Open or closed loop control device for a blood treatment machine for controlling clearance during dialysis - Patent Application 20070122999

Abstract

The present invention relates to an open-loop or closed-loop control device (150) configured to control an extracorporeal blood treatment device (100) in an open-loop or closed-loop manner when the open-loop or closed-loop control device (150) is in signal communication with the extracorporeal blood treatment device (100). The blood treatment device (100) has a dialyzer (303) subdivided by a semipermeable membrane (303c) into a blood chamber (303b) and a dialysate chamber (303a) for extracorporeal treatment of a patient's blood in a blood treatment session. The open-loop or closed-loop control device (150) controls the dialysate flow rate (Q) for extracorporeal blood treatment by the extracorporeal blood treatment device. d,1 , Q d,2 ) for the dialyzer (303) of the blood treatment device (100), and the open-loop or closed-loop control device (150) is further configured to determine the dialysate flow rate (Q d,1 , Q d,2 ) over multiple consecutive time intervals (T1, T2, ..., T N , N∈NN), the first dialysate flow rate (Q d,1 ) and the second dialysate flow rate (Q d,2 ) are determined alternately in each case, and the first dialysate flow rate (Q d,1 ) is the second dialysate flow rate (Q d,2 ) more than

Description

[Technical Field]

[0001] The present invention relates to a control device or a closed-loop control device for controlling or controlling in a closed-loop manner a blood treatment apparatus according to claim 1, and to a blood treatment apparatus according to claim 9, as well as to a digital storage medium according to claim 11, a computer program product according to claim 12, and a computer program according to claim 13 or in the preamble or general terms of each of these claims. [Background technology]

[0002] In hemodialysis performed by a blood treatment device, the efficiency of blood purification by a hemofilter, i.e., a dialyzer, can be indicated by the degree of clearance, which is mainly set by the properties of the hemofilter membrane, the parameters of the hemofilter, and the blood flow rate in the blood chamber and the dialysate flow rate in the dialysate chamber of the hemofilter.

[0003] The blood purification benefiting the patient is reduced at the patient side by recirculation, which refers to the portion of blood already purified in the hemofilter being returned to the patient's vascular system via the venous line and then entering the arterial line without being equilibrated with the total body reservoir. The reasons for this can include cardiopulmonary recirculation or direct recirculation in a vascular access or central venous catheter.

[0004] When referring to a "patient" herein, this refers to a person in need of blood treatment. This designation does not imply any information regarding the gender or other characteristics of this person.

[0005] In hemodialysis (HD), the exchange or removal of uremic toxins occurs primarily by diffusion. This is set by the concentration gradient and clearance between the blood and the dialysis fluid. This mechanism is particularly effective for small molecules such as urea. Because the rate of diffusion decreases with increasing molecular size, diffusion is less effective for larger molecules. In this case, convective removal by ultrafiltration is more effective. This method is used in hemofiltration (HF).

[0006] Hemodialysis and hemofiltration can be combined for hemodiafiltration (HDF). By selecting the operating parameters in HDF, the substance-specific rates of diffusion and convection can be adjusted within certain limits.

[0007] The total dialysis dose achieved in a dialysis treatment is described by the parameter Kt / V, where K is the urea clearance in the hemofilter (units: ml / min), t is the treatment time (units: min), and V is the urea distribution volume or the patient's body fluid (units: ml). All statements made herein about urea also apply to other uremic toxins according to the invention.

[0008] Generally, it is advantageous to select dialysis parameters to achieve as high a dialysis dose as possible. However, undesirable side effects may occur due to the exchange of substances within the hemofilter.

[0009] This includes, among others, dialysis imbalance syndrome, which occurs when removal of primarily small uremic toxins, which can be present in relatively high concentrations (approximately 1-100 mmol / L), occurs too rapidly. One mechanism of harm here is that toxin concentrations in different body compartments have exchanged with each other and become equal during the predialysis period. Because dialysis removal occurs directly from only one compartment (the extracellular compartment), the resulting concentration differences with other compartments, particularly the intracellular compartment and the brain, cause osmotically induced volume shifts, which can lead to neurological symptoms. Urea concentration is particularly responsible for this.

[0010] This primarily affects patients newly treated with long-term hemodialysis or patients undergoing dialysis after a long period without dialysis, for example after a missed dialysis session.

[0011] However, comparable effects are also observed in acute dialysis after acute renal failure or in the treatment of intoxication associated with the removal of alcohol, for example after alcoholism. Summary of the Invention

[0012] An object of the present invention may be to provide a further control device or a closed-loop control device for controlling or controlling in a closed-loop manner a blood treatment apparatus, and a further blood treatment apparatus.

[0013] The object according to the invention is achieved by a control device or a closed-loop control device for controlling or controlling in closed-loop manner a blood treatment apparatus having the features of claim 1, and by a blood treatment apparatus having the features of claim 9. It is further solved by a digital storage medium having the features of claim 11, a computer program product having the features of claim 12 and a computer program having the features of claim 13.

[0014] The control device or closed-loop control device according to the present invention is configured to control or control in a closed-loop manner an extracorporeal blood treatment device when connected in signal communication with the extracorporeal blood treatment device. The blood treatment device serves to treat a patient's blood extracorporeally in a blood treatment session, and for this purpose comprises or is connected to a blood filter (also referred to herein as a dialyzer) that is divided into a blood chamber and a dialysate chamber by a semipermeable membrane. During blood treatment, blood flows through the blood chamber at a predetermined blood flow rate, and during treatment, (fresh) dialysis liquid flows into the dialysis liquid chamber at a predetermined dialysate flow rate, and (used) dialysate flows out of the dialysis liquid chamber. This flow rate through the dialysis liquid chamber is referred to herein as the dialysate flow rate. Here, the dialysate flow rate may refer to the fluid flow rate into and / or out of the dialysis liquid chamber.

[0015] A control device or closed-loop control device according to the present invention is further configured to set or specify a dialysate flow rate for an extracorporeal blood treatment produced by or using an extracorporeal blood treatment apparatus, such that the dialysate flow rates through a dialyzer of the blood treatment apparatus are set or specified such that a first dialysate flow rate and a second dialysate flow rate alternate with each other over a plurality of consecutive time intervals (e.g., the same or different, variable or fixed time intervals) within the blood treatment session under consideration, where the first dialysate flow rate is greater than, or alternatively less than, the second dialysate flow rate.

[0016] The control device or closed-loop control device may be programmed as described above. Alternatively, the calculation unit and / or evaluation unit may be configured as described, i.e., in particular to set or specify the dialysate flow rate. The calculation unit and / or evaluation unit may be part of the control device or closed-loop control device or may be separate therefrom. In the latter case, the control device or closed-loop control device may be in signal communication with the calculation unit and / or evaluation unit or may be arranged to be in signal communication with the calculation unit and / or evaluation unit.

[0017] The blood treatment apparatus according to the present invention is configured to comprise, be connected to or be in signal communication with the control device or closed-loop control device according to the present invention.

[0018] The digital storage medium, in particular a non-volatile storage medium according to the invention, in particular in the form of a machine-readable carrier, in particular in the form of a diskette, CD, DVD, EPROM, FRAM® (Ferroelectric RAM) or SSD (Solid State Drive), carrying in particular electronically or optically readable control signals, can interact with a computer system so that a conventional control device or closed-loop control device of a blood treatment machine can be reprogrammed into a control device or closed-loop control device according to the invention.

[0019] The computer program product according to the present invention comprises a volatile or transitory program code or a program code stored on a machine-readable carrier or signal wave, which, when executed on a computer, causes a conventional control device or a closed-loop control device of a blood treatment apparatus to be reprogrammed into a control device or a closed-loop control device according to the present invention. A computer program product can be understood, for example, according to the present invention as a computer program stored on a carrier, an embedded system which is a comprehensive system comprising a computer program (e.g., an electronic device comprising a computer program), a network of computer-implemented computer programs (e.g., a client / server system, a cloud computing system, etc.), or a computer onto which a computer program is loaded, operated, stored, executed, or developed.

