Estimation method of recirculation rate, analysis device and blood purification device

Abstract

To provide an estimation method of a recirculation rate enabling estimation of a recirculation rate without being limited by a preparation location of a blood marker or an arrangement location of detection means of the blood marker.SOLUTION: An estimation method of a recirculation rate includes the steps of: acquiring data representing an amount of change in blood concentration after recirculation when a blood marker is added to blood to be extracorporeally circulated, data representing a relation between an amount of change in blood concentration after recirculation and blood concentration, and data representing a relation between the amount of change in blood concentration after recirculation and a blood flow rate; creating a model by multivariate analysis or machine learning to obtain a regression equation or a conversion model, with the amount of change in blood concentration after recirculation, blood concentration and a blood flow rate used as an explanatory variables and the recirculation rate as an objective variable; acquiring data representing the amount of change in blood concentration, blood concentration and a blood flow rate of blood flowing through an arterial line or a venous line; and inputting treatment data to the regression equation or the conversion model to estimate the recirculation rate.SELECTED DRAWING: Figure 3A

Description

[Technical Field]

[0001] The present invention relates to a method for estimating a recirculation rate, an analysis device, and a blood purification device. [Background technology]

[0002] In hemodialysis therapy, blood that has passed through a blood purifier is returned from the venous side of the blood circuit, but the returned blood may be directly removed from the arterial side and flow back into the blood purifier. This is called blood recirculation. To obtain sufficient therapeutic effects in hemodialysis therapy, it is desirable to keep the recirculation rate low. Patent Document 1 describes a method for measuring the recirculation rate, in which two detection means are provided in the blood circuit and the concentrations of blood markers measured by the two detection means are compared. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 2019-187888 Summary of the Invention [Problem to be solved by the invention]

[0004] Conventional methods for measuring recirculation rates require the installation of multiple blood marker detection means to compare changes in blood marker concentrations before and after blood recirculation. Furthermore, the locations of the detection means are limited by the location of the blood marker production site. For example, if the blood marker detection means is installed only upstream of the blood marker production site, the detection means cannot determine the blood marker concentration before blood recirculation. This means that recirculation rates cannot be measured.

[0005] An object of the present invention is to provide a method for estimating a recirculation rate, a blood purification device, and an analytical device that enable estimation of a recirculation rate without being restricted by the location of the blood marker production and the location of the blood marker detection means. [Means for solving the problem]

[0006] The method for estimating a recirculation rate in hemodialysis treatment of the present invention includes the following steps: a model data acquisition step of acquiring, using a recirculation rate measurement model, data indicating a change in blood concentration after recirculation when a predetermined amount of blood marker is added to blood circulating extracorporeally, data indicating the relationship between the change in blood concentration after recirculation and blood concentration, and data indicating the relationship between the change in blood concentration after recirculation and blood flow rate; an analysis step of performing model creation by multivariate analysis or machine learning using the model data acquired in the model data acquisition step to determine a regression equation or a transformation model in which the change in blood concentration after recirculation, blood concentration, and blood flow rate are explanatory variables and the recirculation rate is a response variable; an intra-treatment data acquisition step of acquiring data indicating the change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment; and a recirculation rate estimation step of estimating a recirculation rate by inputting the intra-treatment data acquired in the intra-treatment data acquisition step into the regression equation or transformation model determined in the analysis step.

[0007] The analytical device of the present invention is an analytical device that determines a regression equation for estimating the blood recirculation rate in hemodialysis treatment, and is equipped with a model data acquisition unit that uses a recirculation rate measurement model to acquire data indicating the change in blood concentration after recirculation when a predetermined amount of blood marker is added to blood circulating extracorporeally, data indicating the relationship between the change in blood concentration after recirculation and the blood concentration, and data indicating the relationship between the change in blood concentration after recirculation and the blood flow rate, and an analytical unit that performs multivariate analysis or machine learning using the model data acquired by the model data acquisition unit to determine a regression equation or transformation model in which the change in blood concentration after recirculation, the blood concentration, and the blood flow rate are explanatory variables and the recirculation rate is a response variable.

[0008] Furthermore, the blood purification device of the present invention is a blood purification device capable of estimating the blood recirculation rate, and includes a treatment data acquisition unit that acquires data indicating the amount of change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment, and a recirculation rate estimation unit that estimates the recirculation rate by inputting the treatment data acquired by the treatment data acquisition unit into a regression equation determined by an analysis device. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a method for estimating a recirculation rate, a blood purification device, and an analytical device that allows estimation of a recirculation rate without being restricted by the location of the blood marker production and the location of the blood marker detection means. [Brief explanation of the drawings]

[0010] [Figure 1] 1 is a diagram showing a schematic configuration of a blood purification device according to one embodiment of the present invention. [Figure 2] FIG. 1 is a block diagram of a blood purification device. [Figure 3A] FIG. 1 is a flow chart showing an overview of creating an analytical model of a recirculation rate. [Figure 3B] FIG. 1 is a flow chart outlining a method for estimating a recirculation rate. [Figure 4] FIG. 1 is a diagram showing a schematic configuration of a recirculation rate measurement model. [Figure 5] FIG. 1 shows changes in blood concentration over time. [Figure 6] FIG. 1 is a schematic diagram showing a part of a blood purification device. [Figure 7] 10A and 10B show a portion of the model data, where (a) shows the relationship between the change area and the recirculation rate, (b) shows the relationship between the change area and the hematocrit value, (c) shows the relationship between the change area SA and the blood flow rate, and (d) shows the relationship between the change area SA and the UFR / membrane area. [Figure 8] FIG. 10 is a diagram showing an example of a regression equation obtained by multivariate analysis. [Figure 9]FIG. 2 is a schematic diagram of a blood purification device for explaining acquisition of treatment data. [Figure 10] FIG. 10 is a flow chart showing the flow of acquiring treatment data. [Figure 11] FIG. 10 illustrates the control of the pump in the process for acquiring in-treatment data. [Figure 12] FIG. 10 is a diagram illustrating the correlation between actual and estimated recirculation rates. [Figure 13] FIG. 10 is a graph showing the relationship between dialyzer ultrafiltration rate and blood marker detection time. [Figure 14] FIG. 10 is a flow chart showing an outline of a method for estimating the degree of clogging. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, preferred embodiments for carrying out the blood purification device of the present invention will be described with reference to the drawings. The blood purification device of the present invention purifies the blood of patients with renal failure or drug addiction. In addition, the blood purification device of the first embodiment of the present invention is capable of estimating the recirculation rate. In addition, the blood purification device of the second embodiment of the present invention is capable of estimating the degree of clogging in the blood purifier. Clogging in the blood purifier refers to clogging of components such as dialysis membranes provided in blood purifiers such as dialyzers.

[0012] (First embodiment) The first embodiment will be described with reference to Fig. 1. Fig. 1 is a diagram showing the schematic configuration of a blood purification apparatus 100 according to the first embodiment of the present invention.

[0013] (Blood purification device 100) 1, the blood purification apparatus 100 includes a blood circuit 110, a blood purifier 120, an arterial measuring means 111M, a venous measuring means 112M, a dialysate circuit 130, and a control unit 140. A part of the dialysate circuit 130 and the control unit 140 are disposed within a console 102. The console 102 also includes a replacement fluid pump 150 used to add a blood marker to the blood.

[0014] (Blood circuit 110) The blood circuit 110 has an arterial line 111, a venous line 112, a drug line 113, and a drainage line 114. The arterial line 111, the venous line 112, the drug line 113, and the drainage line 114 are all mainly made of flexible soft tubes that allow liquid to flow through them.

