Monitoring device and dialysis system equipped with the same

Abstract

To identify the amount of an extracellular fluid during dialysis.SOLUTION: A monitoring device monitors the concentration of a substance removed by dialysis, in a dialysis drainage discharged from a blood purifier. The monitoring device comprises: a measurement unit which measures with time the concentration of the substance in the dialysis drainage discharged from the blood purifier; and an arithmetic unit which calculates a removal amount of the substance removed by the dialysis from the concentration of the substance measured by the measurement unit and calculates biological information on the basis of the removal amount.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present specification relates to a monitor device that monitors the concentration of a substance removed by dialysis and a dialysis system equipped with the same. [Background technology]

[0002] In dialysis patients, all water ingested accumulates in the body because renal function is abolished. The accumulated water in the body needs to be removed by dialysis treatment. In this case, the target amount of water removal is set so that theoretically it is performed until the amount of body fluid is equal to that of a person with normal renal function. However, in reality, a method for measuring the amount of body fluid with high accuracy has not been established. Therefore, a method for measuring other values ​​related to the amount of body fluid and calculating the amount of body fluid by calculation using the measured values ​​has been developed. For example, Patent Document 1 discloses a method for calculating the amount of extracellular fluid in body fluids by focusing on uric acid (hereinafter, also referred to as the uric acid method). In the uric acid method, the amount of uric acid removed per dialysis treatment is calculated from the uric acid value in serum to calculate the amount of extracellular fluid. For example, by calculating the amount of extracellular fluid, it is possible to set a precise dry weight and grasp the state of excess water in the body. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2019 / 138917 Summary of the Invention [Problem to be solved by the invention]

[0004] In the conventional uric acid method described in Patent Document 1, the uric acid value before and after dialysis is required to calculate the amount of extracellular fluid in the body fluid, so the amount of extracellular fluid can be calculated only after dialysis is completed. In this way, the method of specifying the in vivo condition caused by dialysis based on the concentrations of substances removed by dialysis before and after dialysis can reflect the specified in vivo condition in the next treatment, but cannot reflect it during the treatment.

[0005] The present specification discloses a technique that makes it possible to identify in vivo conditions related to substances removed during dialysis. [Means for solving the problem]

[0006] In a first aspect of the technology disclosed in this specification, a monitoring device monitors the concentration of a substance removed by dialysis. The monitoring device includes a measuring unit that measures the concentration of the substance in the dialysis effluent discharged from a blood purifier over time, and a computing unit that calculates the amount of the substance removed by dialysis from the concentration of the substance measured by the measuring unit and calculates biological information based on the calculated amount removed.

[0007] In the above-mentioned monitor device, the concentration of a substance (e.g., uric acid) in the dialysis effluent that is removed by dialysis is continuously measured during dialysis. Since the concentration of a substance in the dialysis effluent is monitored during dialysis, the amount of the substance removed (i.e., the amount of the substance removed from the start of dialysis to the time of measurement) can be calculated from the measured concentration. If the amount of a substance removed by dialysis, such as uric acid, is identified, it is possible to calculate biological information (e.g., extracellular fluid volume, etc.) that indicates the state within the living body. Therefore, it is possible to identify the biological information at the time when the concentration of the substance in the dialysis effluent is measured. This makes it possible to identify biological information (e.g., extracellular fluid volume, etc.) during dialysis, and to grasp the state of the dialysis patient at any time during dialysis treatment.

[0008] The dialysis system disclosed in this specification includes a dialysis device equipped with a blood purifier and the monitor device of the first aspect. Therefore, it can achieve the same effects as the monitor device. In addition, it is possible to perform dialysis treatment while constantly monitoring the water status in the body of the dialysis patient. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram showing a schematic configuration of a dialysis system according to an embodiment. [Diagram 2] FIG. 4 is a block diagram showing a control system of the monitor device. [Diagram 3] A graph showing the uric acid concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient A, measured by the measurement section of the monitor device, and the uric acid concentration in the dialysis effluent, measured using a conventional uric acid concentration measurement method. [Figure 4] A graph showing the uric acid concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient B, measured by the measurement unit of the monitor device, and the uric acid concentration measured using a conventional uric acid concentration measurement method. [Diagram 5] A graph showing the uric acid concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient C, measured by the measurement section of the monitor device, and the uric acid concentration in the dialysis effluent measured using a conventional uric acid concentration measurement method. [Figure 6] 11 is a flowchart showing an example of a process for calculating an extracellular fluid volume. [Figure 7] (A) is a graph showing the uric acid concentration function of dialysis patient A, and (B) is an enlarged view of a main part (B) of (A). [Figure 8] (A) is a graph showing the uric acid concentration function of dialysis patient B, and (B) is an enlarged view of a main part (B) of (A). [Figure 9] (A) is a graph showing the uric acid concentration function of dialysis patient C, and (B) is an enlarged view of a key part (B) of (A). [Figure 10] FIG. 13 is a diagram for explaining a method for calculating the uric acid concentration (extrapolated value) in the dialysis effluent at the start of dialysis. [Figure 11] 4 is a flowchart showing an example of a process for performing dialysis treatment using the dialysis system according to the present embodiment. [Figure 12] 13 is a graph showing the uric acid concentration function in the dialysis effluent discharged during dialysis treatment, measured by the measurement unit of the monitor device, when poor blood removal occurs during dialysis and shunt care is then performed. FIG. [Figure 13] A graph showing the urea concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient D, measured by the measurement unit of the monitor device, and the urea concentration in the dialysis effluent measured using a conventional urea concentration measurement method. [Figure 14] A graph showing the urea concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient E, measured by the measurement unit of the monitoring device, and the urea concentration in the dialysis effluent measured using a conventional urea concentration measurement method. [Figure 15] A graph showing the urea concentration in the dialysis effluent discharged during dialysis treatment for dialysis patient F, measured by the measurement unit of the monitor device, and the urea concentration in the dialysis effluent measured using a conventional urea concentration measurement method. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The main features of the embodiments described below are listed below. Note that the technical elements described below are independent technical elements that exhibit technical usefulness alone or in various combinations, and are not limited to the combinations described in the claims at the time of filing.

[0011] In a second aspect of the technology disclosed in the present specification, in the first aspect described above, the substance may be uric acid. The biological information may be the extracellular fluid volume. With this configuration, the measurement unit measures the concentration of uric acid over time during dialysis. Uric acid is a substance that correlates with the extracellular fluid volume. Therefore, by measuring the concentration of uric acid during dialysis, the extracellular fluid volume during dialysis can be grasped at any time.

