JP7218660B2 - Extracellular fluid volume standardization device, extracellular fluid volume evaluation device provided with the same, and computer program for standardizing extracellular fluid volume - Google Patents

Description

The present specification relates to a technique for normalizing extracellular fluid volume used to assess the state of water content in a dialysis patient's body (ie, flooded, normal, dehydrated).

In dialysis patients, renal function is abolished, so all ingested water accumulates in the body's extracellular compartments. The amount of water accumulated in the extracellular compartment of the body is removed by dialysis therapy. Continue until the extracellular fluid volume is equal to that of a normal person. Therefore, by obtaining the amount of extracellular fluid after dialysis, it is possible to evaluate whether the amount of water remaining in the extracellular compartment after dialysis is appropriate. For example, Patent Literature 1 discloses an example of a method for calculating the extracellular fluid volume.

JP 2008-264217 A

As described above, obtaining the post-dialysis extracellular fluid volume allows assessment of the amount of water left in the body's extracellular compartment after dialysis. However, the extracellular fluid volume obtained after dialysis is the total extracellular fluid volume in the cells of the whole body. The appropriate total amount of extracellular fluid after dialysis varies depending on the body size of the dialysis patient. A dialysis patient with a large physique has a larger appropriate total extracellular fluid volume after dialysis than a dialysis patient with a small physique. That is, the appropriate total amount of extracellular fluid after dialysis differs for each dialysis patient. In order to define the appropriate amount of extracellular fluid after dialysis for all dialysis patients with substantially the same numerical value, it was necessary to standardize the extracellular fluid volume by some measure of body size.

The post-dialysis extracellular fluid volume obtained using conventional methods is the total extracellular fluid volume in all tissues in the body. However, among tissues in the body, the ratio of extracellular fluid volume to tissue weight differs between adipose tissue and other tissues (Chamney PW, et al.: A whole-body model to distinguish excess fluid from the hydration of major body tissues. Am J Clin Nutr. 2007; 85: 80-89.). That is, even if the body weight is the same, the total extracellular fluid volume in the body differs between lean dialysis patients and obese dialysis patients. Therefore, all body weights, such as post-dialysis body weight, ideal body weight, body surface area, or non-fat body weight, which are currently used to correct extracellular fluid volume, can be used without distinguishing between adipose and non-adipose tissue weights. Correcting the extracellular fluid volume with an index of body size, which reflects only the total weight of the tissues, made it difficult to correctly evaluate whether the extracellular fluid volume was appropriate after dialysis in dialysis patients.

This specification discloses a technique for normalizing extracellular fluid volume used to assess the state of water content within the body of a dialysis patient.

The extracellular fluid volume standardization device disclosed herein is used to evaluate whether the state of the amount of water contained in the body of a dialysis patient is flooded, normal, or dehydrated. The extracellular fluid volume standardization device has an extracellular fluid volume acquisition unit that acquires the extracellular fluid volume in the dialysis patient's body, a height acquisition unit that acquires the dialysis patient's height, and a dialysis patient's weight after dialysis. an intracellular fluid volume acquiring unit that acquires the intracellular fluid volume of a dialysis patient; and a function memory that stores a function that defines the standard blood volume using the height, post-dialysis weight, and intracellular fluid volume as variables. a standard blood volume calculation unit that calculates the standard blood volume of a dialysis patient by substituting the obtained height, the obtained weight after dialysis, and the obtained intracellular fluid volume into a function; a standardization unit that standardizes the extracellular fluid volume obtained by the extracellular fluid volume acquisition unit based on the standard blood volume calculated by the calculation unit.

As a result of intensive research by the present inventors, it was found that the state of the body's water content can be appropriately evaluated by standardizing the extracellular fluid volume based on the standard blood volume calculated using the body fat mass and the intracellular fluid volume. There was found. In the extracellular fluid volume standardization device described above, the obtained extracellular fluid volume is standardized based on the obtained standard blood volume, so that the extracellular fluid volume is corrected to the standardized extracellular fluid volume per standard blood volume. . Since the amount of extracellular fluid is the total amount of extracellular fluid in the body, the appropriate amount differs for each dialysis patient. A dialysis patient's hydration status (flooded, normal, dehydrated) can be assessed. Also, the standard blood volume is correlated with the fat mass and muscle mass. Body fat mass, ie, degree of obesity, can be estimated from height and weight, and is usually displayed using BMI, for example. Specifically, if the BMI is less than 22, it is determined that the person is thin, and if the BMI is lower than this value, it is determined that the lower the weight, the leaner the person is. On the other hand, if the BMI is higher than 22, it is determined that the subject is obese, and if the BMI is higher than this value, it is determined that the subject is obese. By the way, muscle mass correlates with intracellular fluid volume. Therefore, it can be said that the standard blood volume has a correlation with BMI and intracellular fluid volume. Therefore, by calculating the standard blood volume using a function defined by the BMI after dialysis and the intracellular fluid volume after dialysis, an appropriate standard blood volume is calculated according to the degree of obesity and build of the dialysis patient. be able to.

In addition, the extracellular fluid volume evaluation device disclosed in the present specification evaluates whether the state of the amount of water contained in the body of a dialysis patient is an overflow state, a normal state, or a dehydration state. The extracellular fluid volume evaluation device determines the state of water content in the dialysis patient's body based on the extracellular fluid volume standardization device and the extracellular fluid volume standardized by the extracellular fluid volume standardization device. and a determination unit for

The above extracellular fluid volume evaluation device determines the state of water in the dialysis patient's body based on the extracellular fluid volume standardized by the above extracellular fluid volume standardization device. Therefore, it is possible to achieve the same effect as the extracellular fluid volume standardization device described above.

The present specification also discloses a computer program for standardizing the extracellular fluid volume used to evaluate whether the state of the water content in the body of a dialysis patient is a flooded state, a normal state, or a dehydrated state. . The computer program comprises a computer, an extracellular fluid volume acquisition unit that acquires the extracellular fluid volume in the body of the dialysis patient, a height acquisition unit that acquires the height of the dialysis patient, and a weight of the dialysis patient after dialysis. A weight acquisition unit, an intracellular fluid volume acquisition unit that acquires the intracellular fluid volume of a dialysis patient, height and weight after dialysis (for example, BMI calculated from height and weight after dialysis), and intracellular fluid volume A function storage unit that stores a function that defines the standard blood volume as a variable, and the obtained height and the obtained weight after dialysis (for example, the BMI calculated from the obtained height and the obtained weight after dialysis). By substituting the obtained intracellular fluid volume into the function, the standard blood volume calculation unit calculates the standard blood volume of the dialysis patient, and the extracellular fluid is calculated based on the standard blood volume calculated by the standard blood volume calculation unit. It functions as a calculation unit that standardizes the extracellular fluid volume acquired by the volume acquisition unit.

The figure which shows the system configuration|structure of the extracellular fluid volume calculation apparatus which concerns on an Example. 4 is a flow chart showing an example of a process of determining the state of the amount of water contained in the body of a dialysis patient by the computing device; Schematic diagram showing substances distributed in intracellular and extracellular compartments. FIG. 3 is a diagram showing the relationship between the membrane area of the dialyzer and the overall mass transfer-area coefficient of uric acid. The flowchart which shows an example of the process which an arithmetic unit calculates an extracellular fluid volume. FIG. 10 is a diagram showing the extracellular fluid volume standardized by the method of the comparative example for the overflow group, the normal group, and the dehydration group. FIG. 10 is a diagram showing extracellular fluid volumes standardized by the method of Example for the overflow group, the normal group, and the dehydration group.

The main features of the embodiments described below are listed. It should be noted that the technical elements described below are independent technical elements, and exhibit technical usefulness alone or in various combinations, and are not limited to the combinations described in the claims as of the filing. do not have.

(Feature 1) In the extracellular fluid volume standardization device disclosed in the present specification, the function is BV as the standard blood volume, ICV as the intracellular fluid volume, and body fat mass calculated from height and weight after dialysis. When the index to be reflected (body mass index) is BMI and a and b are constants, it may be defined by the formula represented by Equation 36 below. With such a configuration, the standard blood volume can be calculated with high accuracy.

