Dialysis device with a device for determining at least two hemodialysis parameters

Description

[0001] The invention relates to a dialysis device with a device for determining at least one first and second hemodialysis parameter. Furthermore, the invention relates to a dialysis system with a dialysis device comprising a dialyzer and an extracorporeal blood circulation, and a device for determining at least one first and second hemodialysis parameter. The invention also relates to a computer program product comprising commands which, when executed by a computer, cause the program to perform a method for determining at least one first and second hemodialysis parameter during a dialysis treatment with a dialysis device.

[0002] In chronic blood purification therapies such as hemodialysis, hemofiltration, and hemodiafiltration, blood is passed through an extracorporeal blood circuit via a blood treatment unit, such as a dialyzer or filter. Hereinafter, dialyzer and filter are used synonymously. Access to the vascular system is often surgically created via an arteriovenous fistula, which is generally punctured with an arterial and venous cannula. The use of a vascular graft is also possible. When the term "vascular access" is used below, it refers to any type of access to a patient's vascular system. Specifically, vascular access refers to the enlarged blood vessels created by connecting an artery and a vein in the patient. This vessel may also be a graft-constructed vessel.

[0003] Various parameters are of interest for monitoring dialysis treatment; these are referred to below as hemodialysis parameters.

[0004] A hemodialysis parameter relevant to dialysis efficiency is the dialysis dose Kt / V, which is a dimensionless quantity. The dialysis dose is the quotient of the product of urea clearance K (ml / min) and dialysis duration t (min) and the urea distribution volume V. Clearance is the amount of blood plasma that is completely removed from a specific substance per unit of time as it passes through the kidneys or the membrane of a dialyzer. "Dialysance" is a common term in dialysis literature (e.g., Petitclerc, Gotch, etc.) when referring to the approximation of a reference concentration, such as sodium, i.e., when the substance in question is present on both sides of the membrane. Online determination of the ionic dialysance can be performed to determine the clearance of small molecules, such as urea. The relationship between the terms clearance K and dialysance D is explained below.

[0005] For physicians, clearance K is "the partial flow (in ml / min) of blood that is completely cleared of the substance in question." Mathematically, however, the restriction to the case where transport occurs into a space where the substance is not present is unnecessary. The underlying kinetics (one-pool model) is described by V * dc b / dt = - K (cb - cd ), where V: volume of distribution, dc: change in concentration, b: blood, d: dialysate; K: "transmembrane flow", "reaction kinetics", ...; and depends directly on the membrane properties and the diffusion coefficient of the substance in question, with the units [K] = ml / min, [c] = number / ml, V: volume of distribution. For cd = 0, the term clearance would be used. For cd > 0, K still correctly describes the kinetics, but the intuitive definition is then "partial flow that is completely brought to the concentration of the dialysate." The term "dialysis" is used for this.In dialysis, the term "clearance" is generally used to refer to substances not present in the dialysate (e.g., urea, creatinine, beta-2-methylglyoxal, antibiotics), while "dialysance" refers to substances present in the dialysate (e.g., sodium). Numerically, sodium dialysance would always be equivalent to sodium clearance, with sodium clearance being used when dialyzing against RO water. Clearance K and dialysance D, as used in this description, are synonymous.

[0006] Several state-of-the-art methods exist for determining clearance K (dialysance). A widely used method is the measurement of ionic dialysance using the so-called Online Clearance Monitoring OCM (Fresenius Medical Care), which allows for the indirect determination of urea clearance during dialysis. Since the treatment duration (t) is known, the system can determine the dialysis dose Kt / V online during dialysis after inputting the urea distribution volume (V).

[0007] The online determination of clearance is based on the temporal change of a physical or chemical property of the dialysis fluid within the dialysis fluid system. A physical or chemical property of the dialysis fluid is changed upstream of the dialyzer, and the temporal change of the physical or chemical property of the dialysis fluid downstream of the dialyzer, attributable to this upstream change, is recorded. This temporal change of the physical or chemical property of the dialysis fluid within the dialysis fluid system is subsequently referred to as the bolus.

[0008] EP 0 911 043 B1 describes a dialysis device that includes a computing and evaluation unit configured to determine the dialysance D from the quantity of a substance added as a bolus to the dialysate upstream of the dialyzer, the integral over time of the change in the concentration of that substance in the dialysate downstream of the dialyzer attributable to the bolus, and the dialysate flow rate. A bolus can be administered, for example, by changing the sodium ion concentration, such as by adding a NaCl-containing solution. This addition can be performed online by varying the dosage volume of a concentrate. The change can be achieved by adding more or less concentrate (compared to the baseline dosage). This allows for changes in the form of a positive or negative bolus in both directions.It should be noted that it is not necessary to add a pure NaCl solution as a concentrate; a solution of various ions can also be added. For bolus generation, the conductivity is generally the only relevant factor; that is, the shape of the bolus, which can be described by its area, amplitude, and / or duration, is influenced by the change in concentration of all ions present in the dialysate.

[0009] Another important hemodialysis parameter for dialysis treatment is the "blood access flow," which is referred to below as blood flow in the vascular access Qa. Various methods for determining Qa are currently available. Methods for determining Qa are known that are based on measuring clearance in different blood flow directions.

[0010] EP 0 928 614 B1 describes a dialysis device that has a means of detecting a temporal change in the physical or chemical properties of the dialysis fluid in the dialysis fluid system, attributable to the bolus, for two different dialysis conditions. Under the first dialysis condition, the first blood line delivers blood from a downstream part of a patient's vascular access into the dialyzer, and the second blood line delivers blood from the dialyzer towards an upstream part of the vascular access. Under the second dialysis condition, the first blood line delivers blood from an upstream part of the vascular access, and the second blood line delivers blood towards a downstream part of the vascular access.The established method for determining Qa is based on ascertaining a dialysance value for the first dialysis condition and a dialysance value for the second dialysis condition, and then calculating the blood flow in the vascular access Qa from these two dialysance values. The determination of clearance (dialysance) for the different dialysis conditions can be performed online using established methods (Online Clearance Monitoring, OCM).

[0011] From US Patent 2005 / 0148923 A1, a dialysis device is known which has a device for determining a hemodialysis parameter. The dialysis device has a dialyzer that is divided by a semipermeable membrane into a first compartment, which is part of an extracorporeal blood circuit, and a second compartment, which is part of a dialysis fluid system. The determination of the hemodialysis parameter is based on generating a measurable change in the concentration of a substance in the blood circuit, wherein the concentration of this substance in the dialysis fluid system is measured at the outlet of the dialyzer, and the dialysis parameter is determined based on the integrated concentration.

[0012] The invention is based on the objective of determining at least two hemodialysis parameters during dialysis treatment with the greatest possible accuracy and with the lowest possible burden on the patient.

[0013] The solution to this problem is achieved according to the invention with the features of the independent claims. The dependent claims relate to preferred embodiments of the invention.

[0014] The dialysis device according to the invention comprises a device for determining at least one first and second hemodialysis parameter. The dialysis device is configured to be connected to a dialyzer, which is divided by a semipermeable membrane into a first compartment, which is part of an extracorporeal blood circulation, and a second compartment, which is part of a dialysis fluid system. The dialysis device is further configured to be connected to a first and a second blood line, which are connected to an inlet and outlet of the first compartment of the dialyzer, respectively. The blood lines (blood tubing system) are part of the extracorporeal blood circulation.

