Method for determining sodium and bicarbonate ion concentrations of dialysis fluids

Abstract

The invention relates to a method for determining the sodium and / or bicarbonate ion concentration of a dialysis fluid, to the use of the method for proportioning a dialysis fluid, and to the use of an extracorporeal blood treatment device for carrying out the method.

Description

Field of the Invention

[0001] The present invention relates to a method for determining the sodium and bicarbonate ion concentrations of a dialysis fluid, to the use of a method for formulating a dialysis fluid, and to the use of an extracorporeal blood treatment device for performing a method for determining the sodium and bicarbonate ion concentrations of a dialysis fluid. Background Art

[0002] Extracorporeal blood treatment, such as hemodialysis, involves passing a patient's blood through a dialyzer while a dialysis fluid also passes through the dialyzer. In the dialyzer, the blood and the dialysis fluid are in contact through a semipermeable membrane, such that mass transfer can occur between the patient's blood and the dialysis fluid. Such dialysis treatment aims to detoxify the blood of a patient suffering from renal failure and remove excess water from the body.

[0003] The dialysis fluid consists of highly purified water, an alkaline fluid (also referred to as an alkaline concentrate or bicarbonate concentrate), and an acidic fluid (also referred to as an acid concentrate). The alkaline fluid or alkaline concentrate typically contains sodium bicarbonate (NaHCO 3 ). The acidic fluid or acid concentrate preferably contains sodium chloride (NaCl), potassium chloride (KCl), magnesium chloride (MgCl 2 ), calcium chloride (CaCl 2 ), glucose, and an acid such as acetic acid (CH 3 COOH).

[0004] Typically, metering pumps and conductivity probes are used to prepare or formulate the dialysis fluid. After adding the alkaline fluid to highly purified water (which may also be referred to as osmotic water) by means of a first metering pump, one probe measures the conductivity. After adding the acidic fluid by means of another metering pump, another probe measures the conductivity of the entire dialysis fluid. The amounts of the added alkaline fluid and acidic fluid are adjusted based on the measured conductivity (so-called conductivity-controlled formulation).

[0005] The correct composition of the dialysis fluid is of utmost importance for the health and life expectancy of the patient. This is particularly true with regard to the sodium and bicarbonate ion concentrations. The aforementioned concentrations are typically measured indirectly via the conductivity in an extracorporeal blood treatment device. This measurement is based on a linear model that approximately calculates the relationship between conductivity and concentration. This requires conversion factors specific to the base fluid and the acid fluid (conversion factors specific to the concentrate). The coefficients used for the specific base fluid and the specific acid fluid used must be experimentally determined by determining the composition of the specific base fluid and the specific acid fluid for a defined conductivity in a laboratory. Using the measured conductivity and the experimentally determined concentrations allows the calculation of the conversion factors. However, this method has various disadvantages. For example, the relevant laboratory tests for each base fluid and acid fluid must be performed locally at the dialysis center. This results in significant costs. In addition, the quality of the conversion factors to be determined depends on the quality of the specific laboratory tests. Measurement errors in determining the concentration lead to systematic errors in the composition of the dialysis fluid. Another problem lies in the instability of the samples required for determining the concentration. Due to the escape of carbon dioxide (CO2) into the air, the bicarbonate ion concentration is distorted over time. In addition, insoluble calcium carbonate (CaCO3) precipitates, which also leads to a distortion of the bicarbonate ion concentration. Finally, the calculation of the conversion factors is a complex and thus time-consuming problem and also requires additional training of some of the staff involved.

[0006] EP 2 494 998 B1 discloses a method for monitoring the concentration of a dialysis fluid, in which the conductivity varies proportionally based on the mixing ratio. This method only works in a relative manner. Thus, if there is an initial error or inaccuracy in the composition, the error is carried forward with each change in the mixing ratio. Summary of the Invention

[0007] An object of the present invention is to provide a method for determining the sodium and bicarbonate ion concentrations of a dialysis fluid, which at least partially avoids the disadvantages known from the prior art. Another object of the present invention is to provide a method for the use of preparing or formulating a dialysis fluid and the use of an extracorporeal blood treatment device for performing a method for determining the sodium and bicarbonate ion concentrations of a dialysis fluid.

[0008] According to the present invention, these objects are achieved by the method according to independent claim 1, the use of the method according to claim 17, and the use of the extracorporeal blood treatment device according to claim 18. Preferred embodiments of the present invention are the subject matter of the dependent claims. The wording of all claims is hereby incorporated into this specification by express reference. Detailed Description

[0009] According to a first aspect, the present invention provides a method for determining the sodium ion concentration and the bicarbonate ion concentration of a dialysis fluid, in particular for hemodialysis and / or peritoneal dialysis.

[0010] The method includes (in particular in chronological or non-chronological order) the following steps:

[0011] a) Providing a dilute alkali fluid by mixing an alkali fluid having a bicarbonate ion concentration (bicarbonate ion concentration), in particular a defined (i.e., specified or known) or undefined bicarbonate ion concentration, with water (i.e., high-purity water or osmotic water) in a defined (i.e., specified or known) mixing ratio, and providing a dilute acid fluid by mixing an acid fluid having a sodium ion concentration, in particular a defined (i.e., specified or known) or undefined sodium ion concentration, and an acid concentration, in particular a defined (i.e., specified or known) or undefined acid concentration, with water (i.e., high-purity water or osmotic water) in a defined (i.e., specified or known) mixing ratio;

[0012] b) Preparing a pre-dialysis fluid by adding (in particular continuously or discontinuously) the dilute alkali fluid to water (i.e., high-purity water or osmotic water);

[0013] c) Determining a target value of the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid based on the bicarbonate ion concentration of the dialysis fluid and / or the pre-dialysis fluid, in particular a defined (i.e., specified or known) or undefined bicarbonate ion concentration, and a parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration), and determining a target value of the conductivity (in particular the final conductivity or the total conductivity) of the dialysis fluid based on the sodium ion concentration of the dialysis fluid, in particular a defined (i.e., specified or known) or undefined sodium ion concentration, and a parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid (in particular the final conductivity or the total conductivity) or vice versa (i.e., for converting the conductivity of the dialysis fluid (in particular the final conductivity or the total conductivity) into sodium ion concentration);

[0014] d) Measuring the conductivity of the pre-dialysis fluid;

[0015] e) Comparing the conductivity of the pre-dialysis fluid measured according to step d) with the target value of the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid determined according to step c), and, if necessary, further adding (in particular continuously or discontinuously) the dilute alkali fluid to the pre-dialysis fluid, in particular by means of a feed pump, until the target value of the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid has been reached or has been substantially reached (so-called closed-loop controller).

[0016] f) preparing the dialysis fluid by adding (in particular continuously or discontinuously) a dilute acid fluid to the pre-dialysis fluid,

[0017] g) measuring the conductivity of the dialysis fluid (in particular the final conductivity or the total conductivity),

[0018] h) comparing the conductivity of the dialysis fluid measured according to step g) with the target value of the conductivity of the dialysis fluid determined according to step c), and if necessary, further adding (in particular continuously or discontinuously) the dilute acid fluid to the dialysis fluid, in particular by means of a further feed pump, until the target value of the conductivity of the dialysis fluid has been reached or has been substantially reached (so-called closed-loop controller), and

[0019] i) determining the bicarbonate ion concentration of the dialysis fluid based on the conductivity of the pre-dialysis fluid measured according to step d) and a parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration), and determining the sodium ion concentration of the dialysis fluid based on the conductivity of the dialysis fluid measured according to step g) and a parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa (i.e., for converting the conductivity of the dialysis fluid into sodium ion concentration),

[0020] wherein the parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration) and the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa (i.e., for converting the conductivity of the dialysis fluid into sodium ion concentration) are both automatically determined.