[0015] One end of the arterial line 111 is connected to a blood inlet 122a of a blood purifier 120, which will be described later. The arterial line 111 is provided with an arterial connector 111a, an arterial bubble detector 111b, and a blood pump 111c.

[0016] The arterial connector 111a is disposed at the other end of the arterial line 111. A needle to be inserted into the patient's blood vessel is connected to the arterial connector 111a. The arterial bubble detector 111b detects the presence or absence of air bubbles in the tube. The blood pump 111c is disposed downstream of the arterial bubble detector 111b in the arterial line 111. The blood pump 111c pumps out liquids such as blood and priming solution from inside the arterial line 111 by squeezing the tube that constitutes the arterial line 111 with a roller.

[0017] One end of venous line 112 is connected to a blood outlet 122b of blood purifier 120, which will be described later. Venous line 112 is provided with a venous connector 112a, a venous air bubble detector 112b, a drip chamber 112c, and a venous clamp 112d.

[0018] The venous connector 112a is located at the other end of the venous line 112. A needle to be inserted into the patient's blood vessel is connected to the venous connector 112a. The venous air bubble detector 112b detects the presence or absence of air bubbles in the tube. The drip chamber 112c is located upstream of the venous air bubble detector 112b. The drip chamber 112c stores a certain amount of blood or air to remove air bubbles and coagulated blood that have entered the venous line 112 and to measure venous pressure. The venous clamp 112d is located downstream of the venous air bubble detector 112b. The venous clamp 112d is controlled in accordance with the result of bubble detection by the venous air bubble detector 112b to open and close the flow path of the venous line 112.

[0019] Drug line 113 supplies a drug required during hemodialysis to arterial line 111. One end of drug line 113 is connected to drug pump 113a that delivers the drug. The other end of drug line 113 is connected to arterial line 111. Drug line 113 is also provided with clamping means (not shown). The flow path is closed by the clamping means except when a drug is being injected. In the first embodiment, the other end of drug line 113 is connected to arterial line 111 downstream of blood pump 111c.

[0020] The drain line 114 is connected to the drip chamber 112c. A drain line clamp 114a is disposed on the drain line 114. The process of washing and purifying the blood circuit 110 and the blood purifier 120 is called the priming process. The drain line 114 is a line for draining the priming solution during the priming process.

[0021] (Blood Purifier 120) The blood purifier 120 includes a cylindrical container body 121 and a dialysis membrane (not shown) housed inside the container body 121. The dialysis membrane may be, for example, a dialyzer. The interior of the container body 121 is partitioned by the dialysis membrane into a blood flow path and a dialysate flow path (neither of which is shown).

[0022] A blood inlet 122a and a blood outlet 122b are formed in the container body 121. The blood inlet 122a and the blood outlet 122b are connected to the blood circuit 110. The container body 121 also has a dialysate inlet 123a and a dialysate outlet 123b. The dialysate inlet 123a and the dialysate outlet 123b are connected to the dialysate circuit 130.

[0023] (Arterial side measurement means 111M) The arterial measuring means 111M is a sensor for measuring the condition of blood drawn from a patient. The arterial measuring means 111M is provided in the arterial line 111. In the first embodiment, the arterial measuring means 111M is disposed in the arterial line 111 near the blood inlet 122a of the blood purifier 120.

[0024] (Venous side measuring means 112M) The venous measuring means 112M is a sensor for measuring the state of blood being returned to the patient. The venous measuring means 112M is provided in the venous line 112. In the first embodiment, the venous measuring means 112M is disposed in the venous line 112 between the blood purifier 120 and the drip chamber 112c. The venous measuring means 112M is not essential for measuring blood recirculation. However, by measuring and comparing changes in the state of blood in both the arterial line 111 and the venous line 112, the measurement accuracy of blood recirculation can be improved compared to measuring blood recirculation based only on changes in the state of blood in the arterial line 111.

[0025] The blood condition measured by the arterial side measurement means 111M and the venous side measurement means 112M specifically includes the hematocrit value, hemoglobin value, and electrical resistivity, which change depending on the blood concentration. In the first embodiment, the hematocrit value is measured as an index showing the blood condition.

[0026] Furthermore, the arterial measuring means 111M and the venous measuring means 112M can continuously measure the state of the blood, thereby enabling the arterial measuring means 111M and the venous measuring means 112M to obtain data on changes over time regarding the state of the blood.

[0027] Furthermore, the arterial side measuring means 111M and the venous side measuring means 112M can acquire data on the blood flow rate in addition to the state of the blood. Note that the blood flow rate can also be measured by means other than the arterial side measuring means 111M and the venous side measuring means 112M. Alternatively, the blood flow rate can be measured by a measuring means, and the set speed of the blood pump can be used as data in addition to the acquired data.

[0028] According to the above-described blood circuit 110 and blood purifier 120, blood extracted from the artery of a dialysis patient, who is the subject, flows through the arterial line 111 by the blood pump 111c and is introduced into the blood flow path of the blood purifier 120. The blood introduced into the blood purifier 120 is purified by the dialysate flowing through the dialysate circuit 130, which will be described later, via the dialysis membrane. The blood purified in the blood purifier 120 flows through the venous line 112 and is returned to the subject's veins.

[0029] (dialysate circuit 130) In the first embodiment, the dialysate circuit 130 is configured as a so-called sealed volume control type dialysate circuit 130. The dialysate circuit 130 includes a dialysate supply line 131a, a dialysate drain line 131b, a dialysate inlet line 132a, a dialysate outlet line 132b, and a dialysate delivery unit 133.

[0030] The dialysate delivery unit 133 includes a dialysate chamber 1331, a bypass line 1332, and a water removal and backfiltration pump 1333. The dialysate chamber 1331 is composed of a hard container capable of holding a certain volume of dialysate. The certain volume means, for example, 300 mL to 500 mL. The interior of this container is divided by a soft diaphragm into a delivery fluid storage unit 1331a and a waste fluid storage unit 1331b. The diaphragm is also called a diaphragm. The bypass line 1332 connects the dialysate outlet line 132b and the dialysate drain line 131b.

[0031] The water removal / back-filtration pump 1333 is disposed in the bypass line 1332. The water removal / back-filtration pump 1333 is configured by a pump that drives the dialysis fluid inside the bypass line 1332 so as to be able to send the dialysis fluid in the water removal direction and the back-filtration direction. The water removal direction is the direction in which the dialysis fluid flows toward the dialysate drain line 131b. The back-filtration direction is the direction in which the dialysis fluid flows toward the dialysate outlet line 132b.

[0032] The base end of the dialysate supply line 131a is connected to a dialysate supply device (not shown), while the tip end of the dialysate supply line 131a is connected to a dialysate chamber 1331. The dialysate supply line 131a supplies the dialysate to a dialysate supply storage portion 1331a of the dialysate chamber 1331.

[0033] The dialysate introduction line 132a connects the dialysate chamber 1331 and the dialysate inlet 123a of the blood purifier 120. As a result, the dialysate introduction line 132a introduces the dialysate accommodated in the liquid supply accommodation section 1331a of the dialysate chamber 1331 into the dialysate-side flow path of the blood purifier 120.

[0034] The dialysate outlet line 132b connects the dialysate outlet 123b of the blood purifier 120 to the dialysate chamber 1331. As a result, the dialysate outlet line 132b delivers the dialysate discharged from the dialysate-side flow path of the blood purifier 120 to the waste fluid storage section 1331b of the dialysate chamber 1331.

[0035] The base end of the dialysate drain line 131b is connected to the dialysate chamber 1331. As a result, the dialysate drain line 131b discharges the effluent of the dialysate contained in the effluent container 1331b.

