Patent Application
20220143284
The invention relates to an apparatus for extracorporeal treatment of blood and a method for determining a parameter indicative of the progress of an extracorporeal blood treatment (referred to as effectiveness parameter), in particular a purification treatment whose purpose is to alleviate renal insufficiency, such as—without limitation—hemodialysis or hemodiafiltration. It is also disclosed a method of determining said parameter indicative of the progress of an extracorporeal blood treatment. For instance, the parameter may be one of:
In an haemodialysis treatment a patient's blood and a treatment liquid approximately (but not necessarily) isotonic with blood flow are circulated in a respective compartment of haemodialyser, so that, impurities and undesired substances present in the blood (urea, creatinine, etc.) may migrate by diffusive transfer from the blood into the treatment liquid. The ion concentration of the treatment liquid is chosen so as to correct the ion concentration of the patient's blood. In a treatment by haemodiafiltration, a convective transfer by ultrafiltration, resulting from a positive pressure difference created between the blood side and the treatment-liquid side of the membrane of a haemodiafilter, is added to the diffusive transfer obtained by dialysis.
It is of interest to be able to determine, throughout a treatment session, one or more parameters indicative of the progress of the treatment so as to be able, where appropriate, to modify the treatment conditions that were initially fixed or to at least inform the patient and the medical personnel about the effectiveness of the treatment. The knowledge of one or more of the following parameters may make it possible to follow the progress of the treatment, and for instance may allow assessing the suitability of the initially fixed treatment conditions:
The determination of these parameters requires precise knowledge of a physical or chemical characteristic of the blood. As it can be understood, determination of this characteristic cannot in practice be obtained by direct measurement on a specimen for therapeutic, prophylactic and financial reasons. Indeed, it is out of the question taking—in the course of a treatment—multiple specimens necessary to monitor the effectiveness of the treatment from a patient who is often anemic; furthermore, given the risks associated with handling specimens of blood which may possibly be contaminated, the general tendency is to avoid such handling operations; finally, laboratory analysis of a specimen of blood is both expensive and relatively lengthy, this being incompatible with the desired objective of knowing the effectiveness of a treatment while the treatment is still ongoing.
Several methods have been proposed for in vivo determining haemodialysis parameters without having to take measurements on blood samples. Document EP 0547025 describes a method for determining the concentration of a substance, such as sodium, in a patient's blood subjected to a haemodialysis treatment. This method also makes it possible to determine the dialysance D—for example for sodium—of the haemodialyser used. The method comprises the steps of circulating a first and a second haemodialysis liquids having different sodium concentrations in succession through the haemodialyser, measuring the conductivity of the first and second dialysis liquids upstream and downstream of the haemodialyser, and computing the concentration of sodium in the patient's blood (or the dialysance D of the haemodialyser for sodium) from the values of the conductivity of the liquid which are measured in the first and second dialysis liquids upstream and downstream of the haemodialyser. Document EP 0658352 describes another method for the in vivo determination of haemodialysis parameters, which comprises the steps of: making at least a first and a second treatment liquids, having a characteristic (the conductivity, for example) associated with at least one of the parameters (the ion concentration of the blood, the dialysance D, the clearance K, Kt/V, for example) indicative of the treatment, flow in succession through the haemodialyser, 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 hemodialyzer; measuring, in each of the first and second treatment liquids, two values of the characteristic, respectively upstream and downstream of the hemodialyzer; making a third treatment liquid flow through the hemodialyzer while the characteristic of the second liquid has not reached a stable value downstream of the hemodialyzer, the value of the characteristic in the third liquid upstream of the hemodialyzer being different from the value of the characteristic in the second liquid upstream of the hemodialyzer; measuring two values of the characteristic in the third liquid, respectively upstream and downstream of the hemodialyzer; and computing 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 the in vivo determination of the haemodialysis parameters which does not require taking measurements on blood samples is described in document EP 0920877. This method includes the steps of: making a treatment liquid flow through the exchanger, this treatment liquid having a characteristic which has an approximately constant nominal value upstream of the exchanger; varying the value of the characteristic upstream of the exchanger and then re-establishing the characteristic to its nominal value upstream of the exchanger; measuring and storing 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 this characteristic caused upstream of the exchanger; determining the area of a downstream perturbation region bounded by a baseline and a curve representative of the variation with respect to time of the characteristic; and computing the parameter indicative of the effectiveness of a treatment from the area of the downstream perturbation region and from the area of an upstream perturbation region bounded by a baseline and a curve representative of the variation with respect to time of the characteristic upstream of the exchanger. Document EP2732834 describes an apparatus for extracorporeal treatment of blood comprising a control unit which is configured to calculate values of a parameter relating to treatment effectiveness based on measures of the conductivity in the spent dialysate line. The value of the effectiveness parameter is calculated using one or more values representative of the conductivity in the spent dialysate line obtained relying on a mathematical model. The control unit causes an upstream (with respect to the treatment unit) variation of the value of a characteristic Cdin in the fresh treatment liquid with respect to a prescription baseline Cdset and then re-establishes the characteristic Cdin in the fresh treatment liquid to said prescription baseline Cdset. The upstream variation causes a corresponding and timely delayed downstream (with respect to the treatment unit) variation of the same characteristic Cdout in the spent liquid flowing in the spent dialysate line. The control unit is configured to receive at least one parametric mathematical model, which puts into relation the characteristic Cdin in the fresh treatment liquid with the characteristic Cdout in the spent liquid. In order to determine the parameters of the parametric mathematical model, the control unit is configured to receive, e.g. from a sensor, measures of a plurality of values taken by a reference portion of the downstream variation of the characteristic Cdout in the spent liquid, wherein the reference portion, which is used by the control unit to characterize the mathematical model, has a duration ΔTR significantly shorter than an entire duration ΔTV of the downstream variation. The above described methods require a relatively short—compared to treatment time—modification of the value of a characteristic of the dialysis liquid (the conductivity, for example) and then the re-establishment of this characteristic to its initial value, which is