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    公开号:ES2628375T9
    申请号:ES12198335.7T
    申请日:2012-12-20
    公开日:2018-01-04
    发明作者:Paolo Rovatti；Alessandro SURACE
    申请人:Gambro Lundia AB；
    IPC主号:
    专利说明:

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    DESCRIPTION
    An apparatus for extracorporeal blood treatment
    The present invention relates to an apparatus for extracorporeal blood treatment that has the ability to monitor parameters such as the variation of blood volume, conductivity or concentration of dialysis fluid and water removed from the patient and thereby performed appropriate control stages in order to provide a comfortable treatment to the patient. The apparatus for extracorporeal blood treatment can be, for example, a hemodialysis and / or hemodiafiltration apparatus.
    Apparatus for extracorporeal blood treatment comprise at least one treatment unit (for example a dialyzer or a hemofilter or a hemodiafilter or an ultrafilter or a plasma filter or a filtration unit of another type) having a semipermeable membrane that separates The treatment unit in two chambers. An extracorporeal blood circuit allows the circulation of blood taken from a patient internally with respect to the first chamber. At the same time, and usually in a counter-current direction with respect to blood, a treatment fluid is circulated through an appropriate circuit in the second chamber of the treatment unit. This type of blood treatment device can be used for the removal of excess solutes and fluids from the blood of patients suffering from kidney failure. A particular type of blood treatment apparatus, known as a hemofiltration or hemodiafiltration apparatus, comprises the presence of one or more infusion lines configured to send a replacement fluid to the extracorporeal blood circuit. The infusion line or lines may be connected upstream and / or downstream with respect to the treatment unit.
    The blood treatment apparatus described above can be controlled in various ways. For example, the apparatus can be controlled volumetrically to have predetermined flow rates along the various fluid transport lines. Alternatively, the apparatus can be controlled such that the transmembrane pressure (indicated herein as TMP) follows a set value. Application WO2005IB01482 illustrates an apparatus and a process for establishing the value of TMP at a level that is such that the ultrafiltration flow rate is maximized and therefore the volume of fluid infused into the patient. This solution is advantageous since it maximizes the ultrafiltration and infusion flow rates, thus improving the exchange by convection through the membrane and the purification of the blood in terms of unwanted particles.
    Although the publication cited above offers an advantageous procedure for establishing TMP, fluid extraction from a patient does not always correspond to a comfortable treatment for the patient. Technical solutions are also known, described for example in patent document EP778783, in which the blood treatment apparatus is controlled in such a way that two parameters, ie the variation of the blood volume and the rate of weight loss are they maintain a range of acceptability while controlling the conductivity of the dialysis fluid (i.e. the fluid at the entrance to the second chamber of the treatment unit) and the rate of weight loss. Although this type of control has led to benefits for the patient undergoing treatment and has allowed two objectives to be achieved with a single treatment, it should be noted that the use of the method of EP778783 has been essentially limited to hemodialysis devices.
    In addition, from WO2012 / 127298 a hemodiafiltration apparatus is known which determines the patient's blood volume, ultrafiltration flow rate, conductivity or concentration of a liquid that crosses the dialysis line and / or the infusion line. , and the infusion flow rate (Qinf). The apparatus comprises a control unit to control the variation of blood volume and to apply a transmembrane pressure (TMP) to values that allow to maximize exchanges by convection.
    US4923613 discloses a dialysis machine in which, to determine the level of sodium in the blood, the conductivity of the dialysis fluid is brought to an equilibrium conductivity value, for which the conductivity in the outflow of the exchanger at a time t is equal to the conductivity in the inlet flow to the same exchanger at a time t-tL.
    Summary
    An object of the present invention is to make available an apparatus for the treatment of blood that can integrate efficient control over a plurality of prescription parameters such as total weight loss, blood volume change and plasma conductivity / concentration.
    A further objective of the present invention is to provide an apparatus that can implement an integrated control over a plurality of prescription parameters avoiding conflicts between controls and which aims to improve patient comfort during treatment.
    Another object of the invention is to provide an apparatus that can operate the control based as much as possible on the patient's feedback.
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    At least one of the aforementioned objectives is substantially achieved by a blood treatment apparatus as in one or more of the appended claims.
    At least one of the foregoing objects is substantially achieved by an apparatus according to one or more of the appended claims.
    Description of the drawings
    The invention will be described with the aid of the figures of the drawings, by way of non-limiting example, which illustrate some aspects of the invention. In particular:
    - Figure 1 is a schematic illustration of a first example of a blood treatment apparatus of the invention;
    - Figure 2 is a schematic view of a second example of a blood treatment apparatus of the invention;
    - Figure 3 is a block diagram related to the calculation, for example periodically, of control values for the ultrafiltration rate / weight loss rate and for the concentration / conductivity of the dialysis fluid performed by the control unit and which then apply to the device;
    - figure 4 is a flow chart showing a control method according to the invention, which can be carried out by means of the control unit of an apparatus, for example, of the type illustrated in figure 1 or figure 2;
    - Figure 5 is a time diagram showing an establishment procedure according to an aspect of the invention, which can be carried out by means of the control unit of an apparatus, for example, of the type illustrated in Figure 1 and Figure 2 , during or after the completion of the control procedure of Figure 4; Y
    - Figures 6 and 7 are time diagrams showing the progression of the TMP transmembrane pressure during the establishment of the TMP, in one aspect of the invention.
    Detailed description
    The following description refers to examples of apparatus for extracorporeal blood treatment, such as for example a hemodialysis or a hemodiafiltration apparatus, which implement aspects of the present invention. Figures 1 and 2 are non-limiting examples schematically showing two possible embodiments of hemodiafiltration apparatus suitable for implementing aspects of the present invention.
    With reference to Figures 1 and 2, reference number 1 designates in its entirety an apparatus for extracorporeal blood treatment. The apparatus 1 comprises at least one treatment unit 2, for example a hemofilter or a hemodiafilter, having at least a first chamber 3 and at least a second chamber 4 separated from each other by a semipermeable membrane 5.
    A blood withdrawal line 6 is connected to an inlet opening of the first chamber 3 and is capable, under operating conditions of connection to a patient, of withdrawing blood from a vascular access V1 inserted for example in a fistula F of the patient . A blood return line 7, connected to an outlet port of the first chamber, is configured to receive the treated blood from the treatment unit and to return the treated blood to an additional vascular access V2 connected to the patient's fistula. Note that the configuration of the vascular access can be of any nature: for example a catheter, a path implanted in the patient, a cannula, a needle, etc. The blood withdrawal line 6, the first chamber 3 of the treatment unit and the blood return line 7 to the patient are in practice part of an extracorporeal blood circuit 8 which, during the use of the apparatus 1, provides the blood circulation externally with respect to the patient's body when undergoing treatment.
    In the example of Figure 1, an infusion line 9 of a replacement fluid is connected to the blood withdrawal line 6, upstream of the first chamber 3. Alternatively, the infusion line 9 may be connected to the line return 7, downstream of the first chamber 3. In the example of figure 2 an infusion line 9a is connected downstream of unit 2, while an infusion line 9b is connected upstream of unit 2. With Referring to the example of both Figure 1 and Figure 2, note that additional infusion lines can also be provided, for example connected downstream or upstream of the treatment unit. The apparatus 1 further comprises a dialysate circuit comprising at least one fluid evacuation line 10 connected to an outlet orifice of the second chamber 4 to receive at least one filtered fluid through the semipermeable membrane. In the examples of Figures 1 and 2, the dialysate circuit also includes a dialysis line 11 for supplying a new treatment fluid at the entrance to the second chamber 4; a fluid checking element 12 can be used to selectively allow or inhibit a
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    passage of fluid through the dialysis line 11, depending on whether it is desired or not, to have a purification by means of a diffusion effect internally with respect to the treatment unit.
