Extracorporeal device and method for removing secondary membranes - Patents.com

Abstract

An extracorporeal blood treatment device and method are provided for removing a secondary membrane formed on a semipermeable membrane of a dialyzer during extracorporeal blood treatment. The extracorporeal blood treatment device operates in a first mode of operation in which the dialysate outlet valve is open to allow dialysate to flow through the dialyzer inlet line, through the dialysate chamber, and into the dialyzer outlet line. The extracorporeal blood treatment device operates in a second mode of operation to remove the secondary membrane from the semipermeable membrane. During the second mode of operation, the dialysate outlet valve is closed for a duration such that dialysate is prevented from flowing through the dialyzer outlet line. A backflush procedure occurs in which a volume of dialysate passes from the dialysate chamber through the semipermeable membrane and into the blood chamber.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 188,624, filed May 14, 2021, which is incorporated by reference in its entirety into this specification. [Technical field]

[0002] The present invention relates to devices and methods for extracorporeal blood treatment, such as by hemodialysis, hemofiltration, and hemodiafiltration. [Background technology]

[0003]

[0003] Renal replacement therapy systems are used for patients who must have their blood treated outside the body. Extracorporeal blood treatment can be used to extract undesirable substances or molecules from the patient's blood and, if necessary, add desirable substances or molecules to the blood. Extracorporeal blood treatment is accomplished by passing blood through a dialyzer. A semipermeable membrane separates the dialyzer into a blood chamber and a dialysate chamber. Blood drawn from the patient is introduced into the blood chamber and flows through the semipermeable membrane. The semipermeable membrane selectively allows substances in the blood to flow from the blood chamber through the semipermeable membrane into the dialysate chamber. The semipermeable membrane also selectively allows substances in the dialysate chamber to flow through the semipermeable membrane into the blood chamber, depending on the type of treatment.

[0004]

[0004] Several different types of extracorporeal blood treatments can be performed. In hemofiltration (HF) treatment, blood flows through a semipermeable membrane, and undesirable substances and toxins from the blood are drawn through the semipermeable membrane and carried away by the dialysate. Meanwhile, desirable substances are added to the blood, typically by metering a substitution fluid, also known as dialysate or replacement fluid, into the blood before or after the blood passes through the dialyzer and before it is returned to the patient. In hemodialysis (HD) treatment, dialysate containing desirable substances is introduced into the dialysate chamber of the dialyzer. Undesirable substances from the blood can pass through the semipermeable membrane into the dialysate, and desirable substances from the dialysate can pass through the semipermeable membrane into the blood. In hemodiafiltration (HDF) treatment, blood and dialysate exchange substances as in HD, and, as in HF, substances are added to the blood, typically by metering dialysate into the treated blood before it is returned to the patient. Ultrafiltration (UF) involves the removal of undesirable substances from the blood by convection through a semipermeable membrane into the dialysate chamber.

[0005]

[0005] Blood clotting, also called coagulation, is usually reduced by using anticoagulants such as heparin. However, during treatment, substances from the blood, such as, for example, clotted blood, pathogenic cytokines, chemokines, myocardial depressant factor, and C'-activated protein, can clog the semipermeable membrane of the dialyzer. This phenomenon is sometimes called membrane fouling or secondary membrane formation. The effect on the semipermeable membrane is a gradual decrease in flux and a change in semipermeable membrane selectivity. Membrane fouling occurs mainly due to concentration polarization and the adsorption or deposition of proteins on the surface or in the pores of the semipermeable membrane. Concentration polarization is the result of a concentration gradient due to the accumulation of solutes near the surface of the semipermeable membrane. This accumulation of solutes is also called secondary membrane. The adsorption or deposition of proteins on the surface or in the pores is caused by proteins adsorbed or trapped in the pores of the semipermeable membrane, which changes the properties of the semipermeable membrane. When areas of the semipermeable membrane begin to become less effective, measures must be taken to maintain the same treatment efficiency.

[0006]

[0006] The secondary membrane has traditionally been managed by rinsing the blood circuit and changing the filter. However, these procedures are time-consuming and require treatment to be stopped. Other devices and methods for removing the secondary membrane during treatment require the use of an additional set of dialysate lines, sensors, pumps, etc., which are more complicated than necessary and require expensive modifications to the extracorporeal blood treatment device.

[0007]

[0007] Therefore, there is a need for a device and method for removing secondary films formed during extracorporeal blood treatment that is efficient and allows for inexpensive modification of existing extracorporeal blood treatment devices. Summary of the Invention

[0008] It is a feature of the present invention to provide an extracorporeal device and method for removing a secondary membrane from a semipermeable membrane of a dialyzer.

[0009] Another feature of the present invention is to provide an extracorporeal device and method for removing the secondary membrane from the semipermeable membrane of a dialyzer during extracorporeal treatment of a patient.

[0010] A further feature of the present invention is to provide an extracorporeal device for intermittently removing the secondary membrane from the semipermeable membrane of the dialyzer during extracorporeal treatment of the patient.

[0011]

[0011] Yet a further feature of the present invention is to provide a modification to an extracorporeal device that intermittently removes the secondary membrane from the semipermeable membrane of the dialyzer during extracorporeal treatment of a patient.

[0012]

[0012] An additional feature of the present invention is providing an extracorporeal device that intermittently introduces a controlled amount of dialysate from the dialysate chamber, through the semipermeable membrane, into the blood chamber of the dialyzer to remove the secondary membrane from the semipermeable membrane during extracorporeal treatment of the patient.

[0013]

[0013] A further feature of the present invention is to provide an extracorporeal device that detects the buildup of secondary membrane on the semipermeable membrane of a dialyzer during extracorporeal treatment of a patient and removes the secondary membrane from the semipermeable membrane upon detection of buildup.

[0014]

[0014] Yet another feature of the present invention is to provide a processor for an extracorporeal device programmed or otherwise configured to execute a set of instructions for removing a secondary membrane from a semipermeable membrane during extracorporeal treatment of a patient.

[0015]

[0015] Yet another feature of the present invention is to provide a processor for an extracorporeal device programmed or otherwise configured to execute a set of instructions for detecting a buildup of secondary membrane on a semipermeable membrane of a dialyzer during extracorporeal treatment of a patient, and removing the secondary membrane from the semipermeable membrane upon detection of the buildup.

[0016]

[0016] Additional features and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The objectives and other advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the description and the appended claims.

[0017]

[0017] To achieve these and other advantages, and in accordance with the objects of the present invention, as embodied and broadly described herein, the present invention relates to an extracorporeal blood treatment device. The extracorporeal blood treatment device includes a dialyzer having a blood chamber, a dialysate chamber, a dialysate inlet, a dialysate outlet, and a semipermeable membrane. The blood chamber and the dialysate chamber are separated from each other by the semipermeable membrane. A dialyzer inlet line leads to the dialysate inlet and is configured to supply dialysate to the dialysate chamber. A dialyzer outlet line leads away from the dialysate outlet and is configured to carry dialysate out of the dialysate chamber. A dialysate pump is configured to pump dialysate through the dialyzer inlet line to the dialysate chamber and out of the dialysate chamber through the dialyzer outlet line.

[0018]

[0018] For example, a flow pump downstream of the return line and / or an ultrafiltrate pump may be configured to be switched between an operating state and a non-operating state, in which the ultrafiltrate pump draws liquid from the blood chamber through the semipermeable membrane into the dialysate chamber and withdraws it from the dialysate chamber.

[0019]

[0019] The dialysate pump is configured to operate in a first operating mode of the extracorporeal blood treatment device and a second operating mode of the extracorporeal blood treatment device. The first operating mode operates in a configuration in which the dialysate outlet valve is open so that dialysate flows through the dialyzer inlet line, through the dialysate chamber, and into the dialyzer outlet line. The second operating mode operates in a configuration in which the dialysate outlet valve is closed for a certain duration, the ultrafiltrate pump is switched to a non-operating state, and dialysate is prevented from flowing through the dialyzer outlet line, and a certain amount of dialysate passes from the dialysate chamber through the semipermeable membrane into the blood chamber. A balancing chamber can be equipped, which allows the valve to be closed and then reopened to complete the balancing chamber cycle.

[0020]

[0020] The present invention further relates to an extracorporeal blood treatment device having a processor and a sensor or sensor system in communication with the processor. The sensor or sensor system is configured to generate sensor data, and the processor is configured to process the sensor data. The processor is further configured to switch the extracorporeal blood treatment device from a first operating mode to a second operating mode for a period of time based on the processed sensor data.

[0021] The present invention further relates to a processor configured to determine, based on the sensor data, that secondary material is building up on the semipermeable membrane, and when the processor determines that secondary material is building up on the semipermeable membrane, the processor expedites switching the extracorporeal blood treatment device from a first operating mode to a second operating mode for a period of time.

[0022]

[0022] The present invention also relates to a blood treatment method comprising utilizing the extracorporeal blood treatment device of the present invention for treating a patient's blood and intermittently removing the secondary membrane from the semipermeable membrane during blood treatment.

[0023]

[0023] The present invention also relates to a processor for an extracorporeal device programmed or otherwise configured to execute a set of instructions for removing a secondary membrane from a semipermeable membrane during extracorporeal treatment of a patient.

[0024]

[0024] The present invention also relates to a processor for an extracorporeal device programmed or otherwise configured to execute a set of instructions for detecting a buildup of secondary membrane on a semipermeable membrane of a dialyzer during extracorporeal treatment of a patient, and removing the secondary membrane from the semipermeable membrane upon detection of the buildup.

[0025]

[0025] The present invention further relates to a blood treatment method, comprising: a) providing an extracorporeal blood treatment device including a dialyzer having a blood chamber, a dialysate chamber, and a semipermeable membrane, where the blood chamber and the dialysate chamber are separated from each other by a semipermeable membrane, and the dialysate chamber has a dialysate outlet valve; b) treating blood in a first operating mode by pumping dialysate through the dialysate chamber using a dialysate pump, pumping blood through the blood chamber using a blood pump, and drawing ultrafiltrate from the dialysate chamber using an ultrafiltrate pump; c) detecting a build-up of secondary membrane on the semipermeable membrane while treating blood in the first operating mode; and d) upon detection of the build-up, switching from the first operating mode to a second operating mode, where the second operating mode includes closing the dialysate outlet valve for a duration and stopping the ultrafiltrate pump to prevent dialysate from flowing out of the dialysate chamber, thereby allowing a quantity of dialysate to pass from the dialysate chamber through the semipermeable membrane to the blood chamber. Ultrafiltration does not necessarily have to be associated with preventing flow, but may be controlled to ensure accurate calculation of ultrafiltration rates.

[0026]

[0026] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary and explanatory and are intended to provide further explanation of the invention as defined in the claims.