generally the prescribed value. Since, deviations from the prescription are not desirable and since the above described methods require a minimum duration of the introduced modification, it derives that all these methods can be carried out only few times during a treatment. Document US 2001004523 describes a solution for continuously determining a parameter (D, Cbin, K, Kt/V) indicative of the effectiveness of an extracorporeal blood treatment comprising the steps of: causing a succession of sinusoidal variations in the characteristic (Cd) a treatment liquid upstream of the exchanger, continuously storing in memory a plurality of values (Cdin1 . . . Cdinj . . . Cdinp) of the characteristic (Cd) upstream of the exchanger, measuring and continuously storing in memory a plurality of values (Cdout1 . . . Cdoutj . . . Cdoutp) adopted by the characteristic (Cd) downstream of the exchanger in response to the variations in the characteristic (Cd) which are caused upstream of the exchanger, computing—each time that a predetermined number of new values (Cdoutj) of the characteristic (Cd) downstream of the exchanger has been stored—a parameter (D, Cbin, K, Kt/V) indicative of the effectiveness of the extracorporeal blood treatment, from a first series of values (Cdinj) of the characteristic (Cd) upstream of the exchanger, from a second series of values (Cdoutj) of the characteristic (Cd) downstream of the exchanger. Another apparatus and method for determining a parameter indicative of the progress of an extracorporeal blood treatment is disclosed in document EP2687248, which describes an apparatus for extracorporeal treatment of blood wherein a control unit is configured to calculate values of a parameter relating to treatment effectiveness based on measures of the conductivity in the spent dialysate line subsequent to an alternating conductivity perturbation continuously imposed on the preparation line of fresh dialysis fluid. The control unit is configured to cause a plurality of consecutive and continuously repeated variations Vk of the characteristic Cd around the prescription baseline Cdset in the liquid flowing in the preparation line. The variations define for instance a square wave around the prescription baseline. The above methods, which require a continuous perturbation in the characteristic of the treatment liquid, prevent execution of tasks, other than the one for measuring the effectiveness parameter, which may affect the concerned characteristic (conductivity/concentration) of the dialysis fluid. Indeed, while the control system is executing the effectiveness parameter detection, the control system will not execute other tasks taking an active control on the conductivity/composition of the dialysis liquid (e.g. tasks acting on the sodium concentration of the dialysis liquid in response to detection of certain parameters such as blood concentration). Furthermore, the system dynamic may depend on the working conditions, like dialysis fluid flow and dialyzer type and the system is not always able to converge to a meaningful solution. In some cases, with low dialysis fluid flows and filters with large areas (or vice versa) the measure could fail.
It is therefore an object of the present invention to provide an apparatus and a method configured to reliably calculate an effectiveness parameter one or more times during treatment without substantially impairing on prescription delivered to the patient and minimally affecting the operation flexibility of the blood treatment apparatus. In particular, it is an object to tune and optimize said method and an apparatus configured to calculate the effectiveness parameter even just one time without substantially impairing on prescription delivered to the patient. Additionally, it is an object providing a method and an apparatus which may be implemented with no need of high computational power and time machine. Another auxiliary object is an apparatus capable of operating in a safe manner A further auxiliary object is an apparatus capable of automatically calculate the effectiveness parameter and inform the operator accordingly.
At least one of the above objects is substantially reached by an apparatus according to one or more of the appended claims. Apparatus and methods according to aspects of the invention and capable of achieving one or more of the above objects are here below described.
A 1st aspect concerns an apparatus for extracorporeal treatment of blood comprising:
a blood treatment unit having a primary chamber and a secondary chamber separated by a semi-permeable membrane;
a preparation line having one end connected to an inlet of a secondary chamber of the treatment unit and configured to convey fresh treatment liquid to the secondary chamber, the fresh treatment liquid presenting a characteristic which is one selected in the group of:
It is noted that having knowledge of the effluent flow rate and of the ultrafiltration flow rate is equivalent to knowing the flow rate of the fresh treatment liquid in the preparation line in a hemodialysis treatment; in an HDF treatment, knowledge of the effluent flow rate, infusion flow rate and of the ultrafiltration flow rate is equivalent to knowing the flow rate of the fresh treatment liquid in the preparation line.
It is also noted that the flow rate in the preparation line may be the set flow rate or a measured flow rate in the preparation line (if relevant, the same applies to the other mentioned flow rates, namely effluent flow rate, infusion flow rate, ultrafiltration flow rate).
In an additional aspect, the control unit execute the task including receiving a blood or plasma flow rate at the inlet of the primary chamber (e.g., set or measured blood/plasma flow rate) and including computing said amplitude and/or said duration over time of the upstream variation to be caused as a function of the blood or plasma flow rate, the computing of the amplitude and/or said duration over time of the upstream variation being made either as a function of both the flow rate (or of the parameter correlated to the flow rate) of the fresh treatment liquid in the preparation line and the blood (or plasma) flow rate, or as a function of the blood (or plasma) flow rate.
In an additional aspect, the control unit execute the task including receiving an efficiency parameter of the blood treatment unit, such as clearance or dialysance or mass transfer area coefficient K0A, and including computing said amplitude and/or said duration over time of the upstream variation to be caused as a function of the efficiency parameter of the blood treatment unit, the computing of the amplitude and/or said duration over time of the upstream variation being made as a function of anyone of (let alone or in any combination) the flow rate (or of the parameter correlated to the flow rate) of the fresh treatment liquid in the preparation line, the blood (or plasma) flow rate and/or the efficiency parameter of the blood treatment unit. The efficiency parameter may be received from a memory or an input device of the apparatus, or may be calculated.
In a 2nd aspect according to the 1st aspect/previous aspects, the amplitude and/or the duration over time are/is higher if the flow rate of the fresh treatment liquid is lower and wherein the amplitude and/or the duration over time are/is lower if the flow rate of the fresh treatment liquid (and/or the blood or plasma flow rate) is higher.
In another aspect according to anyone of the previous aspects, the computed duration over time being between 50 s (being in particular a prefixed minimum duration over time) and 200 s (being in particular a prefixed maximum duration over time), optionally between 90 s and 150 s.
In another aspect according to anyone of the previous aspects, the characteristic is the conductivity in the fresh liquid and, optionally, the computed amplitude of conductivity being between 0.4 mS/cm (milliSiemens/centimeter) and 1.1 mS/cm, optionally between 0.5 mS/cm and 1 mS/cm (absolute values).
