WO2005107928A2 - Metabolic detoxification system and method - Google Patents
Metabolic detoxification system and method Download PDFInfo
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- WO2005107928A2 WO2005107928A2 PCT/US2005/006003 US2005006003W WO2005107928A2 WO 2005107928 A2 WO2005107928 A2 WO 2005107928A2 US 2005006003 W US2005006003 W US 2005006003W WO 2005107928 A2 WO2005107928 A2 WO 2005107928A2
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- ultrafiltrate
- blood
- operative
- recirculation circuit
- pump
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
- A61M1/3475—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate with filtrate treatment agent in the same enclosure as the membrane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
- A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
- A61M1/3489—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents by biological cells, e.g. bioreactor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/38—Removing constituents from donor blood and storing or returning remainder to body, e.g. for transfusion
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/20—Accessories; Auxiliary operations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1694—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes with recirculating dialysing liquid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1698—Blood oxygenators with or without heat-exchangers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3623—Means for actively controlling temperature of blood
Definitions
- the present invention relates generally to metabolic detoxification, and more particularly to an extracorporeal blood filtration and detoxification system and method employing a recirculation circuit.
- the processing of blood has been performed to remove a variety of blood constituents for therapeutic purposes.
- blood processing methods include hemodialysis that allows to remove metabolic waste products from the blood of patients suffering from inadequate kidney function. Blood flowing from the patient is filtrated to remove these waste products, and then returned to the patient.
- the method of plasmapheresis also processes blood using tangential flow membrane separation, to treat a wide variety of disease states. Membrane pore sizes can be selected to remove the unwanted plasma constituents.
- Blood can be also processed using various devices utilizing biochemical reactions to modify biological constituents that are present in blood. For instance, blood components such as bilirubin or phenols can be gluconized or sulfated by the in vitro circulation of blood plasma across enzymes that are bonded to membrane surfaces.
- Embodiments of the present invention overcome the foregoing and various other shortcomings of conventional technology, providing an extracorporeal blood filtration and detoxification system and method employing a recirculation circuit.
- a system and method provide liver support for multiple therapeutic applications related to acute liver disease, allowing for either the potential regeneration of the impaired or partial liver to a healthy state, or the support of the patient with acute liver failure until all or part of a suitable donor organ can be found for transplant.
- FIG. 1 is a simplified block diagram illustrating one embodiment of an extracorporeal filtration and detoxification system.
- FIG. 2 is a simplified block diagram illustrating one embodiment of a blood control unit operative in conjunction with a recirculation circuit.
- FIG. 3 is a simplified block diagram illustrating one embodiment of a recirculation circuit.
- FIG. 4A is a simplified flow diagram illustrating the general operation of one embodiment of a method of extracorporeal filtration and detoxification.
- FIG. 4B is a simplified flow diagram illustrating the general operation of one embodiment of a method of treating ultrafiltrate.
- FIG. 5 is a simplified block diagram illustrating another embodiment of a recirculation circuit.
- FIG. 6 is a simplified flow diagram illustrating the general operation of another embodiment of a method of extraco ⁇ oreal filtration and detoxification.
- active cartridge refers to a hollow fiber based cartridge comprising cells (such as, for example, the C3A cell line) having utility in therapeutic applications and detoxification processes.
- blood circuit refers to a circuit of tubing connected to a double lumen catheter and operative to circulate blood from a patient to a blood control unit and back to the patient.
- C3A cell line refers to a sub-clone of the human hepatoblastoma cell line HepG2.
- C3A cells may be contained in the extracapiUary space of one or more active cartridges.
- An example of the external organ assist device which is preferably used with the system is a cell line commercially available from Baylor College of Medicine and designated as C3A. This cell line has been deposited at the American Type Culture Collection under ATCC No. CRL- 10741.
- detoxification device refers to a cartridge, canister, or other device that provides a means of removal of specific or non-specific molecules from a fluid stream. Examples would be a dialysis cartridge, an adsorption cartridge, or a filter.
- ECS extracapiUary space
- ICS intracapillary space
- the ICS is the flow path for whole blood or the ultrafiltrate fluid.
- recirculation circuit refers to a circuit generally enabling filtration, detoxification, and treatment of ultrafiltrate fluid; in some implementations, a recirculation circuit generally encompasses a reservoir, an oxygenator, and one or more active cartridges.
- TMP transmembrane pressure
- the amount of ultrafiltration may generally be determined by the TMP across the cartridge membrane; accordingly, TMP and the amount and rate of ultrafiltration may generally be a function of the operational characteristics of an ultrafiltrate pump as well as various physical properties (e.g. pore size and surface area) of the membrane employed in the ultrafiltrate generator.
- UF ultrafiltrate
- the term "ultrafiltrate generator” refers to a device comprising or embodied as a "blank” active cartridge (i.e. a hollow fiber cartridge which does not contain therapeutically active cells) and operative to separate plasma fluid (ultrafiltrate) from cellular blood components.
- the hollow fibers may be composed of a semi-permeable membrane which has, for example, a nominal molecular weight cut-off of approximately 100,000 Daltons in some implementations.
- blood may be circulated through the ICS of the hollow fibers; ultrafiltrate, comprising blood plasma and various macromolecules, passes through the membrane fiber walls into the recirculation circuit, where it is circulated through one or more active cartridges.
- ultrafiltration refers generally to a process during which ultrafiltrate is pulled from whole blood across the semi-permeable membrane of the UFG.
- an ultrafiltrate pump may control the rate of ultrafiltrate production, while the pore size of the hollow fiber membrane of the UFG may control the amount of ultrafiltrate permeating the membrane.
- FIG. 1 is a simplified block diagram illustrating one embodiment of an extracorporeal filtration and detoxification system.
- system 10 generally comprises a blood control unit 20, a heparin pump 30, an ultrafiltrate generator UFG 40, a recirculation circuit 50, and can optionally include other detoxification devices.
- system 10 embodies a continuous therapy device generally operable to draw blood (facilitated by a blood pump 21 , for example) from a patient into blood control unit 20 via an appropriate conduit or other device such as a double lumen catheter, for instance, or the e ⁇ uivalent thereof.