(Feature 2) The extracellular fluid volume standardization device disclosed in the present specification may further include a uric acid concentration acquisition unit that acquires the plasma uric acid concentration of a dialysis patient before and after dialysis. The extracellular fluid volume acquisition unit may calculate the extracellular fluid volume after dialysis based on the balance of uric acid before and after dialysis. According to such a configuration, it is possible to accurately calculate the extracellular fluid volume after dialysis.

(Feature 3) In the extracellular fluid volume standardization device disclosed in this specification, the extracellular fluid volume may be calculated based on the impedance of the dialysis patient.

Hereinafter, an extracellular fluid volume evaluation device 10 according to an example will be described. The extracellular fluid volume evaluation device 10 is used to evaluate whether the state of the amount of water contained in the body of a dialysis patient is an overflow state, a normal state, or a dehydration state. Whether a dialysis patient is overhydrated (i.e., the patient is flooded) or dehydrated (i.e., the patient is dehydrated), intracellular It is known that the amount of water in compartment 40 changes very little, only the amount of water in extracellular compartment 50 increases or decreases. Therefore, it is the amount of extracellular fluid after dialysis that needs to be adjusted by water removal by dialysis. Therefore, by obtaining the extracellular fluid volume of the dialysis patient after dialysis, it is possible to evaluate whether the extracellular fluid volume of the dialysis patient is appropriate after dialysis. On the other hand, for example, the amount of extracellular fluid in a dialysis patient after dialysis calculated using a method such as the impedance method is the total amount of extracellular fluid in the body of the dialysis patient. Therefore, if the dialysis patient is large, the appropriate amount of extracellular fluid after dialysis will be large, and if the dialysis patient is small, the appropriate amount of extracellular fluid after dialysis will be less. That is, the appropriate value for the total amount of extracellular fluid after dialysis differs for each dialysis patient. Therefore, the calculated total amount of extracellular fluid cannot be used to accurately evaluate the amount of water (extracellular fluid amount) in the body of a dialysis patient after dialysis. Therefore, in order to evaluate whether or not the amount of extracellular fluid in dialysis patients after dialysis is appropriate, the amount of extracellular fluid after dialysis is standardized. Hereinafter, the total amount of extracellular fluid in the body of a dialysis patient is simply referred to as "extracellular fluid amount", and the standardized extracellular fluid amount calculated by the extracellular fluid amount evaluation device 10 is referred to as "standard extracellular fluid amount. ”.

As shown in FIG. 1 , the extracellular fluid volume evaluation device 10 is composed of an arithmetic device 12 and an interface device 30 . The computing device 12 can be configured by a computer including, for example, a CPU, a ROM, a RAM, and the like. When the computer executes the programs, the arithmetic device 12 functions as the extracellular fluid volume calculator 20, the standard blood volume calculator 22, the extracellular fluid volume standardizer 24, the determination unit 26, and the like shown in FIG. The processing of the extracellular fluid volume calculator 20, the standard blood volume calculator 22, the extracellular fluid volume standardizer 24, and the determination unit 26 will be described in detail later.

Further, as shown in FIG. 1, the computing device 12 includes a patient information storage unit 14, a dialysis information storage unit 16, and a calculation method storage unit 18. The patient information storage unit 14 stores various information regarding dialysis patients. The patient information storage unit 14 stores dialysis patient information input via the interface device 30, and dialysis patient information calculated by the extracellular fluid volume calculation unit 20, the standard blood volume calculation unit 22, and the extracellular fluid volume standardization unit 24. store information about The dialysis patient information input via the interface device 30 includes, for example, the dialysis patient's plasma uric acid concentration before and after dialysis, hematocrit value, plasma urea concentration before and after dialysis, height, weight after dialysis, and the like. The information on the dialysis patient calculated by the extracellular fluid volume calculation unit 20 is the extracellular fluid volume of the dialysis patient calculated based on the information input via the interface device 30 (i.e., the extracellular fluid volume in the dialysis patient's body). total amount of liquid). The information about the dialysis patient calculated by the standard blood volume calculator 22 is the post-dialysis intracellular fluid volume and the standard blood volume of the dialysis patient calculated based on the information input via the interface device 30 . The information about the dialysis patient calculated by the extracellular fluid volume standardization unit 24 is the information input via the interface device 30 and the extracellular fluid volume and standard blood volume of the dialysis patient calculated by the extracellular fluid volume calculation unit 20. It is the standard extracellular fluid volume of the dialysis patient calculated based on the standard blood volume of the dialysis patient calculated by the calculator 22 .

The dialysis information storage unit 16 stores various information related to dialysis. The dialysis information storage unit 16 stores information on dialysis input via the interface device 30 and information on dialysis calculated by the extracellular fluid volume calculation unit 20 . The dialysis-related information input via the interface device 30 includes, for example, the amount of water removed by dialysis, the dialysis time, the blood flow rate and dialysate flow rate passing through the dialyzer during dialysis, the membrane area of the dialyzer used for dialysis, the dialysis It is the general mass transfer-area coefficient for urea of the dialyzer used in The dialysis-related information calculated by the extracellular fluid volume calculation unit 20 is, for example, the overall mass transfer-area coefficient for uric acid in the dialyzer used for dialysis, which is calculated based on the information input via the interface device 30, They are uric acid clearance, amount of uric acid removed, and the like.

The calculation method storage unit 18 stores various formulas used to calculate the post-dialysis extracellular fluid volume, standard blood volume, and standard extracellular fluid volume. For example, the calculation method storage unit 18 stores formulas represented by numbers 3, 6 to 9, 13, 15, 23, 26, 32, and 35, which will be described in detail below. The extracellular fluid volume calculation unit 20, the standard blood volume calculation unit 22, and the extracellular fluid volume standardization unit 24 are stored in the patient information storage unit 14 and the dialysis information storage unit 16 in the formulas stored in the calculation method storage unit 18. Various numerical values used for calculating the extracellular fluid volume after dialysis are calculated by substituting various numerical values.

The interface device 30 is a display device that provides (outputs) various information calculated by the extracellular fluid volume evaluation device 10 to the operator, and is an input device that receives instructions and information from the operator. For example, the interface device 30 can display to the operator the calculated extracellular fluid volume after dialysis, the standard extracellular fluid volume, the amount of water contained in the dialysis patient's body, and the like. The interface device 30 also provides various information about dialysis patients (plasma uric acid concentration before and after dialysis, hematocrit value, plasma urea concentration before and after dialysis, height, weight after dialysis, etc.), various information about dialysis (water removal amount, dialysis time, blood flow rate through the dialyzer, dialysate flow rate through the dialyzer, membrane area of the dialyzer used for dialysis, overall mass transfer-area coefficient for urea in the dialyzer used for dialysis, etc.) be able to.

Next, the process of determining the state of the amount of water contained in the body of a dialysis patient using the extracellular fluid volume evaluation device 10 will be described. The extracellular fluid volume evaluation device 10 of the present embodiment standardizes the extracellular fluid volume of the dialysis patient (that is, the total amount of extracellular fluid in the body of the dialysis patient) using the standard blood volume of the dialysis patient, A standardized extracellular fluid volume (standard extracellular fluid volume) is used to evaluate the amount of water contained in the body of a dialysis patient.

As shown in FIG. 2, the computing device 12 first acquires the post-dialysis extracellular fluid volume of the dialysis patient (S12). Arithmetic device 12 may calculate the extracellular fluid volume after dialysis of a dialysis patient using various information input from interface device 30. For example, an external device (illustrated omitted), etc., of the dialysis patient after dialysis may be acquired via the interface device 30 . As an example of a method of acquiring the post-dialysis extracellular fluid volume of a dialysis patient, a process of calculating the post-dialysis extracellular fluid volume of a dialysis patient by the computing device 12 will be described below.

