DIALYSIS MACHINE HAVING THE CAPABILITY OF DETERMINING A PREDIALYTIC PROPERTY IN THE BLOOD OF A DIALYSIS PATIENT

Abstract

The invention relates to a dialysis machine having the capability of determining a predialytic property in the blood of a dialysis patient which has an extracorporeal blood circuit, a dialyzate circuit, a dialyzer and a processing unit, wherein at least one sensor for determining a property of the dialyzate is arranged in the dialyzate circuit. The processing unit is configured such that temporal evaluation ranges are fixed during an initial phase of the dialysis treatment, in which temporal evaluation ranges all stability criteria from a predefined group are satisfied; and in that only measured values determined by the at least one sensor within these temporal evaluation ranges are used for determining a predialytic property of the patient's blood.

Claims

1. A dialysis machine having an extracorporeal blood circuit, a dialyzate circuit, a dialyzer and a processing unit, wherein at least one sensor for determining a property of the dialyzate is arranged in the dialyzate circuit, characterized in that the processing unit is configured such that temporal evaluation ranges are fixed during an initial phase of the dialysis treatment, in which temporal evaluation ranges all stability criteria from a predefined group are satisfied; and in that only measured values determined by the at least one sensor within these temporal evaluation ranges are used for determining a predialytic property of the patient's blood.

2. A dialysis machine in accordance with claim 1, characterized in that a first conductivity sensor is arranged upstream of the dialyzer in the dialyzate circuit and a second conductivity sensor is arranged downstream of the dialyzer; and in that the processing unit is configured such that measured values of the conductivity value of the dialyzate downstream and upstream of the dialyzer determined within the temporal evaluation ranges are used for the determination of a predialytic ion concentration, preferably a sodium ion concentration, in the blood plasma of the dialysis patient.

3. A dialysis machine in accordance with claim 1, characterized in that the processing unit is furthermore configured such that measured values from a plurality of temporal evaluation ranges, and preferably from all temporal evaluation ranges, are used for determining the predialytic property of the patient's blood.

4. A dialysis machine in accordance with claim 1, characterized in that the processing unit is further configured such that the initial phase of the dialysis treatment ends when a preset treatment duration or a preset treatment efficiency has been reached; and/or in that the initial phase of the dialysis treatment ends at the end of the first 30 minutes, 20 minutes, 10 minutes or 5 minutes of the dialysis treatment.

5. A dialysis machine in accordance with claim 1, characterized in that the processing unit is further configured such that a stability criterion is satisfied when the standard deviation and/or change range of the conductivity measured upstream and/or downstream of the dialyzer is smaller than a threshold value stored in the processing unit.

6. A dialysis machine in accordance with claim 1, characterized in that the processing unit is further configured such that a stability criterion is satisfied when a certain blocking time has elapsed after an event from the group change of the dialyzate flow, change of the blood flow, change of the substituate flow, change of the UF rate, change of the dialyzate composition, bypass switchover, pump stop, infusion of cleaning solution into the extracorporeal blood circuit, self-test of the system, user actions, wherein the blocking time is optionally less than 2 minutes and lies, for example, between 15 and 90 seconds or between 30 and 60 seconds.

7. A dialysis machine having an extracorporeal blood circuit, a dialyzate circuit, a dialyzer and a processing unit, wherein a first sensor is arranged upstream of the dialyzer in the dialyzate circuit and a second sensor is arranged downstream of the dialyzer, preferably a dialysis machine in accordance with one of the preceding claims, characterized in that the processing unit is configured such that determined measured values upstream of the dialyzer at first time and determined measured values downstream of the dialyzer at a later second time are used as corresponding value pairs for determining a predialytic property of the patient's blood, with the time offset between the first and second times being approximated to the flow time of the dialyzate between the first and second sensors or corresponding thereto.

8. A dialysis machine in accordance with claim 7, characterized in that the first and second sensors are conductivity sensors; and in that the processing unit is configured such that the determined measured values are the conductivities of the dialyzate upstream and downstream of the dialyzer; and in that these conductivities are used as corresponding value pairs for determining the predialytic ion concentration, preferably the sodium ion concentration, in the blood plasma of the dialysis patient.

9. A dialysis machine in accordance with claim 7, characterized in that the processing unit is furthermore configured such that the time offset is calculated from the volume of the hydraulic system between the two sensors and the dialysis flow; or in that the time offset is determined with reference to the time difference between the detection of a disturbance at the first and second sensors.

