Diagnosis assistance image display device, target liquid purification device, and target liquid purification system

Abstract

The present invention provides, for example, a diagnosis assistance image display device that is for confirming, during target liquid purification, a blood pressure regulation mechanism which occurs during hemodialysis and during purification of a target liquid other than blood, and that is for suitably managing a target liquid purification operation. A diagnosis assistance image display device B displays, in a coordinate system which has a first axis representing a first variable that indicates a parameter related to peripheral circulation or time fluctuations therein and which has a second axis representing a second variable that indicates a parameter related to the blood flow rate or time fluctuations therein, a plot in which the difference in value of a third variable indicating the blood pressure at a prescribed time or time fluctuations in the blood pressure during a prescribed period is represented in coordinates of the first and second variable values at the prescribed time or during the prescribed period by the difference in design.

Description

Diagnostic support image display device, target fluid purification device, and target fluid purification system

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

[0002] Hypotension during hemodialysis, particularly during hemodialysis, is one of the most frequent complications of hemodialysis (Non-Patent Documents 1 and 2). It is known that hypotension during hemodialysis affects the prognosis of hemodialysis patients (Non-Patent Documents 3, 4, 5, and 6). Various factors contribute to hypotension during hemodialysis (Non-Patent Documents 1, 7, and 8). Patients who experience hypotension during dialysis may experience impaired normal vascular resistance and volume responses to decreased blood volume. Various factors are known to contribute to this decline in normal vascular reactivity, including bioincompatibility reactions due to the use of dialysis membranes and dialysate, cytokine induction, 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 suffer from hypertension, which is known to be caused not only by increased blood volume due to renal dysfunction but also by 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 diabetic hemodialysis patients may have an inappropriate heart rate response to hypovolemia due to autonomic neuropathy (Non-Patent Document 11).

[0004] 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.Andrew D: Why is Intradialytic Hypotension the Commonest Complication of Outpatient Dialysis Treatments?. Kidney International Reports. 8(3), 405-418, 2023.Cheng JL, Chih YC: Interigent system to predict intradialytic hypotension in chronic hemodialysis. Journal of the Formosan Medical Association. 117(10), 888-893, 2018.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.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.Shoji T, Yoshiharu T: Dialysis Hypotension and Mortality Multicenter Prospective Study. The Japanese Society for Dialysis Therapy. 36(6), 1181-1182, 2003.Hanjie Z, Priscila P: Association of all - cause mortality with pre - dialysis systolic blood pressure and its peridialytic change in chronic hemodialysis patients. Nephrology Dialysis Transplantation. 35(9), 1602-1608, 2020.Magdalene MA, Jennifer EF: Intradialytic Blood Pressure Abnormalities: The Highs, The Lows and All That Lies Between. American Journal of Nephrology. 42(5), 337-350, 2016.Jeroen K, Ali B: EBPG guideline on hemodynamic instability. Nephrology Dialysis Transplantation. 22(2), ii22-ii44, 2007.C Venkata SR, Andrew ZF: Management of hypertension in hemodialysis patients. Current Hypertension Reports. 292-298, 2009.Alice D, Mauro FFM: Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications. World Journal of Diabetes. 12(6), 855-867, 2021.James SS, Terrence S: Physiology, Arterial Pressure Regulation -StatPearls - NCBI Bookshelf.Susanna C, Antonio L: Immune System Dysfunction and Inflamation in Hemodialysis Patients: Two Sides of the Same Coin. Journal of Clinical Medicine. 11(13), 3759, 2022.Maria M, Eleftherios D: Effects of a Combined Intradialytic Exercise Training Program and Music on Cardiac Autonomic Nervous System Activity in Hemodialysis Patients. Life. 12(8), 1276, 2022.Peter K: Cause and Consequences of Sympathetic Hyperactivity in Chronic Kidney Disease. Blood purification. 24(1), 95-99, 2005.Aaron I, Raelene E: Diabetic Autonomic Neuropathy. Diabetes Care. 26(5), 1553-1579, 2003.

[0005]

[0006] In addition to the fact that multiple factors are involved in blood pressure fluctuations during hemodialysis, the blood pressure regulatory mechanisms of hemodialysis patients also differ depending on their underlying diseases. Therefore, in order to appropriately manage various types of hypotension during hemodialysis, it is necessary to understand the blood pressure regulatory mechanisms of each individual dialysis patient.

