Image display device for diagnosis support, object liquid purifier, and object liquid purification system

Abstract

To provide an image display device for diagnostic support, etc. for checking a blood pressure adjusting mechanism that is generated during hemodialysis and when purifying object liquid other than blood during object liquid purification and for appropriately managing an object liquid purification operation.SOLUTION: An image display device B for supporting diagnosis displays a plot for showing, by a difference in the design, a difference in a value of a third variable indicating a temporal variation of blood pressure in a predetermined time point or blood pressure in a predetermined period in coordinates of a value of a first variable and a value of a second variable in the predetermined time point or in the predetermined period in a coordinate system with the first variable indicating parameters related to peripheral circulation or time variation thereof as a first axis, and with the second variable indicating parameters related to a blood flow rate or time variation thereof as a second axis.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a diagnostic support image display device, a target liquid purification device, and a target liquid purification system. [Background technology]

[0002] Hypotension during target fluid purification, especially during hemodialysis, is one of the most frequent complications of hemodialysis (Non-Patent Document 1, Non-Patent Document 2). It is known that hypotension during dialysis affects the prognosis of hemodialysis patients (Non-Patent Document 3, Non-Patent Document 4, Non-Patent Document 5, Non-Patent Document 6). Various factors are involved in hypotension during hemodialysis (Non-Patent Document 1, Non-Patent Document 7, Non-Patent Document 8). In patients who become hypotensive during dialysis, the normal response of vascular resistance and capacity to a decrease in blood volume may be impaired. It is known that various factors are involved in such a decrease in normal vascular reactivity, such as bioincompatibility reactions due to the use of dialysis membranes and dialysis fluids, induction of cytokines, increased nitric oxide production, and vasopressin deficiency (Non-Patent Document 9).

[0003] Hemodialysis patients may have complex abnormalities in the blood pressure regulation mechanism due to underlying diseases. Many hemodialysis patients have hypertension, which is known to be due not only to an increase in blood volume due to renal dysfunction, but also to vasoconstrictor blood pressure regulation mechanisms such as the renin-angiotensin system and the sympathetic nervous system (Non-Patent Document 10). Furthermore, it has been observed that in diabetic hemodialysis patients, the heart rate response to a decrease in blood volume may not function properly due to autonomic neuropathy (Non-Patent Document 11). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Halle MP, Hilaire D: Intradialytic Hypotension and Associated Factors among Patients on Maintenance Hemodialysis A Single - Center Study in Cameroon. Saudi Journal of Kidney Diseases and Transplantation. 31(1), 215-223, 2020. [Non-Patent Document 2] Andrew D: Why is Intradialytic Hypotension the Commonest Complication of Outpatient Dialysis Treatments?. Kidney International Reports. 8(3), 405-418, 2023. [Non-Patent Document 3] Cheng JL, Chih YC: Interigent system to predict intradialytic hypotension in chronic hemodialysis. Journal of the Formosan Medical Association. 117(10), 888-893, 2018. [Non-Patent Document 4] Johanna K, Loes MV: The prevalence of Intradialytic Hypotension in Patients on Conventional Hemodialysis: A Systematic Review eith Meta-Analysis. American Journal of Nephrology. 49(6), 497-506, 2019. [Non-Patent Document 5] Jongha P, Connie MR: A comparative effectiveness research study of the change in blood pressure during hemodialysis treatment and survival. Kidney International. 84(4), 795-802, 2013.

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

[0005] In addition to the fact that multiple factors are involved in blood pressure fluctuations during hemodialysis, the blood pressure regulation mechanisms of hemodialysis patients also differ depending on their underlying diseases. Therefore, in order to provide appropriate management of various types of hypotension during hemodialysis, it is necessary to understand the individual blood pressure regulation mechanisms of dialysis patients.

[0006] Therefore, the present invention aims to provide a diagnostic support image display device, a target fluid purification device, and a target fluid purification system that can check the blood pressure regulation mechanism that occurs during hemodialysis and when purifying target fluids other than blood, and that can appropriately manage the target fluid purification operation. [Means for solving the problem]

[0007] In order to solve the above problems, the diagnostic support image display device of the present invention is characterized by having the following invention-specifying features.

[0008] (1) The diagnostic support image display device of the present invention is characterized in that it displays a plot in a coordinate system having a first variable indicating a parameter related to peripheral circulation or its variation over time as a first axis and a second variable indicating a parameter related to blood flow or its variation over time as a second axis, in which the plot shows the difference in the value of a third variable indicating blood pressure at a specified time or variation over a specified period of time on the coordinates of the value of the first variable and the value of the second variable at a specified time or period of time, by using differences in design.

[0009] (2) In addition, in the diagnosis support image display device of (1), The design preferably represents a time series variation of at least one of the first variable, the second variable and the third variable.

[0010] (3) In the diagnosis support image display device according to (1) or (2), It is preferable that an area for identifying factors that affect blood pressure is displayed on the coordinate system by surrounding it with a line.

[0011] In order to solve the above problems, the target liquid purification device of the present invention is characterized by having the following invention-specific features.