[0012] In a third aspect of the technology disclosed in the present specification, in the first aspect described above, the substance may be urea. The biological information may be intracellular fluid volume. With this configuration, the measurement unit measures the concentration of urea over time during dialysis. Urea is a substance that correlates with the amount of bodily fluid. Therefore, by measuring the concentration of urea during dialysis, the amount of bodily fluid during dialysis can be grasped at any time.

[0013] In a fourth aspect of the technology disclosed in the present specification, in any one of the first to third aspects described above, the measurement unit may be provided with an electrode sensor, a near-infrared spectroscopic sensor, or a Raman spectroscopic sensor that detects the concentration of the substance in the dialysis effluent.

[0014] In a fifth aspect of the technique disclosed in the present specification, in any one of the first to fourth aspects described above, the monitor device may further include an abnormality detection unit that detects an abnormality in dialysis based on a change over time in the concentration of a substance measured by the measurement unit. When dialysis treatment is performed normally, the concentration of the substance changes regularly. On the other hand, when an abnormality such as poor blood removal occurs, the concentration of the substance changes irregularly. Therefore, the abnormality detection unit can detect whether an abnormality has occurred in dialysis treatment from the change over time in the concentration.

[0015] In a sixth aspect of the technology disclosed in this specification, in the fifth aspect, the monitor device may further include a notification unit that notifies a user of an abnormality when the abnormality detection unit detects an abnormality. With this configuration, it is possible to notify a user of the occurrence of an abnormality.

[0016] In a seventh aspect of the technology disclosed in the present specification, in the second aspect described above, the monitor device may further include a storage unit that stores an extracellular fluid volume at blood pressure drop, which is the extracellular fluid volume when blood pressure drop occurred in past dialysis, and a notification unit that notifies the user that blood pressure drop is likely to occur when the extracellular fluid volume calculated by the calculation unit becomes equal to or less than a reference value set based on the extracellular fluid volume at blood pressure drop. When the extracellular fluid volume becomes smaller than the appropriate volume, blood pressure drop occurs. In other words, if the appropriate volume of extracellular fluid does not change, blood pressure drop is likely to occur when water is removed to the extracellular fluid volume when blood pressure drop occurred in the past. For this reason, by storing the extracellular fluid volume at blood pressure drop when blood pressure drop occurred in the past and setting the reference value based on the extracellular fluid volume at blood pressure drop, a state where blood pressure drop is likely to occur can be specified. By notifying the user when the calculated extracellular fluid volume reaches the reference value, the user can be notified that blood pressure drop is likely to occur before blood pressure drop occurs. For this reason, the user (e.g., a medical professional, etc.) can take appropriate measures before blood pressure drop occurs.

[0017] In the eighth aspect of the technique disclosed in the present specification, in the second aspect described above, the monitor device may further include a storage unit that stores a blood pressure drop concentration, which is the concentration of a substance in the dialysis effluent when blood pressure drop occurred in a past dialysis, and a notification unit that notifies the user that blood pressure drop is likely to occur when the concentration of the substance measured by the measurement unit becomes equal to or lower than a reference value set based on the blood pressure drop concentration. The concentration of the substance in the dialysis effluent correlates with the extracellular fluid volume. Therefore, if water is removed until the concentration of the substance in the dialysis effluent when blood pressure drop occurred in the past is the same as the concentration of the substance in the dialysis effluent when blood pressure drop occurred in the past, blood pressure drop is likely to occur. Therefore, by storing the blood pressure drop concentration when blood pressure drop occurred in the past and setting a reference value based on the blood pressure drop concentration, a state in which blood pressure drop is likely to occur can be specified. By notifying the user when the concentration of the substance in the dialysis effluent reaches the reference value, the user can be notified that blood pressure drop is likely to occur before blood pressure drop occurs.

[0018] In a ninth aspect of the technique disclosed in the present specification, in any one of the first to eighth aspects, the calculation unit may further calculate at least one of the blood concentration and the serum concentration of the substance from the amount of removal. With this configuration, the blood concentration and the serum concentration of a specific substance in a living body during dialysis can be grasped at any time. EXAMPLES

[0019] Example 1 A dialysis system 1 according to the present embodiment will be described with reference to the drawings. As shown in Fig. 1 and Fig. 2, the dialysis system 1 includes a monitor device 10 and a dialysis device 30 including a dialyzer 32. Note that a known device can be used for the dialysis device 30, and therefore a detailed description thereof will be omitted.

[0020] The monitor 10 is a device that monitors the concentration of a specific substance in the dialysis effluent during dialysis and calculates biological information indicating the state of the living body during dialysis. In this embodiment, the monitor 10 monitors the uric acid concentration in the dialysis effluent during dialysis and calculates the extracellular fluid volume during dialysis. Since uric acid hardly passes through the red blood cell membrane, it is almost always present in the extracellular compartment in the living body. Therefore, the uric acid concentration correlates with the extracellular fluid volume. The monitor 10 includes a reaction section 12, a dialysis effluent supply path 14, a pump 16, a first reaction liquid supply section 18, a second reaction liquid supply section 20, a measurement section 22, a calculation section 24, a monitor 26, and an input device 28.

[0021] The reaction section 12 reacts the dialysis effluent with a reaction liquid for measuring the uric acid concentration. The reaction section 12 is connected to a dialysis effluent supply path 14 that supplies the dialysis effluent to the reaction section 12. One end of the dialysis effluent supply path 14 is connected to the discharge path 36 of the dialysis device 30, and the other end is connected to the reaction section 12. The discharge path 36 discharges the dialysis fluid from the dialyzer 32 to the discharge section 34. A pump 16 is installed in the dialysis effluent supply path 14, and the dialysis effluent in the discharge path 36 is sent to the reaction section 12 by the pump 16. The pump 16 operates at a predetermined interval to send the dialysis effluent to the reaction section 12. In this embodiment, the pump 16 operates every 5 minutes. When the pump 16 operates, a predetermined amount of dialysis effluent is sent. In this embodiment, when the pump 16 operates, 3.3 μL of dialysis effluent is sent.