[0007] 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, in particular, when purifying target fluids other than blood, while the target fluid is being purified, and that can appropriately manage the target fluid purification operation.

[0008] 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.

[0009] The diagnostic support image display device of the present invention is characterized in that it displays a plot that represents, by means of differences in design, differences in the value of a third variable that indicates blood pressure at a specified time or time period on the coordinates of the value of the first variable and the value of the second variable in a coordinate system having a first axis representing a parameter related to peripheral circulation or its variation over time and a second axis representing a parameter related to blood flow or its variation over time.

[0010] In the diagnosis support image display device having the above configuration, it is preferable that the design represents a time series variation of at least one of the first variable, the second variable, and the third variable.

[0011] In any one of the above-described image display devices for diagnosis support, it is preferable that an area for identifying factors that affect blood pressure is displayed on the coordinate system by being surrounded by a line.

[0012] 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.

[0013] The target fluid purification device of the present invention is a target fluid purification device for removing at least one target substance from a patient's unpurified target fluid, and is characterized by comprising: a first measuring device for measuring a parameter related to the patient's peripheral circulation or a first variable indicating its time variation; a second measuring device for measuring a parameter related to the patient's blood flow rate or a second variable indicating its time variation; and a third measuring device for measuring a parameter related to the patient's blood pressure or a third variable indicating its time variation.

[0014] Furthermore, in the target liquid purification device having the above configuration, it is preferable to include a control unit that controls the operation of the target liquid purification device based on at least one variable selected from the first variable measured by the first measuring device, the second variable measured by the second measuring device, and the third variable measured by the third measuring device.

[0015] 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.

[0016] A target fluid purification system of the present invention is characterized by comprising: any one of the above-described image display devices for diagnosis support; and any one of the above-described target fluid purification devices.

[0017] Furthermore, in the target liquid purification system having the above configuration, it is preferable to execute a process for storing in a storage device at least one variable selected from the first variable measured by the first measuring device, the second variable measured by the second measuring device, and the third variable measured by the third measuring device.

[0018] Blood pressure is generally affected 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 primarily controlled by the sympathetic nervous system.

[0019] Therefore, with any of the above-described diagnostic support image display devices, target fluid purification devices, or target fluid purification systems, it is possible to learn about changes in the mechanism of blood pressure fluctuations by simultaneously observing the state of peripheral circulation and the state of blood flow rate in addition to blood pressure fluctuations. Therefore, since the target fluid purification process and the like can be managed according to the mechanism of blood pressure fluctuations, it is possible to safely perform the target fluid purification process while appropriately managing blood pressure. Furthermore, 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 harm to the patient caused by medical accidents and the like.

[0020] 1 is a diagram showing an outline of a subject fluid purification system according to one embodiment of the present invention; 2 is a diagram showing an outline of a main body of a subject fluid purification system according to one embodiment of the present invention; 3 is an example of a display image displayed on a diagnostic support image display device according to the present invention; 4 is an example of a display image in which the ranges of blood pressure abnormalities due to vasopressin fluctuations, the range of blood pressure abnormalities due to renin-angiotensin system fluctuations, the range of blood pressure abnormalities due to sympathetic nervous system fluctuations, and the range of blood pressure abnormalities due to vasodilatory action are enclosed by lines on the coordinate system of FIG. 3; 5 is a diagram showing time series fluctuations in arterial blood pressure in the extracorporeal circulation group and the subject fluid purification group in this experiment; 6 is a diagram showing time series fluctuations in blood oxygen saturation in the extracorporeal circulation group and the subject fluid purification group in this experiment; 7 is a diagram showing time series fluctuations in heart rate in the extracorporeal circulation group and the subject fluid purification group in this experiment; 8 is a diagram showing time series fluctuations in ΔBP-ΔSpO2-ΔHR and arterial blood pressure in the extracorporeal circulation group; 9 is a diagram showing time series fluctuations in ΔBP-ΔSpO2-ΔHR and arterial blood pressure in the subject fluid purification group;

[0021] Next, one embodiment of the present invention will be described with reference to the drawings.

