a filter at the location indicated at
337, a drip chamber may be used. Suitable drip chambers are
currently available with air vents and microfilters effective to
remove pyrogens, so they may be substituted for the filter 337.
Also, in some cases, it may be that there is very little risk that
the replacement fluid is contaminated with pyrogens, the filter 337
may serve as a mechanism for removing only air or other gases. In
such cases, drip chambers which remove gas (either with or without
a vent), could be employed at the above location in the fluid
circuit.
[0086] Referring now to FIGS. 6, 7, and 8 the last chance filter or
drip chamber (or combination device) 510 may be installed in a
cartridge 520 that holds and orients blood and fluid circuits for a
hemofiltration machine 540. In the embodiment shown, which is
described substantially in U.S. patent application Ser. No.
09/513,773 filed Feb. 25, 2000 and entitled: "Fluid Processing
Systems and Methods Using Extracorporeal Fluid Flow Panels Oriented
Within A Cartridge," hereby incorporated by reference in its
entirety as if fully set forth herein, fluid circuit components may
be held in a cartridge 520 and clamped (as shown in FIG. 8 with the
machine closing as illustrated by the arrow 665) within a receiving
gap 530 in a blood treatment machine such as hemofiltration machine
540. The cartridge 520 may have a preferred orientation which may
insure a correct orientation for the last chance filter or drip
chamber (or combination device) 510 if required by the particular
device chosen. To insure orientation of the last chance filter or
drip chamber (or combination device) 510, the latter is preferably
held by the cartridge 520 in a fixed orientation with respect to
the cartridge 520.
[0087] In an alternative embodiment, the last chance filter or drip
chamber (or combination device) 520 may be accompanied by a device
660 for measuring the quality of the replacement fluid, such as
conductivity or density. This may provide a last-chance check that
the replacement fluid is of the correct type. For example, where
such fluids are derived from mixtures, if the proportion is not
exactly what is required, infusion could be harmful to the patient
225. An example of a device 660 to test the fluid could be a
wettable pair of contacts (not shown) formed in a tubing set 650 of
the cartridge may be used in conjunction with a resistance
measurement device to measure the ion concentration of the fluid.
Alternatively, a non-wettable sensor, such as an inductive
conductivity cell could be used. Other kinds of fluid quality
sensors could be employed such as specific-molecule detectors built
on silicon wafers and temperature sensors.
[0088] Preferably, the tubing set 650 and cartridge 620 of which it
is a part form a disposable component that is used for one
treatment and disposed of. Note that the fluid quality sensor 660
may used alone or together with the last chance filter or drip
chamber (or combination device) 510. Note, although FIGS. 6 and 7
are detailed, they are intended to show various components
figuratively and do not reveal the details of the routing necessary
to achieve the flow paths discussed with respect to them or as
illustrated elsewhere.
[0089] Referring now also to FIG. 9, the tubing set and cartridge
assembly 610, discussed previously, may incorporate the batch
replacement fluid container 625 as part of a sterile replaceable
set 690. The filter 615 may have a tube 622 with a connector 620
for attachment to a source fluid 250. A tube 635 may connect the
filter to the batch replacement fluid container 625, which may be
fitted with another tube 630 connected by a connector 648, which
may be permanent or removable, to convey fluid to the tubing set
and cartridge assembly 610. Referring now also to FIG. 10, the
batch replacement fluid container 625 may also be fitted with
additional connectors 670 and/or extensions (not shown) to permit
the batch replacement fluid container to be used for priming blood,
replacement fluid, and/or waste lines. For example, as discussed in
U.S. patent application Ser. No. 09/905,246, filed Jul. 12, 2001,
entitled: "Devices and Methods For Sterile Filtering of Dialysate,"
which is hereby incorporated by reference as if fully set forth in
its entirety herein, replacement fluid is circulated through a
replacement fluid container 740 to flush air out of all the fluid
circuiting (not all shown) of a blood treatment apparatus 710. As
described in detail in the '246 application incorporated by
reference above, the venous (return) and arterial (supply) blood
lines 725 and 730 may be temporarily connected via connectors 750
to the replacement fluid container 740 and fluid circulated through
the container 740 until gas bubbles are substantially purged from
the corresponding circuits. Note, the replacement fluid container
740 corresponds to the containers 147 (FIG. 1), 247 (FIG. 3), and
625 (FIG. 9) in the foregoing figures and to respective containers
in the application incorporated by reference immediately above. The
air and other gases may settle in the replacement fluid container
740 as the fluid circulates. Liberation of the gases would
ordinarily be promoted by the application of heat from a heater 775
(with power source 770), which may be employed as discussed with
regard to the embodiments of FIGS. 1-3 or in any suitable way to
bring the temperature of the replacement fluid to body temperature.