[0020] The term "machine-readable carrier" as used herein refers, in certain embodiments of the invention, to a carrier containing data or information that can be interpreted by software and / or hardware. The carrier may for example be a data carrier such as a diskette, CD, DVD, USB stick, flash card or SD card, as well as any other storage mentioned herein or any other storage medium mentioned herein.

[0021] The computer program according to the present invention comprises program code by which a conventional control device or closed-loop control device of a blood treatment apparatus is reprogrammed into a control device or closed-loop control device according to the present invention.

[0022] Embodiments according to the present invention may comprise one, some or all of the features described below in any combination, unless a person skilled in the art considers a particular combination to be technically impossible.

[0023] In all of the above and below, the use of expressions such as "may be" or "may have" should be understood as synonymous with "preferably is" or "preferably has", respectively, and is intended to exemplify embodiments according to the present invention.

[0024] Whenever numerical terms are used herein, those skilled in the art should recognize or understand them as indicating a lower limit of the numerical value. Therefore, unless this leads to a contradiction obvious to those skilled in the art, those skilled in the art should understand, for example, "one" (or "a / an") as including "at least one." This understanding is also equally encompassed by the present invention as the interpretation that a numerical term, for example, "one" (or "a"), may alternatively mean "exactly one," whenever this is clearly technically possible as seen by those skilled in the art. Both of these understandings are encompassed by the present invention and apply to all numerical terms used herein.

[0025] Those skilled in the art should understand spatial information such as "top," "bottom," "left," or "right," whenever described herein, as spatial designations with reference to alignment and / or in use in the figures attached hereto, with "bottom" being closer to the center of the Earth or the bottom edge of the figure than "top."

[0026] Advantageous developments of the invention are the subject matter of the dependent claims and embodiments.

[0027] Whenever embodiments are described herein, they represent exemplary embodiments according to the present invention and should not be construed as limiting.

[0028] When the subject matter of the present invention is disclosed herein as comprising one or several features in a particular embodiment, it is also disclosed herein that the subject matter of the present invention does not explicitly comprise one or several of the features in other embodiments of the present invention, e.g., by way of a disclaimer. Therefore, for every embodiment described herein, it is also applicable that the opposite embodiment, e.g., formulated as a negation, is also disclosed.

[0029] When method steps are described herein, a control device or closed-loop control device according to the present invention is in some embodiments configured to perform one, some or all of these in any combination, particularly when these method steps are automatically executable steps, or preferably to correspond by name to the designation of the respective method step (e.g., "determining" as a method step and "apparatus / determining device" in the case of an apparatus / device) and to control accordingly corresponding apparatus / devices which may also be part of the apparatus(es) according to the present invention or which may be connected thereto in signal communication.

[0030] When described herein as programmed or configured, these terms may be interchangeable in some embodiments.

[0031] When signal communication or a communication connection between two components is described herein, this may be understood to mean the connection that exists during use. It may also be understood that provisions for such signal communication (whether wired, wireless, or otherwise implemented) exist, for example, by coupling both components, for example, by pairing, etc.

[0032] Pairing is a process performed in connection with a computer network to establish an initial link between computer units for the purpose of communication. The best-known example of this is the establishment of a Bluetooth® connection, by which various devices (e.g., smartphones, headphones) connect to each other. Pairing is sometimes also called bonding.

[0033] A control device or closed-loop control device may facilitate the execution of all or substantially all of the method steps disclosed herein. The methods disclosed herein may be substantially or entirely performed by a control device or closed-loop control device. It may be performed in part by a control device or closed-loop control device, and in particular, steps that do not require or are not associated with human intervention and / or initialization may be performed by a control device or closed-loop control device. A control device may be used solely as a control device or as a closed-loop control device as well.

[0034] In some embodiments, the control device or closed-loop control device is on or in the blood treatment apparatus, for example, with other components or devices of the blood treatment apparatus within a common housing of the blood treatment apparatus.

[0035] In some embodiments, the control device or closed-loop control device includes, is in signal communication with, or is arranged for signal communication with a measuring device for measuring at least one characteristic value of clearance. In these embodiments, the control device or closed-loop control device is configured to determine a level or value of the first dialysate flow rate and / or the second dialysate flow rate based on the at least one characteristic value of clearance. Alternatively, it is configured to determine a target value of the first dialysate flow rate and / or the second dialysate flow rate based on the at least one characteristic value.

[0036] In some embodiments, the control device or the closed-loop control device comprises an estimation device for estimating the clearance instead of a measurement device. This can be easily done, for example, if the dialyzer parameter K0A and the set or measured flow rate are known. This is economically important, especially for "low-cost devices" or emergency devices that do not perform clearance measurements.

[0037] In some embodiments, a communication device is provided that allows a user to make inputs for determining the clearance. Such inputs may be or may include a preset mean or target clearance K_target (related to the entire treatment session or to individual time intervals) that is intended to be achieved by the treatment session, parameters of the hemofilter, their effective values, the patient's shunt flow rate, its cardiac output, recirculation rates known from previous treatments, and results of clearance determinations from previous treatments of the currently treated patient or other patients.

[0038] In some embodiments, the control device or closed-loop control device is configured to set or specify, for a considered time interval of the plurality of time intervals, a first time fraction during which dialysis fluid is delivered through the dialysis fluid chamber at a first dialysate flow rate within the considered time interval, and additionally or alternatively, a second time fraction during which dialysis fluid is delivered through the dialysis fluid chamber at a second dialysate flow rate within the considered time interval.

[0039] In some embodiments, the first dialysate flow rate may be the same, i.e., constant, during each time interval, or alternatively, may be different during some or all of the time intervals of the blood treatment session.

[0040] In some embodiments, the second dialysate flow rate may be the same, i.e., constant, during each time interval, or alternatively, may be different during some or all of the time intervals of the blood treatment session.

[0041] In some embodiments, the control device or closed-loop control device specifies or sets a pattern in which the first and second dialysate flows alternate through the dialyzer, and in some embodiments, the control device or closed-loop control device specifies or sets the points in time for the process of switching between the first and second dialysate flow rates, e.g., periodically and continuously.

[0042] In some embodiments, the first dialysate flow rate may be a maximum dialysate flow rate adjustable in the blood treatment device. Alternatively or additionally, the second dialysate flow rate through the dialysate fluid chamber may be zero.

[0043] Such a dialysate flow rate through the dialysate chamber equal to zero can be achieved, for example, by switching off the production of dialysate or its delivery, or by directing the dialysate past the dialysate chamber, for example, by a bypass line.

[0044] In some embodiments of the control device or closed-loop control device, a first time portion during which dialysis fluid is transported through the dialysis fluid chamber at a first dialysis fluid flow rate within the time interval under consideration, and a second time portion during which dialysis fluid is transported through the dialysis fluid chamber of the hemofilter at a second dialysis fluid flow rate within the time interval under consideration, can be set so that during the time interval under consideration, blood transported through the blood chamber of the hemofilter is purified as it passes through the blood chamber at a preset average clearance.

[0045] In some embodiments, the control device or closed-loop control device is configured, during use, to be in signal communication with one or more sensors of the measuring device and / or to determine clearance from signals communicated to it by the sensors, or otherwise.

[0046] In some embodiments, the control device or closed-loop control device is configured to vary a first portion of time during which dialysis liquid is conveyed through the dialysis liquid chamber at the first dialysis liquid flow rate within the time interval under consideration, and / or a second portion of time during which dialysis liquid is conveyed through the dialysis liquid chamber at the first dialysis liquid flow rate within the time interval under consideration, based on values ​​determined, in particular measured, by the sensor, so as to achieve a preset average clearance within the time interval under consideration.

[0047] In some embodiments, the control device or closed-loop control device comprises or is in signal communication with a communication device by which one or several values, such as a time portion value, a duration or time interval, a mean clearance value, a clearance in a first time portion or a second time portion, or the like, can be input, which values ​​are particularly suitable for or provided for setting or defining the dialysate flow rate required for the extracorporeal blood treatment.