    The apparatus 1 of both Figure 1 and Figure 2 comprises sensors (S1, S2, S3, S4, S5, S6, S7, S8, S9, S10) to determine the values assumed during the treatment by certain parameters described below. in this document in more detail. Of course, other sensors may also be present in the apparatus 1.
    Transmembrane pressure (TMP, Transmembrane Pressure)
    During the treatment it is necessary to move unwanted fluid and particles from the first chamber 3 to the second chamber 4 of the treatment unit 2. The movement of fluid and particles creates a transmembrane pressure that is defined as the average pressure applied on the side from the first camera to the side of the second camera. The transmembrane pressure (designated hereinafter in abbreviated form as TMP) can be determined in a practical manner in various ways. For example, an estimate of the TMP transmembrane pressure can be calculated as follows.
    1) In a case where (see Figures 1 and 2) four pressure sensors are present, of which one S1 is in the supply line 11, another S2 in the evacuation line 10, another S3 in the line of withdrawal of blood 6 and a fourth S4 on the return line 7, an estimate of the value of TMP can be determined by the control unit 15 using the pressure signals from sensors S1 to S4 that adopt the formula:
    image 1
    where:
    Pi is the pressure detected by the S1 sensor Po is the pressure detected by the S2 sensor Ps is the pressure detected by the S3 sensor Pv is the pressure detected by the S4 sensor
    2) In a case where the apparatus includes three pressure sensors, of which one S2 is in the evacuation line 10, another S1 in the dialysis line 11 and another S4 is from the return line 7, an estimate of the value of TMP can be determined by the control unit 15, using the pressure signals from said three sensors with the formula:
    image2
    where:
    Po is the pressure detected by the S2 sensor Pi is the pressure detected by the S1 sensor Pv is the pressure detected by the S4 sensor
    3) Finally, in one case the apparatus includes two pressure sensors, of which one is in the evacuation line 10 and one in the return line 7, an estimate of the value of TMP can be determined by the control unit 15 using Pressure signals from sensors S2 and S4 with the formula:
    TMP = Pv-Po
    where:
    Po is the pressure detected by the S2 sensor Pv is the pressure detected by the S4 sensor
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    Naturally, the above formulas are by way of example only and other sensors and other formulas can be adopted to determine the TMP.
    Infusion flow rate (Qinf)
    The apparatus may comprise an infusion flow rate sensor S5 Qinf of the replacement fluid through the infusion line 9 or the infusion lines 9a, 9b. The sensor or S5 sensors for detecting the flow may in practice be volumetric sensors, mass sensors such as for example Coriolis sensors, weight sensors such as scales, pump revolution sensors or other types of sensors: As the type of sensors that can be used is not important for the present invention and since the techniques and sensors for detecting absolute or differential flow values are known and are within the skill of the person skilled in the art, no further details are provided. .
    In the case illustrated in Figures 1 and 2, the infusion flow rate sensors comprise sensors S5 configured to determine the number of revolutions of the infusion pumps, sending a corresponding signal to the control unit 15 which is configured to calculate a flow rate along the respective infusion line based on the rate of revolutions detected and certain calibration factors.
    Ultrafiltration Flow Rate (UFR)
    The apparatus 1 may further comprise at least one sensor S6 for detecting the ultrafiltration flow rate through the semipermeable membrane 5. For example, a flow sensor S6a may be present in the evacuation line 10 and a flow sensor S6a in the dialysis line 11 to provide the control unit 15 with the momentary value of the respective flows and therefore allow the control unit to calculate a momentary value of the ultrafiltration flow rate as the difference between the flow rate a through the evacuation line 10 and the flow rate through the dialysis line 11. Alternatively, a differential sensor can be provided, active in the evacuation line and the dialysis line and therefore capable of directly providing a signal related to The ultrafiltration flow rate. As an additional alternative (not shown), an ultrafiltration line can be provided that branches off the evacuation line 10: in this case the flow rate in the dialysis line 11 and in the evacuation line 10 downstream of the branch point can be kept balanced so that the ultrafiltration flow rate is identical to the flow rate through the ultrafiltration line that can be measured with an appropriate flow sensor (for example of the S6 sensor type) or by means of a scale. The sensor or sensors S6, S6a, S6b may in practice be volumetric sensors, mass sensors such as for example Coriolis sensors, weight sensors such as for example scales, pump revolution sensors, or other sensors : since the type of sensors that can be used is not important for the present invention and since the techniques and sensors for detecting absolute or differential flow values are known and are within the skill of the person skilled in the art, they are not included Additional details in this description.
    Weight Loss Rate (WLR, Weiaht Loss Rate)
    The WLR weight loss rate can be measured by subtracting the infusion rate (for example as measured above) from the UFR ultrafiltration flow rate (for example as described above) because the three rates just mentioned are linked using the ratio UFR = Qinf + WLR. In other words, having sensors S6 and S5 available, the control unit 15 may be programmed to derive (for example: to calculate mathematically) the weight loss rate WLR. As an additional alternative a sensor can be provided that is capable of providing a signal that facilitates the rate of weight loss: for example a sensor capable of differentially measuring the rate taken from the evacuation line and subtracting the flow rate through of the dialysis line and / or the rate or flow rates through the infusion line or lines. The sensor can be substantially a mass flow sensor (for example a Coriolis type sensor), a volumetric sensor, an electromagnetic sensor, a weight sensor (such as a scale capable of weighing fluid pockets) or another type of sensor.
    Blood volume
    The apparatus 1 comprises an S7 sensor to detect the variation of the blood volume (BV%, Blood Volume) or a parameter from which the variation of the blood volume can be calculated in relation to the blood of a patient undergoing treatment. The blood volume variation sensor can be, for example, an optical sensor, capable of detecting a variation in the optical properties of the blood through a portion of a calibrated tube. For example, a detection of the variation of the blood volume can comprise calculating, by means of the control unit 15, a variation in percentage of the blood volume circulating in the patient (BV%) from the beginning of the hemodialysis treatment (or hemofiltration, or hemodiafiltration) based on the measurement of hemoglobin concentration in the blood, according to the known formula:
    image3
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    where HGBo represents the hemoglobin concentration at the start of treatment and HGBt the hemoglobin concentration at time t at which BV% is calculated.
    The hemoglobin concentration can be calculated based on the variation of optical absorbance at a predetermined wavelength, detected by an optical sensor, of the blood flowing in the blood withdrawal line 6. The optical sensor is associated, for example, with a tube section that has the appropriate optical properties that have been previously measured or are known. Naturally, the HGB values can be measured alternatively with other techniques such as measuring other properties of the blood (for example: capacitance, impedance), without departing from the scope of the present invention.
    Weightloss
    The apparatus 1 can also determine the weight loss over a period of time, for example from the start of treatment to a certain time t: for example the control unit 15 can be programmed to integrate the weight loss rate WLR over time. Alternatively, a weight loss sensor may be provided, for example a sensor intended to detect the variation of the overall weight of a patient during treatment, or a sensor intended to directly detect the overall weight of the net fluid drawn net of a patient.