[0036] According to the above-described dialysate circuit 130, the interior of the hard container constituting the dialysate chamber 1331 is partitioned by a soft separating membrane, i.e., a diaphragm. As a result, in the dialysate circuit 130, the amount of dialysate drawn out from the dialysate chamber 1331 and the amount of effluent collected in the dialysate chamber 1331 can be made equal. The amount of dialysate drawn out from the dialysate chamber 1331 is equal to the amount of dialysate supplied to the dialysate supply container 1331a. Furthermore, the amount of effluent collected in the dialysate chamber 1331 is equal to the amount of effluent collected in the effluent container 1331b.

[0037] As a result, when the water removal and backfiltration pump 1333 is stopped, the flow rate of the dialysis fluid introduced into the blood purifier 120 can be made equal to the amount of dialysis fluid discharged from the blood purifier 120. The dialysis fluid discharged from the blood purifier 120 is also called drainage fluid.

[0038] When the water removal / backfiltration pump 1333 is driven to send fluid in the water removal direction, a predetermined amount of water is removed from the blood at a predetermined speed in the blood purifier 120. When the water removal / backfiltration pump 1333 is driven to send fluid in the backfiltration direction, a predetermined amount of dialysate is injected into the blood circuit 110 in the blood purifier 120. Injecting a predetermined amount of dialysate into the blood circuit 110 is also called backfiltration.

[0039] (control unit 140) The control unit 140 is configured with an information processing device such as a computer. Specifically, as shown in Fig. 2, the control unit 140 controls the operation of the blood purification apparatus 100 by executing a control program. Specifically, the control unit 140 controls the operation of various pumps, including a replacement fluid pump 150P, and clamps arranged in the blood circuit 110 and the dialysate circuit 130, to execute various processes performed by the blood purification apparatus 100. The various processes include, for example, a priming process, a blood removal process, a dialysis process, a replacement fluid process, and a blood return process.

[0040] Of the various steps mentioned above, the dialysis step and the fluid replacement step will be described. (dialysis process) In the dialysis process, excess water is removed from the patient and waste products are removed. In the dialysis process, the patient's blood is introduced from the arterial connector 111a and purified in the blood purifier 120 through the arterial line 111. The purified blood is returned to the patient through the venous line 112 and the venous connector 112a.

[0041] During the dialysis process, arterial connector 111a and venous connector 112a are connected to needles inserted into the patient's blood vessels, drainage line clamp 114a is closed, and venous clamp 112d is open.

[0042] (fluid replacement process) The fluid replacement step is a step aimed at increasing the patient's circulating blood volume. The fluid replacement step can be performed as needed when symptoms such as a drop in blood pressure or cramps occur during the dialysis step. The fluid replacement step can also be performed multiple times at regular intervals during the dialysis step in a planned manner to prevent a drop in blood pressure and improve peripheral circulation.

[0043] As a replacement fluid injection means, a blood purifier 120, a dialysis fluid introduction line 132a, a dialysis fluid discharge line 132b, and a dialysis fluid delivery section 133 are used, and the back-filtered dialysis fluid injected into the venous line 112 via the blood purifier 120 can be used as a replacement fluid.

[0044] The manner in which the fluid replacement step is performed is not limited to injecting the fluid replacement into the venous line 112 via the blood purifier 120. As another manner in which the fluid replacement step is performed, for example, depending on the configuration of the blood circuit 110, the fluid replacement can also be injected directly into the arterial line 111 or the venous line 112.

[0045] In the fluid replacement step, as in the dialysis step, the arterial connector 111a and the venous connector 112a are connected to needles that are inserted into the patient's blood vessels, respectively, and the drainage line clamp 114a is closed and the venous clamp 112d is open.

[0046] As explained above, the patient's circulating blood volume increases by the amount of fluid injected during the fluid replacement process. Therefore, in order to remove water to the patient's target weight during the dialysis process, if the water removal rate is constant, the dialysis process time must be extended. Furthermore, by increasing the water removal rate to remove the amount of water increased by the fluid replacement, it is possible to remove water to the target weight without extending the dialysis process time.

[0047] (Estimation of recirculation rate) The estimation of the recirculation rate will now be described. In the blood purification apparatus 100 of this embodiment, the recirculation rate can be estimated without measuring the state of blood before recirculation using the venous measuring means 112M. The estimation of the recirculation rate involves obtaining model data using a recirculation rate measurement model, performing multivariate analysis on the obtained model data, deriving a regression equation through the multivariate analysis, obtaining treatment data during hemodialysis treatment, and estimating the recirculation rate by inputting the treatment data into the regression equation. The estimation flow is shown below.

[0048] FIG. 3A is a flow diagram outlining the development of an analytical model for recirculation rate. (S1) S1 is the start step. At S1, the flow of estimating the recirculation rate starts. Here, S1 represents step 1. The same applies to the other steps. (S2) S2 is a model data acquisition step. In S2, data to be used for multivariate analysis in S3 is acquired. Data acquisition is performed using a recirculation rate measurement model. The data acquired in S2 is used as model data. (S3) S3 is the analysis step. In S3, the model data acquired in S2 is subjected to multivariate analysis. This multivariate analysis derives a regression equation with the recirculation rate as the response variable. (S4) S4 is the end step, at which the flow for creating the analytical model of the recirculation rate ends.

[0049] FIG. 3B is a flow chart showing a schematic configuration of the recirculation rate estimation method of this embodiment. (S11) S11 is the start step. At S11, the flow of estimating the recirculation rate begins. (S12) S12 is a treatment data acquisition step. In S12, data to be input into the regression equation derived in S3 is measured during actual treatment. Data can be measured from blood circulating in the arterial line or venous line. The data acquired in S12 is used as treatment data. (S13) S13 is a recirculation rate estimation step. In S13, the treatment data acquired in S12 is input into the regression equation derived in S3, thereby obtaining an estimated recirculation rate. (S14) S14 is the end step, at which the flow for estimating the recirculation rate ends.

[0050] In the above description, the multivariate analysis may be model creation by machine learning, in which case the regression equation may be a transformation model, and the input of treatment data into the regression equation may be treatment data into the transformation model.

[0051] The model data acquisition step S2 will now be described. (Recirculation rate measurement model) The recirculation rate measurement model 200 will be described with reference to Fig. 4. Fig. 4 is a diagram showing the schematic configuration of the recirculation rate measurement model 200. In the recirculation rate measurement model 200, the parts of the living body connected to the arterial side connector 111a and the venous side connector 112a in the blood purification apparatus 100 shown in Fig. 1 are replaced with a blood bottle 202 and a drainage bottle 204, etc. The following describes the recirculation rate measurement model 200, focusing on the differences from the blood purification apparatus 100 shown in Fig. 1.

[0052] The recirculation rate measurement model 200 includes a blood bottle 202 and a drainage bottle 204. Blood is supplied from the blood bottle 202 to the blood purifier 120 and other devices via the blood removal line 220 and arterial side connector 111a. This blood flow is indicated by arrow AR1.

[0053] The blood purified by the blood purifier 120 passes through the venous side connector 112a, passes through the return line 222, and returns to the blood bottle 202. This blood flow is indicated by an arrow AR2.

[0054] A first three-way stopcock 231 is disposed in the blood removal line 220. A second three-way stopcock 232 and a third three-way stopcock 233 are disposed in the return line 222. The first three-way stopcock 231 and the second three-way stopcock 232 are connected by a recirculation line 226. A metering pump 240 is provided in the recirculation line 226.

[0055] The third three-way stopcock 233 is connected to the drain bottle 204 via the drain line 224 .

[0056] In the recirculation rate measurement model 200, the flow direction of the three three-way stopcocks can be switched between a non-recirculating state and a recirculating state.