- UFG 40 may receive whole blood from blood pump 21 and separate UF fluid from cellular components substantially as set forth below. While cellular components may be returned from UFG 40 to the patient (as indicated by conduit or fluid line 41, for example) via the venous access, UF may be drawn from UFG 40 (as indicated by conduit or fluid line 42, for example) by an ultrafiltrate pump 22 for redirection through recirculation circuit 50. Following treatment in recirculation circuit 50, UF may be recombined with cellular components for reintroduction to the patient.
- a heparin infusion pump 30 can be used to introduce heparin into the whole blood upstream of UFG 40.
- heparin, an acidic mucopolysaccharide, or various derivatives thereof may provide anticoagulant effects; other anticoagulant agents may be appropriate depending upon, among other things, the nature of the detoxification treatment and various other system parameters.
- FIG. 2 is a simplified block diagram illustrating one embodiment of a blood control unit operative in conjunction with a recirculation circuit. Overall operation of system 10 and the various components thereof may generally correspond to that set forth above with reference to FIG. 1.
- Blood control unit 20 as contemplated herein may be a dual pump continuous dialysis-type machine; in that regard, blood control unit 20 may be embodied, for example, in a Diapact(TM) CRRT (Continuous Renal Replacement Therapy) Machine such as manufactured by B. Braun.
- TM Diapact
- CRRT Continuous Renal Replacement Therapy
- a detoxification cartridge (or cartridges), may be placed in various places within the blood and ultrafiltrate circuits.
- blood control unit 20 may comprise two pumps (blood pump 21 and UF pump 22) as noted above.
- Blood pump 21 may enable circulation of a patient's whole blood through UFG 40 and facilitate return of cellular blood components to the patient, for example, through line 41.
- UF pump 22 may draw UF from UFG 40 (e.g. through line 42 as noted above) and deliver the UF to assist with recombination of treated UF with the cellular components of a patient's blood by maintaining a predetermined or dynamically adjusted hydrostatic head, for example.
- heparin infusion pump 30 may provide heparin or a similar anticoagulation agent to the blood circuit upstream of UFG 40; similarly, a glucose infusion pump 51 may provide a supply of glucose to the UF upstream of recirculation circuit 50 to nourish the C3A or other active cells.
- heparin pump 30 and glucose pump 51 may comprise or be implemented in Harvard Ohmeda Dual Syringe Pumps, for example, or equivalents thereof. Pumps 30 and 51 are illustrated in representative form only; irrespective of the type of pumping apparatus implemented, pumps 30 and 51 may deliver fluid at a predetermined constant rate, for example, or at a dynamically adjustable rate.
- pumps 30 and 51 may comprise suitable sensors or sensor inputs, actuators, and control electronics operative in accordance with sensor output and control signals to adjust flow rates dynamically as a function of overall flow rate through blood control unit 20 and recirculation circuit 50, respectively.
- Indications of overall flow rate may be obtained, for example, from output provided by flow rate or pressure sensors distributed at various locations in the circuits substantially as set forth below.
- FIG. 2 An exemplary embodiment shown by FIG. 2 includes five fluid pressure transducers generally operative to detect absolute value as well as variances or perturbations in fluid pressures throughout the tubing system of blood control unit 20. Additionally or alternatively, fluid flow meters may be inco ⁇ orated at similar or equivalent points in the indicated flow stream. Each pressure transducer in the FIG. 2 embodiment may be covered or sheathed by a respective transducer protector as is generally known in the art. Additional pressure sensors may be located throughout the circuit to measure and control the fluid flow paths.
- Blood withdrawal pressure may be measured as indicated at point BW.
- the blood withdrawal monitors fluid pressure and any pressure fluctuations of the outflow of blood from a patient to blood pump 21.
- Blood pump discharge pressure may be measured as indicated at point P3.
- the blood pump discharge pressure sensor monitors the inlet pressure of the next distal component to the blood pump, and any fluctuations or variations thereof.
- Blood return pressure may be measured as indicated at point BR. As shown by immediately proximal as well as the fluid pressure of the inflow of whole blood back to the patient.
- blood control unit 20 may also comprise a blood leak detector 23 and one or more valve assemblies 24.
- Blood leak detector 23 may be located within the UF line (e.g. downstream of UF pump 22 as depicted in FIG. 2), and may be operative to identify whole or hemolyzed blood present in the UF fluid. The presence of such whole blood or other cellular constituents may evidence a failure or degradation of UFG 40 efficacy, and may generally indicate a need to replace, clean, or otherwise to maintain the hollow fiber cartridge implemented at UFG 40.
- Valve assembly 24 may be embodied in any of various control valves or other fluid regulation apparatus generally known in the art.
- valve assembly 24 may be a safety or one-way valve, permitting only unidirectional fluid flow to a patient; in this implementation, upstream pressure fluctuations may not create negative pressure or suction at the venous access of the patient.
- valve assembly 24 may be selectively or dynamically activated responsive to control signals or sensor input (e.g. from pressure or flow sensors at point PV or at other locations in blood control unit 20) such that fluid flow may be regulated at or near a constant rate as upstream pressures vary over time, or shut off completely.
- UFG 40 generally comprises one or more "blank" hollow fiber cartridges operative to separate UF from cellular components of the whole blood drawn from a patient.
- a priming solution such as saline, for example
- Alternative methods can be used for plasma separation, if desired. For example, centrifugation can be used.
- UFG 40 may be implemented as an independent system component, i.e. distinct or physically separated from blood control unit 20; in the exemplary embodiment, independent maintenance, repair, or substitution of blood control unit 20, UFG 40, or constituent parts thereof, for example, may be facilitated by the fact that each is may be inco ⁇ orated into or integral with blood control unit 20; this embodiment may provide advantages attendant with shorter or more direct fluid flow through cartridges employed at UFG 40, and accordingly, may reduce power consumption and increase overall system efficiency.
- hollow fiber filter cartridges implemented at UFG 40 may be configured to allow easy removal and replacement with respect to blood control unit 20.
- air detectors may be implemented to detect air bubbles or other gaseous contaminants within the circulating fluids.