    Conductivity or concentration
    The apparatus 1 further comprises at least one S8 conductivity or sodium concentration sensor (or concentration of another substance to be monitored) of the liquid flowing through the dialysis line 11. For example, the conductivity or concentration sensor S8 may also be located immediately downstream of a device to regulate a composition of the dialysis fluid and / or replacement fluid, which will be described more fully below.
    Ultrafiltration device
    The apparatus 1 further comprises an ultrafiltration device 20 for regulating ultrafiltration or TMP transmembrane pressure between the first and second chamber of the treatment unit. The ultrafiltration device 20 is connected to the control unit 15 and is active in at least one of the extracorporeal circuit and the dialysate circuit. The first regulating device may comprise: a pump 13 located in the fluid evacuation line 10, or two blood pumps located one upstream and one downstream of the filter unit 2 and controlled at different speeds, or a pump 13 in the dialysis line 11 and a pump 14 in the evacuation line 10 that are controlled at different speeds to generate a net ultrafiltration flow rate through the membrane. Of course, other combinations of one or more pumps or valves properly disposed in the blood line or the fluid evacuation line or the dialysate line are possible. In the example illustrated in Figures 1 and 2, the device 20 comprises an ultrafiltration pump 13 that operates in the evacuation line and capable of extracting fluid from the second chamber. In the example of figure 2 there is also a treatment fluid supply pump 14 operating in the dialysate line: therefore, in this case the ultrafiltration device 20 comprises both the ultrafiltration pump and the supply pump, which are differentially controlled to create a UFR ultrafiltration flow through the membrane. The control unit 15 can send orders to the ultrafiltration device 20 (in the example of Figures 1 and 2, pumps 13 and 14) so that the measured value of TMP corresponds to the value set for tMp. In this case, the control unit acts continuously or periodically on the ultrafiltration device 20 so that, moment by moment, the measured TMP corresponds to the established TMP value prescribed for that moment (pressure control TMP). Thus, the UFR ultrafiltration flow rate through the membrane and therefore the amount of fluid removed from the blood present in the first chamber is a function of the TMP applied. Alternatively, the control unit 15 may be programmed so that the ultrafiltration flow rate UFR follows one or more values set for the ultrafiltration flow rate (volumetric control): in this case, the TMP will be variable and the unit of The control will act on the ultrafiltration device 20 to maintain the ultrafiltration flow rate constantly close to or equal to a reference value or values prescribed or calculated for the UFR.
    Fluid Preparation Section
    The apparatus 1 may further comprise a fluid preparation section 30 to regulate a composition of the dialysis liquid and / or the replacement liquid. In the example of Figure 1 and Figure 2, the fluid preparation section 30 comprises one, two or more concentrate vessels 31, 32, 33 located in respective injection lines 31a, 32a, 33a that are configured to deliver substances such as electrolytes, buffering agents or others towards a preparation line 35 of the liquid located upstream of the dialysis line 11. The concentrate containers may comprise concentrates in the liquid or solid state, for example powder. Injection pumps 31b, 32b, 33b may be present in the injection lines to circulate fluid along the respective injection line to the preparation line 35 that collects the liquid, for example water, from a source 36. source 36 may comprise tap water or an ultrapure liquid source or
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    other: to the water collected from the source and possibly subjected to filtration phases 36a (not detailed since they are known and not relevant to the present invention) the necessary substances are provided by the injection lines of the fluid preparation section 30. The concentration or conductivity sensor S8 is capable of providing the control unit 15 with a signal relative to the conductivity or concentration of a predetermined substance (eg sodium) of the fluid leaving line 35 and entering the line. dialysis line 11. Note that, optionally, additional concentration or conductivity sensors S9 and S10 may be located on line 35, respectively in correspondence with the segments of line 35 that extend between the injection points of the lines of injection 33a and 32a and between the injection points of injection lines 32a and 31a. The control unit can act on the device 30 and in particular on the pumps 31b, 32b, 33b in order to regulate the conductivity Cd or the concentration, for example of sodium NaD, of the liquid flowing into the dialysis line 11. In the example of Figure 1, the infusion line 9 collects the fluid from an independent source 37 (for example a bag containing replacement fluid) that is independent and distinct from the source 36, while the line Preparation 35 supplies exclusively to the dialysis line 11. In the example of Figure 2, the infusion lines 9a and 9b, as well as the dialysis fluid line collect fluid from the supply line 35, so that the composition of the dialysis fluid through line 11 and through infusion lines 9a, 9b is the same.
    Control unit
    As already indicated, the apparatus according to the invention uses at least one control unit 15. This control unit 15 may comprise a digital processor (CPU) with an associated memory 15a (or associated memories), an analog type circuit , or a combination of one or more digital processing units with one or more analog processing circuits. In the present description and in the claims it is indicated that the control unit 15 is "configured" or "programmed" to execute certain steps: this can be achieved in practice by any means that allows the control unit 15 to be configured or programmed. For example, in the case of a control unit 15 comprising one or more CPUs, one or more programs are stored in an appropriate memory: containing the program or programs instructions which, when executed by the control unit 15, cause the control unit 15 executes the steps described and / or claimed in relation to the control unit 15. Alternatively, if the control unit 15 is of the analog type, then the circuit assembly of the control unit 15 is designed to include a set of circuits configured, in use, to process electrical signals to execute the steps of the control unit 15 disclosed or claimed in the p resente document. As illustrated in the examples of Figures 1 and 2, the control unit is connected with the ultrafiltration device 20, with the preparation section 30, with a user interface 22, with the sensors S1 to S10 described above and with the various actuator elements (blood pump 21, infusion pumps 16, 16a, 16b, ultrafiltration pump 13, dialysis pump 11 and valve 12) located along lines 7, 8, 9, 9a, 9b, 10, 11 and is configured or programmed to perform the procedures described herein.
    In one aspect of the invention (see Figures 3 and 4), the control unit 15 is programmed or configured to perform, at times of control t temporarily one after the other (for example moments t can be temporarily equidistant), a control procedure 50 comprising the steps described hereinbelow.
    The control unit will also be programmed to perform, in combination with the control procedure, a TMP establishment procedure: the TMP establishment sequence and the control procedure are coordinated by the control unit to prevent negative interactions.
    Referring to Figures 3 and 4, the calculation of control values for the ultrafiltration rate / weight loss rate and for the concentration / conductivity is described hereinbelow. In a first step 100, the control procedure comprises receiving, for example via interface 22, prescription values of the variation of the target BV% blood volume, the WLobjective weight loss and the conductivity of the Cbobjective plasma or concentration of Naobjective sodium that must be achieved in the patient at a predetermined treatment time. For example, the user interface 22 can allow entering said prescription values and the selection of a treatment time value T within which the prescription values must be achieved. Then, in step 101, the control procedure based on the prescription values and the treatment time value T, determines respective target profiles that describe the desired progression over time (or trajectory) of the variation of:
    - a first parameter BV% tray (t) relative to the change in blood volume in the blood circulating in the extracorporeal blood circuit between the start of treatment and a respective time of treatment time (t); the first parameter may be in practice the change in blood volume that takes place between the start of the treatment and the moment t in the blood circulating in the extracorporeal blood circuit;
    - a second parameter UFtray (t), WLtray (t) relative to the amount of ultrafiltration volume or UFmed weight loss volume (t); WLmed (t) accumulated until the time of treatment time (t) from the start of treatment; the second parameter can be either the accumulated ultrafiltration volume or the weight loss volume
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    accumulated (note that the ultrafiltration volume and the weight loss volume have coincident values in those cases in which there is pure hemodialysis and therefore no infusion of fluid in the extracorporeal blood circuit or directly to the patient);
    - a third parameter Cbtray (t) related to conductivity or concentration for at least one substance in the blood circulating in the extracorporeal blood circuit at a respective time (t) during the treatment; In practice, the third parameter may be the concentration of sodium in the blood that circulates in the extracorporeal circuit at time t.