10. A dialysis machine in accordance with claim 7, characterized in that the processing unit is furthermore configured such that the time offset is adapted, provided that the flow speed of the dialyzate changes in the course of the treatment.

11. A dialysis machine in accordance with claim 2, characterized in that the processing unit is furthermore configured such that a predialytic plasma-equivalent conductivity is determined with reference to the conductivity values determined upstream and downstream of the dialyzer; and in that further subsequently the ion concentration in the plasma of the dialysis patient is determined from the predialytic plasma-equivalent conductivity.

12. A dialysis machine in accordance with claim 11, characterized in that the processing unit is furthermore configured such that the predialytic plasma-equivalent conductivity is determined by extrapolation of instantaneous plasma-equivalent conductivities which are determined for the temporal evaluation ranges and/or while considering the time offset from the conductivity values upstream and downstream of the dialyzer, with the extrapolation preferably comprising a regression of the instantaneous plasma-equivalent conductivities as a function of the time or as a function of the Kt/V value.

13. A dialysis machine in accordance with claim 7, characterized in that the processing unit is furthermore configured such that a predialytic plasma-equivalent conductivity is determined with reference to the conductivity values determined upstream and downstream of the dialyzer; and in that further subsequently the ion concentration in the plasma of the dialysis patient is determined from the predialytic plasma-equivalent conductivity.

Description

[0037] Further details and advantages of the invention result from the enclosed Figures and with reference to the embodiments described in the following. There are shown in the Figures:

[0038] FIG. 1: a diagram of the calculated plasma conductivity with and without consideration of the flow time t.sub.F;

[0039] FIG. 2: a diagram of the time curve of conductivities, flows and calculated clearance;

[0040] FIG. 3: a schematic representation of a dialysis machine in accordance with the invention with the capability of estimating the predialytic sodium ion concentration in the blood plasma of a dialysis patient;

[0041] FIG. 4: a diagram which shows a fit of the plasma conductivity when applied against the treatment duration; and

[0042] FIG. 5: a diagram which shows a fit of the plasma conductivity when applied against the dialysis dosage Kt/V.

[0043] FIG. 3 shows schematic representation of an embodiment of a dialysis machine in accordance with the invention with the capability of estimating the predialytic sodium ion concentration in the blood plasma of a dialysis patient.

[0044] In this respect, a blood circuit 1 is in communication with a dialyzate circuit 2 via a dialyzer 3. The dialyzate circuit 2 comprises a concentrate metering unit 4 as well as pumps, valves and sensors not shown in more detail in the Figure. The measurement of the temperature-compensated dialyzate-side conductivity upstream and downstream of the dialyzer takes place using first and second conductivity cells 5 and 6. Flow sensors and the conductivity cells communicate measured data continuously to the processing unit 7. The algorithms described further subsequently for determining the predialytic sodium ion concentration in the blood plasma of the dialysis patient are stored in said processing unit. The processing unit 7 is in communication with a user interface 8 for reporting to the user. Data from the processing unit 7 or from the user interface 8 can be transmitted via a data network 9 to an external computer for further storage and processing.

[0045] The algorithm stored in the processing unit 7 comprises the following elements:

[0046] Calculating c.sub.bi While Taking Account of the Delay Time t.sub.F.

[0047] The delay time t.sub.F(Q.sub.d) can be calculated directly with knowledge of the hydraulic properties of the system between the conductivity cells 5 and 6 and the dialyzate flow with a constant dialyzate flow Q.sub.d. The delay occurring in the dialyzer 6 due to its volume can be seen from the dialyzer type which either manually or automatically (e.g. by marking the dialyzer using an RFID tag or by a barcode and reading by a corresponding unit). Alternatively, t.sub.F can take place from the time delay of the response in c.sub.do to a conductivity change in c.sub.di (e.g. conductivity pulse for determining the clearance, cf. FIG. 1). If Q.sub.d(t.sub.i) differs at a time t.sub.j from the dialyzate flow present on the determination of t.sub.F at the time t.sub.M, t.sub.FQ.sub.d(t.sub.j) can be determined by extrapolation, e.g. by

[00005]$\begin{array}{cc}{t}_F\left(t_j\right)=t_F.Math.\frac{Q_d\left(t_M\right)}{Q_d\left(t_j\right)}.& \left[5\right]\end{array}$

[0048] Subsequently, c.sub.bi is calculated according to the initially shown formula 4. It must be taken into account in this respect that the storage of the relevant data only takes place at time intervals Δt.sub.s for reasons of capacity. An improvement in the calculation of c.sub.bi can therefore be achieved by a shortening of Δt.sub.s in the time interval required for the calculation of the initial plasma Na to an acceptable minimum. Alternatively, an interpolation of intermediate value for c.sub.bi can take place on the basis of the adjacent stored data.