[0027]

[0027] The drawings depict various design features of the present invention. Like reference identifiers in different drawings may refer to like features unless otherwise indicated. The drawings are not necessarily to scale. [Brief description of the drawings]

[0028] [Figure 1]

[0028] FIG. 1 is a schematic diagram of an extracorporeal blood treatment device according to one embodiment of the present invention. [Figure 2A]

[0029] 1 is a table of device setting variables and corresponding correction factors for modifying a base time and generating a time interval. [Figure 2B]

[0030] 1 is a table of device setting variables and corresponding correction factors for modifying a base time and generating a time interval. [Diagram 3]

[0031] 1 is a table of device output variables and corresponding correction factors for correcting a base time and generating a time interval. [Figure 4A]

[0032] FIG. 2 is a left portion of a schematic diagram of an extracorporeal blood treatment device according to one embodiment of the present invention. [Figure 4B] FIG. 2 is a right portion of a schematic diagram of an extracorporeal blood treatment device according to one embodiment of the present invention. [Figure 5A]

[0033] 3 is an upper portion of a flow chart illustrating method steps performed according to a method according to an embodiment of the present invention; [Figure 5B] 4 is a lower portion of a flow chart illustrating method steps performed according to a method according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029]

[0034] The present invention includes an extracorporeal blood treatment device and a method of treatment using the extracorporeal blood treatment device. The extracorporeal blood treatment device includes a dialyzer having a blood chamber, a dialysate chamber, a dialysate inlet, a dialysate outlet, and a semipermeable membrane. The blood chamber and the dialysate chamber are separated from each other by the semipermeable membrane. The dialyzer inlet line leads to the dialysate inlet and is configured to supply dialysate to the dialysate chamber. The dialyzer outlet line runs away from the dialysate outlet and is configured to carry dialysate out of the dialysate chamber. The dialysate pump is configured to pump dialysate through the dialyzer inlet line to the dialysate chamber and out of the dialysate chamber through the dialyzer outlet line. The dialysate outlet valve can be opened or closed to allow or restrict the flow of dialysate from the dialysate chamber of the dialyzer.

[0030]

[0035] The extracorporeal blood treatment device may further include a balancing device having a balancing chamber. A balancing inlet line leads to the balancing chamber and is configured to supply fresh dialysate from a dialysate source into the balancing chamber. A balancing outlet line leads away from the balancing chamber and is configured to carry spent dialysate from the balancing chamber to a drain. During priming, fresh dialysate can be circulated through the separate halves of the balancing chamber and can be drained. A dialyzer inlet line extends from the balancing chamber and is configured to supply dialysate from the balancing chamber to the dialysate chamber, and a dialyzer outlet line leads to the balancing chamber and is configured to supply dialysate from the dialysate chamber into the balancing chamber.

[0031]

[0036] The extracorporeal blood treatment device is configured to operate in a first and a second operating mode during treatment of a patient or during priming of the device. The first operating mode operates in a configuration in which the dialysate outlet valve is open to allow dialysate to flow through the dialyzer inlet line, through the dialysate chamber, and into the dialyzer outlet line. The second operating mode operates in a configuration in which the dialysate outlet valve is closed for a duration, preventing dialysate from flowing through the dialyzer outlet line, and allowing a volume of dialysate to pass from the dialysate chamber through the semipermeable membrane and into the blood chamber. During treatment, flowing dialysate back from the dialysate chamber through the semipermeable membrane into the blood chamber clears secondary membrane build-up, allowing for more efficient flow through the semipermeable membrane and thus more efficient treatment of the patient. During priming, flowing dialysate back from the dialysate chamber through the semipermeable membrane into the blood chamber also clears secondary membrane build-up present in a reused dialyzer, allowing for more efficient subsequent treatment of the patient.

[0032]

[0037] The extracorporeal blood treatment device includes an extracorporeal blood circuit. The extracorporeal blood circuit is in fluid communication with the blood chamber dialyzer via the blood chamber inlet and blood chamber outlet of the dialyzer. The extracorporeal blood circuit includes a blood pump, a blood supply line leading to the blood chamber inlet, and a blood removal line leading away from the blood chamber outlet. The blood pump is configured to pump blood through the blood supply line and blood chamber inlet into the blood chamber and out of the blood chamber through the blood chamber outlet and blood removal line. During treatment of a patient, blood flows through the blood chamber of the dialyzer and dialysate containing desirable substances is introduced into the dialysate chamber of the dialyzer. Undesirable substances from the blood can pass through the semipermeable membrane into the dialysate and desirable substances from the dialysate can pass through the semipermeable membrane into the blood.

[0033]

[0038] In certain embodiments, the extracorporeal blood treatment device is capable of ultrafiltration. An ultrafiltration line branches off from the dialyzer drain line downstream of the dialysate outlet valve. An ultrafiltrate pump is disposed on the ultrafiltration line. The ultrafiltrate pump is configured to be switched between an operating state and a non-operating state. During the operating state, the ultrafiltrate pump draws liquid from the blood chamber through the semipermeable membrane into the dialysate chamber and from the dialysate chamber through the dialysate outlet valve. Ultrafiltration further enhances the removal of undesirable substances from the blood by convection through the semipermeable membrane into the dialysate chamber.

[0034]

[0039] The extracorporeal blood treatment device may further include treatment with a substitution fluid. In such an embodiment, the extracorporeal blood treatment device includes a substitution fluid line and a substitution fluid pump disposed on the substitution fluid line. In certain embodiments, the substitution fluid line branches off from the dialysate inlet line and merges with the blood removal line for a post-dilution treatment. In other embodiments, the substitution fluid line branches off from the dialysate inlet line and merges with the blood supply line for a pre-dilution treatment. The substitution fluid line may be provided with a first substitution fluid pump and a second substitution fluid pump disposed on the substitution fluid line and may merge with both the blood supply line and the blood removal line for a mixed dilution treatment. The substitution fluid pump may be configured to pump the substitution fluid from the dialysate inlet line through the substitution fluid line to the blood removal line and / or the blood supply line, for example after passing through a second filter to further remove impurities resulting from direct contact of the substitution fluid with blood. Substitution fluid can be introduced during a hemofiltration procedure, in which desired substances are added to the blood by metering substitution fluid into the blood either before and / or after the blood passes through a dialyzer as it flows through a semipermeable membrane procedure, in an amount equal to the fluid removed from the blood chamber of the dialyzer to maintain fluid volume. Introduction of substitution fluid can also occur during a hemodiafiltration procedure, in which the blood and dialysate exchange substances similar to hemodialysis, but in addition substitution fluid is added to the blood in an amount equal to the fluid removed from the blood chamber of the dialyzer to maintain fluid volume.

[0035]

[0040] Each of the pumps and valve(s) of the extracorporeal treatment device can be controlled depending on the type of treatment and whether the extracorporeal treatment device is operating in a first or second operating mode. During a first operating mode of a hemodialysis treatment, the dialysate valve is open while there is no alarm, the dialysate pump is activated to continuously pump dialysate through the dialysate chamber, and the blood pump is activated to continuously pump blood through the blood chamber. During a second operating mode of a hemodialysis treatment, the dialysate outlet valve is closed for a duration, the dialysate pump speed can be increased, decreased, or maintained at a speed compared to the first operating mode, and the blood pump can be turned off or the blood pump speed can be increased, decreased, or maintained at a speed compared to the first operating mode.

[0036]

[0041] During a first operating mode of the hemofiltration treatment, the dialysate valve is open, the dialysate pump is turned off or operates at a minimum speed, e.g., 100 ml / min, the blood pump is activated to continuously pump blood through the blood chamber, the ultrafiltrate pump is in an operating state where the ultrafiltrate pump draws liquid from the blood chamber through the semipermeable membrane into the dialysate chamber and out of the dialysate chamber, and the substitution fluid pump is activated to pump substitution fluid into the blood supply line, the blood removal line, or both. During a second operating mode of the hemofiltration treatment, the dialysate outlet valve is closed for a duration, the dialysate pump pumps dialysate through the dialysate chamber, the substitution pump is turned off, the ultrafiltration pump is in a non-operating state, and the blood pump can be turned off or the blood pump speed can be increased, decreased, or maintained at a speed compared to the first operating mode.

[0037]

[0042] During a first operating mode of the hemodiafiltration treatment, the dialysate valve is open, the dialysate pump is activated to continuously pump dialysate through the dialysate chamber, the ultrafiltrate pump is in an operating state where the ultrafiltrate pump draws fluid from the blood chamber through the semipermeable membrane into the dialysate chamber and out of the dialysate chamber, the substitution fluid pump is activated to pump replacement fluid into the blood supply line, the blood removal line, or both, and the blood pump is activated to continuously pump blood through the blood chamber. During a second operating mode of the hemodiafiltration treatment, the dialysate outlet valve is closed for a duration, the dialysate pump speed can be increased, decreased, or maintained at a speed compared to the first operating mode, the substitution pump is turned off, the ultrafiltration pump is in a non-operating state, the blood pump can be turned off, or the blood pump speed can be increased, decreased, or maintained at a speed compared to the first operating mode.

[0038]

[0043] As described above, the second mode of operation operates in a configuration in which the dialysate outlet valve is closed for a duration, preventing dialysate from flowing through the dialyzer drain line, and a volume of dialysate passes from the dialysate chamber through the semipermeable membrane and into the blood chamber. The extracorporeal treatment device can enter the second mode of operation multiple times during treatment, with each second mode of operation being of relatively short duration. The timing can be based on possible dialysate flow rates of 100 ml / min to 1000 ml / min, which are standard in some dialysis machines, such as the Fresenius Medical Care model 5008s. At a high flow rate of 1000 ml / min, the balancing cycle can take only about 2 seconds, and at a low flow rate of 100 ml / min, the balancing cycle can take about 21 seconds. Approximately 15% to 20% can be added to these times to account for the time that the dialysate return line valve is closed. In the absence of a balancing chamber, only the closing time is relevant. Taking these considerations into account, the duration of the second mode of operation may range from about 0.3 to 5 seconds if the device is not equipped with a balancing chamber, and may range from 2 to 30 seconds if the device is equipped with a balancing chamber. The duration of the second mode of operation may be dependent on the dialysate flow rate to ensure that a known amount of fluid is introduced.

[0039]

[0044] Due to the short duration of one or more second operating modes, a small amount of dialysate may pass from the dialysate chamber through the semipermeable membrane and into the blood chamber. For example, the amount of dialysate entering the blood chamber may be 3 ml to 6 ml, or up to 20 ml. Larger amounts may be used when operating in a priming mode or under conditions that cause strong secondary membrane formation.

[0040]

[0045] During each second mode of operation, a small amount of dialysate enters the bloodstream. A small amount of dialysate may be removed from the bloodstream during each subsequent first mode of operation. To do so, the ultrafiltration pump may be configured to operate at a faster speed during at least some time frame of the first mode of operation (other than the initial first mode of operation) to remove an amount of liquid from the blood chamber equivalent to the amount of dialysate introduced in the preceding second mode of operation. For example, the ultrafiltrate pump may be configured to remove an amount of liquid from the blood, which may be, for example, 3 ml to 6 ml or up to 20 ml. A larger amount may be removed when operating under conditions that cause strong secondary membrane formation.