[0057] (without recirculation) The flow of blood without recirculation is indicated by arrow L10. Without recirculation, blood flows from the blood bottle 202 through the blood removal line 220 toward the arterial connector 111a. The first three-way stopcock 231, located between the blood bottle 202 and the arterial connector 111a, is opened so that the blood does not flow through the recirculation line 226 but flows through the blood removal line 220. Therefore, the entire amount of blood flows toward the arterial connector 111a.

[0058] Regarding the blood returning from venous connection part 112a to blood bottle 202, the second and third three-way stopcocks 232 and 233 are opened in the following directions. That is, the second three-way stopcock 232 is opened so that the blood does not flow through recirculation line 226, but rather all of the blood flows through return line 222. The third three-way stopcock 233 is opened so that the blood does not flow through blood bottle 202, but rather all of the blood flows through drain line 224. This is to prevent blood markers from flowing into the blood removal line. Therefore, the entire amount of blood from venous connection part 112a flows through drain line 224 and into drain bottle 204.

[0059] (Recirculating state) The flow of blood during recirculation is indicated by arrow L11. During recirculation, blood flows from the blood bottle 202 through the blood removal line 220 toward the arterial connection part 111a. The first three-way stopcock 231 located along the line is opened in three directions, including the recirculation line 226, so that blood flows through the blood removal line 220. The blood flow up to this point is the same as when not recirculating. Note that when the metering pump 240 is stopped, the flow path of the recirculation line 226 is blocked, and therefore blood does not flow from the blood removal line 220 to the return line 222.

[0060] During recirculation, the blood flowing through the recirculation line 226 merges with the blood flowing through the blood removal line 220 at the first three-way stopcock 231. This blood flowing through the recirculation line 226 corresponds to the recirculated blood.

[0061] A portion of the blood flowing from venous connection 112a through return line 222 is recirculated, and the remainder is discarded in a drain bottle. With respect to the return flow of blood from venous connection 112a toward blood bottle 202, the opening directions of second and third three-way stopcocks 232 and 233 are oriented as follows: second three-way stopcock 232 is opened so that a portion of the blood flows through recirculation line 226 and the remaining blood flows through return line 222.

[0062] The opening direction of the third three-way stopcock 233 is such that the entire amount of blood flows through the drainage line 224 .

[0063] A state in which blood is recirculating can be created by orienting the opening directions of second three-way stopcock 232 and third three-way stopcock 233 as described above. Also, by adjusting the opening direction of second three-way stopcock 232 and the ratio of the blood flow rate by blood pump 111c and the flow rate by metering pump 240, various recirculation rates can be achieved.

[0064] (blood markers) Blood Markers: As blood markers to be added to extracorporeally circulated blood, for example, backfiltration replacement fluid, online replacement fluid (pre-dilution or post-dilution), and filtration can be used.

[0065] Backfiltration replacement fluid refers to the injection of replacement fluid into the dialyzer included in the blood purifier 120. Predilution refers to the injection of replacement fluid into the blood upstream of the blood purifier 120. Postdilution refers to the injection of replacement fluid into the blood downstream of the blood purifier 120. Filtration refers to the removal of water in the filtration direction in the dialyzer included in the blood purifier 120.

[0066] The application of a blood marker means temporarily changing the blood concentration by injecting or filtering a replacement fluid into the blood. This temporarily changed blood concentration becomes the marker. Note that the replacement fluid may be a fluid other than the dialysis fluid, or the dialysis fluid may be used as the replacement fluid.

[0067] (Blood marker administration) The positions on the line where the blood marker is applied to the blood will be explained. Figure 4 shows the points where the blood marker is applied, from point P1 to point P4. The points where the blood marker is applied are the points where replacement fluid is injected into the blood or the points where the blood is filtered.

[0068] Point P1 indicates the point at which the first blood marker is applied. The first blood marker application point P1 is the point at which the blood marker is applied when the blood marker is applied by backfiltration. The first blood marker application point P1 is located, for example, on dialysate introduction line 132a.

[0069] Point P2 indicates the point at which the second blood marker is applied. The second blood marker application point P2 is the point at which the blood marker is applied when the blood marker is pre-diluted. The second blood marker application point P2 is located, for example, on the arterial line 111.

[0070] Point P3 indicates the point at which the third blood marker is applied. The third blood marker application point P3 is the point at which the blood marker is applied when the blood marker is post-diluted. The third blood marker application point P3 is located, for example, on the venous line 112.

[0071] Point P4 indicates the application point of the fourth blood marker. The fourth application point P4 is the application point of the blood marker when the blood marker is filtration. The fourth application point P4 is located, for example, on the dialysate outlet line 132b.

[0072] (Blood concentration measurement) Adding blood markers to the blood through fluid replacement decreases blood concentration. Adding blood markers to the blood through filtration increases blood concentration. This change in blood concentration is detected by the measuring unit. The measuring unit is the part that measures blood concentration over time. The measuring unit is located in different positions depending on the type of blood marker.

[0073] The measurement unit was configured as the following recirculation rate measurement model 200 so as to measure blood before it passed through the blood purifier. That is, it was placed upstream of the point where the blood marker was applied and downstream of the recirculation line 226. This is because the blood that flowed through the recirculation line 226 corresponds to the recirculated blood.

[0074] If the blood marker is backfiltration, post-dilution, or filtration, the measurement unit can be the arterial measurement means 111M, because the arterial measurement means 111M is disposed upstream of the first and third application points P1 and P3 and downstream of the recirculation line 226.

[0075] If the blood marker is pre-diluted, the measurement unit can be the second arterial measurement means 111M'. The second arterial measurement means 111M' is arranged downstream of the first three-way stopcock 231 in the return line 222. If the blood marker is pre-diluted, the measurement unit cannot be the arterial measurement means 111M. This is because the arterial measurement means 111M is arranged downstream of the second application point P2 and downstream of the recirculation line 226.

[0076] (Blood marker detection) Detection of blood markers by fluid replacement will be described with reference to Figures 5 and 6. Figure 5 shows the change over time in blood concentration measured by the measurement unit. Figure 6 is a schematic diagram showing a part of the blood purification device 1. Detection of blood markers by filtration is similar, except that the change in blood concentration is the opposite of that by fluid replacement.

[0077] In the graph shown in Figure 5, the horizontal axis is time and the vertical axis is hematocrit value. Here, hematocrit value is used as a value indicating blood concentration. Hematocrit value is a numerical value indicating the percentage of red blood cells in the blood by volume. As shown in Figure 6, when blood to which a blood marker has been added is recirculated in the living body, a change in blood concentration is detected at the measurement unit. This is because the change in blood concentration due to the addition of the blood marker is detected at the measurement unit without being attenuated in the living body.

[0078] H in Figure 5 A indicates the average hematocrit value. As shown in Figure 5, for the blood after recirculation, the time T S Due to the blood markers infused with fluid, the hematocrit value began to drop sharply at time T1, and the hematocrit value reached an average value of H A The time T B At time T, the hematocrit reaches its lowest value and begins to rise. B Hematocrit value and average H A The difference between and is the drop width H B is.

[0079] The hematocrit value is calculated at time T E At time T1 to time T E The average hematocrit value H A The amount of change from S A This change amount is S A In Figs. 5 and 6, the change area S A The change area S A corresponds to the change in blood concentration.

[0080] The time T1 is the timing at which the detector begins to detect the marker added by recirculation, and is calculated from the filling volume in the circuit and the speed of the blood pump. For example, if the blood filling volume in the circuit is 200 mL and the blood pump speed is 250 mL / min, 200 / 250=0.8(≒50 seconds=(T1-T s )) becomes. By having the detector start detection from time T1, the detection accuracy can be improved and false detection can be suppressed.