[0012] (4) The subject liquid purification device of the present invention is 1. A subject fluid purification device for removing at least one subject substance from an unpurified subject fluid of a patient, comprising: a first measuring device for measuring a first variable indicative of a parameter related to the peripheral circulation of the patient or its time variation; a second measuring device for measuring a second variable indicative of a parameter related to blood flow of the patient or its time variation; and a third measuring device for measuring a third variable indicating a parameter related to the patient's blood pressure or its time variation.

[0013] (5) In addition, in the target liquid purification device described in (4), It is preferable to provide a control unit that controls the operation of the target liquid purification device based on at least one of a first variable measured by the first measuring device, a second variable measured by the second measuring device, and a third variable measured by the third measuring device.

[0014] In order to solve the above problems, the target liquid purification system of the present invention is characterized by having the following invention-specific features.

[0015] (6) The target liquid purification system of the present invention is A diagnostic support image display device according to any one of (1) to (3), The present invention is characterized by comprising the target liquid purification device according to (4) to (5).

[0016] In addition, in the target liquid purification system described in (6), It is preferable to execute a process for storing at least one of a first variable measured by the first measuring device, a second variable measured by the second measuring device, and a third variable measured by the third measuring device in a memory device. Effect of the Invention

[0017] Blood pressure is generally influenced by peripheral circulation and blood flow. Peripheral circulation is known to be controlled by the sympathetic nervous system, the renin-angiotensin system, and vasopressin, and systems other than the sympathetic nervous system are also involved (Non-Patent Document 12). Blood flow is mainly controlled by the sympathetic nervous system.

[0018] Therefore, according to the diagnostic support image display device, the target fluid purification device, or the target fluid purification system described in any one of (1) to (7) above, it is possible to know the change in the mechanism of blood pressure fluctuation by observing the state of peripheral circulation and the state of blood flow rate at the same time as blood pressure fluctuation. Therefore, since the target fluid purification process and the like can be managed according to the mechanism of blood pressure fluctuation, it is possible to perform the target fluid purification process safely while appropriately managing blood pressure. In addition, since it is possible to quickly detect the state of a target fluid purification patient, such as a dialysis patient, it is possible to reduce the harm to the patient caused by a medical accident, etc. [Brief description of the drawings]

[0019] [Figure 1] 1 is a diagram showing an outline of a target liquid purification system according to an embodiment of the present invention; [Diagram 2] 1 is a diagram showing an outline of a main body of a target liquid purification system according to an embodiment of the present invention; [Diagram 3] 3 is an example of a display image displayed on the diagnosis support image display device of the present invention. [Figure 4] An example of a displayed image in which the range of blood pressure abnormalities due to fluctuations in vasopressin, the range of blood pressure abnormalities due to fluctuations in the renin-angiotensin system, the range of blood pressure abnormalities due to fluctuations in the sympathetic nervous system, and the range of blood pressure abnormalities due to vasodilatory action are surrounded by lines on the coordinate system in Figure 3. [Diagram 5] FIG. 1 shows time series changes in arterial blood pressure in the extracorporeal circulation group and the control fluid purification group in this experiment. [Figure 6] FIG. 13 is a graph showing time series fluctuations in blood oxygen saturation in the extracorporeal circulation group and the target fluid purification group in this experiment. [Figure 7] FIG. 13 is a graph showing time series fluctuations in heart rate in the extracorporeal circulation group and the target fluid purification group in this experiment. [Figure 8] Graph showing time series changes in ΔBP-ΔSpO2-ΔHR and arterial blood pressure in the extracorporeal circulation group. [Figure 9] A graph showing the time series fluctuations of ΔBP-ΔSpO2-ΔHR and arterial blood pressure for the subject fluid purification group. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Next, one embodiment of the present invention will be described with reference to the drawings.

[0021] The target liquid purification system as a first embodiment of the present invention shown in Fig. 1 includes a target liquid purification device A and a diagnostic support image display device B. The target liquid purification device A and the diagnostic support image display device B are connected to each other via their respective wireless communication devices (not shown). As a wireless communication method, any wireless communication method may be used, such as the Internet, Bluetooth (registered trademark), or infrared communication. In addition to wireless communication, the target liquid purification device A and the diagnostic support image display device B may be connected by a wired connection via a lead wire or the like.

[0022] (Configuration of target liquid purification device A) The target fluid purification device A includes a main body 1 for removing at least one target substance from a patient's unpurified target fluid, a first measuring device 2 for measuring a first variable indicating a parameter related to the patient's peripheral circulation or its time variation, a second measuring device 3 for measuring a second variable indicating a parameter related to the patient's blood flow rate or its time variation, and a third measuring device 4 for measuring a third variable indicating a parameter related to the patient's blood pressure or its time variation. The target fluid purification system also executes a process for storing at least one variable of the first variable measured by the first measuring device 2, the second variable measured by the second measuring device 3, and the third variable measured by the third measuring device 4 in a storage device C.