[0021] In the context of the present invention, the parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa may also be referred to as the conversion coefficient for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa.

[0022] In the context of the present invention, the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa may also be referred to as the conversion coefficient for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa.

[0023] In the context of the present invention, the expression "dialysis fluid" should be understood to refer to the fluid used for dialysis (in particular hemodialysis and / or peritoneal dialysis) (in particular ready-to-use or non-ready-to-use fluid), which consists of water (i.e., highly purified water (also called permeate water)), an alkali fluid (also called alkali concentrate), and an acid fluid (also called acid concentrate).

[0024] In the context of the present invention, the expression "alkali fluid" shall be understood to mean an undiluted alkali fluid, i.e., an undiluted bicarbonate concentrate or bicarbonate ion concentrate having a defined concentration of bicarbonate ions.

[0025] In the context of the present invention, the expression "dilute alkali fluid" shall be understood to mean an alkali fluid that has been diluted or is in a diluted state by being mixed with water (i.e., high-purity water or permeate water) in a defined (i.e., specified or known) mixing ratio, particularly with respect to the concentration of said fluid.

[0026] In the context of the present invention, the expression "acid fluid" shall be understood to mean an undiluted acid fluid, i.e., an undiluted acid concentrate or acid concentrate having a defined sodium ion concentration (particularly defined sodium ion, potassium ion, magnesium ion, and calcium ion concentrations) and a defined acid concentration (particularly acetic acid concentration).

[0027] In the context of the present invention, the expression "dilute acid fluid" shall be understood to mean an acid fluid that has been diluted or is in a diluted state by being mixed with water (i.e., high-purity water or permeate water) in a defined (i.e., specified or known) mixing ratio, particularly with respect to the concentration of said fluid.

[0028] In the context of the present invention, the expression "conductivity" refers to electrical conductivity.

[0029] In the context of the present invention, the expression "bicarbonate conductivity" shall be understood to mean the conductivity derived from bicarbonate ions and sodium ions, particularly in a 1:1 ratio of bicarbonate ions and sodium ions.

[0030] In the context of the present invention, the expression "final conductivity or total conductivity of the dialysate fluid" shall be understood to mean the conductivity derived from all ionic species (particularly cationic species) present in the dialysate fluid, preferably the conductivity derived from particularly sodium ions and preferably potassium ions, magnesium ions, and calcium ions.

[0031] The conductivity measured according to steps d) and g) can in each case be particularly temperature-compensated conductivity.

[0032] In the context of the present invention, the expression "temperature-compensated conductivity" shall be understood to mean the conductivity corresponding to the conductivity at room temperature or an ambient temperature of 25 °C.

[0033] In the context of the present invention, the expression "substantially achieved" used in the context of step e) means that the conductivity of the pre-dialysate fluid measured according to step d) may deviate from the target value of the bicarbonate conductivity of the dialysate fluid and / or the pre-dialysate fluid by ≤ 1%, particularly < 1%.

[0034] In the context of the present invention, the expression "substantially achieved" used in the context of step h) means that the conductivity of the dialysis fluid measured according to step g) may deviate from the target value of the conductivity of the dialysis fluid by ≤ 1%, in particular < 1%.

[0035] Step c) can be carried out in particular before or after step a) or step b), in particular between step a) and b), or preferably between step b) and d).

[0036] In the context of the present invention, the expression "high-purity water" or permeate water should be understood to mean sterile water without electrolytes or without any detectable electrolytes, i.e., the electrolyte content is at most 0.01 mEq / l. In addition, high-purity water or permeate water may in particular have a conductivity of ≤ 1.1 μS / cm at 20 °C and / or a bacterial endotoxin concentration of < 0.25 IU / ml (approx. 25 ng / l) and / or a total organic carbon (TOC) concentration of ≤ 0.5 mg / l and / or a nitrate concentration of ≤ 0.2 mg / l.

[0037] The automatic determination of the parameters for converting conductivity into sodium and bicarbonate ion concentrations or vice versa makes it possible to minimize or avoid the disadvantages associated with conventional methods mentioned at the beginning. Thus, expensive, time-consuming and error-prone laboratory tests and subsequent calculations can be dispensed with. This will lead to a significant simplification of the preparation and execution of extracorporeal blood treatment, in particular improving the safety for the patient to be treated.

[0038] In one embodiment of the present invention, the base fluid also has a sodium ion concentration, in particular a defined (i.e., specified or known) or undefined sodium ion concentration.

[0039] In particular, the base fluid is provided in the form of an alkaline aqueous solution. Preferably, the base fluid is provided in the form of an alkaline aqueous solution containing sodium bicarbonate, which is also known as sodium hydrogen carbonate (NaHCO 3 ). In the context of the present invention, such a solution may also be referred to as an alkaline sodium bicarbonate aqueous solution or an alkaline sodium hydrogen carbonate aqueous solution.

[0040] The base fluid may have a bicarbonate ion concentration of 600 mmol / l to 1500 mmol / l, in particular 1000 mmol / l to 1500 mmol / l. For example, the base fluid may have a bicarbonate ion concentration of 1000 mmol / l or 1300 mmol / l.

[0041] In addition, the base fluid may have a sodium ion concentration of 600 mmol / l to 1500 mmol / l, in particular 1000 mmol / l to 1500 mmol / l. For example, the base fluid may have a sodium ion concentration of 1000 mmol / l or 1300 mmol / l.

[0042] The acidic fluid may also have at least one further cation species concentration (in particular a defined (i.e., specified or known) or undefined cation species concentration), in particular selected from a potassium ion concentration (in particular a defined (i.e., specified or known) or undefined potassium ion concentration), a magnesium ion concentration (in particular a defined (i.e., specified or known) or undefined magnesium ion concentration), a calcium ion concentration (in particular a defined (i.e., specified or known) or undefined calcium ion concentration), and combinations of at least two of the foregoing cation species concentrations.

[0043] In a further embodiment of the invention, the acidic fluid also has a potassium ion concentration (in particular a defined (i.e., specified or known) or undefined potassium ion concentration), a magnesium ion concentration (in particular a defined (i.e., specified or known) or undefined magnesium ion concentration), and a calcium ion concentration (in particular a defined (i.e., specified or known) or undefined calcium ion concentration).

[0044] The acid of the acidic fluid can in principle be an inorganic acid and / or an organic acid. The acid can in particular be selected from hydrochloric acid, acetic acid, lactic acid, acetoacetic acid, citric acid, malic acid, maleic acid, pyruvic acid, succinic acid, and combinations (in particular mixtures) of at least two of the foregoing acids.

[0045] Preferably, the acidic fluid contains acetic acid as the acid.

