Patent Description:
Due to various causes, a person's renal system may fail. Toxic end products of metabolism (urea, creatinine, uric acid, and others) may accumulate in blood and tissue.

Kidney failure and reduced kidney function have been treated with dialysis. Dialysis treatment for replacement of kidney functions is critical to many people because the treatment is life saving.

HF is accomplished by adding substitution or replacement fluid to the extracorporeal circuit during treatment (typically ten to ninety liters of such fluid). The substitution fluid and the fluid accumulated by the patient in between treatments is ultrafiltered over the course of the HF treatment, providing a convective transport mechanism that is particularly beneficial in removing middle and large molecules (in hemodialysis there is a small amount of waste removed along with the fluid gained between dialysis sessions, however, the solute drag from the removal of that ultrafiltrate is not enough to provide sufficient convective clearance).

In addition, substitution solution is provided directly to the extracorporeal circuit, making increased ultrafiltration possible, which in turn yields convective clearance.

Most HD (HF, HDF) treatments occur in centers. A trend towards home hemodialysis ("HHD") exists today in part because HHD may be performed daily, offering therapeutic benefits over in-center hemodialysis treatments, which occur typically bi- or tri-weekly. Studies have shown that more frequent treatments remove more toxins and waste products than treatments occurring less frequently, but lasting longer. A patient receiving more frequent treatments does not experience as much of a down cycle as does an in-center patient, who has built-up two or three day's worth of toxins prior to a treatment. In certain areas, the closest dialysis center may be many miles from the patient's home causing door-to-door treatment time to consume a large portion of the day. HHD may take place overnight or during the day while the patient relaxes, works or is otherwise productive. <INSERT PAGE 2A>.

In any of the above modalities, it is necessary to prime the associated equipment prior to running a treatment on a patient. Priming typically involves displacing air with a physiologically compatible solution such as dialysis fluid or saline. Air may however be difficult to remove from certain areas of a blood circuit, such as within the membranes of a dialyzer. Pockets of air may remain even after being flushed with a solution.

An improved priming system and method is needed accordingly.

The examples described herein disclose automated systems and methods applicable, for example, to fluid delivery for: plasmapherisis, hemodialysis ("HD"), hemofiltration ("HF") hemodiafiltration ("HDF"), continuous renal replacement therapy ("CRRT"), apheresis, autotransfusion, hemofiltration for sepsis, and extracorporeal membrane oxygenation ("ECMO") therapies (extracorporeal therapies). Any of the extracorporeal therapies may require that the blood circuit including a blood filter (dialyzer, hemofilter, etc.) be primed prior to being connected to the patient. The present <Document <CIT> discloses a degassing module for removal of air and other gases during operation of a medical therapy device that delivers any one of hemodialysis, hemodiafiltration and hemofiltration. The degassing module has a flow-through first chamber that has a hydrophobic vent membrane that has an exterior and interior side forming a portion of the flow-through chamber.

Document <CIT> discloses an extracorporeal blood circuit for use with a venous return line and an arterial line coupled to a patient. The extracorporeal blood circuit can include a venous air removal device coupled to the venous return line. The venous air removal device can perform an active air removal function. The extracorporeal blood circuit can include a sensor that determines a blood level in the venous air removal device, a purge line coupled to the venous air removal device, and a controller connected to the sensor. The controller can cause the venous air removal device to perform the active air removal function through the purge line when the blood level is less than a threshold. > disclosure sets forth systems and methods that use carbon dioxide ("CO<NUM>") gas to initially prime the blood circuit. CO<NUM> gas is better able than a priming fluid to dislodge air trapped in the membranes, and indeed within the pores of the membranes, of a blood filter. CO<NUM> gas may also be better at flushing air out of pockets located within other areas of the blood circuit, e.g., pockets created by the housing of a drip chamber of the blood circuit, or pockets created by the sealing of connectors to tubes (or the connectors themselves), or tubes to tubes, within the blood circuit. In short, CO<NUM> gas is better able to enter and flush small open spaces than is typical priming fluid.

There are two primary embodiments for performing the CO<NUM> gas prime of the present disclosure. In one primary embodiment, CO<NUM> gas is created by the system itself but outside of the extracorporeal or blood circuit. Here, CO<NUM> gas is transported into the blood circuit or set. In a second primary embodiment, CO<NUM> gas is carried by the fluid creating the CO<NUM> gas into the extracorporeal or blood circuit and released.

In the first primary embodiment, a CO<NUM> gas chamber may be provided, which receives the constituent fluids that mix together to form CO<NUM> gas and then stores at least a portion of the CO<NUM> gas. The constituent fluids that mix together to form CO<NUM> gas may include bicarbonate (e.g., from B-concentrate) and any one of: (i) a citric acid solution, (ii) an acetic acid solution (e.g., from A-concentrate), (iii) a lactic acid solution, (iv) a malic acid solution, (v) a hydrochloric ("HCl") acid solution, (vi) a phosphoric acid solution, (vii) any other biocompatible acid solution (e.g., an acid whose anion is present in a human body), and (v) blends thereof. The system in an embodiment uses A-concentrate and B-concentrate to make a dialysis fluid for treatment. If using A-concentrate and B-concentrate to also make the CO<NUM> gas generation fluid, then no additional source of acid is needed, however, the CO<NUM> gas generation fluid made from A-concentrate and B-concentrate will be formulated differently, e.g., have a different or lower pH, than the treatment fluid made from A-concentrate and B-concentrate.

If using citric acid solution, an acetic acid solution or any other acid solution other than A-concentrate, then a separate source of the additional acid is provided, then the CO<NUM> gas generation fluid will have a different constituent makeup than the dialysis treatment fluid. In any case, an accurate metering pump may be provided to pump, in any order, bicarbonate solution in a desired amount and any of the acid solutions in a desired amount into the gas chamber. The bicarbonate and acid mix to form CO<NUM> gas over the course of a short period of time.

A CO<NUM> gas line is provided in one embodiment to run from an upper portion of the CO<NUM> gas chamber to a desired gas injection location. The CO<NUM> gas line may be opened or closed during the formation of CO<NUM> gas (which happens very quickly, on the order of seconds) depending upon how much pressure the CO<NUM> gas line is rated to hold. The desired injection location may, for example, be the fresh dialysis fluid line leading to a port of the blood filter, be a substitution fluid line leading to the arterial or venous blood line, or be a line leading to a port of the machine for receiving the connected blood lines for priming. In any case, the desired injection location is positioned and arranged to deliver the CO<NUM> gas into the blood circuit.

Under certain circumstances, it may be required to lower the pressure downstream from the CO<NUM> gas chamber to help draw the CO<NUM> gas from the CO<NUM> priming fluid. The underpressure may be created for example by operating the blood pump in reverse to place the dialyzer and the CO<NUM> gas line leading to the dialyzer under a negative pressure. The blood pump may also be operated (e.g., multiple times in normal and reverse directions) during the CO<NUM> gas prime to help distribute the CO<NUM> gas to all portions of the blood circuit or set. The CO<NUM> gas during the CO<NUM> gas prime pushes air in one embodiment out of a vent provided for example with a venous air trap of the blood set. As shown below, an alternative to an underpressure, or perhaps in addition to the underpressure, the CO<NUM> priming fluid may be mixed or stirred to release the CO<NUM> gas.

In addition to, or alternatively to, the use of an underpressure to release CO<NUM> gas from the CO<NUM> gas generation fluid, the metering pump may also operate with a recirculation line that recirculates the CO<NUM> gas generation fluid to thereby stir and agitate the CO<NUM> gas generation fluid. Stirring and agitating the CO<NUM> gas generation fluid helps to release the CO<NUM> gas from the fluid. It is contemplated to stir and agitate the CO<NUM> priming fluid at a location elevationally below a location where the CO<NUM> gas is collected and then delivered to the blood set.

When the CO<NUM> gas prime has been completed, the system and method of the first primary embodiment may then perform an additional prime of the blood set using a priming fluid such as saline or dialysis fluid prepared for treatment. The priming fluid such as saline or dialysis fluid prepared for treatment may absorb the CO<NUM> gas and/or expel the gas from the blood circuit, e.g., via the vent of the venous air trap. The dual stage prime, in addition to the CO<NUM> gas prime, results in superior air removal.