[0015] The device for determining hemodialysis parameters comprises a device for generating a temporal change in a physical or chemical characteristic of the dialysis fluid contained in the dialysis fluid system in a dialysis fluid supply line to the dialyzer in the form of a bolus, and a device for detecting a temporal change in the physical or chemical characteristic of the dialysis fluid in a dialysis fluid discharge line from the dialyzer that is attributable to the bolus. The change in the physical or chemical characteristic can be measured upstream of the second compartment of the dialyzer, and the change in the characteristic attributable to the change in the parameter can be measured downstream of the second compartment of the dialyzer.

[0016] The change in the parameter can be made for a first dialysis condition, under which the first blood line carries blood from a downstream part of a vascular access of the patient and the second blood line carries blood towards an upstream part of the vascular access, and / or for a second dialysis condition, under which the first blood line carries blood from an upstream part of the vascular access and the second blood line carries blood towards a downstream part of the vascular access.

[0017] Physical or chemical parameters can be various properties of the dialysis fluid that can be measured within the dialysis system. These properties can be measured directly, or parameters that correlate with them can be measured. For example, the parameter could be the concentration of a substance in the dialysis fluid (substance concentration), such as the concentration of one or more electrolytes, particularly the sodium concentration. Other parameters could include the conductivity or optical properties of the dialysis fluid, such as the absorbance or the rotation angle of light (glucose) or the propagation speed of ultrasound. Alternatively, chemical sensors can be used for measurement.

[0018] Furthermore, the dialysis device according to the invention has a computing and evaluation unit that interacts with the device for generating a change in a physical or chemical parameter and the device for detecting a temporal change in a physical or chemical parameter, and which is configured such that at least one value for the clearance of the dialysis treatment is determined on the basis of the change in the physical or chemical parameter in the form of a bolus, and at least one hemodialysis parameter is determined on the basis of the at least one value for the clearance.

[0019] The inventor recognized that the nature of the temporal change of the parameter for determining individual hemodialysis parameters, i.e., the shape of the bolus, can be crucial both from the perspective of achieving the most accurate measurement possible and from the perspective of minimizing the burden on the patient. In particular, it has become apparent that a bolus administered for a clearance measurement to determine the dialysis dose Kt / V is not equally suitable for a clearance measurement to determine the blood flow in the vascular access Qb with sufficient accuracy.

[0020] The dialysis device according to the invention also takes into account that it has been shown in practice that various boundary conditions must be met for the determination of hemodialysis parameters, in particular for determining the dialysis dose Kt / V or the blood flow in the vascular access Qa.

[0021] The dialysis device according to the invention is characterized in that different boluses are administered for the different measurements. A "large bolus" is administered for determining the first hemodialysis parameter, while a "small bolus" is administered for determining the second hemodialysis parameter. A small bolus generally has the advantage of less burden on the patient, while a large bolus generally has the advantage of greater measurement accuracy.

[0022] The device for generating a change in a physical or chemical parameter is designed in such a way that that, for the determination of a first hemodialysis parameter, at least one bolus for the determination of the first hemodialysis parameter with a first quantity (A) is generated, wherein the computing and evaluation unit is configured such that, on the basis of the change in the physical or chemical characteristic in the form of at least one bolus for the determination of the first hemodialysis parameter, at least one value for the clearance of the dialysis treatment is determined, on the basis of whichon the basis of which the first hemodialysis parameter is determined, and that, for the determination of a second hemodialysis parameter, at least one bolus for the determination of the second hemodialysis parameter with a second quantity (A') is generated, wherein the computing and evaluation unit is configured such that, on the basis of the change in the physical or chemical characteristic in the form of at least one bolus for the determination of the second hemodialysis parameter, at least one value for the clearance of the dialysis treatment is determined, on the basis of which the second hemodialysis parameter is determined.

[0023] A first aspect of the invention provides that the first quantity (A) is larger than the second quantity (A'), while a second aspect provides that the distance of the first quantity (A) to a reference quantity is greater than the distance of the second quantity (A') to a reference quantity.

[0024] The size of the bolus is determined by its shape. The shape of the bolus can be characterized by an integral (area) or by the amplitude and / or duration of the bolus. The temporal progression of the change does not need to be described exactly, but can also be approximated.

[0025] The quotient between the first area (A) and the second area (A') is in particular greater than 2.5, in particular greater than 2.7, in particular greater than 3.

[0026] One embodiment according to the first aspect of the invention provides that the at least one bolus for determining the first hemodialysis parameter is characterized by a first area and the at least one bolus for determining the second hemodialysis parameter by a second area, wherein the area of ​​the first area (first area) is larger than the area of ​​the second area (second area). Consequently, with a "large bolus," the first hemodialysis parameter can generally be determined with higher accuracy, but this could result in the determination of this parameter being associated with a greater burden for the patient. While the second hemodialysis parameter can generally only be determined with lower accuracy with a "small bolus," any potential burden on the patient is eliminated.In this context, the area of ​​the bolus is understood to be the area of ​​the region that lies between the graph of a function describing the change over time of the physical or chemical parameter and the graph of a reference function.

[0027] The reference function can be a baseline determined by the behavior of the physical or chemical parameter before and / or after the bolus. The baseline can be a straight line, a curve, or any other function that deviates from a straight line. The straight baseline can have no slope or a slope. The baseline can describe the behavior of the parameter, adjusted for noise signals or fluctuations.

[0028] While measurement accuracy can generally be improved by taking multiple measurements and statistically evaluating the results, this approach has the disadvantage that determining the hemodialysis parameter is relatively time-consuming and could place a greater burden on the patient due to the multiple measurements.

[0029] According to the second aspect of the invention, a reference value is defined, wherein the size of the at least one bolus for determining the first hemodialysis parameter and the size of the at least one bolus for determining the second hemodialysis parameter are referenced to this reference value. The reference value can be the noise in the system, and the distance to the reference value can be a signal-to-noise ratio. For accurate measurement, the largest possible signal-to-noise ratio is generally sought, which increases with increasing bolus size, but this also increases the burden on the patient. Analogous to the first aspect, the second aspect of the invention aims for a larger signal-to-noise ratio for determining the first hemodialysis parameter than for determining the second hemodialysis parameter.

[0030] The advantages of the invention are particularly evident when the first hemodialysis parameter is the blood flow in the vascular access Qb or of a recirculation flow in a vascular system and the second hemodialysis parameter is the dialysis dose Kt / V.

[0031] To determine the blood flow in the vascular access, the device for generating a change in a physical or chemical parameter can be designed such that, for a first dialysis condition, a first bolus with the first area (A) is generated, and for the second dialysis condition, a second bolus with the first area (A) is generated, wherein the computing and evaluation unit is configured such that, based on the change in the physical or chemical parameter in the form of the first bolus with the first area (A) under the first dialysis condition, a first value for the clearance is determined, and based on the change in the physical or chemical parameter in the form of the second bolus under the second dialysis condition, a second value for the clearance is determined, on the basis of which the blood flow in the vascular access is determined.

[0032] Under the first dialysis condition, the first blood line delivers blood from a downstream part of the patient's vascular access and the second blood line delivers blood towards an upstream part of the vascular access, and under the second dialysis condition, the first blood line delivers blood from an upstream part of the vascular access and the second blood line delivers blood towards a downstream part of the vascular access.

[0033] In other words, the dialysis condition encompasses the needle orientation, which can be described, for example, as normal or inverted. Changing the needle orientation, or the first and second dialysis conditions, also includes exchanging the needles or reversing the flow through the needles. This can be achieved, for example, by reversing the blood pump's flow direction or by using a flow reversal device that connects the venous needle (used in normal treatment) to the arterial blood tubing (or a section thereof) and vice versa. This flow reversal device can be manually operated or automatically controlled. An example of a manually operated flow reversal device is the Twister® from Fresenius Medical Care Germany GmbH.