[0046] In addition, the acidic fluid may also contain osmotically active compounds. The osmotically active compounds can be selected from glycine, monosaccharides, disaccharides, polysaccharides, sugar alcohols, gelatin, amino acids, and combinations (in particular mixtures) of at least two of the foregoing osmotically active compounds. The monosaccharides can be selected from glucose, fructose, galactose, and combinations (in particular mixtures) of at least two of the foregoing monosaccharides. The disaccharides can be selected from sucrose, maltose, trehalose, and combinations (in particular mixtures) of at least two of the foregoing disaccharides. The polysaccharides can be selected from dextrin, starch, polyglucose, hydroxyethyl starch, and combinations (in particular mixtures) of at least two of the foregoing polysaccharides. The sugar alcohols can be selected from xylitol, mannitol, sorbitol, and combinations (in particular mixtures) of at least two of the foregoing sugar alcohols. The amino acids can in principle be essential amino acids and / or non-essential amino acids.

[0047] Preferably, the acidic fluid contains glucose as the osmotically active compound.

[0048] In particular, the acidic fluid is provided in the form of an acidic aqueous solution. Preferably, the acidic fluid is provided in the form of an acidic aqueous solution that contains sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and an acid (in particular acetic acid or citric acid).

[0049] Particularly preferably, the acidic fluid is provided in the form of an acidic aqueous solution comprising sodium chloride, potassium chloride, magnesium chloride, calcium chloride, an osmotically active compound (in particular glucose), and an acid (in particular acetic acid or citric acid). For the possible osmotically active compounds and the possible acids, full reference is made to the foregoing.

[0050] The acidic fluid may have a sodium ion concentration of from 95 mmol / l to 110 mmol / l, in particular from 100 mmol / l to 103 mmol / l.

[0051] Furthermore, the acidic fluid may have a potassium ion concentration of >0 mmol / l to 5 mmol / l, in particular from 1 mmol / l to 4 mmol / l.

[0052] Furthermore, the acidic fluid may have a magnesium ion concentration of >0 mmol / l to 1.5 mmol / l, in particular 0.5 mmol / l.

[0053] Furthermore, the acidic fluid may have a calcium ion concentration of >0 mmol / l to 3 mmol / l, in particular from 1 mmol / l to 1.5 mmol / l.

[0054] Steps d) and g) are preferably carried out using a conductivity probe or conductivity electrode or other suitable conductivity measuring device or equipment.

[0055] When carrying out step a), the alkaline fluid may be mixed with water in a defined mixing ratio of 1:30 or 1:36, and / or the acidic fluid may be mixed with water in a defined mixing ratio of 1:34 or 1:44. Suitable mixing ratios can advantageously be found on the label or marking of the container containing the alkaline fluid or acidic fluid. It is also advantageous that all acid types that can be used for extracorporeal blood treatment can be taken into account.

[0056] In a further embodiment of the invention, the target value of the bicarbonate conductivity of the dialysis fluid and / or the predialysis fluid is determined by means of a linear model, in particular according to the following formula (1):

[0057] BICLF = c bic (mmol / l) x Λ m，bic (1)

[0059] where

[0060] BICLF is the target value of the bicarbonate conductivity of the dialysis fluid and / or the predialysis fluid, c bic is the concentration of bicarbonate ions in the dialysis fluid and / or the predialysis fluid

[0061] and

[0062] Λ m，bicA parameter for converting the concentration of bicarbonate ions into the conductivity of bicarbonate or vice versa.

[0063] In a further embodiment of the present invention, the target value of the conductivity of the dialysis fluid is determined by means of a linear model, in particular according to the following formula (2):

[0064] ENDLF = {[c Na+,总 (mmol / l) - c bic (mmol / l)] x Λ m，acid} + [c bic (mmol / l) x Λ m，bic (2)

[0066] Where

[0067] ENDLF is the target value of the conductivity of the dialysis fluid,

[0068] c Na+,总 is the sodium ion concentration of the dialysis fluid,

[0069] c bic is the bicarbonate ion concentration of the dialysis fluid and / or the predialysis fluid,

[0070] Λ m，acid is a parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa

[0071] And

[0072] Λ m，bic is a parameter for converting the bicarbonate ion concentration into the conductivity of bicarbonate or vice versa.

[0073] In a further embodiment of the present invention, the parameter for converting the bicarbonate ion concentration into the conductivity of bicarbonate or vice versa and the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa are automatically determined based on the concentration of the dilute base fluid and / or the dilute acid fluid, preferably and in particular entirely based on the concentration of the dilute acid fluid. This has the advantage that the method is not restricted in any way with respect to the base fluid and / or the acid fluid (preferably the acid fluid). Therefore, the method can in principle be carried out with all commercially available base fluids and acid fluids.

[0074] In a further embodiment of the present invention, the parameter for converting the bicarbonate ion concentration into the conductivity of bicarbonate or vice versa is automatically determined based on the bicarbonate ion concentration of the dilute base fluid and the acid concentration of the dilute acid fluid.

[0075] ​In a further embodiment of the present invention, the parameters for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa are automatically determined based on the bicarbonate ion concentration of the dilute alkaline fluid, the sodium ion concentration of the dilute alkaline fluid, the sodium ion concentration of the dilute acidic fluid, the potassium ion concentration of the dilute acidic fluid, the magnesium ion concentration of the dilute acidic fluid, the calcium ion concentration of the dilute acidic fluid, and the acid concentration of the dilute acidic fluid.

[0076] In a further embodiment of the present invention, the parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa is determined according to the following formula (3):

[0077]

[0078] where

[0079] Λ m，bic is the parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa,

[0080] c bic，0 is the bicarbonate ion concentration of the dilute alkaline fluid

[0081] and

[0082] c acid，0 is the acid concentration of the dilute acidic fluid.

[0083] The above embodiments of the present invention are based on the following assumptions / considerations:

[0084] If the dilute alkaline fluid is provided in the form of an alkaline sodium bicarbonate aqueous solution, the dilute alkaline fluid contains, in particular, substantially two types of charged components, namely sodium ions and bicarbonate ions. These components are individually charged and thus contribute to the conductivity of the pre-dialysis fluid. If the relationship between conductivity and concentration is approximated by a linear model, this means that each charged component of the dilute alkaline fluid in the pre-dialysis fluid contributes the same share to the conductivity. The parameter for converting conductivity into bicarbonate ion concentration describes the contribution of sodium bicarbonate per defined volume element to the conductivity (mS / cm) / (mmol / l).

[0085] For the bicarbonate ion concentration (in particular approximately 35 mmol / l) commonly used in extracorporeal blood treatment (in particular dialysis), the parameter for converting conductivity into bicarbonate ion concentration can be experimentally determined to be 0.083 (mS / cm) / (mmol / l). However, it must be taken into account that the bicarbonate ion concentration of the pre-dialysis fluid does not correspond to the bicarbonate ion concentration of the dialysis fluid. This is mainly due to two reasons:

[0086] First, the predialytic fluid is diluted by adding a dilute acid fluid. The exact degree of dilution depends in particular on whether a 1+34 or 1+44 acid fluid is used. In the context of the present invention, the expression "1+34 acid fluid" means mixing 1 part of acid fluid and 34 parts of water (i.e., highly pure water or permeate water) to obtain the corresponding dilute acid fluid. Correspondingly, in the context of the present invention, the expression "1+44 acid fluid" means mixing 1 part of acid fluid and 44 parts of water (i.e., highly pure water or permeate water) to obtain the corresponding dilute acid fluid. In addition, the proportion of the dilute acid fluid also depends on the sodium ion concentration set on the extracorporeal blood treatment device. The device generally adds more dilute acid fluid at higher sodium ion set values. Overall, the bicarbonate ion concentration is reduced by 1.7% to 3.3%. On average, the bicarbonate ion concentration is reduced especially by approximately 2.6%. Therefore, compensation is achieved by increasing the parameter for converting conductivity to bicarbonate ion concentration by 2.6% to 0.0852 (mS / cm) / (mmol / l).