The second primary embodiment, in which CO<NUM> gas is carried by the CO<NUM> gas generation fluid into the blood set where it is released, does not need a CO<NUM> gas chamber or separate metering pump. The CO<NUM> gas generation fluid may again be formed via a bicarbonate solution and any of the acid solutions discussed herein, e.g., (i) a citric acid solution, (ii) an acetic acid solution (e.g., from A-concentrate), (iii) a lactic acid solution, (iv) a malic acid solution, (v) a hydrochloric ("HCl") acid solution, (vi) a phosphoric acid solution, (vii) any other biocompatible acid solution, and (v) blends thereof. The CO<NUM> gas generation fluid may be delivered to the blood circuit via any of the entry locations discussed herein, e.g., at the dialyzer port, substitution port, or arterial and venous line connection port.

An underpressure may again be needed to separate the CO<NUM> gas from the CO<NUM> gas generation fluid. The underpressure may be created by running different pumps at different speeds and/or by subjecting a portion of a blood line for which CO<NUM> gas contact is desired to a negative or intake side of a pump, e.g., a peristaltic blood pump. The blood pump may again be run in normal and reverse directions multiple times to ensure that the CO<NUM> gas is separated effectively from the CO<NUM> gas generation fluid and distributed effectively to all portions of the blood set.

When the CO<NUM> gas prime of the second primary embodiment has been completed, the system and method of the present disclosure again perform an additional prime of the blood set using a priming fluid such as saline or dialysis fluid prepared for treatment. The priming fluid such as saline or dialysis fluid prepared for treatment may absorb the CO<NUM> gas and/or expel the gas from the blood circuit, e.g., via the vent of the venous air trap.

The extracorporeal therapy system of the invention is according to claims <NUM>-<NUM>; a priming method for an extracorporeal therapy system of the invention is according to claims <NUM>-<NUM>.

In light of the present disclosure it is therefore an advantage of the present disclosure to provide an extracorporeal therapy system and method having improved priming.

It is another advantage of the present disclosure to provide an extracorporeal therapy system and method capable of generating its own CO<NUM> gas for priming.

It is a further advantage of the present disclosure to provide a relatively inexpensive system and method to improve priming.

It is still another advantage of the present disclosure to provide a system and method to improve priming that is physiologically compatible.

It is still a further advantage of the present disclosure to provide a system and method to improve priming that is time efficient.

It is yet another advantage of the present disclosure to provide a system and method to improve priming that requires little or no additional setup.

Still another advantage of the present disclosure is to reduce the amount of typical priming fluid, e.g., saline, which reduces cost and fluid priming time.

The advantages discussed herein may be found in one, or some, and perhaps not all of the embodiments disclosed herein. Additional features and advantages are described herein, and will be apparent from, the following Detailed Description and the figures.

The examples described herein are applicable to any medical fluid therapy system that delivers a medical fluid, such as blood, dialysis fluid, substitution fluid, purified or sterilized water, liquid concentrate, or an intravenous drug. The examples are particularly well suited for kidney failure therapies, such as all forms of hemodialysis ("HD"), plasmapherisis, hemofiltration ("HF") hemodiafiltration ("HDF"), continuous renal replacement therapy ("CRRT"), apheresis, autotransfusion, hemofiltration for sepsis, and extracorporeal membrane oxygenation ("ECMO") treatments, referred to herein collectively or generally individually as an extracorporeal therapy. Moreover, the systems and methods described herein may be used in clinical or home settings. Extracorporeal therapy system 10a in the examples below is described as a renal failure therapy system having a machine <NUM> that creates online dialysis fluid for treatment.

Referring now to <FIG>, one embodiment for a renal failure therapy system 10a employing an improved priming method or procedure of the present disclosure is illustrated. System 10a includes a machine <NUM> having an enclosure or housing. The housing of machine <NUM> holds the contents of a dialysis fluid circuit <NUM> described in detail below. The housing of machine <NUM> also supports a user interface <NUM>, which allows a nurse or other operator to interact with system 10a. User interface <NUM> may have a monitor screen operable with a touch screen overlay, electromechanical buttons, e.g., membrane switches, or a combination of both. User interface <NUM> is in electrical communication with at least one processor <NUM> and at least one memory <NUM>. At least one processor <NUM> and at least one memory <NUM> also electronically interact with, and where appropriate control, the pumps, valves and sensors described herein, e.g., those of dialysis fluid circuit <NUM>. At least one processor <NUM> and at least one memory <NUM> are referred to collectively herein as a control unit <NUM>. The dashed lines extending from control unit <NUM> are electrical or signal lines leading to and/or from pumps, valves, sensors, the heater and other electrical equipment of system 10a.

Dialysis fluid circuit <NUM> includes a purified water line <NUM>, an A-concentrate line <NUM> and a bicarbonate B-concentrate line <NUM>. Purified water line <NUM> receives purified water from a purified water device or source <NUM>. The water may be purified using any one or more process, such as, reverse osmosis, carbon filtering, ultraviolet radiation, electrodeionization ("EDI"), and/or ultrafiltering.

An A-concentrate pump <NUM>, such as a peristaltic or piston pump, pumps A-concentrate from an A-concentrate source <NUM> to mix with purified water from purified water line <NUM> via A-concentrate line <NUM>. Conductivity cell <NUM> measures the conductive effect of the A-concentrate on the purified water, sends a signal to control unit <NUM>, which uses the signal to properly proportion the A-concentrate by controlling A-concentrate pump <NUM>. The A-conductivity signal may be temperature compensated via a reading from temperature sensor <NUM>.

A B-concentrate pump <NUM>, such as a peristaltic or piston pump, in the illustrated embodiment pumps purified water from purified water line <NUM>, through B-concentrate line <NUM> and a B-concentrate source or bicarbonate cartridge <NUM> located along B-concentrate line <NUM>, into a mixture of purified water and A-concentrate leaving conductivity sensor <NUM>. Conductivity cell <NUM> measures the conductive effect of the B-concentrate on the purified water/A-concentrate mixture, sends a signal to control unit <NUM>, which uses the signal to properly proportion the B-concentrate by controlling B-concentrate pump <NUM>. The B-conductivity signal may also be temperature compensated via a reading from temperature sensor <NUM>.

Purified water is degassed prior to receiving the concentrates, removing bubbles from the water. The water is degassed in a chamber <NUM> via a degassing pump <NUM>, placed in fluid communication with degassing chamber <NUM>. A heater <NUM> controlled by control unit <NUM> heats the purified water for treatment to body temperature, e.g., <NUM>. The fluid exiting conductivity cell <NUM> is therefore freshly prepared dialysis fluid, properly degassed and heated, and suitable for sending to dialyzer <NUM> for treatment. Fresh dialysis fluid for a renal therapy treatment, such as hemodialysis, hemofiltration or hemodiafiltration, may be said to be made from a formula or at least one setpoint, e.g., conductivity setpoints for sensors <NUM> and <NUM>, which is (are) specified according to a physiological constituency of the dialysis fluid that is suitable for treatment, e.g., suitable for the patient. The treatment formula or at least one setpoint may be different than ones described below to create dialysis fluid for priming, referred to herein as a priming fluid, wherein that dialysis fluid is formulated or regulated to create carbon dioxide ("CO<NUM>") gas.

It is worth noting that priming blood set <NUM> is most often done using a priming fluid, which may be hung on a stand, and which is normally a saline solution. When priming using an online fluid (dialysis machine <NUM> itself produces the priming fluid), there are several options depending upon the type of machine <NUM>. For example, the priming fluid may be dialysis fluid prepared for treatment, an A-concentrate based solution (possibly not the best alternative) or a sodium chloride fluid if machine <NUM> is able to separate a source of sodium from its other concentrates. Each of the examples listed above, including saline, is different than the CO<NUM> producing priming solutions of the present disclosure.

<FIG> further illustrates a fresh dialysis fluid pump <NUM>, such as a gear pump, which delivers fresh dialysis fluid for treatment to dialyzer <NUM>. Control unit <NUM> controls fresh dialysis fluid pump <NUM> to deliver fresh dialysis fluid to the dialyzer at a specified flowrate. A used dialysis fluid line <NUM> via a used dialysis fluid pump <NUM> returns used dialysis fluid from dialyzer <NUM> to a drain <NUM>. Control unit <NUM> controls used dialysis fluid pump <NUM> to pull used dialysis fluid from dialyzer <NUM> at a specified flowrate. An air separator <NUM> separates air from the used dialysis fluid line <NUM>. A pressure sensor <NUM> senses the pressure of used dialysis fluid line <NUM> and sends a corresponding pressure signal to control unit <NUM>.

Conductivity cell <NUM> measures the conductivity of used fluid flowing through used dialysis fluid line <NUM> and sends a signal to control unit <NUM>. The conductivity signal of cell <NUM> may also be temperature compensated via a reading from temperature sensor <NUM>. A blood leak detector (not illustrated), such as an optical detector, looks for the presence of blood in used dialysis fluid line <NUM>, e.g., to detect if a dialyzer membrane has a tear or leak. A heat exchanger <NUM> in the illustrated embodiment recoups heat from the used dialysis fluid exiting dialysis fluid circuit <NUM> to drain <NUM>, preheating the purified water traveling towards heater <NUM> to conserve energy.