- one or more air detectors may be inco ⁇ orated into the blood circuit at selected locations in blood control unit 20, and one or more additional air detectors may also be inco ⁇ orated at selected locations in recirculation circuit 50.
- numerous suitable mechanical filtration systems may be employed to remove unwanted gaseous contamination.
- one or more of such filtration systems may be selectively operative responsive to output from one or more air detectors. Accordingly, while representation of some of the hardware has been omitted for clarity, it will be appreciated that the present disclosure contemplates detection and removal of air and other gaseous bubbles from the fluidic system, particularly at or near venous access to the patient.
- FIG. 3 is a simplified block diagram illustrating one embodiment of a recirculation circuit.
- recirculation circuit 50 is generally fed by glucose infused UF; in that regard, output from UF pump 22 (i.e. untreated UF) may be infused with glucose or a similar substance from glucose pump 51 through a valve assembly 61 or other flow regulation device prior to, or in conjunction with, introduction into recirculation circuit 50.
- valve assembly 61 may permit only unidirectional fluid flow (i.e. from pump 51 to the UF line) such that pressure fluctuations do not draw UF from the line and into pump 51.
- valve assembly 61 may be selectively or dynamically activated responsive to control signals or sensor input (e.g. from pressure or flow sensors at selected locations in recirculation circuit 50) such that glucose may be delivered at a predetermined constant rate, for example, or at a dynamically adjustable rate as a function of overall flow
- the exemplary recirculation circuit 50 generally comprises a recirculation pump 53, an oxygenator 54, one or more active cartridges 55 or clusters of cartridges, and a reservoir 52.
- the recirculation circuit may optionally contain one or more detoxification devices D, as shown by FIG. 3.
- oxygenator 54, active cartridges 55, and reservoir 52, or some combination thereof may be disposed in a heating chamber 59 or other environmentally controlled room or space.
- recirculation circuit 50 may include one or more additional filters 56 inte ⁇ osed between reservoir 52 and the point at which treated UF is recombined with cellular components from UFG 40.
- a UF return pump may be used to deliver ultrafiltrate through the filter, or filters. If desired, the locations of oxygenator 54 and active cartridges 55 can be optionally switched.
- untreated UF output from UF pump 22 may be directed to reservoir 52 following glucose infusion.
- reservoir 52 may comprise or be implemented as an arterial filter such as manufactured by Sorin, for example.
- reservoir 52 may generally serve as a holding tank or container, storing sufficient UF to account for any difference in flow rates between the blood circuit in blood control unit 20 and recirculation circuit 50.
- a level sensor and control or a weighing system may be used to maintain fluid balance in the recirculation circuit.
- Recirculation pump 53 may be embodied in a peristaltic pump such as manufactured by Watson Marlow, for example, or any other suitable shaft driven pumping mechanism such as those employing reciprocating pumps, centrifugal pumps, and the like. In operation, recirculation pump 53 may drive circuit 50, drawing UF from reservoir 52, circulating the UF fluid through oxygenator 54 and active cartridges 55 and back into reservoir 52. Other pumping systems can be used if desired. For example, the blood and UF pumping system COBE CV Stockert SIII can be used.
- Oxygenator 54 may comprise, or be embodied in, any of various membrane oxygenators generally known in the art or other types of oxygenators developed and operative in accordance with known principles. In operation, oxygenator 54 may provide oxygen for utilization in the detoxification or therapeutic process executing in active cartridges 55. Accordingly, the type, nature, and operational characteristics of oxygenator 54 may be selected as a function of the type and quantity of active cells (such as C3A cells, circuit 50, and other system parameters. In some implementations employing C3A cells, for example, oxygenator 54 may be embodied in a Monolyth M(TM) oxygenator such as manufactured by Sorin.
- TM Monolyth M(TM) oxygenator
- heating chamber 59 may comprise or implement any number of environmental control apparatus known in the art and generally operative to maintain selected environmental operating conditions for oxygenator 54, active cartridges 55, and reservoir 52.
- some implementations may benefit from maintaining the foregoing system components at a constant 37°C, or within a predetermined or specified range close to that temperature. It will be appreciated that optimum temperatures, temperature ranges, and acceptable deviations therefrom may be influenced by the type and quantity of active cells implemented in active cartridges 55, ambient conditions and overall UF flow rates through recirculation pump 53, the nature and character of treatment or processes occurring in active cartridges 55, and the like.
- recirculation circuit 50 inco ⁇ orates a Certomat(TM) heating chamber apparatus manufactured by B. Braun.
- recirculation circuit 50 may inco ⁇ orate one or more active cartridges 55, each of which may be embodied as or comprise a hollow fiber filter. Accordingly, each active cartridge 55 may comprise a bundle of hollow fibers employing a semi-permeable membrane. Surrounding these fibers, in the ECS, one or more types of active cells may be utilized to treat the UF in a selected manner as the UF circulates through the ICS. The character, quantity, density, and genetic composition of active cells facilitating treatment in active cartridges 55 may be selected as a function of the overall functionality of system 10 in which recirculation circuit 50 is employed. As set forth herein, an exemplary embodiment of system 10 and recirculation circuit 50 inco ⁇ orates C3A cells, though other alternatives exist, depending upon, inter alia, the desired utility of system 10 and the nature of the contaminant sought to be removed or treated.
- hollow fiber active cartridges 55 may have a nominal molecular weight cut-off of greater than 70,000 Daltons, for example, allowing middle molecular weight molecules such as albumin to cross the membrane. Macromolecules produced by the C3A or other active cells may be able to diffuse into the UF circulating through the ICS; similarly, albumin-carrying toxins are able to diffuse from the ICS to the mechanisms described above, multiple cartridges may be employed in parallel, for example, or in series.
- UF may be pumped through the lumen (ICS) of the hollow fiber cartridge, allowing toxins, nutrients, glucose, and dissolved oxygen from the UF to diffuse across the membrane into the ECS, where the active cells may metabolize them. Metabolites, along with albumin and other proteins produced by the cells, may diffuse back across the membrane into the UF for return to the patient.
- ICS lumen
- treated UF may be returned to reservoir 52.