[0034] In both dialysis conditions, preferably all other parameters influencing clearance are the same or nearly the same during measurements. If these other parameters are not the same, the dialysis device can be designed such that, when determining the blood flow in the vascular access or a recirculation flow in a vascular system, the results are mathematically corrected for the influence of these differences in other parameters at certain clearance values. For example, an increased dialysis fluid flow can be corrected by means of a stored relationship between clearance and dialysis fluid flow. This relationship can be stored in the form of a table, an equation, or an algorithm.

[0035] An alternative embodiment provides that the dialysis device is designed such that, in the first dialysis condition, a clearance value is not measured but estimated, and in the second dialysis condition, a clearance value is measured using the method described above by changing a physical or chemical parameter. The blood flow in the vascular access Qa is then determined using the estimated clearance value and the measured clearance value.

[0036] Estimating clearance instead of measuring it is generally only sufficiently accurate for determining the first dialysis parameter during the first dialysis condition, particularly blood flow in the vascular access, since fistula recirculation is not expected or is at least minimal during the first dialysis condition. However, fistula recirculation does occur during the second dialysis condition. Therefore, estimating the second dialysis parameter during the second dialysis condition is pointless.

[0037] The alternative embodiment with an estimation of the clearance instead of a measurement for determining the first clearance value under the first dialysis condition for determining the first dialysis parameter, in particular the blood flow in the vascular access, is of its own inventive significance, i.e. the determination of the first dialysis parameter with this method can be carried out independently of the determination of a second dialysis parameter and independently of the inventive principle of measuring boluses of different sizes.

[0038] In the alternative embodiment, to determine the blood flow in the vascular access Qa, the device for generating a change in a physical or chemical parameter is designed such that a bolus with the first area (A) is generated for a second dialysis condition, wherein the computing and evaluation unit is configured such that a first clearance value is determined based on an estimate of the clearance for the first dialysis condition and a second clearance value is determined based on the change in the physical or chemical parameter in the form of the bolus with the first area (A) under the second dialysis condition, on the basis of which the blood flow in the vascular access is determined.

[0039] If the determination of the first hemodialysis parameter, in particular the blood flow in the vascular access Qa, is carried out according to the procedure described above based on an estimation of the first clearance value instead of a measurement of the clearance value with a bolus, the dialysis device may optionally be further configured to perform individual steps for the determination of Qa only when certain conditions are met that indicate sufficient accuracy.

[0040] The dialysis device can be set up in such a way that, after the estimation of the first clearance value, the measurement of the second clearance value is only carried out if a predetermined condition for the estimation of the first clearance value is met, for example, if the estimated clearance value does not meet certain plausibility criteria, for example, if the deviation of the estimated clearance value from a predetermined value is too large.

[0041] If the deviation is too large, the first clearance value can be measured after administering a bolus to obtain a value with sufficient accuracy. Then the second clearance value can be measured.

[0042] Instead of verifying the estimated first clearance value, the blood flow in vascular access Qa, determined from the first and second clearance values ​​after estimating and measuring the second clearance value, can also be checked. If the blood flow in vascular access Qa is not meaningful or deviates too significantly from an expected measured blood flow value in the vascular access, the blood flow can be determined based on two consecutive measurements with a first and second bolus. For this purpose, the dialysis machine can be configured to also perform a measurement of the first clearance value.

[0043] Clearance can be estimated, for example, using the equations published in Sargent, A. & Gotch, F., "Principles and biophysics of Dialysis" in "Replacement of renewal function by dialysis", 4th ED. To determine an estimated clearance value, certain dialyzer parameters can be determined in the laboratory, or manufacturer specifications can be used, such as a code (barcode) or printed number on the dialyzer that the user must transfer, or a parameter stored in the dialysis machine by selecting a dialyzer type. Furthermore, blood flow, dialysate flow, ultrafiltration flow across the dialyzer membrane, and / or substitution flow can be considered. The equation used for clearance or dialysance might be (without ultrafiltration or substitution flow): D = Q b e γ − 1 e γ − Q b Q d , γ = k 0 A Q d − Q b Q b Q d ko A Mass transfer coefficient-membrane area product Q b is the blood flow through the dialyzer Q d is the efficient dialysate flow through the dialyzer.

[0044] The clearance can also be estimated using the method described in EP 1 698 360 B1. EP 1 698 360 B1 discloses the following method for estimating the clearance: The clearance K, which changes over time during therapy, is calculated according to the following equation: K t = K L * C t K is the clearance value that changes with the treatment time t. KL is the clearance of the respective dialyzer type determined under laboratory conditions. C(t) is a correction factor that describes the reduction in filtration efficiency KL over the treatment time, e.g., due to the formation of a secondary membrane. C is less than or equal to 1, C(t) = 1 - (X1 * t), where X1 is an empirically determined patient / filter factor.

[0045] KL is a function of several device parameters: K L = f Q b ; Q d ; Q u ; FT Qb is the blood flow through the dialyzer. Qd is the efficient dialysate flow through the dialyzer. QU is the ultrafiltration flow across the membrane. FT is the filter type.

[0046] KL is usually determined from tables or three-dimensional matrices whose values ​​were measured under laboratory conditions and which are given in the instructions for use of the different dialyzers.

[0047] If the first clearance value is estimated or measured under the first dialysis condition and the second clearance value is measured under the second dialysis condition, the first dialysis parameter, in particular the blood flow in the vascular access Qa, can be calculated from the first and second clearance values.

[0048] The blood flow in vascular access Qa can be calculated from equation (4) given in the following figure description.

[0049] Alternatively, the blood flow in vascular access Qa can be determined using the following equation: Qa = 1 / R − 1 * Qb Qa is the blood flow in the vascular access; R is the fistula recirculation (with reversed needle position); Qb is the blood flow through the dialyzer.

[0050] To determine the blood flow in the vascular access Qa according to the equation above, the recirculation in the vascular access (fistula recirculation) R must first be determined. The recirculation in the vascular access can also be estimated. An estimate for recirculation in the vascular access can be derived from measured clearance and estimated clearance under different dialysis conditions, for example, from the ratio of measured clearance to estimated clearance, taking cardiopulmonary recirculation into account.

[0051] A procedure for determining the blood flow rate in the vascular access by estimating the clearance can therefore include the following steps: 1. Estimating clearance based on dialyzer parameters (e.g., manufacturer data, barcode, etc.); 2. Changing the dialysis condition, in particular inverting the needle orientation; 3. Measuring clearance under the changed dialysis condition or with the needle inverted; 4. Determining the blood flow rate in the vascular access Qa using the estimated and measured clearance, where step 4 may include steps 4a1 and 4b1 or step 4a2; 4a1. Estimating recirculation in the vascular access from measured and estimated clearance, for example, from the ratio of measured clearance to estimated clearance, taking cardiopulmonary recirculation into account. The estimated clearance obtained using, for example, the estimation methods described above may be too high due to cardiopulmonary recirculation.To determine recirculation in the vascular access, cardiopulmonary recirculation can therefore be estimated, for example, by using a typical value or a value previously determined for the patient and thus reducing the estimated clearance. For example, as a first approximation, it can be assumed that total recirculation is the sum of cardiopulmonary recirculation and recirculation in the vascular access, and accordingly, the estimated clearance is reduced by the proportion of cardiopulmonary recirculation. As another approximation, total recirculation can be estimated from the estimated clearance and the measured clearance, and then, to determine recirculation in the vascular access, cardiopulmonary recirculation can be subtracted from total recirculation; 4b1. Determination of the blood flow value in the vascular access, for example, according to the formula Qa = (1 / R-1)*Qb; 4a2.Determination of the blood flow rate in the vascular access using equation (4), and optionally a determination of the recirculation according to the formula Qa = (1 / R-1)*Qb solved for R. .