[0023] An example of the main body 1 of the subject liquid purification device A of the present invention is shown in Fig. 2. As shown in Fig. 2, the main body 1 includes a separation device 100, an unpurified subject liquid passage 11, a purification subject liquid passage 12, a regeneration section 200, a dialysis fluid passage 21, a regenerated liquid passage 22, a drainage passage 24, and a first replacement fluid passage 412. Note that the regeneration section 200, the dialysis fluid passage 21, the regenerated liquid passage 22, the drainage passage 24, and the first replacement fluid passage 412 may be omitted.

[0024] The separation device 100 is separated into a first portion 110 and a second portion 120 by a target liquid purification membrane 102. The target liquid purification membrane 102 has a pore size that allows the target substance contained in the unpurified target liquid F11 (e.g., blood, plasma, dialysis effluent, blood filtrate) to pass through. The "target substance" is, for example, at least one ion selected from potassium ions, ammonium ions, calcium ions, magnesium ions, phosphate ions, bicarbonate ions, and organic acid ions, urea, creatinine, uric acid, peptides, proteins, and other disease-causing substances that accumulate in the body when the patient becomes ill. The separation device 100 is configured to generate a filtered dialysis liquid F21 by passing the unpurified target liquid F11 containing the target substance from the first portion 110 through the target liquid purification membrane 102 and introducing it into the second portion 120, and to generate a purified target liquid F12 by removing the target substance contained in the unpurified target liquid F11 through the passage.

[0025] The unpurified liquid passage 11 is configured to introduce the unpurified liquid F11 drawn out from the patient's body into a first portion 110 of the separation device 100. The purification target liquid passage 12 is configured to lead the purification target liquid F12 out of the first portion 110 of the separation device 100 and introduce it into the patient's body. The separation device 100 is configured, for example, by a dialyzer, the first portion 110 being the internal space of hollow fibers formed by a dialysis membrane, and the second portion 120 being the space around the hollow fibers through which the dialysis fluid and / or regenerated fluid flows.

[0026] In this embodiment, the separation device 100 is configured as a "countercurrent separation device" in which the flow direction of the unpurified target liquid F1 in the first portion 110 and the flow direction of the regenerated liquid F22 in the second portion 120 are opposite or in opposite directions, but in other embodiments, the separation device 100 may be configured as a "parallel current separation device" in which the flow direction of the unpurified target liquid F11 in the first portion 110 and the flow direction of the regenerated liquid F22 in the second portion 120 are parallel or in the same direction.

[0027] The regeneration unit 200 may have an adsorbent that adsorbs the target substance. The adsorbent may be activated carbon, an adsorbent based on activated carbon, a porous adsorbent, an adsorbent made of a cation exchange resin, an anion exchange resin, zirconia ceramics, zeolite, or a mixture thereof. The regeneration unit 200 may be configured to remove at least a portion of the target substance by contacting a portion of the dialysis fluid (the second fluid F212) with the adsorbent, thereby generating a regenerated fluid F22 in which the concentration of the target substance is reduced.

[0028] The filtrate passage 21 is configured to lead the filtrate F21 out of the second part 120 of the separation device 100 and introduce a part of the filtrate F21, a second liquid F212, into the regeneration section 200. The drain passage 24 branches off from the filtrate passage 21 and is configured to discard the first liquid F211 as a drainage liquid out of the first liquid F211 and the second liquid F212 resulting from the separation of the filtrate F21. The flow rate of the drainage liquid in the drain passage 24 (the discarded amount of the filtrate F21) may be appropriately controlled in consideration of the flow rate of the regenerated liquid F22 in the second part 120 of the separation device 100 based on the inflow rate of the replacement liquid (fresh dialysis liquid) into the regenerated liquid passage 22 and / or the outflow rate of the regenerated liquid F22 from the regenerated liquid passage. The regenerated liquid passage 22 is configured to introduce the regenerated liquid F22 from the regeneration section 200 into the second part 120 of the separation device 100.

[0029] The first replacement fluid passage 412 is configured to directly introduce the first replacement fluid F41 into the purification target fluid passage 12. The "replacement fluid" means, for example, fresh dialysis fluid or a replacement fluid for filtration. The first replacement fluid F41 may be introduced from the purification target fluid passage 12 downstream of the separation device 100, or may be introduced from the non-purified target fluid passage 11 upstream of the separation device 100, and the first replacement fluid F41 may be omitted.

[0030] A single-path type may be used in which the regeneration unit 200, the dialysis fluid passage 21, the regenerated fluid passage 22, the drainage passage 24, and the first replacement fluid passage 412 are omitted. As described above, the regeneration unit 200, the dialysis fluid passage 21, the regenerated fluid passage 22, the drainage passage 24, and the first replacement fluid passage 412 are not essential components of the present invention and may be omitted.