[0022] The reaction section 12 is connected to a first reaction liquid supply section 18 and a second reaction liquid supply section 20. The first reaction liquid supply section 18 is configured to supply 150 μL of the first reaction liquid to the reaction section 12 after the dialysis effluent is supplied to the reaction section 12. The second reaction liquid supply section 20 is configured to supply 50 μL of the second reaction liquid to the reaction section 12 after the first reaction liquid is supplied to the reaction section 12. The first reaction liquid contains 200 mmol / L of Good's buffer solution, 0.3 U / mL of ascorbic acid oxidase, 1.5 U / mL of peroxidase, and 0.04 mmol / L of N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline sodium (HDAOS). The second reaction liquid contains 100 mmol / L of Good's buffer solution, 0.3 U / mL of uricase, and 2.0 mmol / L of 4-aminoantipyrine (4-AA). The uric acid concentration in the dialysis effluent can be measured by mixing the first and second reaction solutions with the dialysis effluent. After three minutes have elapsed since the first and second reaction solutions reacted with the dialysis effluent in the reaction unit 12, the dialysis effluent after the reaction is transferred from the reaction unit 12 to the measurement unit 22.

[0023] The measuring unit 22 includes a sensor 23, and measures the uric acid concentration in the dialysis effluent by the sensor 23. Specifically, the measuring unit 22 is configured to irradiate the dialysis effluent after the reaction with 600 nm wavelength light and measure the absorbance at 600 nm. The sensor 23 is an absorbance sensor, but may be other sensors such as an electrode sensor, a near-infrared spectroscopy sensor, or a Raman spectroscopy sensor. In addition, the measuring unit may measure the uric acid concentration in the dialysis effluent without using the reaction solution as described above, as long as it can measure the uric acid concentration in the dialysis effluent. The uric acid concentration in the dialysis effluent can be measured by reacting the dialysis effluent with the first reaction solution and the second reaction solution described above and measuring the absorbance at 600 nm. The measuring unit 22 outputs the measurement data to the calculation unit 24.

[0024] The calculation unit 24 can be configured by, for example, a computer equipped with a CPU, a ROM, a RAM, and the like. As shown in FIG. 2, the calculation unit 24 is connected to the reaction unit 12, the pump 16, the first reaction liquid supply unit 18, the second reaction liquid supply unit 20, and the measurement unit 22, and controls the reaction unit 12, the pump 16, the first reaction liquid supply unit 18, the second reaction liquid supply unit 20, and the measurement unit 22, respectively. The calculation unit 24 also calculates the amount of extracellular fluid during dialysis using the measurement data measured by the measurement unit 22. The method of calculating the amount of extracellular fluid will be described in detail later. The calculation unit 24 is also connected to the monitor 26, and displays the calculated amount of extracellular fluid on the monitor 26. The input device 28 accepts input of various information and outputs the input information to the calculation unit 24.

[0025] In a verification conducted by the present inventors, it was confirmed that the measurement unit 22 of the monitor device 10 of this embodiment accurately measured the uric acid concentration in the dialysis effluent discharged during dialysis treatment.

[0026] In the verification, hemodialysis was performed on three chronic dialysis patients A to C, and the uric acid concentration in the dialysis effluent measured by the measuring unit 22 of the monitoring device 10 of this embodiment during dialysis treatment was recorded.

[0027] As a comparative example, dialysis treatment was performed on the same three chronic dialysis patients A to C, and the dialysis effluent was collected during dialysis treatment, and the uric acid concentration in the dialysis effluent was measured using the uricase-peroxidase method, a conventionally known method for measuring uric acid (hereinafter simply referred to as the "conventional uric acid concentration measurement method").

[0028] The conventional uric acid concentration measurement method was carried out as follows. 8 μL of dialysis effluent was collected six times in total, 5 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 240 minutes after the start of dialysis treatment. In the conventional uric acid concentration measurement method, the uric acid concentration can be measured using a commercially available uric acid measurement reagent (e.g., UA-L by Serotec).

[0029] When measuring the absorbance, first, the absorbance of the standard solution (uric acid solution) was measured. In detail, 320 μL of reagent A was added to 8 μL of the standard solution and mixed. Reagent A contains N-ethyl-N(-2-hydroxy-3-sulfopropyl)-m-toluidine sodium dihydrate (TOOS) and the like. After heating at 37°C for 5 minutes, the absorbance at wavelengths of 560 to 600 nm (hereinafter also referred to as absorbance 1) was measured using the dialysate as a control. Next, 80 μL of reagent B was further mixed with the standard solution mixed with reagent A. Reagent B contains 4-aminoantipyrine, uricase and the like. After heating at 37°C, the absorbance at wavelengths of 560 to 600 nm (hereinafter also referred to as absorbance 2) was measured using the dialysate as a control. Next, 320 μL of reagent A was added to each of the collected dialysis effluents, mixed, and heated at 37° C. for 5 minutes, and then the absorbance at wavelengths of 560 to 600 nm (hereinafter also referred to as absorbance 3) was measured using the dialysis fluid as a control. Next, 80 μL of reagent B was further mixed with each of the dialysis effluents mixed with reagent A, and heated at 37° C., and then the absorbance at wavelengths of 560 to 600 nm (hereinafter also referred to as absorbance 4) was measured using the dialysis fluid as a control.

[0030] Next, the uric acid concentration in each of the collected dialysis effluents was calculated using the formula represented by the following equation 1.

[0031]

number

[0032] 3 to 5 show the uric acid concentration in the dialysis effluent measured by the measuring unit 22 of the monitor device 10 of the present embodiment and the uric acid concentration in the dialysis effluent measured by the conventional uric acid concentration measuring method for each of the three chronic dialysis patients A to C. In FIG. 3 to FIG. 5, the vertical axis shows the uric acid concentration in the dialysis effluent, and the horizontal axis shows the dialysis treatment time. The solid line shows the uric acid concentration in the dialysis effluent measured by the measuring unit 22 of the monitor device 10 of the present embodiment, and the dashed line shows the uric acid concentration in the dialysis effluent measured by the conventional uric acid concentration measuring method. As shown in FIG. 3 to FIG. 5, for each of the three chronic dialysis patients A to C, the uric acid concentration in the dialysis effluent measured by the measuring unit 22 of the monitor device 10 of the present embodiment and the uric acid concentration in the dialysis effluent measured by the conventional uric acid concentration measuring method were approximately equal. In this way, it was confirmed that the uric acid concentration in the dialysis effluent measured by the measuring unit 22 during dialysis treatment was accurately measured in the monitor device 10 of the present embodiment.