- Reservoir 52 may collect both untreated UF transported from UF pump 22 as well as treated UF which has already passed through active cartridges 55. Implementation of reservoir 52 as indicated may enable higher or lower flow rates through recirculation circuit 50 than through the blood circuit, as required, whereas UF may be supplied from recirculation circuit 50 downstream to the patient at a suitable rate.
- UF from reservoir 52 may pass through one or more additional filters 56 or filter series prior to reintroduction to the blood circuit.
- three in-line (i.e. arranged in series) cell filters may employ a membrane pore size of approximately 0.45 ⁇ m, for example.
- Additional filters 56 may provide a safety feature, preventing possible transmission of C3A or other active cells to the patient; accordingly, the pore size of membranes employed at additional filters 56 may generally be selected as a function of the type of cells utilized at active cartridges 55 or the nature and average size of other contaminants sought to be filtered.
- Additional filters 56 may be placed immediately upstream of the juncture of recirculation circuit 50 and the blood circuit as indicated in FIG. 3.
- UF may be circulated through a series of active cartridges 55 comprising, in some embodiments, C3A cells or other active cells operative to effectuate one or more selected therapeutic treatments.
- active cartridges 55 the UF passes through the ICS of a bundle of hollow fibers, each comprising a semi-permeable membrane.
- the C3 A or other active cells may be disposed in the ECS of active cartridges 55.
- the semi-permeable membrane fibers cellular products such as albumin, transferrin, ⁇ -1-antitrypsin, ⁇ -fetoprotein, and others. Simultaneously, the semi-permeable membrane fibers permit passage of toxins and metabolic necessities (e.g. such as glucose and oxygen) from the UF to the active cells.
- the UF may be subject to additional filtration such as by additional filters 56; as noted above, additional filtration may comprise employing three or more 0.45 ⁇ m in-line cell filters.
- additional filtration may comprise employing three or more 0.45 ⁇ m in-line cell filters.
- UF may then be recombined with the cellular components of the patient's blood in the blood circuit.
- the recombined whole blood and UF may be returned to the patient through the double lumen catheter, regulated by valve assembly 24 substantially as set forth above.
- the foregoing circulation strategy may be maintained continuously for the duration of therapy facilitated by system 10 and recirculation circuit 50 utilizing active cartridges 55.
- the C3A cell line is a subclone of the human hepatoblastoma cell line HepG2, and is typically available through American Type Culture Collection (ATCC).
- HepG2 the parent cell line, was derived from a hepatoblastoma excised from a 15-year old Caucasian male from Argentina in 1975 in Philadelphia, Pennsylvania, USA.
- the C3A cell line has demonstrated such liver-specific functionality, and has been described herein by way of example only, and not by way of limitation.
- Recirculation circuit 50 may further comprise various other components as indicated in FIG. 3.
- Valve assemblies 62 and 65 may prevent back-flow and provide regulated flow rates on the suction side and the pressure side, respectively, of recirculation pump 53.
- some embodiments may employ dynamically activated valve assemblies, which may be selectively adjusted to control flow rates precisely; appropriate sensors, such as temperature, pressure, or flow meters and associated art will appreciate that various techniques and flow control apparatus are generally known and encompassed herein.
- a priming reservoir 63 may provide necessary fluid to prime, for example, recirculation pump 53 and active cartridges 55 (if required) as well as the conduits or tubing making up recirculation circuit 50; in that regard, a collection reservoir 64 may be provided downstream of active cartridges 55, for example, to collect priming fluid prior to therapy or to flush recirculation circuit 50 for maintenance. Additionally, maintenance or replacement of various components such as recirculation pump 53, for example, and active cartridges 55, in particular, may be facilitated by valves, quick-disconnect couplings, or other flow restricting mechanisms disposed at various locations in recirculation circuit 50.
- a quick-disconnect coupling at both the upstream and downstream sides of active cartridges 55 may facilitate maintenance and significantly contribute to system flexibility. Where active cartridges 55 may quickly and easily be isolated from recirculation circuit 50, additional or replacement active cartridges 55 may be selectively inserted or substituted responsive to efficiency degradation, modification of treatment strategy, or other factors.
- each of the components of system 10 may be selected with particularity to support the biological, chemical, or other functionality of the therapeutic cells within active cartridges 55, to circulate blood and UF through the conduits at selected flow rates, and ultimately to provide the selected therapy. Accordingly, the functional characteristics of each component may be influenced by design choices made with respect to other aspects of system 10.
- one continuous dialysis-type machine supporting suitable therapeutic processes is the B. Braun Diapact(TM) CRRT machine noted above, which may provide sufficient flexibility to satisfy various system requirements with respect to blood control unit 20.
- blood pump 21 may be configured and operative to circulate blood from the patient through UFG 40 and back to the patient at a flow rate of approximately 200 mL/min during therapy
- UF pump 22 may deliver UF from UFG 40 to recirculation circuit 50 at a flow rate of approximately 20 mL/min during therapy.
- Treated UF may be recombined with whole blood for return to the patient at a similar 20 mL/min rate.
- a continuous heparin infusion (provided by heparin infusion pump 30) may be used to provide heparin or another suitable anticoagulation agent to the blood circuit of system 10.
- the Harvard Ohmeda dual syringe pump may provide appropriate heparin flow rates.
- the heparin may be infused at a constant rate into the blood circuit immediately downstream of the blood pump inco ⁇ orated into the Diapact(TM) CRRT machine as indicated in FIGS. 1 and 2, for example.
- the degree of anticoagulation may be monitored with the patient's Partial Thromboplastin Times (PTTs) drawn at regular intervals.
- PTTs Partial Thromboplastin Times
- a sliding scale algorithm may determine the heparin dosing and infusion rate which, as set forth in detail above, may be modified dynamically, facilitated by appropriate sensors, actuators, and control electronics, for example.
- UFG 40 may implement a blank hollow fiber filter cartridge (i.e. one which contains neither C3A nor other active cells) operative to separate cellular components of blood from UF.
- the hollow fibers generally comprise a semi -permeable membrane having a nominal molecular weight cut-off of greater than about 70,000 Daltons.