A fluid bypass line <NUM> allows fresh dialysis fluid to flow from fresh dialysis fluid line <NUM> to used dialysis fluid line <NUM> without contacting dialyzer <NUM>. A fresh dialysis fluid tube <NUM> extends from machine <NUM> and carries fresh dialysis fluid from fresh dialysis fluid line <NUM> to dialyzer <NUM>. A used dialysis fluid tube <NUM> also extends from machine <NUM> and carries used dialysis fluid from dialyzer <NUM> to used dialysis fluid line <NUM>.

Dialysis circuit <NUM> also includes an ultrafiltration ("UF") system <NUM>. UF system <NUM> monitors the flowrate of fresh dialysis fluid flowing to dialyzer <NUM> (and/or as substitution fluid flowing directly to the blood set <NUM>) and used fluid flowing from dialyzer <NUM>. UF system <NUM> may include fresh and used flow sensors, which send signals to control unit <NUM> indicative of the fresh and used dialysis fluid flowrates, respectively. Control unit <NUM> uses the signals to set used dialysis fluid pump <NUM> to pump faster than fresh dialysis fluid pump <NUM> by a predetermined amount to remove a prescribed amount of UF from the patient over the course of treatment.

An ultrafilter (not illustrated) may also be provided to further purify the fresh dialysis fluid before being delivered via dialysis fluid line <NUM> and fresh dialysis fluid tube <NUM> to dialyzer <NUM>. Alternatively or additionally, one or more ultrafilter may be used to purify the fresh dialysis fluid from fresh dialysis fluid line <NUM> to the point where the fluid may be used as a substitution fluid to perform from pre- or post-dilution hemofiltration or hemodiafiltration.

System 10a provides plural valves <NUM>, e.g., solenoid valves, each under the control of control unit <NUM> to selectively control a prescribed treatment. In particular, valve <NUM> in bypass line <NUM> selectively opens and closes the bypass line, e.g., to work with valve <NUM> of fresh dialysis fluid line <NUM> to set machine <NUM> into a bypass mode when, for example, the prepared dialysis fluid is incorrect in any way (composition, temperature). Bypass line valve <NUM> is accordingly used mainly for safety reasons. Valve <NUM> in fresh dialysis fluid line <NUM> selectively opens and closes the fresh dialysis fluid line. Valve <NUM> in used dialysis fluid line <NUM> selectively opens and closes the used dialysis fluid line. Valves <NUM> and 92w are located in purified water line <NUM> to selectively open and close the purified water line to purified water source <NUM>, to deaerate the purified water, and to deliver the purified water for mixing with the concentrates. Multiple valves <NUM> are also provided to operate UF system <NUM>.

Valves 92b1 and 92b2 in the illustrated embodiment may be used in a priming sequence for bicarbonate cartridge <NUM>. In the illustrated embodiment, bicarbonate cartridge <NUM> holds a powder concentrate that is contacted with purified water, dissolving the bicarbonate powder to form a saturated concentrate. In one possible priming sequence, control unit <NUM> causes valves 92b1 and 92w to close and valve 92b2 to open. Fresh dialysis fluid pump <NUM> is operated, creating a sub-atmospheric pressure in the cartridge. Control unit <NUM> then opens valve 92b1 to introduce purified water. Cartridge <NUM> is primed and when the conductivity cell <NUM> senses a rise in conductivity, letting control unit <NUM> know that the priming sequence is finished and to close valve 92b2.

It should be appreciated that the dialysis fluid circuit <NUM> is simplified and may include other structure (e.g., more valves) and functionality not illustrated. Also, dialysis fluid circuit <NUM> illustrates one example of a hemodialysis ("HD") pathway. It is contemplated to provide one or more ultrafilter (not illustrated) in fresh dialysis fluid line <NUM> to create substitution fluid for hemofiltration ("HF"). It is also contemplated to provide one or more ultrafilter in one or more line(s) branching off of fresh dialysis fluid line <NUM> to create substitution fluid, in addition to the fresh dialysis fluid in line <NUM>, for hemofiltration ("HF") or hemodiafiltration ("HDF").

<FIG> further illustrates one embodiment of a blood circuit or set <NUM> that may be used with machine <NUM> of system 10a. Blood circuit or set <NUM> includes a dialyzer <NUM> having many hollow fiber semi-permeable membranes, which separate dialyzer <NUM> into a blood compartment and a dialysis fluid compartment. The dialysis fluid compartment during treatment is placed in fluid communication with a distal end of fresh dialysis fluid tube <NUM> and a distal end of used dialysis fluid tube <NUM>. For HF and HDF, a separate substitution tube, in addition to fresh dialysis fluid tube <NUM>, is placed during treatment in fluid communication with one or both of arterial line <NUM> extending from an arterial access needle or cannula (not illustrated) or venous line <NUM> extending to a venous access needle or cannula (not illustrated). For HDF, dialysis fluid also flows through dialysis fluid tube <NUM> to dialyzer <NUM>, while for HF, dialysis fluid flow through tube <NUM> is blocked.

An arterial pressure pod 108a may be placed upstream of blood pump <NUM> (such as a peristaltic or volumetric membrane pump), while venous line <NUM> includes a pressure pod 108v. Pressure pods 108a and 108v operate with blood pressure sensors (not illustrated) mounted on the housing of machine <NUM>, which send arterial and venous pressure signals, respectively, to control unit <NUM>. Venous line <NUM> includes a venous drip chamber <NUM>, which removes air from the patient's blood before the blood is returned to the patient. Venous chamber <NUM> may be provided with a hydrophobic or hydrophilic vent <NUM>.

In the illustrated embodiment, arterial line <NUM> of blood circuit or set <NUM> is operated by blood pump <NUM>, which is under the control of control unit <NUM> to pump blood at a desired flowrate. System 10a also provides multiple blood side electronic devices that send signals to and/or receive commands from control unit <NUM>. For example, control unit <NUM> commands pinch clamps (<FIG> and clamp <NUM> in <FIG>) to selectively open or close arterial line <NUM> and/or venous line <NUM>. A blood volume sensor ("BVS", not illustrated) may be located along arterial line <NUM> upstream of blood pump <NUM>. An air detector (not illustrated) may be provided to look for air in venous blood line <NUM>.

<FIG> further illustrates structure for enabling CO<NUM> gas to be generated in dialysis fluid circuit <NUM> and to be delivered to blood circuit <NUM> for priming purposes. In particular, dialysis fluid circuit <NUM> shows a bicarbonate priming line <NUM>, running to a first three-way solenoid valve 192a under control of control unit <NUM>. A metering pump <NUM> under control of control unit <NUM>, such as a volumetric or membrane pump, or perhaps an accurately controlled peristaltic pump or gear pump is located between first three-way solenoid valve 192a and a second three-way solenoid valve 192b under control of control unit <NUM>.

The third leg of first three-way solenoid valve 192a is connected fluidly to a citric acid line <NUM> leading to a citric acid source <NUM>. Citric acid for source <NUM> may for example be provided in a concentration of <NUM>% to <NUM>% by volume and in one preferred embodiment <NUM>% by volume. The upper citric acid limit is affected by the need to avoid the formation of precipitation. An upper limit of <NUM>% to <NUM>% should avoid such formation. To avoid shipping water and to avoid replacing the concentrate as much as possible, the concentration should be as high as possible. Lower citric acid concentrations are otherwise theoretically useable as long as the citric acid level is not so low that bacteria is allowed to form.

The second and third legs of second three-way solenoid valve 192b in the illustrated embodiment are connected fluidly to a gas generation chamber <NUM> and a return line <NUM>. Gas generation chamber <NUM> may be made of metal or plastic as desired and includes an inlet for receiving fluids from metering pump <NUM> and an outlet in fluid communication with a CO<NUM> gas line <NUM>, which is connected fluidly to fresh dialysis fluid line <NUM>. Return line <NUM> returns fluids used to make CO<NUM> gas to a point upstream of dialysis fluid pump <NUM>, e.g., to bicarbonate B-concentrate line <NUM>. Return line <NUM> allows control unit <NUM> to verify via the conductivity sensors that bicarbonate concentrate is present at valve 192b before opening the valve to fill gas generation chamber <NUM>. Without such verification, the system may instead first fill gas generation chamber <NUM> with purified water, possibly causing an incorrect amount of concentrate to be delivered to the chamber. Return line <NUM> helps to ensure that bicarbonate priming line <NUM> is primed with bicarbonate fluid prior to infusing fluid into gas generation chamber <NUM>.