[0081] (Model data) In this embodiment, the recirculation rate measurement model 200 is used to acquire model data for determining a regression equation, which will be described later. The model data includes data showing the change in blood concentration after recirculation when a predetermined amount of blood marker is added to extracorporeally circulating blood, data showing the relationship between the change in blood concentration after recirculation and blood concentration, data showing the relationship between the change in blood concentration after recirculation and blood flow rate, data showing the relationship between the blood marker detection time, which is the time from recirculation to detection of the blood marker, and the type of dialyzer used in the recirculation rate measurement model, and data showing the relationship between the type of dialyzer and the change in blood concentration after recirculation. The predetermined amount of blood marker is not particularly limited, and can be, for example, the minimum amount that can be detected.

[0082] The aforementioned measuring unit can be configured to measure items other than blood concentration, such as blood flow rate, in addition to blood concentration. Alternatively, a measuring unit separate from the aforementioned measuring unit can be provided to measure items other than blood concentration.

[0083] The model data can be acquired under the following conditions, for example: The model parameters and their setting values are listed below. Planned amount of fluid replacement: 20 mL Fluid replacement rate: 250mL / min

[0084] Also, the change area S A The following is a list of examples of the change factors and the corresponding test conditions: Recirculation rate: 0% or more and 100% or less Ht (hemacrit value (bovine blood type)): 10% to 50% Blood flow (QB:Quantity of Blood flow): 100mL / min or more and 400mL / min or less UFR / membrane area: 6 or more and 52.3 or less UFR: 12mL / mmHg / hr or more and 84mL / mmHg / hr or less Membrane area: 0.8 square meters or more and 2.5 square meters or less

[0085] UFR refers to the ultrafiltration rate of the dialyzer. Membrane area refers to the area of the hollow fiber membrane. The recirculation rate can be set to various rates by adjusting the opening direction of each of the three-way stopcocks or the output of the metering pump 240.

[0086] Figure 7 shows some of the model data obtained using the recirculation rate measurement model 200. Figure 7(a) shows the change area S A Fig. 7(b) is a graph showing the relationship between the change area S A 7(c) is a graph showing the relationship between the change area S A 7(d) is a graph showing the relationship between the change area S A 1 is a graph showing the relationship between the UFR and the membrane area. Note that the UFR / membrane area usually varies depending on the type of dialyzer.

[0087] 7(a) to 7(d) show the cases where the blood marker is back-filtered, pre-diluted, and post-diluted. As shown in FIGS. 7(a), 7(b), and 7(d), the change area S A and recirculation rate, change area S A and hemacrit value, and the change area S A The relationship between the UFR and the membrane area has a linear characteristic correlation.

[0088] The strength of the correlation is shown in Fig. 7(d) as the change area S A A correlation has been shown between UFR and UFR / membrane area, except in cases where blood markers are post-diluted and do not pass through the blood purifier.

[0089] Also, as shown in Figure 7(c), the change area S AThe relationship between the BP and blood flow (QB) has an exponential characteristic correlation.

[0090] The analysis step S3 will now be described. (Multivariate analysis) The model data acquired in the model data acquisition step S2 is subjected to multivariate analysis. The model data is a combination of two correlated values. By analyzing the model data, a regression equation with the recirculation rate as the response variable is obtained.

[0091] As an example of multivariate analysis, the change area S shown in Figure 7(a) A The model data showing the relationship between the recirculation rate and the change area S shown in Fig. 7(b) A The model data showing the relationship between the hematocrit value and the change area S A Multivariate analysis is performed using model data showing the relationship between UFR and UFR / membrane area.

[0092] 8 is a diagram showing an example of a regression equation obtained by multivariate analysis. The analysis method used for the multivariate analysis is not particularly limited. For example, multiple regression analysis can be used as the analysis method.

[0093] Change area S A Model data showing the relationship between the area change and the recirculation rate, S A and hemacrit value, and the change area S A When performing multivariate analysis using model data showing the relationship between UFR and membrane area, and determining a regression equation with recirculation rate as the objective variable, the explanatory variables are the change in blood concentration after recirculation, blood concentration, and blood flow rate. Here, the change in blood concentration after recirculation is determined by the change area S A The content is the same as above.

[0094] (Variation) The types of model data used in the multivariate analysis and the explanatory variables of the regression equation are not limited to the above examples. Any data that is correlated with the recirculation rate can be used for the multivariate analysis. In addition, explanatory variables can be set according to the data used in the multivariate analysis.

[0095] Another example will be explained. The time from administration of the blood marker to detection of the blood marker is defined as the blood marker detection time. The blood marker detection time can also be added as an explanatory variable in the regression equation. The blood marker detection time is correlated with the type of dialyzer. The type of dialyzer corresponds to UFR / membrane area shown in Figure 7(d). This is because UFR / membrane area is determined by the type of dialyzer. Furthermore, UFR / membrane area is calculated by the change area S A Furthermore, the change area S A is correlated with the recirculation rate. Therefore, when deriving a regression equation with the recirculation rate as the objective variable, data on blood marker detection time can be included in the data used for multivariate analysis. Furthermore, by including data on blood marker detection time in the multivariate analysis, blood marker detection time can be included as an explanatory variable in the regression equation.

[0096] Specifically, the following additional data are acquired: data showing the relationship between the blood marker detection time and the type of dialyzer used in the recirculation rate measurement model; and data showing the relationship between the type of dialyzer and the amount of change in blood concentration after recirculation. More precisely, the blood marker detection time is the time from when a predetermined amount of blood marker is added to the extracorporeally circulating blood to when the blood marker is detected after recirculation.

[0097] Next, multivariate analysis is performed including the additional data obtained. In this way, a regression equation can be obtained that includes the blood marker detection time as an explanatory variable.

[0098] In determining the blood marker detection time, the time point at which the blood marker is detected is the time T B That is, when detecting a blood marker, the change in blood concentration is acquired over time. Then, after administering the blood marker, the time when the blood concentration changes from a decrease to an increase can be regarded as the time when the blood marker is detected.

[0099] By increasing the types of model data and the types of explanatory variables in the regression equation, it may be possible to use the regression equation to estimate a circulation rate that is closer to the actual recycling rate.

[0100] Each step from step S1 to step S3 for obtaining the regression equation can be performed, for example, by an analysis device equipped with recirculation rate measurement model 200. This analysis device can include a model data acquisition unit that acquires model data using recirculation rate measurement model 200, and an analysis unit that performs multivariate analysis using the model data to obtain the regression equation.

[0101] The treatment data acquisition step S12 will now be described. In the treatment data acquisition step S12, various data are acquired during actual hemodialysis treatment. To distinguish the data acquired during hemodialysis treatment from model data acquired using a recirculation rate measurement model, the data acquired during treatment is referred to as treatment data. The treatment data is acquired in order to estimate the recirculation rate by inputting the data into a regression equation.

[0102] The type of data acquired as treatment data corresponds to the explanatory variables of the regression equation used to estimate the recirculation rate. For example, if the explanatory variables of the regression equation are the change in blood concentration after recirculation, blood concentration, and blood flow rate, the change in blood concentration after recirculation, blood concentration, and blood flow rate are acquired during treatment. Furthermore, if the explanatory variables of the regression equation include blood marker detection time, the blood marker detection time is also acquired during treatment.

[0103] The type of blood marker used when acquiring treatment data should be the same as the type of blood marker used when acquiring model data. For example, if backfiltration was used as a blood marker when acquiring model data, backfiltration should also be used as a blood marker when acquiring treatment data. This allows for more accurate estimation of the recirculation rate.

[0104] (Treatment device) 9 is a diagram showing the schematic configuration of the blood purification apparatus 100 used to acquire treatment data. The following explanation will focus on the parts that are different from those explained in FIGS.