In another aspect according to anyone of the previous aspects, the flow rate of the fresh treatment liquid is lower than a prefixed maximum flow rate, being at most 850 ml/min, in particular the flow rate of the fresh treatment liquid being between 250 ml/min and 850 ml/min, optionally between 300 ml/min and 800 ml/min. The prefixed minimum flow rate of the fresh treatment liquid being for example 200 ml/min, or 300 ml/min.
In a 3rd aspect according to any one of the preceding aspects, the amplitude and/or the duration over time are/is inversely proportional with respect to the flow rate of the fresh treatment liquid (and/or the blood or plasma flow rate).
In a 4th aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is performed through at least one mathematical formula; wherein optionally the mathematical formula is an interpolating curve; wherein optionally the interpolating curve is computed starting from “m” points, each point being defined by a flow rate value of the fresh treatment liquid and by a duration over time value and/or by an amplitude value corresponding to said flow rate value; wherein optionally “m” is equal to or greater than two.
In a 5th aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a prefixed maximum flow rate of the fresh treatment liquid. The prefixed maximum flow rate of the fresh treatment liquid may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a difference between the flow rate of the fresh treatment liquid and a prefixed maximum flow rate of the fresh treatment liquid. In particular, the difference between the flow rate of the fresh treatment liquid and a prefixed maximum flow rate of the fresh treatment liquid being multiplied by a multiplying factor.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a prefixed minimum flow rate of the fresh treatment liquid. The prefixed minimum flow rate of the fresh treatment liquid may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a difference between a prefixed minimum flow rate of the fresh treatment liquid and the flow rate of the fresh treatment liquid. In particular, the prefixed minimum flow rate of the fresh treatment liquid and the flow rate of the fresh treatment liquid being multiplied by a multiplying factor.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a difference between a prefixed maximum flow rate of the fresh treatment liquid and a prefixed minimum flow rate of the fresh treatment liquid.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a prefixed maximum duration over time, in particular corresponding to a minimum flow rate of the apparatus. The prefixed maximum duration over time may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time is a function of a prefixed minimum duration over time, in particular corresponding to a maximum flow rate of the apparatus. The prefixed minimum duration over time may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the two preceding aspects, computing the amplitude and/or the duration over time is a function of a difference between the prefixed maximum duration over time and the prefixed minimum duration over time.
In a further aspect according to the preceding aspect, computing the amplitude and/or the duration over time is a function of a ratio between the difference between the prefixed maximum duration over time and the prefixed minimum duration over time and the difference between a prefixed maximum flow rate of the fresh treatment liquid and a prefixed minimum flow rate of the fresh treatment liquid. In particular, the ratio being the multiplying factor.
In a further aspect according to any one of the preceding aspects, computing the duration over time includes a sum of a main term based on the flow rate of the fresh treatment liquid and an auxiliary term being a time duration, in particular the time duration being a prefixed minimum duration over time or a prefixed maximum duration over time.
In a further aspect according to any one of the preceding aspects, the task comprises:
In a 6th aspect according to the preceding aspect, the task further comprises:
In a 7th aspect according to any one of the preceding aspects, the duration over time is computed using the mathematical formula:
ΔT=((ΔTmin−ΔTmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔTmin
where:
Qdial is the flow rate of the fresh treatment liquid in the preparation line (note that Qdial is the current set or actual flow rate of the fresh treatment liquid in the preparation line; Qdial is generally the flow rate of the fresh treatment liquid in the preparation line at the time the calculation is made);
Qdialmax is a prefixed maximum flow rate of the fresh treatment liquid in the preparation line of the apparatus;
ΔTmin is a prefixed minimum duration over time corresponding to the maximum flow rate of the apparatus;
Qdialmin is a prefixed minimum flow rate of the fresh treatment liquid in the preparation line of the apparatus;
ΔTmax is a prefixed maximum duration over time corresponding to the minimum flow rate of the apparatus.
In a further aspect according to any one of the preceding aspects, computing the amplitude is a function of a difference between a prefixed maximum flow rate of the fresh treatment liquid and a prefixed minimum flow rate of the fresh treatment liquid.
In a further aspect according to any one of the preceding aspects, computing the amplitude is a function of a prefixed maximum amplitude, in particular corresponding to a minimum flow rate of the apparatus. The prefixed maximum amplitude may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the preceding aspects, computing the amplitude is a function of a prefixed minimum amplitude, in particular corresponding to a maximum flow rate of the apparatus. The prefixed minimum amplitude may be received from a memory or an input device of the apparatus, or may be calculated, based on e.g., an apparatus set-up.
In a further aspect according to any one of the two preceding aspects, computing the amplitude is a function of a difference between the prefixed maximum amplitude and the prefixed minimum amplitude. In a further aspect according to the preceding aspect, computing the amplitude is a function of a ratio between the difference between the prefixed maximum amplitude and the prefixed minimum amplitude and the difference between a prefixed maximum flow rate of the fresh treatment liquid and a prefixed minimum flow rate of the fresh treatment liquid. In particular, the ratio being the multiplying factor.
In a further aspect according to any one of the preceding aspects, computing the amplitude includes a sum of a main term based on the flow rate of the fresh treatment liquid and an auxiliary term being an amplitude, in particular the amplitude being a prefixed minimum amplitude or a prefixed maximum amplitude.
In an 8th aspect according to any one of the preceding aspects, the task comprises:
In a 9th aspect according to the preceding aspect, the task further comprises:
In a 10th aspect according to any one of the preceding aspects, the amplitude is computed using the mathematical formula:
ΔCin=((ΔCmin−ΔCmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔCmin
where:
Qdial is the flow rate of the fresh treatment liquid in the preparation line;
Qdialmax is a prefixed maximum flow rate of the fresh treatment liquid in the preparation line of the apparatus;
ΔCmin is a prefixed minimum amplitude corresponding to the maximum flow rate of the apparatus;
Qdialmin is a prefixed minimum flow rate of the fresh treatment liquid in the preparation line of the apparatus;
ΔCmax is a prefixed maximum amplitude corresponding to the minimum flow rate of the apparatus.