    In summary, the target profiles provide, at each moment of time, the prescription values of the first parameter BV% tray (t), the second parameter UFtray (t), WLtray (t) and the third parameter Cbtray (t). In step 101, the control unit can also be configured to calculate the allowed bands AB (t) for each of the first parameter BV% tray (t), the second parameter UFtray (t), WLtray (t) and the third parameter Cbtray (t).
    Note that (as an alternative to be calculated by the control unit based on the respective prescription values that must be reached at the end of the treatment and on the treatment time value T) a user can enter said target profiles for the prescription values or they can be previously stored in a memory connected to the control unit.
    It should be noted that the conductivity of the Cbobjective plasma or the concentration for at least one substance in Naobjective blood that must be reached at the end of the treatment time T can be calculated based on an initial value for the same parameter. For example, the control unit 15 may be configured to impose that said prescription value of Cbobjective conductivity or concentration for at least one Naobjective substance in blood to be reached at the end of the treatment time T is equal to the value of the conductivity or concentration for at least one substance in the blood at the beginning of the treatment, in particular as measured or as established by the user. In this case, the control unit may be configured to execute a measurement task (described in detail below in this document) at the beginning of the treatment to measure the conductivity or concentration value for at least one substance in blood. at the beginning of the treatment and then impose that said measured value be equal to the objective value.
    Again with reference to Figures 3 and 4, in step 102, the control unit 15 is configured to execute two control procedures: the two control procedures are logically distinct, but can be implemented in a single software task executed by the control unit or in a single circuit block part of the control unit. When the first control procedure is executed, the control unit 15 is configured to:
    - receive (step 102a) measured values of the first parameter BV% med (t) relative to the change in blood volume in the blood circulating in the extracorporeal blood circuit between the start of treatment and a respective time of treatment time t,
    - receive (step 102a) measured values of the second parameter relative to the amount of ultrafiltration volume UFmed (t) or WLmed (t) accumulated up to the time of treatment time t from the start of treatment,
    - receiving (step 101a) prescription values of the first parameter BV% tray (t) and the second parameter UFtray (t) or WLtray (t) that must have been reached in the patient at the time of treatment time t,
    - controlling the ultrafiltration (step 103) through the membrane 5 of the treatment unit 2 acting on the ultrafiltration device 20, at least based on the measured values of the first and second parameters (at time t) and on the Prescription values of the same first and second parameters (at time t). In practice, the control unit may be programmed to control the ultrafiltration device 20 and to adjust it based on the discrepancy between the prescription values of the first and second parameters and the respective measured values.
    When the second control procedure is executed, the control unit is configured to:
    - receiving (step 102a) a measured value of the third parameter Cbmed (t) relative to the conductivity or concentration for at least one substance in the blood circulating in the extracorporeal blood circuit at a respective time point t during the treatment;
    - receive (step 101a) the prescription value of the third parameter Cbtray (t) that must be reached in the patient at the time of time t;
    - control (step 103) the fluid preparation section to adjust the conductivity Cd, or the concentration of at least one NaD substance, in the new dialysis liquid flowing in the dialysate line at least based on said measured value Cbmed (t) and based on said prescription value for the third parameter Cbtray (t). For example, adjusting the conductivity or concentration (for example, Na concentration) in the new dialysis fluid can
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    be carried out by the control unit based on the discrepancy between the prescription and the measured values (at time t) for the third parameter.
    According to a more sophisticated alternative, the second control procedure also uses the measured value of the first parameter BV% med (t) relative to the change in blood volume in the blood circulating in the extracorporeal blood circuit between the start of the treatment and the time of treatment time t, and the prescription value of the first parameter BV% tray (t) to be achieved in the patient at the time of treatment time t. In this alternative, the second control method comprises controlling the fluid preparation section to adjust the conductivity Cd, or the concentration of at least one NaD substance in the new dialysis fluid flowing in the dialysate line at least based on the measured values of the first and third parameters BV% med (t), Cbmed (t) and in the prescription values of the first and third parameters BV% tray (t), Cbtray (t). For example, the adjustment of the conductivity or concentration (for example, concentration of Na) in the new dialysis fluid can be performed by the control unit depending on the discrepancy between the prescription and the measured values (at time t) for the third parameter and depending on the discrepancy between the prescription and the measured values (at time t) for the first parameter.
    The step of receiving the measured value of the third parameter Cbmed (t) comprises ordering the execution of a measurement task comprising the following steps:
    - causing the new treatment liquid to flow in the preparation line (19) to the secondary chamber (4) with the conductivity, or the concentration for at least one substance, at an established baseline value (C-set) which is either constant or variable in a known way over time;
    - causing the spent liquid to flow out of the secondary chamber (4) into the spent dialysate line (13);
    - causing a variation upstream of the conductivity, or of the concentration for at least one substance, (Cdentrada) in the new treatment liquid with respect to said prescription baseline thereby causing a corresponding downstream variation and delayed in the time of the conductivity, or of the concentration for at least one substance, (Cdsalida) in the spent liquid flowing in the spent dialysate line (13);
    - measure one or more values adopted by said variation downstream of the conductivity or concentration for at least one substance (Cdsalida) in the spent liquid;
    - determine the measured value of the third parameter (Cbmed (t)) relative to conductivity or concentration for at least one substance in the blood, comparing said one or more measured values adopted by said variation downstream with one or more values adopted by said upstream variation.