[0105] During actual hemodialysis treatment, the arterial line 111 and the venous line 112 are connected to the living body.

[0106] 9 indicates the point at which the blood marker is applied when the blood marker is applied by backfiltration. The point at which the blood marker is applied corresponds to the case where the blood purification device 100 is under automatic backfiltration control.

[0107] Arrow B in Figure 9 indicates the flow of fluid replacement etc. when the blood marker is pre-diluted. When fluid replacement etc. flows in the direction of arrow B, it corresponds to the case where the blood purification apparatus 100 is automatically controlled for pre-dilution online.

[0108] Arrow C in Figure 9 indicates the flow of fluid replacement etc. when the blood marker is post-diluted. When fluid replacement etc. flows in the direction of arrow C, this corresponds to the case where the blood purification apparatus 100 is automatically controlled for post-dilution online.

[0109] 9 indicates the point at which the blood marker is applied when the blood marker is filtration. The point at which the blood marker is applied corresponds to the case where the blood purification apparatus 100 is under filtration control.

[0110] 9, a replacement fluid pump 150 used to add a blood marker to blood is provided on a console 102 of a blood purification apparatus 100 used for treatment. Replacement fluid or dialysis fluid as replacement fluid is supplied from the replacement fluid pump 150 to a second addition point P2 or a third addition point P3 via a replacement fluid line 152.

[0111] Specifically, when the blood marker is pre-diluted, replacement fluid or the like is supplied by pressure from replacement fluid pump 150 along arrow B through replacement fluid line 152 to second supply point P2.

[0112] Furthermore, when the blood marker is post-diluted, replacement fluid or the like is pressurized by replacement fluid pump 150 and supplied along arrow C through replacement fluid line 152 to third supply point P3.

[0113] In the blood purification apparatus 100 shown in Figure 9, a pressure monitor line 160 is connected to the drip chamber 112c. Figure 9 also shows examples of the flow rates of each line.

[0114] (measurement) Measurement of blood concentration and the like will now be described. Measurement can be performed by the measurement unit described above. The measurement unit described above includes, for example, the arterial side measurement means 111M or the second arterial side measurement means 111M'. For example, a circulating blood volume monitor (hematocrit measurement device) can be used as the measurement unit. Furthermore, the blood purification device 100 of this embodiment does not require measurement of blood concentration and the like on the venous side. In the blood purification device 100 of this embodiment, the recirculation rate can be estimated by measuring blood concentration and the like only on the arterial side.

[0115] An example of acquiring treatment data will be described in more detail with reference to Figures 10 and 11. Figure 10 is a flow diagram showing the flow of acquiring treatment data. Also, Figure 11 is a diagram showing the control of each pump in each step for acquiring treatment data. Below, the measurement flow during treatment will be described with reference to Figures 10 and 11. K2 in Figure 10 means step 2. The same applies to the other steps. Also, the step numbers in Figure 10 correspond to the step numbers in Figure 11.

[0116] (Process 1) Step 1 is a step before the start of the measurement flow for acquiring treatment data. In step 1, the water removal and backfiltration pump 1333 rotates forward, reverse, or is stopped as appropriate. In FIG. 11, the water removal and backfiltration pump 1333 is simply referred to as the water removal pump. The replacement fluid pump 150 rotates or is stopped as appropriate. The blood pump 111c is rotating, and dialysis treatment is being performed.

[0117] (Process 2) The measurement flow starts in step 2. In step 2, the ultrafiltration pump 1333, the replacement fluid pump 150, and the blood pump 111c are operating in the same manner as in step 1.

[0118] (Step 3) Step 3 is a circulation step. In step 3, the ultrafiltration pump 1333 and the replacement fluid pump 150 are stopped. The blood pump 111c operates in the same manner as in step 1. This allows blood to circulate through the blood circuit 110 without the supply of replacement fluid or the like.

[0119] (Step 4) Step 4 is a step of determining whether the blood purification state is stable. In step 4, it is determined whether the blood purification state is stable. Since step 4 is a step of determining whether the blood purification state is stable, the ultrafiltration pump 1333 and the replacement fluid pump 150 are stopped, as in step 3.

[0120] If it is determined that the state of blood purification is stable, proceed to step 5. If it is not determined that the state of blood purification is stable, proceed to step 8 and the measurement flow ends. Whether the state of blood purification is stable or not can be determined, for example, by changes in blood concentration over time.

[0121] (Step 5) Step 5 is a circuit internal pressure stabilization step. In step 5, the blood pump 111c is stopped in addition to the ultrafiltration pump 1333 and the fluid replacement pump 150, which were stopped in step 4. By stopping the blood circulation, the internal pressure of the blood circuit 110 is stabilized.

[0122] (Step 6) Step 6 is a blood marker application step. Control of the water removal pump 1333 and the replacement fluid pump 150 differs depending on the type of blood marker applied. When the blood marker is backfiltration, the backfiltration replacement fluid is controlled by rotating the water removal pump 1333 in the reverse direction and stopping the replacement fluid pump 150. When the blood marker is filtration, the water removal is controlled by rotating the water removal pump 1333 in the forward direction and stopping the replacement fluid pump 150.

[0123] When the blood marker is pre-dilution or post-dilution, the online fluid replacement control causes the water removal pump 1333 to rotate in reverse and the fluid replacement pump 150 to rotate. In the case of pre-dilution, a fluid replacement or the like is infused into the arterial line 111 from the second infusion point P2. On the other hand, in the case of post-dilution, a fluid replacement or the like is infused into the venous line 112 from the third infusion point P3.

[0124] Regardless of the type of blood marker applied, the blood pump 111c rotates at a rotation speed of, for example, 30 mL / min.

[0125] (Step 7) Step 7 is the blood marker measurement step. The blood pump 111c rotates under the conditions before measurement. This allows blood circulation to continue as it did during treatment. Meanwhile, the ultrafiltration pump 1333 and the replacement fluid pump 150 are stopped. This allows the effects of only the blood markers applied in step 6 to be measured.

[0126] (Step 8) Step 8 is the final step. The ultrafiltration pump 1333, the replacement fluid pump 150, and the blood pump 111c continue to operate in the state of step 7.

[0127] (Step 9) Step 8 is a step after measurement. Measurement is completed in step 8. Therefore, the ultrafiltration pump 1333, the fluid replacement pump 150, and the blood pump 111c return to the states of step 1, which is a step before measurement.

[0128] The supply of replacement fluid, measurement of various values, operation of each pump, and the like related to the acquisition of treatment data as described above can be controlled by the control unit 140 described above.

[0129] The recirculation rate estimation step S13 will now be described. In S13, the treatment data acquired in S12 is input into the regression equation derived in S3. This makes it possible to obtain an estimated recirculation rate.

[0130] An example of the correlation between the recirculation rate estimated in step S13 and the actual recirculation rate is shown in FIG. 12. FIG. 12 is a diagram showing the correlation between the estimated recirculation rate and the actual recirculation rate. The horizontal axis of the graph shown in FIG. 12 is the actual recirculation rate. The vertical axis of the graph shown in FIG. 12 is the estimated recirculation rate. The actual recirculation rate is the actual recirculation rate. The estimated recirculation rate is the recirculation rate estimated in step S13.

[0131] As shown in FIG. 12, there is a correlation between the estimated recirculation rate and the actual recirculation rate. The estimated recirculation rate is approximately equal to the actual recirculation rate. The graph in FIG. 12 shows an example in which backfiltration replacement fluid was used as the blood marker. Even when online replacement fluid (pre-dilution or post-dilution) or filtration was used as the blood marker, the estimated recirculation rate was approximately equal to the actual recirculation rate, as in the example of backfiltration replacement fluid shown in FIG. 12.