[0031] The first measuring device 2 is a device for measuring a parameter related to the peripheral circulation of the patient or a first variable indicating its time variation. Here, the parameter related to the peripheral circulation of the patient is, for example, blood oxygen saturation (SpO2), an index by a laser Doppler blood flowmeter or an ultrasonic Doppler blood flowmeter, or a perfusion index. In the present invention, it is preferable to use blood oxygen saturation as the parameter related to the peripheral circulation of the patient from the viewpoint of ease of measurement. It is preferable that the first measuring device 2 is attached to the patient's hand and measures the blood oxygen saturation. In addition, it is preferable that the first measuring device 2 is connected to the main body 1 of the target fluid purification device A via a lead wire, and the parameter related to the peripheral circulation of the patient is stored in the storage device C via the lead wire.

[0032] In the above embodiment, the first measuring device 2 is attached to the patient's hand, but this is not limiting, and it may be provided as part of the blood circuit of the target fluid purification device, or it may be attached to a part of the patient's body other than the hand. Also, in the above embodiment, the first measuring device 2 is connected to the main body of the target fluid purification device A via a lead wire, but this is not limiting, and it may be connected to the main body part 1 of the target fluid purification device A using any wireless communication method such as the Internet, Bluetooth (registered trademark), or infrared communication.

[0033] The second measuring device 3 is a device for measuring a parameter related to the patient's blood flow rate or a second variable indicating its time variation. Here, the parameter related to the patient's blood flow rate is, for example, heart rate (HR), cardiac output, etc. In the present invention, it is preferable to use heart rate as the parameter related to the patient's blood flow rate because of the ease of measurement. The second measuring device 3 can also simultaneously measure the blood oxygen saturation level from a blood oxygen saturation meter attached to the patient's hand. In addition, the second measuring device 3 is preferably connected to the main body 1 of the target liquid purification device A via a lead wire, and the parameter related to the patient's blood flow rate is stored in the storage device C via the lead wire.

[0034] In the above embodiment, the second measuring device 3 is attached to the patient's hand, but this is not limited thereto, and it may be provided as part of the blood circuit of the target fluid purification device, or may be attached to a part of the patient's body other than the hand. Also, in the above embodiment, the second measuring device 3 is connected to the main body 1 of the target fluid purification device A via a lead wire, but this is not limited thereto, and it may be connected to the main body 1 of the target fluid purification device A using any wireless communication method such as the Internet, Bluetooth (registered trademark), or infrared communication.

[0035] The third measuring device 4 is a device for measuring a parameter related to the patient's blood pressure or a third variable indicating its time variation. Here, the parameter related to the patient's blood pressure is the blood pressure in the upper arm, etc. In particular, in the present invention, the third measuring device 4 preferably measures the blood pressure in the upper arm of the patient, and is preferably placed near the upper arm of the patient. Moreover, the third measuring device 4 is preferably connected to the main body 1 of the target liquid purification device A via a lead wire, and the parameter related to the patient's blood pressure is stored in the storage device C via the lead wire.

[0036] In the above embodiment, the third measuring device 4 is placed near the upper arm, but this is not limited thereto, and it may be provided in a part of the blood circuit of the subject fluid purification device, or measurement may be performed at a location where an artery or vein is located other than the upper arm. Also, in the above embodiment, the third measuring device 4 is connected to the main body 1 of the subject fluid purification device A via a lead wire, but this is not limited thereto, and it may be connected to the main body 1 of the subject fluid purification device A using any wireless communication method such as the Internet, Bluetooth (registered trademark), or infrared communication.

[0037] From the viewpoint of accurately monitoring the condition of the patient, each of the first measuring device 2, the second measuring device 3, and the third measuring device 4 preferably performs sampling at intervals of 10 seconds to 60 minutes, and more preferably, from the viewpoint of data storage and processing, performs sampling at intervals of 1 to 20 minutes.

[0038] The target liquid purification device A may further include a control unit for controlling the target liquid purification process. The control unit is composed of a storage device C (memory such as RAM, ROM, EEPROM, SSD, HDD, etc.) for storing and holding programs (software) and data, an arithmetic processing unit (single-core processor, multi-core processor, CPU, etc.) for reading necessary programs and / or data from the storage device C and executing predetermined arithmetic processing, and an I / O circuit, etc. As described below, the control unit controls the flow rate of the replenishment liquid or the amount of water removed in the target liquid purification process, and controls the operation of the target liquid purification device as a whole. Note that the storage device C, the arithmetic processing unit, and a part of the I / O circuit, etc. may be provided independently of the control unit, or may be configured as an integrated unit. The control unit is provided with an abnormality detection unit, which detects an abnormality (e.g., a sudden blood pressure change, a low blood pressure state) during purification of the target liquid based on the first variable, the second variable, the third variable, etc., and notifies the abnormality.

[0039] (Configuration of diagnostic support image display device) The diagnostic support image display device B is a personal computer or a mobile phone (smartphone), and includes any information terminal device. The diagnostic support image display device B displays various information in the target liquid purification process, such as the flow rate of the replenishment liquid, the elapsed time in the purification of the target liquid, the total amount of inflowing replenishment liquid, the composition of the unpurified target liquid F11, and the composition of the purified target liquid F12. The diagnostic support image display device B may be provided in a remote device that remotely operates or remotely manages the target liquid purification device A.