[0052] The accuracy of the approaches via 4a1 and 4a2 depends on the accuracy of the estimates. The estimated clearance can be calculated from the manufacturer's specifications and the flow rates. However, this overestimates the clearance because the reduction due to cardiopulmonary recirculation is not taken into account. Overestimating the clearance when using the recirculation approach (step 4a.1) leads to high values ​​for recirculation and thus to low values ​​for Qa (step 4b.1). Directly substituting the estimated clearance into equation (4) leads to the same result (step 4a2). Therefore, when estimating the clearance from the manufacturer's specifications, a typical value for cardiopulmonary recirculation (e.g., 5%, 10%, or 15%) can be used to improve the estimated clearance.

[0053] To determine blood flow in the vascular access, the device for generating a change in a physical or chemical parameter can be designed such that the concentration of a substance in the dialysis fluid, particularly the sodium concentration, is increased for determining the first and second clearance values ​​under the first and second dialysis conditions, or decreased for determining the first and second clearance values ​​under the first and second dialysis conditions. When referring to a change in "a substance, particularly the sodium concentration," this always implies that, in the case of ions, the corresponding counterion concentrations must also be changed. For example, elemental sodium is not present in the solution, but rather positively charged sodium ions. The corresponding negative counterions can be chloride ions. Typically, the negative counterions are chloride ions.Other counterions in a conventional dialysis fluid are carbonate or bicarbonate ions. In other words, changing the concentration of a substance involves changing the concentration of one or more types of uncharged molecules, and changing the concentration of one ion and one counterion involves changing the concentration of several types of ions and counterions.

[0054] The inventor recognized that a bolus of sufficient size for determining the dialysis dose Kt / V is not sufficient for determining the blood flow in the vascular access Qa with sufficient accuracy and reliability. The reason for this appears to be that determining the blood flow in the vascular access Qa requires two values, and the equation for calculating Qa incorporates two values, meaning that measurement errors can have a much greater impact than if a hemodialysis parameter were determined based on only one measurement.

[0055] One embodiment of the dialysis device according to the invention provides a control and computing unit that interacts with the device for generating a change in a physical or chemical parameter and the device for measuring a temporal change in a physical or chemical parameter. During blood treatment, this control and computing unit initiates the generation and recording of the change in the physical or chemical parameter to determine a hemodialysis parameter. The control and computing unit can automatically perform the change and recording of the parameter during blood treatment, taking into account specific time parameters. The time for a single or double determination of a dialysis parameter, or the time points for multiple determinations of a dialysis parameter, can be stored in a memory of the control and computing unit.The times can also be entered by medical personnel via an input unit and read into the memory. The control and processing unit can also perform the necessary evaluations of the measurement signals and the calculations, or be programmed to do so.

[0056] The control and processing unit can be designed such that, to determine the first hemodialysis parameter, particularly the blood flow in the vascular access (Qa), the generation and recording of the change in the physical or chemical parameter during blood treatment is initiated only once or twice. A single Qa measurement is generally sufficient. It has been shown that high measurement accuracy can be achieved for Qa determination using a larger bolus. In practice, a variation of approximately 20% is tolerable for Qa measurement to allow trend analysis at typical blood flow rates of approximately 1200 ml / min, which may require a clearance measurement reproducibility of 2% regardless of needle orientation. Since Qa is measured only once per dialysis treatment, a larger bolus is more readily tolerated.

[0057] The control and processing unit can be configured to repeatedly initiate the generation and recording of changes in the physical or chemical parameter during blood treatment to determine the second hemodialysis parameter. Timeframes can be set automatically or manually by medical personnel. It has been shown that sufficient measurement accuracy can be achieved for determining the dialysis dose Kt / V using a bolus smaller than the bolus used to determine blood flow in the vascular access (Qb). Since a small bolus poses no burden to the patient, multiple measurements can be performed without difficulty during blood treatment.

[0058] The device for generating a change in a physical or chemical parameter can be configured for determining the first hemodialysis parameter such that the concentration of a substance in the dialysis fluid, particularly the sodium concentration, is increased or decreased for determining the first and second clearance values ​​under the first and second dialysis conditions. Determining the first hemodialysis parameter with two "negative" boluses has the advantage that the substance concentration in the dialysis fluid, especially the sodium concentration, is not increased. An increase in sodium concentration can lead to an increase in the patient's blood pressure.Determining the first hemodialysis parameter with two "positive" boluses is associated with a lower risk of intradialytic drops in blood pressure and cramps that can be caused by a decrease in Na concentration.

[0059] If multiple measurements are required to determine the second dialysis parameter, the device for generating a change in a physical or chemical parameter can be designed such that the concentration of a substance in the dialysis fluid, particularly the sodium concentration, is increased for a preceding measurement and decreased for a subsequent measurement, or decreased for a preceding measurement and increased for a subsequent measurement. Alternating the administration of a "positive" and a "negative" bolus has the advantage of a smaller change in the substance concentration in the dialysis fluid, especially the sodium concentration.

[0060] Furthermore, the invention relates to a computer program product comprising commands which, when the program is executed by a computer, cause it to perform the above-described methods for determining at least one first and second hemodialysis parameter during a dialysis treatment with a dialysis device.

[0061] An embodiment of the invention is described in detail below with reference to the figures.

[0062] They show: Fig. 1 an embodiment of the dialysis device according to the invention in a simplified schematic representation, Fig. 2A the device for specifying a dialysis condition of the dialysis device, wherein a first dialysis condition is specified, Fig. 2B the device for specifying a dialysis condition of the dialysis device, wherein a second dialysis condition is specified, Fig. 3 the change over time of the physical or chemical properties of the dialysis fluid at the inlet and outlet of the dialyzer, Fig. 4 the first and second change over time of the physical or chemical properties of the dialysis fluid at the inlet of the dialyzer for determining a first hemodialysis parameter, wherein a positive bolus is administered, Fig. 5 the change over time of the physical or chemical properties of the dialysis fluid at the inlet of the dialyzer for determining a second hemodialysis parameter, Fig.6. The first and second temporal changes in the physical or chemical properties of the dialysis fluid at the dialyzer inlet for determining a first hemodialysis parameter, whereby a negative bolus is administered. Fig. 7. A sequence of positive and negative boluses for the continuous determination of the second hemodialysis parameter during blood treatment. Fig. 8. The conductivity of the dialysis fluid upstream and downstream of the dialyzer, measured in an experiment. Fig. 9. A flowchart illustrating the determination of a first dialysis parameter based on a first and a second measurement of a first and second clearance value, respectively, under a first and second dialysis condition. Fig. 10. A flowchart illustrating the determination of a first dialysis parameter based on an estimation of a first clearance value and a measurement of a second clearance value under a first and second dialysis condition, respectively.

[0063] Fig. 1 The essential components of an embodiment of the dialysis device according to the invention are shown in a simplified schematic representation. Since the measurement methods for determining the hemodialysis parameters are themselves part of the prior art, only those aspects of the methods essential to the invention are described.