[0022] The target liquid purification system as a first embodiment of the present invention shown in Figure 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 wireless communication devices (not shown). Any wireless communication method may be used for the wireless communication, 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 also be connected by a wired connection via lead wires or the like.

[0023] (Configuration of target fluid purification device A) The target fluid purification device A comprises a main body 1 that removes at least one target substance from a patient's unpurified target fluid, a first measuring device 2 for measuring a parameter related to the patient's peripheral circulation or a first variable indicating its temporal variation, a second measuring device 3 for measuring a parameter related to the patient's blood flow rate or a second variable indicating its temporal variation, and a third measuring device 4 for measuring a parameter related to the patient's blood pressure or a third variable indicating its temporal variation. The target fluid purification system also executes processing to store 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.

[0024] Figure 2 shows an example of the main body 1 of the target fluid purification device A of this embodiment. As shown in Figure 2, the main body 1 includes a separation device 100, an unpurified target fluid passage 11, a purification target fluid passage 12, a regeneration unit 200, a dialysis fluid passage 21, a regenerated fluid passage 22, a drainage passage 24, and a first replenishment fluid passage 412. Note that the regeneration unit 200, the dialysis fluid passage 21, the regenerated fluid passage 22, the drainage passage 24, and the first replenishment fluid passage 412 may be omitted.

[0025] The separation device 100 is separated into a first portion 110 and a second portion 120 by a target fluid purification membrane 102. The target fluid purification membrane 102 has a pore size that allows target substances contained in the unpurified target fluid F11 (e.g., blood, plasma, dialysis effluent, hemofiltrate) to pass through. The "target substance" refers to a pathogenic substance that accumulates in the body when a disease occurs, such as 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, and proteins. The separation device 100 is configured to pass the unpurified target fluid F11 containing the target substance from the first portion 110 through the target fluid purification membrane 102 and introduce it into the second portion 120 to produce a filtered dialysis fluid F21, and to remove the target substances contained in the unpurified target fluid F11 through the passage, thereby producing a purified target fluid F12.

[0026] The unpurified liquid passage 11 is configured to introduce the unpurified liquid F11 drawn from the patient's body into a first section 110 of the separation device 100. The purification target liquid passage 12 is configured to lead the purification target liquid F12 from the first section 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 section 110 being the internal space of hollow fibers made of dialysis membranes, and the second section 120 being the space around the hollow fibers through which dialysate and / or regenerated liquid flows.

[0027] In this embodiment, the separation device 100 is configured as a "countercurrent separation device" in which the flow direction of the unpurified liquid F1 in the first portion 110 and the flow direction of the regenerated liquid F22 in the second portion 120 are opposite or opposite to each other. However, without being limited to this, in other embodiments, the separation device 100 may be configured as a "parallel current separation device" in which the flow direction of the unpurified 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.

[0028] The regeneration unit 200 may have an adsorbent that adsorbs the target substance. Examples of the adsorbent include activated carbon or an adsorbent based on activated carbon, a porous adsorbent, a cation exchange resin, an anion exchange resin, a zirconia-based ceramic, a zeolite, and mixtures 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 producing a regenerated fluid F22 having a reduced concentration of the target substance.

[0029] The filtrate passage 21 is configured to discharge the filtrate F21 from the second portion 120 of the separation device 100 and introduce a portion 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 drain, out of the first liquid F211 and the second liquid F212 resulting from 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 based on the inflow rate of the replacement fluid (fresh dialysis fluid) into the regeneration liquid passage 22 and / or the outflow rate of the regeneration liquid F22 from the regeneration liquid passage, taking into account the flow rate of the regeneration liquid F22 in the second portion 120 of the separation device 100. The regeneration liquid passage 22 is configured to introduce the regeneration liquid F22 from the regeneration section 200 into the second portion 120 of the separation device 100.

[0030] The first replacement fluid passage 412 is configured to directly introduce a first replacement fluid F41 into the purification target fluid passage 12. The "replacement fluid" refers to, for example, fresh dialysate 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 unpurified target fluid passage 11 upstream of the separation device 100. Alternatively, the first replacement fluid F41 may be omitted.