In a 11th aspect according to any one of the preceding aspects, optionally the minimum flow rate of the apparatus is between 250 ml/min and 350 ml/min and, optionally, the maximum flow rate of the apparatus is between 750 ml/min and 850 ml/min and, optionally, the mid flow rate of the apparatus is between 500 ml/min and 600 ml/min.
In a 12th aspect according to any one of the preceding aspects, optionally the minimum duration over time corresponding to the maximum flow rate of the apparatus is between 80 s and 100 s and, optionally, the maximum duration over time corresponding to the minimum flow rate of the apparatus is between 140 s and 160 s and, optionally, the mid duration over time corresponding to the mid flow rate of the apparatus is between 110 s and 130 s.
In a 13th aspect according to any one of the preceding aspects, the characteristic is the conductivity in the fresh liquid and, optionally, the minimum amplitude corresponding to the maximum flow rate of the apparatus is between 0.4 mS/cm and 0.6 mS/cm and, optionally, the maximum amplitude corresponding to the minimum flow rate of the apparatus is between 0.9 mS/cm and 1.1 mS/cm and, optionally, the mid amplitude corresponding to the mid flow rate of the apparatus is between 0.7 mS/cm and 0.8 mS/cm.
In a 14th aspect according to any one of the preceding aspects, computing the amplitude and/or the duration over time comprises: selecting the amplitude and/or the duration over time among a plurality of fixed amplitudes and/or fixed durations over time stored in the control unit and each corresponding to a range which the received flow rate falls in.
In a 15th aspect according to the preceding aspect, said range is one of a plurality of ranges of flow rate stored in the control unit.
In a 16th aspect according any of the preceding aspects 1, 2, 14 or 15, said task comprises:
In a 17th aspect according to the preceding aspect, the “n” fixed durations over time comprise:
In an 18th aspect according to any of the preceding aspects 1, 2, 14 to 17, said task comprises:
In a 19th aspect according to preceding aspect, the “n” fixed amplitudes comprise:
In a 20th aspect according to any of the preceding aspects 16 to 19, the “n” ranges of the flow rate comprise:
In a 21st aspect according any of the preceding aspects, said task comprises: causing the upstream variation of the value of the characteristic such that the upstream variation of the value of the characteristic is all above or all below the prescription baseline and wherein said amplitude is a difference between the prescription baseline and a maximum or a minimum of the upstream variation.
In a 22nd aspect according to any one of the preceding aspects from 1 to 20, said task comprises: causing the upstream variation of the value of the characteristic such that the upstream variation of the value of the characteristic comprises at least one part above the prescription baseline and at least one part below the prescription baseline; the duration over time being a sum of partial durations over time of said at least one part above the prescription baseline and said at least one part below the prescription baseline; optionally, said amplitude being a difference between a maximum and a minimum of the upstream variation; optionally, said part/s above the prescription baseline and said part/s below the prescription baseline being arranged consecutively one after the other; optionally, said part/s above the prescription baseline being arranged alternately with said part/s below the prescription baseline.
In a 23rd aspect according to the preceding aspect, causing the upstream variation of the value of the characteristic such that a total area of the part or parts of the upstream variation of the value of the characteristic above the prescription baseline is equal to or substantially equal to a total area of the part or parts of the upstream variation of the value of the characteristic below the prescription baseline.
A 24th aspect concerns apparatus for extracorporeal treatment of blood comprising:
a blood treatment unit having a primary chamber and a secondary chamber separated by a semi-permeable membrane;
a preparation line having one end connected to an inlet of a secondary chamber of the treatment unit and configured to convey fresh treatment liquid to the secondary chamber, the fresh treatment liquid presenting a characteristic which is one selected in the group of:
In a 25th aspect according to any one of the preceding aspects 22 or 23 or 24, said task comprises:
In a 26th aspect according to anyone of the preceding aspects, the characteristic in the fresh treatment liquid is conductivity and optionally the maximum allowed conductivity absolute value is between 15 mS/cm and 16 mS/cm and optionally the minimum allowed conductivity absolute value is between 12 mS/cm and 13 mS/cm.
In a 27th aspect according to any one of the preceding aspects, said task comprises: causing the upstream variation of the value of the characteristic such that the upstream variation of the value of the characteristic or the parts of the upstream variation of the value of the characteristic has/have a rectangular or substantially rectangular shape or is/are bell-shaped or substantially bell-shaped.
In a 28th aspect according to any one of the preceding aspects, said task comprises the following steps:
In a 29th aspect according to the preceding aspect, said parameter comprises one selected in the group of:
A 30th aspect concerns a method for determining an effectiveness parameter which may be used in an apparatus for extracorporeal treatment of blood comprising:
a blood treatment unit having a primary chamber and a secondary chamber separated by a semi-permeable membrane;
a preparation line having one end connected to an inlet of a secondary chamber of the treatment unit and configured to convey fresh treatment liquid to the secondary chamber, the fresh treatment liquid presenting a characteristic which is either the conductivity in the fresh treatment liquid or the concentration of at least one substance (for instance sodium or calcium or potassium) in the fresh treatment liquid;
a spent dialysate line having one end connected to an outlet of said secondary chamber and configured to remove spent liquid from the secondary chamber, the spent liquid presenting a characteristic which is either the conductivity in the fresh treatment liquid or the concentration of at least one substance (for instance sodium or calcium or potassium) in the fresh treatment liquid;
wherein the method comprises:
In a 31st aspect according to the preceding aspect, the method comprises:
The method of the 30th and 31st aspects may be used adopting the apparatus of any one of aspects from the 1st to the 29th.
Aspects of the invention are shown in the attached drawings, which are provided by way of non-limiting example, wherein:
Non-limiting embodiments of an apparatus 1 for extracorporeal treatment of blood—which may implement innovative aspects of the invention—are shown in
The apparatus 1 may be configured to determine a parameter indicative of the effectiveness of the treatment delivered to a patient (here below also referred to as effectiveness parameter). The effectiveness parameter may be one of the following:
Note that a parameter proportional to one of the above parameters or known function of one or more of the above parameters may alternatively be used as ‘effectiveness’ parameter.