[0064] In operation, the dialysis device is connected to a dialyzer and an extracorporeal blood tubing system. The dialysis device is programmed to perform the inventive method for determining the dialysis parameters when connected to both a dialyzer and an extracorporeal blood tubing system, as well as to a patient.

[0065] The dialysis device according to the invention can be equipped with a dialyzer 1, which is divided by a semipermeable membrane 2 into a first compartment 3 and a second compartment 4. The first compartment 3 of the dialyzer 1 is part of a Fig. 1 The extracorporeal blood circulation 5 is shown in dashed lines, and the second compartment 4 of the dialyzer 1 is part of a dialysis fluid system 6 shown in dashed lines.

[0066] The extracorporeal blood circuit 5 comprises a first blood line 7, to one end of which a first cannula 8 is connected, and a second blood line 9, to one end of which a second cannula 10 is connected. The first cannula 8 is connected to a downstream portion 11 of a vascular access 12 of the patient, and the second cannula 10 is connected to an upstream portion 13 of the vascular access 12. The direction of blood flow in the vascular access is indicated by an arrow. The other end of the first blood line 7 is connected to an inlet 3a of the first compartment 3, and the other end of the second blood line 9 is connected to an outlet 3b of the first compartment 3, so that the patient's blood flows from the downstream portion 11 of the vascular access into the first compartment 3 and from the first compartment 3 into the upstream portion 13 of the vascular access 12. The blood is pumped in the extracorporeal blood circulation 5 by a blood pump 14.

[0067] The dialysis device can include a device 15 for specifying a first and a second dialysis condition, which is shown in a highly simplified form in Figures 1A and 1B. The device 15 for specifying a dialysis condition is designed such that a first dialysis condition can be specified in which the first blood line 7 delivers blood from the downstream part 11 of the vascular access 12 and the second blood line 8 delivers blood towards the upstream part 13 of the vascular access 12, and a second dialysis condition can be specified in which the first blood line 7 delivers blood from the upstream part 13 of the vascular access 12 and the second blood line 9 delivers blood towards the downstream part 11 of the vascular access 12. Fig. 2A shows the direction of blood flow under the first dialysis condition and Fig. 2B This shows the direction of blood flow under the second dialysis condition. In the vascular-side sections of the tubules, the blood flow is reversed.

[0068] The device 15 for specifying a dialysis condition can include an automatically actuated arrangement of valves that allow an exchange of device-side and patient-side sections of the blood lines, as shown with dashed lines in Figures 1A and 1B.

[0069] Device 15 can also be a manually operated device that is not connected to the dialysis machine, in particular to a control unit of the dialysis machine. The dialysis machine can have an input device with which medical personnel can enter the desired dialysis condition. The input device can also indicate which dialysis condition has been set or that the dialysis condition has been changed, for example, from one dialysis condition to a second. One such device is the so-called Twister® from Fresenius Medical Care Deutschland GmbH.

[0070] The dialysate is supplied by a dialysate supply device 16, to which a dialysate supply line 17 is connected, leading to an inlet 4a of the second compartment 4 of the dialyzer 2. A dialysate discharge line 18 is connected to the outlet 4b of the second compartment 4, leading to a drain (not shown). The dialysate is pumped through the second compartment 4 of the dialyzer 1 in the dialysate system 6 by a dialysate pump 19.

[0071] The dialysis device has a device 20 for determining a first hemodialysis parameter and a second hemodialysis parameter. In the present embodiment, the first hemodialysis parameter is the dialysis dose Kt / V and the second hemodialysis parameter is the blood access flow Qa.

[0072] The device 20 for determining hemodialysis parameters comprises a device 21 for generating a temporal change of a physical or chemical characteristic of the dialysis fluid in the dialysis fluid system 6 in the dialysis fluid supply line 17 upstream of the second compartment 4 and a device 22 for detecting the temporal change of the characteristic in the dialysis fluid discharge line 18 downstream of the second compartment 4, which is attributable to the temporal change of the characteristic upstream of the dialyzer. In addition, the characteristic can also be detected in the dialysis fluid supply line 17 upstream of the second compartment 4 of the dialyzer 1.

[0073] The change in the parameter upstream of dialyzer 1 over time is subsequently referred to as the input bolus, and the change in the parameter downstream of the dialyzer over time as the output bolus. The output bolus is thus the system's response to the input bolus.

[0074] In the present embodiment, the physical or chemical parameter is the concentration c of a substance in the dialyzer fluid, in particular the sodium concentration, which is changed upstream of the dialyzer 1, i.e., increased or decreased for a predetermined time interval. The device 21 for generating a temporal change of a physical or chemical parameter is, in the present embodiment, part of the device 16 for supplying the dialyzer fluid, which allows a change in the sodium concentration of the dialysate for a predetermined time interval.

[0075] In the present embodiment, the device 22 for detecting the physical or chemical parameter includes a conductivity sensor 22A, which measures the conductivity of the dialysis fluid in the dialysis fluid discharge line 18 as a quantity correlated with the Na concentration. The device 22 for detecting the physical or chemical parameter may also include a further conductivity sensor 22B, which measures the conductivity of the dialysis fluid in the dialysis fluid supply line 17. If the shape of the inlet bolus is known, the conductivity sensor 22B in the dialysis fluid supply line 17 can be omitted. Otherwise, the conductivity in the dialysis fluid supply line 17 can be measured using the conductivity sensor 22B.

[0076] Fig. 3 Figure 1 shows the incoming and outgoing boluses. In this embodiment, the bolus is characterized by the area between the graph of a function describing the change over time of a physical or chemical parameter, for example, the sodium concentration c(t) or the conductivity, and the graph of a reference function. The area is a measure of the bolus size; that is, a larger bolus has a larger area than a smaller bolus. The reference function can be a linear function: f(t) = mt + B, where m is the slope of the function and B is a predetermined base value. In this embodiment, the slope is 1. The base value B can be the sodium concentration (conductivity) of the blood before the bolus is administered. The area of ​​the incoming and outgoing boluses can be determined by calculating the integral over a predetermined integration interval.

[0077] Alternatively, or in combination, other parameters can be used to characterize the bolus and thus determine hemodialysis parameters. An alternative characteristic parameter for the bolus can be its amplitude and duration. The area can be estimated from the amplitude and duration. The amplitude and duration of the bolus alone can also be meaningful parameters if a relationship between the size and duration of a bolus is known.

[0078] The following describes the determination of hemodialysis parameters based on the surface area of ​​the bolus. The other parameters can be used in a comparable manner.

[0079] The dialysis device includes a computing and evaluation unit 23 that interacts with the device 21 for generating a change in a physical or chemical parameter and the device 22 for recording the parameter. This unit can be part of a central computing and control unit 24 of the dialysis device. The central computing and control unit 24 is connected via control and signal lines S1 to S6 to the dialysis fluid pump 19, the blood pump 14, the device 15 for specifying the dialysis conditions, the device 21 for generating a change in a physical or chemical parameter (input bolus), and the conductivity sensors 22A and 22B of the device 22 for recording the parameter (output bolus).The computing and control unit 24 is configured in such a way that the individual components of the dialysis device are controlled during the dialysis treatment in such a way that the following procedure steps for determining the hemodialysis parameters are carried out.

[0080] The individual process steps of a first embodiment for determining a first dialysis parameter are described in Fig. 9 shown.