[0041]

[0046] Flow pumps, degassing pumps, auxiliary pumps, combinations thereof, and the like may be used by the extracorporeal treatment device. One or more of such pumps may drive the circulation of fresh dialysate or cleansing solution, etc., through the dialysate circuit. The pumps may be controlled to circulate liquids, such as, for example, a priming solution, dialysate, a wash solution, a rinse solution, or combinations thereof, through the dialysate circuit.

[0042]

[0047] The extracorporeal blood treatment device of the present invention can include a computing system. The computing system can include a processor, a memory, and a user interface. A data processing program (software) can be loaded onto the memory and executed on the processor to perform the method steps. The computing system communicates with the dialysate pump, the blood pump, the substituate pump, the ultrafiltration pump, the valves, and the sensors via wired or wireless communication. The computing system can automatically control the pumps and valves via instructions provided by the software, the user can manually control the pumps and valves using the user interface, pre-programmed routines can be executed, artificial intelligence can be implemented to better control the treatment and / or future treatments, and similar control features can be implemented.

[0043]

[0048] The sensor may be configured to generate sensor data of the extracorporeal blood treatment device, and the computing system may be configured to use the sensor data to determine when to change the extracorporeal blood treatment device from a first operating mode to a second operating mode, from the second operating mode to the first operating mode, or both. In certain embodiments, the computing system is configured to operate the extracorporeal blood treatment device in an initial first operating mode stage for a primary operating time frame, the initial first operating mode stage beginning at the beginning of the treatment. The primary operating time frame may include 20 minutes to 80 minutes, 30 minutes to 70 minutes, 40 minutes to 60 minutes, or 50 minutes. Upon expiration of the primary operating time frame, the computing system may automatically convert the extracorporeal blood treatment device from the first operating mode to the second operating mode for a secondary operating time frame. The duration of the second operating mode may be in the range of about 0.3 to 5 seconds if the device is not equipped with a balancing chamber, and may be in the range of 2 to 30 seconds if the device is equipped with a balancing chamber. The duration of the second operating mode may depend on the dialysate flow rate to ensure that a known amount of fluid is introduced. The length of each backflush routine or second operating mode may be calculated independently.

[0044]

[0049] The primary operating time frame may be calculated based on a base time that the computing system automatically modifies depending on at least one device setting variable, such as a plurality of device setting variables, and the base time may be preset to, for example, 60 minutes, 70 minutes, 75 minutes, 80 minutes, or 90 minutes.

[0045]

[0050] The device setting variables may include the type of dialyzer used during the treatment, the type of treatment selected (hemofiltration, hemodialysis, or hemodiafiltration), the substitution pump speed, the ultrafiltration pump speed, the blood pump speed, whether substitution fluid is provided to the blood line upstream or downstream of the dialyzer, the preset ultrafiltration coefficient associated with the dialyzer, the amount of hemodiafiltration bolus, or a combination thereof. The device setting variables are used to determine how much the computing system modifies the base time of the primary operating time frame. For example, if the ultrafiltration pump speed, the blood pump speed, or a combination thereof, is set to an increased speed, the base time is decreased since such a change increases the rate of accumulation of secondary membranes. If the replacement fluid flow rate is increased and added at post-dilution, the result is expected to be more provocative of secondary membrane formation.

[0046]

[0051] With the decrease in base time, the computing system can switch the extracorporeal blood treatment device from the first operating mode to the second operating mode sooner to remove excess buildup of secondary membrane and maintain efficient treatment. For example, an earlier backflush may be desirable to better remove urea. In addition, the type of treatment can affect the rate of buildup of secondary membrane. For example, secondary membrane may build up at a faster rate during hemofiltration and hemodiafiltration compared to hemodialysis when replacement fluid is introduced into the blood after the dialyzer. Alternatively, secondary membrane formation may build up at a slower rate during hemofiltration and hemodiafiltration compared to hemodialysis due to blood dilution when replacement fluid is introduced into the blood before the dialyzer. Thus, the computing system adjusts the base time based on device setting data entered, for example, before, during, or during treatment, during hemodiafiltration or during hemofiltration compared to hemodialysis.

[0047]

[0052] During the treatment, the computing system periodically receives sensor data from the sensor. Using the sensor data, the computing system can determine device output variables and adjust the base time of the primary operating time frame based on the device output variables. In a particular embodiment, the sensor senses urea levels and pressures in the dialysate line and blood line of the extracorporeal blood treatment device, and the sensor data is provided to the computing system. The computing system can use the sensor data to determine device output variables of venous pressure, transmembrane pressure difference, change in ultrafiltration coefficient, change in hematocrit, change in transmembrane pressure difference, change in clearance, or combinations thereof. The computing system can then adjust the base time of the primary operating time frame based on the device output variables. For example, if the transmembrane pressure difference is detected to have increased, if the ultrafiltration coefficient is detected to have decreased, or combinations thereof, the computing system can decrease the base time based on the obtained device output variables. This is because an increase in the transmembrane pressure difference and a decrease in the ultrafiltration coefficient indicate a stronger buildup of the secondary membrane, and thus a need to turn on the second operating mode earlier.

[0048]

[0053] In certain embodiments, the duration for which the dialysate outlet valve is closed during the secondary operating time frame of the second operating mode can include a base volume to be delivered from the dialysate chamber into the blood chamber of the dialyzer. The duration for which the dialysate outlet valve is closed depends primarily on the dialysate flow rate to ensure that a base volume is delivered from the dialysate chamber into the blood chamber of the dialyzer. Furthermore, the base volume itself delivered from the dialysate chamber into the blood chamber of the dialyzer can be automatically modified by the computing system depending on device setting variables and device output variables. As with modifications to the primary operating time frame, examples of device setting variables can include the type of dialyzer used during the treatment, the type of treatment selected (hemofiltration, hemodialysis, or hemodiafiltration), blood pump speed, substitution pump speed, ultrafiltration pump speed, or combinations thereof. If the substitution pump speed, ultrafiltration pump speed, blood pump speed, or combinations thereof are increased, the base volume delivered into the blood chamber of the dialyzer during the secondary operating time frame can be increased, as such device settings may increase the rate of build-up of the secondary membrane. Thus, the base volume delivered into the blood chamber of the dialyzer during the secondary operating time frame can be increased so that the computing system can maintain the extracorporeal blood treatment device in the second operating mode for a longer time frame to remove excess buildup on the secondary membrane and maintain efficient treatment. Examples of device output variables can include venous pressure, transmembrane pressure difference, change in ultrafiltration coefficient, change in hematocrit, change in transmembrane pressure difference, change in clearance, or combinations thereof, determined by the computing system using sensor data from the sensor. The computing system can then adjust the base volume delivered into the blood chamber of the dialyzer during the secondary operating time frame based on the device output variables. For example, if the transmembrane pressure difference is detected to have increased, if the ultrafiltration coefficient is detected to have decreased, or combinations thereof, the computing system can increase the base volume delivered into the blood chamber of the dialyzer during the secondary operating mode based on the obtained device output variables.This is because an increase in the transmembrane pressure difference and a decrease in the ultrafiltration coefficient indicate a stronger buildup of the secondary membrane and thus the need for the second operating mode to deliver a greater amount of fluid from the dialysate chamber to the blood chamber of the dialyzer.

[0049]

[0054] In certain embodiments, the computing system is configured to switch the extracorporeal blood treatment device between a first and a second operating mode in an alternating sequence at a predetermined frequency during treatment. Each of the multiple operating modes includes a respective operating time frame. The computing system is configured to modify each of the respective operating time frames, and therefore the frequency, based on device setting variables, device output variables, or both. For example, if the ultrafiltration pump speed, blood pump speed, or a combination thereof is set to an increased speed, the base time is decreased because such a change increases the rate of accumulation of secondary membranes. If the replacement fluid flow rate is increased and added at post-dilution, the result is expected to cause more secondary membrane formation. In addition, if the device output variables include an increased transmembrane pressure difference, a decreased ultrafiltration coefficient, or a combination thereof, the computing system can increase the frequency of the secondary operating time frames, because an increase in the transmembrane pressure difference and a decrease in the ultrafiltration coefficient indicate a stronger accumulation of secondary membranes, and thus a need to operate the second operating mode more frequently.

[0050]

[0055] The computing system can modify the frequency of the first and second operating modes of the extracorporeal blood treatment device by comparing the ultrafiltration coefficient, the transmembrane pressure difference, or a combination thereof with the initial calculated values. For example, the computing system can determine the ultrafiltration coefficient, the transmembrane pressure difference, or both at the start of the treatment or within 1-20 minutes, 5-15 minutes, or 10 minutes after the start of the treatment to determine the initial calculated values. If the ultrafiltration coefficient, the transmembrane pressure difference, or both are determined after a significant delay from the start of the treatment, the initial calculated values ​​of the ultrafiltration coefficient and the transmembrane pressure difference can be modified accordingly. For example, typically, a 33% drop in the ultrafiltration coefficient occurs in the first 30 minutes of the treatment. For an initial calculated value calculated after 10 minutes, the following formula can be used to adjust the initial calculated value: adjusted ultrafiltration coefficient initial calculated value = (initial calculated ultrafiltration coefficient at time t) * (1 + (0.33 * (time t) / 30)) where t is less than 30. If the initial calculated ultrafiltration coefficient occurs after 30 minutes, use 1.33 as the multiplier.

[0051]

[0056] After the computing system switches the extracorporeal blood treatment device from a first operating mode to a second operating mode and then back to the first operating mode, the ultrafiltration coefficient, the transmembrane pressure difference, or both can be determined again by the computing system using the sensors, and these values ​​can then be compared to the initial calculated values ​​to determine the extent of secondary membrane buildup removal. If it is determined that secondary membrane buildup is not being adequately removed, the computing system can adjust the frequency and time frame of the first and second operating modes of the extracorporeal blood treatment device. The ultrafiltration coefficient, the transmembrane pressure difference, or both can be determined by the computing system each time the second operating mode is switched back to the first operating mode to determine if adjustments to the frequency and time frame need to be made.

[0052]

[0057] The number and timing of each backflush can be determined independently and can be based on an initial setting, device output data, rate of change, or a combination thereof, etc. The duration of the second operating mode or backflush can range from about 0.3 to 5 seconds if the device is not equipped with a balancing chamber, and can range from 2 to 30 seconds if the device is equipped with a balancing chamber. The duration of the second operating mode can be dependent on the dialysate flow rate to ensure that a known amount of fluid is introduced. Control signals received from the computing system can control valves, pumps, or combinations thereof to initiate a backflush, maintain the backflush time, terminate the backflush, and / or switch back to the first operating mode.