[0049] Elimination of Ranges in Which No Reliable Calculation of C.sub.bi is Possible.

[0050] Time ranges in which what was calculated as described above does not correspond to the real value due to different stability criteria are not taken into account for the further evaluation. They include the following stability criteria: [0051] changes in the presets by the user or by automatic settings of dialyzate, blood flow and substituate flow as well as of the ultrafiltration rate or of the dialyzate composition (desired values for sodium and bicarbonate, change of the concentrate, etc.); [0052] bypass switchovers and pump stops in self-tests of the system or as a consequence of user actions (e.g. opening of doors and covers).

[0053] On changes, c.sub.bi is marked as invalid for a duration t.sub.D.sub._.sub.change.j from the time of the change. t.sub.D.sub._.sub.change.j is stored in the processing unit 7 and can adopt different values depending on the disturbance (e.g. 1 minute after the bypass switchover, 30 seconds after a change of the blood pump rate). Rules can also be stored according to which t.sub.D.sub._.sub.change.j depends on the degree of the change of a parameter (e.g. 30 seconds on a change of the dialyzate flow by 100 ml/min, 60 seconds on a change by >300 ml/min).

[0054] Furthermore, an insufficient stability of c.sub.di and c.sub.do can be used as a trigger for a blocking time t.sub.D.sub._.sub.stab.j. c.sub.bi can thus be marked as invalid for so long until a sufficient stability is again present. The following stability criteria for instability can be applied in this respect: [0055] fluctuation of the LF (c.sub.di or c.sub.do), expressed e.g. as a standard deviation above a predefined threshold value; [0056] change rate of the LF, expressed e.g. as a straight line increase, above a predefined threshold value.

[0057] After eliminating the values of c.sub.bi marked as invalid, the values which can be used for the further evaluation remain in the memory of the processing unit (cf. FIG. 4, solid line).

[0058] Extrapolation of c.sub.bi to the Predialytic Value

[0059] For the extrapolation of c.sub.bi to the predialytic value, all remaining values of c.sub.bi up to a maximum initial dialysis duration t.sub.max are used. The maximum initial dialysis duration t.sub.max is determined from the time within which the changes in the concentration of the sodium ions in the blood plasma of the dialysis patient for physiological considerations can have taken place either only within a limited range or in a largely predictable manner, e.g. on modeling the mass transfer between the blood and the dialyzate by a 1-pool model as in formula 6 shown below:

[00006]$\begin{array}{cc}{c}_{\mathrm{bi}}\left(t\right)=c_{\mathrm{di}}+\left(c_{\mathrm{bi}}\left(0\right)-c_{\mathrm{di}}\right).Math.e^{-\frac{\mathrm{Kt}}{V}}& \left[6\right]\end{array}$

[0060] The maximum initial dialysis duration t.sub.max can in this respect e.g. be a fixed time, e.g. 30 minutes, or the time up to which a specific treatment efficiency, e.g. Kt/V=0.3, is reached.

[0061] The interpolation then takes place e.g. by regression with a polynomial of the order n. Preferred orders are n=0 (mean value formation) and n=1 (linear regression) with the remaining sampling points (cf. FIG. 4, dotted line). Another option is the extrapolation by means of a non-linear function, e.g. the modeling of an exponential increase or drop of c.sub.bi.

[0062] Instead of a temporal interpolation, an interpolation can also take place on the basis of a model for the change of c.sub.bi as in Formula 6 (cf. FIG. 5). A polynomial-based regression is also possible here: It applies in a first approximation: e.sup.−x≈1−x, where the deviation for x<0.3 amounts to less than 5%. It thus applies to Kt/V<0.3 in a good approximation:

[00007]$\begin{array}{cc}{c}_{\mathrm{bi}}\left(t\right)=c_{\mathrm{bi}}\left(0\right)+\left(c_{\mathrm{di}}-c_{\mathrm{bi}}\left(0\right)\right).Math.\left(\frac{\mathrm{Kt}}{V}\right)& \left[7\right]\end{array}$

[0063] c.sub.bi(0) can thus also be determined by a linear fit of an application against Kt/V (cf. FIG. 5). Changes in the flows determining the clearance can hereby be determined better.