[0081] The central control and processing unit 24 can, for example, comprise a general-purpose processor, a digital signal processor (DSP) for continuous processing of digital signals, a microprocessor, an application-specific integrated circuit (ASIC), an open-source graphics processing unit (FPGA), or other integrated circuits (ICs) or hardware components to execute the individual process steps for controlling the blood treatment device. A data processing program (software) can run on the hardware components to carry out the process steps.

[0082] Furthermore, an input unit 25 is provided, which is connected to the computing and control unit 24 via a signal line S 7. The input unit 25 allows medical personnel to enter data relating to the determination of hemodialysis parameters. The input unit 25 may have a keyboard. A display unit 26 is provided for displaying the hemodialysis parameters. The input and display units may also be configured as a touch-sensitive screen 27 (touchscreen).

[0083] At the start of the dialysis treatment, or after a fixed time interval has elapsed, or after the medical staff has pressed a button 25A on the touchscreen 27, the blood flow in the vascular access Qa (blood access flow) is determined (step 101).

[0084] The device 15 for specifying the dialysis condition specifies the first dialysis condition ( Fig. 2A ), in order to determine an initial value for the clearance (dialysance) (step 102). The device 21 for generating a change in a physical or chemical parameter then generates an inlet bolus I with a predetermined area ΔM 1 (step 103) ( Fig. 3 The device 22 for recording a physical or chemical parameter then records the input bolus I with area ΔM 1 upstream of the dialyzer 1 and the output bolus II with area ΔM 2 downstream of the dialyzer by measuring the conductivity of the dialyzing fluid upstream and downstream of the dialyzer 1 using the conductivity sensors 22A and 22B. The measured values ​​are stored in a memory 23A of the computing and evaluation unit 24 (step 104).

[0085] The amount of substance ΔM1 supplied upstream of the dialyzer and the amount of substance ΔM2 discharged downstream of the dialyzer are given as follows: ΔM 1 = Qd * ∫ dcDi * dt ΔM 2 = Qd * ∫ dcDo * dt where Qd is the dialyzing fluid flow rate, cDi is the dialysate concentration at the inlet and cDo is the dialysate concentration at the outlet of the second compartment 4 of the dialyzer 1 and t is the time.

[0086] The calculation and evaluation unit 24 can calculate a first value for the dialysance D according to the following equation (step 105): D = Qd * ΔMi − ΔMo / ΔMi

[0087] More complex equations can also be used to determine dialysance, taking into account additional parameters such as the ultrafiltration rate (Qf) and / or substitution rate (Qs). These equations for determining dialysance have been known for a long time and are described in the literature. One such more complex equation might look like this: D = (Qd + Qs + Qf) * (1 - ΔM2 / ΔM1) and is included in equation (3) as a possible embodiment.

[0088] The dialysis fluid flow rate Qd is specified by the dialysis fluid pump 19, which is controlled by the control and computing unit 24 with the corresponding flow rate.

[0089] After the first value for dialysance has been determined, facility 21 specifies the second dialysis condition (step 106) ( Fig. 2B ), in order to determine a second value for the clearance (dialysance). The device 21 for generating a change in a physical or chemical parameter then generates another inlet bolus with a predetermined area (step 107). The second inlet bolus preferably has the same or at least approximately the same area as the first inlet bolus. The conductivity sensor 22A upstream of the dialyzer 1 then detects the inlet bolus and the conductivity meter 22B downstream of the dialyzer detects the outlet bolus (step 108).

[0090] As mentioned above, the dialysis machine can also be programmed so that the incoming boluses are not measured directly, but can be calculated over time based on the amount of sodium added. The same applies to other parameters characterizing the incoming boluses if the flow rates and behavior of the dialysis fluid within the dialysis system are known.

[0091] After calculating ΔM1 and ΔM2 according to equation (1) and equation (2) respectively, the computation and evaluation unit calculates the second value D' for the dialysance according to equation (3) (step 109).

[0092] The blood flow in the vascular access Qa is now calculated by the calculation and evaluation unit according to the following equation (step 110): Qa = D * D ′ / D − D ′ , where D is the first value of the dialysance and D' is the second value of the dialysance.

[0093] More complex equations can also be used that take into account additional parameters, such as ultrafiltration rate (Qf) and / or blood water flow (bwf). These equations for determining dialysance have been known for a long time and are described in the literature. One such more complex equation might look like this: Qa = 1 / bwf * (D-Qf)*D' / (D-D') and is included in equation (3) as embodiments.

[0094] The blood flow in vascular access Qa is displayed on display unit 26 (step 11).

[0095] Fig. 4 shows the infusion bolus for the first and second clearance measurements. The area is in Fig. 4 The device 21 for generating the inlet bolus increases the substance concentration of the dialysis fluid cD, in particular the Na concentration, from the base value B to a maximum value MAX, i.e. the determination of the blood flow in the vascular access Qa is carried out with two positive boluses, which are characterized by the same area A.

[0096] Fig. 6 Figure 1 shows an alternative embodiment with a negative input bolus for the first clearance measurement and a negative input bolus for the second clearance measurement. The area is shown in Figure 2. Fig. 6 again denoted by A and the baseline value by B. The device 21 for generating the inlet bolus reduces the substance concentration of the dialysis fluid cD, in particular the Na concentration, from the baseline value B to a minimum value MIN, i.e. the determination of the blood flow in the vascular access Qa is carried out with two negative boluses, which are characterized by the same area A.

[0097] Before performing the clearance measurements to determine the first hemodialysis parameter, the dialysis fluid flow and / or the blood flow can be increased to a preset value by increasing the speed of the dialysis fluid pump 19 or the blood pump 14, respectively, via the control unit 24. After the clearance measurement, the dialysis fluid flow and / or the blood flow can be reduced back to the previously set value.

[0098] The computing and control unit 24 can, after the clearance measurements for determining the first hemodialysis parameter, also specify an operating mode that reduces the concentration of the administered substance, in particular the introduced salt. Measures for reducing the salt content in the dialysate over a predetermined period or with a predetermined profile are described, for example, in DE 3 223 051 A1.

[0099] The procedure for clearance measurement as such is described in EP 0 911 043 B1 and the procedure for determining the blood access flow Qa on the basis of two successive clearance measurements as such is described in detail in EP 0 928 614 B1.

[0100] The blood flow measurement in the vascular access described above is performed only once during dialysis treatment, either automatically or after the medical staff presses button 25A.

[0101] The dialysis device according to the invention provides not only for the determination of the blood flow in the vascular access, but also for the determination of the dialysis dose kt / V during the dialysis treatment.

[0102] During dialysis treatment, the device 21 generates an input bolus, preferably under the first dialysis condition, by increasing or decreasing the Na concentration of the dialysis fluid from the base value B to produce a physical or chemical property.

[0103] Fig. 5 The diagram shows an inlet bolus A', increasing the Na concentration. The physical or chemical parameter detection device 22 then detects the inlet bolus upstream of dialyzer 1 and the outlet bolus downstream of dialyzer 1 by measuring the conductivity of the dialysis fluid with the conductivity sensors 22A and 22B upstream and downstream of dialyzer 11. The measured values ​​are stored in the memory 23A of the processing and evaluation unit 23, and the dialysance D (clearance K) is calculated according to equation (3). After determining the dialysance D (clearance K), the processing and evaluation unit 23 calculates the dialysis dose Kt / V, which is displayed by the display unit 26.

[0104] While the first hemodialysis parameter (blood access flow) is determined solely on the basis of an inlet bolus having an area A, the second hemodialysis parameter (dialysis dose) is determined solely on the basis of an inlet bolus having an area A', where the area A is at least 2.5 times, in particular at least 2.7 times, in particular at least 3 times as large as the area A' ( Fig. 4, Fig. 5 ).