[0031] A single-path system may be adopted in which the regeneration unit 200, the dialysate filtrate passage 21, the regenerated liquid passage 22, the drainage passage 24, and the first replacement liquid passage 412 are omitted. As described above, the regeneration unit 200, the dialysate filtrate passage 21, the regenerated liquid passage 22, the drainage passage 24, and the first replacement liquid passage 412 are not essential components of the present invention and may be omitted.

[0032] The first measuring device 2 is a device for measuring a parameter related to the patient's peripheral circulation or a first variable indicating its time variation. Here, the parameter related to the patient's peripheral circulation may be, for example, blood oxygen saturation (SpO2), an index measured by a laser Doppler blood flowmeter or an ultrasonic Doppler blood flowmeter, or a perfusion index. In this embodiment, blood oxygen saturation is preferably used as the parameter related to the patient's peripheral circulation for ease of measurement. The first measuring device 2 is preferably worn on the patient's hand and measures blood oxygen saturation. The first measuring device 2 is preferably connected to the main body 1 of the subject fluid purification device A via lead wires, and the parameter related to the patient's peripheral circulation is stored in the storage device C via the lead wires.

[0033] In the above embodiment, the first measuring device 2 is attached to the patient's hand, but this is not a limitation and the first measuring device 2 may be provided as part of the blood circuit of the subject fluid purification device, or may be attached to a part of the patient's body other than the hand. Furthermore, in the above embodiment, the first measuring device 2 is connected to the main body 1 of the subject fluid purification device A via a lead wire, but this is not a limitation and the first measuring device 2 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.

[0034] The second measuring device 3 is a device for measuring a parameter related to the patient's blood flow or a second variable indicating its time variation. Here, the parameter related to the patient's blood flow 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 for ease of measurement. The second measuring device 3 can also simultaneously measure blood oxygen saturation using a blood oxygen saturation meter worn on the patient's hand. Furthermore, the second measuring device 3 is preferably connected to the main body 1 of the subject fluid purification device A via lead wires, and the parameter related to the patient's blood flow is stored in the storage device C via the lead wires.

[0035] In the above embodiment, the second measuring device 3 is attached to the patient's hand, but this is not limited thereto, and the second measuring device 3 may be provided as part of the blood circuit of the subject fluid purification device, or may be attached to a part of the patient's body other than the hand. Furthermore, in the above embodiment, the second measuring device 3 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 the second measuring device 3 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.

[0036] 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, for example, blood pressure in the upper arm. In particular, in the present invention, the third measuring device 4 preferably measures blood pressure in the patient's upper arm, and is preferably placed near the patient's upper arm. Furthermore, the third measuring device 4 is preferably connected to the main body 1 of the subject fluid purification device A via lead wires, and the parameter related to the patient's blood pressure is stored in the memory device C via the lead wires.

[0037] 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 placed in a part of the blood circuit of the subject fluid purification device, or in a part where an artery or vein other than the upper arm can be measured. 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.

[0038] From the viewpoint of accurately monitoring the patient's condition, it is preferable that each of the first measuring device 2, the second measuring device 3, and the third measuring device 4 performs sampling at intervals of 10 seconds to 60 minutes, and more preferably, at intervals of 1 to 20 minutes from the viewpoint of data storage and processing.

[0039] The target fluid purification device A may further include a control unit that controls the target fluid purification process. The control unit includes a storage device C (such as a RAM, ROM, or EEPROM, or a SSD or HDD) that stores and retains programs (software) and data, a calculation processing unit (such as a single-core processor, a multi-core processor, or a CPU) that reads the necessary programs and / or data from the storage device C and executes predetermined calculations, and an I / O circuit. As described below, the control unit controls the flow rate of the replenisher fluid or the amount of water removed during the target fluid purification process, thereby controlling the operation of the target fluid purification device as a whole. Note that the storage device C, the calculation processing unit, and the I / O circuit may be provided independently of the control unit, or may be integrated into the control unit. The control unit includes an abnormality detection unit that detects an abnormality (e.g., a sudden change in blood pressure or a low blood pressure state) during the target fluid purification process based on the first variable, the second variable, or the third variable, and reports the abnormality.