Degassing pump <NUM> under control of control unit <NUM> is in one embodiment used mainly to create low pressure in a degassing loop that includes heater <NUM> and degassing chamber <NUM> to degas the water for priming and treatment. To make CO<NUM> gas generation fluid in an embodiment, system 10a may be currently producing dialysis fluid for treatment, however, it is not a necessity that system 10a is doing so. Bicarbonate cartridge <NUM> should be primed in any case however. As illustrated, return line <NUM> is positioned and arranged such the control unit <NUM> advantageously does not have to stop B-concentrate pump <NUM> to provide bicarbonate solution for CO<NUM> gas generation. Control unit <NUM> causes metering pump <NUM> to pump through or from bicarbonate cartridge <NUM> (dry or liquid source) to valve 192b and further into return line <NUM>. When the bicarbonate solution reaches a point just ahead of valve 92w, the bicarbonate solution may begin to enter the main fresh dialysis fluid line <NUM>, so that the bicarbonate solution is sensed by conductivity sensors <NUM> and <NUM> feeding corresponding signals to control unit <NUM>.

Control unit <NUM> then causes valve 192b to switch, so that the bicarbonate solution enters gas generation chamber <NUM>. Control unit <NUM> may cause A- and B-concentrate pumps <NUM> and <NUM> to run at fixed, e.g., slower, operating speeds, so that concentrate pumps <NUM> and <NUM> continue to prepare dialysis fluid for treatment (assuming dialysis fluid is being prepared), while preparing B-concentrate for CO<NUM> gas generation. In an embodiment, the dialysis fluid for treatment is used at this time (prior to treatment) to prime fresh dialysis fluid line <NUM> and used dialysis fluid line <NUM>.

When a desired amount of bicarbonate solution has been added to gas generation chamber <NUM>, the acid step is started, e.g., adding either citric acid from citric acid source <NUM>, A-concentrate from A-concentrate source <NUM> or some other acid containing fluid. Dependent on which acid fluid is used, the acid pumping sequence may vary. Using citric acid from source <NUM> is straight forward in the illustrated embodiment, namely, control unit <NUM> causes metering pump <NUM> to pull a desired amount of citric acid from source <NUM> into gas generation chamber <NUM>. If A-concentrate from source <NUM> is used instead, control unit <NUM> performs a priming sequence similar to that for the B-concentrate, where A-concentrate is used to prepare dialysis solution for treatment and A-concentrate for CO<NUM> gas generation simultaneously (e.g., where the dialysis fluid for treatment is used at this time (prior to treatment) to prime fresh dialysis fluid line <NUM> and used dialysis fluid line <NUM>). Here again, control unit <NUM> may cause A- and B-concentrate pumps <NUM> and <NUM> to run at fixed, e.g., slower, operating speeds. In one embodiment, control unit <NUM> ensures that an acid solution is provided at the entrance of valve 192b. Conductivity sensors <NUM> and <NUM> operating with control unit <NUM> are used again to detect when the acid solution has entered main fresh dialysis fluid line <NUM>. The acid solution is then metered into gas generation chamber <NUM> in the same manner as described above for the bicarbonate solution.

Control unit may alternatively cause the A- and B-concentrate pumps <NUM> and <NUM> to be actively controlled during the A- and B-concentrate delivery for CO<NUM> gas generation. Being actively controlled in an embodiment means the speed of pumps <NUM> and <NUM> may change due to feedback presented to control unit <NUM>. Here, control unit <NUM> may be able to detect when A- and B-concentrate delivery for CO<NUM> gas generation has been completed by noting a change to the speed or the pump revolutions over time for A- or B-concentrate pumps <NUM> and <NUM>.

Next, with the port to bicarbonate priming line <NUM> of first three-way solenoid valve 192a closed and its other two ports open, the port to return line <NUM> of second three-way solenoid valve 192b closed and its other two ports open, and valve <NUM> in CO<NUM> gas line <NUM> open or closed as desired, metering pump <NUM> pumps a specified amount of citric acid (e.g., in a specified concentration) from source <NUM> via citric acid line <NUM> into gas generation chamber <NUM> to mix with the bicarbonate solution.

With the pathway through second three-way solenoid valve 192b between metering pump <NUM> and return line <NUM> closed, and valve <NUM> in CO<NUM> gas line <NUM> open or closed as desired, the citric acid and bicarbonate solution may be allowed to mix for a specified period of time, e.g., a short period of time such as from a few seconds to <NUM> seconds, to produce a volume of CO<NUM> gas that will pressurize inside gas generation chamber <NUM>. Once the specified CO<NUM> gas production period has ended, and with the most downstream valve <NUM> in fresh dialysis fluid line <NUM> closed and the pathway through second three-way solenoid valve 192b between metering pump <NUM> and return line <NUM> closed, control unit <NUM> in one embodiment causes valve <NUM> in CO<NUM> gas line <NUM> to open (if previously closed), allowing the pressurized CO<NUM> gas inside chamber <NUM> to flow through CO<NUM> gas line <NUM>, a distal portion of dialysis fluid line <NUM>, and fresh dialysis fluid tube <NUM> into blood circuit <NUM> via dialyzer <NUM>. If valve <NUM> in CO<NUM> gas line <NUM> has instead been open during CO<NUM> gas formation, then the CO<NUM> gas migrates naturally along gas line <NUM>.

In one embodiment, control unit <NUM> causes valve <NUM> in CO<NUM> gas line <NUM> to be open during CO<NUM> gas production (to allow for CO<NUM> gas formation and the use of lower pressure components). In an alternative embodiment, control unit <NUM> may cause valve <NUM> in CO<NUM> gas line <NUM> to be closed during CO<NUM> generation. Here, a pressure gauge in signal communication with control unit <NUM> may be located appropriately, e.g., along gas line <NUM>, and/or a pressure relief valve set at an appropriate operating limit may be provided along gas line <NUM> to ensure that pressurized CO<NUM> does not exceed a limit set for gas line <NUM>.

During the CO<NUM> priming of the present disclosure, arterial line <NUM> and venous line <NUM> are connected together at their distal ends, forming a loop that traps the CO<NUM> gas within blood circuit <NUM>. Hydrophobic or hydrophilic vent <NUM> located on venous drip chamber <NUM> allows the heavier CO<NUM> gas to push the lighter air in blood circuit <NUM> out of the circuit. CO<NUM> gas is better able than a priming fluid to dislodge air trapped in the membranes, and indeed within the pores of the membranes, of dialyzer <NUM>. CO<NUM> gas may also be better at flushing air out of pockets located within blood circuit <NUM>, e.g., pockets created by the housing of dialyzer <NUM>, pockets created by the housing of venous drip chamber <NUM>, or even pockets created by the sealing of connectors to tubes (or the connectors themselves), or tubes to tubes, within blood circuit <NUM>. In short, CO<NUM> gas is better able to enter and flush small open spaces than is typical priming fluid.

In an alternative embodiment, arterial line <NUM> and venous line <NUM> may be connected to each other via a disposable piece (not illustrated) containing the venting function (e.g., venting air to atmosphere or trapping the air) instead of incorporating the venting function at venous drip chamber <NUM>. In a further alternative embodiment, the air and CO<NUM> gas are removed from blood set <NUM> via a pressure measurement line <NUM> illustrated below in connection with <FIG>.

In an embodiment, the bicarbonate solution and citric acid reaction within chamber <NUM> creates a volume of CO<NUM> gas, which is a multiple (e.g., 4X) of the total volume of blood circuit <NUM>, including dialyzer <NUM> and drip chamber <NUM>. Thus if the total volume of blood circuit <NUM> is about two-hundred fifty milliliters ("mL"), the volume of CO<NUM> created within chamber <NUM> and delivered to blood circuit <NUM> may be about one liter. Given the ability of CO<NUM> gas to reach and purge small air pockets, and the multiple blood circuit volume's worth of CO<NUM> gas produced for priming, it is believed that virtually all of the air will be removed from blood circuit <NUM> via the CO<NUM> gas prime.