In this embodiment, the amount of extracellular fluid after dialysis is calculated by focusing on the balance of uric acid in the extracellular compartment 50 before and after dialysis. As shown in FIG. 3, the body's water compartment is divided into an intracellular compartment 40 and an extracellular compartment 50 , which is further divided into an interstitial compartment 52 and a vascular compartment 54 . Uric acid is distributed in both the intracellular compartment 40 and the extracellular compartment 50, but does not pass through the cell membrane 42 during the dialysis time of about 4 hours. Uric acid, on the other hand, passes through the capillary membrane 56 . Therefore, by focusing on the balance of uric acid in the extracellular compartment 50 before and after dialysis, the amount of extracellular fluid after dialysis can be calculated.

A method for calculating the extracellular fluid volume after dialysis based on the balance of uric acid in the extracellular compartment 50 before and after dialysis will be described in more detail. The amount of uric acid removed from the extracellular compartment 50 by dialysis (hereinafter also referred to as "uric acid removal amount") is the amount of uric acid distributed in the extracellular compartment 50 before dialysis and the amount of uric acid distributed in the extracellular compartment 50 after dialysis. matches the difference of By the way, the amount of uric acid distributed in the extracellular compartment 50 can be calculated as the product of the amount of extracellular fluid and the concentration of uric acid in the extracellular compartment 50 . Therefore, the following formula (1) holds. In addition, _acid E indicates the amount of uric acid removed, _ecf Vs indicates the amount of extracellular fluid before dialysis, _ecf Ve indicates the amount of extracellular fluid after dialysis, and _acid Cs indicates the concentration of uric acid in the extracellular compartment 50 before dialysis. and _acid Ce indicates the post-dialysis uric acid concentration in the extracellular compartment 50 . Note that since uric acid crosses the capillary membrane 56 , the uric acid concentration in the vascular compartment 54 is equal to the uric acid concentration in the interstitial compartment 52 . Also, since the extracellular compartment 50 is a combined compartment of the vascular compartment 54 and the interstitial compartment 52 , the uric acid concentration in the extracellular compartment 50 is also the uric acid concentration in the vascular compartment 54 . Therefore, the uric acid concentration in the extracellular compartment 50 is also the plasma uric acid concentration.

Next, the balance of water during dialysis in the extracellular compartment 50 will be described. The difference between the amount of extracellular fluid before dialysis and the amount of extracellular fluid after dialysis corresponds to the amount of water removed from the body by dialysis (hereinafter also simply referred to as "water removal amount"). Therefore, the following formula (2) holds. In addition, _dial EW indicates the amount of water removed.

From the equations represented by Equations 1 and 2 above, the equation represented by Equation 3 below is obtained.

As described above, the uric acid concentration _acid Cs before dialysis in the extracellular compartment 50 is equal to the plasma uric acid concentration before dialysis, and the uric acid concentration _acid Ce after dialysis in the extracellular compartment 50 is equal to the plasma uric acid concentration after dialysis. . The plasma uric acid concentration _acid Cs before dialysis and the plasma uric acid concentration _acid Ce after dialysis can be obtained as measured values. Also, the amount of water removed _dial EW can be acquired as an actual measurement value. Therefore, if the uric acid removal amount _acid E can be obtained or calculated, the post-dialysis extracellular fluid amount _ecf Ve can be calculated using the above equation (3). A method for calculating the uric acid removal amount _acid E will be described below.

In this example, the calculation of the amount of uric acid removed _acid E requires the uric acid clearance of the dialyzer, and the calculation of the uric acid clearance of the dialyzer requires the overall mass transfer-area coefficient of uric acid of the dialyzer. In this example, the overall mass transfer-area coefficient of uric acid in the dialyzer used for dialysis is calculated based on the membrane area of the dialyzer. In detail, based on the membrane area of the dialyzer used for dialysis, the overall mass transfer-area coefficient for uric acid in the dialyzer was calculated, and the calculated overall mass transfer-area coefficient for uric acid, the blood flow rate passing through the dialyzer, and the dialyzer were calculated. The uric acid clearance of the dialyzer is calculated from the passing dialysate flow rate, and the uric acid removal amount _acid E is calculated using the calculated uric acid clearance.

Next, a method for calculating the uric acid clearance of the dialyzer will be described in detail. Plasma uric acid concentration is known to decrease exponentially during dialysis. Therefore, the following formula (4) holds. _Acid C(t) indicates the plasma uric acid concentration at time t during dialysis. Further, when _acid A is a coefficient and Td is a dialysis time, it is expressed by Equation 5 below.

From the above equations 4 and 5, the following equation 6 is obtained.

Also, the uric acid removal rate at time t during dialysis can be calculated by multiplying the uric acid clearance of the dialyzer at time t by the plasma uric acid concentration _acid C(t) at time t. Therefore, the following formula (7) is established. Note that _acid F(t) indicates the uric acid removal rate at time t during dialysis, and _acid K(t) indicates uric acid clearance at time t during dialysis.

The dialyzer uric acid clearance _acid K(t) is a variable that depends on time t. Uric acid is distributed both in plasma and in blood cells (Nagendra S, et al: A comparative study of plasma uric acid, erythrocyte uric acid and urine uric acid levels in type 2 diabetic subjects. Merit Research Journal 3: 571- 574, 2015) and does not permeate the red blood cell membrane. Thus, uric acid is removed during dialysis only from the plasma compartment in the blood passing through the dialyzer (Eric Descombes, et al: Diffusion kinetics of urea, creatinine and uric acid in blood during hemodialysis. Clinical implications. Clinical Nephrology 40: 286-295, 1993). Therefore, when calculating the dialyzer uric acid clearance _acid K(t), the plasma flow rate through the dialyzer is used instead of the blood flow rate through the dialyzer. By the way, the hematocrit value increases with time during dialysis as the blood is concentrated by water removal during dialysis. Therefore, plasma flux does not remain constant during dialysis. Therefore, the dialyzer uric acid clearance _acid K(t), which is calculated using the blood plasma flow rate through the dialyzer, also changes as the blood plasma flow rate through the dialyzer changes over time. That is, the dialyzer uric acid clearance _acid K(t) becomes a variable dependent on time t. Therefore, when calculating the amount of uric acid removed _acid E, the uric acid removal rate at time t calculated using the formula represented by Equation 7 is changed from t = 0 to t = Td at regular intervals (for example, at intervals of 0.1 minute ). That is, the uric acid removal amount _acid E is calculated using the following equation (8).

The uric acid clearance _acid K(t) at time t can be calculated using known formulas for calculating the clearance of dialyzer solutes. That is, the uric acid clearance _acid K(t) at time t can be calculated using the following equation (9). In addition, _acid KOA indicates the overall mass transfer-area coefficient for uric acid in the dialyzer, Q _Pt indicates the plasma flow rate through the dialyzer at time t during dialysis, and Q _D indicates the dialysate flow rate through the dialyzer. .

The dialysate flow rate Q _D passing through the dialyzer can be obtained as a measured value. Therefore, if the overall mass transfer-area coefficient _acid KOA for uric acid in the dialyzer and the plasma flow rate Q _Pt through the dialyzer at time t can be obtained or calculated, the uric acid clearance _acid K(t) at time t can be calculated.

A method for calculating the overall mass transfer-area coefficient _acid KOA for uric acid in the dialyzer will be described. As a result of intensive studies by the present inventors, it was found that when a hollow-fiber dialyzer is used, there is a correlation between the total transfer substance-area coefficient _acid KOA for uric acid in the dialyzer and the membrane area of the dialyzer. In the following, the relationship between the global transport mass-area coefficient _acid KOA for uric acid in the dialyzer and the membrane area of the dialyzer will be described.

An example of calculating the overall mass transfer-area coefficient for uric acid for dialyzers with different membrane areas based on ex vivo experiments using bovine blood will be described. As the dialyzer, there are four types of hollow fiber type (PES-SEαeо series, manufactured by Nipro Corporation) belonging to the same series and having membrane areas of 1.1 m ² , 1.5 m ² , 2.1 m ² and 2.5 m ² . was used. Bovine blood with a hematocrit value of 32% was flowed through each dialyzer at 200 mL/min, and dialysate was flowed at 500 mL/min in countercurrent flow. One minute after starting to flow bovine blood (hereinafter also simply referred to as "blood") through each dialyzer, blood was collected at the blood inlet and blood outlet of each dialyzer, immediately centrifuged, and the plasma uric acid concentration was measured. Based on these measured values, the ex vivo uric acid clearance of each dialyzer was calculated using the formula shown in Equation 10. K indicates the uric acid clearance of the dialyzer, Cin indicates the plasma uric acid concentration at the blood inlet of the dialyzer, Cout indicates the plasma uric acid concentration at the blood outlet of the dialyzer, and QP indicates the plasma flow rate through the dialyzer.