[0040] (Configuration of diagnostic support image display device) The diagnostic support image display device B is a personal computer, a mobile phone (smartphone), or the like, and includes any information terminal device. The diagnostic support image display device B displays various information in the target fluid purification process, such as the flow rate of the replenishment fluid, the elapsed time in the target fluid purification process, the total amount of replenishment fluid flowing in, the composition of the unpurified target fluid F11, and the composition of the purified target fluid F12. The diagnostic support image display device B may be provided in a remote device that remotely operates or remotely manages the target fluid purification device A.

[0041] Furthermore, the diagnostic support image display device B displays a plot in a coordinate system having a first axis representing a parameter related to peripheral circulation or its temporal variation, and a second axis representing a parameter related to blood flow or its temporal variation, in which the value of the first variable at a predetermined time or period and the value of the second variable represent the coordinate of the value of the third variable representing blood pressure at a predetermined time or period, expressed by different designs. Figure 3 shows an example of an image displayed on the diagnostic support image display device B. The coordinate system shown in Figure 3 has the time difference (ΔHR) of heart rate as the second variable over a predetermined period on the vertical axis and the time difference (ΔSpO2) of blood oxygen saturation as the first variable over a predetermined period on the horizontal axis. Here, the vertical axis represents ΔHR and the horizontal axis represents ΔSpO2, but this is not limiting, and the vertical and horizontal axes may be reversed. Furthermore, although blood oxygen saturation and heart rate are shown on the horizontal and vertical axes, 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.

[0042] 3 further shows a design representing the difference in the value of the time difference (ΔBP) of blood pressure as a third variable over a predetermined period of time, plotted on the coordinates of the values ​​of the first variable and the second variable over a predetermined time or period of time, where the design is represented by a circle whose radius increases as the absolute value of the time difference of blood pressure increases, and whose color 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 the time difference is negative.

[0043] That is, the diagnostic support image display device B displays the time fluctuations of the patient's heart rate and blood oxygen saturation during or before and after the purification of the target fluid in the form of a scatter plot on the coordinate system. The design shown in Figure 3 is a bubble chart in which the time fluctuations of blood pressure (ΔBP) are plotted in color when positive and in white when negative, and the absolute value of the time difference in blood pressure over a predetermined period is represented by the size of the plot.

[0044] 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 derivative, an Nth-order derivative of time (N is any integer; including 0), an Nth-order derivative of discretized time over a predetermined period of time, etc. Furthermore, the difference in this embodiment is preferably a forward difference, but may also be any other difference such as a backward difference or a central difference.

[0045] The diagnosis support image display device B preferably displays the data in the form of a bubble chart, but is not limited to this and may display any other diagram such as a heat map, radar chart, bar graph, or line graph.

[0046] The design may be composed of multiple design parts. For example, a design for a predetermined period may be displayed as one design part on the diagnostic support image display device B, and then a design for a next predetermined period may be displayed as another design part simultaneously with the first design part or as a video. When simultaneously displaying the first design part and the other design part, the first design part and the other design part may be expressed to represent a time series variation of at least one of the first variable, the second variable, and the third variable. For example, the first design part and the other design part may be connected by an arrow or the like, or an expression such as a color change according to the change over time may be added. Furthermore, the number of design parts may be two or more. When the first design part and the other design part are displayed as a video, i.e., when the design is displayed as a dynamic design, the design may be generated by animation, such as displaying one design part followed by another design part a few seconds later.

[0047] The diagnostic support image display device B may display a region that specifies factors that affect blood pressure, enclosed by a line on the coordinate system described above. Factors that affect blood pressure include biological hormones of the vasopressin system, biological hormones of the renin-angiotensin system, fluctuations in the sympathetic nervous system, and vasodilatory action.