[0040] In addition, the diagnostic support image display device B displays a plot showing the difference in the value of the first variable at a predetermined time or a predetermined period and the value of the third variable indicating the time variation of blood pressure at the predetermined time or during the predetermined period on the coordinates of the value of the second variable in a coordinate system having a first axis representing a parameter related to peripheral circulation or its time variation, and a second axis representing a parameter related to blood flow or its time variation, by a difference in design. FIG. 3 shows an example of an image displayed on the diagnostic support image display device B. The coordinate system shown in FIG. 3 has the time difference (ΔHR) of the heart rate as the second variable over a predetermined period on the vertical axis and the time difference (ΔSpO2) of the blood oxygen saturation as the first variable over a predetermined period on the horizontal axis. Here, the vertical axis is ΔHR and the horizontal axis is ΔSpO2, but this is not limited thereto, and the vertical axis and the horizontal axis may be reversed. In addition, blood oxygen saturation and heart rate are shown on the horizontal and vertical axes, respectively. However, as mentioned above, a parameter related to peripheral circulation other than blood oxygen saturation or a first variable indicating its time variation may be shown on the horizontal axis, and a parameter related to blood flow other than heart rate or a second variable indicating its time variation may be shown on the vertical axis.

[0041] In Fig. 3, a design representing the difference in the value of the time difference (ΔBP) of blood pressure as a third variable over a predetermined period is further plotted on the coordinates of the value of the first variable and the value of the second variable over a predetermined time or period. Here, the design is represented by a circle, the radius of the circle increases as the absolute value of the time difference of blood pressure increases, and the color of the circle represents the difference in the third variable, with gray being shown when the time difference of blood pressure is positive and white being shown when it is negative.

[0042] That is, the diagnostic support image display device B displays the design in the form of a scatter diagram in the coordinate system of the time fluctuation of the patient's heart rate and time fluctuation of the blood oxygen saturation during or before and after purification of the target fluid. The design shown in Fig. 3 is displayed in the form of a bubble chart in which the time fluctuation of blood pressure (ΔBP) is drawn in color when plotted if it is positive, and drawn in white if it is negative, and the absolute value of the time difference of blood pressure over a specified period is represented by the size of the plot.

[0043] In this embodiment, the first variable, the second variable, and the third variable are each expressed as a time difference over a predetermined period of time, but this is not limiting, and each may be a time differential, an Nth order differential of time (N is any integer; including 0), an Nth order differential of discretized time over a predetermined period of time, etc. In addition, the difference in this embodiment is preferably a forward difference, but may be any difference such as a backward difference or a central difference.

[0044] It is preferable that the diagnosis support image display device B is expressed in the form of a bubble chart, but is not limited to this and any other drawing such as a heat map, a radar chart, a bar graph, or a line graph may be displayed.

[0045] The design may be composed of multiple design parts. For example, after a design for an arbitrary predetermined period is displayed as one design part on the diagnostic support image display device B, a design for the next predetermined period can be displayed as another design part simultaneously with the one design part or as an image. At this time, when the one design part and the other design part are displayed simultaneously, the one design part and the other design part may be expressed so as to represent a time series variation of at least one of the first variable, the second variable, and the third variable. For example, the one design part and the other design part may be connected by an arrow line or the like, or an expression such as changing the color according to the time change may be added. In addition, the design part may be two or more. The one design part and the other design part may be displayed as an image, that is, when the design is displayed as a dynamic design, it may be generated by animation such that the one design is displayed and then the other design is displayed a few commas later.

[0046] The diagnostic support image display device B may display an area that specifies factors that affect blood pressure by surrounding it with a line on the above-mentioned coordinate system. Factors that affect blood pressure include biohormones of the vasopressin system, biohormones of the renin-angiotensin system, fluctuations in the sympathetic nervous system, vasodilatory action, etc.

[0047] FIG. 4 shows an embodiment of a display image in which a region specified as a blood pressure change caused by a change in biohormone of the vasopressin system, a region specified as a blood pressure change caused by a change in biohormone of the renin-angiotensin system, a region specified as a blood pressure change caused by a change in the sympathetic nervous system, and a region specified as a blood pressure change caused by vasodilatory action are surrounded by lines on the coordinate system. Here, the region R1 is a range of blood pressure abnormalities caused by changes in the sympathetic nervous system. In general, when the sympathetic nervous system is excited, the heart rate increases and the peripheral blood vessels tend to expand (reduce blood oxygen saturation). The region R2 is a range of blood pressure abnormalities caused by changes in the sympathetic nervous system. In general, when the sympathetic nervous system is inhibited, the heart rate increases and the peripheral blood vessels tend to contract (increase blood oxygen saturation). The region R3 is a range of blood pressure abnormalities caused by activation of the renin-angiotensin system. Generally, when the renin-angiotensin system is activated, peripheral blood vessels constrict (blood oxygen saturation increases), while heart rate does not change, so ΔHR changes from positive to negative values. Therefore, in region R3, ΔHR changes from positive to negative values, and ΔSpO2 takes a negative value. The R4 region is the range of blood pressure abnormalities caused by vasopressin. Generally, heart rate is not affected by vasopressin. Therefore, in region R4, ΔHR changes from positive to negative values, and ΔSpO2 takes a negative value. The effect of vasopressin-induced vasoconstriction on ΔSpO2 is fundamentally weaker than the effect of the renin-angiotensin system, so region R4 takes a value closer to the origin than region R3.