[0053]

[0058] The present invention also enables existing extracorporeal blood treatment devices to be programmed, such as with a computer program, instruction set, algorithm, or combination thereof, as described herein. For example, new or existing devices and processors that include or control existing valves, pumps, and sensors can be configured and / or programmed to carry out the methods and procedures of the present invention.

[0054]

[0059] FIG. 1 is a schematic diagram showing various components of an extracorporeal blood treatment device in which the present teachings can be implemented. The extracorporeal blood treatment device includes a blood circuit and a dialysate circuit. The blood circuit and the dialysate circuit together with a dialyzer 1 form the fluid system of the extracorporeal blood treatment device. The dialyzer 1 has a blood chamber 2 and a dialysate chamber 3 separated by a semipermeable membrane 4. A blood supply line 5 along which a blood pump 6 is provided leads from a patient arterial port 7 to a blood inlet 48 of the blood chamber 2. An aortic valve 8 can be located along the blood supply line 5 upstream of the blood pump 6. A blood removal line 9, in which a liquid chamber 10 can be located, leads from a blood outlet 52 of the blood chamber 2 to a patient venous port 11. A venous valve 12 can be placed along the blood removal line 9 downstream of the liquid chamber 10.

[0055]

[0060] The dialysate circuit has a dialysate source 13 for supplying fresh dialysate. The dialysate source 13 is connected to the inlet of a first chamber 15A of the pair of balancing chambers 15 via a first portion 14A of a dialysate supply line 14. A second portion 14B of the dialysate supply line 14 connects the outlet of the first chamber 15A to the dialysate inlet 40 of the dialysate chamber 3. The fresh dialysate can be used as a flushing fluid or a preparation fluid. The dialysate outlet 44 of the dialysate chamber 3 is connected to the inlet of the second chamber 15B of the balancing chamber 15 via a first portion 16A of a dialysate removal line 16. A dialysate flow pump 17 is disposed along the first portion 16A of the dialysate removal line 16. The outlet of the second chamber 15B is connected to a drain 18 via a second portion 16B of the dialysate removal line 16. The balancing chamber 15 can have two or more chambers.

[0056]

[0061] A dialysate inlet valve 19 is located along the dialysate supply line 14 upstream of the dialysate chamber 3. A dialysate outlet valve 20 is located along the dialysate removal line 16 downstream of the dialysate chamber 3. An air separation chamber or air separator 55 may be disposed along the first portion 16A of the dialysate removal line 16 downstream of the dialysate outlet valve 20 and upstream of the dialysate pump 17. The water level in the air separator 55 is shown in FIG. 1. The dialysate inlet valve 19 and the dialysate outlet valve 20 may be electromagnetically actuable valves.

[0057]

[0062] An ultrafiltrate line 23 branches off from the air separator 55 and leads to the second portion 16B of the dialysate removal line 16. An ultrafiltrate pump 24 is provided along the ultrafiltrate line 23. An air removal line 25, along which a bypass valve 26 is provided, leads from the top of the air separator 55 to the second portion 16B of the dialysate removal line 16. The blood pump 6, the dialysate pump 17, and the ultrafiltrate pump 24 may be occlusion pumps. If the pumps are occlusion pumps, specific valves for providing a sealed volume may be omitted.

[0058]

[0063] The extracorporeal blood treatment device may also have a substitution fluid pump 35 for pumping substitution fluid, also referred to herein as replacement fluid, into the extracorporeal blood circuit via a substitution fluid line 36, upstream or downstream of the blood chamber 2. A substitution fluid valve 37 may be provided along the substitution fluid line 36 upstream of the substitution fluid pump 35, for example as shown in FIG. 1. Depending on whether the substitution fluid is injected into the extracorporeal blood circuit upstream or downstream of the blood chamber, a difference in the accumulation of the secondary membrane may occur. The difference in the accumulation caused by the two different injection points may be taken into account by applying the respective correction factors described herein. Depending on whether the substitution fluid is injected into the extracorporeal blood circuit continuously or as a bolus, upstream or downstream of the blood chamber, a difference in the accumulation of the secondary membrane may also occur. The difference in the accumulation caused by the two different injection points of the bolus may also occur. The difference in the accumulation caused by the two different injection points of the bolus may also occur.

[0059]

[0064] The extracorporeal blood treatment device may include a computing system 27 for controlling the pumps and valves. The computing system 27 may include, for example, a general-purpose processor 27A, a digital signal processor (DSP) for continuously processing digital signals, a microprocessor, an application specific integrated circuit (ASIC), an integrated circuit of logic elements, a field programmable logic array (FPGA), or other integrated circuits (ICs) or hardware components for performing the individual method steps described herein. The computing system 27 further includes a memory 27B for storing data processing programs (software) that may be executed on the hardware components to perform the method steps. The computing system 27 further includes a user interface 27C. The user interface 27C may include hardware, software, firmware, or combinations thereof for allowing a user to communicate and send commands to the computing system 27. For example, the user interface 27C may include, but is not limited to, a display, a touch screen display, a keyboard, a keypad, a mouse, a virtual reality interface, an augmented reality interface, a voice command interface, one or more speakers, one or more microphones, and combinations thereof.

[0060]

[0065] The computing system 27 is connected via control or data lines (not shown) to the dialysis pump 17, the blood pump 6, the ultrafiltrate pump 24, the substituate pump 35, the dialysate inlet valve 19, the dialysate outlet valve 20, the blood inlet valve 8, the blood outlet valve 12, the bypass valve 26 and the substituate valve 37, so that via the computing system 27 the flow rates of the pumps can be set and the valves and the bypass valves can be actuated. The valves and the bypass valves have actuating members (not shown) that can act on the fluid lines.

[0061]

[0066] The extracorporeal blood treatment device may further include sensors 32, 33, 41, and 47 connected to the computing system 27 via data lines 32A, 33A, 41A, and 47A, respectively. Sensor 47 is a dialysate supply pressure sensor that measures the pressure in the dialysate supply line 14. Sensor 32 is a dialysate removal pressure sensor that measures the pressure in the dialysate first portion 16A of the dialysate removal line. Sensor 41 is a blood supply pressure sensor that measures the blood pressure in the blood supply line 5 downstream of the blood pump 6. Sensor 33 is a blood removal pressure sensor that measures the pressure in the blood removal line 9. Sensors 32, 33, 41, and 47 measure the pressure in their respective fluid lines and generate sensor data that is sent to and processed by the computing system 27. The computing system 27 may use the sensor data to determine transmembrane pressure differences, ultrafiltration coefficients, and other values. Sensors may also include urea sensors, air separator pressure sensors, and similar sensors that may be used in extracorporeal blood treatment devices. Optionally, sensors 41 and 47 may be included to improve the accuracy of the calculated transmembrane pressure and the calculated ultrafiltration coefficient, for example, during treatment.

[0062]

[0067] Sensors 32, 33, 41, and 47 are configured to generate sensor data for the extracorporeal blood treatment device, and computing system 27 is configured to use the sensor data to determine when to change the extracorporeal blood treatment device from a first operating mode to a second operating mode and from the second operating mode to the first operating mode.

[0063]

[0068] At the time of use, a user may begin by inputting device setting variables into the computing system 27, or the device setting variables may be preloaded into the computing system 27. The device setting variables may include, but are not limited to, the type of dialyzer used during the treatment, the type of treatment selected (e.g., hemofiltration, hemodialysis, or hemodiafiltration), the substitution fluid pump speed, the ultrafiltration pump speed, the blood pump speed, whether the substitution fluid is provided to the blood line upstream or downstream of the dialyzer, the preset ultrafiltration coefficient, the amount of the hemodiafiltration bolus, whether the bolus is injected pre-dilution or post-dilution, and combinations thereof. The computing system 27 may modify the base time of the primary operating time frame, the base time of the secondary operating time frame, or combinations thereof based on the device setting variables. To start the treatment, the patient arterial port 7 and the patient venous port 11 are connected to the patient, and the extracorporeal blood treatment device starts the treatment in the first operating mode for the modified primary operating time frame. Upon expiration of the modified primary operating time frame, the computing system 27 may switch the extracorporeal blood treatment device to the second operating mode for a modified second operating time frame.

[0064]

[0069] While the extracorporeal blood treatment device is operating, the computing system 27 periodically receives sensor data from the sensors 32, 33, 41, and 47. Using the sensor data, the computing system 27 can determine device output variables and adjust the base times of the primary and secondary operating time frames based on the device output variables. In a particular embodiment, the sensors 32, 33, 41, and 47 sense the clearance levels and pressures in the dialysate lines 14 and 16 and blood lines 5 and 9 of the extracorporeal blood treatment device, and the sensor data can be transmitted to the computing system 27. The computing system 27 then determines the device output variables and uses the sensor data to select predetermined coefficients or corrections based on venous pressure, transmembrane pressure difference, changes in ultrafiltration coefficient, changes in hematocrit, changes in transmembrane pressure difference, changes in clearance, and combinations thereof, and the like. Along the blood line 5, for example, a fluid management monitoring tool incorporating photo-optical technology for non-invasively measuring absolute hematocrit and continuous oxygen saturation can be attached. Additionally, such an attached device, commonly referred to as CLiC, may also be configured to calculate percent change in intravascular blood volume and oxygen saturation of the dialysis patient. Computing system 27 may then adjust the base times of the primary and secondary operating time frames based on the device output variables.

[0065]

[0070] As an example, if the transmembrane pressure difference is detected as increasing or the ultrafiltration coefficient is detected as decreasing, or a combination thereof, the computing system 27 can decrease the base time based on the obtained device output variables. Decreasing the base time can be performed based on a conclusion that an increase in the transmembrane pressure difference and a decrease in the ultrafiltration coefficient indicate a buildup of secondary membrane on the semipermeable membrane of the dialyzer, and thus a need to perform the second operating mode sooner, for a longer time frame, or both.

[0066]

[0071] 2A and 2B show a table of device setting variables with four columns including type of device setting variable, discrete modifier, percent modifier, and coefficient of modification. The type of device setting variable is a variable set by the user of the device or by the computing system before or during the patient's treatment. The discrete modifier, percent modifier, and coefficient of modification are pre-programmed data points used by the computing system to adjust the base time before switching to the second operating mode based on the input device setting variable. Specifically, the discrete modifier is the amount of time in minutes that the computing system subtracts from or adds to the base time. The percentage modifier is the percentage of the base time that the computing system subtracts from or adds to the base time. The modification coefficient is a coefficient used by the computing system to adjust the base time and thereby determine the time interval before each second operating mode (backflush). The correction factors are calculated based on the percentage modifier and are not used when the discrete modifier is subtracted from or added to the base time. The correction factors and the formulas that use them are detailed below.