[0033] Next, a process for calculating the extracellular fluid volume using the monitor device 10 of this embodiment will be described. As shown in Fig. 6, first, the calculation unit 24 acquires measurement data from the measurement unit 22, which measures the uric acid concentration in the dialysis effluent over time during dialysis (S12). When dialysis treatment is started, the measurement unit 22 measures the uric acid concentration in the dialysis effluent over time (specifically, every 5 minutes). The measurement unit 22 outputs the measurement data to the calculation unit 24.

[0034] Next, the calculation unit 24 generates a relational equation (hereinafter also referred to as "uric acid concentration function") indicating the uric acid concentration in the dialysis effluent of the dialysis patient over time from the acquired measurement data (S14). The inventors have found that the uric acid concentration function can be expressed as a composite function of two exponential terms using the nonlinear least squares method. The uric acid concentration function can be expressed by the following equation 2. Note that C indicates the uric acid concentration in the dialysis effluent, t indicates the elapsed time during dialysis treatment, and A0, A1, A2, B1, and B2 indicate coefficients.

[0035]

number

[0036] The coefficients A0, A1, A2, B1, and B2 are determined by plotting the measurement data measured by the measurement unit 22. Therefore, the coefficients A0, A1, A2, B1, and B2 are different values ​​for each dialysis patient. Dialysis treatment is a symptomatic treatment, and it can be said that there is no significant change in each dialysis treatment. Therefore, when dialysis treatment is performed on the same dialysis patient under the same conditions, the same uric acid concentration function can be used. The same conditions means that the conditions during dialysis treatment, such as the status of the membrane of the dialyzer 32 used and the water removal speed, are approximately the same. The generated uric acid concentration function is stored in the memory (not shown) of the calculation unit 24.

[0037] Figures 7 to 9 show the uric acid concentration functions of dialysis patients A, B, and C, respectively. As shown in Figures 7 to 9, when the measurement data of the uric acid concentration in the dialysis effluent for each dialysis patient A, B, and C is plotted over time to generate the uric acid concentration function, the uric acid concentration function can be expressed by the above formula 2. Note that the coefficients A0, A1, A2, B1, and B2 of the uric acid concentration function are different values ​​for each of the dialysis patients A, B, and C.

[0038] Next, the calculation unit 24 calculates the total amount of uric acid removed in the dialysis effluent using the uric acid concentration function (S16). Specifically, the calculation unit 24 uses the uric acid concentration function to perform a definite integration of the uric acid concentration in the dialysis effluent measured over time by the measurement unit 22 using the trapezoidal rule. For example, when calculating the amount of uric acid removed in the dialysis effluent up to a specific time T during dialysis treatment, the calculation unit 24 calculates the total amount of uric acid removed in the dialysis effluent measured at each time t1,...,t n The uric acid concentration in the dialysis effluent is integrated by the trapezoidal rule, and the total amount of uric acid removed from the dialysis effluent up to time T is calculated.

[0039] Next, the calculation unit 24 calculates the uric acid concentration in the dialysis effluent at the start of dialysis treatment using the uric acid concentration function (S18). As shown in Figs. 7 to 9, the uric acid concentration in the dialysis effluent decreases rapidly from the start of dialysis until a predetermined time, and then decreases gradually after the predetermined time has passed from the start of dialysis. At the start of dialysis treatment, there is a delay time until the uric acid removed from the dialysis membrane passes through the waste liquid route on the dialysis fluid side and is measured by the measurement unit 22 of the monitor device 10, so the uric acid concentration in the dialysis effluent changes significantly near the start of dialysis. For this reason, the uric acid concentration in the dialysis effluent at the start of dialysis deviates from the value of the uric acid concentration function generated in step S14 at time t=0, but the uric acid concentration (extrapolated value) in the dialysis effluent at the start of dialysis can be calculated from the uric acid concentration function generated in step S14 and the actual measured value of the uric acid concentration in the dialysis effluent. Therefore, the uric acid concentration in the dialysis effluent at the start of dialysis is calculated using the formula expressed by the following equation 3. Note that, C(t p ) indicates the peak concentration of uric acid in the dialysis effluent, and t p is C(t p ), C(t0) indicates the uric acid concentration (extrapolated value) in the dialysis effluent at the start of dialysis, and t0 indicates the time when C(t0) is reached.

[0040]

number

[0041] C(t p ) is the largest value (peak value) among the actual measured values ​​of the uric acid concentration measured by the measurement unit 22, and therefore can be identified from the measurement results by the measurement unit 22. p is C(t p ) and the uric acid concentration function.

[0042] In addition, t0 can be calculated by the following method. Fig. 10 shows an example of a function of the uric acid concentration in the dialysis effluent discharged during dialysis treatment, measured by the measurement unit 22. S1 is the time t pS2 is the area of ​​the triangle from the start of dialysis to the time t0 when the uric acid concentration in the dialysis effluent reaches its peak value. p The trapezoid area from the start of dialysis to the end of dialysis is shown. At this time, the time when the area of ​​S1 and the area of ​​S2 become equal is the uric acid concentration t0 in the dialysis effluent at the start of dialysis. p ), t p By substituting t0 and t1 into the equation (3), the uric acid concentration C(t0) in the dialysis effluent at the start of dialysis can be calculated as an extrapolated value.

[0043] Next, the calculation unit 24 calculates the serum uric acid concentration at the start of dialysis treatment (S20) using the uric acid concentration in the dialysis effluent at the start of dialysis calculated in step S18. If the plasma flow rate is QP, the blood flow rate is QB, and the hematocrit value at elapsed time t during dialysis treatment is Ht, the following equation 4 is established.

[0044]

number

[0045] The clearance of uric acid during dialysis treatment can be calculated using the formula 5 below. Note that CL indicates the clearance of uric acid during dialysis treatment, QD indicates the dialysate flow rate, and KoA indicates the overall mass transfer-area coefficient used to estimate the performance of the dialyzer 32. KoA can be calculated using the formula 6 below. Note that MA indicates the membrane area of ​​the dialyzer 32.

[0046]

number

[0047]

number

[0048] The serum uric acid concentration can be calculated using the following formula 7.

[0049]

number

[0050] From the above, the calculation unit 24 can calculate the serum uric acid concentration using the formulas expressed by the above numbers 4 to 7. The plasma flow rate QP, the blood flow rate QB, the hematocrit value Ht at the elapsed time t during dialysis treatment, and the membrane area of ​​the dialyzer 32 can be easily obtained. The calculation unit 24 calculates the serum uric acid concentration at the start of dialysis treatment using the uric acid concentration in the dialysis effluent at the start of dialysis treatment calculated in step S18 and the formulas expressed by the above numbers 4 to 7.