[0132] The steps of obtaining the estimated recirculation rate in steps S12 and S13 can be performed, for example, under the control of the control unit 140 of the blood purification apparatus 100. When performed under the control of the control unit 140, the control unit 140 can include a treatment data acquisition unit that acquires treatment data using each unit arranged in the blood circuit 110, and a recirculation rate estimation unit that inputs the treatment data acquired by the treatment data acquisition unit into a regression equation determined by an analysis device to estimate the recirculation rate.

[0133] The method for estimating the recirculation rate of the first embodiment makes it possible to estimate the recirculation rate without being restricted by the location of the blood marker production and the location of the blood marker detection means, because there is no need to place a measurement means on the venous side, and there is more freedom in determining the location of the blood marker production and the location of the blood marker detection means.

[0134] (Second embodiment) A second embodiment will be described. The second embodiment relates to a method for estimating the degree of clogging of a dialyzer used in the blood purifier 120. The second embodiment will be described below, focusing on the differences from the first embodiment.

[0135] The degree of clogging of the dialyzer can be estimated based on the blood marker detection time, which is the time from when a predetermined amount of blood marker is added to the extracorporeally circulating blood to when the blood marker is detected after passing through the dialyzer.

[0136] In determining the blood marker detection time, the time point at which the blood marker is detected is the time T B That is, to detect a blood marker, blood concentration is acquired over time. Then, after administering the blood marker, the time when the blood concentration changes to an extreme value can be regarded as the time when the blood marker is detected.

[0137] Figure 13 shows the relationship between UFR and time T B Figure 13 shows the relationship between UFR per unit area and time T B 13 is a graph showing the relationship between the UFR / ESA and the time T B UFR is the ultrafiltration rate of the dialyzer. ESA is the membrane area of the dialyzer. Time T B indicates the blood marker detection time.

[0138] As shown in Figure 13, as UFR increases, T B This indicates that as the dialyzer's water permeability increases, the blood marker detection time decreases. In other words, as the dialyzer's water permeability decreases, the blood marker detection time increases. Here, the decrease in dialyzer water permeability is caused by clogging of the dialyzer. Therefore, the graph in Figure 13 indicates that as the dialyzer becomes clogged, the blood marker detection time increases.

[0139] From the above, it is possible to estimate the degree of clogging of the dialyzer by measuring the blood marker detection time. Measuring the blood marker detection time not only identifies the type of dialyzer as described in the first embodiment, but also makes it possible to estimate the degree of clogging of the membrane during dialysis treatment. Furthermore, by measuring the blood marker detection time over time, it is possible to estimate the degree of clogging over time.

[0140] In the second embodiment, the application of the blood marker to the blood and the measurement of the blood concentration can be performed by the same means as in the first embodiment.

[0141] However, in the second embodiment, the blood marker is applied by one of the following methods: injecting replacement fluid into the blood upstream of the blood purifier 120, injecting replacement fluid into the blood purifier 120 in the backfiltration direction, and performing dehydration in the blood purifier 120 in the filtration direction. In other words, in the first embodiment, the blood marker was applied by selecting from backfiltration replacement fluid, online replacement fluid (pre-dilution or post-dilution), and filtration. In contrast, in the second embodiment, the blood marker is applied by any of backfiltration, pre-dilution, and filtration. In post-dilution, the replacement fluid is supplied downstream of the blood purifier 120. Therefore, post-dilution is inappropriate for detecting clogging in the blood purifier 120. For application of the blood marker during backfiltration, pre-dilution, or filtration, the same means as those described in the first embodiment can be used as the blood marker application means in the second embodiment.

[0142] The flow of the method for estimating the degree of clogging of a dialyzer described above can be summarized as follows: Figure 14 is a flow chart showing the flow of the method for estimating the degree of clogging of a dialyzer.

[0143] (S21) The estimation flow starts in step S21. (S22) Step S22 is a blood marker application step. In step S22, a predetermined amount of blood marker is applied to the extracorporeally circulating blood in actual hemodialysis treatment using the blood purifier 120. The predetermined amount may be, for example, an amount that does not interfere with treatment and allows detection of the blood marker. (S23) Step S23 is a blood marker detection step, in which blood markers are detected from the blood that has passed through the blood purifier 120. (S24) Step S24 is a blood marker detection time acquisition step, in which the blood marker detection time, which is the time from when the blood marker is applied to when the blood marker is detected, is acquired. (S25) Step S25 is a clogging degree estimation step, in which the degree of clogging of the dialyzer included in the blood purifier 120 is estimated from the blood marker detection time acquired in step S24. (S26) At step S26, this estimation flow ends.

[0144] The method for estimating the degree of clogging, specifically, the above-mentioned steps S22 to S25, can be performed, for example, under the control of the control unit 140 of the blood purification apparatus 100. When performed under the control of the control unit 140, the control unit 140 controls the blood marker applying means that applies a blood marker to the blood in the blood purifier 120 or the arterial line 111, and the arterial side measuring means 111M or the second arterial side measuring means 111M' that is provided in the arterial line 111 and measures the state of the blood circulating through the arterial line 111, and can estimate the degree of clogging of the blood purifier 120 based on the blood marker detection time.

[0145] It is also possible to obtain a quantitative relationship between the blood marker detection time and the degree of clogging in the dialyzer in advance, which allows the degree of clogging in the dialyzer to be estimated with high accuracy by measuring the blood marker detection time.

[0146] Furthermore, the relationship between the blood marker detection time and the degree of clogging can be obtained for each dialyzer, because the relationship between the blood marker detection time and the degree of clogging may differ depending on the type of dialyzer.

[0147] Although each preferred embodiment of the blood purification apparatus of the present invention has been described above, the present invention is not limited to the above-described embodiments and can be modified as appropriate.

[0148] For example, in the second embodiment, the object for estimating the degree of clogging is not limited to the dialyzer. If the blood purifier 120 is equipped with a component other than the dialyzer, such as a dialysis membrane for blood purification, that component can also be the object. Clogging can also be estimated by measuring the blood concentration before recirculation.

[0149] The estimation of the degree of clogging described above can be performed without changing the treatment operation of a normal blood purification device. Furthermore, by understanding the clogging of the membrane over time, it is possible to control filtration or backfiltration that reflects the clogging state. Furthermore, the combination of treatment conditions, dialyzer, and blood circuit varies from patient to patient. Understanding the degree of clogging of the dialyzer makes it possible to maximize the dialyzer membrane characteristics and perform optimal dialysis that is most suitable for the patient.