[0067]

[0072] Examples of types of device setting variables include replacement fluid rate, ultrafiltrate (UF) rate, and blood flow rate. A user or a computing system can set the replacement fluid rate, UF rate, and blood flow rate. The computing system can then subtract or add time to the base time to determine when the computing system can switch the blood extracorporeal device from a first operating mode to a second operating mode to backflush the semipermeable membrane. For example, if the blood flow rate is set to 200 ml / min, the percent modifier is -3%, thus calculating a time reduction of 3% of the base time. Similarly, if the UF rate is set to 2000 ml / hr, the percent modifier is -10%, thus calculating a time reduction of 10% of the base time. Increasing the ultrafiltrate and blood flow rates will increase the rate of secondary membrane accumulation, thus making it desirable to backflush the semipermeable membrane earlier during the procedure rather than later.

[0068]

[0073] Other exemplary types of device setting variables included in the tables of FIG. 2A and FIG. 2B include the type of dialyzer used in the extracorporeal blood treatment device (OPTIFLUX and Dialyzer (Custom)), hemodiafiltration bolus volume, change in ultrafiltration rate (Δ), change in blood flow rate (Δ), and change in replacement fluid rate (Δ). In these examples, discrete and percentage modifiers are provided. If the type of device setting includes both discrete and percentage modifiers, only one of the modifiers is applied. For example, the larger of the two may be applied to the base time based on the time remaining to switch from a first operating mode to a second operating mode. For example, if an OPTIFLUX 250 NR dialyzer is used in the extracorporeal treatment device, the discrete modifier is −4 minutes and the percentage modifier is −10%. If the base time is 60 minutes, a 10% deduction is equivalent to a 6 minute subtraction (−6 minutes). A discrete modifier of -4 minutes is less than -6 minutes in absolute value, therefore a % modifier of -10% will be applied to the base time to determine the time interval.

[0069]

[0074] The table in FIG. 2B also shows the correctors for pre-dilution and post-dilution of the replacement fluid entering the blood. Pre-dilution is when the replacement fluid is pumped into the bloodline upstream of the dialyzer, and post-dilution is when the replacement fluid is pumped into the bloodline downstream of the dialyzer. As shown in the table in FIG. 2B, for pre-dilution, the percentage corrector for the replacement fluid rate is multiplied by −1, and for post-dilution, the percentage corrector for the replacement fluid rate is multiplied by 1. By multiplying the replacement fluid rate corrector by −1, the negative percentage corrector for the replacement fluid rate becomes a positive percentage corrector, thus increasing the base time instead of decreasing it. This is because the faster the pre-diluted blood flows through the dialyzer, the faster the rate of secondary membrane formation on the semipermeable membrane is reduced. Thus, as shown in Figures 2A and 2B, if the substitution flow rate is set to 100 ml / min, the percent modifier is -2%, and therefore a time reduction of 2% of the base time is calculated for postdilution HF or HDF therapy, and a time increase of +2% or 2% of the base time is calculated for predilution HF or HDF therapy. Similarly, for predilution HF or HDF therapy, increasing the replacement fluid rate beyond 100 ml / min results in a modifier to the base time of +4 minutes or +10%, rather than the -4 minutes or -10% used for postdilution HF or HDF therapy.

[0070]

[0075] FIG. 3 is a table of device output variables, with four columns including type of device output variable, discrete modifier, percentage modifier, and correction factor. The device output variables are based on sensed readings from sensors of the extracorporeal blood treatment device sensed during the patient's treatment. Thus, the device output variables are distinct from the device setting variables, since the device output variables are dynamically detected in real time by the computing system, whereas the device setting variables are set by the user or computing system before or at the start of the treatment. The discrete modifier is the amount of time in minutes that is subtracted from or added to the base time, and the percentage modifier is the percentage of time that is subtracted from or added to the base time. The correction factor is a coefficient used in the formula to adjust the base time and determine the time interval before each second mode of operation (backflush).

[0071]

[0076] The table of FIG. 3 provides exemplary percentage subtractions and corresponding correction factors for each range of detected venous pressure and detected transmembrane pressure. The table of FIG. 3 further provides exemplary minute subtractions and percentage subtractions for the change in ultrafiltration coefficient (Δ), the change in hematocrit (Hct) concentration (Δ), the change in transmembrane pressure (Δ), and the change in clearance (K) (Δ). Delta is the sensed variable that is compared to the sensed variable obtained at or near the beginning of the procedure. If the type of device output variable includes both a discrete modifier and a percentage modifier, only one of the modifiers is applied. For example, the modifier that provides the larger of the two additions or subtractions is applied to the base time. If a discrete modifier is applied, the correction factor is ignored.

[0072]

[0077] To provide some examples of how to modify the base time to obtain the time interval before backflush using the tables of Figures 2A, 2B, and 3, the following formulas can be used: Formula I: T i =T B ·Rn Q s Q uf Q b X d P v P tm Here, T i is the time interval before backflush, and T B is the base time, and R n is the run number correction factor (cm), and Q s is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q uf is cm based on UF velocity, and Q b is blood flow in cm, and X d is cm based on the type of dialysis machine, and P v is based on venous pressure in cm, and P tm is in cm based on transmembrane pressure.

[0073]

[0078] Example 1: In this exemplary embodiment, the base time (T B ) is set to 60 minutes. The device setting variables of the extracorporeal blood treatment device can be set to include: The substitution flow rate can be set to 200 ml / min. The percent corrector for a substitution rate of 200 ml / min is -4%, so Q s The correction factor for Q is 0.96. The extracorporeal blood treatment device may be set up for a hemodiafiltration procedure in which replacement fluid is introduced into the blood line upstream of the dialyzer, i.e., predilution. For predilution, the percent corrector for the substitution flow is multiplied by -1, so that the percent corrector is equal to +4%. Q for a predilution procedure s Q used in the post-dilution procedure to determine s The intermediate variable Q is equal to the value sn (Q s normal) is used, and then the correction value Q sm (Q s Q sm To calculate Q, the formula used is sm =2-Q sn, . Thus, in this particular example using the predilution treatment method, Q s =Q sm = 2 - 0.96, which is 1.04. The ultrafiltration rate can be set to 1250 ml / hr. The percent corrector for an ultrafiltration rate of 1250 ml / min is -6%, so the correction factor Q uf is 0.94. The blood flow rate can be set to 200 ml / min. The percent corrector for a blood flow rate of 200 ml / min is -3%, so Q b When the OPTIFLUX 160NR dialyzer is used for extracorporeal blood treatment, the table shows a percent modifier of zero (0) for the OPTIFLUX 160NR dialyzer, therefore, X d is 1.

[0074]

[0079] The device output variables of the extracorporeal blood treatment device may be detected during treatment as follows: The computing system may detect that the treatment has just begun and is therefore considered a first run. The percent corrector for the first run is -40%, therefore R n is equal to 0.6. The pressure sensor can detect that the venous pressure is 250 mmHg. The percent corrector for a venous pressure sensed at 250 mmHg is -4%, so P v is 0.96. The pressure sensor is capable of detecting a transmembrane pressure of 250 mmHg. The percent corrector for a sensed transmembrane pressure of 250 mmHg is -6%, so P tm is 0.94, which is a -6% modifier.

[0075]

[0080] T B is equal to 60 minutes, R n is equal to 0.6, and Q s is equal to 1.04, and Q uf is equal to 0.94, Q b is equal to 0.97, and X d is equal to 1, and P v is equal to 0.96, Ptm With T equal to 0.94, each of the correction coefficients is inserted into Eq. 1, i.e., i =T B ·R n Q s Q uf Q b X d P v P tm and the time interval T for the first run. i This time interval is the time interval from the start of the procedure to the first backflush, i.e. the time of operation in the first operating mode before switching to the second operating mode. The formula for calculating the first time interval is therefore 60 min × (·)0.6·1.04·0.94·0.97·1.0·0.96·0.94=30.8. Therefore, the T i is equal to approximately 30.8 minutes.

[0076]

[0081] In this example, the first operating mode is initially run on the extracorporeal blood treatment device for approximately 30.8 minutes. Upon expiration of the 30.8 minute time interval, the computing system switches the extracorporeal blood treatment device from the first operating mode to the second operating mode to perform a backflush to remove secondary membrane buildup.

[0077]

[0082] Example 2: After performing the second operating mode for a certain time frame based on a second base time of, for example, 5 seconds, the computing system switches the extracorporeal blood treatment device back to the first operating mode for a modifiable base time of 60 minutes. The base time is adjusted again based on the device setting variables and the device output variables. For the second time frame operating in the first operating mode, the machine setting variables are generally the same as the above example, except for the 40% reduction based on the first run, i.e., there is no run number correction factor. For the second run, the run number correction factor for the run number modifier is 1.0, i.e., there is no change in the base time based on the number of runs. Since the second run is a subsequent run and not the first run, the base time is not reduced by 40%. Therefore, the formula for calculating the second iteration of the first operating mode is 60 minutes x (·)1.04·0.94·0.97·1.0·0.96·0.94=51.34 minutes. Thus, backflushing is again performed, executed, or conducted approximately 51.34 minutes after switching from the second mode of operation back to the first mode of operation. This second time interval may be adjusted based on application of one or more variables and / or changes and corresponding correction factors shown in the tables of FIGS. 2A, 2B, and 3.

[0078]

[0083] Example 3: The 51.34 minutes calculated above in Example 2 defines the second time interval in the first operating mode under generally standard conditions. However, if during the second time interval in the first operating mode it is determined that the ultrafiltration coefficient has decreased by more than 15% after, for example, 30 minutes after entering the first operating mode for the second time, and furthermore that the transmembrane pressure has increased by more than 5% after 15 minutes after entering the first operating mode for the second time, then two additional time interval shortenings (corrections) are made. As shown in the table of FIG. 3, each of these two device output variables specifies that either a discrete corrector of 4 minutes or a corrector of -10% should be applied.