[0048] In some embodiments, the blood treatment device of the present invention comprises or is connected to a dialyzer, the dialyzer being separated by a semipermeable membrane into a blood chamber and a dialysate chamber, and blood can flow through the blood chamber at a predetermined blood flow rate and dialysate can flow through the dialysate chamber at a predetermined dialysate flow rate.

[0049] In some embodiments, the blood treatment device is embodied as a dialysis device, a hemodialysis device, a hemofiltration device, or a hemodiafiltration device, particularly as a device for acute renal replacement therapy, long-term renal replacement therapy, or continuous renal replacement therapy (CKRT).

[0050] In some embodiments, changes in clearance are not caused by changes in blood flow rate. However, even if changes in blood flow rate cause changes in clearance, the control device or closed-loop control device is not configured to selectively affect clearance by modifying blood flow rate. In other words, in these embodiments, blood flow rate does not play a role in the flow rate calculations made by the control device or closed-loop control device to achieve a desired or preset average clearance, not specifically for each time interval.

[0051] In some embodiments, the control device or closed-loop control device is not configured to determine the difference between the clearance based on the value measured by the sensor and a preset average clearance, particularly for each time interval, and in particular is not configured to prompt an increase or decrease in dialysate flow rate based on a calculation of said difference.

[0052] Some or all embodiments of the present invention may have one, some, or all of the above and / or the following advantages.

[0053] One of the advantages of the present invention may be that it is possible to reduce the clearance K without or while reducing the previously existing drawbacks.

[0054] For technical reasons, a minimum flow rate is usually required for dialysis operation. When the clearance K is influenced by the present invention, changes in blood flow rate, which are made by mostly manual adjustments by the user or by complex adjustments on the part of the manufacturer of the monitoring system of the blood treatment device, are impractical and can therefore be advantageously omitted.

[0055] Another possibility for reducing the clearance K is a parallel flow principle arrangement, i.e., blood and dialysis fluid flow through the hemofilter in the same direction, which can achieve a reduction of approximately 20%. However, during patient treatment, it is practically impossible to switch to the more efficient counterflow principle, in which blood and dialysis fluid flow through the hemofilter in opposite directions. A further advantage of the present invention can be that a reduction in the clearance K can also be achieved with the more efficient counterflow principle.

[0056] A further advantage of the present invention resides in the avoidance of hemofiltration (without diffusion exchange), which advantageously allows for low convection and therefore low clearance K (typically in devices equipped for hemofiltration). Hemofiltration methods without diffusion exchange are available only for a small portion of devices on the market due to increased technical effort and associated costs. Therefore, the present invention makes it possible to avoid increased technical effort and save the significantly higher associated costs. Furthermore, the applicability of the present invention is significantly increased compared to hemofiltration methods (without diffusion exchange).

[0057] A blood treatment device with a fixed flow rate is less complex and less expensive. For this reason, the dialysate flow rate in prior art blood treatment devices is also not arbitrarily adjustable for technical reasons, but is often set by or at a few fixed or specific minimum flow rates, such as 300 ml / min and 500 ml / min. The problem of the lack of closed-loop control on the dialysate side when reducing the clearance K can also be advantageously avoided by the present invention.

[0058] Another advantage of the present invention may be that it allows for the addition of drugs to the arterial branch of the system, rather than the venous branch, as is common practice. This allows for the addition of drugs to be performed on the negative pressure side of the extracorporeal system, thereby enabling a device in which the withdrawal of the drug from the reservoir containing the drug to be added can be performed solely by the negative arterial pressure of the extracorporeal system. This may help save time and reduce personnel requirements. Furthermore, the infusion pump of the blood treatment device (or an external pump for this purpose) may be advantageously omitted.

[0059] All advantages achievable by the method steps described herein may be achieved, to an unimpaired extent, by using the device according to the present invention in certain embodiments according to the present invention.

[0060] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which like reference symbols indicate identical or similar elements, in which: [Brief explanation of the drawings]

[0061] [Figure 1] 1 shows a schematic simplified fluid line structure of a blood treatment device according to the present invention in a first embodiment. [Figure 2] 1 shows a blood treatment apparatus according to the invention with a control device or closed-loop control device according to the invention in a first embodiment in use; [Figure 3] 10 shows the clearance-controlled change in dialysate flow rate over time during treatment of a patient with a blood treatment apparatus according to the invention, comprising a control device or closed-loop control device according to the invention in a further embodiment. [Figure 4] 1 shows a kinetic two-pool model for the exchange of substances between body compartments IC and EC. [Figure 5a] A simulation of the substance concentration transition assuming an intercompartmental clearance of 800 ml / min is shown. [Figure 5b]A simulation of the substance concentration transition assuming an intercompartmental clearance of 100 ml / min is shown. [Figure 6a] 1 shows possible concentration profiles on the dialysate side downstream of a hemofilter without fluid removal by ultrafiltration. [Figure 6b] 1 shows possible concentration profiles on the dialysate side downstream of a hemofilter with fluid removal by ultrafiltration. DETAILED DESCRIPTION OF THE INVENTION

[0062] Figure 1 shows a fluid line diagram of a blood treatment device 100 according to the present invention in a first embodiment, which is partially represented in a highly schematic and simplified form with only a single component.

[0063] The blood treatment device 100, shown at least partially equipped and ready to use, is connected to an extracorporeal blood circuit 300, which may be connected to the patient's vascular system (not shown) for treatment using double needle access or, for example, by using an additional Y-connector (reference Y) shown in Figure 1, which is optionally not part of the blood treatment device 100, but which in other embodiments is part of the blood treatment device 100. The blood circuit 300, optionally in its multiple sections, may be present on or in a blood cassette.

[0064] The pumps, actuators, and / or valves in the area of ​​the blood circuit 300 are connected in signal communication to the blood treatment apparatus 100 of the present invention or, if control or closed-loop control is required, to a control device or closed-loop control device 150 included in the blood treatment apparatus.

[0065] The blood circuit 300 includes (or is connected to) a patient arterial tubing clamp 302 and an arterial connection needle (not shown in FIG. 1) on the arterial section or on the patient arterial line, blood withdrawal line, or first line 301.

[0066] The blood circuit 300 also includes (or is connected to) a patient venous tubing clamp 306 and a venous connection needle (not shown in FIG. 1) of the venous section, patient venous line, blood return line, or second line 305.

[0067] A blood pump 101 is provided in or on the first line 301, and an optional substitution fluid pump 111 is connected to the dialysis fluid inlet line 104 for delivering fresh dialysis fluid (substitution fluid) that has been filtered, for example, in a filtration step (filter F2).

[0068] An optional substitution fluid line 105 may be fluidly connected, for example, to the dialysis liquid inlet line 104. Using a substitution fluid pump 111, substitution fluid may be introduced into a line section, for example, into the arterial line section 301 or the venous line section 305 of the blood circuit 300 (here, between the blood chamber 303b of the blood filter 303 and the venous air separation chamber or venous blood trap 329), via optional associated lines 107a or 109a, either by pre-dilution with an optional pre-dilution valve 107 or by post-dilution with an optional post-dilution valve 109.

[0069] The hemofilter 303 comprises a blood chamber 303b connected to the arterial line section 301 and the venous line section 305. The dialysate chamber 303a of the hemofilter 303 is connected to a dialysate inlet line 104 leading to the dialysate chamber 303a and to a dialysate outlet line 102 guiding the dialysate, i.e. the used dialysate, away from the dialysate chamber 303a. Suitable connectors, which may in particular be releasably connected to one another, on the one hand on the dialysate inlet line 104 or on the dialysate outlet line 102 and on the dialysate port of the hemofilter 303, serve for this purpose.

[0070] The dialysate fluid chamber 303a and the blood chamber 303b are separated from each other by a substantially semi-permeable membrane 303c, which represents the partition between the blood side, which contains the extracorporeal blood circuit 300, and the machine side, which contains the dialysis fluid circuit or dialysate circuit, which is shown to the left of membrane 303c in FIG.