[0087] Secondly, the dilute acid fluid contains an acid which will neutralize some of the bicarbonate ions. The products formed are carbonic acid and a salt of said acid (e.g., acetate or citrate). Therefore, a second compensation of the conversion factor is required to account for this neutralization. The ready-to-use dialytic fluid generally contains a bicarbonate ion concentration of 32 mmol / l and 3 mmol / l of the salt of said acid (especially acetate). Therefore, 35 mmol / l of bicarbonate ions must be provided, since 3 mmol / l are neutralized by the acid (especially acetic acid). The conversion factor is compensated to 0.0852 x 35 / 32 = 0.09319 (mS / cm) / (mmol / l).

[0088] Overall, this results in the above formula (3).

[0089] In a further embodiment of the present invention, the parameter for converting the sodium ion concentration to the conductivity of the dialytic fluid or vice versa is determined according to the following formula (4):

[0090]

[0091] where

[0092] Λ m，acid，kor is the parameter for converting the sodium ion concentration to the conductivity of the dialytic fluid or vice versa,

[0093] is the sodium ion concentration of the dilute acid fluid which results in a conductivity of the dilute acid fluid of 11 mS / cm,

[0094] and

[0095] The acid concentration of a dilute acid fluid having a sodium ion concentration resulting in a conductivity of 11 mS / cm for the dilute acid fluid.

[0096] In a further embodiment of the present invention, the sodium ion concentration of the dilute acid fluid resulting in a conductivity of 11 mS / cm for the dilute acid fluid is determined according to the following formula (5):

[0097] (5)

[0099] where

[0100] is the sodium ion concentration of the dilute acid fluid resulting in a conductivity of 11 mS / cm for the dilute acid fluid,

[0101] and

[0102] Λ m，acid is an uncorrected parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity) or vice versa (i.e., for converting the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity) into the sodium ion concentration).

[0103] In a further embodiment of the present invention, the uncorrected parameter Λ for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa m，acid is determined according to the following formula (6):

[0104]

[0105] where

[0106] Λ m，acid is the uncorrected parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa,

[0107] is the sodium ion concentration of the dilute acid fluid,

[0108] is the potassium ion concentration of the dilute acid fluid,

[0109] is the magnesium ion concentration of the dilute acid fluid

[0110] and

[0111] is the calcium ion concentration of the dilute acid fluid.

[0112] In a further embodiment of the present invention, the acid concentration of a dilute acid fluid having a sodium ion concentration resulting in a conductivity of 11 mS / cm for the dilute acid fluid is determined according to the following formula (7):

[0113]

[0114] wherein

[0115] is the acid concentration of the dilute acid fluid having a sodium ion concentration resulting in a conductivity of 11 mS / cm,

[0116] c bic，0 is the bicarbonate ion concentration of the dilute base fluid,

[0117] c acid，0 is the acid concentration of the dilute acid fluid,

[0118] is the sodium ion concentration of the dilute acid fluid

[0119] and

[0120] is the sodium ion concentration of the dilute acid fluid resulting in a conductivity of 11 mS / cm of the dilute acid fluid.

[0121] The four foregoing embodiments of the present invention are based on the following assumptions / considerations:

[0122] The dilute acid fluid preferably contains sodium, potassium, magnesium and calcium ions, especially as components of sodium chloride, potassium chloride, magnesium chloride and calcium chloride. Therefore, the foregoing components contribute to the conductivity of the dilute acid fluid.

[0123] In principle, the acid concentration of the dilute acid fluid contributes little to the conductivity, because the acid in the dilute acid fluid is usually an acid that only slightly dissociates in aqueous solution. However, the dilute acid fluid is added to the pre-dialysis fluid containing bicarbonate ions to prepare the dialysis fluid, resulting in an acid-base reaction. The resulting salt of the acid, such as acetate, contributes to the conductivity. In contrast, the neutralization of bicarbonate ions (by reaction with the acid) results in the formation of carbonic acid, which contributes little or no to the conductivity. Therefore, the net conductivity hardly changes or does not change, so this contribution can be ignored.

[0124] Since bicarbonate has been added when the dilute acid fluid is added to the pre-dialysis fluid, there are two factors related to the total conductivity: the contribution of the previously determined bicarbonate ions, and the contribution of the dilute acid fluid. The contribution of the dilute acid fluid is also approximated by a linear model, where it is assumed that each component in the dilute acid fluid that contributes to the conductivity contributes equally to the conductivity. The required sodium ion concentration is normalized.

[0125] In principle, the contribution of the dilute acid fluid to the conductivity can be determined according to the following formula:

[0126] Contribution of the dilute acid fluid to the conductivity = Sodium ion concentration of the dilute acid fluid x Parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa.

[0127] As described above, not only sodium chloride in the dilute acid fluid but also optionally other electrolytes contribute to the conductivity, and these other electrolytes are preferably potassium chloride, magnesium chloride, and calcium chloride. The greater the proportion of the other electrolytes, the greater the contribution of the dilute acid fluid per required sodium ion to the conductivity. Thus, in principle, the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa varies with the proportion of the electrolytes.

[0128] In the context of the present invention, it is (simplistically) assumed that each electrolyte contributes equally to the conductivity. It has been determined experimentally that the contribution of sodium chloride to the conductivity is 0.09921 (mS / cm) / (mmol / l) at a concentration of particularly about 140 mmol / l, and 140 mmol / l is a typical concentration for extracorporeal blood treatment (particularly dialysis).

[0129] Therefore, the method described here (so far) defines a parameter for converting the concentration into the conductivity or vice versa for the dilute acid fluid according to the above formula (6).

[0130] However, the aforementioned conversion parameter requires a further compensation factor. This is because the total sodium ion concentration is the result of two contributions, namely the sodium ion contribution from the dilute acid fluid and the sodium ion contribution from the dilute base fluid. For the sodium ion contribution from the dilute base fluid, the existing method assumes that one sodium ion is added for each bicarbonate ion. However, this is not entirely correct. The above-mentioned neutralization of the acid in the dilute acid fluid reduces the proportion of bicarbonate ions in the dialysis fluid. In the context of the present invention, this has been taken into account for the parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa by means of a compensation calculation. However, the proportion of sodium ions attributable to the dilute base fluid is not affected by the neutralization that occurs when the dilute acid fluid is added to the predialysis fluid. Ultimately, the proportion of sodium ions increased by the dilute base fluid is thus greater than the proportion of bicarbonate ions. For the dilute acid fluid, this additional proportion of sodium ions can be taken into account by appropriately modifying the parameter for converting the concentration into the conductivity or vice versa.

[0131] This is achieved by first calculating the sodium ion concentration that results in a conductivity of 11 mS / cm solely due to sodium ions. This conductivity value typically corresponds to the contribution of the dilute acid fluid to the conductivity of a dialysis fluid with a total conductivity of 14 mS / cm, where 3 mS / cm of the conductivity is attributable to bicarbonate ions. This sodium ion concentration can be determined according to the above formula (5).