- total fluid volume in the ICS may approach approximately 95 mL, whereas total fluid volume in the ECS may be approximately 130 mL.
- the Harvard Ohmeda dual syringe pump may be implemented as glucose pump 51, maintaining a continuous glucose infusion calculated to provide adequate glucose levels to the cells within active cartridges 55 during therapy.
- the glucose may be infused at a constant rate into the UF line upstream of the connection with recirculation circuit 50 as indicated in FIGS. 2 and 3, for example.
- a sliding scale algorithm may determine the glucose infusion rate which, as set forth in detail above, may be modified dynamically, facilitated by appropriate sensors, actuators, and control electronics, for example.
- the Watson Marlow peristaltic pump mentioned above may be implemented as recirculation pump 53, providing constant UF flow from reservoir 52, through oxygenator 54 and the active cartridges 55, and back to reservoir 52.
- the pump may provide a flow rate sufficient to supply adequate nutrients and oxygenation to sustain the cells in active cartridges 55; in the case of the system parameters noted above, this flow rate may be approximately 2 L/min of UF flow. Accordingly, any pump capable of providing such a flow rate under the same operating conditions may be implemented.
- membrane oxygenator 54 may be positioned within the recirculation circuit at a point upstream of active cartridges 55 to assure that sufficient oxygen is provided to the active cells during therapy.
- total fluid volume of oxygenator 54 may approach approximately 300 mL.
- an gas flow meters (not shown) may be coupled between the gas supplies and oxygenator 54; as is generally known in the art, such gas flow meters may facilitate regulation of the amount of oxygen delivered to oxygenator 54, ensuring sufficient oxygenation to sustain the therapeutically active cells maintained in active cartridges 55.
- the C3A cells may be contained within active cartridges 55 in the ECS outside of the membrane walls of the hollow fibers; membrane pore size may be selected such that the possibility of C3A cells leaving active cartridges 55 during treatment is exceedingly low.
- a number such as three or more, for example, coupled in series
- Whatman Polycap TC in-line cell filters may be placed in the UF return line, immediately upstream of the point where treated UF recombines with the venous return circuit.
- the total fluid volume per filter may be approximately 75 mL.
- System 10 may be designed to provide continuous treatment; accordingly, one or more auxiliary batteries or other uninterruptible power supplies may be provided at various locations in system 10.
- An example of a suitable back-up battery system comprises a Clary & ONE AC 1300, which may provide an uninterruptible power supply for approximately 40 minutes to all system components (such as pumps 21, 22, 30, 51, and 53, for example) during operation. Additionally or alternatively, each powered component of system 10 may be provided with a respective uninterruptible power supply.
- System 10 generally comprises segments of tubing or conduits that make up the blood circuit and recirculation circuit 50.
- collection bags or reservoirs 64,63 may be inco ⁇ orated into the circuits to collect priming and shipping solutions prior to patient use, for example, or to facilitate recirculation circuit 50 may generally be constructed in accordance with known materials and techniques to provide conduits suitable for therapeutic or clinical use.
- FIG. 4A is a simplified flow diagram illustrating the general operation of one embodiment of a method of extraco ⁇ oreal filtration and detoxification.
- the processes depicted in FIG. 4A may be facilitated by the various components, or appropriate combinations thereof, illustrated in FIGS. 1 and 2.
- a method of extraco ⁇ oreal filtration and detoxification of blood may begin by drawing blood from a patient as indicated at block 411. Blood may be drawn using various apparatus or devices generally known in the art, such as a double lumen catheter, for example.
- UFG 40 may be inco ⁇ orated in a blood control unit 20, or may be implemented independently; in either of the foregoing embodiments, whole blood may be delivered from the patient to UFG 40 by a blood pump 21, whereas UF may be drawn through the semi-permeable membrane of UFG 40 by a dedicated UF pump 22.
- a dedicated UF pump 22 may be illustrated in FIG. 4A, it will be appreciated from the foregoing discussion and examination of FIGS. 1-3 that cellular components of the whole blood passing through UFG 40 may be returned to the patient, for example, through the venous access of the double lumen catheter described above.
- Circulating or treating UF independently of the cellular components of whole blood may be facilitated by a recirculation circuit such as illustrated and described in detail with reference to FIG. 3.
- treating UF as contemplated at block 413 generally comprises circulating the UF through one or more active cartridges containing or comprising C3A or other active cells in the ECS of a hollow fiber filter.
- Recombining treated UF and the cellular components of whole blood as indicated at block 414 may utilize or involve a simple valve assembly or fluid conduit junction, for example.
- the recombining operation at block 414 generally represents the reintroduction of treated UF from recirculation circuit 50 to the blood circuit coursing through blood control unit 20 substantially as illustrated and described above with reference to FIGS. 1-3.
- rate computed as a function of the desired rate at which whole blood is returned to the patient In rate computed as a function of the desired rate at which whole blood is returned to the patient.
- Returning whole blood to the patient as indicated at block 415 may involve utilizing valve assemblies or otherwise regulating the flow rate in accordance with the patient's physical condition and internal blood pressure requirements.
- the returning operation at block 415 may employ or comprise some or all of the following features or hardware: dynamically adjustable valve assemblies enabling precise pressure control or flow regulation; safety valves or back flow restrictors preventing upstream pressure variations from reversing the direction of blood flow; and gas bubble detection and removal apparatus or devices.
- FIG. 4B is a simplified flow diagram illustrating the general operation of one embodiment of a method of treating ultrafiltrate.
- the processes depicted in FIG. 4B are related to operation of recirculation circuit 50, for example, and accordingly may be facilitated by the various components, or appropriate combinations thereof, illustrated in FIG. 3.
- Treating UF in accordance with the FIG. 4B method generally relates to the operation depicted at block 413 of FIG. 4 A.
- drawing UF through a membrane as indicated at block 421 may represent an aspect of generating UF, such as with UFG 40, for example; accordingly, the drawing operation of block 421 may also be associated with the separating operation of block 412 in FIG. 4A.
- the process at block 421 is included in FIG. 4B for the sake of clarity and thoroughness.
- UF may be checked or analyzed for leaks.