It should be appreciated that blood circuit <NUM> and in particular dialyzer <NUM> should be substantially dry or as dry as possible (in one embodiment completely dry) for the CO<NUM> gas prime. Most dialyzers are shipped in a dry state. Even if shipped wet, or if cleaned for reuse using an aqueous cleaner or disinfectant, the dialyzer may be allowed to dry before CO<NUM> gas prime. It is also contemplated to pump heated air from dialysis fluid circuit <NUM> to blood circuit <NUM> if needed to aid in such drying. Also, to the extent that blood pump <NUM>, e.g., a peristaltic blood pump, occludes arterial line <NUM>, a nurse or clinician may be instructed to leave the arterial line <NUM> disconnected from the actuator of blood pump <NUM> during the CO<NUM> gas prime. If arterial line <NUM> is placed in operable communication with blood pump <NUM>, however, it is desirable to run the blood pump during the CO<NUM> gas priming so that air is more readily removed from arterial line <NUM> and so that CO<NUM> gas reaches all portions of blood set <NUM>.

A priming fluid, such as dialysis fluid formulated for treatment or saline, is then used to remove CO<NUM> gas from blood circuit <NUM>. Dialysis fluid formulated for treatment is delivered in one backfiltration priming embodiment from dialysis fluid circuit <NUM>, e.g., via fresh dialysis fluid line <NUM> to blood circuit <NUM> via dialyzer <NUM>, while saline may alternatively be delivered directly to arterial line <NUM> or venous line <NUM>, e.g., via blood pump <NUM> or perhaps via gravity. It is contemplated that the priming will displace the CO<NUM> gas in two ways. In one way, the heavier priming fluid pushes the CO<NUM> gas from hydrophobic or hydrophilic vent <NUM> located on venous drip chamber <NUM> just like the CO<NUM> gas pushed the lighter air from vent <NUM>. In another way, the dialysis fluid or saline under higher pressure, e.g., while running blood pump <NUM>, will absorb or dissolve the CO<NUM> gas.

It is contemplated that the purging in combination with the absorbing or dissolving of the CO<NUM> gas will remove most all of the gas prior to treatment. It should be appreciated however that CO<NUM> is a physiologically compatible substance that is readily absorbed in the patient's bloodstream and removed from the body via breathing. Thus trace amounts of CO<NUM> remaining after the fluid prime are not harmful to the patient and are instead handled naturally. It is believed that the two stage, CO<NUM> gas and fluid prime, even further improves air removal.

In addition to blood set or circuit <NUM>, control unit <NUM> may also be programmed to remove any remaining CO<NUM> priming fluid including its constituents from gas generation chamber <NUM> prior to allowing the patient to connect to blood set <NUM> and/or prior to performing a subsequent CO<NUM> priming sequence. In one embodiment, control unit <NUM> causes metering pump <NUM> to run in reverse, pulling any remaining fluid from gas generation chamber <NUM> through three-way solenoid valve 192b, and pushing the fluid back through three-way solenoid valve 192a, priming fluid line <NUM> and B-concentrate line <NUM> into fresh dialysis fluid line <NUM>, and via fluid bypass line <NUM> into drain line <NUM> to drain <NUM>. CO<NUM> gas from CO<NUM> gas line <NUM> backfills the fluids removed from gas generation chamber <NUM>. Gas generation chamber <NUM> may therefore be filled with atmospheric CO<NUM> gas upon commencing a subsequent CO<NUM> priming sequence. Care should be taken that only CO<NUM> gas, and no fluid from dialyzer <NUM>, is pulled into gas generation chamber <NUM> to avoid any potential contamination. In this sequence, concentrate pumps <NUM> and <NUM> may be locked at their present flow rates. Conductivity cell <NUM> may be used with control unit <NUM> at the end of the sequence to confirm fluid removal from gas generation chamber <NUM>.

The above example described the preparation of CO<NUM> gas using a separate citric acid supply <NUM>. In an alternative embodiment, citric acid supply <NUM> and associated citric acid line <NUM> are removed, and an A-concentrate from A-concentrate source <NUM> is used instead. A-concentrates vary in physiological composition from manufacturer to manufacturer and from type to type. It is believed however that most if not all A-concentrates will work at least to some degree in combination with bicarbonate to create CO<NUM>. One suitable A-concentrate for preparing CO<NUM> gas has a dilution ratio if <NUM> (e.g., having <NUM> mmol/l of acetic acid).

With the removal of citric acid supply <NUM> and associated citric acid line <NUM>, A-concentrate may be pumped from A-concentrate source <NUM>, through a portion of A-concentrate line <NUM> and A-concentrate priming line <NUM>, to the same port of three-way solenoid valve 192a that connected formerly to citric acid line <NUM>. In the illustrated arrangement of <FIG>, A-concentrate may therefore be metered via metering pump <NUM> to gas generation chamber <NUM> in the same manner described above for citric acid.

<FIG> illustrates an either/or scenario in which either (i) citric acid supply <NUM> and associated citric acid line <NUM> are present while priming line <NUM> is not present, or (ii) A-concentrate priming line <NUM> is present to use A-concentrate from A-concentrate source <NUM> instead, while citric acid supply <NUM> and associated citric acid line <NUM> are not present. It is expressly contemplated however for system 10b to provide both options at once, in which both citric acid supply <NUM> and associated citric acid line <NUM> and A-concentrate priming line <NUM> are provided. Here, a three-way valve under control of control unit <NUM>, e.g., similar to three-way solenoid valves 192a and 192b, may be added at the juncture of lines <NUM> and <NUM> to allow control unit <NUM> to open either a path including citric acid supply <NUM> and associated citric acid line <NUM> or a path including A-concentrate priming line <NUM> and A-concentrate source <NUM>, as desired by the operator.

Like above, with the fluid pathway through three-way solenoid valve 192b to metering pump <NUM> opened, and valve <NUM> in CO<NUM> gas line <NUM> open or closed as desired, the A-concentrate and bicarbonate solution may be allowed to mix for a specified period of time, e.g., for enough time to allow a downstream underpressure to be formed to pull CO<NUM> gas out of the mixture, producing a volume of CO<NUM> gas that will pressurize inside gas generation chamber <NUM>. Once the specified CO<NUM> gas production period has ended, and with the most downstream valve <NUM> in fresh dialysis fluid line <NUM> closed and the fluid pathway through second three-way solenoid valve 192b to metering pump <NUM> opened to allow for circulation within the loop including lines <NUM> and <NUM>, control unit <NUM> causes valve <NUM> in CO<NUM> gas line <NUM> to open (if previously closed), allowing the pressurized CO<NUM> gas inside chamber <NUM> to flow through CO<NUM> gas line <NUM>, a distal portion of dialysis fluid line <NUM>, and fresh dialysis fluid tube <NUM> into blood circuit <NUM> via dialyzer <NUM>. If valve <NUM> in CO<NUM> gas line <NUM> has instead been open during CO<NUM> gas formation, CO<NUM> gas migrates naturally along CO<NUM> gas line <NUM> as discussed above. Blood circuit <NUM> is then primed with CO<NUM> gas as described above.

It should be noted that when using A-concentrate to create carbon dioxide gas, it is likely that an underpressure needs to be created downstream from gas generation chamber <NUM> for the CO<NUM> to be released from the mixed solutions. For example, with dialyzer <NUM> being dry, control unit <NUM> may cause blood pump <NUM> to run in reverse to pull a negative pressure through arterial line <NUM> leading to dialyzer <NUM>, the dialyzer itself, fresh dialysis fluid tube <NUM> leading to dialyzer <NUM>, CO<NUM> gas line <NUM>, and a distal portion of dialysis fluid line <NUM>. Also, system 10a using A-concentrate to create carbon dioxide gas is configured to mitigate or prevent the creation of precipitation, such as calcium carbonate. With A-concentrate, the amount (or perhaps a concentration of the concentrate leading to the amount) of acid in the solution is selected to create an amount of CO2 gas needed for priming.

It is also contemplated that when using A-concentrate for the acid solution, a surplus of the A-concentrate may be needed. Without the surplus, it is more likely that precipitation will form in gas generation chamber <NUM>, which is undesirable. Assuming the use of a bicarbonate concentrate having a concentration of <NUM> mmol/l (e.g., from B-concentrate in liquid form stored in a canister), pumping <NUM> (see table below) of that B-concentrate into the chamber will produce <NUM> mmol of sodium bicarbonate. In comparison, pumping <NUM> of 45x A-concentrate (as is done in the table below) will produce about <NUM> mmol of HAc. But if instead BiCart® powdered bicarbonate cartridge solution provided by the assignee of the present disclosure is used, the concentration of <NUM> of resulting bicarbonate fluid leaving the cartridge is in the range of <NUM> mmol/l depending upon temperature. Here, to minimize precipitation, approximately <NUM>/<NUM> (<NUM>% more) 45x A-concentrate may be added, resulting in about <NUM> of A-concentrate and <NUM> mmol HAc. <NUM> of A-concentrate and <NUM> of BiCart® produced bicarbonate solution will then yield about <NUM> to <NUM> of CO<NUM> gas depending on the temperature of the mixture. To produce instead a desired lesser amount of CO<NUM> gas (e.g., <NUM>), the amount of sodium bicarbonate is lowered to in turn lower the A-concentrate needed.