[0048] In addition to the above-mentioned embodiment, the diagnostic support image display device B may further add a region of the normal range or a region of abnormal blood pressure caused by the influence of other biological hormones to the coordinate system. Furthermore, the diagnostic support image display device B may further display a graph related to the time series fluctuation of the first variable, the time series fluctuation of the second variable, or the time series fluctuation of the third variable.

[0049] The diagnosis support image display device B may display a diagram based on the values ​​of the first variable, the second variable, and the third variable in the past target fluid purification process stored in the storage device C. In other words, the blood pressure fluctuations and their causes in the past target fluid purification of the patient may be displayed before the target fluid purification. EXAMPLES

[0050] Next, an embodiment of the present invention will be described with reference to the drawings.

[0051] (Test Subject) Sprague Dawley rats (male, 10 weeks or older, CLEA Japan, Inc.) were used in the experiment. The rats were raised in a temperature- and humidity-controlled room at 25°C (relative humidity 50%) with a 12:12 hour light:dark period. The rats were anesthetized with 3% isoflurane during surgery and 1.5% isoflurane during perfusion.

[0052] This study was conducted in accordance with the "Basic Guidelines for Proper Conduct of Animal Experiments in Academic Research Institutions." Approval was obtained from the Animal Experimentation Committee of the Kitasato University School of Allied Health Sciences (approval number 19-05-3).

[0053] (Experimental group) The experimental groups were divided into an extracorporeal circulation group and a target fluid purification group. The extracorporeal circulation group was an experimental group using rats in which blood collected from the femoral artery was returned to the femoral vein via an unpurified target fluid passage 11 (Labolan (registered trademark), silicone tube 1×3, 9-869-03, AS ONE Corporation, Japan). In other words, the extracorporeal circulation group was a group in which the experiment was carried out without using a separation device. The target fluid purification group was a group in which blood collected from the femoral artery as unpurified target fluid F11 was returned to the separation device 100 (target fluid purification membrane 102 is polyethersulfone, membrane area: 141 cm) via an unpurified target fluid passage 11 (Labolan (registered trademark), silicone tube 1×3, 9-869-03, AS ONE Corporation, Japan). 2, 140 hollow fibers, and an effective length of 160 mm.) and then the purification target liquid F12 derived from the separation device 100 is returned to the femoral vein via a purification target liquid passage 12 (Labolan (registered trademark), silicone tube 1×3, 9-869-03, AS ONE Corporation, Japan). In the target liquid purification group, the experiment was performed without passing through the regeneration section 200, the dialysis fluid passage 21, the regenerated fluid passage 22, the drainage passage 24, and the first replacement fluid passage 412. There was no significant difference in the body size of the rats between the groups (extracorporeal circulation group: 398.0±14.2 g, target liquid purification group: 348.1±25.1 g).

[0054] (Experimental environment) The unpurified target fluid passage F11 was disinfected by sealing it overnight with peracetic acid and then connected to the main body of the target fluid purification device A, which had been sterilized by X-ray. Lactated Ringer's solution (Lactec Injection, Otsuka Pharmaceutical) was used to prime the unpurified target fluid passage F11, the main body of the target fluid purification device A, and the purified target fluid F12. The priming volume was 1.8 mL in the extracorporeal circulation group and 3.6 mL in the target fluid purification group.

[0055] (Experimental Outline) Rats in each experimental group were anesthetized with 3% isoflurane and the tail vein was cannulated using a 24G indwelling needle (SurfloFlash (registered trademark), intravenous cannula 24G x 3 / 4, Terumo). Then, one side of the groin was incised, and the femoral vein and femoral artery were separated. The femoral vein was cannulated using a 20G infusion cannula (SurfloFlash (registered trademark), infusion cannula 20G x 1 1 / 4, Terumo), and the femoral artery was cannulated using a 24G infusion cannula. After the operation, a 4-hour circulation experiment was performed for each experimental group. Extracorporeal circulation was performed at a blood flow rate (QB) of 1.0 mL / min using a peristaltic pump (SJ-1211H, Atto, Japan). The replacement fluid F41 (dialysis fluid) was filled with lactated Ringer's solution, and the dialysate side of the dialyzer was closed to prevent flow during blood contact. To prevent blood clotting, heparin was administered. Heparin was administered as a bolus injection of 0.50 units / g at the start of circulation, and was continuously infused one hour after the start of circulation. The activated clotting time (ACT) was measured every hour during circulation, and the amount of heparin administered was adjusted so that the ACT was around 350 seconds.