In below description and in
As mentioned at the beginning of the detailed description, the apparatus 1 is capable of determining an effectiveness parameter. In this regard, the control unit 10 of the apparatus 1 is configured for commanding execution of a number of procedures including a task specifically devoted to the determination of the parameter indicative of the effectiveness of the extracorporeal blood treatment. The task devoted to determination of the effectiveness parameter comprises the steps described herein below. First, the control unit 10 is configured for receiving at least one prescription baseline Cdset for the characteristic Cdin in the fresh treatment liquid; the characteristic may be the concentration for one substance in the dialysis liquid (e.g. the sodium concentration, or the calcium concentration), or the concentration for a group of substances in the dialysis liquid (such as the electrolyte concentration) or the conductivity of the dialysis liquid. Furthermore, the set value for the prescription baseline may be either pre set in a memory connected to the control unit 10 or, alternatively, it may be entered by the user via user interface 12. Although the prescription baseline is frequently a constant value, it may alternatively comprise a time-variable value which changes during treatment according to a prefixed law. The control unit 10, acting on appropriate actuators such as pumps 21 and 17, causes circulation of dialysis fluid through lines 19 and 13 and through the secondary chamber 4 of the treatment unit 2. In greater detail, the control unit 10 is configured for causing fresh treatment liquid to flow in the preparation line 19 to the secondary chamber 4 with the characteristic being at said prescription baseline Cdset: the characteristic at the baseline value may for instance be achieved by appropriately controlling the concentrate pumps 105, 108 of the preparation section 100. Furthermore, the control unit 10 is configured for reading the value of the characteristic through the spent dialysis fluid using sensor 109a. Depending upon the case, sensor 109a may for instance be a conductivity sensor, or a concentration sensor (sensitive to one or more substances).
In addition to command the circulation of dialysis liquid in lines 19 and 13, the control unit 10, e.g. by acting one or more concentrate pumps 105, 108, causes an upstream variation of the value of the characteristic Cdin in the fresh treatment liquid with respect to said prescription baseline Cdset and then re-establishes the characteristic Cdin in the fresh treatment liquid to said prescription baseline Cdset. Note that the alteration of the characteristic may be made using any means able to momentarily change the characteristic of the dialysis liquid, e.g. the conductivity or the concentration for one or more substances in the fresh dialysis fluid: for instance, a bolus pump configured to inject a predefined bolus of saline may be used for this purpose. The upstream variation causes a corresponding and timely delayed downstream variation of the same characteristic Cdout in the spent liquid flowing in the spent dialysate line:
The control unit 10 is also configured to receive at least one parametric mathematical model which puts into relation the characteristic Cdin in the fresh treatment liquid with the characteristic Cdout in the spent liquid. The parametric mathematical model, which mathematically describes the components interposed between the two sensors 109, 109a, may for instance be pre-stored in a memory connected to the control unit 10, or it may be transferred to said memory via user interface 12 or via other input means such as a data reader, or it may be remotely transmitted from a remote source. The parametric model mathematically models the portion of hydraulic circuit between the sensors 109 and 109a and presents a prefixed number of free parameters that are determined as described herein below in order to characterize the parametric mathematical model into one single model. In practice, the parametric mathematical model defines a family of mathematical models and is univocally characterized only once the parameters of the model are determined.
In order to determine the parameters of the parametric mathematical model, the control unit 10 is configured to receive, e.g. from sensor 109a, measures of a plurality of values taken by a reference portion 200 of the downstream variation of the characteristic Cdout in the spent liquid. The measured values taken by the reference portion 200 of the variation in the characteristic Cdout may be measured by first identifying the initiation of a ramp-up or of a ramp-down portion of the downstream variation with respect to a respective baseline value of the same characteristic Cdout in the spent liquid, and then by measuring the plurality of values, as values taken by said ramp-up portion or ramp-down portion of said downstream variation. According to an aspect of the invention, the reference portion 200 which is used by the control unit 10 to characterize the mathematical model has a duration ΔTR significantly shorter than the entire duration ΔTV of the downstream variation: duration ΔTR may be less than 70% and optionally less than 50% of duration ΔTV. This is visible e.g. in
The computation of the at least one significant value or directly of the effectiveness parameter comprises determining the value Cdout(n) of characteristic Cdout in the spent liquid at time instant (n) by using as input to the mathematical model:
The mathematical model—for instance a time invariant linear (LTI) model—may be represented in the time domain by the following recursive equation:
y(n)=a0·u(n)+b1·y(n−1)+b2·y(n−2)+ . . . bm·y(n−m),
Thus, the value Cdout(n) of characteristic Cdout in the spent liquid at time instant (n) subsequent to said reference portion is calculated with the following recursive equation:
Cd
out(n)=a0·Cdin(n)+b1·Cdout(n−1)+b2·Cdout(n−2)+ . . . bm·Cdout(n−m),
wherein:
Cdout(n) is the calculated value of the outlet characteristic at time instant (n),
Cdin(n) is the known value of the inlet characteristic at time instant (n),
Cdout(n−1), Cdout(n−2), . . . , Cdout(n−m) are values of the outlet characteristic at preceding time instants (n−1, n−2, . . . n−m) prior to time instant (n) and recursively computed through the mathematical model. a0, b1, b2, . . . , bm are constant parameters that characterize the mathematical model, as estimated by using said measured values of the reference portion of the downstream variation.
In the frequency domain and using the z-Transform—the mathematical model is described by a transfer function H(z) having at least one zero and at least one pole. In an embodiment, the transfer function H(z) comprises a plurality of poles, e.g. from 2 to 5 poles, and is described by one of the following:
H(z)=Cdout(z)/Cdin(z)=a0/(1−b1·z−1−b2·z−2−b3·z−3−b4·z−4−b5·z−5),
H(z)=Cdout(z)/Cdin(z)=a0/(1−b1·z−1−b2·z−2−b3·z−3·b4·z−4),
H(z)=Cdout(z)/Cdin(z)=a0/(1−b1·z−1−b2·z−2−b3·z−3),
H(z)=Cdout(z)/Cdin(z)=a0/(1−b1·z−1−b2·z−2),
wherein
a0, b1, b2, b3, b4, b5 are constant parameters of the model, as estimated by using said measured values of the reference portion of the downstream variation.