[0064] Conversion to the Predialytic Sodium Ion Concentration in the Blood Plasma of the Dialysis Patient

[0065] The predialytic plasma-equivalent conductivity c.sub.bi(0) determined as described above can now be converted by means of a model for the relationship between temperature-compensated conductivity and electrolyte composition to a predialytic sodium ion concentration in the blood plasma of a dialysis patient ĉ.sup.Na.sub.bi(0).

[00008]$\begin{array}{cc}\begin{array}{c}{\tilde{c}}_{\mathrm{bi}}^{\mathrm{Na}}\left(0\right)=.Math.f\left(c_{\mathrm{bi}}\left(0\right),{\tilde{c}}_{\mathrm{bi}}^j\left(0\right)\right)\\ =.Math.a_0+a_1.Math.c_{\mathrm{bi}}\left(0\right)+\underset{j}{.Math.}.Math.b_j.Math.{\tilde{c}}_{\mathrm{bi}}^j\left(0\right)\end{array}& \left[8\right]\end{array}$

[0066] ĉ.sup.j.sub.bi(0) designates the concentration of electrolytes other than Na, e.g. potassium, which have an influence on the conductivity. Their concentration can be determined by the user by a blood analysis and can be input manually via the user interface 8 or via a data link 9 with an external memory medium or a database. A higher precision can be achieved with knowledge of ĉ.sup.j.sub.bi(0), with the adopting of standard values generally being sufficient. The factors a.sub.0, a.sub.1 and b.sub.j are in this respect fixedly stored in the processing unit.

[0067] Storage and Trend Analysis

[0068] The predialytic sodium ion concentration in the blood plasma of the dialysis patient ĉ.sup.Na.sub.bi(0) can now be displayed at the user interface 8 or can be forwarded via the data link 9 to an external storage medium or to a database. The user can be informed from a trend analysis of the current and past determinations of ĉ.sup.Na.sub.bi(0) of systematic trends of the predialytic sodium ion concentration in the blood plasma of the dialysis patient and its fluctuation. By a comparison of the determined change rate and of the fluctuation of ĉ.sup.Na.sub.bi(0) with stored reference values, the user can be informed of critical values of these parameters on the exceeding of predefined limits.

[0069] The dialysis machine in accordance with the invention described in more detail above therefore inter alia comprises the following capabilities for determining the predialytic sodium ion concentration of a dialysis patient due to the algorithm stored in the processing unit and the construction features described further above:

[0070] A range in which stable conductivities and dialysis conditions are present can be looked for in the initial phase of the dialysis (e.g. <10 min) by means of the processing unit from data sets stored therein and comprising conductivities and flows and information on disturbances of the dialysis regime (e.g. bypass switchovers). For this purpose, different stability criteria (e.g. time interval from the last concentration change or change in the pump conveying rate, standard deviation or increase in conductivity) are stored and evaluated in the processing unit. An averaging of c.sub.di and c.sub.do can take place within this range to reduce fluctuations. The time offset between c.sub.di and c.sub.do present due to the hydraulic flow paths can be taken into account in that the values of c.sub.di at the time t, but of c.sub.do at the time t+t.sub.F, are used in the calculation of c.sub.bi, where t.sub.F corresponds to the flow time of the dialyzate between the two conductivity sensors. If a determination of c.sub.bi is not possible within the first 5 minutes of the dialysis treatment due to instable dialysis conditions, sampling points can be determined at times of stable dialysis conditions for c.sub.bi within the first 30 minutes of the dialysis treatment and an extrapolation to the initial value can be carried out at the start of dialysis. The value of the initial c.sub.bi determined in this manner is converted by means of an electrolyte model into a predialytic sodium ion concentration in the blood plasma of the dialysis patient, since ĉ.sup.Na.sub.bi(0)=f (c.sub.bi). The predialytic sodium ion concentration in the blood plasma of the dialysis patient ĉ.sup.Na.sub.bi(0) can be stored in a patient-specific manner on an internal or external storage medium (patient card, transmission via network, etc.) at the latest at the end of the dialysis treatment. Together with the ĉ.sup.Na.sub.bi(0) from previous treatments, the variability of ĉ.sup.Na.sub.bi(0) can be calculated and provided to the physician as a display parameter. ĉ.sup.Na.sub.bi(0) and its variability can be displayed directly after its calculation instead of at the end of the dialysis. This is generally possible immediately after the first successful OCM measurement (after an approximately 20 minute treatment duration). It can, however, also only be possible later on a delay in the first successful OCM measurement.