- a blood leak detector 23 (FIG. 2) may be located within the UF line downstream of UFG 40.
- Checking for leaks as indicated at block 422 and decision block 431 generally comprises analyzing the composition of UF downstream of UFG 40 and identifying whole or hemolyzed blood present in the UF fluid. As set forth above, the presence of such whole blood or other cellular constituents in the UF may indicate a need to replace, clean, or otherwise to maintain (block 432) the hollow fiber cartridge implemented at UFG 40.
- Untreated UF inout to recirculation circuit 50 mav be nrovided to reservoir 52 a ⁇ or other nutrients, heparin or other anticoagulation agents, or other fluids into recirculation substantially as set forth above. It will be appreciated that the operation depicted at block 424 may occur prior to blocks 422 or 423, for example, or elsewhere in the FIG. 4B embodiment. In that regard, more than one fluid infusion may occur at selected locations throughout recirculation circuit 50 of FIG. 3 (and thus at various locations in FIG. 4B) depending upon the type and quantity of fluid to be infused, the nature and requirements of the active cells maintained in active cartridges, overall flow rate of UF through the circuit, and other system parameters.
- primer solution at block 411 and the collection of primer solution at block 427 may occur where indicated or elsewhere in FIG. 4B, depending, for example, upon the particular system components requiring priming. If reservoir 52 requires priming in the FIG. 3 embodiment, for instance, priming at block 441 may occur prior to providing UF to reservoir 52 at block 423. Valve assemblies, quick- disconnect couplings, collection bags, or other apparatus enabling primer collection at block 427 may be selectively located in recirculation circuit 50 as a function of the particular arrangement or relative orientation of system components. Accordingly, the operations at block 441 and block 427 may be duplicated or relocated in the FIG. 4B embodiment, depending upon the number and relative locations of system components (e.g. such as pump 53, oxygenator 54, and active cartridges 55) requiring priming.
- system components e.g. such as pump 53, oxygenator 54, and active cartridges 55
- UF may be oxygenated at block 425 and treated at block 426.
- Various aspects of the oxygenation process e.g. pressure, partial pressures and composition of any air/gas mixture, infusion rates, and the like
- the oxygenation process e.g. pressure, partial pressures and composition of any air/gas mixture, infusion rates, and the like
- treating or detoxifying UF may generally occur in active cartridges at block 426.
- the operational characteristics and specific chemical, biological, and other processes associated with block 426 may be influenced by the intended overall operation of system 10 (i.e. the type of treatment required), and may be selectively adjusted, controlled, or otherwise manipulated in accordance with the specific hardware components implemented in recirculation circuit 50.
- Treated UF may be returned to reservoir 52 as indicated at block 428 and reservoir or other fluid container at both ends of a recirculation circuit 50 may allow or enable a system and method of treating UF to operate at a different flow rate than that maintained in the blood circuit of a treatment system 10.
- filtering at block 429 may include passing UF through one or more in-line (i.e. arranged in series) cell filters, each having a membrane pore size of approximately 0.45 ⁇ m, for example. Additionally or alternatively, filtering at block 429 may comprise passing UF through hollow fiber cartridges having very small pore sizes (such as 0.1 - 0.2 ⁇ m, for example), ammonia traps, charcoal filters, mechanical filters, and the like.
- the specific hardware or filtering apparatus selected for the block 429 operation may generally be influenced or dictated by the type of cells utilized at active cartridges 55 or the nature and average size of other contaminants sought to be filtered. Filtering at block 429 may occur immediately upstream of the juncture of recirculation circuit 50 and the blood circuit as indicated in FIG. 3. It will be appreciated that UF which is neither processed at block 429 nor returned to the patient may be recirculated for additional treatment as represented by the loop from block 428 back up to block 423.
- FIG. 5 is a simplified block diagram illustrating another embodiment of a recirculation circuit.
- the FIG. 5 embodiment may be implemented in conjunction with system 10 such as illustrated and described above with reference to FIGS. 1 and 2.
- various elements represented in FIG. 5 generally correspond to those described in detail above with reference to FIG. 3, and may comprise, embody, or inco ⁇ orate some or all of the functionality and the structural or operational characteristics set forth above.
- like reference numerals generally represent like, similar, or equivalent components embodying the foregoing attributes as well as additional features or aspects set forth below.
- blood control unit 20 pumps 30 and 51, additional filters 56, and UFG 40, as well as valve assemblies 61 and 24, for example, may generally correspond to those previously described, and may operate substantially as set forth in detail above.
- valve assemblies 61 and 24 may generally correspond to those previously described, and may operate substantially as set forth in detail above.
- the locations of oxygenator may be provided for use with either the FIG. 3 or the FIG. 5 recirculation circuit 50, though particular advantages may be attendant with implementation of such a modified UFG 40 in the FIG. 5 arrangement.
- UFG 40 may inco ⁇ orate or comprise synthetic fibers (such as polysulfone, for example, or an equivalent thereof) having increased membrane permeability; these fibers may facilitate increased or improved transfer of proteins (especially albumin, having an approximate molecular weight of 68,000 Daltons) across the semi-permeable membrane.
- a modified UFG 40 may allow more efficient albumin transfer from the whole blood to the UF. In some embodiments, this efficient albumin transfer at UFG 40 may result in a greater quantity of albumin available for transfer to the therapeutic cells in active cartridges 55.
- Many toxins are known to bind to albumin, and UFG 40 modified to comprise polysulfone fibers may permit a higher rate of transfer of these albumin-bound toxins to the active therapeutic cells.
- UFG 40 may prevent a significant amount (less than, for example, 10 %) of fibrinogen (having an approximate molecular weight of 340,000 Daltons) to be transported across the membranes from whole blood to the UF.
- a polysulfone UFG and 0.2 micron cartridges available from Minntech Co ⁇ . can be used.
- the FIG. 5 recirculation circuit 50 may provide or inco ⁇ orate some or all of the following refinements: superior hollow fiber cartridge materials and more appropriate fiber porosity; utilization of Community of Europe (CE) marked components; data acquisition, consolidation, storage, and reporting, as well as realtime or near real-time display of active cartridge metabolic data; reduced risk of contamination during set-up or initialization; open arrangement of system components; and a more efficient filtration configuration and design.