[0132] This proportionality model assumes that one sodium ion is added for each bicarbonate ion. However, this does not apply to the bicarbonate ions after reaction with the acid in the dilute acid fluid. In fact, for each bicarbonate ion eliminated by the acid, an additional sodium ion is added.

[0133] Thus, in the third step, the acid concentration of the dilute acid fluid with a sodium ion concentration contribution to the conductivity of 11 mS / cm for a dialysis fluid with a total conductivity of 14 mS / cm is determined according to the above formula (7).

[0134] The parameter for converting the sodium ion concentration to the conductivity of the dialysis fluid or vice versa can be calculated in the fourth step according to the above formula (4), i.e., dividing 11 mS / cm by the total amount of sodium ions added by the dilute acid fluid, which is corrected by the amount of sodium ions that are ignored due to the acid-base reaction between the bicarbonate of the dilute base fluid and the acid of the dilute acid fluid.

[0135] Preferably, when performing step i), the bicarbonate ion concentration of the dialysis fluid is determined by means of a linear model, in particular according to the following formula (8):

[0136] c + bic (mmol / l) = BICLF + / Λ m，bic (8)

[0138] where

[0139] c + bic is the bicarbonate ion concentration of the dialysis fluid,

[0140] BICLF + is the conductivity of the pre-dialysis fluid measured according to step d),

[0141] and

[0142] Λ m，bic is the parameter for converting the bicarbonate ion concentration to the bicarbonate conductivity or vice versa.

[0143] More preferably, when performing step i), the sodium ion concentration of the dialysis fluid is determined by means of a linear model, in particular according to the following formula (9):

[0144] c + Na+,总 (mmol / l) = {ENDLF + - [c + bic (mmol / l) x Λ m，bic} / Λ m，acid，kor + c + bic (mmol / l) (9)

[0146] where

[0147] c + Na+,总 is the sodium ion concentration of the dialysate fluid,

[0148] ENDLF + is the conductivity of the dialysate fluid measured according to step g),

[0149] c + bic is the bicarbonate ion concentration of the dialysate fluid,

[0150] Λ m，acid，kor is a parameter for converting the sodium ion concentration into the conductivity of the dialysate fluid or vice versa

[0151] and

[0152] Λ m，bic is a parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa.

[0153] Alternatively, the parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa can be determined according to the following formula (3#):

[0154]

[0155] where

[0156] Λ m，bic is a parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa.

[0157] Therefore, in this case, the parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa is independent of the dilute base fluid and / or dilute acid fluid used, especially the dilute acid fluid used.

[0158] In addition, the parameter for converting the sodium ion concentration into the conductivity of the dialysate fluid or vice versa can be determined according to the following formula (4#):

[0159]

[0160] where

[0161] Λ m，acid is a parameter for converting the sodium ion concentration into the conductivity of the dialysate fluid or vice versa,

[0162] is the sodium ion concentration of the dilute acid fluid,

[0163] is the potassium ion concentration of the dilute acid fluid,

[0164] is the magnesium ion concentration of the dilute acid fluid

[0165] and

[0166] is the calcium ion concentration of the dilute acid fluid.

[0167] In this case, when performing step i), the sodium ion concentration of the dialysate is determined by means of a linear model, in particular according to the following formula (9#):

[0168] c + Na+,总 (mmol / l) = {ENDLF + - [c + bic (mmol / l) x Λ m，bic} / Λ m，acid + c + bic (mmol / l)

[0169] (9#)

[0170] where

[0171] c + Na+,总 is the sodium ion concentration of the dialysate,

[0172] ENDLF + is the conductivity of the dialysate measured according to step g),

[0173] c + bic is the bicarbonate ion concentration of the dialysate,

[0174] Λ m，acid is the parameter for converting the sodium ion concentration to the conductivity of the dialysate or vice versa

[0175] and

[0176] Λ m，bic is the parameter for converting the bicarbonate ion concentration to the bicarbonate conductivity or vice versa.

[0177] The set value of the bicarbonate ion concentration input by the user into the extracorporeal blood treatment device (in particular a dialysis machine) is evaluated by the extracorporeal blood treatment device as the bicarbonate ion concentration after acid neutralization of the dilute acid fluid, i.e., as the bicarbonate ion concentration c BIC，post of the dialysate. From this concentration, the bicarbonate ion concentration before acid neutralization with the dilute acid fluid, i.e., the bicarbonate ion concentration c BIC，pre of the predialysate, is determined according to the following formula (1*):

[0178]

[0179] wherein

[0180] c bic，pre is the bicarbonate ion concentration of the pre-dialysis fluid,

[0181] c bic，post is the bicarbonate ion concentration specified for the dialysis fluid,

[0182] c Na，set is the sodium ion concentration specified for the dialysis fluid,

[0183] c bic，0 is the bicarbonate ion concentration of the dilute base fluid,

[0184] is the sodium ion concentration of the dilute acid fluid and

[0185] c acid，0 is the acid concentration of the dilute acid fluid.

[0186] Then the value c BIC，pre is inserted into formula (3) as the set value of the bicarbonate ion concentration. This results in, according to formula (3#) above, the parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa being independent of the dilute base fluid and / or dilute acid fluid used, especially the dilute acid fluid. The parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa is obtained according to formula (4#) above.

[0187] Therefore, at the bicarbonate and sodium ion concentrations specified for the dialysis fluid, the actual concentration of other cationic species in the dialysis fluid (especially a combination of at least two selected from the potassium ion concentration, magnesium ion concentration, calcium ion concentration, and the concentration of the aforementioned cationic species) can be advantageously determined according to the following formula (10):

[0188]

[0189] wherein

[0190] c X，act is the actual concentration of other cationic species in the dialysis fluid (especially a combination of at least two selected from the potassium ion concentration, magnesium ion concentration, calcium ion concentration, and the concentration of the aforementioned cationic species),

[0191] c Na，set is the sodium ion concentration specified for the dialysis fluid,

[0192] c bic，pre is the bicarbonate ion concentration of the pre-dialysis fluid,

[0193] c X，0The concentration of other cationic species of the dilute acid fluid (in particular, a combination of at least two selected from the potassium ion concentration, magnesium ion concentration, calcium ion concentration, and the concentration of the aforementioned cationic species),

[0194] is the sodium ion concentration of the dilute acid fluid,

[0195] c acid，0 is the acid concentration of the dilute acid fluid and

[0196] c bic，0 is the bicarbonate ion concentration of the dilute base fluid.

[0197] In addition, it is advantageously possible to determine the total buffer of the dialysis fluid at the bicarbonate and sodium ion concentrations specified for the dialysis fluid.

[0198] The total buffer can be specified according to the selected dilute acid fluid:

[0199] Acetic acid and citric acid (example: SW 380, Citradial):

[0200] In this case, the total buffer is the same as the bicarbonate ion concentration before neutralization with the acid of the dilute acid fluid, i.e., the same as the bicarbonate ion concentration of the predialysis fluid, because each neutralized bicarbonate produces a corresponding acid salt:

[0201] Total buffer = c BIC，pre (11)

[0202] Hydrochloric acid (example: Lympha)

[0203] In this case, the total buffer is the same as the bicarbonate ion concentration after neutralization with the acid of the dilute acid fluid, i.e., the same as the bicarbonate ion concentration of the dialysis fluid. In the case of hydrochloric acid, the acid salt formed is only chloride, which is not metabolized into bicarbonate in the body like acetate and citrate.