Plasma is the name for the compartment of blood excluding blood cell components. Therefore, the blood plasma flow rate QP passing through the dialyzer in Equation 10 is calculated by Equation 11 below. Ht indicates the hematocrit value, and Q _B indicates the blood flow rate through the dialyzer.

As mentioned above, the hematocrit value of the bovine blood used in the above ex vivo experiments was 32%, and the blood flow rate QB through each _dialyzer was 200 mL/min. Substituting these values into Equation 11, therefore, the plasma flow rate QP through each dialyzer used in this experiment is 136 mL/min.

Next, using the following formula (12) derived by modifying the formula (9), the overall transfer substance-area coefficient for uric acid of each dialyzer was calculated. In addition, _KoA indicates the overall transfer mass-area coefficient for uric acid of each dialyzer, QD indicates the dialysate flow rate through each dialyzer in the above ex vivo experiment, and K is the above ex vivo experiment. Uric acid clearance of each dialyzer measured is shown. As described above, in the above ex vivo experiment, the dialysate flow rate QD through each _dialyzer was 500 mL/min, and the plasma flow rate QP through each dialyzer was 136 mL/min.

When the overall transfer mass-area coefficient for uric acid in each dialyzer was calculated as described above, the following results were obtained.

FIG. 4 is a graph showing the relationship between the dialyzer membrane area and the overall transport mass-area factor for uric acid for the results shown in Table 1 above. As shown in FIG. 4, a correlation represented by the following equation (13) was recognized between the membrane area of the dialyzer and the overall transfer substance-area coefficient of uric acid.

From the above, by inputting the membrane area of the dialyzer used for dialysis into the equation expressed by Equation 13 above, the overall transfer substance-area coefficient _acid KOA of uric acid can be calculated.

Next, a method for calculating the plasma flow rate Q _Pt through the dialyzer at time t during dialysis will be described. The amount of plasma compartment in a patient's blood is given by the equation given in Equation 14 below. In addition, PV indicates plasma volume, BV indicates blood volume, and Ht indicates hematocrit value.

Rewriting the equation (14) into the relationship between the blood flow velocity passing through the dialyzer and the plasma flow velocity at time t during dialysis, the equation (15) is obtained. Here, Ht(t) indicates the hematocrit value (%) at time t during dialysis, _QB indicates the blood flow rate through the dialyzer at time t during dialysis, and _QPt indicates the blood flow rate through the dialyzer at time t during dialysis. shows the plasma flux through the The blood flow rate QB through the _dialyzer is constant during dialysis.

Here, the blood circulation velocity Q _B passing through the dialyzer does not change with time and can be obtained as an actual measurement value. Therefore, if the hematocrit value Ht(t) at time t can be calculated, the plasma flow rate Q _Pt passing through the dialyzer can be calculated. Therefore, a method for calculating the hematocrit value Ht(t) at time t will be described.

If the water removal rate is constant, the blood volume in the body during dialysis will decrease substantially linearly. This is confirmed by the inventors by observing the measurement results of a BV meter (blood volume meter). Therefore, if the blood volume at time t during dialysis is defined as BV(t) and the blood volume at t=0 is defined as BVs, the blood volume BV(t) at time t during dialysis is given by the following equation (16): It is shown by the formula that expresses However, α usually takes a negative value.

By defining the blood volume at the end of dialysis as BVe and substituting t=Td into the equation (16), the α value can be calculated.

By rewriting the above equation (17), the following equation (18) is obtained.

By substituting α calculated by the equation (18) into the equation (16), the following equation (19) is obtained.

On the other hand, the total number of red blood cells in the body is constant and does not change over time. This means that the total red blood cell volume is also constant and does not change over time. By the way, the total red blood cell volume in the body is obtained as the product of the blood volume in the body and 1/100 of the hematocrit value. Therefore, the following equations 20 to 22 are obtained. TE indicates the total volume of red blood cells in the body.

The following equation (23) is obtained from the equation (19) and the equations (20-22).

The hematocrit value Hts before dialysis and the hematocrit value Hte after dialysis can be obtained as measured values. Also, as described above, the dialysis time Td can be obtained as an actual measurement value. Therefore, by substituting the hematocrit value Hts before dialysis, the hematocrit value Hte after dialysis, and the dialysis time Td into the equation represented by Equation 23 above, the hematocrit value Ht(t) at time t during dialysis can be obtained. can be calculated. Then, by substituting the hematocrit value Ht(t) at time t calculated using the formula 23 into the formula 15 and the obtained blood flow rate Q _B passing through the dialyzer, The plasma flux Q _Pt through the dialyzer can be calculated. That is, the plasma flow rate Q _Pt passing through the dialyzer at time t can be calculated from the hematocrit value Hts before dialysis, the hematocrit value Hte after dialysis, the dialysis time Td, and the blood flow rate Q _B .

9, the overall mass transfer-area coefficient _acid KOA of the dialyzer for uric acid calculated using Eq. 13, and the plasma flux through the dialyzer at time t calculated using Eq. 15. By substituting the rate Q _Pt and the dialysate flow rate Q _D , which is constant throughout the course of dialysis, the uric acid clearance _acid K(t) at dialyzer time t can be calculated. That is, the membrane area of the dialyzer used for dialysis, the pre-dialysis hematocrit value Hts, the post-dialysis hematocrit value _Hte , the dialysis time Td, the blood flow rate QB, and the dialysate that is constant throughout the course of dialysis The uric acid clearance _acid K(t) at time t of the dialyzer used for dialysis can be calculated from the flow rate Q _D .

8, the uric acid clearance _acid K(t) at time t calculated using the formula 9, and the plasma uric acid concentration _acid C at time t calculated using the formula 6 ( By substituting t), the uric acid removal amount _acid E can be calculated. That is, the membrane area of the dialyzer used for dialysis, the plasma uric acid concentration _acid Cs before dialysis, the plasma uric acid concentration _acid Ce after dialysis, the hematocrit value Hts before dialysis, the hematocrit value Hte after dialysis, and the dialysis time The uric acid removal amount _{acid E} can be calculated from Td, the blood flow rate QB passing through the dialyzer, and the dialysate flow rate _QD passing through the dialyzer.

Furthermore, the amount of uric acid removed _acid E calculated using the formula represented by Formula 8 in addition to the formula represented by Formula 3, the obtained plasma uric acid concentration _acid Cs before dialysis, the plasma uric acid concentration _acid Ce after dialysis, and the amount of water removed _dial EW. By substituting , the post-dialysis extracellular fluid volume _ecf Ve can be calculated.

From the above, in this example, the extracellular fluid volume _ecf Ve after dialysis is the plasma uric acid concentration _acid Cs before dialysis, the plasma uric acid concentration _acid Ce after dialysis, the hematocrit value Hts before dialysis, and the hematocrit value Hts after dialysis. Calculate from the value _Hte , the amount of water removed _dial EW, the dialysis time Td, the blood flow rate QB passing through the dialyzer, the dialysate flow rate _QD passing through the dialyzer, and the membrane area of the dialyzer used for dialysis. can be done.