[0105] The ratio between the area A and A' of the infusion bolus for determining the first and second hemodialysis parameters can be defined based on the signal-to-noise ratio. This ratio can be calculated using an algorithm based on the signal-to-noise ratio, or the corresponding values ​​can be stored in memory 23A of the processing and evaluation unit 23. Memory 23A can also store values ​​that specify a particular pulse shape and / or pulse duration for the infusion bolus.

[0106] While the blood flow in the vascular access (Qa) is determined using a relatively large bolus, the dialysis dose (Kt / V) is determined using a relatively small bolus. Due to the large bolus, the blood flow in the vascular access can be determined with high accuracy. Generally, a single measurement of the blood flow in the vascular access, preferably at the beginning of dialysis treatment, is sufficient. The dialysis dose, on the other hand, is preferably determined several times during dialysis treatment.

[0107] Fig. 7 This shows a sequence of initial boluses for determining the dialysis dose. A positive bolus for a preceding measurement is followed by a negative bolus for a subsequent measurement, where a positive sodium bolus is associated with an increase in sodium concentration and a negative sodium bolus is associated with a decrease in sodium concentration.

[0108] Other sequences can be programmed alternatively or additionally. With an alternating sequence of positive and negative boluses, every second bolus can be directed upwards; with a sequence of positive boluses, all boluses can be directed to values ​​greater than the baseline. Preferably, the dialysis machine is controlled according to alternating boluses or solely with positive boluses. Figuren 3 bis 7 These are for illustrative purposes only.

[0109] Fig. 8 The graph shows the conductivity measured upstream and downstream of the dialyzer in an experiment as a function of time t. The measured conductivity correlates with the concentration of the substance (Na concentration) in the dialyzer fluid. Fig. 8 The substance concentration (conductivity) upstream of dialyzer 1 (inlet bolus) is denoted by cdi and the substance concentration (conductivity) downstream of dialyzer (outlet bolus) is denoted by cdo.

[0110] Upper and lower limits can be specified for conductivity, which must not be exceeded or fallen below when generating a positive or negative bolus, respectively. These limits can be set in such a way as to eliminate any burden on the patient.

[0111] In the embodiment described above, the first clearance value is determined based on a change in a physical or chemical property of the dialysis fluid. An alternative embodiment for determining the blood flow in the vascular access Qa involves estimating the first clearance value D instead of measuring it. Fig. 10 Figure 1 shows the individual process steps of the alternative embodiment. Process steps 100 and 101 and 103 to 108 correspond to process steps 100, 101 and 105 to 110 of the first embodiment ( Fig. 9In this regard, reference is made to the description of the first embodiment for determining the first clearance value. Instead of process steps 102, 103, and 104 of the first embodiment, the first clearance value D is estimated in the second embodiment (step 102). The computing and evaluation unit 23 can determine an estimated value for the first clearance value according to the method described in EP 1 698 360 B1 or calculate it according to the equations published in Sargent, A. & Gotch, F., "Principles and biophysics of Dialysis" in "Replacement of renewal function by dialysis", 4th ED.

[0112] A second aspect of the invention provides that the distance of the first quantity (A) of the first bolus to a reference quantity is greater than the distance of the second quantity (A') of the second bolus to a reference quantity. According to this second aspect, a reference quantity is defined, wherein the size of the at least one bolus for determining the first hemodialysis parameter and the size of the at least one bolus for determining the second hemodialysis parameter are referenced to this reference quantity. In the present embodiment, this reference quantity is the noise in the system, and the distance to the reference quantity is the signal-to-noise ratio. For accurate measurement, the largest possible signal-to-noise ratio is generally desired, which increases with increasing bolus size, but this also increases the burden on the patient.The individual process steps of the second aspect of the invention correspond to those of the first aspect, wherein the dialysis device for determining the first hemodialysis parameter, in particular the blood flow in the vascular access Qa, specifies a bolus which has a larger signal-to-noise ratio than the bolus for determining the second hemodialysis parameter, in particular the dialysis dose.

Claims

1. A dialysis device configured for connecting a dialyser (1) that is divided by a semipermeable membrane (2) into a first compartment (3), which is part of an extracorporeal blood circuit (5), and a second compartment (4), which is part of a dialysis fluid system (6) of the dialysis machine, comprising a device (22) for determining at least one first and second haemodialysis parameter, the device for determining a haemodialysis parameter comprising: a device (21) for generating a change over time in a physical or chemical parameter of a dialysis fluid (I) in a dialysis fluid feed line (17) to the dialyser (1) in the dialysis fluid system (6) in the form of a bolus, a device (22) for detecting a change over time in the physical or chemical characteristic of the dialysis fluid (II) attributable to the bolus in a dialysis liquid discharge line (18) from the dialyser in the dialysis fluid system (6), a computing and evaluating unit (23) cooperating with the device (21) for generating a change over time in a physical or chemical parameter and the device (22) for detecting a change over time in a physical or chemical parameter that is configured such that, on the basis of a change in the physical or chemical parameter, at least one value for the clearance of the dialysis treatment is determined, and, on the basis of the at least one value for the clearance, at least one haemodialysis parameter is determined, characterised in that the device (21) for generating a change in a physical or chemical parameter is designed such that, to determine a first haemodialysis parameter, at least one bolus for determining the first haemodialysis parameter is generated having a first size (A), the computing and evaluating unit (23) being configured such that, on the basis of the change in the physical or chemical parameter in the form of at least one bolus for determining the first haemodialysis parameter, at least one value for the clearance of the dialysis treatment is determined, on the basis of which value or values the first haemodialysis parameter is determined, and in that, to determine a second haemodialysis parameter, at least one bolus for determining the second haemodialysis parameter is generated having a second size (A'), the computing and evaluating unit (23) being configured such that, on the basis of the change in the physical or chemical parameter in the form of at least one bolus for determining the second haemodialysis parameter, at least one value for the clearance of the dialysis treatment is determined, on the basis of which value or values the second haemodialysis parameter is determined, the first size (A) being larger than the second size (A') or the distance between the first size (A) and a reference value being greater than the distance between the second size (A') and a reference value.

2. The dialysis device according to claim 1, characterised in that the at least one bolus for determining the first haemodialysis parameter is characterised by a first area, and the at least one bolus for determining the second haemodialysis parameter is characterised by a second area, the first area content of the first area being greater than the second area content of the second area.

3. The dialysis device according to claim 1 or claim 2, characterised in that the first haemodialysis parameter is a blood flow in the vascular access (Qa) or a recirculation flow in a vascular system.