[0204] Total buffer = c bic，post (12)

[0205] Acetoacetic acid (example: Granuflo)

[0206] In this case, for each additional acetic acid, one more acetate that can be metabolized into bicarbonate is added.

[0207]

[0208] where

[0209] c bic，pre is the bicarbonate ion concentration of the predialysis fluid,

[0210] cNa，set The sodium ion concentration specified for the dialysis fluid

[0211] The sodium ion concentration of the dilute acid fluid

[0212] c acid，0 The acid concentration of the dilute acid fluid and

[0213] c bic，0 The bicarbonate ion concentration of the dilute base fluid

[0214] Thus, the method may include a further step j): determining the concentration of at least one other constituent of the dialysis fluid, wherein the at least one other constituent is selected from potassium ions, magnesium ions, calcium ions, total buffer, and combinations of at least two of the foregoing constituents of the dialysis fluid

[0215] In a further embodiment of the present invention, the concentration of the base fluid and / or the acid fluid is stored or preserved on an extracorporeal blood treatment device, particularly a hemodialysis device or a peritoneal dialysis device, preferably a dialysis machine, particularly a hemodialysis machine or a peritoneal dialysis machine, or some other system

[0216] In a further embodiment of the present invention, at least a part (particularly only a part or the whole of the method) of the method is performed by an extracorporeal blood treatment device, particularly a hemodialysis device or a peritoneal dialysis device, preferably a dialysis machine, particularly a hemodialysis machine or a peritoneal dialysis machine

[0217] Furthermore, it may be preferred to perform the method only semi - automatically or fully automatically. In other words, it may be particularly preferred that only several steps (i.e., only some steps) or all steps of the method are performed automatically

[0218] In a further embodiment of the present invention, depending on the bicarbonate ion concentration determined according to step i), a further addition (particularly continuous or discontinuous addition) of the dilute base fluid to the pre - dialysis fluid is performed, and / or depending on the sodium ion concentration determined according to step i), a further addition (particularly continuous or discontinuous addition) of the dilute acid fluid to the dialysis fluid is performed

[0219] According to a second aspect, the present invention provides the use of the method according to the first aspect of the present invention for preparing or formulating a dialysis fluid (particularly for hemodialysis and / or peritoneal dialysis, preferably hemodialysis)

[0220] For further features and advantages of the said use, particularly those related to the method, full reference is made to the discussion regarding the first aspect of the present invention. The features and advantages described in relation to the method are also applicable, mutatis mutandis, to the use according to the second aspect of the present invention

[0221] According to a third aspect, the present invention provides an extracorporeal blood treatment device, in particular a hemodialysis device and / or a peritoneal dialysis device, preferably a hemodialysis device, particularly for performing the method according to the first aspect of the present invention, or provides the use of an extracorporeal blood treatment device (in particular a hemodialysis device and / or a peritoneal dialysis device, preferably a hemodialysis device) for performing the method according to the first aspect of the present invention.

[0222] The device may in particular comprise a first mixing chamber for mixing water (i.e., highly purified water or permeate water) with a dilute alkali fluid to form a predialysis fluid and a second mixing chamber for mixing the predialysis fluid with a dilute acid fluid to form a dialysis fluid.

[0223] Furthermore, the device may comprise a first feed pump for feeding the dilute alkali fluid into the first mixing chamber and a second feed pump for feeding the dilute acid fluid into the second mixing chamber.

[0224] Furthermore, the device may comprise a temperature sensor for measuring the temperature of the predialysis fluid and a conductivity sensor for measuring the conductivity of the predialysis fluid.

[0225] Furthermore, the device may comprise a temperature sensor for measuring the temperature of the dialysis fluid and a conductivity sensor for measuring the conductivity of the dialysis fluid.

[0226] Furthermore, the device may comprise software for comparing the measured conductivity of the predialysis fluid with a target value of the bicarbonate conductivity of the dialysis fluid and / or the predialysis fluid and for comparing the measured conductivity of the dialysis fluid with a target value of the conductivity of the dialysis fluid.

[0227] Furthermore, the device may comprise a controller for controlling the feed rate of the dilute alkali fluid into the first mixing chamber according to the measured conductivity of the predialysis fluid and for controlling the feed rate of the dilute acid fluid into the second mixing chamber according to the measured conductivity of the dialysis fluid.

[0228] The aforementioned components of the device may in particular be part of a dialysis fluid providing unit of the device.

[0229] Preferably, the extracorporeal blood treatment device is in the form of a dialysis machine, in particular for hemodialysis and / or peritoneal dialysis, preferably hemodialysis.

[0230] For further features and advantages of the device or the use of the device, in particular those related to the method, full reference is made to the discussion regarding the first aspect of the present invention. The features and advantages described in relation to the method also apply, mutatis mutandis, to the device or the use of the device according to the third aspect of the present invention.

[0231] The advantages of the method according to the invention are summarized again here as follows:

[0232] By means of the method according to the invention, the conversion factors for the alkali fluid (alkali concentrate or bicarbonate concentrate) and the acid fluid (acid concentrate) can be determined based only on the standard concentrations of the alkali fluid and / or the acid fluid (especially only the acid fluid), without any laboratory experimental determination. These factors are optimized for the standard concentrations of the alkali fluid and / or the acid fluid (especially only the acid fluid). In this range, the experimentally determined model error is advantageously less than 1 mmol / l for sodium ions and bicarbonate ions.

[0233] Therefore, the conversion factors that had to be determined by technicians before no longer need to be stored in extracorporeal blood treatment devices (especially dialysis machines). Instead, only the standard concentrations of the alkali fluid and / or the acid fluid (especially the acid fluid) used need to be configured in the machine. Such activities do not require trained technicians, but can be performed, for example, by dialysis nurses.

[0234] Further features and advantages of the invention will become apparent from the claims and the following description of the preferred exemplary embodiments of the invention, which are schematically illustrated by means of the drawings. It should be understood that the invention is not limited thereto. Description of the Drawings

[0235] Figure 1 The dialysis fluid supply unit of a dialysis machine for performing the method according to the invention is shown,

[0236] Figure 2 A closed-loop controller for setting the feed rate of the pump for feeding the dilute alkali fluid is shown,

[0237] Figure 3 A closed-loop controller for setting the feed rate of the pump for feeding the dilute acid fluid is shown,

[0238] Figure 4 The determination of the target values of the bicarbonate conductivity of the pre-dialysis fluid and the conductivity of the dialysis fluid is shown,

[0239] Figure 5 The user interface of a dialysis machine for performing the method according to the invention is shown, and

[0240] Figure 6 The flowchart of the method according to the invention is shown.

[0241] Examples

[0242] Figure 1 One embodiment of the device 1 for performing the method according to the invention is schematically shown.

[0243] The device 1 includes a dialysis fluid supply unit 2.

[0244] In the dialysis fluid supply unit 2, osmotic water, an alkali fluid diluted by mixing an alkali fluid having a defined or undefined bicarbonate ion concentration with water, and an acid fluid diluted by mixing an acid fluid having a defined or undefined sodium ion concentration and a defined or undefined acid concentration with water are mixed to form a dialysis fluid. The dialysis fluid is optionally fed to a dialyzer (not shown) of the device 1 at a later time.