Notably, a different mathematical model and approach may be used to determine the second outlet value Cdout2.
Indeed, the response in the spent dialysate (effluent) line to the conductivity step, may be the input for the differential evolution algorithm that uses a mathematical model to predict the system response at the steady state. The differential evolution algorithm is an alternative method that optimizes the problem by iteratively trying to improve a candidate solution with regard to a given measure of quality. Such method is commonly known as metaheuristic as it makes few or no assumptions about the problem being optimized and can search very large spaces of candidate solutions. It has been proved from practical evidences that running a differential evolution algorithm for about 1000 generations provides a meaningful result for the second outlet value Cdout2 in about 1 minute of computations on PC104 board. Other strategies different from the previously described mathematical models might be used, but the differential evolution algorithm has proven good and reliable results in most cases. Then, the calculated second outlet value Cdout2 is used as significant value for the computation of at least one value of a parameter (D, Cbin, K, K·t/V) indicative of the effectiveness of the extracorporeal blood treatment. In accordance with an aspect, if the parameter comprises is effective dialysance D, each computed value Dk of the dialysance each respective variation is obtained using the formula:
D
k=(Qdial+WLR)·[1−(Cdout2−Cdout1)/(Cdin2−Cdin1)]
where:
Cdout1 is the first outlet value taken by the characteristic in the spent dialysate line downstream of the secondary chamber in response to the change of characteristic Cdin in the preparation line to said first inlet value Cdin1,
Cdout2 is the calculated second value (namely the significant value) which is representative of the value taken by the characteristic in the spent dialysate line downstream of the secondary chamber in response to the change of characteristic Cdin in the preparation line from said first inlet value Cdin1 to said second inlet value Cdin2,
Cdin1, Cdin2 are first and second inlet values taken by the characteristic (Cd) in the preparation line upstream of the secondary chamber,
Qdial is the fresh treatment liquid flow rate in the preparation line,
WLR is the weight loss rate of a patient under treatment.
In
Once the values Cdout1, Cdout2, Cdout3 have been calculated, the effectiveness parameter may be determined based on these calculated values and on one or more inlet values of the conductivity, e.g. Cdin1, Cdin2, Cdin3.
For instance if dialysance is to be calculated, the following formula may be adopted:
D=(Qdial+WLR)[1−(2×Cdout1−Cdout2−Cdout3)/(2×Cdin1−Cdin2−Cdin3)]
where:
Cdout1 is the first outlet value taken by the characteristic in the spent dialysate line downstream of the secondary chamber in response to the change of characteristic Cdin in the preparation line to said first inlet value Cdin1,
Cdout2 is the calculated second value (namely one of the significant values) which is representative of the value taken by the characteristic in the spent dialysate line downstream of the secondary chamber in response to the change of characteristic Cdin in the preparation line from said first inlet value Cdin2 to said second inlet value Cdin2,
Cdout3 is the calculated third value (namely one of the significant values) which is representative of the value taken by the characteristic in the spent dialysate line downstream of the secondary chamber in response to the change of characteristic Cdin in the preparation line from said second inlet value Cdin2 to said third inlet value Cdin3,
Cdin1, Cdin2, Cdin3 are first, second and third inlet values taken by the characteristic (Cd) in the preparation line upstream of the secondary chamber,
Qdial is the fresh treatment liquid flow rate in the preparation line,
WLR is the weight loss rate of a patient under treatment.
According to a further embodiment, see
Then, using e.g. the formulas described in EP 0920877, the control unit computes at least one value of a parameter (D, Cbin, K, K·t/V) indicative of the effectiveness of the extracorporeal blood treatment by comparing the calculated downstream variation/perturbation and the upstream variation/perturbation.
In accordance with a further aspect of the invention, the control unit 10 may also be configured to determine the baseline of the downstream curve representative of the values Cdout(t) taken over time by said characteristic in the spent dialysate line downstream of the secondary chamber. The baseline of the downstream curve Cdout(t) may be determined using measured values of the characteristic Cdout in the spent liquid or using a calculated curve representative of the downstream variation which has been previously determined using the characteristic mathematical model. In this second option only measured values of the characteristic Cdout in the spent liquid during said reference portion are used for the determination of the free parameters to identify the characteristic mathematical model; then using said identified characteristic mathematical model, a downstream curve Cdout(t) representative of the values taken by the characteristic Cdout in the spent liquid is mathematically determined and the baseline thereof identified.
The control unit may be configured to determine an angular deviation a between the baseline of the downstream curve Cdout(t) with respect to the prescription baseline Cdset, and to compensate for said angular deviation by angularly rotating the downstream curve to obtain a corrected downstream curve Cdout-correct(t), as shown in a the enlarged representation of
According to a yet further aspect, the control unit 10 is configured to remove undesired noise from the characteristic Cdout. In accordance with an aspect, the control unit may receive measured values of the characteristic Cdout in the spent liquid during said reference portion, estimate the free parameters of the parametric mathematical model to identify the characteristic mathematical model, determine a downstream curve Cdout(t) representative of the values taken by the characteristic Cdout in the spent liquid using said identified characteristic mathematical model, analyze a frequency spectrum of the downstream curve Cdout(t), filter out harmonics of said frequency spectrum of the downstream curve Cdout(t) lying at frequencies higher than a prefixed threshold to eliminate noise and undesired perturbations possibly present in the downstream curve and obtain a corrected downstream curve Cdout-correct(t).
Although the above description referred to one single parametric mathematical model, the control unit 10 may further be configured for storing a plurality of mathematical models each of which puts into relation the characteristic (Cdin) in the fresh treatment liquid with the characteristic (Cdout) in the spent liquid. In this case the control unit may be configured for selecting the mathematical model to be used for computing the at least one significant value of said downstream variation based on certain factors such as for instance: the shape of the upstream variation (one mathematical model may be better suited for a long step variation/perturbation while another model may more properly operate for a short sinusoidal change), the type of blood treatment unit used by the apparatus, whether or not particular hydraulic components are present in the circuit section between sensor 109 and sensor 109a.
Aspects of the invention are also disclosed in
The method comprises the following steps.