[0051] In addition, in the verification conducted by the present inventors, it was confirmed that the serum uric acid concentration at the start of dialysis treatment can be calculated with high accuracy by using the method of step S20 described above. In the verification, the serum uric acid concentration at the start of dialysis treatment calculated in step S20 described above (i.e., extrapolated value) was compared with the serum uric acid concentration measured using blood collected before dialysis. The uric acid concentration in the dialysis effluent at the start of dialysis (extrapolated value), the dialysis conditions of the dialysis patient (blood flow rate, dialysis fluid flow rate, membrane area of ​​the dialyzer 32, and hematocrit value), the plasma flow rate calculated using the formula represented by the above formula 4, the overall mass transfer-area coefficient KoA of the dialyzer 32 calculated using the formula represented by the above formula 6, and the uric acid clearance CL calculated using the formula represented by the above formula 5 are shown in Table 1 below.

[0052] [Table 1]

[0053] The serum uric acid concentration at the start of dialysis was calculated using the values ​​in Table 1 and the formula expressed by Equation 7. The calculated serum uric acid concentration at the start of dialysis (calculated using extrapolated values ​​according to the method of this embodiment) and the serum uric acid concentration before dialysis obtained by blood sampling are shown in Table 2 below.

[0054] [Table 2]

[0055] As shown in Table 2 above, the serum uric acid concentration at the start of dialysis in this embodiment (i.e., calculated using extrapolated values) and the serum uric acid concentration at the start of dialysis based on the blood sampling results were approximately consistent, confirming their equivalence.

[0056] Next, the calculation unit 24 calculates the serum uric acid concentration at a specific time T during dialysis (S22). The serum uric acid concentration at a specific time T during dialysis is calculated by the following procedure. The calculation unit 24 acquires the uric acid concentration in the dialysis effluent at time T from the measurement unit 22. The calculation unit 24 also acquires the hematocrit value at time T. The hematocrit value can be measured by a device such as a blood volume monitor device. The calculation unit 24 can acquire the measured hematocrit value from the input device 28. The calculation unit 24 substitutes the uric acid concentration and hematocrit value in the dialysis effluent at time T acquired, the plasma flow rate QP, the blood flow rate QB, the dialysate flow rate QD, and the overall mass transfer-area coefficient KoA of the dialyzer 32 into the formulas represented by the above numbers 3 to 6 to calculate the serum uric acid concentration at time T.

[0057] Next, the calculation unit 24 calculates the amount of extracellular fluid at a specific time T during dialysis (S24). Uric acid is distributed both inside and outside the cells, and hardly moves between the inside and outside of the cells in the short time from the start to the end of dialysis treatment (i.e., a few hours). For this reason, it can be considered that only the uric acid present in the extracellular fluid is removed during dialysis treatment. Therefore, it can be said that the uric acid distribution volume is approximately equal to the amount of extracellular fluid. Therefore, the amount of extracellular fluid can be calculated by calculating the uric acid distribution volume. The uric acid distribution volume can be calculated using the formula expressed by the following equation 8.

[0058]

number

[0059] The calculation unit 24 can calculate the uric acid distribution volume by substituting the total amount of uric acid removed calculated in step S16, the uric acid concentration in the dialysis effluent at the start of dialysis treatment calculated in step S20, and the serum uric acid concentration at a specific time T during dialysis calculated in step S22 into the formula represented by the above formula 6. That is, the amount of extracellular fluid at a specific time T during dialysis is calculated.

[0060] In this embodiment, the uric acid concentration in the dialysis effluent is automatically measured by the measuring unit 22 during dialysis treatment. This can save the operator time and effort, and the uric acid concentration in the dialysis effluent can be easily measured at shorter intervals than when the uric acid concentration in the dialysis effluent is measured manually during dialysis treatment. This makes it easy to increase the number of measurement points, and allows the extracellular fluid volume to be accurately determined.

[0061] Next, a process of performing dialysis treatment will be described using the dialysis system 1 of this embodiment. When performing dialysis treatment using the dialysis system 1, a uric acid concentration function generated in a previous dialysis treatment is used.

[0062] As shown in Fig. 10, first, the calculation unit 24 acquires an already-generated uric acid concentration function (hereinafter also referred to as an already-generated uric acid concentration function) (S100). The already-generated uric acid concentration function is stored in a memory (not shown) of the calculation unit 24. The calculation unit 24 reads out the already-generated uric acid concentration function stored in the memory. The calculation unit 24 may acquire the already-generated uric acid concentration function input via the input device 28.

[0063] Next, the calculation unit 24 acquires the value of the extracellular fluid volume when a drop in blood pressure occurred in the previous dialysis treatment (S110). When the extracellular fluid volume becomes less than the appropriate volume, dehydration occurs and a drop in blood pressure occurs. Furthermore, a drop in blood pressure may occur even before the extracellular fluid volume reaches the appropriate volume. When a drop in blood pressure occurs, it becomes necessary to take measures such as slowing down the water removal speed, stopping water removal, or providing fluid replacement. If a drop in blood pressure has occurred in the previous dialysis treatment, there is a high possibility that a drop in blood pressure will occur when the same extracellular fluid volume is reached. If a drop in blood pressure has occurred in the previous dialysis treatment, the value of the extracellular fluid volume at that time is acquired.

[0064] Next, the calculation unit 24 sets a reference value (hereinafter also simply referred to as "reference value") for notifying the medical staff that a blood pressure drop may occur, based on the value of the extracellular fluid volume acquired in step S110 (S120). The reference value is set to a value slightly larger than the value of the extracellular fluid volume acquired in step S110. This makes it possible to notify the medical staff that a blood pressure drop may occur before the extracellular fluid volume reaches the volume at which the blood pressure drop occurred. Note that if a blood pressure drop has not occurred in the previous dialysis treatment, or if the extracellular fluid volume at which the blood pressure drop occurred in the previous dialysis treatment is unknown, steps S110 and S120 are skipped.

[0065] Next, the calculation unit 24 executes dialysis treatment and acquires the uric acid concentration in the dialysis effluent at a predetermined time interval (S130). Specifically, the measurement unit 22 of the monitor device 10 measures the uric acid concentration in the dialysis effluent every 5 minutes. The calculation unit 24 acquires the measurement data measured every 5 minutes from the measurement unit 22.