    In practice (in order to determine the conductivity or concentration of a substance (such as Na, for example) in blood) any one of the procedures disclosed in the following publications may be adopted. EP 0547025 describes a method for determining the conductivity or concentration of a substance, such as sodium, in the blood of a patient undergoing dialysis treatment. This method also makes it possible to determine the dialysis D (for example for sodium) of the blood treatment unit or dialyzer used. The method comprises the steps of circulating first and second dialysis fluids having different sodium concentrations successively through the second chamber of the blood treatment unit, measuring the conductivity of the first and second dialysis fluids upstream and downstream of the dialyzer, and calculate the concentration of sodium in the patient's blood (or dialysis D of the dialyzer for sodium) from the values of the conductivity of the liquid that are measured in the first and second dialysis liquids upstream and downstream of the dialyzer. EP 0658352 describes another method for in vivo determination of dialysis parameters (including the conductivity or concentration of a substance, such as sodium, in the blood of a patient) comprising the steps of: making at least some liquids of first and second treatment, which have a characteristic (the conductivity, for example) associated with at least one of the parameters (the concentration of blood ions, the dialysis D, the clearance K, Kt / V, for example) indicative of the treatment, flow successively through the dialyzer, the value of the characteristic in the first liquid upstream of the exchanger being different from the value of the characteristic in the second liquid upstream of the dialyzer; measure, in each of the first and second treatment liquids, two characteristic values, respectively upstream and downstream of the dialyzer; cause a third treatment liquid to flow through the dialyzer, while the characteristic of the second liquid has not reached a stable value downstream of the dialyzer, the value of the characteristic in the third liquid being upstream of the dialyzer different from the value of the characteristic in the second liquid upstream of the dialyzer; measure two characteristic values in the third liquid, respectively upstream and downstream of the dialyzer; and calculate at least one value of at least one parameter indicative of the progress of the treatment from the measured values of the characteristic in the first, second and third treatment liquids. Another method for in vivo determination of dialysis parameters (including the conductivity or concentration of a substance, such as sodium, in the blood of a patient) that does not require taking measurements in blood samples is described in EP 0920877. This method includes the steps of: having a treatment liquid flow through the exchanger, having this liquid of
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    treatment a characteristic that has an approximately constant nominal value upstream of the exchanger; vary the value of the characteristic upstream of the exchanger and then reset the characteristic to its nominal value upstream of the exchanger; measure and store in memory a plurality of values adopted by the characteristic of the treatment liquid downstream of the exchanger in response to the variation in the value of its characteristic caused upstream of the exchanger; determine the area of a downstream disturbance region limited by a baseline and a curve representative of the variation with respect to the time of the characteristic; and calculate the parameter indicative of the efficacy of a treatment from the area of the disturbance region downstream and from the area of a disturbance region upstream limited by a baseline and a representative curve of the variation with respect to time of the upstream feature of the exchanger. Naturally, any other procedure adapted for the determination in vivo of the conductivity or concentration in blood for a substance without blood sampling can be adopted in an equivalent manner. For example, US 2001004523 describes a solution for continuously determining the dialysis / clearance for a substance, the conductivity / concentration in blood comprising the steps of: causing a succession of sinusoidal variations in the characteristic (Cd) of a treatment liquid upstream of the exchanger, continuously store in memory a plurality of values (Cdentrada1 ... Cdentradaj ... Cdentradap) of the characteristic (Cd) upstream of the exchanger, measure and store continuously in memory a plurality of values (Cdsalida1 ... Cdsalidaj ... Cdsalidap) adopted by the characteristic (Cd) downstream of the exchanger in response to variations in the characteristic (Cd) that are caused upstream of the exchanger, calculate (each time a predetermined number of new values (Cdsalidaj) of the characteristic (Cd) downstream of the exchanger) has been stored said parameter (D, Cbentrada, K, Kt / V) from a first series of values (Cdentradaj) of the characteristic (Cd) upstream of the exchanger, from a second series of values (Cdsalidaj) of the characteristic (Cd) downstream of the exchanger
    Regardless of how the measurement task is executed in practice, it should be noted that the control unit 15 may be configured to repeat the first control procedure and the second control procedure at a plurality of regular time intervals during the treatment to do match, as much as possible, the measured values of said first, second and third parameters with the respective prescription values. For example, control procedures can be repeated every 15 minutes or every 30 minutes. Furthermore, regardless of the frequency, the two control procedures can take place substantially with reference to the same time or at different times: for example, once the first control procedure has been completed, the second control procedure can be initiated. control.
    The control unit is configured to repeat the first control procedure more frequently than the second control procedure: for example the first control procedure can be repeated at least once every n minutes, while the measurement task and the second procedure control is repeated no more than once every m minutes, where n is an integer <m. According to one example, n is between 1 and 5 and m is between 10 and 30. This allows the first control procedure to continuously execute the ultrafiltration adjustment to achieve BV% and WL objectives, while the adjustments in the Dialysis fluid composition (which can be annoying for the patient and require significant measurement time) are repeated less frequently.
    In the embodiment in which the control unit is configured to repeat the measurement task less frequently than the first control procedure thereby receiving the measured values of the third parameter (Cbmed (t)) less frequently than the measured values (BV% med (t), UFmed (t); BV% med (t), WLmed (t)) of the first and second parameters, the control unit 15 can also be configured to estimate the values adopted by the third parameter at intermediate times between two consecutive executions of the measurement task at least based on a mathematical model M, which represents the kinetics of the solutes in a volume of distribution in the patient, and the measured values of the third parameter achieved in said Two consecutive measurement tasks. This allows a plurality of estimated values of the third parameter to be obtained between each two really consecutive measured values of the same third parameter. The estimated values can be used instead of the values measured in vivo if the second control procedure is executed more frequently than the measurement task: in other words if conductivity / blood concentration values in vivo are not actually measured Cb when the second control procedure is executed, then the estimated values can be used.
    The mathematical model adopted is not relevant for the purpose of this description and any mathematical model M representative of the kinetics of solutes in the volume of distribution in patient V can be used, for example according to a single compartment model. The volume of distribution V is determined for each patient based on the objective of WL® weight loss, the total accumulated weight loss WL® and the volume of body water TBW estimated for example based on information such as age, gender, height and weight of the patient. For example, some example formulas to calculate the volume of body water TBW are as follows:
    Input parameters: gender, height [cm], weight [kg], age [years],% volume Output parameters: body water volume (TWB) [l]
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    Watson formula
    if gender = "masculine", then
    TWB = 2,447 - (0,09516 * age) + (0.1074 * height) + (0.3362 * weight) if gender = “female”, then
    TWB = -2.097 + (0.1069 * height) + (0.2466 * weight)
    Hume-Weyer formula
    if gender = "masculine", then
    TWB = (0.194786 * height) + (0.296785 * weight) - 14.012934 if the gender = “female”, then
    TWB = (0.344547 * height) + (0.183809 * weight) - 35.270121 Mellits-Cheek formula
    if gender = "male" and height <132.7 cm, then TWB = -1.927 + (0.465 * weight) + (0.045 * height) if gender = "male" and height> 132.7 cm, then TWB = -21,993 + (0.406 * weight) + (0.209 * height) if the gender = “female” and the height <110.8 cm, then TWB = 0.076 + (0.507 * weight) + (0.013 * height) if the gender = "female" and height> 110.8 cm, then TWB = -10.313 + (0.252 * weight) + (0.154 * height)
    Percent formula
    TWB = weight *% volume / 100
    According to a further aspect of the invention, during the execution of the measurement task, the control unit may be configured to prevent changes in the conductivity or concentration of the dialysis liquid applied by any task or procedure other than the measurement task. In particular (during the execution of said control stage of the fluid preparation section) the control unit may be configured to verify whether said measurement task is being executed. If the verification confirms that the measurement task is running, the control unit waits until the completion of at least said variation upstream of the conductivity, or of the concentration for at least one substance (indent), in the new treatment liquid with respect to said prescription baseline, before allowing any other control procedure, for example the first control procedure, to adjust the conductivity Cd, or the concentration of at least one NaD substance, in the new dialysis fluid that flows in the dialysate. This provision allows a more reliable measure of Cb.
    Hereinafter, it is now described how each of the first and second control procedures can function in terms of the algorithm used to determine the control values (step 102c in figure 4; blocks 102c ', 102c "in the figure 3) of the parameters used to adjust ultrafiltration and respectively the composition of the dialysis fluid.