[0071] The arrangement of Figure 1 includes an optional detector 315 for detecting air and / or blood. The arrangement of Figure 1 optionally further includes one or two pressure sensors PS1 (upstream of blood pump 101) and PS2 (downstream of blood pump 101) (measuring the pressure upstream of hemofilter 303 ("pre-hemofilter")) at the locations shown in Figure 1. A further pressure sensor, such as pressure sensor PS3, may be provided downstream of venous bubble trap 329.

[0072] In FIG. 1, an optional single-needle chamber 317 is used as a buffer and / or compensation reservoir in a single-needle approach where the patient is connected to the extracorporeal blood circuit 300 using only one of the two blood lines 301, 305.

[0073] An addition point 325 for heparin or other particularly local anticoagulant may optionally be provided.

[0074] 1, optional mixing device 163 is shown, which provides pre-set mixtures for each solution from container A (for A concentrate via concentrate supply 166) and container B (for B concentrate via concentrate supply 168) for use by blood treatment apparatus 100. The solutions contain water from water source 155 (online, e.g., as reverse osmosis water, or from a bag), which is heated, e.g., in heating device 162.

[0075] An optional pump 171, which may be referred to as a concentrate pump or sodium pump, is fluidly connected to and / or conveys out of the mixing device 163 and a source of sodium, such as container A. An optional pump 173 associated with container B, such as for bicarbonate, can be seen.

[0076] 1 further shows a drain 153 for drainage. An optional heat exchanger 157 and an optional first flow pump 159 suitable for degassing complete the illustrated arrangement.

[0077] An optional pressure sensor PS4 may be provided downstream of the blood filter 303 on the water side, but preferably upstream of the optional ultrafiltration pump 131 in the dialysate outlet line 102, to measure the filtrate pressure or membrane pressure of the blood filter 303.

[0078] The ultrafiltration pump 131 provides a means for removing a precise amount of fluid from the balancing circuit as specified by the user and / or by the control device or closed loop control device 150 .

[0079] Blood exiting the hemofilter 303 flows through an optional venous bubble trap 329, which may include a degassing device 318 and may be in fluid communication with a pressure sensor PS3.

[0080] 1 includes a control device or closed-loop control device 150 according to the present invention, which may be in wired or wireless signal communication with any of the components described herein, particularly or specifically with the blood pump 101, to control or regulate the blood treatment apparatus 100.

[0081] By using a device for online mixing of the dialysis fluid, fluctuations in the sodium content can occur within certain limits, controlled by the control device or closed-loop control device 150. For this purpose, the measured values ​​determined by the conductivity sensors 163a, 163b in particular can be taken into account. If it turns out that it is necessary or desirable to adjust the sodium content (sodium concentration) of the dialysis fluid or substitution fluid, this can be done by adjusting the delivery speed of the sodium pump 171.

[0082] Furthermore, the treatment device 100 comprises a device for transporting fresh dialysis fluid and dialysate. An optional first valve V24 may be provided between the first flow pump 159 and the hemofilter 303, and this first valve V24 opens and closes the inlet flow towards the hemofilter 303. An optional second flow pump 169 is provided, for example downstream of the hemofilter 303, for transporting the dialysate to the drain 153. A second valve V25 may be provided between the hemofilter 303 and the second flow pump 169, and this second valve V25 opens and closes the outlet flow.

[0083] Furthermore, the blood treatment apparatus 100 optionally comprises a device 161 for balancing the flow into or out of the machine-side dialyzer 303. The balancing device 161 is preferably located in the line section between the first flow pump 159 and the second flow pump 169.

[0084] Sensors such as optional conductivity sensors 163 a, 163 b serve to determine conductivity, which in some embodiments is temperature compensated, and fluid flow rates upstream and downstream of the dialyzer 303.

[0085] One or more of the optional temperature sensors 165a, 165b may be provided, the temperature values ​​provided by which may be used to determine a temperature compensated conductivity.

[0086] A leak sensor 167 is optionally provided, which may be provided in different locations.

[0087] Further flow pumps may be provided in addition to or instead of the one designated by reference numeral 169, for example.

[0088] In FIG. 1, each of the multiple optional valves is designated V, and the bypass valve is designated VB.

[0089] A pressure sensor PS5 may be provided to measure the pressure in the dialysis fluid inlet line 104.

[0090] The control device or closed-loop control device 150, in some embodiments, determines electrolyte balance and / or fluid balance based on measurements from the optional sensors described above.

[0091] Filters F1 and F2 may be provided connected in series.

[0092] Even when non-pure water is used, the filter F1 serves to produce a dialysis liquid of sufficient purity, illustratively here by means of the mixing device 163, which then flows through the hemofilter 303, for example using the countercurrent principle.

[0093] Illustratively, filter F2 serves herein to produce a sterile or sufficiently filtered substitution fluid, e.g., by filtering pyrogens, from the sufficiently pure dialysis fluid leaving first filter F1, which can then be safely added to the blood flowing outside the patient's body and thus ultimately added to the patient's body.

[0094] Although blood treatment device 100 is shown in FIG. 1 as an apparatus for optional hemo(dia)filtration, hemodialysis devices are also covered by the present invention, even though they are not specifically depicted in the figures.

[0095] The arrows shown in FIG. 1 generally indicate the direction of flow in FIG.

[0096] FIG. 2 shows a blood treatment apparatus 100 according to the invention having a control device or closed-loop control device 150 according to the invention in a first embodiment in use.

[0097] Using the blood pump 101, blood is drawn through the vascular access of the patient Pa via the arterial (first) connecting needle and delivered to the blood filter or dialyzer 303 via the first line 301. The blood pump 101 may be part of the blood treatment device 100 or may be integrated into a disposable item. Any suitable method can be used for delivery, for example by a peristaltic pump or impeller pump.

[0098] The hemofilter 303 can be any unit for performing hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or a combination thereof.

[0099] The device comprises means for dialysis fluid preparation, for example as described with reference to Fig. 1, and fresh dialysis fluid is conveyed to the hemofilter 303, in particular into its dialysis fluid chamber 303a, via the dialysis fluid inlet line 104 by a suitable controllable flow pump 169. Here, the flow pump 169 may also be considered or called a "loading pump", via which the dialysis fluid flow rate can be adjusted based on the rotation speed of the flow pump 169.

[0100] The balancing device 161 periodically supplies fresh dialysis fluid into the dialyzer 303 through the filter F1 and the dialyzer valve V24 (also referred to herein as valve for short) by suitable switching of the valves.

[0101] The balancing device 161 in turn ensures that the amount of dialysis fluid flowing into the dialyzer 303 is equal to the amount flowing back through the balancing chambers of the balancing device 161. A pressure sensor between the flow pump 169 and the balancing device 161 detects a filled balancing chamber by increasing pressure and alters the switching (open / closed) of the valves accordingly.

[0102] The flow pump 169 ensures that the dialysate coming from the dialyzer 303 is fed into the balancing chamber of the balancing device 161 .

[0103] In particular, the means for preparing the dialysis fluid itself comprises means for modifying the composition of the dialysis fluid by changing the mixing ratio of the components involved in the online production of the dialysis fluid, for example as described in Figure 1.

[0104] The spent dialysate is returned or returned to optional means 160 for reprocessing the dialysate via dialysate outlet line 102. Optionally, a second flow pump 169 and / or other means for fluid withdrawal by ultrafiltration may serve for this purpose and may be provided in dialysate inlet line 104 or dialysate outlet line 102. Similarly, means for measuring, preferably continuously, the dialysate flow rate may be included in one of these lines 102, 104.

[0105] In some embodiments, the blood treatment apparatus 100 may further comprise means for branching off a partial flow for the purpose of substitution from the total dialysate as specified by the control device or closed-loop control device 150, so that a HF or HDF treatment can be performed using the balancing device 161 (see FIG. 1) for pre- or post-dilution. The partial flow is illustratively conveyed from the flow coming from the balancing device 161 and filter F1 through filter F2 into the subsequent fluid line and introduced into the extracorporeal blood circuit 300 by the substitution fluid pump 111 via the pre-dilution line 107a and / or the post-dilution line 109a.