In addition to citric acid and A-concentrate, other acidic solutions may be combined with the bicarbonate solution to produce CO<NUM> gas. One such acidic solution is marketed under the tradename SelectBag®, which is an acetic acid containing concentrate developed by the assignee of the present disclosure. The SelectBag® solution may be placed at the location of either citric acid bag <NUM> or A-concentrate container <NUM> and used according to the corresponding sequence described above. <NUM> of SelectBag® solution (example used in the table below) contains approximately <NUM> mmol HAc. The amount of sodium bicarbonate should be in the same range to avoid precipitation using SelectBag® solution.

Citric acid from source <NUM> includes no calcium chloride in one embodiment and therefore does not yield a precipitate. Alternatively, when using a dialysis concentrate that contains calcium chloride, for example, system 10a ensures that enough concentrate is provided, so that the pH is held low enough to prevent the formation of precipitation. The SelectBag® solution, for example, contains calcium and acetic acid. When using SelectBag® solution, system 10a again ensures that enough concentrate is added to prevent precipitation due to the calcium. Another possible solution is SelectBag® Citrate solution provided by the assignee of the present disclosure. SelectBag® Citrate solution contains calcium and citric acid. When using SelectBag® Citrate solution, system 10a yet again ensures that enough concentrate is added to prevent precipitation, despite the fact that the solution contains citric acid (even though the citric acid improves the situation because citric acid binds with calcium, lowering the concentration of free ionized calcium, and reducing the risk for precipitation). It is only when a precipitation yielding component such as calcium chloride is not present, such as with pure citric acid, that precipitation is not possible. Even here however, system 10a provides enough acid to yield the correct or desired amount of CO<NUM> gas.

Other suitable acid solutions or blends thereof include a lactic acid solution, a malic acid solution, a hydrochloric ("HCl") acid solution, (vi) a phosphoric acid solution, and (vii) any other biocompatible acid solution. Any one or more of the above-listed acid solutions may be mixed or blended with each other as desired for use with system 10a (and any of the systems described herein). It should also be appreciated that while the mixing of bicarbonate solution and an acid solution has been described as delivering bicarbonate solution first, then acid solution, the order may be reversed for any of the embodiments described herein.

As discussed above, it is contemplated to create and deliver a volume of CO<NUM> gas that is a multiple of the total volume of blood set <NUM> to ensure proper removal of air. The following table shows experimental data performed using saturated B-concentrate mixed alternatively with 45x A-concentrate (mix one part of the concentrate and <NUM> parts purified water to make <NUM> parts of ready fluid), SelectBag® solution, and <NUM>% by volume citric acid. Assuming blood set <NUM> to be <NUM> in total volume, the liquid volumes specified in the table would need to be increased three to seven times to achieve sufficient multiples of the blood set volume. The use of citric acid for example would require <NUM> to <NUM> of total liquid volume to achieve a 4X multiplier of the blood set volume. <NUM> of total liquid volume is believed to be a very reasonable amount.

Please note that the above data is for mixing at atmospheric pressure and a temperature of around <NUM> to <NUM>. It should also be understood that the numbers above are illustrated for the purpose of showing that enough CO<NUM> gas may be produced using a reasonable amount of CO<NUM> gas generation fluid constituents. The actual amounts used in practice will likely be adjusted when precipitation is taken into account. Moreover, reducing downstream pressure, e.g., by reducing the pressure in arterial line <NUM>, reduces the amount of CO<NUM> gas needed (e.g., half the quantity needed at half atmospheric pressure in the bloodlines). It is accordingly contemplated to maintain a low pressure in blood set <NUM>, e.g., at atmospheric or below, during the CO<NUM> gas priming.

Moreover, the example above using <NUM>® solution will likely create significant precipitation and thus may not present a realistic solution. The two citric acid examples having two different input volumes yielding different gas volumes show that test results may vary, for example, based upon environmental temperature and whether or not an underpressure is provided with the reaction. The underpressure may yield gas volume results that exceed what is theoretically possible at atmospheric pressure.

The formulations for the CO<NUM> gas priming mixtures are very likely going to be different than the formulations for treatment fluid, either because different constituents are used or because the same constituents are used in different proportions. Regarding the formulations generally, mixtures may be prepared accurately in two different ways, either by (i) using a formula for the mixture and accurately adding the constituents according to the formula or (ii) using a sensor reading indicative of the overall constituency of the mixture, e.g., conductivity, and sensor feedback to control unit <NUM> to servo to a desired sensor reading setpoint for a desired overall constituency. The different CO<NUM> gas formulations of the present disclosure may be prepared using either mixing accuracy technique.

The above table shows formulas, e.g., (a) formulas <NUM>:<NUM> for bicarbonate/A concentrate, (b) formulas <NUM>:<NUM> and <NUM>:<NUM> for bicarbonate/SelectBag® solution, and (c) formula <NUM>:<NUM> for bicarbonate/citric acid. As discussed above, it is conceivable to use conductivity sensors, setpoints and servo feedback to meet setpoints instead of the above formulas for the priming fluid mixtures. But in any case, the formulation of CO<NUM> gas generation fluid will be different in at least one respect than the formulation of fresh dialysis fluid prepared for treatment.

Referring now to <FIG> an alternative system for making CO<NUM> gas in dialysis fluid circuit <NUM> and delivering such gas to blood circuit <NUM> is illustrated by system 10b. System 10b is the same in many respect to system 10a (including all structure, functionality and alternatives discussed above). System 10b adds a recirculation line <NUM> extending in the illustrated embodiment from a bottom portion of gas generation chamber <NUM> back to a third three-way valve 192c under control of control unit <NUM>, and located upstream of metering pump <NUM>. Bicarbonate and acid solutions are delivered to gas generation chamber <NUM> as described above, but here with the path through third three-way valve 192c to recirculation line <NUM> closed. Once the desired amount of bicarbonate and acid solutions are delivered to gas generation chamber <NUM>, the state of third three-way valve 192c is switched such that the path through third three-way valve 192c to three-way valve 192a is closed, while the path through third three-way valve 192c to recirculation line <NUM> is opened.

During and after formation of the CO<NUM> gas, metering pump <NUM> recirculates the CO<NUM> gas generation fluid down recirculation line <NUM> and back up through third three-way valve 192c to gas generation chamber <NUM>. The recirculation stirs and agitates the CO<NUM> gas generation fluid, causing CO<NUM> gas to be released from the fluid and to flow out of gas generation chamber <NUM> through gas line <NUM>. In an embodiment, recirculation line <NUM> may be fitted with a spiraled member, a staggered flanged member, or other type of turbulator to further disrupt and turbulate the CO<NUM> gas generation fluid and release the CO<NUM> gas.

Referring now to <FIG>, an alternative system for delivering CO<NUM> gas from dialysis fluid circuit <NUM> to blood circuit <NUM> is illustrated by system 10c. System 10c is the same in many respect to system 10a (including all structure, functionality and alternatives discussed above). System 10c may also include recirculation line <NUM>, third three-way valve 192c, and the associated structure and functionality discussed in connection with system 10b. System 10c adds a pressure measurement line <NUM> leading from a top of drip chamber <NUM> to a machine connector <NUM>. In the illustrated embodiment, CO<NUM> gas is produced within machine <NUM> and is delivered to blood set <NUM> as described above. Control unit <NUM> causes blood pump <NUM> to run slowly to remove air from arterial line <NUM> and venous line <NUM> (connected together in <FIG>) and to deliver the air into venous drip chamber <NUM>. Air in chamber <NUM> is in turn led out of blood set <NUM> via venous pressure line <NUM> into the interior of machine <NUM> via valve 92Pv under control of control unit <NUM>.

Referring now to <FIG>, one embodiment for a priming fluid portion of the priming of blood circuit <NUM> of system 10c is illustrated. Here, the patient ends of arterial line <NUM> and venous line <NUM> are disconnected from each other (connected in <FIG>). After CO<NUM> gas priming has been completed, a saline bag or container <NUM> is connected to the distal end of arterial line <NUM>, while an empty drain bag or container <NUM> is connected to the distal end of venous line <NUM>. Blood pump <NUM> under control of control unit <NUM> is operated to pull saline from saline bag or container <NUM> through the portion of arterial line <NUM> upstream of blood pump <NUM>, and to push saline through the portion of arterial line <NUM> downstream from blood pump <NUM>, dialyzer <NUM>, drip chamber <NUM> and venous line <NUM> to drain bag or container <NUM>. The saline prime pushes CO<NUM> gas both to drain bag or container <NUM> and through venous pressure line <NUM> into the interior of machine <NUM> via valve 92Pv under control of control unit <NUM> until a level detector operable with drip chamber <NUM> detects a high fluid level, after which valve 92Pv is closed. Additionally, as discussed above, saline especially under positive pressure will also absorb some of the CO<NUM> gas back into solution. Moreover as discussed above, small amounts of CO<NUM> gas are not harmful to the patient.