- CE Community of Europe
- a detoxification device 59 may be implemented in the UF line upstream of glucose infusion pump 51. It will be appreciated that detoxification device 59 may be located elsewhere in recirculation circuit 50, depending, for example, upon the desired operational flow rate of UF through recirculation pump 53, the type and quantity of active therapeutic cells utilized in active cartridges 55, and other factors. In some embodiments, detoxification device 59 may be situated in the return line, i.e. inte ⁇ osed between filters 79 and the junction with the blood circuit. For treated whole blood prior to infusion into the patient. A cardioplegia heat exchanger from COBE CV (model CSC 14, for example) may satisfy system requirements.
- Reservoir 52 described above with reference to FIG. 3 may be augmented by or replaced with (as in the exemplary FIG. 5 arrangement) one or more hollow fiber filters 79.
- filters 79 may comprise membranes having a pore size of between 0.1 and 0.2 ⁇ m (to capture microbacteria, for example), and may provide a fluid volume of UF similar to that of reservoir 52 (e.g. approximately 200 mL), accommodating or allowing differential flow rates between the blood circuit and recirculation circuit 50 as set forth above.
- the FIG. 5 recirculation circuit 50 may include one or more priming reservoirs 63 upstream of recirculation pump 53 to provide suitable priming fluid or combinations of fluids prior to initiation of therapy or detoxification treatments.
- one or more collection bags or reservoirs 64 may collect priming fluid, for example, or allow one or more components of recirculation circuit 50 to be flushed for maintenance.
- recirculation pump 53 may be a non-CE-marked peristaltic or (roller) pump.
- a centrifugal pump may provide a safer recirculation flow (i.e. little or no over-pressurization and, consequently, less risk of burst tubing) without sacrificing accuracy or ease of operation.
- at least three CE-marked centrifugal pumps currently available may satisfy system requirements: COBE CV (Revolution); Terumo Medical (Sarns Centrifugal System); and Medtronic (Bio-Pump).
- COBE CV Revolution
- Terumo Medical Ses Centrifugal System
- Medtronic Bio-Pump
- FIG. 5 arrangement On the pressure side (i.e. downstream) of recirculation pump 53, the FIG. 5 arrangement inco ⁇ orates a heat exchanger 71 operative in conjunction with oxygenator 54.
- a heater unit 72 such as a water bath and Extraco ⁇ oreal Membrane Oxygenation (ECMO) heater apparatus, for example, may be coupled to heat exchanger 71, enabling or facilitating recirculation circuit 50 to maintain temperatures of the UF in active cartridges 55 at or near 37°C.
- oxygenator 54, heat exchanger 71, and heater unit 72 may generally replace heating chamber 59 implemented in the FIG. 3 configuration.
- ECMO heaters approved for medical or clinical use are currently available from Cincinnati Sub-Zero and Terumo Medical, for example.
- insulation may sustain UF in recirculation circuit 50 at an appropriate or desired temperature, or within a prescribed temperature range.
- a layer of removable insulation may be applied to active cartridges 55 and to the tubing and conduits between oxygenator 54 and active cartridges 55, as well as elsewhere in recirculation circuit 50.
- Oxygenator 54 may be coupled to a gas blender unit 73, which may be embodied as or comprise a medical-grade gas blending device operative to supply gas to oxygenator 54.
- the addition of medical-grade gas blender 73 may provide simultaneous control of both the total gas flow as well as the percentage of oxygen or FiO 2 , i.e. the oxygen concentration may be selectively adjusted to a desired level within the capabilities of gas blender 73.
- an approved medical-grade gas blender is currently available from Sechrist Industries.
- one or more in-line blood gas analyzers 74 and 75 may be implemented upstream or downstream (or both) of cartridge cluster 55. Where two gas analyzers 74,75 are arranged as illustrated in FIG. 5, oxygen and pH differentials from both the upstream and downstream sides of active cartridges 55 may provide important measurements of therapeutic cell function over time during therapy. Samples drawn from system 10 may be compared with off-line or reference measurements both to estimate instantaneous levels and to track oxygen and pH differentials over time. Such measurements and comparisons may be made in real-time using the FIG. 5 arrangement, i.e. multiple in-line analyzers 74, 75. Alternatively, a single in-line analyzer with two sets of flow-through probe chambers may be used. By way of example, one approved analyzer system which satisfies the requirements of recirculation circuit 50 is a CDI 500 apparatus available from Terumo Medical.
- an input or infusion port 76 may be provided downstream of active cartridge cluster 55; alternatively, port may be located upstream of active cartridges 55, or even upstream of oxygenator 54, for example, depending upon the pu ⁇ ose and functional characteristics of the substance to be infused into the UF. In that certain situations.
- infusion port 76 may allow induction of promoters or inducers selected and operative to enhance or to accelerate treatment (i.e. therapeutic or detoxification processes) taking place in active cartridges 55.
- the type, nature, and chemical composition of such promoters or inducers may be selected as a function of the active cells supported in active cartridges 55, for example.
- various promoters are generally known in the art and may be operative to enhance the activity of therapeutic cells.
- fibers may be synthetic, such as the polysulfone fibers described above, with a porosity of approximately 0.2 ⁇ m, for example.
- Synthetic fiber such as polysulfone may provide superior durability and biocompatibility relative to cellulose fibers.
- Higher porosity membranes may also allow essentially all molecules, including larger proteins, to pass between the UF and the active cells in the ECS of the active cartridges 55.
- active cartridges 55 may comprise a cluster of filters arranged either in parallel or in series.
- the additional filters 56 described above with reference to FIG. 3 may be replaced by one hollow fiber cartridge having a pore size of approximately 0.1 - 0.2 ⁇ m and one capsule filter having a similar pore size.
- a hollow fiber unit even with tighter pores, may cause lower back pressure due to significantly increased surface area (e.g. 2.0 m 2 versus the capsule filter having a surface area of about 0.055 m 2 ).
- This configuration may not only prevent contamination present in recirculation circuit 50 from crossing over to the patient's blood line, but also lengthen the time between filter changes during therapy.