Next, a process of calculating the post-dialysis extracellular fluid volume _ecf Ve by the arithmetic unit 12 will be described. As shown in FIG. 5, first, the computing device 12 acquires various types of information about the dialysis patient (S22). Various types of information about dialysis patients are, for example, plasma uric acid concentrations _acid Cs and _acid Ce before and after dialysis, and hematocrit values Hts and Hte before and after dialysis. Various types of information about dialysis patients are acquired, for example, by the following procedure. A method for obtaining the plasma uric acid concentrations _acid Cs and _acid Ce before and after dialysis will be described as an example. First, blood is collected from dialysis patients before and after dialysis. Then, the collected blood before dialysis is centrifuged into blood cells and plasma, the uric acid concentration _acid Cs in the separated plasma is measured, and the collected blood after dialysis is centrifuged into blood cells and plasma, and separated. Uric acid concentration _acid Ce in blood plasma is measured. The method for measuring the uric acid concentration in plasma is not particularly limited. The operator inputs the measured plasma uric acid concentrations _acid Cs and _acid Ce into the interface device 30 before and after dialysis. The input pre- and post-dialysis plasma uric acid concentrations _acid Cs and _acid Ce are output from the interface device 30 to the arithmetic device 12 and stored in the patient information storage unit 14 . Further, the hematocrit values Hts and Hte before and after dialysis are measured from blood samples taken from dialysis patients before and after dialysis, respectively. These measured values are stored in the patient information storage section 14 via the interface device 30 .

Next, the extracellular fluid volume calculation unit 20 acquires various information regarding dialysis (S24). Various information related to dialysis includes, for example, water removal amount _dial EW, dialysis time Td, blood flow rate Q _B through the dialyzer, dialysate flow rate Q _D through the dialyzer, membrane area of the dialyzer, and the like. The amount of water removed _dial EW, the dialysis time Td, the blood flow rate Q _B through the dialyzer, the dialysate flow rate Q _D through the dialyzer, and the membrane area of the dialyzer are input to the interface device 30 by the operator. Then, the amount of water removed _dial EW, the dialysis time Td, the blood flow rate Q _B passing through the dialyzer, the dialysate flow rate Q _D passing through the dialyzer, and the membrane area of the dialyzer are output from the interface device 30 to the arithmetic device 12 and used for dialysis. It is stored in the information storage unit 16 .

In this embodiment, steps S22 and S24 are performed in this order, but the configuration is not limited to this. For example, step S24 may be performed first, and then step S22 may be performed. Moreover, the acquisition order of the plurality of pieces of information acquired in step S22 and the plurality of pieces of information acquired in step S24 is not particularly limited. All the items in steps S22 and S24 may be acquired. For example, the information acquired in step S24 may be acquired before all of the plurality of information acquired in step S22.

Next, the extracellular fluid volume calculation unit 20 uses the value of the membrane area of the dialyzer used for dialysis among the dialysis-related information acquired in step S24 to calculate the overall transfer substance-area coefficient _acid KOA of uric acid. (S26). The overall transfer substance-area coefficient _acid KOA of uric acid is calculated using the formula represented by Equation 13 above stored in the calculation method storage unit 18 . Specifically, the extracellular fluid volume calculation unit 20 substitutes the value of the membrane area of the dialyzer stored in the dialysis information storage unit 16 into the equation represented by Equation 13, and obtains the total transfer substance-area of the dialyzer related to uric acid. Calculate the coefficient _acid KOA. The calculated global transfer substance-area coefficient _acid KOA relating to uric acid in the dialyzer is stored in the dialysis information storage unit 16 .

Next, the extracellular fluid volume calculation unit 20 calculates the information on the dialysis patient acquired in step S22, the information on dialysis acquired in step S24, and the overall transfer substance-area coefficient _acid of uric acid in the dialyzer calculated in step S26. Using KOA, the uric acid clearance _acid K(t) at time t of the dialyzer used for dialysis is calculated (S28). The uric acid clearance of the dialyzer used for dialysis is calculated using the equations represented by Equations 9, 15 and 23 above stored in the calculation method storage unit 18 .

Specifically, the extracellular fluid volume calculation unit 20 first converts the pre-dialysis hematocrit value Hts and the post-dialysis hematocrit value Hte stored in the patient information storage unit 14 into the equation represented by Equation 23, and the dialysis information storage Substituting the dialysis time Td stored in the unit 16, the hematocrit value Ht(t) at time t during dialysis is calculated. Next, the extracellular fluid volume calculation unit 20 adds the hematocrit value Ht(t) at time t calculated using the formula 23 to the formula 15, and the dialyzer stored in the dialysis information storage unit 16. Substitute the blood flow rate through Q _B to calculate the plasma flow rate through the dialyzer at time t, Q _Pt . Then, the extracellular fluid volume calculation unit 20 calculates the total transfer substance of uric acid-area coefficient _acid KOA calculated in step S26 in the equation represented by Equation 9, and the dialyzer at time t calculated using the equation represented by Equation 15. By substituting the plasma flow rate Q _Pt through the dialyzer and the dialysate flow rate Q _D through the dialyzer, the uric acid clearance _acid K(t) at time t in the dialyzer used for dialysis is calculated. The calculated uric acid clearance _acid K(t) at time t is stored in the dialysis information storage unit 16 .

Next, the extracellular fluid volume calculation unit 20 calculates the information on the dialysis patient acquired in step S22, the information on dialysis acquired in step S24, and the uric acid clearance _acid K(t) at time t calculated in step S28. is used to calculate the uric acid removal amount _acid E (S30). The uric acid removal amount _acid E is calculated using the equations represented by Equations 6 and 8 above, which are stored in the calculation method storage unit 18 . Specifically, the extracellular fluid volume calculation unit 20 first converts the plasma uric acid concentration _acid Cs before dialysis and the plasma uric acid concentration after dialysis _acid Ce stored in the patient information storage unit 14 into the equation represented by Equation 6. , the dialysis time Td stored in the dialysis information storage unit 16 is substituted to calculate the plasma uric acid concentration _acid C(t) at time t during dialysis. Then, the extracellular fluid volume calculation unit 20 adds the uric acid clearance _acid K(t) at time t calculated in step S28 to the equation represented by Equation 8, and the amount of dialysis during dialysis calculated using the equation represented by Equation 6. Substituting the plasma uric acid concentration _acid C(t) at time t, the uric acid removal amount _acid E is calculated. The calculated uric acid removal amount _acid E is stored in the dialysis information storage unit 16 .

Finally, the extracellular fluid volume calculation unit 20 uses the information on the dialysis patient acquired in step S22, the information on dialysis acquired in step S24, and the uric acid removal amount _acid E calculated in step S30 to calculate the post-dialysis is calculated ( _S32 ). The post-dialysis extracellular fluid volume _ecf Ve is calculated using the equation represented by Equation 3 stored in the calculation method storage unit 18 .

Specifically, the extracellular fluid volume calculation unit 20 puts the uric acid concentration _acid Cs before dialysis and the uric acid concentration after dialysis _acid Ce into the equation represented by Equation 3, and the water removal amount _dial stored in the dialysis information storage unit 16. By substituting EW and the uric acid removal amount _acid E calculated in step S30, the post-dialysis extracellular fluid amount _ecf Ve is calculated. The calculated post-dialysis extracellular fluid volume _ecf Ve is stored in the patient information storage unit 14 .

In this example, the uric acid clearance of the dialyzer was used to calculate the uric acid removal amount _acid E, but the configuration is not limited to this. For example, it may be obtained by measuring the amount of uric acid removed by the dialysate. Specifically, the uric acid concentration in the effluent dialysate after dialysis may be measured, and the amount of uric acid removed may be calculated by multiplying the measured uric acid concentration by the amount of the effluent dialysate.

Returning to FIG. 2, the continuation of the process of determining the state of the amount of water contained in the dialysis patient's body using the extracellular fluid volume evaluation device 10 will be described. After the process of step S12, that is, when the extracellular fluid volume after dialysis is stored in the patient information storage unit 14, the computing device 12 acquires various information about the dialysis patient (S14). Various types of information about a dialysis patient are, for example, the height of the dialysis patient, the weight after dialysis, the amount of intracellular fluid after dialysis, and the like. The intracellular fluid volume after dialysis may be calculated by the computing device 12 using various information input from the interface device 30, or may be calculated by an external device (not shown) using, for example, an impedance method. The calculated post-dialysis intracellular fluid volume of the dialysis patient may be acquired via the interface device 30 . As an example of a method of acquiring the post-dialysis intracellular fluid volume of a dialysis patient, a process of calculating the post-dialysis intracellular fluid volume of a dialysis patient using the computing device 12 will be described below.