[0106] 2, the blood treatment device 100 comprises two blood-side sensors 402a, 402b and two dialysate-side sensors 400a, 400b, which are arranged upstream and downstream of the blood filter 303, respectively. These sensors 400a, 400b, 402a, 402b are suitable for and are provided for determining the concentration of a substance, such as sodium, contained in the blood or the dialysate, respectively, or a value correlated therewith, by any method of contact or non-contact measurement. In particular, this may involve ion-selective electrodes, conductivity sensors, or spectroscopic devices for measurements in the infrared, visible, or UV range. At least one sensor 400b, 402b is arranged downstream of the blood filter 303 on the blood side or the dialysate side and is used here.

[0107] Sensors of the same or different types may be used so that by combining or based on measurements of different sensors or substance concentrations or values ​​correlated to substance concentrations, it is possible to calculate the clearance K (or dialysance) of one or more substances or groups of substances using a control device or closed-loop control device 150 according to the present invention. This may include methods that do not interfere with the course of treatment and methods that implement variations to the composition or flow rate of the dialysis fluid for the purpose of determining clearance.

[0108] The connections of sensors 400a, 400b, 402a, 402b to the blood-side or dialysate-side measurement points may be permanently installed in blood treatment device 100. Alternatively, the sensors may be fully or partially positioned or inserted only during preparation of blood treatment device 100. In particular, sensors 400a, 400b, 402a, 402b may be part of a blood-side and / or dialysate-side disposable item.

[0109] The connection between the sensors 400a, 400b, 402a, 402b and the control device or closed-loop control device 150 can be wired or wireless.

[0110] In some embodiments, the control device or closed-loop control device 150 is programmed or configured to calculate the clearance K, the dialysis dose Kt, and Kt / V, respectively, based on the measurements of the sensors 400a, 400b, 402a, 402b and other measurements and control variables of the blood treatment machine 100, particularly based on the blood-side and dialysate-side flow rates.

[0111] A value averaged over a time interval may be used instead of or in addition to the currently determined value. If the sensors 400a, 400b, 402a, 402b are conductivity sensors or ion-selective measurement sensors, the control device or closed-loop control device 150 may calculate the resulting blood-side concentration of the substance of interest, particularly during periods of no dialysate flow, from direct calculations and with kinetic models for exchange through different body compartments, for example, by using known equations or equations described herein.

[0112] Values ​​for clearance K, dialysis dose Kt, or substance concentration may be output to a user or external observer via display device 500 and / or communication device 600.

[0113] Furthermore, it may be possible to use the display device 500 and communication device 600 to specify a desired time course of the clearance K, which is implemented using the blood treatment machine 100.

[0114] Additionally, the display device 500 and communication device 600 can be used to display the various dialysate flow rates Q used. d It may be possible to input or receive parameters that allow for calculating an approximation of the clearance K for the dialyzer parameter K0A or its effective value, the patient's shunt flow, cardiopulmonary recirculation rate, cardiac output, recirculation rate known from previous treatments, and results of clearance measurements from previous treatments of the currently treated patient or other patients, among others.

[0115] FIG. 3 shows, in a further embodiment, the time course of the clearance-controlled change in dialysate flow rate during treatment of a patient Pa by a blood treatment device 100 according to the present invention, which is equipped with a control device or closed-loop control device 150 according to the present invention.

[0116] Reference is made to the reference numbers of the preceding figures.

[0117] For simplicity, the following description of Figure 3 is based on the one-pool model, i.e., internal exchanges between the intravascular space (vasculature) and the interstitial and intracellular spaces are not taken into account here. When calculating the dialysis dose Kt / V, these models assume that the patient's systemic urea concentration is equally low immediately after dialysis, which is not the case for a real patient Pa (see also the description of the two-pool model detailed herein).

[0118] The removal of a substance not contained in the dialysis fluid by a purification procedure with clearance K, at a concentration c that is uniformly distributed in the patient with a substance-specific volume of distribution V, can be described in a one-pool model as follows: d(Vc)=-Kc(t)dt (Equation 1)

[0119] Using the constants K and V, the time-dependent solution for concentration is:

number

[0120] If K varies during the procedure, the entire procedure is j and related clearance K j The image may be divided into N consecutive sections having:

[0121]

number

number

[0122] Therefore, with a constant volume of distribution V, the final concentration c(t) is the sum of Σ j K j t j instead, it depends only on the previous treatment duration T dial Clearance averaged over

number

number

[0123] Therefore, the time course of K is independent of the final concentration.

[0124] K j is the dialysis flow rate Q d,j where K(Q d =0)=0.

[0125] Dialysate flow rate Q d in addition to one or more different values ​​of the dialysate flow rate Q through the dialyzer 303. d can be set to zero at each blood treatment machine by switching off the dialysate fluid generation or by temporarily diverting (bypassing) the dialysate fluid past the dialyzer 303. During an online HDF procedure, where online generated dialysate fluid flows through the dialyzer 303 for diffusive mass exchange and is used as a substitution fluid by diverting a partial flow, the dialysate flow rate Q through the dialyzer 303 is d can be reduced by increasing the moiety used for substitution.

[0126] Time interval T j There are two values ​​Q d,1 and Q d,2 By switching between the time part

number

number

[0127] Q d,2 = 0 (i.e., dialysate flow off) and K2 = 0, K - =xK1.

[0128] For semi-continuous operation, the entire procedure may be divided into N consecutive sections j of duration T j and duration T j A predetermined average clearance to be achieved over

number

[0129] To determine x, knowledge of K1 and K2 is required, which can be estimated from a model of the dialyzer 303 as a function of the dialyzer parameter K0A and flow rate.

[0130] Models that can be used to calculate clearance K given knowledge of the dialyzer parameter K0A and the flow rate of the dialyzer 303 are described in the literature (e.g., Sargent & Gotch, "Principles and Biophysics of Dialysis" in "Replacement of renal function by dialysis").

number

[0131] where: D diff denotes the diffusion rate of the clearance K in the dialyzer 303, Q Bi indicates the total flow rate on the blood side. The following applies: For procedures involving dilution after HD and HDF, Q Bi =Q b and For procedures involving pre-HDF dilution, Q Bi =Q b +Q s and Q s is the substitution rate.

[0132] The expected total clearance is then calculated, taking into account the dialysis method used,

number

[0133] where the effective value of the dialyzer parameter (K0A) effIt should be taken into account that a K0A must be used, which differs substantially from the manufacturer's specifications derived from laboratory measurements (e.g., Depner "Dialyzer Performance in the HEMO Study: In Vivo K0A and True Blood Flow Determined from a Model of Cross-Dialyzer Urea Extraction", ASAIO Journal 2004), and takes into account the actual blood characteristics and the nature of the blood circuit.

[0134] On the other hand, however, it is also possible to set K1 and K2 during treatment by means of measurements on the blood side or on the dialysate side in order to be able to react, if necessary, to changing conditions during treatment.

[0135] From equation 6, the following result is obtained:

number

[0136] Advantageously, the interval duration T j is the measurement of K1, and Q d,2 >0 is selected to allow for the measurement of K2 as well. It is also possible to measure only K2 or K1 within each interval and then use the measurement in the next interval, or to adjust the length of the interval so that a long interval with clearance measurements is followed by a short interval without clearance measurements.

[0137] At the start of treatment, mean clearance K1 - is achieved for duration T1. Here, the blood treatment machine 100 operates at two separate dialysate flow settings Q d,1 and Q d,2 where Q d,2 may preferably be zero.

[0138] The treatment is performed with an initial dialysate flow rate Q d,1 It starts with.

[0139] Knowledge of blood flow and effective dialyzer parameters (K0A) eff Based on the estimated value of the clearances K1 and K2, an estimation of the clearances K1 and K2 can now be made according to equation 3, where preferably K2=0. From this, the time portion x1, i.e., the dialysate flow rate Q d,1 The time portion of the interval T1 for which K1 should be set can now be determined according to equation 4. Advantageously, the measurement M 1,1 is done as soon as possible, and a subsequent determination of K1 is made as shown in FIG. 2, so that a more accurate (target) value for x1 can be set.