[0048] Figure 4 shows an embodiment of a display image in which, on the coordinate system, a region identified as having blood pressure fluctuations due to fluctuations in biological hormones of the vasopressin system, a region identified as having blood pressure fluctuations due to fluctuations in biological hormones of the renin-angiotensin system, a region identified as having blood pressure fluctuations due to fluctuations in the sympathetic nervous system, and a region identified as having blood pressure fluctuations due to vasodilatory action are each surrounded by lines. Here, region R1 is the range of blood pressure abnormalities due to fluctuations in the sympathetic nervous system. Generally, when the sympathetic nervous system is excited, the heart rate tends to increase and peripheral blood vessels tend to dilate (decreased blood oxygen saturation). Region R2 is the range of blood pressure abnormalities due to fluctuations in the sympathetic nervous system. Generally, when the sympathetic nervous system is inhibited, the heart rate tends to increase and peripheral blood vessels tend to constrict (increased blood oxygen saturation). Region R3 is the range of blood pressure abnormalities due to 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 fluctuate, causing ΔHR to vary from positive to negative values. Therefore, in region R3, ΔHR varies from positive to negative values, and ΔSpO2 takes a negative value. Region R4 is the range of blood pressure abnormalities caused by vasopressin. Generally, heart rate is not affected by vasopressin. Therefore, in region R4, ΔHR varies from positive to negative values, and takes a ΔSpO2. Because the effect of vasopressin-induced vasoconstriction on ΔSpO2 is fundamentally weaker than the effect of the renin-angiotensin system, region R4 takes a value closer to the origin than region R3.

[0049] In addition to the above-described aspects, the diagnostic support image display device B may further add to the coordinate system a region within the normal range or a region of abnormal blood pressure caused by the influence of other biological hormones. Furthermore, the diagnostic support image display device B may further display a graph relating 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.

[0050] The diagnostic support image display device B may be configured to display a diagram based on the values ​​of the first, second, and third variables in a past target fluid purification process stored in the storage device C. In other words, it may be configured to display the patient's blood pressure fluctuations and their causes associated with past target fluid purification processes before the target fluid purification.

[0051] Next, examples of this embodiment will be described with reference to the drawings.

[0052] (Experimental Subjects) 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 cycle. During surgery, the rats were anesthetized with 3% isoflurane. During perfusion, the rats were anesthetized with 1.5% isoflurane.

[0053] The experiments in this example were conducted in accordance with the "Basic Guidelines for Proper Conduct of Animal Experiments, etc. in Academic Research Institutions." This study was approved by the Animal Experimentation Committee of the Kitasato University School of Allied Health Sciences (approval number 19-05-3).

[0054] (Experimental Groups) Experiments were conducted on rats 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 conducted 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: 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, effective length 160 mm. This experimental group underwent extracorporeal circulation in which the target fluid F12 discharged from the separation device 100 was introduced into a dialysis chamber (Labolan®, silicone tube 1×3, 9-869-03, AS ONE Corporation, Japan) and then returned to the femoral vein via the target fluid passage 12. In the target fluid purification group, the experiment was conducted without passing through the regeneration unit 200, the dialysis fluid passage 21, the regeneration fluid passage 22, the drainage passage 24, and the first replacement fluid passage 412. There was no significant difference in the rat body size between the groups (extracorporeal circulation group: 398.0±14.2 g, target fluid purification group: 348.1±25.1 g).

[0055] (Experimental environment) The unpurified target fluid passage 11 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 with X-rays. 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.

[0056] (Experimental Procedures) Rats in each experimental group were anesthetized with 3% isoflurane and cannulated into the tail vein using a 24G indwelling needle (SurfloFlash®, intravenous cannula 24G x 3 / 4, Terumo). Next, one side of the groin was incised, and the femoral vein and femoral artery were separated. The femoral vein was cannulated using a 20G intravenous cannula (SurfloFlash®, intravenous cannula 20G x 1 1 / 4, Terumo). The femoral artery was cannulated using a 24G intravenous cannula. After surgery, each experimental group underwent a 4-hour circulation experiment. Extracorporeal circulation was performed using a peristaltic pump (SJ-1211H, Atto, Japan) at a blood flow rate (QB) of 1.0 mL / min. The replacement fluid passage 41 (dialysis fluid) was filled with lactated Ringer's solution and closed to prevent flow through the dialysate side of the dialyzer 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 then 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 remained around 350 seconds.

[0057] (Measurement Conditions) Arterial blood pressure was measured from the femoral artery as the third variable, and its fluctuations were recorded. A pulse oximeter sensor probe from a pulse oximeter and heart rate monitor (PhysioSuite® for Mice & Rats, Kent Scientific) was attached to the rat's hand, and blood oxygen saturation (SpO2) was measured as the first variable and heart rate (HR) was measured as the second variable. All parameters were recorded every 15 minutes. In this example, the forward time difference of blood oxygen saturation over 15 minutes (ΔSpO2) was used as the first variable, the forward time difference of heart rate over 15 minutes (ΔHR) was used as the second variable, and the forward time difference of blood pressure over 15 minutes (ΔBP) was used as the third variable.