[0245] The supply or preparation of the dialysis fluid is achieved as follows:

[0246] First, osmotic water OW and a dilute alkali fluid BF are mixed in a first mixing chamber 3 of the dialysis fluid supply unit 2. For this purpose, the dilute alkali fluid BF is fed into the first mixing chamber 3 via a feed pump 4 (in particular a volume-controlled feed pump). In the first mixing chamber 3, ideal mixing occurs between the osmotic water OW and the dilute alkali fluid BF to form a pre-dialysis fluid. Then, the pre-dialysis fluid passes through a temperature sensor TSBIC and a conductivity sensor LFSBIC. The temperature sensor TSBIC is designed to measure the temperature BICT of the pre-dialysis fluid. The conductivity sensor LFSBIC is designed to measure the conductivity BICLF of the pre-dialysis fluid. Preferably, the measured values BICT and BICLF determined by means of the aforementioned sensors are evaluated by software SW to determine the temperature-compensated conductivity of the pre-dialysis fluid.

[0247] In the method according to the invention, the conductivity is later compared with a target value S-BICLF of the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid by means of software SW. Depending on the measured conductivity BICLF, the feed rate FG4 of the feed pump 4 is continuously adjusted by means of software SW so that the conductivity BICLF of the pre-dialysis fluid is as close as possible to the target value S-BICLF of the bicarbonate conductivity (see the closed-loop controller schematically shown in Figure 2 .

[0248] In the next step, the pre-dialysis fluid is mixed with a dilute acid fluid SF in a second mixing chamber 5 of the dialysis fluid supply unit 2. For this purpose, the dilute acid fluid SF is fed into the second mixing chamber 5 via a feed pump 6 (in particular a volume-controlled feed pump). In the second mixing chamber 5, ideal mixing occurs between the pre-dialysis fluid and the dilute acid fluid SF to form a dialysis fluid. Then, the dialysis fluid passes through a temperature sensor TSEND and a conductivity sensor LFSEND. The temperature sensor TSEND is designed to measure the temperature ENDT of the dialysis fluid. The conductivity sensor LFSEND is designed to measure the conductivity ENDLF of the dialysis fluid. Preferably, the measured values ENDT and ENDLF determined by means of the two aforementioned sensors are evaluated by software SW to determine the temperature-compensated conductivity ENDLF.

[0249] In the method according to the invention, the conductivity ENDLF of the dialysis fluid is later compared with the target value S-ENDLF of the conductivity of the dialysis fluid by means of the software SW. Depending on the measured conductivity ENDLF, the feed rate FG6 of the feed pump 6 is continuously adjusted via the software SW so that the conductivity ENDLF is as close as possible to the target value S-ENDLF of the conductivity of the dialysis fluid (see Figure 3 the closed-loop controller shown in).

[0250] Preferably, for safety reasons, the software and the sensor system of the device 1 may have dual-channel redundancy (for clarity, Figure 2 and 3 the second channel is not shown in).

[0251] The target values of the bicarbonate conductivity and the conductivity of the dialysis fluid required for the two closed-loop controllers are determined by the software SW by means of the formulas (1) and (2) mentioned in the general description. The inputs used for this are the target concentrations of sodium ions and bicarbonate ions and the required base fluid and acid fluid, which can be input by the user of the device 1 into the device 1, in particular for performing extracorporeal blood treatment.

[0252] For this purpose, the device 1 may include a corresponding user interface. Figure 4 A suitable user interface 7 is schematically shown in. The user interface 7 includes an input area EF-S-BICLF for the target value of the bicarbonate ion concentration of the dialysis fluid and / or the predialysis fluid, an input area EF-S-NA for the target value of the sodium ion concentration of the dialysis fluid, and an input area EF-SF for the dilute acid fluid. Then, based on the aforementioned target values, the software SW determines the target value S-BICLF of the bicarbonate conductivity of the predialysis fluid and the target value S-ENDLF of the conductivity of the dialysis fluid.

[0253] Any other parameters required for calculating the target value S-BICLF of the bicarbonate conductivity of the dialysis fluid and the target value S-ENDLF of the conductivity can be advantageously stored in the device 1 and thus do not have to be input each time a treatment is performed. For example, appropriate further parameters may be available in the software SW at the factory or may be configured on-site before the treatment.

[0254] Based on the measured conductivity, in particular the temperature-compensated conductivity, the current concentrations of the components of the dialysis fluid can be calculated. In addition to the set parameters, these concentrations can then be displayed on the user interface of the device 1. Figure 5 A suitable user interface is schematically shown in. Figure 5The user interface 8 shown includes an input area EF-S-BICLF for the target value of the bicarbonate ion concentration of the dialysis fluid and / or the predialysis fluid, an input area EF-S-NA for the target value of the sodium ion concentration of the dialysis fluid, a display area AF-BIC for the current bicarbonate ion concentration of the dialysis fluid and / or the predialysis fluid, and a display area AF-NA for the current sodium ion concentration of the dialysis fluid. Optionally, the user interface may further include a display area AF-CA for the current calcium ion concentration of the dialysis fluid, a display area AF-K for the current potassium ion concentration of the dialysis fluid, a display area AF-MG for the current magnesium ion concentration of the dialysis fluid, and a display area AF-TB for the current total buffer concentration of the dialysis fluid.

[0255] For this purpose, the formulas (1), (2), (10), (11), (12) and (13) stated in the general description can be used.

[0256] Figure 6 A flowchart or process diagram of method V according to the present invention is shown.

[0257] Method V according to the present invention is a method for determining the sodium ion concentration and the bicarbonate ion concentration of a dialysis fluid (especially for hemodialysis and / or peritoneal dialysis).

[0258] The method comprises the following steps. The following steps can be performed in chronological order, or - especially at least some steps - not in chronological order.

[0259] Step a) includes providing a dilute base fluid by mixing a base fluid having a bicarbonate ion concentration (bicarbonate ion concentration) (especially a defined or undefined bicarbonate ion concentration) with water (i.e., high-purity water or permeate water) in a defined mixing ratio, and providing a dilute acid fluid by mixing an acid fluid having a sodium ion concentration (especially a defined or undefined sodium ion concentration) and an acid concentration (especially a defined or undefined acid concentration) with water (i.e., high-purity water or permeate water) in a defined mixing ratio.

[0260] In addition to the bicarbonate ion concentration, the base fluid may also have a sodium ion concentration, especially a defined or undefined sodium ion concentration. In particular, the base fluid can be provided in the form of an aqueous sodium bicarbonate solution.

[0261] In addition to the sodium ion concentration, the acid fluid may also have a potassium ion concentration (especially a defined or undefined potassium ion concentration), a magnesium ion concentration (especially a defined or undefined magnesium ion concentration), and a calcium ion concentration (especially a defined or undefined calcium ion concentration).

[0262] In particular, the acidic fluid may be provided in the form of an acidic aqueous solution comprising sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and an acid (in particular acetic acid or citric acid). Optionally, the acidic fluid may further comprise an osmotically active compound, in particular glucose.

[0263] Step b) comprises preparing a pre-dialysis fluid by adding (in particular continuously or discontinuously) a dilute alkaline fluid to water (i.e., highly pure water or permeate water).