[0140] Measurement M to set this K1 1,1 After the end of Q, in some embodiments, a decision is made regarding further procedures in interval T1. d,2 If =K2=0, treatment continues until the time period x1T1 has elapsed. d,1 Continue with Q d =Q d,2 = 0 is set. If the measurement continues long enough that x > 1, T1 is extended, so that after the extended T1 expires, the average clearance K1 - is controlled by this. In this case, the duration of the next time interval and the specification of the average clearance to be achieved in the next time interval can be adjusted. Q d,2 Therefore, if K2 is > 0, the dialysate flow rate Q d,2 is set immediately after the end of the measurement of K1 and is used for the measurement M with the subsequent determination of K2. 2,2 Q d,2 For the case where K2=0, a decision is now made as to the extension of T1 to compensate for the next interval. - If Q d,2 =0 is set.

[0141] In the next interval, the Q determined in the first interval is d,1 and Q d,2The clearance at is used here as the basis for calculating x, since it can be assumed that the clearance changes only slightly at a constant flow ratio.

[0142] Average clearance K N - There may be separate default values ​​for σ for each time interval. However, at each interval, these values ​​may be updated by further measurements with subsequent determination of clearance, where only one or both values ​​may be determined, respectively.

[0143] This procedure allows arbitrarily small values ​​of diffusion clearance to be set in a controlled manner.

[0144] FIG. 4 shows a kinetic two-pool model for the exchange of substances between body compartments IC and EC.

[0145] The one-pool models considered so far cannot explain the clinically observed effect that the concentration of substances in the blood, for example, urea, increases again immediately after the end of dialysis. This effect is called "rebound" and can be explained by a two-pool model that takes into account the internal exchange between the intercellular spaces and the intracellular space, including the intravascular space (vasculature) (see, for example, Gotch, "Replacement of Renal Function by Dialysis").

[0146] Only the extracellular space EC is accessible for dialysis, i.e., the exchange of substances with the intracellular space IC is via the internal clearance K IC This mass exchange occurs even after the end of dialysis, when the concentrations in all compartments EC and IC remain at the value c eq Continue until it is equal to

[0147] The model in Figure 4 shows the intercellular and intracellular space IC, which is the volume V IC and substance concentration c IC Internal clearance K ICThe substance concentration in the intercellular space IC is IC and quantity V EC The concentration of the substance in the extracellular space EC is c EC are adjusted according to the principle of diffusion.

[0148] Clearance K performed during treatment session dial The removal of a substance from the patient's blood is determined by the concentration c di performed during the treatment session depending on

number

[0149] The dialysis volume Kt / V is calculated by rearranging Equation 5 and dividing the blood substance concentration c0 at the start of treatment by the final concentration c end where, in the one-pool model, K is the mean clearance during dialysis. <k>is equivalent to

number

[0150] However, since patients exhibit two-pool behavior, the concentration of substances not contained in the dialysis fluid increases again in the blood after the end of the treatment session, resulting in c eq >c end Therefore, the dialysis volume (Kt / V) calculated from the equilibrated concentration is eq is always the value from the one-pool model (Kt / V) SP , which corresponds in good approximation to the values ​​obtained by continuous device-side measurements and the resulting clearance determination.

[0151] For clinical practice, (Kt / V) eq and (Kt / V) SP Methods are provided for converting between (see, for example, Daugirdas "Solute Solver," available at http: / / www.ureakinetics.org / ).

[0152] The balanced dialysis volume is not affected by the intermittent approach disclosed herein, and as a result the conversion model used remains valid (see Figures 5a and 5b).

[0153] Figure 5a shows a numerical simulation of the substance concentration evolution of a substance such as phosphate, assuming a high intercompartmental clearance of 800 ml / min.

[0154] Numerical simulations have revealed that, for example, (Kt / V) eq =( <k>t / V) eq ( <k>: the mean clearance according to Equation 4) can be shown to be independent of x and T to a good approximation.

[0155] Figure 5a shows the concentration curve Ck for continuous clearance and the concentration curve Ci for intermittent clearance with time portion x = 50%. 50 and the concentration curve Ci at intermittent clearance where the time portion x=75% 75 These are the concentration trends in the intravascular space EC (vasculature) of patients who have direct access to dialysis.

[0156] Above these curves in Figure 5a, the concentration curves Ck for continuous clearance are shown. IC and the concentration curve Ci at intermittent clearance where the time portion x=50% IC50 and the concentration curve Ci in intermittent clearance where the time portion x=75% IC75 These are concentration transitions in the intercellular and intracellular spaces IC.

[0157] In the simulation, the dialysate flow rate Q d,1 with and without dialysate flow (Q d,2 =0) state, the periodic change is <k>was assumed to be the same in all cases.

[0158] Intermittent transitions that "clean" the intravascular space EC have no dialysate flow rate (Q d,2 = 0), the concentration increases repeatedly.

[0159] Overall, it can be seen that the concentration profiles in the intermittent technique are not significantly different from those in continuous clearance, so that when measured against each other, the concentrations are nearly identical at the end of the treatment session up to or after rebound.

[0160] Therefore, (Kt / V) eq and (Kt / V) SP The transformation methods developed for the continuous case are still applicable.

[0161] Figure 5b shows a numerical simulation of the substance concentration evolution of a substance such as phosphate, similar to Figure 5a, assuming a low intercompartmental clearance of 100 ml / min.

[0162] See the description of Figure 5a.

[0163] It can be seen that the concentration profile for the intermittent method does not deviate significantly from that for continuous clearance, so that again after dialysis has ended the concentrations are approximately the same in rebound.

[0164] FIG. 6a shows possible concentration profiles on the dialysate side downstream of the hemofilter 303 during intermittent dialysate flow without ultrafiltration.

[0165] Reference is made to the reference numerals and descriptions of the preceding figures.

[0166] In the graph, the concentration c is shown in arbitrary units (au) over time t (units (min)).

[0167] In the following, only one active dialysate flow rate, Q d,1 and the dialysate flow rate (Q d,2 =0).

[0168] Dialysate flow rate Q d,1 When is active, the substance concentration on the blood side (index "bi") can be set from the concentration on the dialysate side (index "di": dialysate inlet line, "do": dialysate outlet line) (see, for example, Sargent & Gotch, "Principles and biophysics of dialysis" in "Replacement of renal function by dialysis").

number

[0169] At the same time, Q d,2 It can be seen that in the case of K = 0 and simultaneously K2 = 0, no measurement is possible. However, in a first approximation (one-pool model), it can be assumed that the substance concentration does not change when K2 = 0. Therefore, Q d,2 For times when Q = 0, the display shows the active dialysate flow rate, Q = 0, rather than a pause. d,1 The last determined values ​​may be displayed continuously, for example on the display device 500. This is particularly true for plasma sodium.

[0170] In the case of a high concentration difference between blood and dialysis fluid or dialysate, respectively, the concentration profile may alternatively be numerically approximated and displayed with a two-pool model according to Equation 10.

[0171] One possibility for determining the clearance K is spectroscopic measurement of the concentration profile of a marker substance in the used dialysate, i.e., in the dialysate outlet line, or a value correlated thereto, using sensor 400a and equation 11 (e.g., "Adimea" by BBraun).

[0172] Dialysate flow rate Q d,1 When the dialyzer 303 is running, the substance concentration in the outgoing dialysate is always lower than in the blood. If the flow through the dialyzer 303 is switched off, the substance concentration in the dialysate still present in the dialyzer 303 increases by diffusion to the substance concentration in the patient's blood. If the dialysate flow through the sensor 400a is stopped completely, the concentration there will not change, but on the other hand, if only the dialysate flow through the dialyzer 303 is stopped and instead new dialysate liquid is pumped directly to the sensor 400a in the bypass circuit, the concentration there will drop to zero or to the concentration in the new dialysate.

[0173] Dialysate flow rate Q d If the sensor 400a is now switched on again, dialysate with an increased substance concentration will flow to the sensor 400a. Due to complete equilibration during the rest period, the concentration on the dialysate side will briefly equal the concentration on the blood side at the sensor. This is shown diagrammatically in Figure 6a.