[0071] According to the current prior art and to the typical practice in dialysis operation, both the predialytic sodium ion concentration in the blood plasma of the dialysis patient with respect to other electrolytes is a preferred value and the determination thereof by conductivity measurements is a preferred method. An embodiment of the dialysis machine in accordance with the invention based thereon was described above. However, the method described for sodium and for the LF measurement can also be extended to all other substances in which a conclusion on blood-side parameters can be drawn from a dialyzate-side concentration measurement with known clearance. Corresponding sensors are then required for this purpose. If the corresponding substance is already present in the inflowing dialyzate, the conductivity sensors 5 and 6 have to be replaced with sensors which specifically determine the concentration of the substance whose predialytic plasma concentration is to be determined. In this respect, e.g., ion-selective electrodes can be used for measuring the concentration of potassium, calcium, magnesium and chloride. However, other measuring methods are also conceivable for measuring electrolytes, e.g. also by NMR. Sensor 5 can be dispensed with if the concentration upstream of the dialyzer is determined in that a bypass switchover takes place at a specific point in time by which the fresh dialyzate can be measured directly by sensor 6, under the condition that it is ensured that the respective concentration during the time required for the determination of the predialytic plasma value does not change substantially. The value in the fresh dialyzate can likewise already be known from manufacturer's data and from an exact knowledge of the mixing system so that a continuous determination upstream of the dialyzer can be dispensed with. Sensor 5 can in particular be omitted with substances which are not present in the fresh dialyzate. With knowledge of the clearance of these substances, e.g. from the conductivity-based determination of the dialyzer clearance and an approximation to the clearance of the corresponding substance by means of a stored correction factor, their predialytic concentration can be determined according to the above-described method. In this respect, sensor 6 can also determine a spectroscopic value such as the absorption or the fluorescence, wherein a calculation process is stored in the evaluation unit which draws a conclusion on substance concentrations from the spectral measurements. Sensors can be used to determine the glucose concentration which determine the rotation of the polarization direction of polarized light on passing through a measurement path containing the sample solution. Alternatively, the change in the refractive index can be determined by refractometry. As above, a calculation process then has to be stored in the evaluation unit with whose aid a conclusion can be drawn on substance concentrations. Fluctuations in the blood glucose can be an important indicator for an insufficient diabetes treatment. Furthermore, instead of the sensors 5 and 6, a plurality of sensors can be used at their positions with whose aid the predialytic concentration of different substances can be determined in accordance with the described method. A predialytic concentration determined for a first parameter can then be used as described above for improving the precision in the determination of the concentration of a further parameter.

[0072] In summary, it results that the sodium concentration in the blood plasma is an important diagnostic parameter in dialysis patients. The determination of this value by blood analyses is, however, complex and expensive so that alternatives are being looked for. The calculation of the concentration of different substances in the blood via conductivity measurements on the dialyzate side in the extracorporeal circuit is already described in the prior art. This calculation of the predialytic blood concentration is then based on the extrapolation of the values. Reliable measurements are, however, only present after around 20 minutes from the start of treatment. Measurements at the start of the treatment are subject to large fluctuations which result in larger errors in the concentration determination. These errors are reduced by the invention. In accordance with the invention, ranges in the course of treatment in which no reliable calculation is possible are, on the one hand, not considered in the evaluation. On the other hand, the flow time of the dialyzate between the two conductivity sensors is considered in the calculation of the plasma concentration. The results of the conductivity measurements which take place simultaneously are used in the calculation formula in the prior art. If, however, larger fluctuations occur in the conductivity of the dialysis solution, an error occurs due to the time offset which the dialysis solution requires for running through the filter because the difference no longer correctly reflects the concentration change in the filter. This error is reduced by the consideration of the flow time.