[0058] (Results) Figure 5 shows the time series fluctuations of arterial blood pressure in the extracorporeal circulation group and the control fluid purification group (Dialyzer) in this experiment. Referring to Figure 5, arterial blood pressure in both the extracorporeal circulation group and the control fluid purification group showed a significant upward trend 2 hours after the start of perfusion, and a significant downward trend 3 to 4 hours after the start of perfusion.

[0059] Figure 6 shows the time series of blood oxygen saturation (SpO2) in the extracorporeal circulation group (ECG) and the control fluid purification group (Dialyzer) in this experiment. As shown in Figure 6, blood oxygen saturation showed a significant decrease 1 to 3 hours after the start of perfusion in both the ECG and control fluid purification groups. Furthermore, 165 minutes after the start of extracorporeal circulation, blood oxygen saturation in the control fluid purification group was significantly lower than that in the ECG group.

[0060] Figure 7 shows the time series variation of heart rate (HR) in the extracorporeal circulation group (ECG) and the control fluid purification group (Dialyzer) in this experiment. Referring to Figure 7, the heart rate in both the extracorporeal circulation group and the control fluid purification group showed a significant upward trend from 30 to 150 minutes after the start of perfusion, and a significant downward trend from 3 to 4 hours after the start of perfusion. At 3 hours (180 minutes) and 195 minutes after the start of perfusion, the heart rate in the control fluid purification group was significantly higher than that in the extracorporeal circulation group. Arterial blood pressure during the perfusion experiment showed similar fluctuations in the extracorporeal circulation group and the control fluid purification group.

[0061] Although there were differences in blood oxygen saturation and heart rate between the groups, the overall trend in fluctuations was similar. When the data were plotted on a ΔBP-ΔSpO2-ΔHR correlation diagram, the difference between the extracorporeal circulation group and the control fluid purification group was more pronounced.

[0062] Figure 8 shows the time series fluctuations of ΔBP-ΔSpO2-ΔHR and arterial blood pressure over 60 minutes in the extracorporeal circulation group. Figure 9 shows the time series fluctuations of ΔBP-ΔSpO2-ΔHR and arterial blood pressure over 60 minutes in the control fluid purification group. In the ΔBP-ΔSpO2-ΔHR plots shown in Figures 8 and 9, black circles represent positive heart rate time differences, white circles represent negative heart rate time differences, and the diameter of the circle represents the absolute value of the heart rate time difference. In the ΔBP-ΔSpO2-ΔHR correlation diagrams ( Figures 8a and 9a ) from 0 to 1 hour after the start of circulation, an increase in heart rate was observed in addition to an increase in arterial blood pressure in the control fluid purification group ( Figure 8a ). Furthermore, the plots for the control fluid purification group are located in region R1 of Figure 4 .

[0063] 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, with the plots located in region R1. The decrease in blood oxygen saturation was more pronounced in the control fluid purification group (Fig. 9b), with the plots located in regions 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.

[0064] In the correlation diagrams (Fig. 8c, Fig. 9c) 2 to 3 hours after the start of circulation, there was no change in ΔBP, ΔSpO2, or ΔHR in either the extracorporeal circulation group or the control fluid purification group, and the data are plotted near the origin.

[0065] In the correlation diagrams (Fig. 8d, Fig. 9d) 3-4 hours after the start of circulation, a decrease in HR was observed in the extracorporeal circulation group (Fig. 8d), while a decrease in heart rate and an increase in blood oxygen saturation were observed in the target fluid purification group (Fig. 9d). In the extracorporeal circulation group, there was a plot in region R2, and there were plots in regions R3 and R4, which suggests that the sympathetic nervous system was suppressed in both groups, and vasodilatory effects were added to the sympathetic nervous system, causing a decrease in blood oxygen saturation.

[0066] 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 target fluid purification, but the range of fluctuation in blood oxygen saturation was greater during target fluid purification.When these results are expressed in a ΔBP-ΔSpO2-ΔHR correlation diagram, it is suggested that factors that cause blood pressure fluctuations, such as sympathetic nerve excitation and inhibition, can be visually estimated.