[0174] In steps 1.1, 2.1, 3.1 and 4.1, the concentration on the dialysate side decreases according to the relationship with the blood side concentration described in equation 12. In these steps, it is possible to determine the dialysis dose Kt / V.

[0175] The concentration of the dialysate side is measured when the dialysate flow rate is turned off (Q d,2 = 0), there are no further changes in steps 1.2, 2.2 and 3.2. At this stage, a measurement period of several minutes is available, allowing a very accurate measurement of the substance concentration.

[0176] In steps 1.3, 2.3, and 3.3, the dialysate concentration increases briefly up to the blood concentration. Therefore, the blood concentration can be obtained and displayed directly from the peak concentration. On the other hand, determining the dialysis volume Kt / V is not possible in this range, since the increase in concentration corresponds to negative clearance.

[0177] For this reason, the method for determining Kt / V by concentration measurement must be supplemented by a method that excludes steps j.2 and j.3 (j=1,...,N) from the calculation, knowing the time and duration of the pause in the dialysate flow rate, and continues again only when the equilibrium between the substance concentration in the blood and the dialysate has been restored in step j.1. ​​This may be the case, for example, after a waiting period that depends on the dialysate flow rate.

[0178] FIG. 6b shows possible concentration profiles on the dialysate side downstream of the hemofilter 303 during an intermittent dialysate flow with ultrafiltration.

[0179] Reference is made to the reference numerals and descriptions relating to the preceding figures, and in particular to FIG. 6a.

[0180] Dialysis fluid flow pause time (Q d,2 If fluid is removed by ultrafiltration during the UF volumetric flow rate (Q = 0), and if the UF volumetric flow rate is sufficiently high, the dialysate at sensor 400a is replaced by ultrafiltrate, so that the same concentration as in the blood is finally present there and can therefore be measured directly. The removal volume required for this roughly corresponds to the dialysate-side volume of dialyzer 303, i.e., about 100 ml. Therefore, if this method is used to measure blood-side concentrations on the dialysate side, it is advantageous to increase the ultrafiltration rate during the dialysate rest time. In particular, if the dialysate flow rate Q d,1 It may be advantageous to completely turn off ultrafiltration during the phase with , and compensate for it during the period without dialysate flow, so that the overall average UF rate remains unchanged. Information about the dialyzer capacity can be obtained by input, for example by using the communication device 600, or by device-side measurements, for example the time span of a given upstream conductivity change until it reaches the sensor 400a. This allows the system to determine whether a sufficiently large ultrafiltration volume has been delivered and therefore whether a reliable determination of the blood-side concentration is possible.

[0181] The method described herein for measuring the concentration of a substance can also be used when the substance already exists in the new dialysis fluid. This applies in particular to the measurement of the concentration of electrolytes, here in particular sodium, by means of a conductivity cell or an ion-selective electrode. Here, the peak concentrations in steps 1.3, 2.3, and 3.3 without fluid removal (see FIG. 6a) or with fluid removal by ultrafiltration result in the concentrations at the end of steps 1.3, 2.3, and 3.3, the so-called Donnan equilibrium concentrations with the blood-side concentrations in the plasma water. For cations such as sodium, the following applies:

number

[0182] α is the Donnan factor, which depends on the protein concentration in the blood and is typically 0.95. If instead the concentration is given relative to the whole plasma, which is more relevant to medical practice, the amount of protein contained in the plasma must be taken into account, which is approximately 5%. In this case, the following applies:

number

[0183] In contrast, the anion concentration in plasma water and in plasma is reduced, so that the following applies here:

number

[0184] The time during dialysis is often also used to administer medications, such as iron or vitamin supplements. When used for acute dialysis, a wide range of other medications (e.g., painkillers, antibiotics, steroids, etc.) are also administered. Here, it is advantageous to synchronize the administration of these medications with a phase that does not have dialysate flow to avoid dialyzing the administered substance before it has been fully distributed to the patient.

[0185] Further in this regard, addition may be made to the arterial branch of the system rather than the venous branch as is common practice, to avoid immediate dialysation en route through the dialyzer 303.

[0186] Thus, loading can be performed on the negative pressure side of the extracorporeal system, enabling, in certain embodiments, a device in which withdrawal from a reservoir containing the loaded drug is performed solely by the negative arterial pressure of the extracorporeal system.

[0187] The average clearance K to be achieved in each time interval - can be specified based on patient-specific or general empirical values, or based on kinetic models of changes in substance concentrations in various body compartments.

[0188] For example, a patient may know that imbalance syndrome occurs only when diffusion clearance exceeds a certain threshold, e.g., 100 ml / min, in the first 30 minutes of dialysis. This threshold, set based on clinical experience, may also depend on the day of the week and may be different from the threshold for other days, particularly days following a long interval without dialysis (e.g., Monday or Tuesday). This or similar information may be entered via communication device 600 or provided to a control device or closed-loop control device according to the present invention for use in calculations.

[0189] Alternatively, the time-dependent concentration difference between compartments, and therefore, for example, osmolality, can be calculated based on the measured or estimated initial substance concentration in blood and the assumption of initial equilibrium between body compartments, using a multi-compartment model, for example, similar to that described herein as a two-pool model, optionally including brain volume as an additional compartment.The target or desired clearance of the dialysis system can then be calculated so that it does not exceed the critical concentration difference or critical osmolality.This applies, among other things, to molecules such as urea or ethanol.

[0190] Alternatively or additionally, the limit value can be a critical rate of change of the substance concentration. For plasma sodium, for example, empirical values ​​exist here from intensive care units (e.g., daily change <6 mmol / L). Here, the sodium concentration c in the new dialysate dial and according to equations 1 and 10, the following applies: d(Vc Pat )=-K dial (c Pat (t)-c dial )dt (Equation 16)

[0191] With a fixed volume of distribution, V, the following applies to the concentration change over time in a patient:

number

[0192] Δc Pat is given the sodium concentration in the dialysate, c dial At time t max Within Δc Pat,max If the clearance remains limited to the value of K max must remain limited to

number

[0193] This should be explained using the following example.

[0194] V=40L and plasma sodium is c Pat The sodium concentration in the blood of a hyponatremic patient, which is (0) = 120 mmol / L, is returned to the sodium standard range (135 mmol / L to 145 mmol / L) by acute dialysis treatment. Here, the minimum dialysate sodium concentration that can be set on the blood treatment device 100 is c dial = 130mmol / L. max Within a period of 10 hours, the change is Δc Pat,max = 6 mmol / L. Therefore, according to Equation 18, this means that K max This results in a maximum clearance of K = 61 mL / min. With the dialyzer available in the clinic and a minimum blood flow rate of 200 ml / min and a minimum dialysate flow rate of 300 ml / min that can be set on the machine, the estimate from equation 7 is a clearance of K = 122 ml / min, which would cause the plasma sodium to rise too quickly. By periodically switching off the dialysate flow rate (=>K = 0), the time portion x is now set to the clearance target value of K - =K max This value is then transferred to the control device or closed-loop control device 150. Thus, in this case, x=0.5. K can be calculated by measuring during the procedure and determining the resulting clearance, as described herein. - x can be adjusted in a further step so that [Explanation of symbols]