In each of the previous examples, CO<NUM> gas is created in dialysis fluid circuit <NUM> and delivered in gaseous form to blood circuit <NUM>. In an alternative primary embodiment illustrated in <FIG>, system 110a instead causes CO<NUM> gas to be carried within the formulated priming fluid into blood circuit <NUM>, where the CO<NUM> gas is then degassed from the priming fluid to help rid blood circuit <NUM> of small air pockets. System 110a may include any of the structure, functionality and alternatives discussed above for systems 10a, 10b and 10c in combination with the additional structure, functionality and alternatives described below for <FIG>.

In <FIG>, blood circuit <NUM> operates with dialysis fluid circuit <NUM> as shown above, except that gas generation chamber <NUM> and associated plumbing is not needed or provided. <FIG> also illustrate that machine <NUM> may further include a hemodialfiltration ("HDF") port <NUM> and/or a waste handling option ("WHO") port <NUM>. As mentioned above, a portion of fresh dialysis fluid flowing along fresh dialysis fluid line <NUM> may be diverted through one or more ultrafilter to purify the fresh dialysis fluid to such a level that it may be delivered as replacement fluid directly into arterial line <NUM> as illustrated to perform pre-dialyzer or pre-infusion HDF or into venous line <NUM> to perform post-dialyzer or post-infusion HDF. <FIG> illustrate a replacement fluid pump <NUM>, which under control of control unit <NUM> delivers the replacement fluid to blood circuit <NUM> at a desired flowrate. <FIG> illustrate that arterial line <NUM> and venous line <NUM> may be plugged together into WHO port <NUM> to form a loop for the priming fluid and CO<NUM> gas.

It should be appreciated that in any embodiment described herein, CO<NUM> gas, e.g., via gas generation chamber <NUM> of system 10a, or via priming fluid in system 110a, may be introduced into blood circuit <NUM> (i) via fresh dialysis fluid line <NUM> and tube <NUM> or (ii) via a pre-, post-, or pre- and post- HDF port <NUM>. In a further alternative embodiment, CO<NUM> gas may be introduced into blood circuit <NUM> via an air vent line running between drip chamber <NUM> and hydrophobic or hydrophilic vent <NUM>.

In <FIG>, control unit <NUM> of system 110a causes replacement fluid pump <NUM> to pump priming fluid formulated to create CO<NUM> gas into blood circuit <NUM>. The priming fluid formulated to create CO<NUM> may be created using bicarbonate solution and any of the acid solutions described above, e.g., (i) a citric acid solution, (ii) an acetic acid solution (e.g., from A-concentrate), (iii) a lactic acid solution, (iv) a malic acid solution, (v) a hydrochloric ("HCl") acid solution, (vi) a phosphoric acid solution, (vii) any other biocompatible acid solution, and (v) blends thereof. The flowrate of priming fluid formulated to create CO<NUM> gas may be a desired flowrate Qp mL/minute (e.g., from <NUM> to <NUM>/minute) at replacement fluid pump <NUM> and below Qp mL/minute at blood pump <NUM>. The introduction of the priming fluid into blood circuit <NUM> causes much of the air to be pushed out of blood circuit <NUM> via hydrophobic or hydrophilic vent <NUM>.

In <FIG>, control unit <NUM> causes the speed of blood pump <NUM> to be increased, e.g., above Qp mL/minute, so that blood pump <NUM> pumps faster than replacement fluid pump <NUM>, which creates a relatively lower pressure in replacement fluid line <NUM>. Blood pump <NUM> pumping towards dialyzer <NUM> also places venous line <NUM> and the portion of arterial line <NUM> upstream of blood pump <NUM> under negative pressure. Venous drip chamber <NUM> with a hydrophilic filter <NUM> is inverted, e.g., manually, or via an electromechanical actuator under control of control unit <NUM> in <FIG>, so that air is not pulled into blood circuit <NUM>. The relatively low pressure in replacement fluid line <NUM> and the negative pressure in venous line <NUM> and in the portion of arterial line <NUM> upstream of blood pump <NUM> both cause the priming fluid to degas CO<NUM> into those portions of blood circuit <NUM>. The CO<NUM> gas dislodges air pockets in tight portions of blood circuit <NUM> as has been described above.

Control unit <NUM> may then cause blood pump <NUM> in <FIG> to move in reverse to place the priming fluid in the remaining portion of arterial line <NUM> and dialyzer <NUM> under negative pressure to cause the priming fluid to degas CO<NUM> into the remainder of arterial line <NUM> and dialyzer <NUM>. The CO<NUM> gas dislodges air pockets in the remainder of arterial line <NUM> and in the membranes and pores of the membranes of dialyzer <NUM> as has been described above. Control unit <NUM> may cause blood pump <NUM> to reverse back and forth multiple times to repeat the above-described sequence multiple times to ensure that blood circuit <NUM> has been subjected fully to CO<NUM> gas, so that virtually all air within blood circuit <NUM> has been dislodged for removal.

<FIG> illustrates that after the blood circuit <NUM> has been subjected fully to CO<NUM> gas, venous drip chamber <NUM> may be flipped to its normal position, e.g., manually, or via an electromechanical actuator under control of control unit <NUM>. Control unit <NUM> may again reverse blood pump <NUM> multiple times to ensure that all parts of blood circuit <NUM> see positive pressure leading to venous drip chamber <NUM> and its vent <NUM>, so that virtually all air within blood circuit <NUM> has been dislodged for removal.

<FIG> illustrates patient P connected to arterial line <NUM> and venous line <NUM> for treatment. Control unit <NUM> may be programmed such that after the CO<NUM> gas prime of <FIG>, CO<NUM> gas and any remaining CO<NUM> priming fluid for preparing the CO<NUM> gas may be absorbed and/or displaced using dialysis fluid prepared for treatment or saline. As discussed above, CO<NUM> is a physiologically compatible substance that is readily absorbed in the patient's bloodstream and removed from the body via breathing. Any trace amount of CO<NUM> remaining after the fluid prime of <FIG> and <FIG> is not harmful to the patient and is instead handled naturally.

Referring now to <FIG>, system 110b illustrates an alternative arrangement for carrying CO<NUM> gas within the priming fluid formulated to produce CO<NUM> gas into blood circuit <NUM>, where the CO<NUM> gas is then degassed from the priming fluid to help rid blood circuit <NUM> of small air pockets. System 110b includes all structure, functionality and alternatives discussed above and incorporated into system 110a. System 110b moves replacement fluid line <NUM> and replacement fluid pump <NUM> as shown in the illustrated embodiment, so that replacement fluid is delivered via pump <NUM> under control of control unit <NUM> to venous line <NUM> (post-dilution) instead of to arterial line <NUM> (pre-dilution) in <FIG>. Either system 110a and 110b may be configured to have pre- or post- dilution or pre- and post-dilution replacement fluid delivery. System 110b also moves hydrophilic vent <NUM> to be just in front of, or to be part of, machine connector <NUM>. Any of systems 10a to 10c, 110a or 110b may have hydrophilic vent <NUM> arranged as shown in <FIG>.

System 110b of <FIG> in the illustrated embodiment also includes a WHO pump <NUM> located within machine <NUM> (WHO pump may be any of the types of pumps described for metering pump <NUM>), which is under control of control unit <NUM> and is positioned and arranged to pull liquid from blood set <NUM> via WHO port <NUM>. A WHO valve <NUM>WHO under control of control unit <NUM> is located within machine <NUM> between WHO port <NUM> and WHO pump <NUM>. Any of systems 10a to 10c, 110a or 110b may have WHO pump <NUM> and WHO valve <NUM>WHO arranged as shown in <FIG>. System 110b of <FIG> in the illustrated embodiment further includes an air pump <NUM> located within machine <NUM> (air pump <NUM> may be any of the types of pumps described for metering pump <NUM>), which is under control of control unit <NUM> and is positioned and arranged to push or pull air to or from venous drip chamber <NUM> of blood set <NUM>. Air pump <NUM> is located between machine connector <NUM> and valve 92Pv in the illustrated embodiment. Any of systems 10a to 10c, 110a or 110b may have air pump <NUM> arranged as shown in <FIG>.