[0079]

[0084] Regarding the decrease in the ultrafiltration coefficient, if it is detected 30 minutes after the second entry into the first operating mode, then about 21.34 minutes should have remained before the second entry into the second operating mode. A -10% reduction in the ΔUFC cm = 0.9. The discrete corrector value is compared to the % value to apply using the formula: % time value to apply = (time remaining) * (1 - correction factor). For ΔUFC, the % time value to apply is (21.34 min) * (1 - 0.9) = 2.134 min. Then, since 4 minutes is longer than 2.134 minutes, the discrete corrector is used for the detected decrease in ultrafiltration coefficient. Using the same comparison method, for the increase in transmembrane pressure 15 minutes after entering the first operating mode for the second time, the % time value to apply is calculated as (51.34 min - 15 min) * (1 - 0.9) = 3.634 minutes. Again, the 4 minute discrete corrector is used since it is larger, resulting in a total of 8 minutes being subtracted from the 51.34 minute interval. The 8 minutes result from a 4 minute reduction based on ΔUFC and a 4 minute reduction based on ΔTMP for a total of 8 minutes using the table shown in FIG. 3. As a result, the control system will cause the system to backflush after the corrected time interval of 43.34 minutes instead of 51.34 minutes. Under such circumstances, the second iteration of the first operating mode will last for 43.34 minutes. Accordingly, in circumstances where the clearance coefficient, transmembrane pressure, or a combination thereof, etc., have changed significantly during the procedure, Equation II is used to calculate the second time interval, as shown here for the case where it has been determined that only the discrete corrector is applied. Formula II: T i =(T B ·R n Q s Q uf Q b X d P v P tm )+Mod X Here, T i is the time interval before backflush, and T B is the base time, and R nis the run number correction coefficient (cm), and Q s is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q uf is cm based on UF velocity, and Q b is blood flow in cm, and X d is cm based on the type of dialysis machine, and P v is based on venous pressure in cm, and P tm is based on the transmembrane pressure difference in cm, and Mod X is the sum of the discrete modifiers to be taken into account. In the above example 3, Mod X is the sum of the discrete modifier ΔTMP(5%) and the discrete modifier ΔUFC>15%(reduction). From Figure 3, we can see that ΔTMP(5%) is equal to -4 minutes and ΔUFC>15%(reduction) is equal to -4 minutes. Therefore, Mod X is -8 minutes. Therefore, the processor would otherwise use the correction factor T B , R n , Q s , Q uf , Q b , X d , P v , and P tm Compared to calculations based only on T i Subtract 8 minutes from the Mod X Taking into account the time interval T i is 43.43 minutes instead of 51.43 minutes. Mod X can be any applicable value.

[0080]

[0085] The other correction factors shown in Figures 2A, 2B, and 3 can also be taken into account by application of Equation III shown below. Formula III: T i+1 =(T B ·R n Q s Q uf Q b X d P v P tm )+(-(T i -T Ei )·(1-XA ))+Mod X Here, T i+1 is the newly calculated time interval before backflush, and T i is the originally calculated time interval before backflush, and T B is the base time, and R n is the run number correction coefficient (cm), and Q s is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q uf is cm based on UF velocity, and Q b is blood flow in cm, and X d is cm based on the type of dialysis machine, and P v is based on venous pressure in cm, and P tm is based on the transmembrane pressure difference in cm, and T Ei is the time since the start of the current first operating mode, and Mod X is the sum of the discrete correctors to be taken into account, and X A is an additional applicable correction factor. T i+1 , T i , and T Ei The i shown in indicates the iterative nature of formula III.

[0081]

[0086] Example 4: In an example in which a clearance decrease of more than 15% was detected 10 minutes after entering the first operating mode for the second time, X A = ΔK cm = 0.9. For simplicity, R n , Q s , Q uf , Q b , X d , P tm , and P v is equal to 1, so T i =T b = 60 minutes. As in Example 3 above, a comparison is made to determine the (-(T i -T Ei )·(1-X A)) and the discrete modifier for the associated device output variable or device setting variable is determined. For a decrease in the device output variable of greater than 15% clearance, the discrete modifier is -4 minutes. The % value to apply is calculated as (-(60 minutes - 10 minutes) * (1 - 0.9) = -5 minutes. Negative five (-5) minutes has a greater absolute value than -4 minutes, therefore the % value to apply is used in place of the discrete modifier. Thus, Equation III becomes 60 minutes + (-5 minutes) = 55 minutes = T i+1 It becomes.

[0082]

[0087] To illustrate the iterative nature of Equation III, in another exemplary case, a 15% increase in hematocrit (Hct) is detected 13 minutes into the first operating mode for the second time in addition to a detection of a decrease in clearance of more than 15% 10 minutes into the first operating mode for the second time. The percentage to apply for the detected increase in hematocrit is calculated as (-(55 min-13 min)*(1-0.9))=-4.2 min, and the discrete modifier for an increase in the device output variable of Hct>15% is -4 min. Negative 4.2 (-4.2) min has a greater absolute value than -4 min, and therefore the percentage to apply is used in place of the discrete modifier. Thus, Equation III becomes 55 min+(-4.2 min)=50.8 min=T i+1 As a result, the newly calculated time interval T i+1 is shortened twice to a final value of 50.8 minutes. The second backflush therefore occurs more than 9 minutes earlier than if the applicable percentage had not been introduced.

[0083]

[0088] Formula IV shown below is, for example, Q s or P tm may be used to account for cases where a parameter such as has a change that warrants a change in the value of the applied % modifier. Formula IV: T i+1 =(T B ·R n Q s Q uf Qb X d P v P tm )+((T i -T Ei )·((2-Y Aold )*Y Anew ))-(T i -T Ei ))+(-((T i -T Ei )·(1-X A ))+Mod X Here, T i+1 is the newly calculated time interval before backflush, and T i is the originally calculated time interval before backflush, and T B is the base time, and R n is the run number correction coefficient (cm), and Q s is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q uf is cm based on UF velocity, and Q b is blood flow in cm, and X d is cm based on the type of dialysis machine, and P v is based on venous pressure in cm, and P tm is based on the transmembrane pressure difference in cm, and T Ei is the time since the start of the current first operating mode, and Mod X is the sum of the discrete correctors to be taken into account, and X A is an additional applicable correction factor, Y Aold It is observed that Q has changed s , Q uf , Q b , X d , P tm , or P v is the previously applicable correction factor for Y Anew It is observed that Q has changed s , Q uf , Q b , X d , P tm , or P v is the new applicable correction factor for T i+1, T i , and T Ei The i shown in indicates the iterative nature of formula IV.

[0084]

[0089] Example 5: After 5 minutes in the first operating mode for the second time, the blood flow rate is detected to increase from 125 ml / min to 175 ml / min. As in Example 4, for simplicity, R n , Q s , Q uf , X d , P tm , and P v Assume that Q is equal to 1. For a blood flow rate of 125 ml / min, b is also equal to 1, so T i =T b = 60 min. The % corrector provided by the blood flow device setting variable varies from 0% to -3%, so Y Aold =Q b =1 and Y Anew = 0.97. In this specification, it is called the corrected percentage value to be applied ((T i -T Ei )·((2-Y Aold )*Y Anew ))-(T i -T Ei ) is calculated as ((60 min - 5 min) · ((2 - 1) * 0.97) - (60 min - 5 min)) = -1.65 min. Therefore, equation IV is 60 min + (-1.65 min) = 58.35 min = T i+1 It becomes.

[0085]

[0090] To illustrate the iterative nature of Equation IV, suppose an increase in blood flow from 125 ml / min to 175 ml / min is detected 5 minutes after entering the first operating mode for the second time, followed by a decrease in blood flow from 175 ml / min back to 125 ml / min 10 minutes after entering the first operating mode for the second time. As a result of the second change in blood flow, the % modifier provided by the blood flow device setting variable changes from -3% to 0%, and thus Y Aold = 0.97 and Y Anew= 1. The corrected percentage to be applied is calculated as ((58.35 min - 10 min) ((2 - 0.97) * 1) - (58.35 min - 10 min)) = + 1.45 min. Therefore, Equation IV is 58.35 min + (1.45 min) = 59.8 min = T i+1 Equation IV ensures that the Q b , Q s , Q uf , X d , P tm , and P v Any variations in are accommodated.

[0086]

[0091] Figures 2A, 2B, and 3 are not intended to be limiting of the correction factors that may be considered or used for a particular device or method, but are illustrative of a number of correction factors that may be applied. The values ​​of the discrete and % correctors are not limiting.

[0087]

[0092] A correction to the starting TMP value can be made for use when an increase in TMP is detected to account for adjustments to the dialysate flow rate, substitution fluid flow rate, and blood flow rate and their effects on the transmembrane pressure. For example, if the TMP is detected to have increased by 2% and then the blood flow rate, dialysate flow rate, or substitution fluid flow rate is changed, the result is an associated change to TMP. The newly stabilized TMP value is then (Q s , Qd, or Q b3. Based on the 2% increase in TMP detected previously, a revised baseline TMP value is generated such that revised baseline TMP*(1.02)=(stabilized baseline TMP). The revised baseline TMP value is then used as the basis for detecting a ΔTMP that truly warrants a modification of the pre-backflush time interval. In this way, the detection of an increase in TMP that is the basis for adjusting the calculated pre-backflush time interval shown in the bottom row of FIG. 3 is not falsely triggered by an adjustment in the dialysate flow rate, substitution flow rate, or blood flow rate. A change in the pre-backflush time interval will not be made unless a 5%, 10%, or 15% increase in the revised baseline TMP is detected, and the change will be implemented via application of a discrete modifier or a % value to apply according to Equation III. Any additional necessary modifications to the calculated pre-backflush time interval that result from changes in the values ​​of the device setting variables dialysate flow rate, replacement flow rate, blood flow rate, or changes in the value of the device output variable transmembrane pressure difference will be addressed by revised % values ​​to be applied in Equation IV, as necessary.

[0088]

[0093] 4A and 4B are respectively the left and right parts of a schematic diagram of a dialysate circuit 400 of another embodiment of an extracorporeal blood treatment device. Line terminals A, B, C, and D shown in FIG. 4A are continued and are in fluid communication with line terminals A, B, C, and D shown in FIG. 4B, respectively. The extracorporeal blood treatment device includes a dialyzer 401 with a blood chamber 402 and a dialysate chamber 403 separated by a semipermeable membrane 404. The dialysate circuit 400 includes a water source 413 for making fresh dialysate. The water source 413 is connected via a first portion 416A of a supply line 416, where the water is mixed with bicarbonate provided by a bicarbonate pump 450 and mixed with electrolytes provided by a concentrate pump 460 to form the dialysate. The dialysate then travels through a second portion 416B of the supply line 416, from where it travels into the fresh dialysate side 406A of the first balancing chamber 406 and into the fresh dialysate side 408A of the second balancing chamber 408. The fresh dialysate that leaves the fresh dialysate sides 406A and 408A then travels through a third portion 416C of the supply line 416 and enters the dialysate inlet 440 of the dialysate chamber 403. The fresh dialysate may be used as a flushing fluid or a preparation fluid. The pressure of the dialysate in the supply line 416 may be sensed by a pressure transducer 433 located along the third portion 416C of the supply line 416 just before it enters the dialysate chamber 403.

[0089]

[0094] A dialysate outlet 444 of the dialysate chamber 403 is connected to a dialysate removal line 418. Spent dialysate, ultrafiltrate, a combination thereof, or fresh dialysate during priming exits the dialysate outlet 444 and travels through the dialysate removal line 418. The pressure in the dialysate removal line 418 can be sensed by a pressure transducer 432 disposed along the dialysate removal line 418.