The intracellular fluid volume after dialysis can be calculated by subtracting the extracellular fluid volume after dialysis _ecf Ve from the total body fluid volume after dialysis. Therefore, the following equation (24) holds. Note that _wb Ve indicates the total body fluid volume after dialysis, and _icf Ve indicates the intracellular fluid volume after dialysis.

As described above, the post-dialysis extracellular fluid volume _ecf Ve is calculated by the extracellular fluid volume calculation unit 20 and stored in the patient information storage unit 14 . Therefore, if the total body fluid volume _wb Ve after dialysis can be calculated, the intracellular fluid volume _icf Ve after dialysis can be calculated using the above equation (24).

Next, a method for calculating the post-dialysis total body fluid volume _wb Ve will be described. Because urea crosses cell membranes 42 (see FIG. 3), it is distributed throughout the body's water compartments. Therefore, focusing on the distribution of urea, the post-dialysis total body fluid volume _wb Ve is calculated.

The amount of urea removed by dialysis (hereinafter also referred to as “urea removal amount”) corresponds to the difference between the amount of urea distributed throughout the water compartment before dialysis and the amount of urea distributed throughout the water compartment after dialysis. The total body fluid volume before dialysis is equal to the sum of the total body fluid volume after dialysis _wb Ve and the water removal volume _dial EW. Therefore, the following equation (25) holds. In addition, _urea E indicates the amount of urea removed, _urea Cs indicates the urea concentration before dialysis in the entire water compartment, and _urea Ce indicates the urea concentration after dialysis in the entire water compartment.

By rewriting the above equation (25), the following equation (26) is obtained.

The pre-dialysis urea concentration _urea Cs across the water compartment matches the pre-dialysis plasma urea concentration, and the post-dialysis _urea Ce across the water compartment matches the post-dialysis plasma urea concentration. Therefore, the urea concentration _urea Cs before dialysis in the entire moisture compartment and the urea concentration _urea Ce after dialysis in the entire moisture compartment can be obtained as actual measurement values. Also, as described above, the amount of water removed _dial EW can be obtained as an actual measurement value. Therefore, if the urea removal amount _urea E can be obtained or calculated, the post-dialysis total body fluid amount _wb Ve can be calculated.

The urea removal amount _urea E may be obtained, for example, by measuring the amount of urea removed by the dialysate, or may be calculated based on the urea clearance of the dialyzer used for dialysis. A method for calculating the urea removal amount _urea E from the urea clearance of the dialyzer will be described below.

It is known that the plasma urea concentration decreases exponentially during dialysis. Therefore, the following equation (27) holds. Note that _urea C(t) represents the plasma urea concentration at time t during dialysis. Also, _urea A is a coefficient, which is calculated using the following equation (28). Td indicates dialysis time.

From the above equations 27 and 28, the following equation 29 is obtained.

Also, the urea removal rate at time t during dialysis can be calculated as the product of the dialyzer urea clearance and the plasma urea concentration _urea C(t) at time t. Therefore, the following formula (30) holds. where _urea F(t) represents the urea removal rate at time t during dialysis, and _urea K represents the urea clearance of the dialyzer.

The urea clearance of the dialyzer is the overall mass transfer-area coefficient for urea of the dialyzer described in the catalog attached to the dialyzer (hereinafter also referred to as the "catalog value of the overall mass transfer-area coefficient for urea in the dialyzer"). , can be calculated using known formulas from the blood flow rate through the dialyzer during dialysis and the dialysate flow rate through the dialyzer during dialysis. Urea is distributed in both plasma and blood cell compartments. That is, urea is distributed to all compartments in the blood. Therefore, the blood flow rate through the dialyzer is used when calculating the urea clearance of the dialyzer. Since the blood flow rate through the dialyzer is substantially constant during dialysis, the urea clearance _urea K of the dialyzer is a constant independent of time t. Therefore, the urea removal amount _urea E can be calculated by integrating the equation represented by the above equation 30 from t=0 to t=Td. Therefore, the urea removal amount _urea E is calculated using the following equation (31).

From the above equations 29 and 31, the following equation 32 is obtained.

The dialysis time Td can be obtained as a measured value. Further, as described above, the plasma urea concentration _urea Cs before dialysis and the plasma urea concentration _urea Ce after dialysis can be obtained as actual measurement values.

From the above, the equation represented by Equation 32 above gives the catalog value of the overall mass transfer-area coefficient for urea in the dialyzer, the blood flow rate through the dialyzer during dialysis, and the dialysate flow rate through the dialyzer during dialysis. By substituting the obtained dialysis time Td, the plasma urea concentration _urea Cs before dialysis, and the plasma urea concentration _urea Ce after dialysis together with the urea clearance _urea K of the dialyzer calculated from , the urea removal amount _urea E can be calculated. Then, by substituting the calculated urea removal amount _urea E, the obtained plasma urea concentration _urea Cs before dialysis, the plasma urea concentration _urea Ce after dialysis, and the amount of water removed _dial EW into the equation represented by Equation 26 above, The post-dialysis total body fluid volume _wb Ve can be calculated. That is, the post-dialysis total body fluid volume _wb Ve is calculated from the plasma urea concentration _urea Cs before dialysis, the plasma urea concentration _urea Ce after dialysis, the amount of water removed _dial EW, the dialysis time Td, and the urea clearance _urea K. can.

In this embodiment, the urea clearance _urea K of the dialyzer is calculated using the catalog value of the overall mass transfer-area coefficient for urea of the dialyzer, but the configuration is not limited to this. For example, a catalog attached to a dialyzer may describe urea clearance at a given blood flow rate and a given dialysate flow rate instead of the overall mass transfer-area coefficient for urea for that dialyzer. In such a case, calculate the overall mass transfer-area coefficient for urea from the blood flow rate, dialysate flow rate, and urea clearance listed in the catalog, and calculate the overall mass transfer-area coefficient for urea. The urea clearance of the dialyzer may be calculated from the blood flow rate through the dialyzer and the dialysate flow rate through the dialyzer during dialysis.

The post-dialysis total body fluid volume _wb Ve is calculated using the equations represented by Equations 26 and 32 stored in the calculation method storage unit 18 . Specifically, the standard blood volume calculation unit 22 first calculates the pre- and post-dialysis plasma urea concentrations _urea Cs and _urea Ce stored in the patient information storage unit 14, and the dialysis information storage unit 16 to The urea removal amount _urea E is calculated by substituting the stored dialysis time Td and the catalog value of the overall mass transfer-area coefficient _urea KOA for urea in the dialyzer. Next, the standard blood volume calculation unit 22 calculates the urea removal amount _urea E calculated using the formula 32 in addition to the formula 26, and the plasma urea concentration before and after dialysis stored in the patient information storage unit 14 _urea By substituting Cs, _urea Ce, and the amount of water removed _dial EW stored in the dialysis information storage unit 16, the post-dialysis total body fluid amount _wb Ve is calculated.

Then, the standard blood volume calculation unit 22 substitutes the calculated total post-dialysis body fluid volume _wb Ve and the post-dialysis extracellular fluid volume _ecf Ve calculated in step S12 into the above equation (24), Calculate intracellular fluid volume _icf Ve after dialysis. The calculated post-dialysis total body fluid volume _wb Ve is stored in the patient information storage unit 14 .

Next, the standard blood volume calculator 22 calculates the standard blood volume of the dialysis patient (S16). As described above, the appropriate value for the total amount of extracellular fluid after dialysis differs for each dialysis patient. This is because the amount of fat and muscle in the body influences, as well as height and weight. A standard blood volume is used to normalize the extracellular fluid volume after dialysis to account for these effects.

Here, a method for calculating the standard blood volume will be described. As a method of calculating the standard blood volume, a method of calculating based on height and weight has been reported. For example, as a method of calculating the standard blood volume in consideration of the degree of obesity (that is, the amount of fat in the body), Lemmens' equation expressed by Equation 33 below is known. BV indicates a standard blood volume, and BMI indicates a body mass index (hereinafter referred to as BMI) calculated by weight/(height) ² .

"22" in the above equation (33) is the BMI for men with average fat mass. Therefore, BMI/22 represents the degree of obesity. That is, in the formula represented by Equation 33 above, fat mass is taken into account.