Replacement fluid circuits including line 735, blood circuits
including lines 725 and 730, and waste fluid circuits including
line 780 may all be flushed with fluid from the container 740. The
details of the blood treatment apparatus and its internal plumbing
can vary. Replacement fluid may be transferred from the replacement
fluid line 735 or from the blood line 735 to the waste line, for
example through a filter, to flush the waste portion of the circuit
including the waste line 780. Replacement fluid may circulate
through the blood circuit including lines 725 and 730 as indicated
to flush the blood circuit, at least a portion of which may be
closed as indicated by the arterial and venous lines 730 and
735.
[0090] Disposable components, such as the circuit sets of FIGS. 8
and 9 or the batch replacement fluid container 625 alone, or other
components that may be used with the embodiments disclosed may be
packaged with instructions for preparing infusible replacement
fluid. For example, the source fluid 150/250 or a concentrate which
may be mixed to make the same (FIGS. 1 and 3) may be supplied with
instructions for sterile filtering the fluid as described in the
instant specification. Such may constitute packages of consumables
or reusable components.
[0091] Note that benefits of the filtering method and apparatus
discussed above may best be achieved by performing the filtration
just prior to treatment, although this is not required. The
filtering method may be performed at the treatment site. For
example, non-sterile concentrate may be stored at the residence of
a patient. The concentrate may be diluted with distilled water in a
source fluid container (e.g., 196 of FIG. 1) at the residence and
processed as discussed in the instant application. Because the
infusible fluid is generated at the treatment site, the need for
regulatory-cleared fluids, such as might be obtained from a
manufacturer, is not avoided. Cost savings and storage-space
economies can thus be realized by the patient. This is particularly
important in view of the fact that renal replacement therapies are
often administered many times per week and storage and cost of
consumables can present a serious problem in a residence or any
other facility.
[0092] Referring now to FIG. 11, a blood treatment machine, a
portion of which is illustrated figuratively at 810, may permit a
pump 845 that, during treatment, conveys replacement fluid to a
patient, to be used for sterile filtering a non-sterile source
fluid. Here, the machine 810 has a common guide 850 that
accommodates a fluid line 815 through which fluid is conveyed by
the pump 845, for example a peristaltic pump. During treatment, the
line 815-825 may be guided by a first selected guide 830 in a first
direction toward other components of an internal fluid circuit (not
shown) as indicated at 825. During sterile-filtering, fluid may be
pumped by the same pump 845 through a line 815-820 that is allowed
to pass out of the blood treatment machine 810 via a different
guide 835. This allows the line 815-820 to be fed to an external
connection to the sterile fluid container (not shown) as indicated
at 820.
[0093] Referring now to FIGS. 12-14, a patient 640 receives a blood
treatment by a continuous process performed by a blood treatment
machine 610. The process extracts fluid from the blood of the
patient 640 which must be replaced to prevent the patient 640 from
dehydrating. For example, the treatment process may be
hemofiltration or hemodiafiltration. In such processes, blood may
be drawn from the patient 640 through an access 650 and returned to
the patient 640 through the same access 650.
[0094] As is known in the art, the treatment process provided by
the blood treatment machine 610 may remove substantial quantities
of fluids including electrolytes from the patent's 640 blood. As
part of the process, as is also known, fluid may be provided to the
patient 640 during treatment. During hemofiltration, for example,
multiple liters of fluid may be required to replace what is
withdrawn from the patient during treatment. Such fluid may require
multiple standard containers 10-30 to make up a sufficient quantity
to treat the patient 640.
[0095] The desired low levels of endotoxins discussed above may be
provided by means of a manifold 683 having inline filters 681 on
each arm 665 of the manifold 683. The manifold 683 has a header 655
connecting each arm 665 to a common feed line 645. Referring to
FIGS. 13 and 14, filters may be located on each arm 740 of a
manifold 770 as indicated at 776 or on a common feed line 790 as
indicated at 779. Either embodiment may include spikes 778 or other
suitable connectors for connecting to the source containers 10-30.
Again, the filters 681, 776, and 779 are preferably configured to
ensure levels of endotoxins in the filtered product are lower than
5 EU/Kg./hr. of treatment time and no more than 0.03 EU/ml.
[0096] Although the foregoing invention has been described by way
of illustration and example, it will be obvious that certain
changes and modifications may be practiced that will still fall
within the scope of the appended claims. For example, the devices
and methods of each embodiment can be combined with or used in any
of the other embodiments.
* * * * *