[0195] 100 Blood treatment device 101 Blood Pump 102 Dialysis fluid outlet line 104 Dialysis fluid inlet line 105 Displacement fluid line 107 Pre-dilution valve 107a Line associated with the pre-dilution valve 109 Post-dilution valve 109a Line associated with the post-dilution valve 111 Displacement fluid pump 131 Ultrafiltration Pump 150 Control devices or closed-loop control devices 153 Drainage Channel 155 Water source 157 Heat exchanger 159 First Flow Pump 160 Means for reprocessing dialysis fluid 161 Balancing Devices 162 Heating Devices 163 Mixed Devices 163a Conductivity Sensor 163b Conductivity Sensor 165a temperature sensor 165b Temperature Sensor 166 Concentrate supply section 167 Leak Sensor 168 Concentrate supply section 169 Second Flow Pump 171 Pump, Sodium Pump 173 Pump, bicarbonate pump 300 Extracorporeal blood tubing set or blood circuit 301 First line (arterial line section) 302 Patient Arterial Tube Clamp 303 Blood filters or dialysis machines 303a Dialysis fluid chamber 303b Blood Chamber 303c semi-permeable membrane 305 Second line (venous line section) 306 Patient venous tube clamp 315 Air Bubble Detector (ABD) 317 Single Needle Chamber 318 Degassing Device 325 Heparin Addition Point 329 (Venous) Bubble Trap 400a Measuring device, sensor, dialysate side 400b Measuring device, sensor, dialysate side 402a Measuring device, sensor, blood side 402b Measuring device, sensor, blood side 500 display devices 600 Communication Devices A container, A concentrate, sodium B container, B concentrate, bicarbonate Ck concentration curves in the intercellular and intravascular spaces at and during continuous clearance Ci 50 Concentration curves in the intercellular and intravascular spaces with time fraction x=50% during intermittent clearance Ci 75 Concentration curves in the intercellular and intravascular spaces with time fraction x=75% during intermittent clearance Ck IC Concentration curves in the intracellular space with continuous clearance Ci IC50 Concentration curve in the intracellular space at time fraction x=50% with intermittent clearance Ci IC75 Concentration curve in the intracellular space at time fraction x=75% during intermittent clearance Extracellular and intravascular spaces (vasculature) of patients with EC F1 Filter F2 Filter IC Intercellular and intracellular spaces K Clearance K1 First Clearance K2 Second Clearance K j - Time interval T j (j=1,…,N,

[0196]

number

[0197] (hereinafter referred to as "N∈NN"), the (predefined) average clearance M j,1 Time interval T j First dialysate flow rate Q for (j=1,…,N, N∈NN) d,1 Measurement at M j,2 Time interval T j Second dialysate flow rate Q for (j=1,…,N, N∈NN) d,2 Measurement at Pa patient PS1 Arterial Pressure Sensor (Optional) PS2 Arterial Pressure Sensor (Optional) PS3 pressure sensor (optional) PS4 pressure sensor for measuring filtrate pressure PS5 pressure sensor for measuring the pressure in the dialysis fluid inlet line Q b blood flow rate Q d Dialysate flow rate Q d,1 First dialysate flow rate Q d,2 Second dialysate flow rate t Time axis T j Time interval (j=1,…,N, N∈NN) V-valve V24 valve V25 valve VB Bypass valve x j Interval T j a time portion with a first dialysate flow rate in j = 1,...,N, N∈NN 1-x j Interval T j a time portion with a second dialysate flow rate in j = 1,...,N, N∈NN Y Y-connector< / k> < / k> < / k> < / k>

Claims

1. 1. A control device or closed-loop control device configured to control or control in a closed-loop manner an extracorporeal blood treatment device when connected in signal communication with the extracorporeal blood treatment device, the extracorporeal blood treatment device comprising a dialyzer divided into a blood chamber and a dialysis fluid chamber by a semipermeable membrane for treating a patient's blood extracorporeally in a blood treatment session; Here, The control device or the closed loop control device controls the dialysate flow rate (Q) through the dialyzer for extracorporeal blood treatment by the extracorporeal blood treatment apparatus. ｄ，１ , Q ｄ，２ ), Here, The control device or the closed loop control device controls the dialysate flow rate (Q ｄ，１ , Q ｄ，２ ) for a plurality of consecutive time intervals (T １ , T ２ , ..., T Ｎ , N∈NN), the first dialysate flow rate (Q ｄ，１ ) and the second dialysate flow rate (Q ｄ，２ ) are set alternately with each other, and the first dialysate flow rate (Q ｄ，１ ) is the second dialysate flow rate (Q ｄ，２ ) a control device or closed-loop control device.

2. The control device or the closed-loop control device is provided with a measuring device for measuring or an estimating device for estimating at least one characteristic value of the clearance K, or is connected to the measuring device or the estimating device, and is configured to control the first dialysate flow rate (Q ｄ，１ ) and / or the second dialysate flow rate (Q ｄ，２ ) is determined based on the at least one characteristic value of the clearance K, or the first dialysate flow rate (Q ｄ，１ ) and / or the second dialysate flow rate (Q ｄ，２ 2. The control device or closed-loop control device of claim 1, wherein the clearance K is determined based on the at least one characteristic value of the clearance K.

3. The plurality of time intervals (T １ , T ２ , ..., T Ｎ ) from each time interval (T ｊ , j=1,...,N, N∈NN), the first time portion (x ｊ ) and the first time portion (x ｊ ) at or during the time interval under consideration (T ｊ ) into the first dialysate flow rate (Q ｄ，１ a first time portion (x ) of the dialysis fluid delivered through the dialysis fluid chamber; ｊ ), and / or the dialysis fluid is ｊ ) into the second dialysate flow rate (Q ｄ，２ ) conveyed through the dialysis fluid chamber in a second time portion (1−x ｊ 3. A control device or closed-loop control device according to claim 1 or 2, configured to set a

4. The first dialysate flow rate (Q ｄ，１ ) is the maximum dialysate flow rate (Q ｍａｘ ), and / or the second dialysate flow rate (Q ｄ，２ 4. A control device or closed-loop control device according to claim 1, wherein:

5. The dialysis fluid is ｊ ) into the first dialysate flow rate (Q ｄ，１ ) the first time portion (x ｊ ), and the dialysis fluid is ｊ ) into the second dialysate flow rate (Q ｄ，２ ) the second time portion (1−x ｊ ) is the time interval under consideration (T ｊ ) the blood transported through the blood chamber during the blood flow is greater than a preset average clearance (K ｊ － 5. A control device or closed loop control device according to claim 3 or 4, configured to purify blood as it passes through the blood chamber.

6. In use, the sensor is adapted to communicate signals with one or several sensors of the measuring device and / or to receive clearance (K １ , K. ２ 6. A control device or closed-loop control device according to any one of claims 1 to 5, configured to determine

7. Pre-set average clearance (K ｊ － ) based on the value determined by the sensor, the dialysis fluid is adjusted to achieve the time interval (T ｊ ) into the first dialysate flow rate (Q ｄ，１ ) the first time portion (x ｊ ) and / or the dialysis fluid during the time interval under consideration (T ｊ ) into the second dialysate flow rate (Q ｄ，２ ) the second time portion (1−x ｊ 7. A control device or closed-loop control device according to claim 6, configured to regulate:

8. The dialysate flow rate (Q ｄ，１ , Q ｄ，２ ) is the value (x ｊ , 1-x ｊ , T.K. ｊ － , K. １ , K. ２ 8. A control device or closed-loop control device according to claim 1, comprising a communication device for inputting a command value.

9. 9. A blood treatment apparatus for extracorporeal blood treatment, characterized in that the blood treatment apparatus comprises a control device or a closed-loop control device according to any one of claims 1 to 8 or is connected in signal communication to said control device or said closed-loop control device.

10. The blood is then pumped through a preset blood flow rate (Q ｂ ) and a blood chamber in which the dialysis fluid can flow at a preset dialysate flow rate (Q ｄ 10. The blood treatment device of claim 9, comprising or connected to a dialyzer separated by a semipermeable membrane into a dialysate chamber through which the blood can flow.

11. A digital storage medium, in particular a floppy disk, memory card, CD or DVD, EPROM, FRAM or SSD, having electronically readable control signals, adapted to interact with a programmable computer system so that a conventional control device or closed-loop control device of a blood treatment machine is reprogrammed into a control device or closed-loop control device according to any one of claims 1 to 8.

12. A computer program product having program code as signal waves or stored on a machine readable carrier for interacting with a programmable computer system such that a conventional control device or a closed loop control device of a blood treatment apparatus is reprogrammed into a control device according to any one of claims 1 to 8.

13. 9. A computer program having a program code configured to, when the computer program is run on a computer, reprogram a conventional control device or a closed-loop control device of a blood treatment apparatus into a control device according to any one of claims 1 to 8.

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