"70" in the above equation (33) is defined as the blood volume per 1 kg body weight of a male having an average muscle mass. In other words, muscle mass is not taken into account in the equation expressed by Equation 33 above. However, since muscle mass differs for each dialysis patient, it is necessary to consider not only individual differences in fat mass but also individual differences in muscle mass when calculating the standard blood volume.

Also, Gilcher's rule of five shown in Table 2 below is known as a guideline for blood volume per kg of body weight.

More muscle mass means more blood volume, less muscle mass means less blood volume. Gilcher's rule of five, shown in Table 2 above, defines the blood volume per kg of body weight in "thin" patients as less than in patients of "standard" physique. defined as a higher volume of blood per kg of body weight than in patients of "normal" physique. By using Gilcher's rule of five shown in Table 2 above, it is possible to correct "70" in the above equation (33) according to the sex and physique of the dialysis patient. However, it is necessary to judge from the appearance of each dialysis patient whether each dialysis patient corresponds to "thin", "normal" or "muscular" in Gilcher's rule of five shown in Table 2 above. There is, and it is entrusted to the subjectivity of the examiner. Therefore, it cannot be said that the standard blood volume can be accurately calculated simply by applying Gilcher's rule of five shown in Table 2 above to the equation represented by Equation 33 above.

Therefore, the present inventors conducted extensive studies and found that intracellular fluid volume is used to consider individual differences in muscle mass. Muscle mass is altered by hypertrophy or atrophy of individual muscle cells. Then, when the muscle cells are hypertrophied, the intracellular fluid volume inevitably increases by the hypertrophy of the muscle cells. On the other hand, when muscle cells atrophy, the intracellular fluid volume inevitably decreases by the amount of muscle cell atrophy. Focusing on the fact that there is a correlation between the muscle volume and the intracellular fluid volume, the standard blood volume is calculated using the intracellular fluid volume in consideration of individual differences in muscle volume.

Here, an example of a method for calculating the blood volume per kg body weight based on the intracellular fluid volume will be described. Among the 39 dialysis patients, 3 male patients who were clearly thin visually were selected as dialysis patients with low muscle mass, and the post-dialysis intracellular fluid volume of the 3 patients was calculated. The intracellular fluid volume after dialysis was calculated using the method described above. The average intracellular fluid volume after dialysis of these three dialysis patients with low muscle mass was calculated to be 208 mL/kg. In addition, from among the 39 dialysis patients, 3 male patients who were visually clearly muscular were selected as dialysis patients with a large amount of muscle. When the post-dialysis intracellular fluid volume was similarly calculated for these three dialysis patients with large muscle mass, the average value was calculated to be 510 mL/kg. Here, since it can be assumed that the intracellular fluid volume and the blood volume are proportional, based on the intracellular fluid volume of the above six dialysis patients, the blood volume per kg of body weight can be expressed by the following equation 34. . BV _x indicates the blood volume per 1 kg of body weight. In addition, the equation represented by the following equation 34 was derived based on the intracellular fluid volume of male dialysis patients, but the inventors of the present invention can also apply the equation represented by the following equation 34 to female dialysis patients. One thing has been confirmed.

By substituting “70” in the above equation (33) for the above equation (34), the following equation (35) is obtained.

Note that the above equation represented by Equation 35 can be rewritten into the following equation represented by Equation 36 using constants a and b.

In the equation expressed by Equation 34, the blood volume per 1 kg of body weight is calculated in consideration of individual differences in muscle mass. For this reason, the equation represented by the above equation 34 is replaced by the equation represented by the above equation 33 with "70" indicating the blood volume per kg body weight of a male having an average muscle mass. can be used to calculate a standard blood volume that takes into consideration not only individual differences in fat mass but also individual differences in muscle mass.

The standard blood volume that takes into account both individual differences in fat mass and individual differences in muscle mass (hereinafter also simply referred to as "standard blood volume") is obtained by using the above formula 35 stored in the calculation method storage unit 18. calculated using Specifically, the standard blood volume calculation unit 22 first calculates the BMI from the height and weight after dialysis stored in the patient information storage unit 14 . Next, the standard blood volume calculation unit 22 substitutes the intracellular fluid volume stored in the patient information storage unit 14 and the calculated BMI into the equation represented by Equation 34 to calculate the standard blood volume. The calculated standard blood volume is stored in the patient information storage unit 14 .

Next, the extracellular fluid volume standardization unit 24 standardizes the post-dialysis extracellular fluid volume _ecf Ve obtained in step S12 using the standard blood volume calculated in step S16 (S18). That is, the extracellular fluid volume standardization unit 24 calculates the standard extracellular fluid volume. Specifically, the extracellular fluid volume standardization unit 24 first multiplies the body weight stored in the patient information storage unit 14 by the standard blood volume. Since the standard blood volume stored in the patient information storage unit 14 is the standard blood volume per 1 kg of body weight, the total blood volume in the body of the dialysis patient is represented by the standard blood volume by multiplying the body weight of the dialysis patient. be able to. Then, the extracellular fluid volume standardization unit 24 divides the post-dialysis extracellular fluid volume _ecf Ve by the product of body weight and standard blood volume. This allows the post-dialysis extracellular fluid volume _ecf Ve (ie, the total extracellular fluid volume in the dialysis patient's body after dialysis) to be normalized to the extracellular fluid volume per liter of standard blood volume.

Next, the determining unit 28 uses the extracellular fluid volume standardized in step S18 (that is, the standard extracellular fluid volume) to determine the state of water content in the body of the dialysis patient (S20). The standard extracellular fluid volume calculated in step S18 is the extracellular fluid volume per kg body weight calculated in consideration of the fat mass and muscle mass of the dialysis patient. Therefore, regardless of the physique of the dialysis patient, the state of the amount of water in the body of the dialysis patient can be determined using the predetermined threshold value. Specifically, when the standard extracellular fluid volume is within a predetermined range, the determination unit 28 determines that the dialysis patient is in a normal state. On the other hand, when the standard extracellular fluid volume is greater than the predetermined range, the determination unit 28 determines that the dialysis patient is in a flooded state, and when the standard extracellular fluid volume is less than the predetermined range, the determination unit 28 performs dialysis. Determine that the patient is dehydrated. The determination result (that is, which of the flooded state, normal state, and dehydrated state) is displayed on the interface device 30 .

Note that even if the standard extracellular fluid volume is within a predetermined range, if it is near the upper limit within the predetermined range, the determination unit 28 determines that there is a possibility of a flooded state, and determines that the standard cell Even if the amount of external fluid is within a predetermined range, it may be determined that "there is a possibility of dehydration" when it is near the lower limit of the predetermined range. By making such a determination, the doctor can be notified to check the condition of the dialysis patient more carefully.

In the verification conducted by the present inventors, it has been confirmed that the state of the water content in the body of a dialysis patient can be determined based on the standard blood volume calculated using the formula (35). In the validation, 38 dialysis patients were classified into flooded, dehydrated and normal groups.

There were 9 dialysis patients classified into the flooding group, and they were classified into the flooding group by the following procedure. First, among the 39 dialysis patients, 10 dialysis patients who had edema in the lower extremities after the completion of hemodialysis on the first regular blood collection day were once classified into the flooding group (hereinafter referred to as the provisional flooding group). Thereafter, 10 dialysis patients classified into the provisional flooding group underwent hemodialysis with the dry weight lowered by 0.2-0.5 kg every 1-2 weeks. From the first regular blood sampling date to the regular blood sampling date 3 months later, 9 patients who did not experience a drop in blood pressure during dialysis or fatigue after dialysis, and no edema in the lower extremities after hemodialysis were examined. Edema that occurred on the day of routine blood sampling was determined to be due to flooding and was classified as the flooding group. One of the 10 patients classified into the provisional flooding group had a blood pressure increase during dialysis, before edema in the lower extremities disappeared after hemodialysis, while the dry weight was lowered and hemodialysis was performed. decreased. For this reason, the edema that occurred on the first routine blood collection day could not be confirmed as edema due to overflow, and this subject was excluded from the overflow group.