    The first control procedure comprises determining at time t at least a first error parameter ERR_BV_UF (t) (step 102b) based on the difference between the measured value of the first parameter BV% med (t) at the time of control t and the corresponding prescription value for the same first parameter BV% tray (t), and in the difference between a measured value of the second parameter UFmed (t) or WLmed (t) accumulated at the time t and a corresponding prescription value for the same second UFtray (t) or WLtray (t) parameter. The first control procedure provides control of ultrafiltration through said membrane at time t (UFR®), acting on the
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    ultrafiltration device 20, at least based on the value of said first error parameter and the value applied to the ultrafiltration rate at a time of previous control (UFR (t-At)):
    image4
    The second control procedure comprises determining at least a second error parameter ERR_BV_Na® (step 102b) based on the difference between the value of the third parameter Cdmed (t) at time t and a corresponding prescription value for the same third parameter Cbtray ( t), and the difference between the measured value of the first parameter BV% med (t) and a corresponding prescription value for the same first parameter BV% tray (t). Then, the second control procedure provides control of the fluid preparation section to adjust at the time of time t the conductivity Cd, or the concentration of at least one NaD substance, in the new dialysis fluid flowing in the line of dialysate, at least based on the value of said second error parameter and the value applied to the conductivity or concentration in the dialysis fluid at a time of previous control (NaD (t-At)):
    Nao (t) = f (NaD (t-At>; ERR_BV_Na (t))
    Finally, according to a further aspect of the invention that is particularly useful when the apparatus includes at least one infusion line (for example line 9 or lines 9a, 9b) configured for infusion of a replacement fluid and connected to the extracorporeal circuit , the control unit may also be configured to execute a tMp establishment procedure (see Figures 5 and 6) comprising:
    - receive measured values of a fourth parameter (UFR; Qinf) relative to the ultrafiltration rate through the membrane or to the infusion rate through said infusion line and measured values of a fifth parameter relative to transmembrane pressure (TMP ) through said membrane;
    - apply a first increase (8TMPn) to a first value of the first parameter (TMPn) to reach a second transmembrane pressure value (TMPn + i);
    - determine a variation between the value of the fourth parameter (AUFR (n); AQiNF (n)) measured at the first transmembrane pressure (TMPn) and the value of the fourth parameter (AUFR (n + i) QiNF (n + i)) measured at the second transmembrane pressure value (TMPn + i);
    - compare the variation of the value of the fourth parameter (AUFR (n); AQiNF (n)) with a reference value and, if the value of said variation is greater than the reference value, apply a second increase (STMPn + i) at the second transmembrane pressure in order to reach a third value of the transmembrane pressure value TMPn + 2;
    - repeat the previous steps of the TMP establishment procedure until a maximum or substantially maximum TMP value is reached;
    - establishing said maximum value of TMP or substantially maximum value of TMP or a predetermined fraction thereof as an established value for TMP over the course of at least a time interval during treatment.
    The above establishment procedure is performed if the apparatus is intended to be controlled also based on the TMP and for example maximize the volume of infused fluid as much as possible, thereby increasing the exchange by convection. The establishment procedure is performed at a time of establishment indicated by T and possibly repeated a plurality of times during a treatment. For example, the establishment procedure can be performed while performing or performing one or both control procedures. For example, the control unit is configured to repeat both the control procedures (in a plurality of control moments t that are temporarily consecutive with each other) and the procedure of setting the TMP (in a plurality of control moments t which they are temporarily consecutive with each other). In practice, the control unit may be configured to apply the control value or values determined using the first and second control procedures for a period of time At after each control moment t, cyclically repeating the control procedures throughout the entire treatment. In parallel, the control unit is also configured to perform the establishment sequence in a plurality of consecutive establishment moments T temporarily with one another, applying the TMP thus determined.
    In more detail with respect to the establishment procedure and with reference to one embodiment, the establishment procedure comprises the following steps, which are intended to identify an optimal value of TMP in which maximization of ultrafiltration is obtained. Acting on the pump i3, the control unit determines a first STMPn increase to reach a second transmembrane pressure value TMPn + i; then the sequence comprises measuring or calculating an AUFR variation (n) between the ultrafiltration flow UFR through the membrane 5 at the first transmembrane pressure TMPn and the ultrafiltration flow UFR at the second transmembrane pressure TMPn + i: the flow variation ultrafiltration is determined either by directly measuring the flow of
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    ultrafiltration or indirectly taking into account both the flux variations of the AQiNF replacement liquid (n) along the infusion line and the AWLR (n) weight loss rate variations due to the control procedure. After this, the control sequence comprises comparing the variation of the AUFR ultrafiltration (n) with a reference value and, if the value of the AUFR variation (n) is greater than the reference value, order the pump 13 to apply a second 5TMPn + ia increase in transmembrane pressure in order to reach a third value of TMPn + 2 transmembrane pressure, etc., cyclically repeating the sequence described for successive increases. The variation of the AUFR ultrafiltration flow rate is compared with a reference flow rate, for example 3 ml / min and, if the ultrafiltration flow rate is greater than 3 ml / min, the ultrafiltration pump is ordered 13 that establishes an increase in TMP that is greater than the previous one. Thus, if after the first variation of TMP the corresponding variation in the ultrafiltration flow rate is sufficiently high and therefore to indicate that the treatment unit is operating in an area sufficiently distant from the plateau area (with reference to the characteristic ultrafiltration / TMP curve relative to the treatment unit), the sequence described above is repeated, increasing the TMP again. Note that, for example, the control unit can greatly increase the amplitude of the next pressure increase, thereby accelerating the search for and setting the optimal TMP. If, on the other hand, the value of the AUFR variation of the ultrafiltration flow is less than the reference value, the TMP establishment procedure is interrupted, as will be described more fully below in the present document, since the unit in this case considers that it has reached the optimal TMP and therefore maintains it as the established value.
    Figure 5 shows a system of Cartesian coordinate axes in which the x-axis represents the time and the axis and the pressure TMP the pressure TMP established moment by moment: Figure 5 shows an embodiment of a TMP setting sequence which can be carried out by means of a control unit that is part of the apparatus 1 of the type illustrated in Figure 1 or Figure 2. After a manual order or an automatic procedure, a TMP establishment procedure is initiated by the control unit. First (START in Figure 5), the control unit maintains the TMP at a value of TMP1 for a first time interval M2. At the end of the first time interval M2, a pressure increase of 20 mmHg is applied to the established TMP value, passing to a set value of TMP2, with a consequent activation of the ultrafiltration pump 13 and the infusion pump 16 (or at least one of the pumps 16a, 16b in the case of figure 2). If, in the interval t2-t3, the variation in the AUFR ultrafiltration flow rate is greater than 3 ml / min, for example 12 ml / min, the successive increase in the established value of TMP is optionally applied to more than 20 mmHg and, in the illustrated example, at 60 mmHg. Note that in the meantime, if the control procedure performed during establishment has varied the WLR weight loss rate, the control unit would take it into account in the evaluation of the effective increase in ultrafiltration at each TMP increase: or AUFR variation is measured directly or, if the variation is calculated based on the variation in the infusion flow, the eventual contribution provided by the WLR weight loss flow variation is added to the infusion flow. In response to the new established value of TMP, ie TMP3, the control unit also orders the acceleration of the infusion pump to balance the effect of the greater ultrafiltration. Note also that the duration of the interval t3-t4 is not necessarily equal to that of the interval t2-t3: for example the unit 15 may be configured to apply a variable interval, which becomes larger as a function of the increase in the TMP than It precedes, with the aim of allowing a transient adaptation for the ultrafiltration pump and the pump or infusion pumps. Even with reference to figure 5, at time t4 a new increase in TMP, 20 mmHg, is applied and after an additional interval T (in figure 5: t4-ts), the increase in ultrafiltration flow is verified. If, as in the case illustrated, the variation of the AUFR flow rate is less than 3 ml / min, it is considered that the establishment sequence has been completed (“END” in Figure 5) and the final TMP value is applied reached (ie TMP4 in Figure 5) as the set value. Otherwise, a new increase in TMP is applied, which can be again 20 mmHg or can be a function of the measured variation AUFR in the ultrafiltration flow uFr.