[0056] (Measurement conditions) As the third variable, arterial blood pressure was measured from the femoral artery, and its fluctuation was recorded. A pulse oximeter and a pulse oximeter sensor probe of a heart rate monitor (PhysioSuite® for Mice & Rats, Kent Scientific) were attached to the rat's hand, and blood oxygen saturation (SpO2) was measured to obtain the first variable, and heart rate (HR) was measured to obtain the second variable. All items were recorded every 15 minutes. In this example, the forward time difference of blood oxygen saturation (ΔSpO2) in 15 minutes was used as the first variable, the forward time difference of heart rate (ΔHR) in 15 minutes was used as the second variable, and the forward time difference of blood pressure (ΔBP) in 15 minutes was used as the third variable.

[0057] (result) Figure 5 shows the time series changes in arterial blood pressure in the extracorporeal circulation group and the target fluid purification group (Dialyzer) in this experiment. As shown in Figure 5, the arterial blood pressure in both the extracorporeal circulation group and the target fluid purification group showed a significant upward trend at 2 hours after the start of perfusion, and a significant downward trend at 3 to 4 hours after the start of perfusion.

[0058] Figure 6 shows the time series fluctuation of blood oxygen saturation (SpO2) in the extracorporeal circulation group and the target fluid purification group (Dialyzer) in this experiment. As shown in Figure 6, blood oxygen saturation showed a significant downward trend 1 to 3 hours after the start of perfusion in both the extracorporeal circulation group and the target fluid purification group. In addition, 165 minutes after the start of extracorporeal circulation, the blood oxygen saturation in the target fluid purification group was significantly lower than that of the extracorporeal circulation group.

[0059] Figure 7 shows the time series fluctuations of heart rate (HR) in the extracorporeal circulation group and the target fluid purification group (Dialyzer) in this experiment. As shown in Figure 7, the heart rate showed a significant upward trend from 30 to 150 minutes after the start of perfusion in both the extracorporeal circulation group and the target fluid purification group, and showed a significant downward trend from 3 to 4 hours after the start of perfusion. At 3 hours (180 minutes) and 195 minutes after perfusion, the heart rate in the target fluid purification group was significantly higher than that of the extracorporeal circulation group. The arterial blood pressure during the perfusion experiment showed similar fluctuations in the extracorporeal circulation group and the target fluid purification group.

[0060] Although there were differences between the groups in blood oxygen saturation and heart rate, the overall trend of change was similar. When the data was plotted on a ΔBP-ΔSpO2-ΔHR correlation diagram, the difference between the extracorporeal circulation group and the target fluid purification group was more significant.

[0061] FIG. 8 shows the time series fluctuations of ΔBP-ΔSpO2-ΔHR and arterial blood pressure for 60 minutes in the extracorporeal circulation group. FIG. 9 shows the time series fluctuations of ΔBP-ΔSpO2-ΔHR and arterial blood pressure for 60 minutes in the control fluid purification group. In the ΔBP-ΔSpO2-ΔHR shown in FIG. 8 and FIG. 9, black circles indicate that the time difference of the heart rate is positive, white circles indicate that the time difference of the heart rate is negative, and the diameter of the circle indicates the absolute value of the time difference of the heart rate. In the ΔBP-ΔSpO2-ΔHR correlation diagrams (FIG. 8a and FIG. 9a) from 0 to 1 hour after the start of circulation, an increase in the heart rate was observed in addition to an increase in arterial blood pressure in the control fluid purification group (FIG. 8a). In addition, the plots in the control fluid purification group are located in the region R1 of FIG. 4.

[0062] In the correlation diagrams (Fig. 8b and Fig. 9b) 1 to 2 hours after the start of circulation, an increase in heart rate and a decrease in blood oxygen saturation were observed, and the plots were located in area R1. The decrease in blood oxygen saturation was more pronounced in the control fluid purification group (Fig. 9b), and the plots were located in areas R3 and R4, suggesting that in addition to excitation of the sympathetic nervous system, increased vasopressin and / or activation of the renin-angiotensin system may have occurred.

[0063] In the correlation diagrams (Figures 8c and 9c) 2 to 3 hours after the start of circulation, there were no changes in ΔBP, ΔSpO2, or ΔHR in either the extracorporeal circulation group or the target fluid purification group, and the data are plotted near the origin.

[0064] In the correlation diagrams (Fig. 8d, Fig. 9d) 3 to 4 hours after the start of circulation, a decrease in HR was observed in the extracorporeal circulation group (Fig. 8d), while in the target fluid purification group, an increase in blood oxygen saturation was observed in addition to a decrease in heart rate (Fig. 9d). In the extracorporeal circulation group, there is a plot in area R2, and there are plots in areas R3 and R4, which suggests that the sympathetic nervous system was suppressed in both groups, and vasodilatory action was added to the sympathetic nervous system, causing a decrease in blood oxygen saturation.

[0065] In this study, blood pressure, blood oxygen saturation, and heart rate were measured during extracorporeal circulation, and the arterial blood pressure, blood oxygen saturation, and heart rate fluctuated in a similar manner during extracorporeal circulation and during purification of the target fluid, but the fluctuation range of blood oxygen saturation was greater during purification of the target fluid. By expressing these results in a ΔBP-ΔSpO2-ΔHR correlation diagram, it was suggested that the factors behind blood pressure fluctuations, such as sympathetic nerve excitation and inhibition, could be visually estimated.