[0090]

[0095] By operation of the ultrafiltrate pump 423 and the flow pump 417, dialysate removed from the dialysate chamber 403 may be moved to a drain 480 or into the spent dialysate side 406B and spent dialysate side 408B of the balancing chambers 406 and 408, respectively. A pressure sensor 419 is provided downstream of the flow pump 417 and configured to sense the pressure in the lines downstream of the pump 417. The ultrafiltrate pump 423 may be part of an ultrafiltration system 422. During priming, dialysate removed along the dialysate removal line 418 may be moved at least in part along the dialysate recirculation line 415 by the degassing pump 425. A dialysate outlet valve 420 is located along the dialysate removal line 418 downstream of the dialysate chamber 403 and the outlet 444. The dialysate outlet valve 420 remains open during a first mode of operation described herein and is closed for a duration during a second mode of operation described herein.

[0091]

[0096] 5A and 5B show a flow chart of a method of treating a patient using the extracorporeal blood treatment device of FIG. 1 or FIG. 4A and FIG. 4B. The extracorporeal blood treatment device starts the treatment in a first operating mode. The computing system then launches a secondary membrane mediation algorithm, which constitutes entering a second operating mode, in step 300. If the treatment is hemodiafiltration or hemofiltration, the substitution fluid pump is stopped in step 320. If it is a hemodialysis treatment instead, this step is skipped. In step 330, the ultrafiltration pump is stopped. In step 340, the transmembrane pressure limit and the venous pressure limit can be widened. During a typical treatment using the extracorporeal blood treatment device, the transmembrane pressure and the venous pressure are monitored to detect malfunctions. In anticipation of the dialysate outlet valve being closed for a certain duration, the TMP limit is temporarily widened to the machine hard limit to prevent the detection of malfunctions. If applicable, a step involving adapting the dialysate flow rate and the blood flow rate can be provided, as shown in step 345. As a result of the shutting off of the ultrafiltration pump in step 330 and the optional adaptation of the dialysate flow rate and blood flow rate in step 345, the venous pressure limit is temporarily extended to the machine hard limit in step 340 to prevent detection of a malfunction.

[0092]

[0097] When the balancing chamber is part of the device, monitoring for the start of a new balancing chamber cycle occurs in step 350. The balancing chamber cycles through two states, in a first state the new side of the balancing chamber is filled and the used side of the balancing chamber is emptied, and in a second state the used side of the balancing chamber is filled and the new side of the balancing chamber is emptied.

[0093]

[0098] If a balancing chamber is present but a balancing chamber cycle is not initiated, the process may be prevented from moving to the next step until a balancing chamber cycle is initiated. If a balancing chamber is not present, step 350 is skipped. Induction of volume introduction is then accomplished in step 360 by closing the dialysate outlet valve and disabling checks for flow error and the need for a pressure hold test (PHT).

[0094]

[0099] Closing the dialysate outlet valve will occur for the first part of the balancing chamber cycle if a balancing chamber is present, and then the dialysate outlet valve will reopen to allow the balancing chamber cycle to complete. Alternatively, closing the dialysate outlet valve will occur for the duration of step 360 if a balancing chamber is not present. A check is then made in step 370 to determine whether the balancing cycle is complete. The process should not move to the next step unless the balancing cycle is complete and ready to move from the first state to the second state or from the second state to the first state. One exception is the unexpected event that the venous pressure exceeds the machine hard limit during the second operating mode as a result of the dialysate outlet valve remaining closed, in which case the dialyzer is immediately isolated by closing the dialysate inlet valve to ensure patient safety. Once the balancing cycle is complete, the process induces recovery in step 380 by restoring the ultrafiltration rate, restoring the dialysate flow rate, blood flow rate, and substitution flow rate if applicable, and restoring the flow error / PHT check after two balancing chamber cycles. Completion of step 380 constitutes the completion of the second mode of operation and re-entering the first mode of operation.

[0095]

[0100] Upon re-entering the first mode of operation, the transmembrane pressure limit and the venous pressure limit are restored and the fluid volume introduced into the patient as a result of the backflush is recovered by increasing ultrafiltration for approximately 5-10 minutes, step 390. The ultrafiltration coefficient is then recalculated, step 400, by triggering the UF / PHT, if an ultrafiltration calculation is available.

[0096]

[0101] Entry into the second mode of operation from the first mode of operation should be assumed to occur when the system is in an alarm-free state and only if the dialysate conductivity, dialysate temperature, arterial pressure, venous pressure, and transmembrane pressure differential are within their respective tolerances prior to entry. When the arterial pressure, venous pressure, and / or transmembrane pressure differential values ​​are near their respective upper or lower alarm limits, the blood flow rate, dialysate flow rate, or a combination thereof, may be adjusted during the second mode of operation to minimize changes in the arterial pressure, venous pressure, and / or transmembrane pressure differential.

[0097]

[0102] Additionally, if the machine is priming and enters the second mode of operation when no patient is connected, it should be assumed that the base volume delivered into the blood chamber of the dialyzer during the second mode of operation may be delivered at the upper range of durations described herein. The time interval before backflush during priming is not based on Equations I-IV, and entering the secondary mode of operation during priming may occur at the beginning of priming, at the end of priming, at some point during priming, or during a combination thereof.

[0098]

[0103] The present invention may include any combination of these various features or embodiments, as described above and / or below, as set out in the text and / or paragraphs. Any combination of the features disclosed herein is considered part of the present invention, and no limitations are intended as to which features may be combined.

[0099]

[0104] Applicant specifically incorporates the entire contents of all cited documents into this disclosure.Furthermore, when an amount, concentration, or other value or parameter is given as either a range, a preferred range, or a list of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed from any pair of upper range or preferred value and any lower range or preferred value, regardless of whether the ranges are separately disclosed.When a range of numerical values ​​is described herein, unless otherwise stated, the range is intended to include its endpoints, as well as all integers and fractions within the range.The scope of the present invention is not intended to be limited to the specific values ​​described when defining a range.

[0100]

[0105] Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims and equivalents thereof.

Claims

1. 1. An extracorporeal blood treatment device comprising: a dialyzer comprising a blood chamber, a dialysate chamber, a dialysate inlet, a dialysate outlet, and a semipermeable membrane, wherein the blood chamber and the dialysate chamber are separated from each other by the semipermeable membrane; a dialyzer inlet line communicating with the dialysate inlet and configured to supply dialysate to the dialysate chamber; a dialyzer drain line configured to carry dialysate away from the dialysate outlet and out of the dialysate chamber; a dialysate pump configured to pump dialysate through the dialyzer inlet line to the dialysate chamber and out of the dialysate chamber through the dialyzer outlet line; A dialysate outlet valve; a blood pump configured to pump blood through the dialyzer and into the blood chamber; a balancing device comprising a balancing chamber, a balancing inlet line communicating with the balancing chamber and configured to supply dialysate from a dialysate source into the balancing chamber, and a balancing outlet line leading away from the balancing chamber and configured to carry dialysate from the balancing chamber to a drain; Equipped with the dialyzer inlet line extends from the balancing chamber and is configured to supply dialysate from the balancing chamber to the dialysate chamber; the dialyzer outlet line leads to the balancing chamber and is configured to supply dialysate from the dialysate chamber into the balancing chamber; the dialysate pump, the blood pump, or both, are configured to operate in a first mode of operation of the extracorporeal blood treatment device and in a second mode of operation of the extracorporeal blood treatment device; the first mode of operation is operated in a configuration in which the dialysate outlet valve is open to allow dialysate to flow through the dialyzer inlet line, through the dialysate chamber, and into the dialyzer outlet line; the second mode of operation is in a configuration in which the dialysate outlet valve is closed for a duration, preventing dialysate from flowing through the dialyzer drain line, and allowing a volume of dialysate to pass from the dialysate chamber through the semipermeable membrane and into the blood chamber. Extracorporeal blood treatment devices.

2. 2. The extracorporeal blood treatment device of claim 1, wherein the dialysate pump and the blood pump are configured to operate at a first operating speed and a second operating speed, and wherein the dialysate pump and the blood pump are configured to operate at their respective first operating speeds during the first operating mode and at their respective second operating speeds during the second operating mode.

3. 2. The extracorporeal blood treatment device of claim 1, further comprising an ultrafiltrate pump configured to be switched between an operating state and a non-operating state, wherein in the operating state, the ultrafiltrate pump draws liquid from the blood chamber through the semi-permeable membrane and into the dialysate chamber and withdraws liquid from the dialysate chamber, and wherein the ultrafiltrate pump is switched to the non-operating state in the second mode of operation.

4. 10. The extracorporeal blood treatment device of claim 1, further comprising a processor and a sensor in communication with the processor and configured to generate sensor data, the processor configured to process the sensor data and switch the extracorporeal blood treatment device from the first operating mode to the second operating mode for a time frame based on the processed sensor data.

5. 5. The extracorporeal blood treatment device of claim 4, wherein the processor is configured to perform an initial first operating mode phase over a primary operating time frame, the initial first operating mode phase beginning at the start of treatment, and the processor is configured to switch the extracorporeal blood treatment device from a first operating mode to the second operating mode upon expiration of the operating time frame.

6. 5. The extracorporeal blood treatment device of claim 4, wherein the processor is configured to perform an initial first operational mode phase over a primary operational time frame, the initial first operational mode phase beginning at the start of priming, and the processor is configured to switch the extracorporeal blood treatment device from a first operational mode to the second operational mode upon expiration of the operational time frame.

7. 6. The extracorporeal blood treatment device of claim 5, wherein the processor is configured to alternate the extracorporeal blood treatment device between the first and second operating modes in a sequence of a plurality of operating modes at a frequency during treatment, each of the plurality of operating modes having a respective operating time frame.

8. 8. The extracorporeal blood treatment device of claim 7, wherein the processor is configured to modify at least one of the frequencies and each of the respective operating time frames based on at least one device setting variable, at least one device output variable, or both, the at least one device output variable being determined by the sensor data.

9. 9. The extracorporeal blood treatment device of claim 8, wherein the at least one device setting variable comprises at least one of a type of treatment, a substitution fluid flow rate, an ultrafiltration flow rate, a blood flow rate, a dialyzer type, a substitution fluid bolus amount, or a combination thereof.

10. 9. The extracorporeal blood treatment device of claim 8, wherein the at least one device output variable comprises at least one of urea clearance, ultrafiltration coefficient, venous pressure, transmembrane pressure, run rate, hematocrit, or a combination thereof.

11. the processor is programmed to switch from the first mode of operation to a second mode of operation upon expiration of a time interval calculated according to Formula I; Formula I: T ｉ = T Ｂ · R ｎ · Q ｓ · Q ｕｆ · Q ｂ · X ｄ · P ｖ · P ｔｍ Here, T ｉ is the time interval before backflush, T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ The extracorporeal blood treatment device of claim 5 , wherein m is based on transmembrane pressure in cm.