    Figure 6 illustrates a situation in which the steps described above are repeated until the TMP3 pressure is reached; then, the establishment process may comprise the variation of TMP in one or two predetermined entity stages in order to allow the stabilization of the control system. The variation or variations of TMP remain less than or equal to a relatively low value, for example 20 mmHg. For example, Figure 6 shows a stabilization stage, designated by s. After an additional time interval t4-t5, the sequence repeats the steps described above with reference to intervals from t2 to t4. In other words, at time t5, a pressure increase of 20 mmHg is applied to the value of the TMP that passes to a set value TMP5 with a consequent activation of the ultrafiltration pump 13 and the infusion pump 16 (or at least one of the pumps 16a, 16b in the case of figure 2) to balance the effect of the greater ultrafiltration. If, as in Figure 6, in the ts-ts interval, the AUFR variation of the UFR ultrafiltration flow rate is above 3 ml / min, for example 12 ml / min, the successive increase of the established value of TMP it is applied to more than 20 mmHg and, in the illustrated example, to 60 mmHg. In response to the new established value of TMP (TMP6), the control unit also orders the acceleration of the infusion pump to balance the effect of increased ultrafiltration, according to one of the control strategies described above. Then a new increase of TMP of 20 mmHg will be applied and after an additional interval T, the increase in the AUFR ultrafiltration flow rate will be verified. If in response the UFR varies an AUFR value that is less than 3 ml / min, the establishment sequence is considered to have concluded. Otherwise, the described process is repeated again. In general, the establishment process comprises that at the beginning an increase in TMP with a predetermined value is applied, which may be the same or may vary during treatment, but is known a priori and is usually relatively small, by
    example 20 mmHg. The increases after the first (8TMPn + i) are either stabilization increases as described above, and therefore also of 20 mmHg or known and relatively small values, or TMP values calculated according to the variation value of the AUFR measured or estimated ultrafiltration corresponding to the increase in the immediately anterior transmembrane pressure (STMPn), or increases in the TMP that are always constant and a priori of known amplitude. The previous phases are repeated until, after a pressure stage, the variation of the ultrafiltration flow rate meets the final condition of the sequence: at this point, the control unit is configured to order the regulating device 20 to establish, as the operating transmembrane pressure, the last pressure at which the value of the control parameter is less than the value of the respective reference value.
    10
    If during the completion of the transmembrane establishment procedure there is a change in the rate of weight loss, for example due to the intervention of the first control procedure (this may happen since the control procedure is repeated quite frequently), the sequence of establishment involves two actions. First, the variation of the ultrafiltration flow rate, if it is estimated based on the variation of the infusion rate, takes into account any variation in the weight loss rate, that is in each time interval tn -tn + i, (see Figures 5 and 6 for example) the AUFR variation is calculated as AQinf + AWLR.
    权利要求:
    Claims (15)
    [1]
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    1. An apparatus for extracorporeal blood treatment, comprising:
    - at least one treatment unit (2) having at least a first chamber (3) and at least a second chamber (4) separated from each other by a semipermeable membrane (5);
    - at least one blood withdrawal line (6) connected to an inlet opening of the first chamber and configured to take blood from a patient,
    - at least one blood return line (7) connected to an outlet opening of the first chamber and configured to return the treated blood to the patient, forming the blood withdrawal line (6), the blood return line ( 7) and the first chamber part of an extracorporeal blood circuit (8);
    - a dialysate circuit comprising:
    at least one dialysis line (11) connected to the inlet port of the second chamber (4) and configured to transport new dialysis fluid to the second chamber (4),
    at least one fluid evacuation line (10) connected to an outlet port of the second chamber (4) and configured to discharge the spent dialysis fluid exiting the second chamber (4), and
    a fluid preparation section connected to the dialysis line (11) and configured to adjust the conductivity, or concentration for at least one substance, in the new dialysis fluid;
    - at least one ultrafiltration device (20) connected to the dialysate circuit and configured to determine ultrafiltration through the membrane from the first to the second chamber;
    - a control unit (15) connected to the ultrafiltration device (20) and the fluid preparation section and configured to perform a first control procedure comprising:
    receive measured values of:
    a first parameter (BV% med (t)) related to the change in blood volume in the blood circulating in the extracorporeal blood circuit between the start of treatment and a respective time of treatment time (t), and
    a second parameter relative to the amount of ultrafiltration volume (UFmed (t); WLmed (t)) accumulated until the time of treatment time (t) since the start of treatment, and
    receive prescription values of the first parameter (BV% tray (t)), and of the second parameter (UFtray (t); WLtray (t)) that must be achieved in the patient at the time of treatment time (t);
    controlling ultrafiltration through said membrane, acting on the ultrafiltration device (20), at least based on the measured values of the first and second parameters and the prescription values of the same first and second parameters;
    the control unit (15) also being configured to perform a second control procedure comprising:
    receive a measured value of a third parameter (Cbmed (t)) relative to the conductivity or concentration for at least one substance in the blood circulating in the extracorporeal blood circuit at a respective time (t) during the treatment;
    receive a prescription value of the third parameter (Cbtray (t)) that must be achieved in the patient at the time (t);
    control the fluid preparation section to adjust the conductivity (Cd), or the concentration of at least one substance (NaD), in the new dialysis fluid flowing in the dialysate line at least based on said measured value (Cbmed ( t)) and in said prescription value for the third parameter (Cbtray (t));
    characterized in that the step of receiving a measured value of the third parameter (Cbmed (t)) comprises ordering the execution of a measurement task comprising the following steps:
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    cause the new treatment liquid to flow in the preparation line (19) to the secondary chamber (4) with the conductivity, or concentration for at least one substance, at a set baseline value (C established) that either it is constant or it varies in a known way over time;
    cause the spent liquid to flow out of the secondary chamber (4) into the spent dialysate line (13);
    cause a variation upstream of the conductivity, or of the concentration for at least one substance, (Cdentrada) in the new treatment liquid with respect to said prescription baseline thereby causing a corresponding downstream variation in the conductivity time, or concentration for at least one substance, (Cdsalida) in the spent liquid flowing in the spent dialysate line (13);
    measure one or more values adopted by said variation downstream of the conductivity or concentration for at least one substance (Cdsalida) in the spent liquid;
    determining the measured value of the third parameter (Cbmed (t)) relative to conductivity or concentration for at least one substance in the blood, comparing said one or more measured values adopted by said downstream variation with one or more values adopted by said upstream variation.
    and because the control unit is configured to prohibit any intervention in the composition of the new treatment liquid by any task other than the measurement task, while the variation of the conductivity or concentration applied on the new treatment liquid performed takes place through the measurement task.
    [2]
    2. - The apparatus according to the preceding claim, wherein the control unit (15) is configured to repeat the first control procedure and the second control procedure at a plurality of regular time intervals during the treatment to make them coincide , as much as possible, the measured values of said first, second and third parameters with the respective prescription values.
    [3]
    3. - The apparatus according to any one of the preceding claims, wherein the control unit (15) is configured to repeat the first control procedure either with the same frequency as, or more frequently than, the second procedure of control.
    [4]
    4. - The apparatus according to any one of the preceding claims 2 to 3, wherein the control unit (15) is configured to repeat the first control procedure at least once every n minutes, and to repeat the measurement task and the second control procedure no more than once every m minutes, where n is an integer <A m.
    [5]
    5. - The apparatus according to claim 4, wherein n is between 1 and 5 and m is between 10 and 30.