[0150] <1> Using a recirculation rate measurement model, when a predetermined amount of blood marker is added to the extracorporeally circulating blood, Data showing the change in blood concentration after recirculation; Data showing the relationship between the change in blood concentration after recirculation and the blood concentration; and a model data acquisition step of acquiring data showing the relationship between the change in blood concentration after recirculation and the blood flow rate; an analysis step of creating a model by multivariate analysis or machine learning using the model data acquired in the model data acquisition step, and determining a regression equation or a transformation model with the change in blood concentration after recirculation, blood concentration, and blood flow rate as explanatory variables and the recirculation rate as a response variable; a treatment data acquisition step of acquiring data indicating a change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment; a recirculation rate estimation step of estimating a recirculation rate by inputting the treatment data acquired in the treatment data acquisition step into the regression equation or transformation model obtained in the analysis step. <2> The change in blood concentration after the recirculation and the change in blood concentration of the blood circulating through the arterial line or the venous line are represented as an area surrounded by a time axis and a line indicating the blood concentration at each time. <1> A method for estimating a recirculation rate according to claim 1. <3> The blood concentration is a hematocrit value. <1> or <2> A method for measuring a recirculation rate according to claim 1. <4> The multivariate analysis is a multiple regression analysis. <1> from <3> A method for measuring a recirculation rate according to any one of the above. <5> In the model data acquisition step, Additional data showing the relationship between the blood marker detection time, which is the time from when a predetermined amount of blood marker is added to the blood circulating extracorporeally to when the blood marker is detected after recirculation, and the type of dialyzer used in the recirculation rate measurement model; and Obtain additional data showing the relationship between dialyzer type and the amount of change in blood concentration after recirculation. In the analyzing step, Perform a multivariate analysis including the additional data, A regression equation is obtained that includes the blood marker detection time as an explanatory variable, In the treatment data acquisition step, acquiring data indicating the blood marker detection time during hemodialysis treatment; In the recirculation rate estimation step, the recirculation rate is estimated by further inputting the blood marker detection time acquired in the treatment data acquisition step into the regression equation or transformation model obtained in the analysis step; <1> from <4> A method for estimating a recirculation rate according to any one of the above. <6> The hemodialysis treatment is performed using a blood purification device, the recirculation rate measurement model and the blood purification device include a blood purifier; The administration of the blood marker includes: injecting a replacement fluid into the blood upstream of the blood purifier; injecting a replacement fluid into the blood downstream of the blood purifier; flowing replacement fluid in a back-filtration direction in a dialyzer included in the blood purifier; The method is performed by one of performing water removal in the filtration direction in a dialyzer included in the blood purifier and providing a blood marker by filtration. <1> from <5> A method for estimating a recirculation rate according to any one of the above. <7> The time point at which the change in blood concentration after recirculation begins to be measured is determined from the filling volume of the circuit and the speed of the blood pump in the recirculation rate measurement model. <1> from <6> A method for estimating a recirculation rate according to any one of the above. <8> An analysis device for determining a regression equation for estimating a blood recirculation rate in hemodialysis treatment, comprising: Using the recirculation rate measurement model, when a predetermined amount of blood marker is added to the extracorporeally circulating blood, Data showing the change in blood concentration after recirculation; Data showing the relationship between the change in blood concentration after recirculation and the blood concentration; and a model data acquisition unit that acquires data showing the relationship between the amount of change in blood concentration after recirculation and the blood flow rate; and an analysis unit that performs multivariate analysis or machine learning using the model data acquired by the model data acquisition unit to obtain a regression equation or a transformation model in which the change in blood concentration after recirculation, the blood concentration, and the blood flow rate are used as explanatory variables and the recirculation rate is used as a response variable. <9> A blood purification device capable of estimating a blood recirculation rate, a treatment data acquisition unit that acquires data indicating a change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment; <8> and a recirculation rate estimation unit that estimates a recirculation rate by inputting treatment data acquired by the treatment data acquisition unit into the regression equation or transformation model determined by the analysis device described in claim 1. [Explanation of symbols]

[0151] 100 Blood Purification Device 102 Console 110 Blood circuit 111 Arterial line 112 Venous line 113 Drug Line 114 Drainage Line 120 Blood Purifier 121 Container body 130 Dialysate circuit 133 Dialysate feeding section 1331 Dialysis fluid chamber 1332 Bypass Line 1333 Water removal and backfiltration pump 140 Control Unit 150 Infusion pump 152 Fluid replacement line 160 Pressure Monitor Line 200 Recirculation Rate Measurement Model 202 Blood Bottle 204 Drainage Bottle 220 Blood Drainage Line 222 Return Line 224 Drainage Line 226 Recirculation Line 231 First three-way stopcock 232 Second three-way stopcock 233 Third three-way stopcock 240 Metering Pump

Claims

1. Using a recirculation rate measurement model, when a predetermined amount of blood marker is added to the extracorporeally circulating blood, Data showing the change in blood concentration after recirculation; Data showing the relationship between the change in blood concentration after recirculation and the blood concentration; and a model data acquisition step of acquiring data showing the relationship between the change in blood concentration after recirculation and the blood flow rate; an analysis step of creating a model by multivariate analysis or machine learning using the model data acquired in the model data acquisition step, and determining a regression equation or a transformation model with the change in blood concentration after recirculation, blood concentration, and blood flow rate as explanatory variables and the recirculation rate as a response variable; a treatment data acquisition step of acquiring data indicating a change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment; a recirculation rate estimation step of estimating a recirculation rate by inputting the treatment data acquired in the treatment data acquisition step into the regression equation or transformation model obtained in the analysis step.

2. 2. The method for estimating a recirculation rate according to claim 1, wherein the change in blood concentration after recirculation and the change in blood concentration of the blood circulating through the arterial line or the venous line are expressed as an area surrounded by a time axis and a line indicating the blood concentration at each time.

3. The method for measuring a recirculation rate according to claim 1 or 2, wherein the blood concentration is a hematocrit value.

4. The method for measuring a recirculation rate according to claim 1 or 2, wherein the multivariate analysis is a multiple regression analysis.

5. In the model data acquisition step, Additional data showing the relationship between the blood marker detection time, which is the time from when a predetermined amount of blood marker is added to the blood circulating extracorporeally to when the blood marker is detected after recirculation, and the type of dialyzer used in the recirculation rate measurement model; and Obtain additional data showing the relationship between dialyzer type and the amount of change in blood concentration after recirculation. In the analyzing step, Perform a multivariate analysis including the additional data, A regression equation is obtained that includes the blood marker detection time as an explanatory variable, In the treatment data acquisition step, acquiring data indicating the blood marker detection time during hemodialysis treatment; In the recirculation rate estimation step, The method for estimating a recirculation rate according to claim 1 or 2, wherein the recirculation rate is estimated by further inputting the blood marker detection time acquired in the treatment data acquisition step into the regression equation or transformation model obtained in the analysis step.

6. The hemodialysis treatment is performed using a blood purification device, the recirculation rate measurement model and the blood purification device include a blood purifier; The administration of the blood marker includes: injecting a replacement fluid into the blood upstream of the blood purifier; injecting a replacement fluid into the blood downstream of the blood purifier; flowing replacement fluid in a back-filtration direction in a dialyzer included in the blood purifier; 3. The method for estimating a recirculation rate according to claim 1, wherein the method is carried out by one of removing water in the filtration direction in a dialyzer included in the blood purifier and providing a blood marker by filtration.

7. 3. The method for estimating a recirculation rate according to claim 1, wherein the time point at which the change in blood concentration after recirculation begins to be measured is determined from the circuit filling volume and the blood pump speed in the recirculation rate measurement model.

8. An analysis device for determining a regression equation for estimating a blood recirculation rate in hemodialysis treatment, comprising: Using the recirculation rate measurement model, when a predetermined amount of blood marker is added to the extracorporeally circulating blood, Data showing the change in blood concentration after recirculation; Data showing the relationship between the change in blood concentration after recirculation and the blood concentration; and a model data acquisition unit that acquires data showing the relationship between the amount of change in blood concentration after recirculation and the blood flow rate; and an analysis unit that performs multivariate analysis or machine learning using the model data acquired by the model data acquisition unit to obtain a regression equation or a transformation model in which the change in blood concentration after recirculation, the blood concentration, and the blood flow rate are used as explanatory variables and the recirculation rate is used as a response variable.

9. A blood purification device capable of estimating a blood recirculation rate, a treatment data acquisition unit that acquires data indicating a change in blood concentration, blood concentration, and blood flow rate of blood circulating through an arterial line or a venous line during hemodialysis treatment; a recirculation rate estimation unit that estimates a recirculation rate by inputting treatment data acquired by a treatment data acquisition unit into the regression equation or transformation model determined by the analysis device of claim 8.

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