[0066] Next, the calculation unit 24 judges whether one hour has passed since the start of dialysis (S140). When dialysis treatment is performed normally, the uric acid concentration in the dialysis effluent changes regularly according to the formula expressed by the above formula 2. On the other hand, if some abnormality occurs during dialysis treatment, the uric acid concentration in the dialysis effluent changes irregularly. For example, in a chronic dialysis patient with a problem in vascular access, blood removal failure may occur during dialysis. As shown in FIG. 11, when blood removal failure occurs, the change in the uric acid concentration in the dialysis effluent becomes irregular. Therefore, an abnormality during dialysis can be detected from the change in the uric acid concentration in the dialysis effluent. As shown in FIG. 3 to FIG. 5 and FIG. 7 to FIG. 9, the rate of change in the uric acid concentration in the dialysis effluent is large during the initial period from the start of dialysis (for example, about one hour), but after a while (for example, after about one hour or more has passed), the rate of change in the uric acid concentration in the dialysis effluent becomes smaller. Therefore, after some time has passed since the start of dialysis, specifically after one hour has passed since the start of dialysis, it is possible to determine whether or not an abnormality has occurred by comparing the measured value with the immediately preceding measurement value (i.e., the uric acid concentration measured 10 minutes before).On the other hand, during the initial period after the start of dialysis, specifically within one hour of the start of dialysis, it is possible to determine whether or not an abnormality has occurred by comparing the measured value with the already-formed uric acid concentration function, rather than with the immediately preceding measurement value.

[0067] If one hour has not passed since the start of dialysis (NO in step S140), the calculation unit 24 plots the uric acid concentration in the dialysis effluent obtained in step S130 to generate a uric acid concentration function in the current dialysis (hereinafter also referred to as the current uric acid concentration function) (S150). If it is within one hour since the start of dialysis, the calculation unit 24 uses the already-formed uric acid concentration function to determine whether an abnormality has occurred, but even if dialysis is performed normally, it may not match the already-formed uric acid concentration function. For example, the amount of uric acid accumulated in the body before dialysis treatment may differ for each dialysis treatment, and the uric acid concentration at the start of dialysis may differ from the value of t=0 of the already-formed uric acid concentration function. In this case, even if dialysis is performed normally, if the uric acid concentration function is generated based on the current dialysis treatment, the current uric acid concentration function will not match the already-formed uric acid concentration function. However, the present inventors have found that while the value of t=0 is shifted, the state (curve) of the curve of the uric acid concentration function is approximately the same for the same patient in the same condition. This means that only the intercept value has changed between the current uric acid concentration function and the already produced uric acid concentration function, resulting in a parallel shift in the upward and downward directions.

[0068] Therefore, the calculation unit 24 compares the already-produced uric acid concentration function acquired in step S100 with the current uric acid concentration function generated in step 150, and judges whether the states of the curves (curves) are substantially the same or not (S160). That is, the calculation unit 24 judges whether the states of the curves of the already-produced uric acid concentration function and the current uric acid concentration function are different or substantially the same (whether the intercept value has changed and the curves have simply moved up and down in parallel or not).

[0069] If the curve states are substantially the same (YES in step S160), the calculation unit 24 determines that the dialysis treatment is being performed in the same manner as the previous dialysis treatment, and determines that the dialysis treatment is being performed normally. Then, the process proceeds to step S200. The process after step S200 will be described in detail later.

[0070] On the other hand, if the state of the curve is different (NO in step S160), the calculation unit 24 determines that the dialysis treatment is not being performed in the same manner as the previous dialysis treatment, and determines that an abnormality has occurred in the dialysis treatment. The calculation unit 24 then notifies the medical staff via the monitor 26 that an abnormality has occurred (S170).

[0071] In this embodiment, the calculation unit 24 can notify an abnormality at the timing when it detects that the already-produced uric acid concentration function and the state of the curve do not match, so that medical personnel can quickly know that an abnormality has occurred. Therefore, for example, a shunt care or other measures can be taken quickly.

[0072] If one hour has passed since the start of dialysis (YES in step S140), the calculation unit 24 calculates the rate of change between the uric acid concentration in the dialysis effluent obtained in step S130 and the uric acid concentration in the dialysis effluent obtained at the immediately preceding measurement timing (i.e., the uric acid concentration measured 10 minutes ago by the measurement unit 22) (S180), and judges whether the calculated rate of change is within a predetermined value (S190). As described above, when dialysis is performed normally, the rate of change with respect to the immediately preceding uric acid concentration (i.e., the uric acid concentration 10 minutes ago) is small. Therefore, by comparing with the immediately preceding measured value, it is possible to judge whether an abnormality has occurred.

[0073] If the rate of change is within a predetermined value (YES in step S190), the calculation unit 24 determines that the dialysis treatment is being performed normally. In this embodiment, the predetermined value is 5%. Note that the predetermined value is not particularly limited and may be greater than 5% or less than 5%. Then, the process proceeds to step S200. Note that the process after step S200 will be described in detail later.

[0074] On the other hand, if the rate of change exceeds the predetermined value (NO in step S190), the calculation unit 24 determines that an abnormality has occurred in dialysis. For example, if an abnormality occurs such as a problem with vascular access causing insufficient blood removal, the change in the uric acid concentration in the dialysis effluent becomes irregular and the rate of change exceeds the predetermined value. In this case, the calculation unit 24 notifies the medical staff via the monitor 26 that an abnormality has occurred (S170).

[0075] If dialysis treatment is being performed normally (YES in step S160 or YES in step S190), the calculation unit 24 calculates the extracellular fluid volume (S200). The process of calculating the extracellular fluid volume executes the process shown in FIG. 6 described above. If the answer is YES in step S160, the processes of steps S12 and S14 in FIG. 6 are not executed, and instead the current uric acid concentration function generated in step S150 is used. If the answer is YES in step S190, the process of step S12 in FIG. 6 is not executed, and instead the uric acid concentration in the dialysis effluent obtained up to this point is used.