4. The dialysis device according to claim 3, characterised in that the dialysis device is configured for connection to an extracorporeal blood circuit (5) that comprises a first bloodline (7) and a second bloodline (9) that is to be connected to an inlet (3a) or outlet (3b) of the first compartment (3) of the dialyser (1), and in that for determining the blood flow in the vascular access (Qa), the device (21) for generating a change in a physical or chemical parameter is designed such that, for a first dialysis condition, a first bolus having the first area content (A) and, for a second dialysis condition, a second bolus having the first area content (A) is generated, the computing and evaluating unit (24) being configured such that, on the basis of the change in the physical or chemical parameter in the form of the first bolus having the first area content (A) under the first dialysis condition, a first value for the clearance is determined and, on the basis of the change in the physical or chemical parameter in the form of the second bolus under the second dialysis condition, a second value for the clearance is determined, on the basis of which values the blood flow in the vascular access is determined, or, to determine the blood flow in the vascular access (Qa), the device (21) for generating a change in a physical or chemical parameter is designed such that a bolus having the first area content (A) is generated for a second dialysis condition, the computing and evaluation unit being configured such that, on the basis of an estimate of the clearance for the first dialysis condition, a first value for the clearance is determined and, on the basis of the change in the physical or chemical parameter in the form of the bolus having the first area content (A) under the second dialysis condition, a second value for clearance is determined, on the basis of which values the blood flow in the vascular access is determined, wherein, under the first dialysis condition, the first bloodline (7) conveys blood from a downstream portion (11) of a vascular access (12) of the patient and the second bloodline (9) conveys blood towards an upstream portion (13) of the vascular access (11) and, under the second dialysis condition, the first bloodline (7) conveys blood from an upstream part (13) of the vascular access (12) and the second bloodline (9) conveys blood towards a downstream portion (11) of the vascular access (11).

5. The dialysis device according to any of claims 1 to 4, characterised in that the second haemodialysis parameter is the dialysis dose Kt / V, K being the clearance, t the dialysis time and V the urea distribution volume.

6. The dialysis device according to claim 5, characterised in that for determining the dialysis dose Kt / V, the device (21) for generating a change in a physical or chemical parameter is designed such that a bolus is generated having the second area content (A'), the computing and evaluating unit (23) be configured such that, on the basis of the change in the physical or chemical parameter in the form of the bolus having the second area content (A'), a value for the clearance is determined, on the basis of which value the dialysis dose Kt / V is determined.

7. The dialysis device according to any of claims 1 to 6, characterised in that a controlling and computing unit cooperating with the device (21) for generating a change in a physical or chemical parameter and the device (22) for detecting a change over time in a physical or chemical parameter (24) is provided, which controlling and computing unit is configured such that the generation and detection of the change in the physical or chemical parameter is started during the blood treatment to determine the first or second haemodialysis parameter.

8. The dialysis device according to claim 7, characterised in that the controlling and computing unit (24) is configured such that, to determine the first haemodialysis parameter, the generation and detection of the change in the physical or chemical parameter is started only once or only twice during the blood treatment and / or in that, to determine the second haemodialysis parameter, the generation and detection of the change in the physical or chemical parameter is started multiple times during the blood treatment.

9. The dialysis device according to any of claims 4 to 8, characterised in that, to determine the first haemodialysis parameter, the device (21) for generating a change in a physical or chemical parameter is designed such that the substance concentration of a substance in the dialysis fluid, in particular the Na concentration, is increased to determine the first and second values of the clearance under the first and second dialysis conditions or the value of the clearance under the second dialysis condition or decreased to determine the first and second values of the clearance under the first and second dialysis conditions or the value of the clearance under the second dialysis condition and / or to determine the second haemodialysis parameter, the device (21) for generating a change in a physical or chemical parameter is designed such that the substance concentration of a substance in the dialysis fluid, in particular the Na concentration, is increased for a previous measurement and decreased for a subsequent measurement or decreased for a previous measurement and increased for a subsequent measurement.

10. A dialysis system comprising a dialysis device according to any of claims 1 to 9, and comprising a dialyser that is divided by a semi-permeable membrane (2) into a first compartment (3), which is part of an extracorporeal blood circuit (5), and a second compartment (4), which is part of a dialysis fluid system (6) of the dialysis device, and comprising an extracorporeal blood circuit that comprises a first bloodline (7) and a second bloodline (9) that is connected to an inlet (3a) or outlet (3b) of the first compartment (3) of the dialyser (1).

11. A computer program product that comprises commands that, when the program is executed by a computer, cause the computer to carry out a method for determining at least one first and second haemodialysis parameter during a dialysis treatment with a dialysis device, wherein the method comprises the following method steps: Generating at least one change over time in a physical or chemical parameter of a dialysis fluid (I) in a dialysis fluid feed line (17) to a dialyser (1) in a dialysis fluid system (6) in the form of a bolus, Detecting at least one change over time in the physical or chemical parameter of the dialysis fluid (II) attributable to the at least one bolus in a dialysis fluid discharge line (18) from the dialyser in the dialysis fluid system (6), Determining at least one value for the clearance of the dialysis treatment on the basis of the at least one change in the physical or chemical parameter in the form of a bolus, and determining at least one haemodialysis parameter on the basis of the at least one value for the clearance, wherein, to determine a first haemodialysis parameter, at least one bolus for determining the first haemodialysis parameter is generated having a first size (A), at least one value for the clearance of the dialysis treatment being determined on the basis of the change in the physical or chemical parameter in the form of at least one bolus for determining the first haemodialysis parameter, on the basis of which value the first haemodialysis parameter is determined, and to determine a second haemodialysis parameter, at least one bolus for determining the second haemodialysis parameter is generated having a second size (A'), at least one value for the clearance of the dialysis treatment being determined on the basis of the change in the physical or chemical parameter in the form of at least one bolus for determining the second haemodialysis parameter, on the basis of which value the second haemodialysis parameter is determined, the first size (A) being larger than the second size (A') or the distance between the first size (A) and a reference value being greater than the distance between the second size (A') and a reference value.

12. The computer program product according to claim 11, wherein the method is characterised in that the at least one bolus for determining the first haemodialysis parameter is characterised by a first area and the at least one bolus for determining the second haemodialysis parameter is characterised by a second area, the first area content of the first area being greater than the second area content of the second area.

13. The computer program product according to claim 11 or claim 12, wherein the method is characterised in that the first haemodialysis parameter is a blood flow in the vascular access (Qa) or a recirculation flow in a vascular system.

14. The computer program product according to claim 13, wherein the method is characterised in that, to determine the blood flow in the vascular access (Qa), a first bolus having the first area content (A) is generated for a first dialysis condition and a second bolus having the first area content (A) is generated for a second dialysis condition, a first value for the clearance being determined on the basis of the change in the physical or chemical parameter in the form of the first bolus having the first area content (A) under the first dialysis condition and a second value for the clearance being determined on the basis of the change in the physical or chemical parameter in the form of the second bolus under the second dialysis condition, on the basis of which values the blood flow in the vascular access is determined, or , to determine the blood flow in the vascular access (Qa) for a second dialysis condition, a bolus having the first area content (A) is generated, a first value for the clearance being determined on the basis of an estimate of the clearance for the first dialysis condition and a second value for the clearance being determined on the basis of the change in the physical or chemical parameter in the form of the bolus having the first area content (A) under the second dialysis condition, on the basis of which values the blood flow in the vascular access is determined, wherein, under the first dialysis condition, the first bloodline (7) conveys blood from a downstream portion (11) of a patient's vascular access (12) and the second bloodline (9) conveys blood towards an upstream portion (13) of the vascular access (11) and, under the second dialysis condition, the first bloodline (7) conveys blood from an upstream portion (13) of the vascular access (12) and the second bloodline (9) conveys blood towards a downstream portion (11) of the vascular access (11).

15. The computer program product according to any of claims 12 to 14, characterised in that the second haemodialysis parameter is the dialysis dose Kt / V, where K is the clearance, t is the dialysis time and V is the urea distribution volume, and in that, to determine the dialysis dose Kt / V, a bolus having the second area content (A') is generated, a value for the clearance being determined on the basis of the change in the physical or chemical parameter in the form of the bolus having the second area content (A'), on the basis of which value the dialysis dose Kt / V is determined.