The calculation of the effectiveness parameter may be made using any one of the formulas described above.
Here below an example is described, with reference to
Furthermore, the example makes reference to conductivity variations and corresponding measures: of course the same procedure may be adopted using variations, and corresponding measures, in the concentration of at least one substance in the dialysis liquid.
Referring now to the diagram of
D
k=(Qdial+WLR)·[1−(Cdout2−Cdout1)/(Cdin2−Cdin1)]
According to one aspect of the invention, instead of measuring the conductivity values until time 950 s, measures are taken only during reference portion ΔTR (please refer to
Then, using the following a one-zero and three-pole model:
The following parameters are estimated using the measured values of Cdout during reference portion ΔTR:
By feeding an idealized unit step (i.e. a calculated step) of appropriate length (e.g. 200 to 300 s) to this model and by suitably adding the baseline value Cdout1 to the model output, we get a signal as shown in
The following table shows the measured versus computed values of Cdout in the neighborhood of time n=910 where the good match between measured and computed values can be seen.
The calculated significant value Cdout2 at time 910 is 13.59 mS/cm is very close to the corresponding measured value (13,58656872 mS/cm). Thus, the dialysance calculation using the above formula and relying on the calculated value Cdout2 of 13.59 mS/cm will provide exactly the same result as when using a measured valued for Cdout2, while requiring actual measurements only during ΔTR.
According to one aspect of the invention, the control unit is configured to compute the extent (duration over time ΔT and/or the amplitude ΔCin) of the mentioned upstream variation of the value of the characteristic Cdin in the fresh treatment liquid with respect to said prescription baseline Cdset as a function of the working conditions of the apparatus and in particular of the flow rate Qdial of the fresh treatment liquid in the preparation line 19 and/or of another parameter correlated to the flow rate Qdial. Indeed, a parameter proportional to the flow rate Qdial or a known function of the flow rate Qdial may alternatively be used as flow rate Qdial. Extent of the upstream variation is computed in order to tune and optimize said upstream variation as a function of the effective flow rate Qdial and to minimize the effects of undesired modifications of the characteristic of the dialysis liquid on patients. In this way, the best duration over time ΔT and/or the best amplitude ΔCin are/is set at each flow rate Qdial of the fresh treatment liquid during treatment, meaning that the best compromise “precision vs treatment interruption” is ensured and unnecessary machine time to determine the effectiveness parameter is avoided.
Note that this aspect related to the optimization of the upstream variation may also be independent from the implementation of the parametric mathematical model detailed above. Indeed, the values correlated to the downstream variation may also be all measured and/or calculated in some other way and used to compute said at least one value of a parameter indicative of the effectiveness of the extracorporeal blood treatment without using the parametric mathematical model.
As schematically shown in
It is feasible to reduce the duration over time ΔT and/or the amplitude ΔCin as a function of increase of the flow rate Qdial of the fresh treatment liquid. In other words, the amplitude ΔCin and/or the duration over time ΔT are/is increased if the flow rate Qdial of the fresh treatment liquid is reduced and the amplitude ΔCin and/or the duration over time ΔT are/is reduced if the flow rate Qdial of the fresh treatment liquid is increased.
The computed duration over time may be between 50 s and 200 s, optionally between 90 s and 150 s. The characteristic Cdin may be the conductivity in the fresh treatment liquid and the computed amplitude of said conductivity may be between 0.4 mS/cm and 1.1 mS/cm, optionally between 0.5 mS/cm and 1 mS/cm. The flow rate Qdial of the fresh treatment liquid during treatment being may be between 250 ml/min and 850 ml/min, optionally between 300 ml/min and 800 ml/min. According to some embodiments, the duration over time ΔT and/or the amplitude ΔCin are/is inversely proportional with respect to the flow rate of the fresh treatment liquid. According to some embodiments, the duration over time ΔT and/or the amplitude ΔCin are/is computed through an interpolating curve (a method of the invention is illustrated in
Duration over time ΔT may be computed using the following interpolating curve.
ΔT=((ΔTmin−ΔTmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔTmin i)
where:
Qdial is the flow rate of the fresh treatment liquid in the preparation line, e.g. measured by the flow sensor 110 during treatment or set as working parameter;
Qdialmax is a maximum flow rate of the apparatus (e.g between 750 ml/min and 850 ml/min);
ΔTmin is a minimum duration over time corresponding to the maximum flow rate of the apparatus (e.g between 80 s and 100 s);
Qdialmin is a minimum flow rate of the apparatus (e.g between 250 ml/min and 350 ml/min);
ΔTmax is a maximum duration over time corresponding to the minimum flow rate of the apparatus (e.g between 140 s and 160 s).
Said maximum flow rate Qdialmax, said a minimum duration over time ΔTmin, said a minimum flow rate Qdialmin, said maximum duration over time ΔTmax are values pre-stored in the memory of the control unit 10 as factory settings or transferred to said memory via user interface 12 or via other input means, such as a data reader, or it may be remotely transmitted from a remote source.
Amplitude ΔCin may be computed using the following interpolating curve.
ΔCin=((ΔCmin−ΔCmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔCmin ii)
where:
Qdial is the flow rate of the fresh treatment liquid in the preparation line;
Qdialmax is the maximum flow rate of the apparatus;
ΔCin is a minimum amplitude corresponding to the maximum flow rate of the apparatus (e.g a conductivity amplitude between 0.4 mS/cm and 0.6 mS/cm);
Qdialmin is the minimum flow rate of the apparatus;
ΔCmax is a maximum amplitude corresponding to the minimum flow rate of the apparatus (e.g a conductivity amplitude between 0.9 mS/cm and 1.1 mS/cm).
Said maximum flow rate Qdialmax, said a minimum amplitude ΔCmin, said a minimum flow rate Qdialmin, said maximum amplitude ΔCmax are values pre-stored in the memory of the control unit 10 as factory settings or transferred to said memory via user interface 12 or via other input means, such as a data reader, or it may be remotely transmitted from a remote source.