[0067] It is known that when blood comes into contact with the target fluid purification membrane 102, bioincompatibility reactions such as cytokine production occur (Non-Patent Document 13). The correlation diagram makes it easy to distinguish between the extracorporeal circulation group and the target fluid purification group. Furthermore, the correlation diagram also makes it easy to distinguish between the extracorporeal circulation group and the target fluid purification group. Thus, the correlation diagram is simple and considered useful for considering factors that contribute to blood pressure fluctuations during dialysis. Currently, hemodynamic monitoring is based on blood pressure and heart rate, or, in the case of the autonomic nervous system, on the R-R interval (Non-Patent Document 14). This example demonstrates that adding monitoring that reflects vasoconstriction and vasodilation, such as blood oxygen saturation, can provide particularly useful information about blood pressure fluctuations during hemodialysis.

[0068] Furthermore, the data used in this study were obtained from experiments using normal rats. Hemodialysis patients may exhibit persistent sympathetic nervous system overactivity, which is due to signals generated in the damaged kidney being transmitted to the cardiovascular center in the brainstem via afferent renal nerves (Non-Patent Document 15). Diabetic hemodialysis patients also frequently develop autonomic neuropathy due to reduced intraneuronal blood flow, neurohypoxia, and decreased nerve conduction velocity caused by hyperglycemia (Non-Patent Document 16). Therefore, when comparing clinical data from hemodialysis patients with the results from 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, this analytical method is useful for blood pressure management in dialysis patients.

[0069] Therefore, with the diagnostic support image display device, target fluid purification device, or target fluid purification system of the present invention, changes in the mechanism of blood pressure fluctuations can be identified by monitoring blood oxygen saturation, an index that reflects blood pressure fluctuations as well as heart rate and vasoconstriction. This allows the target fluid purification process to be managed according to the mechanism of blood pressure fluctuations, making it possible to safely perform the target fluid purification process while appropriately managing blood pressure. Furthermore, the condition of a target fluid purification patient, such as a dialysis patient, can be quickly detected, reducing harm to the patient caused by medical accidents and the like.

[0070] Although the present invention has been described based on the embodiments and examples, the present invention can be used in other ways within the scope of the object of the present invention and within the technical scope thereof, in addition to the above-mentioned embodiments and examples. Furthermore, the embodiments and examples of the present invention can be easily modified and altered by those skilled in the art.

[0071] A: Target fluid purification device B: Diagnostic support image display device 1: Main body 2: First measuring device 3: Second measuring device 4: Third measuring device 11: Unpurified target fluid passage 12: Purified target fluid passage 21: Filtration dialysis fluid passage 22: Regenerated fluid passage 24: Drainage fluid passage 100: Separation device 102: Target fluid purification membrane 110: First part 120: Second part 200: Regeneration section 210: Replacement fluid / regenerated fluid concentrator 412: First replacement fluid passage F11: Unpurified target fluid F12: Fluid to be purified F21: Filtration dialysis fluid F211: First fluid (drainage fluid) F212: Second fluid F22: Regenerated fluid F41: First replacement fluid.

Claims

1. A diagnostic support image display device characterized by displaying a plot showing the difference in the value of a third variable indicating blood pressure at a specified time or the time variation of blood pressure over a specified period of time on the coordinates of the value of the first variable and 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, 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.

2. An image display device for diagnostic support as described in claim 1, characterized in that the design represents a time series variation of at least one of the first variable, the second variable, and the third variable.

3. A diagnostic support image display device according to claim 1, characterized in that an area for identifying factors affecting blood pressure is displayed in said coordinate system by being surrounded by a line.

4. A target fluid purification device for removing at least one target substance from a patient's unpurified target fluid, comprising: a first measuring device for measuring a first variable indicating a parameter related to the patient's peripheral circulation or a parameter that indicates its time variation; a second measuring device for measuring a second variable indicating a parameter related to the patient's blood flow rate or a parameter that indicates 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 parameter that indicates its time variation.

5. A target liquid purification device as described in claim 4, characterized in that it comprises 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 target liquid purification system comprising: a diagnostic support image display device according to any one of claims 1; and a target liquid purification device according to claim 4.

7. A target liquid purification system as described in claim 6, characterized in that the target liquid purification system executes a process for storing in a memory device 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.

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