[0076] When the amount of extracellular fluid is calculated, the calculation unit 24 judges whether or not the amount of extracellular fluid calculated in step S200 is equal to or less than the reference value set in step S120 (S210). As described above, the reference value is a value slightly larger than the value of the amount of extracellular fluid when a drop in blood pressure occurred in the previous dialysis treatment, and indicates that there is a high possibility that a drop in blood pressure will occur if water is removed any further. If the amount of extracellular fluid calculated in step S200 is larger than the reference value (NO in step S210), the calculation unit 24 judges that the amount of extracellular fluid is still excessive, and causes the monitor 26 to display the amount of extracellular fluid calculated in step S200 (S220). Then, the process returns to step S130, and the processes of steps S130 to S230 are repeated. That is, the same processes are repeated for the measurement data measured by the measurement unit 22 10 minutes after the previous measurement.

[0077] On the other hand, if the extracellular fluid volume calculated in step S200 is below the reference value (YES in step S210), the calculation unit 24 determines that there is a high possibility of a drop in blood pressure occurring, and causes the monitor 26 to display the fact that there is a high possibility of a drop in blood pressure occurring, along with the extracellular fluid volume calculated in step S200 (S220).

[0078] If steps S110 and S120 are skipped (i.e., if no drop in blood pressure has occurred in the previous dialysis treatment, or if the extracellular fluid volume at the time when a drop in blood pressure occurred in the previous dialysis treatment is unknown), step S210 is skipped and the process proceeds to step S220. That is, after the extracellular fluid volume is calculated in step S200, the calculated extracellular fluid volume is displayed on monitor 26 (S220). Then, the process returns to step S130, and the processes of steps S130 to S230 are repeated.

[0079] In this embodiment, the uric acid concentration in the dialysis effluent is measured at any time during dialysis treatment, and the extracellular fluid volume during dialysis is calculated from the measured uric acid concentration at any time. This makes it possible to grasp the extracellular fluid volume during dialysis, and to grasp the internal water status of the dialysis patient in real time.

[0080] In this embodiment, the possibility of blood pressure reduction is detected by calculating the extracellular fluid volume and comparing the calculated extracellular fluid volume with a reference value, but the present invention is not limited to such a configuration. For example, when setting the reference value, the value of the extracellular fluid volume when blood pressure reduction occurred in the previous dialysis treatment may be converted to the value of the uric acid concentration in the dialysis effluent, and a value slightly larger than the converted uric acid concentration may be set as the reference value. In this case, the possibility of blood pressure reduction can be detected by comparing the acquired uric acid concentration in the dialysis effluent with the reference value without calculating the extracellular fluid volume from the uric acid concentration in the dialysis effluent.

[0081] Example 2 In the above-mentioned first embodiment, the uric acid concentration in the dialysis effluent was measured, but the present invention is not limited to such a configuration. For example, the urea concentration in the dialysis effluent may be measured using the monitor device 10.

[0082] As shown in FIG. 1, a first reaction liquid supply unit 18 and a second reaction liquid supply unit 20 are connected to the reaction unit 12. The first reaction liquid supply unit 18 is configured to supply 160 μL of a first reaction liquid to the reaction unit 12 after the dialysis effluent is supplied to the reaction unit 12. The second reaction liquid supply unit 20 is configured to supply 40 μL of a second reaction liquid to the reaction unit 12 after the first reaction liquid is supplied to the reaction unit 12. The first reaction liquid contains a carbonate buffer solution, β-nicotinamide adenine dinucleotide phosphate (β-NADPH) 0.3 mmol / L, glutamate dehydrogenase 3.0 U / mL, isocitrate dehydrogenase 1.24 U / mL, isocitrate acid 13 mmol / L, α-ketoglutaric acid 10 mmol / L, and MgCl2 0.18 mmol / L. The second reaction solution contains triethanolamine buffer, urease at 12 U / mL, and disodium ethylenediaminetetraacetate at 100 mmol / L. The urea concentration in the dialysis effluent can be measured by mixing the first reaction solution and the second reaction solution with the dialysis effluent. After 1.5 minutes have elapsed since the first reaction solution and the second reaction solution were reacted with the dialysis effluent in the reaction unit 12, the dialysis effluent after the reaction is transferred from the reaction unit 12 to the measurement unit 22.

[0083] In a verification conducted by the present inventors, it was confirmed that even when the urea concentration was used instead of the uric acid concentration in the monitor device 10 of this embodiment, the urea concentration in the dialysis effluent discharged during dialysis treatment was accurately measured in the measurement unit 22.

[0084] In the verification, hemodialysis was performed on three chronic dialysis patients D to F, and the urea concentration in the dialysis effluent measured by the measuring unit 22 of the monitoring device 10 of this embodiment during dialysis treatment was recorded.

[0085] As a comparative example, dialysis treatment was performed on the same three chronic dialysis patients A to C, and the dialysis effluent was collected during dialysis treatment, and the urea concentration in the dialysis effluent was measured using a conventionally known urea measurement method (hereinafter simply referred to as the "conventional urea concentration measurement method").

[0086] In the conventional urea concentration measurement method, the absorbance of the standard solution (urea solution) was measured first. In detail, 160 μL of reagent A was added to 2.4 μL of the standard solution and mixed. Reagent A contains carbonate buffer, β-nicotinamide adenine dinucleotide phosphate (reduced form) (β-NADPH), glutamate dehydrogenase (GIDH) (derived from yeast), isocitrate dehydrogenase (iCDH) (derived from microorganisms), and α-ketoglutaric acid (α-KG). After heating at 37°C for 5 minutes, the absorbance at a wavelength of 340 nm (hereinafter also referred to as absorbance 1) was measured using the dialysate as a control. Next, 40 μL of reagent B was further mixed with the standard solution mixed with reagent A. Reagent B contains Good's buffer and urease (derived from sword bean). After heating at 37°C, the absorbance at a wavelength of 340 nm (hereinafter also referred to as absorbance 2) was measured using the dialysate as a control. Next, 160 μL of reagent A was added to each of the collected dialysis effluents, mixed, and heated at 37°C for 5 minutes, and then the absorbance at a wavelength of 340 nm (hereinafter also referred to as absorbance 3) was measured using the dialysate as a control. Next, 40 μL of reagent B was further mixed with each of the dialysis effluents mixed with reagent A, and heated at 37°C, and then the absorbance at a wavelength of 340 nm (hereinafter also referred to as absorbance 4) was measured using the dialysate as a control.

[0087] Next, the urine concentration in the dialysis effluent was calculated using the following formula 9.