Five dialysis patients classified into the dehydration group were classified into the dehydration group by the following procedure. First, among the 39 dialysis patients, on the first regular blood collection day, if the blood pressure decreased to the extent that the water removal rate was reduced during hemodialysis, the water removal was stopped, or fluid replacement was required, Alternatively, the 5 dialysis patients who had strong malaise until eating a meal after hemodialysis were temporarily classified into a dehydration group (hereinafter referred to as a temporary dehydration group). Thereafter, 5 dialysis patients classified into the temporary dehydration group were subjected to hemodialysis while increasing the dry weight by 0.2 to 0.5 kg every 1 to 2 weeks. From the first scheduled blood sampling date to the scheduled blood sampling date 3 months later, the first scheduled blood sampling date for 5 subjects who did not experience edema in the lower extremities, decreased blood pressure during dialysis, or malaise after dialysis. We determined that the hypotension during dialysis and malaise after dialysis were due to dehydration, and classified them into the dehydration group. In addition, all five subjects classified into the temporary dehydration group were classified into the dehydration group.

Of the 39 dialysis patients, the normal group included 24 dialysis patients who were not classified into either the provisional flooding group or the provisional dehydration group on the first routine blood sampling day, that is, were asymptomatic. rice field.

For each dialysis patient classified as described above, the extracellular fluid volume after dialysis was standardized with the standard blood volume using various information on the dialysis patient and various information on dialysis obtained on the first regular blood sampling date. Specifically, using the method described above, the extracellular fluid volume and intracellular fluid volume after dialysis were calculated from various information on the dialysis patient and various information on dialysis obtained on the first scheduled blood sampling day. Then, the standard blood volume was calculated from the height, the body weight after dialysis, and the calculated intracellular fluid volume using the equation represented by the above equation 35. After that, the calculated standard blood volume and the body weight after dialysis were used to standardize the calculated extracellular fluid volume after dialysis.

In addition, as a comparative example, for the same dialysis patient, the standard blood volume per 1 kg body weight after dialysis was calculated using the above equation (Lemmens equation) expressed by Equation 33, and the standard blood volume and the body weight after dialysis were calculated. By multiplying , the standard blood volume per body of a dialysis patient was obtained, and this was used to standardize the extracellular fluid volume after dialysis. Hereinafter, the standard blood volume calculated using the above formula 33 may be referred to as "Lemmens' standard blood volume" in order to distinguish it from the standard blood volume calculated by the method of the present embodiment. As described above, Lemmens' standard blood volume takes into consideration only the degree of obesity (that is, the amount of fat in the body) of a dialysis patient, and does not take into account the amount of muscle in the body of a dialysis patient.

FIG. 6 is a graph showing the standard extracellular fluid volume normalized using the Lemmens standard blood volume of the comparative example. As shown in FIG. 6, when the extracellular fluid volume after dialysis was standardized using Lemmens' standard blood volume, the normal group and the overflow group could be distinguished, but the normal group and the dehydrated group could not be distinguished at all. could not. That is, even if the extracellular fluid volume after dialysis is standardized using the Lemmens standard blood volume, which does not take into account the muscle mass in the body of a dialysis patient, the state of the water content in the body after dialysis in the dialysis patient cannot be determined. I didn't.

FIG. 7 is a graph showing the standard extracellular fluid volume standardized using the standard blood volume of this example (that is, the standard blood volume calculated using the formula represented by Equation 35). As shown in FIG. 7, when the extracellular fluid volume after dialysis was standardized using the standard blood volume of this example, the normal group and the overflow group could be distinguished, and the normal group and the dehydrated group could be almost distinguished. was made. Although there are some parts where it is difficult to distinguish between the normal group and the dehydrated group, it is possible to prompt the doctor to make an accurate judgment by judging that there is a possibility of dehydration in this part. . However, since such a part is only a part, it can be said that the normal group and the dehydrated group could be distinguished almost correctly. In this way, by calculating the standard blood volume using the intracellular fluid volume, it is possible to calculate the standard blood volume in consideration of the muscle mass in the dialysis patient's body, and the water content in the dialysis patient's body is in an overflow state. It was confirmed that it was possible to accurately determine whether the condition was dehydrated or normal.

Although specific examples of the technology disclosed in this specification have been described above in detail, these are merely examples and do not limit the scope of the claims. The technology described in the claims includes various modifications and changes of the specific examples illustrated above. In addition, the technical elements described in this specification or in the drawings exhibit technical usefulness alone or in various combinations, and are not limited to the combinations described in the claims at the time of filing.

10: Extracellular fluid volume evaluation device 12: Computing device 14: Patient information storage unit 16: Dialysis information storage unit 18: Calculation method storage unit 20: Extracellular fluid volume calculation unit 22: Standard blood volume calculation unit 24: Extracellular fluid Quantity standardization unit 26: Determination unit 30: Interface device 40: Intracellular compartment 42: Cell membrane 50: Extracellular compartment 52: Interstitial compartment 54: Vascular compartment 56: Capillary membrane

Claims (6)

An extracellular fluid volume standardization device used to evaluate whether the state of the water content in the body of a dialysis patient is an overflow state, a normal state, or a dehydration state,
an extracellular fluid volume acquisition unit that acquires the extracellular fluid volume in the body of the dialysis patient;
a height acquisition unit that acquires the height of the dialysis patient;
a weight acquisition unit that acquires the post-dialysis weight of the dialysis patient;
an intracellular fluid volume acquisition unit that acquires the intracellular fluid volume of the dialysis patient;
a function storage unit that stores a function that defines a standard blood volume using height, weight after dialysis, and intracellular fluid volume as variables;
a standard blood volume calculation unit that calculates the standard blood volume of the dialysis patient by substituting the obtained height, the obtained weight after dialysis, and the obtained intracellular fluid volume into the function; ,
a standardization unit for standardizing the extracellular fluid volume obtained by the extracellular fluid volume acquisition unit based on the standard blood volume calculated by the standard blood volume calculation unit. . The function is defined as follows when the standard blood volume is BV, the intracellular fluid volume is ICV, the body mass index calculated from the height and the weight after dialysis is BMI, and a and b are constants. conditional expression for

The extracellular fluid volume standardization device according to claim 1, defined by: further comprising a uric acid concentration acquisition unit that acquires the plasma uric acid concentration of the dialysis patient before and after dialysis,
The extracellular fluid volume standardization device according to claim 1 or 2, wherein the extracellular fluid volume acquisition unit calculates the extracellular fluid volume after dialysis based on the balance of uric acid before and after dialysis. The extracellular fluid volume standardization device according to claim 1 or 2, wherein the extracellular fluid volume is calculated based on the impedance of the dialysis patient. An extracellular fluid volume evaluation device for evaluating whether the state of the amount of water contained in the body of a dialysis patient is a flooded state, a normal state, or a dehydrated state,
The extracellular fluid volume standardization device according to any one of claims 1 to 4,
an extracellular fluid volume evaluation device, comprising: a determination unit that determines the state of the amount of water contained in the body of the dialysis patient based on the extracellular fluid volume standardized by the extracellular fluid volume standardization device. . A computer program for standardizing the extracellular fluid volume used to evaluate whether the state of the water content in the body of a dialysis patient is a flooded state, a normal state, or a dehydrated state,
the computer,
an extracellular fluid volume acquisition unit that acquires the extracellular fluid volume in the body of the dialysis patient;
a height acquisition unit that acquires the height of the dialysis patient;
a weight acquisition unit that acquires the post-dialysis weight of the dialysis patient;
an intracellular fluid volume acquisition unit that acquires the intracellular fluid volume of the dialysis patient;
a function storage unit that stores a function that defines a standard blood volume using height, weight after dialysis, and intracellular fluid volume as variables;
a standard blood volume calculation unit that calculates the standard blood volume of the dialysis patient by substituting the obtained height, the obtained weight after dialysis, and the obtained intracellular fluid volume into the function; ,
A computer program that functions as a calculation unit that standardizes the extracellular fluid volume obtained by the extracellular fluid volume acquisition unit based on the standard blood volume calculated by the standard blood volume calculation unit.

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