12. 6. The extracorporeal blood treatment device of claim 5, further comprising an extracorporeal blood circuit in fluid communication with the blood chamber, the extracorporeal blood circuit comprising a blood pump, the blood pump being controlled by the processor, the processor configured to reduce a pump speed during the second mode of operation compared to during the first mode of operation.

13. The extracorporeal blood treatment device of claim 1, wherein the amount of dialysate is 3 ml to 20 ml.

14. 1. An extracorporeal blood treatment device comprising: a dialyzer comprising a blood chamber, a dialysate chamber, a dialysate inlet, a dialysate outlet, and a semipermeable membrane, wherein the blood chamber and the dialysate chamber are separated from each other by the semipermeable membrane; a dialyzer inlet line communicating with the dialysate inlet and configured to supply dialysate to the dialysate chamber; a dialyzer drain line configured to carry dialysate away from the dialysate outlet and out of the dialysate chamber; a dialysate pump configured to pump dialysate through the dialyzer inlet line to the dialysate chamber and out of the dialysate chamber through the dialyzer outlet line; A dialysate outlet valve; Equipped with the dialysate pump is configured to operate in a first mode of operation of the extracorporeal blood treatment device and in a second mode of operation of the extracorporeal blood treatment device; the first mode of operation is operated in a configuration in which the dialysate outlet valve is open to allow dialysate to flow through the dialyzer inlet line, through the dialysate chamber, and into the dialyzer outlet line; the second mode of operation is configured such that the dialysate outlet valve is closed for a duration to prevent dialysate from flowing through the dialyzer drain line and a volume of dialysate passes from the dialysate chamber through the semipermeable membrane and into the blood chamber; the second mode of operation is performed continuously for a time frame of 30 seconds or less; The amount of dialysate passing from the dialysate chamber through the semipermeable membrane to the blood chamber during said time frame is between 3 ml and 20 ml.

15. 15. The extracorporeal blood treatment device of claim 14, wherein the dialysate pump and blood pump are configured to operate at a first operating speed and a second operating speed, and wherein the dialysate pump and blood pump are configured to operate at the first operating speed during the first operating mode and at the second operating speed during the second operating mode.

16. 15. The extracorporeal blood treatment device of claim 14, further comprising an ultrafiltrate pump configured to be switched between an operating state and a non-operating state, wherein in the operating state, the ultrafiltrate pump draws liquid from the blood chamber through the semi-permeable membrane and into the dialysate chamber and withdraws liquid from the dialysate chamber, and wherein the ultrafiltrate pump is switched to the non-operating state in the second mode of operation.

17. 17. The extracorporeal blood treatment device of claim 16, wherein the ultrafiltration pump is configured to operate at a faster speed during at least a time frame of the first mode of operation to remove an amount of liquid from the blood chamber equivalent to an amount of dialysate.

18. 15. The extracorporeal blood treatment device of claim 14, further comprising a processor and a sensor in communication with the processor and configured to generate sensor data, the processor configured to process the sensor data and switch the extracorporeal blood treatment device from the first operating mode to the second operating mode for a time frame based on the processed sensor data.

19. 20. The extracorporeal blood treatment device of claim 18, wherein the processor is configured to alternate the extracorporeal blood treatment device between the first and second operating modes in a sequence of a plurality of operating modes at a frequency during treatment, each of the plurality of operating modes having a respective operating time frame.

20. 20. The extracorporeal blood treatment device of claim 19, wherein the processor is configured to modify at least one of the frequencies and each of the respective operating time frames based on at least one device setting variable, at least one device output variable, or both, the at least one device output variable being determined by the sensor data.

21. 21. The extracorporeal blood treatment device of claim 20, wherein the at least one device setting variable comprises at least one of a type of treatment, a substitution fluid flow rate, an ultrafiltration flow rate, a blood flow rate, a dialyzer type, a substitution fluid bolus amount, or a combination thereof.

22. 21. The extracorporeal blood treatment device of claim 20, wherein the at least one device output variable comprises at least one of urea clearance, ultrafiltration coefficient, venous pressure, transmembrane pressure, running rate, hematocrit, or a combination thereof.

23. 15. The extracorporeal blood treatment device of claim 14, further comprising an extracorporeal blood circuit in fluid communication with the blood chamber, the blood chamber further comprising a blood chamber inlet and a blood chamber outlet, the extracorporeal blood circuit comprising a blood pump, a blood supply line leading to the blood chamber inlet, and a blood removal line leading away from the blood chamber outlet, the blood pump configured to pump blood through the blood supply line and the blood chamber inlet into the blood chamber and out of the blood chamber through the blood chamber outlet and the blood removal line.

24. 20. The extracorporeal blood treatment device of claim 18, further comprising an extracorporeal blood circuit in fluid communication with the blood chamber, the extracorporeal blood circuit comprising a blood pump, the blood pump being controlled by the processor, the processor configured to reduce a pump speed during the second mode of operation compared to during the first mode of operation.

25. the processor is programmed to switch from the first mode of operation to a second mode of operation upon expiration of a time interval calculated according to Formula I; Formula I: T ｉ = T Ｂ ·R ｎ ·Q ｓ ·Q ｕｆ ·Q ｂ ·X ｄ ·P ｖ ·P ｔｍ Here, T ｉ is the time interval before backflush, T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ 20. The extracorporeal blood treatment device of claim 18, wherein: m is based on transmembrane pressure in cm.

26. A method of operating an extracorporeal blood treatment device, comprising: The extracorporeal blood treatment device comprises a dialyzer having a blood chamber, a dialysate chamber, and a semipermeable membrane, wherein the blood chamber and the dialysate chamber are separated from one another by the semipermeable membrane, and the dialysate chamber comprises a dialysate outlet valve; activating the extracorporeal blood treatment device to treat the blood in a first mode of operation by a dialysate pump operative to pump dialysate through the dialysate chamber, a blood pump operative to pump blood through the blood chamber, and an ultrafiltrate pump operative to draw ultrafiltrate from the dialysate chamber; while the extracorporeal blood treatment device is operative to treat the blood in the first mode of operation, the extracorporeal blood treatment device is operative to detect a factor that accelerates accumulation of a secondary film on the semipermeable membrane; activating the extracorporeal blood treatment device to switch from the first mode of operation to a second mode of operation, wherein the second mode of operation comprises closing the dialysate outlet valve for a duration and turning off the ultrafiltrate pump, wherein the closing of the dialysate outlet valve prevents dialysate from flowing out of the dialysate chamber and a volume of dialysate passes from the dialysate chamber through the semipermeable membrane to the blood chamber. A method of operating an extracorporeal blood treatment device comprising:

27. ​​The method of operating the extracorporeal blood treatment device as described in claim 26, wherein operating to detect a factor that accelerates accumulation of secondary membrane on the semipermeable membrane comprises detecting an increase in transmembrane pressure difference that exceeds a predetermined percentage value.

28. The method of operating the extracorporeal blood treatment device described in claim 26, wherein operating to detect factors that accelerate accumulation of secondary membrane on the semipermeable membrane comprises detecting a decrease in ultrafiltration coefficient that exceeds a predetermined percentage value.

29. The method of operating the extracorporeal blood treatment device as described in claim 27, wherein operating to detect an increase in transmembrane pressure differential comprises determining a difference in pressure detected by at least two different pressure sensors.

30. The extracorporeal blood treatment device operating to switch from the first operating mode to the second operating mode upon detecting the accumulation comprises switching upon expiration of a pre-backflush time interval calculated according to Equation I; Formula I: T ｉ = T Ｂ · R ｎ · Q ｓ · Q ｕｆ · Q ｂ · X ｄ · P ｖ · P ｔｍ Here, T ｉ is the time interval before backflush, T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ 27. The method of claim 26, wherein is based on transmembrane pressure in cm.

31. The extracorporeal blood treatment device operating to switch from the first operating mode to the second operating mode upon detecting the accumulation comprises switching upon expiration of a pre-backflush time interval calculated according to Equation II: Formula II: T ｉ = (T Ｂ · R ｎ · Q ｓ · Q ｕｆ · Q ｂ · X ｄ · P ｖ · P ｔｍ ) + Mod Ｘ Here, T ｉ is the time interval before backflush, T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ is based on the transmembrane pressure difference in cm, and Mod Ｘ 27. A method according to claim 26, in which x is a sum of discrete correctors to be taken into account.

32. The extracorporeal blood treatment device operable to switch from the first operating mode to the second operating mode upon detecting the accumulation comprises switching upon expiration of a pre-backflush time interval calculated according to Equation III: Formula III: T ｉ＋１ = (T Ｂ · R ｎ · Q ｓ · Q ｕｆ · Q ｂ · X ｄ · P ｖ · P ｔｍ )) + (-( (T ｉ - T Ｅｉ )(1 - X Ａ )))) + Mod Ｘ Here, T ｉ＋１ is the time interval before backflush, T ｉ is the originally calculated time interval before backflush, and T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ is based on the transmembrane pressure difference in cm, and T Ｅｉ is the elapsed time from the start of the current first operating mode, and Mod Ｘ is the sum of the discrete correctors to be taken into account, and X ｐｒｏｄｕｃｔ 27. A method according to claim 26, wherein: x is a product of one or more other applicable correction factors.

33. The extracorporeal blood treatment device operating to switch from the first operating mode to the second operating mode upon detecting the accumulation comprises switching upon expiration of a pre-backflush time interval calculated according to Equation IV; Formula IV: T ｉ＋１ = (T Ｂ · R ｎ · Q ｓ · Q ｕｆ · Q ｂ · X ｄ · P ｖ · P ｔｍ )) + ((T ｉ - T Ｅｉ )· ((2 - Y Ａｏｌｄ ) * Y Ａｎｅｗ )) - (T ｉ - T Ｅｉ )) + ( - ((T ｉ - T Ｅｉ )· (1 - X Ａ )) + Mod Ｘ Here, T ｉ＋１ is the newly calculated time interval before backflush, and T ｉ is the originally calculated time interval before backflush, and T Ｂ is the base time, and R ｎ is the run number correction coefficient (cm), and Q ｓ is cm based on the replacement fluid rate and whether replacement fluid is introduced into the blood before or after the dialyzer, and Q ｕｆ is cm based on UF speed, and Q ｂ is blood flow in cm, and X ｄ is cm based on the type of dialysis machine, and P ｖ is based on venous pressure in cm, P ｔｍ is based on the transmembrane pressure difference in cm, and T Ｅｉ is the elapsed time from the start of the current first operating mode, and Mod Ｘ is the sum of the discrete correctors to be taken into account, and X Ａ is an additional applicable correction factor, Y Ａｏｌｄ The previously applicable correction coefficient R ｎ , Q ｓ , Q ｕｆ , Q ｂ , X ｄ , P ｔｍ , and P ｖ And Y Ａｎｅｗ 27. The method of claim 26, wherein: is a newly applicable correction factor.

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