- Suitable hollow fiber cartridges are presently available from Minntech Co ⁇ . and Spectrum Laboratories, for example.
- a detoxification device 59 may be positioned or located in a similar position as additional filters 56.
- additional filters 56 may comprise or inco ⁇ orate one or more detoxification devices 59, ammonia traps, or similar mechanical or chemical filtration devices generally known in the art or developed and operative in accordance with known principles.
- FIG. 5 design may reduce the number of separate tubing segments required and components may be sterilized together, and the risk of a contamination during set-up may be reduced.
- active cartridges 55 may be bundled or clustered together, and a single quick-disconnect on both the upstream and downstream sides of active cartridge cluster 55 may facilitate maintenance and replacement.
- FIG. 6 is a simplified flow diagram illustrating the general operation of another embodiment of a method of extraco ⁇ oreal filtration and detoxification.
- the processes depicted in FIG. 6 are related to operation of a recirculation circuit, for example, and accordingly may be facilitated by the various components, or appropriate combinations thereof, illustrated in FIG. 5.
- Treating UF in accordance with the FIG. 6 method generally relates to the operation depicted at block 413 of FIG. 4 A.
- drawing UF through a membrane as indicated at block 611 may represent an aspect of generating UF, such as with UFG 40, for example; accordingly, the drawing operation of block 611 may also be associated with the separating operation of block 412 in FIG. 4 A.
- the process at block 611 is included in FIG. 6 for the sake of clarity and thoroughness.
- the operations depicted at blocks 612 and 632, as well as at decision block 631, may generally correspond to similarly labeled blocks illustrated and described above with reference to FIG. 4B.
- untreated UF input to recirculation circuit 50 may be provided to hollow fiber filters 79 as indicated at block 613.
- Infusion of fluid (block 614) may represent introduction of glucose or other nutrients, heparin or other anticoagulation agents, promoters, enhancers, or other fluids into recirculation substantially as set forth above. It will be appreciated that the operation depicted at block 614 may occur elsewhere in the FIG. 6 embodiment, representing selected locations throughout recirculation circuit 50 of FIG. 5; methods and locations of fluid infusion such as represented at block 614 may depend upon the type and quantity of fluid to be infused, the nature and requirements of the active cells maintained in active cartridges, overall flow rate of UF through the circuit, and other system parameters.
- primer solution introduction of primer solution (not shown in FIG. 6) and the collection of primer solution at block 617 may occur where indicated or elsewhere in FIG. 6, depending, for example, upon the particular system components requiring priming. If upstream thereof; additionally, primer collection at block 617 may be selectively located in recirculation circuit 50 as a function of the particular arrangement or relative orientation of system components.
- UF may be oxygenated at block 615 and treated at block 616.
- Various aspects of the oxygenation process e.g. pressure, partial pressures and composition of any air/gas mixture, infusion rates, and the like
- oxygenation at block 615 may be influenced by the quantity, density, nature, and functionality of the active cells (such as C3A cells, for example) maintained in the active cartridges and executing the treatment process at block 616.
- oxygenation at block 615 may comprise receiving gaseous input in accordance with selected conditions or parameters from gas blender 73, and may occur in conjunction with heating UF using heat exchanger 71 and an ECMO heater apparatus 72.
- Treating or detoxifying UF may generally occur in active cartridges at block 616.
- the operational characteristics and specific chemical, biological, and other processes associated with block 616 may be influenced by, among other factors: promoters or enhancers induced into recirculation circuit 50; the intended overall operation of system 10 (i.e. the type of treatment required); operational parameters of system components such as recirculation pump 53; and so forth.
- Therapeutic processes at block 616 may be selectively adjusted, controlled, or otherwise manipulated in accordance with the specific hardware components implemented in recirculation circuit 50.
- one or more data acquisition and analysis components may be inco ⁇ orated in the flow.
- inline blood gas analyzers 74 and 75 are implemented upstream and downstream of cartridge cluster 55, for example, an analyzing operation may be executed both prior to and subsequent to treatment at block 616.
- oxygen and pH differentials from both the upstream and downstream sides of treatment processing may provide important measurements of therapeutic cell function over time during therapy.
- Such measurements, comparisons, and subsequent data processing operations may have utility both in system diagnostics applications as well as in ascertaining the efficacy or thoroughness of treatment at block 616.
- Data can be also acquired and analyzed with respect to flow rates, temperatures and pressures throughout the system.
- Treated UF may be returned to hollow fiber filters 79 as indicated at block 618 and described in detail above.
- Providing (block 613) and returning (block 618) UF to filters 79 at both ends of a recirculation circuit 50 may allow or enable a system and method of treating UF to operate at a different flow rate than that maintained in the blood circuit of a treatment system 10.
- filtering at block 619 may include passing UF through one or more in-line cell filters, hollow fiber cartridges, ammonia traps, charcoal filters, mechanical filters, and so forth.
- UF which is neither processed at block 619 nor returned to the patient may be recirculated for additional treatment as represented by the loop from block 618 back up to block 613.
- FIGs. 4B and 6 are provided by way of example only, and not to the exclusion of other possibilities.
- the present disclosure is not intended to be inte ⁇ reted in any limited sense with respect to the order or sequence of events depicted in FIGS. 4B and 6.
Abstract
Description
Claims
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CA2564859C (en) | 2013-04-09 |
IL178898A0 (en) | 2007-03-08 |
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EP3326669A1 (en) | 2018-05-30 |
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JP2007534440A (en) | 2007-11-29 |
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JP5106102B2 (en) | 2012-12-26 |
AU2005240515A1 (en) | 2005-11-17 |
US20120197174A1 (en) | 2012-08-02 |
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WO2005107928A9 (en) | 2010-02-25 |
CN101005871A (en) | 2007-07-25 |
TWI302103B (en) | 2008-10-21 |
TW200538172A (en) | 2005-12-01 |
US8105491B2 (en) | 2012-01-31 |
AU2005240515B2 (en) | 2010-09-23 |
KR101278429B1 (en) | 2013-06-24 |
EP1747056B1 (en) | 2018-09-26 |
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