[0066] It is known that when blood comes into contact with the target fluid purification membrane 102, a bioincompatible reaction such as cytokine production occurs (Non-Patent Document 13). In the correlation diagram, it is easy to distinguish the difference between the extracorporeal circulation group and the target fluid purification group. In addition, in the correlation diagram, it is easy to distinguish the difference between the extracorporeal circulation group and the target fluid purification group. In this way, the correlation diagram is simple and is considered to be useful in considering the factors of blood pressure fluctuation during dialysis. Currently, circulatory dynamics is monitored based on blood pressure and heart rate, or, in the case of the autonomic nervous system, the RR interval (Non-Patent Document 14). In the present invention, it has been shown that by adding monitoring that reflects vasoconstriction and vasodilation, such as blood oxygen saturation, particularly useful information on blood pressure fluctuation during hemodialysis can be obtained.

[0067] The data used in the present invention were obtained from experiments using normal rats. Hemodialysis patients may show persistent overactivity of the sympathetic nervous system, which is due to signals generated in the damaged kidney being transmitted to the cardiovascular center in the brainstem via the afferent renal nerve (Non-Patent Document 15). Diabetic hemodialysis patients also often suffer from autonomic nerve disorders due to reduced intracellular blood flow caused by hyperglycemia, neurohypoxia, and reduced nerve conduction velocity (Non-Patent Document 16). Therefore, when comparing the clinical data of hemodialysis patients with the results of this study using normal rats, different results are obtained depending on the patient's condition due to differences in the patient's underlying disease. Therefore, the use of this analysis method is useful for blood pressure management in dialysis patients.

[0068] Therefore, according to the diagnostic support image display device, the target fluid purification device, or the target fluid purification system of the present invention, it is possible to know the change in the mechanism of blood pressure fluctuation by observing the blood oxygen saturation, which is an index that reflects the heart rate and vasoconstriction at the same time as the blood pressure fluctuation. Therefore, since the target fluid purification process and the like can be managed according to the mechanism of blood pressure fluctuation, it is possible to safely execute the target fluid purification process while appropriately managing blood pressure. In addition, since it is possible to quickly detect the condition of a target fluid purification patient, such as a dialysis patient, it is possible to reduce the harm to the patient caused by a medical accident, etc. [Explanation of symbols]

[0069] A. Liquid purification equipment B. Diagnostic image display device C‥Storage device 1. Main body 2‥1st measuring device 3‥Second measuring device 4‥Third measuring device 11. Unpurified liquid passage 12. Purification target liquid passage 21‥Filtered dialysate passageway 22‥Regeneration liquid passage 24. Drainage passage 100‥Separation equipment 102. Liquid purification membrane 110‥1st part 120‥Second part 200‥Reproduction section 210‥Replenisher regenerating liquid concentrator 412‥1st replenisher passage F11. Unpurified liquid F12 - Liquid to be purified F21‥Filtration dialysate F211...First liquid (drainage) F212: Second liquid F22‥Regeneration liquid F41‥1st refill fluid.

Claims

1. A diagnostic support image display device characterized in that a plot is displayed in a coordinate system having a first variable indicating a parameter related to peripheral circulation or its variation over time as a first axis and a second variable indicating a parameter related to blood flow or its variation over time as a second axis, in which the plot shows, on the coordinates of the value of the first variable at a specified time or during a specified period of time, the difference in the value of a third variable indicating blood pressure at the specified time or the variation over time of blood pressure during the specified period of time, by using differences in design.

2. 2. The diagnostic support image display device according to claim 1, The image display device for diagnostic support, wherein the design represents a time series variation of at least one of the first variable, the second variable, and the third variable.

3. 2. The diagnostic support image display device according to claim 1, 11. A diagnostic support image display device, comprising: a display device for displaying, in said coordinate system, an area for identifying factors affecting blood pressure, said area being surrounded by lines.

4. 1. A subject fluid purification device for removing at least one subject substance from an unpurified subject fluid of a patient, comprising: a first measuring device for measuring a first variable indicative of a parameter related to the peripheral circulation of the patient or its time variation; a second measuring device for measuring a second variable indicative of a parameter related to blood flow of the patient or its time variation; and a third measuring device for measuring a third variable indicating a parameter related to the patient's blood pressure or a time variation thereof.

5. The target liquid purification device according to claim 4, A target liquid purification device characterized by comprising a control unit that controls the operation of the target liquid purification device based on at least one variable selected from a first variable measured by the first measuring device, a second variable measured by the second measuring device, and a third variable measured by the third measuring device.

6. A diagnostic support image display device according to any one of claims 1 to 3, A target liquid purification system comprising: the target liquid purification device according to claim 4.

7. The target liquid purification system according to claim 6, A target liquid purification system, characterized by executing a process for storing at least one of a first variable measured by the first measuring device, a second variable measured by the second measuring device, and a third variable measured by the third measuring device in a memory device.

Images