    [6]
    6. - The apparatus according to any one of the preceding claims 2 to 5, wherein the control unit (15) is configured to repeat the measurement task less frequently than the first control procedure thereby receiving the measured values of the third parameter (Cbmed (t)) less frequently than the measured values (BV% med (t), UFmed (t); BV% med (t), WLmed (t)) of the first and second parameters, and
    wherein the control unit (15) is further configured to estimate values adopted by the third parameter at intermediate times between two consecutive executions of the measurement task at least based on:
    a mathematical model (M), which represents the kinetics of solutes in a volume of distribution in the patient, and
    the measured values of the third parameter taken in said two consecutive measurement tasks, thereby obtaining a plurality of estimated values of the third parameter between each two really consecutive measured values of the same third parameter.
    [7]
    7. The apparatus according to any one of the preceding claims, wherein the second control procedure comprises receiving the measured value of the first parameter (BV% med (t)) relative to the change in blood volume in the blood circulating in the extracorporeal blood circuit between the start of treatment and the time of treatment time (t), and receive the prescription value of the first parameter (BV% tray (t)) that must be reached in the patient at the time of treatment time (t); wherein the control stage in the second control procedure comprises controlling the fluid preparation section to adjust the conductivity (Cd), or the concentration of at least one substance (NaD), in the new dialysis fluid flowing in the dialysate line at least based on the measured values of the first and third parameters (BV% med (t); Cbmed (t)) and the prescription values of the first and third parameters (BV% tray (t); Cbtray (t)).
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    [8]
    8. - The apparatus according to any one of claims 2 to 7, wherein (during the execution of said control stage of the fluid preparation section) the control unit (15) is configured to:
    - verify if this measurement task is being executed and,
    - if so, wait until the termination of at least said variation upstream of the conductivity, or of the concentration for at least one substance (Cdentrada), in the new treatment liquid with respect to said prescription baseline, and only then
    - allowing the second control procedure to adjust the conductivity, or concentration of at least one substance, in the new dialysis fluid flowing in the dialysate.
    [9]
    9. - The apparatus according to claim 6 in combination with any one of claims 7, 8, wherein the values of the third parameters used as measured values in the second control procedure comprise measured values actually obtained with the execution of said measurement task and estimated values relative to the intermediate time moments between two consecutive of the measurement task.
    [10]
    10. - The apparatus according to any one of the preceding claims, wherein the control unit (15) is configured to:
    receive a value for the total treatment time (T);
    receive prescription values of blood volume variation (BV% target), weight loss (objective WL) and plasma conductivity or concentration for at least one substance in blood (Cbobjective) to be reached at the end of the treatment time ( T);
    determine said prescription values of the first parameter (BV% tray (t)), the second parameter (UFtray (t); WLtray (t)) and the third parameter (Cbtray (t)) based on the respective prescription values that must be reached at the end of the treatment and in the value of treatment time (T).
    [11]
    11. - The apparatus according to the preceding claim, wherein receiving a prescription of the conductivity or concentration in plasma for at least one substance in the blood (Cbobjective) that must be reached at the end of the treatment time (T) comprises imposing that said value of conductivity or concentration prescription for at least one substance in blood (Objective) that must be reached at the end of the treatment time (T) is equal to the value of the conductivity or concentration for at least one substance in blood at the beginning of the treatment, in particular as measured or as set by the user.
    [12]
    12. - The apparatus according to the preceding claim, wherein the control unit (15) is configured to execute the measurement task at the beginning of the treatment to measure the value of the conductivity or concentration for at least one substance in blood at the beginning of treatment
    [13]
    13. - The apparatus according to any one of the preceding claims, wherein the first control procedure comprises:
    - determine at the moment (t) at least a first error parameter (ERR_BV_UF®) based on:
    the difference between the measured value of the first parameter (BV% med (t)) at the time of control (t) and a corresponding prescription value for the same first parameter (BV% tray (t)), and
    the difference between a measured value of the second parameter (UFmed (t); WLmed (t)) accumulated at the time (t) and a corresponding prescription value for the same second parameter (UFtray (t); WLtray (t)); Y
    - controlling the ultrafiltration through said membrane, acting on the ultrafiltration device (20), at least based on the value of said first error parameter;
    and / or in which the second control procedure comprises:
    - determine at least a second error parameter (ERR_BV_Na®) based on:
    the difference between the value of the third parameter (Cdmed (t)) at the moment (t) and a corresponding prescription value for the same third parameter (Cbtray (t)), and
    the difference between the measured value of the first parameter (BV% med (t)) and a corresponding prescription value for the same first parameter (BV% tray (t)); Y
    5
    10
    fifteen
    twenty
    25
    30
    35
    40
    Four. Five
    fifty
    - controlling the fluid preparation section to adjust the conductivity (Cd), or the concentration of at least one substance (NaD), in the new dialysis fluid flowing in the dialysate line at least based on the value of said second error parameter
    [14]
    14. - The apparatus according to any one of the preceding claims, further comprising at least one infusion line configured for infusion of a replacement fluid and connected to the extracorporeal circuit,
    wherein the control unit (15) is further configured to execute a TMP establishment procedure comprising:
    - receive measured values of a fourth parameter (UFR; Qinf) relative to the ultrafiltration rate through the membrane or to the infusion rate through said infusion line and measured values of a fifth parameter relative to transmembrane pressure (TMP )) through said membrane;
    - apply a first increase (8TMPn) on a first value of the first parameter (TMPn) to reach a second transmembrane pressure value (TMPn + i);
    - determine a variation between the value of the fourth parameter (AUFR (n); AQiNF (n)) measured at the first transmembrane pressure (TMPn) and the value of the fourth parameter (AUFR (n + i) QiNF (n + i)) measured at the second transmembrane pressure value (TMPn + i);
    - compare the variation of the value of the fourth parameter (AUFR (n); AQiNF (n)) with a reference value and, if the value of said variation is greater than the reference value, apply a second increase (STMPn + i) at the second transmembrane pressure in order to reach a third value of the transmembrane pressure value TMPn + 2;
    - repeat the previous steps of the TMP establishment procedure until a maximum or substantially maximum TMP value is reached;
    - establishing said maximum value of TMP or substantially maximum value of TMP or a predetermined fraction thereof as an established value for TMP over the course of at least a time interval during treatment.
    [15]
    15. - The apparatus according to any one of the preceding claims, comprising:
    at least one sensor active on the extracorporeal circuit and configured to detect the variation (BV%) of the patient's blood volume;
    at least one sensor active at least on the evacuation line and configured to determine the ultrafiltration rate (UFR) through the membrane,
    at least one sensor active on the dialysis line (ii) and configured to detect the conductivity or concentration for at least one substance (Cd; Na) of the liquid that crosses the dialysis line;
    at least one sensor configured to determine an infusion rate (Qinf) of the replacement fluid that crosses the infusion line;
    at least one sensor configured to determine a transmembrane pressure (TMP) between the first and second chamber;
    in which the above sensors are connected to the control unit (i5).
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    同族专利:
    公开号 | 公开日
    CA2895171C|2020-09-01|
    WO2014097115A3|2014-09-18|
    AU2013365795A2|2015-08-06|
    EP2745863B9|2017-08-30|
    US20150343129A1|2015-12-03|
    AU2013365795B2|2017-11-23|
    EP2745863B1|2017-05-03|
    AU2013365795A1|2015-08-06|
    CN104349803B|2017-03-22|
    US9925321B2|2018-03-27|
    CN104349803A|2015-02-11|
    WO2014097115A2|2014-06-26|
    ES2628375T3|2017-08-02|
    CA2895171A1|2014-06-26|
    EP2745863A1|2014-06-25|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    EP12198335.7A|EP2745863B9|2012-12-20|2012-12-20|An apparatus for extracorporeal blood treatment|
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