[0088]

number

[0089] 13 to 15 show the urea concentration in the dialysis effluent measured by the measuring unit 22 of the monitor device 10 of this embodiment and the urea concentration in the dialysis effluent measured by the conventional urea concentration measuring method for each of the three chronic dialysis patients D to F. In FIG. 13 to FIG. 15, the vertical axis shows the urea concentration in the dialysis effluent, and the horizontal axis shows the dialysis treatment time. The solid line shows the urea concentration in the dialysis effluent measured by the measuring unit of the monitor device of this embodiment, and the dashed line shows the urea concentration in the dialysis effluent measured by the conventional urea concentration measuring method. As shown in FIG. 13 to FIG. 15, for each of the three chronic dialysis patients D to F, the urea concentration in the dialysis effluent measured by the measuring unit 22 of the dialysis system 1 of this embodiment and the urea concentration in the dialysis effluent measured by the conventional urea concentration measuring method were approximately the same. In this way, it was confirmed that the urea concentration in the dialysis effluent measured by the measuring unit 22 during dialysis treatment was accurately measured in the monitor device 10 of this embodiment.

[0090] In this embodiment, the monitor device 10 is used to calculate the amount of body fluid. Urea passes through the red blood cell membrane, and therefore exists in both the intracellular and extracellular compartments in the living body. Therefore, the urea concentration correlates with the amount of body fluid. In this embodiment, the calculation unit 24 replaces uric acid with urea, and replaces the amount of extracellular fluid with the amount of body fluid, and executes a process similar to the process for calculating the amount of extracellular fluid in the above embodiment 1 (the process shown in the flowchart of FIG. 6). Note that, since urea passes through the red blood cell membrane, the hematocrit correction using the formula expressed by the above formula 4 can be omitted. By executing such a process, the amount of body fluid during dialysis can be calculated using the urea concentration in the dialysis effluent measured by the measurement unit 22.

[0091] In the above-mentioned first embodiment, the monitor device 10 monitors the uric acid concentration in the dialysis effluent, and in the above-mentioned second embodiment, the monitor device 10 monitors the uric acid concentration in the dialysis effluent, but the present invention is not limited to such a configuration. For example, the monitor device 10 may include a first measurement unit that monitors the uric acid concentration in the dialysis effluent and a second measurement unit that monitors the uric acid concentration in the dialysis effluent. By including such two measurement units, the calculation unit 24 can calculate the amount of extracellular fluid during dialysis from the uric acid concentration in the dialysis effluent monitored by the first measurement unit, and can calculate the amount of body fluid during dialysis from the urea concentration in the dialysis effluent monitored by the second measurement unit. In addition, the calculation unit 24 can also calculate the amount of intracellular fluid during dialysis from the calculated amount of extracellular fluid during dialysis and the amount of body fluid during dialysis.

[0092] In the above-mentioned first and second embodiments, the uric acid concentration and urea concentration in the dialysis effluent are monitored to calculate the extracellular fluid volume, body fluid volume, and intracellular fluid volume during dialysis, but the present invention is not limited to such a configuration. The monitor device 10 may be configured to monitor the concentration of substances removed by dialysis, such as β2 microglobulin, α1 globulin, and albumin, in the dialysis effluent. The calculation unit 24 may also calculate the amount of removal of these substances from the monitored concentration of the substances. In this case, the amount of removal of the substances to be removed during dialysis treatment can be grasped at any time. Therefore, the treatment time can be extended or the treatment method can be changed during dialysis according to the amount of removal of these substances during dialysis, and advanced treatment according to the situation can be performed.

[0093] Points to note regarding the dialysis system 1 described in the embodiment will be described below. The calculation unit 24 in the embodiment is an example of an "abnormality detection unit" and a "storage unit", and the monitor 26 is an example of an "alarm unit".

[0094] Although specific examples of the technology disclosed in this specification have been described in detail above, these are merely examples and do not limit the scope of the claims. The technology described in the claims includes various modifications and variations of the specific examples exemplified above. Furthermore, the technical elements described in this specification or drawings exhibit technical utility alone or in various combinations, and are not limited to the combinations described in the claims at the time of filing. Furthermore, the technology exemplified in this specification or drawings achieves multiple objectives simultaneously, and achieving one of the objectives itself has technical utility. [Explanation of symbols]

[0095] 1:Dialysis system 10: Monitor device 12: Reaction section 16: Pump 22: Measuring part 24: Arithmetic section 26: Monitor 30: Dialysis machine

Claims

1. 1. A monitoring device for monitoring a concentration of a substance removed by dialysis, comprising: A measuring unit that measures the concentration of the substance in the dialysis effluent discharged from the blood purifier over time; a calculation unit that calculates an amount of the substance removed by dialysis from the concentration of the substance measured by the measurement unit, and calculates biological information based on the calculated amount of removal; A monitor device comprising:

2. the substance is uric acid, The monitor device according to claim 1 , wherein the biological information is an extracellular fluid volume.

3. the substance is urea, The monitor device according to claim 1 , wherein the biological information is an intracellular fluid volume.

4. The monitor device according to claim 1 , wherein the measurement unit includes an electrode sensor, a near-infrared spectroscopic sensor, or a Raman spectroscopic sensor that detects the concentration of the substance in the dialysis effluent.

5. The monitor device according to claim 1 , further comprising an abnormality detection unit that detects an abnormality in dialysis based on a change over time in the concentration of the substance measured by the measurement unit.

6. The monitor device according to claim 5 , further comprising a notification unit that notifies the abnormality when the abnormality is detected by the abnormality detection unit.

7. A memory unit that stores an extracellular fluid volume at the time of blood pressure reduction, which is the extracellular fluid volume at the time when blood pressure reduction occurred in a past dialysis; a notification unit that notifies the user that there is a high possibility of blood pressure reduction occurring when the extracellular fluid volume calculated by the calculation unit becomes equal to or less than a reference value that is set based on the extracellular fluid volume at the time of blood pressure reduction; The monitoring device of claim 2 further comprising:

8. A memory unit that stores a blood pressure drop concentration, which is a concentration of the substance in the dialysis effluent when a blood pressure drop occurred in a past dialysis; a notification unit that notifies a user that there is a high possibility of blood pressure decreasing when the concentration of the substance measured by the measurement unit becomes equal to or lower than a reference value that is set based on the concentration at the time of blood pressure decreasing; The monitoring device of claim 2 further comprising:

9. The monitor device according to claim 1 , wherein the calculation unit further calculates at least one of a blood concentration and a serum concentration of the substance from the amount of the substance removed.

10. A dialysis machine equipped with the blood purifier; A monitor device according to any one of claims 1 to 9; A dialysis system comprising:

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