The interpolating curves of the embodiments mentioned above are each computed starting only from two flow rates Qdialmax and Qdialmin (and corresponding ΔCmax, ΔCmin or ΔTmax, ΔTmin). In other embodiments, the interpolating curves may be computed starting from “m” points wherein “m” is equal to or greater than two. Each of the “m” points is defined by a flow rate value Qdialm of the fresh treatment liquid and by a duration over time ΔTm and/or by an amplitude ΔCm of the characteristic Cdin corresponding to said flow rate value Qdialm. For instance, the interpolating curve is computed starting from the above mentioned maximum flow rate Qdialmax and a minimum flow rate Qdialmin and also from a third point, for instance a mid flow rate Qdialmid of the apparatus comprised between the maximum flow rate Qdialmax and the minimum flow rate Qdialmin and corresponding to a mid duration over time ΔTmid or to a mid amplitude ΔCmid.
Here below an example is described.
The minimum flow rate of the apparatus Qdialmin is 300 ml/min.
The maximum duration over time ΔTmax corresponding to the minimum flow rate Qdialmin of the apparatus is 150 s.
The maximum flow rate of the apparatus Qdialmax is 800 ml/min.
The minimum duration over time ΔTmin corresponding to the maximum flow rate Qdialmin of the apparatus is 90 s.
The maximum amplitude of conductivity ΔCmax corresponding to the minimum flow rate Qdialmin of the apparatus is 1 mS/cm.
The minimum amplitude of conductivity ΔCmin corresponding to the maximum flow rate Qdialmax of the apparatus is 0.5 mS/cm.
The flow rate Qdial of the fresh treatment liquid in the preparation line during treatment is 500 ml/min. The duration over time ΔT of the upstream variation is computed using interpolating curve i):
ΔT=((ΔTmin−ΔTmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔTmin=((90−150)/(800−300))*(500−800)+90=126 s
The amplitude of the upstream variation of conductivity is computed using interpolating curve ii):
ΔCin=((ΔCmin−ΔCmax)/(Qdialmax−Qdialmin))*(Qdial−Qdialmax)+ΔCmin=((0.5−1)/(800−300))*(500−800)+0.5=0.8 mS/cm
According to other embodiments, the amplitude ΔCin and/or the duration over time ΔT are/is selected among “n” fixed amplitudes ΔC1, ΔCn and/or fixed durations over time ΔT1, ΔTn and each corresponding to a range, among “n” ranges ΔQdial1, ΔQdialn of the flow rate, in which the flow rate Qdial of the treatment falls. The plurality of fixed amplitudes ΔC1, ΔCn and/or fixed durations over time ΔT1, ΔTn and the “n” ranges ΔQdial1, ΔQdialn are stored in the memory of the control unit 10 as factory settings or transferred to said memory via user interface 12 or via other input means, such as a data reader, or it may be remotely transmitted from a remote source. The flow rate Qdial of the treatment may be measured through the flow sensor 110 or it is a or pre-set as working parameter of the treatment.
For instance, the control unit 10 receives “n” fixed durations over time ΔT1, ΔTn (e.g. a first, second and third duration over time, respectively of 150 s, 120 s, 90 s) and “n” ranges ΔQdial1, ΔQdialn of the flow rate of the fresh treatment liquid (e.g. a first, second and third ranges of flow rate, respectively between 300-350/400 ml/min, 400-600/650 ml/min, 650-800 ml/min), wherein each of the “n” ranges is allocated to/combined with a fixed duration over time of “n” of said fixed durations over time ΔT1, ΔTn. Then the control unit 10 receives the flow rate Qdial of the treatment and computes the duration over time ΔT of the upstream variation to be generated by comparing the received flow rate Qdial with the “n” ranges ΔQdial1, ΔQdialn and by selecting the fixed duration over time corresponding to the range of said “n” ranges which the flow rate Qdial falls in.
The control unit 10 further receives “n” fixed amplitudes ΔC1, ΔCn (e.g. a first, second and third amplitude of conductivity, respectively of 0.5 mS/cm, 0.7 mS/cm, 1 mS/cm) and the “n” ranges ΔQdial1, ΔQdialn of the flow rate of the fresh treatment liquid, wherein each of the “n” ranges is allocated to/combined with a fixed amplitude of “n” fixed amplitudes ΔC1, ΔCn. Then the control unit 10 receives the flow rate Qdial of the treatment and computes the amplitude ΔCin of the upstream variation to be generated by comparing the received flow rate Qdial with the “n” ranges ΔQdial1, ΔQdialn and by selecting the fixed amplitude ΔCin corresponding to the range of said “n” ranges which the flow rate Qdial falls in.
According to one aspect of the invention, the control unit 10 is configured to compute and generate the upstream variation so that said upstream variation is lower than a maximum allowed value Cdin max (e.g. 1.5 mS/cm) of the characteristic Cdin in the fresh treatment liquid and higher than a minimum allowed value Cdin min (e.g. 0.1 mS/cm) of the characteristic Cdin in the fresh treatment liquid.
If the prescription baseline Cdset is close to the minimum allowed value Cdin min, the upstream variation is computed and generated to be all above said prescription baseline Cdset, as shown in
According to one aspect of the invention, the control unit 10 is configured to compute and generate the upstream variation so that said upstream variation comprises at least two consecutive parts placed one after the other, one part extending above the prescription baseline Cdset and the other part extending below the prescription baseline Cdset (as mentioned above and shown in
As already indicated the apparatus according to the invention makes use of at least one control unit 10. This control unit 10 may comprise a digital processor (CPU) with memory (or memories), an analogical type circuit, or a combination of one or more digital processing units with one or more analogical processing circuits. In the present description and in the claims it is indicated that the control unit 10 is “configured” or “programmed” to execute certain steps: this may be achieved in practice by any means which allow configuring or programming the control unit 10. For instance, in case of a control unit 10 comprising one or more CPUs, one or more programs are stored in an appropriate memory: the program or programs containing instructions which, when executed by the control unit 10, cause the control unit 10 to execute the steps described and/or claimed in connection with the control unit 10. Alternatively, if the control unit 10 is of an analogical type, then the circuitry of the control unit 10 is designed to include circuitry configured, in use, to process electric signals such as to execute the control unit 10 steps herein disclosed.
While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19156537.3 | Feb 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/051684 | 1/23/2020 | WO | 00 |