System 110b of <FIG> further includes a level sensor <NUM> operable with venous drip chamber <NUM> and located to sense a level of liquid within the chamber. Level sensor <NUM> sends a signal indicative of the level of liquid within chamber <NUM> to control unit <NUM>, which reacts accordingly. Any of systems 10a to 10c, 110a or 110b may have a level sensor <NUM> arranged as shown in <FIG>. System 110b of <FIG> also includes a replacement fluid line clamp <NUM> under control of control unit <NUM>. Replacement fluid line clamp <NUM> allows or disallows replacement fluid and other fluids to flow to venous line <NUM> of blood set <NUM>. Any of systems 10a to 10c, 110a or 110b may have a replacement fluid line clamp <NUM> arranged as shown in <FIG>. Still further, System 110b of <FIG> may include a gas/liquid sensor <NUM> under control of control unit <NUM>. Gas/liquid sensor <NUM> is configured to sense the difference between CO<NUM> gas generation fluid and CO<NUM> gas or air residing just below venous drip chamber <NUM>. Any of systems 10a to 10c, 110a or 110c may have a gas/liquid sensor <NUM> arranged as shown in <FIG>.

In <FIG> system 110b fills venous drip chamber <NUM> with CO<NUM> gas generation fluid. In one embodiment, control unit <NUM> causes replacement fluid pump <NUM> to run and fill venous drip chamber <NUM>. WHO pump <NUM> does not need to be operated. Here, in one embodiment, CO<NUM> gas generation fluid and any escaping CO<NUM> gas force air out of blood set <NUM> through drip chamber <NUM>, via venous pressure line <NUM> and into the interior of machine <NUM> via valve 92Pv under control of control unit <NUM>.

In <FIG>, when level sensor <NUM> at venous drip chamber <NUM> senses a high level of CO<NUM> gas generation fluid, CO<NUM> gas generation fluid is pumped or gravity flowed out the bottom of venous drip chamber <NUM> towards WHO port <NUM> via venous line <NUM>. Control unit <NUM> may be programmed to allow CO<NUM> gas generation fluid to flow out the bottom of venous drip chamber <NUM> for a preset period of time or until receiving a signal from a sensor, such as an ultrasonic or capacitive sensor (not illustrated), positioned at a desired location upstream of WHO port <NUM> to detect that no more air is coming down the line.

Control unit <NUM> then causes blood pump <NUM> to pull CO<NUM> gas generation fluid through connected venous line <NUM> and arterial line <NUM> to fill arterial line <NUM> up to dialyzer <NUM>.

<FIG> illustrates one embodiment for filling arterial line <NUM> between blood pump <NUM> and dialyzer <NUM>, the dialyzer itself, and the remainder of venous line <NUM> with CO<NUM> gas generation fluid. Control unit <NUM> causes blood pump <NUM> to pump CO<NUM> gas generation fluid somewhat faster than the rate at which replacement fluid pump <NUM> introduces new CO<NUM> gas generation fluid into blood circuit <NUM>, so that blood pump <NUM>, with arterial and venous lines <NUM> and <NUM> connected together as illustrated and with WHO valve <NUM>WHO closed, pulls CO<NUM> gas generation fluid out of venous drip chamber <NUM> more quickly than replacement fluid pump <NUM> refills the chamber, thereby lowering the liquid level in venous drip chamber <NUM>. The output of blood pump <NUM> fills the positive pressure portion of arterial line <NUM>, dialyzer <NUM> and the portion of venous line <NUM> up to the inlet of replacement fluid line <NUM> with CO2 gas generation fluid. Air is again forced out of blood set <NUM> through drip chamber <NUM>, via venous pressure line <NUM> and into the interior of machine <NUM> via valve 92Pv under control of control unit <NUM>. When all lines of blood set <NUM> are filled with CO<NUM> gas generation fluid, the liquid level within venous drip chamber <NUM> will rise, eventually tripping level sensor <NUM>, telling control unit <NUM> that blood set <NUM> is full.

<FIG> illustrates one embodiment for creating a low pressure in blood set <NUM> to pull CO<NUM> gas out of the CO<NUM> gas generation fluid. Here, control unit <NUM> causes replacement fluid pump <NUM> to stop and closes replacement fluid line clamp <NUM>. Control unit <NUM> further causes (i) WHO pump <NUM> to create a suction through WHO valve <NUM>WHO to the connection of arterial line <NUM> and venous line <NUM>, and (ii) blood pump <NUM> to run slowly to remove gas created inside of dialyzer <NUM> due to the degassing and to deliver CO<NUM> gas to all areas of blood set <NUM>. The suction pressure releases CO<NUM> gas from CO<NUM> gas generation fluid as has been discussed herein. If the level of CO<NUM> gas generation fluid in venous chamber <NUM> falls too low, control unit <NUM> may open replacement fluid line clamp <NUM> and cause replacement fluid pump <NUM> to restore the CO<NUM> gas generation fluid level.

When CO<NUM> gas priming is completed, a saline prime may be performed as illustrated in connection with <FIG>, or dialysis fluid for treatment may be used to flush CO<NUM> gas through drip chamber <NUM>, via venous pressure line <NUM> and into the interior of machine <NUM> via valve 92Pv under control of control unit <NUM>. CO<NUM> gas may additionally be absorbed into saline or dialysis fluid for treatment as described herein.

Referring now to <FIG> and <FIG>, system 110c illustrates an alternative arrangement for carrying CO<NUM> gas within the priming fluid formulated to produce CO<NUM> gas into blood circuit <NUM>, where the CO<NUM> gas is then degassed from the priming fluid to help rid blood circuit <NUM> of small air pockets. System 110c includes all structure, functionality and alternatives discussed above and incorporated into systems 110a and 110b. System 110c moves replacement fluid line <NUM> as shown in the illustrated embodiment, so that replacement fluid is delivered via replacement fluid pump <NUM> under control of control unit <NUM> to arterial line <NUM> (pre-dilution) as with in <FIG>.

Pre-dilution system 110c, unlike pre-dilution system 110a in <FIG>, uses valve 92Pv inside machine <NUM> to close off the air path when needed. It is noted that filter <NUM> in system 110c is a hydrophilic filter in the illustrated embodiment. Filter <NUM> may be used to protect blood from entering and contacting the connection site at machine connector <NUM> and the inside of machine <NUM>.

<FIG> illustrates one example embodiment for filling blood set <NUM>. Control unit <NUM> with replacement fluid line clamp <NUM> open causes blood pump <NUM> to run in reverse direction at a desired speed, pushing CO<NUM> gas generation fluid through connected lines <NUM> and <NUM> and backwards through venous line <NUM> to venous drip chamber <NUM>. Fluid/gas sensor <NUM> in communication with control unit <NUM> eventually sees the CO<NUM> gas generation fluid, which control unit <NUM> reads and causes blood pump <NUM> to stop. Control unit <NUM> then causes replacement fluid pump <NUM> to pump CO<NUM> gas generation fluid to blood set <NUM> including dialyzer <NUM> and the portion of venous line <NUM> to drip chamber <NUM> until level detector <NUM> operable with drip chamber <NUM> sees a high level of fluid.

In <FIG>, system 110c with blood set <NUM> having been filled with CO<NUM> gas generation fluid and with replacement fluid line clamp <NUM> closed, may then create a low pressure in blood set <NUM> in the manner described above in <FIG>, releasing the CO<NUM> gas from the CO<NUM> gas generation fluid to perform the CO<NUM> gas priming as described herein. After the CO<NUM> gas prime, blood set <NUM> may then be primed with dialysis fluid for treatment as has been described herein.

Claim 1:
An extracorporeal therapy system (10a to 10c) comprising:
a dialysis fluid circuit (<NUM>) including dialysis fluid preparation structure (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) configured to prepare a dialysis fluid for an extracorporeal therapy treatment;
a blood circuit (<NUM>) including a blood filter (<NUM>) for use during the extracorporeal therapy treatment;
a blood pump (<NUM>) operable to pump blood through the blood circuit (<NUM>) and blood filter (<NUM>); and
a control unit (<NUM>) operable with the dialysis fluid preparation structure (<NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>) and the blood pump (<NUM>),
wherein said extracorporeal therapy system is characterized by the fact that the control unit (<NUM>) is programmed to prepare a gas generation fluid different than the dialysis fluid for the extracorporeal therapy treatment, wherein the gas generation fluid generates carbon dioxide ("CO<NUM>") gas, and wherein the CO<NUM> gas is used to prime the blood circuit (<NUM>) including the blood filter (<NUM>).