[0264] Step c) comprises determining a target value for the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid based on the bicarbonate ion concentration of the dialysis fluid and / or the pre-dialysis fluid (in particular a defined or undefined bicarbonate ion concentration) and a parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration), and determining a target value for the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity) based on the sodium ion concentration of the dialysis fluid (in particular a defined or undefined sodium ion concentration) and a parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity) or vice versa (i.e., for converting the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity) into sodium ion concentration).

[0265] Step d) comprises measuring the conductivity of the pre-dialysis fluid.

[0266] Step e) comprises comparing the conductivity of the pre-dialysis fluid measured according to step d) with the target value for the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid determined according to step c), and, if necessary, further adding (in particular continuously or discontinuously) the dilute alkaline fluid to the pre-dialysis fluid, in particular by means of a feed pump, until the target value for the bicarbonate conductivity of the dialysis fluid and / or the pre-dialysis fluid has been reached or has been substantially reached.

[0267] Step f) comprises preparing the dialysis fluid by adding (in particular continuously or discontinuously) a dilute acidic fluid to the pre-dialysis fluid.

[0268] Step g) comprises measuring the conductivity of the dialysis fluid (in particular the final conductivity or total conductivity).

[0269] Step h) comprises comparing the conductivity of the dialysis fluid measured according to step g) with the target value for the conductivity of the dialysis fluid determined according to step c), and, if necessary, further adding (in particular continuously or discontinuously) the dilute acidic fluid to the dialysis fluid, in particular by means of a further feed pump, until the target value for the conductivity of the dialysis fluid has been reached or has been substantially reached.

[0270] Step i) comprises determining the bicarbonate ion concentration of the dialysate based on the conductivity of the pre-dialysate fluid measured according to step d) and a parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration), and determining the sodium ion concentration of the dialysate based on the conductivity of the dialysate fluid measured according to step g) and a parameter for converting the sodium ion concentration into the conductivity of the dialysate fluid or vice versa (i.e., for converting the conductivity of the dialysate fluid into sodium ion concentration).

[0271] Method V is particularly characterized by the fact that the parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa (i.e., for converting bicarbonate conductivity into bicarbonate ion concentration) and the parameter for converting the sodium ion concentration into the conductivity of the dialysate fluid or vice versa (i.e., for converting the conductivity of the dialysate fluid into sodium ion concentration) are both automatically determined.

[0272] For further features and advantages of method V, full reference is made to the discussion in the general description.

Claims

1. A method for determining the sodium and bicarbonate ion concentrations of a dialysis fluid, the method comprising the following steps: a) providing a dilute alkaline fluid by mixing an alkaline fluid having a bicarbonate ion concentration with water at a defined mixing ratio, and providing a dilute acid fluid by mixing an acid fluid having a sodium ion concentration and an acid concentration with water at a defined mixing ratio, b) preparing a pre-dialysis fluid by adding said dilute alkaline fluid to water, c) determining a target value for the bicarbonate conductivity of the dialysis fluid and / or pre-dialysis fluid based on the bicarbonate ion concentration of the dialysis fluid and / or pre-dialysis fluid and a parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa, and determining a target value for the conductivity of the dialysis fluid based on the sodium ion concentration of the dialysis fluid and a parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa, d) measuring the conductivity of the pre-dialysis fluid, e) comparing the conductivity of the pre-dialysis fluid measured according to step d) with the target value for the bicarbonate conductivity of the dialysis fluid and / or pre-dialysis fluid determined according to step c) and, if necessary, performing further addition of the dilute alkaline fluid to the pre-dialysis fluid until the target value for the bicarbonate conductivity of the dialysis fluid and / or pre-dialysis fluid has been reached or has substantially been reached. f) preparing the dialysis fluid by adding the dilute acid fluid to the pre-dialysis fluid, g) measuring the conductivity of the dialysis fluid, h) comparing the conductivity of the dialysis fluid measured according to step g) with the target value of the conductivity of the dialysis fluid determined according to step c) and, if necessary, performing further addition of the dilute acid fluid to the dialysis fluid until the target value of the conductivity of the dialysis fluid has been reached or has been substantially reached, and i) determining the bicarbonate ion concentration of the dialysis fluid based on the conductivity of the pre-dialysis fluid measured according to step d) and the parameter for converting the bicarbonate ion concentration into bicarbonate conductivity or vice versa, and determining the sodium ion concentration of the dialysis fluid based on the conductivity of the dialysis fluid measured according to step g) and the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa, The parameters for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa and the parameters for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa are both automatically determined.

2. The method according to claim 1, characterized in that The alkaline fluid also has a sodium ion concentration and is particularly provided in the form of an alkaline aqueous solution comprising sodium bicarbonate.

3. The method according to claim 1 or 2, characterized in that: The acid fluid also has a potassium ion concentration, a magnesium ion concentration and a calcium ion concentration, and is particularly provided in the form of an acidic aqueous solution comprising sodium chloride, potassium chloride, magnesium chloride, calcium chloride and an acid, particularly acetic acid.

4. The method according to any one of the preceding claims, characterized in that The target value for the bicarbonate conductivity of the dialysis fluid and / or pre-dialysis fluid is determined with the aid of a linear model, in particular according to the following formula (1): BICLF=c bic (mmol / l)xΛ m，bic (1) in BICLF is the target value for the bicarbonate conductivity of the dialysis fluid and / or pre-dialysis fluid, c bic is the bicarbonate ion concentration of the dialysis fluid and / or pre-dialysis fluid and Λ m，bic is the parameter used to convert the bicarbonate ion concentration into bicarbonate conductivity or vice versa.

5. The method according to any one of the preceding claims, characterized in that The target value for the conductivity of the dialysis fluid is determined with the aid of a linear model, in particular according to the following formula (2): ENDLF={[c Na+,总 (mmol / l)-c bic (mmol / l)]xΛ m,acid }+[cbic(mmol / l)xΛ m,bic ] (2) in ENDLF is the target value of the conductivity of the dialysis fluid, c Na+,总 is the sodium ion concentration of the dialysis fluid, c bic is the bicarbonate ion concentration of the dialysis fluid and / or pre-dialysis fluid, Λ m，acid is the parameter used to convert the sodium ion concentration into the conductivity of the dialysis fluid or vice versa and Λ m，bic is the parameter used to convert the bicarbonate ion concentration into bicarbonate conductivity or vice versa.

6. The method according to any one of the preceding claims, characterized in that The parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa and the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa are automatically determined based on the concentration of the dilute alkaline fluid and / or the dilute acid fluid, preferably the dilute acid fluid.

7. The method according to any one of the preceding claims, characterized in that The parameter for converting the bicarbonate ion concentration into the bicarbonate conductivity or vice versa is automatically determined based on the bicarbonate ion concentration of the dilute alkaline fluid and the acid concentration of the dilute acid fluid.

8. The method according to any one of the preceding claims, characterized in that The parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa is automatically determined based on the bicarbonate ion concentration of the dilute alkaline fluid, the sodium ion concentration of the dilute alkaline fluid, the sodium ion concentration of the dilute acid fluid, the potassium ion concentration of the dilute acid fluid, the magnesium ion concentration of the dilute acid fluid, the calcium ion concentration of the dilute acid fluid and the acid concentration of the dilute acid fluid.

9. The method according to any one of the preceding claims, characterized in that The parameter used to convert the bicarbonate ion concentration into bicarbonate conductivity or vice versa is determined according to the following formula (3): in Λ m，bic is the parameter used to convert the bicarbonate ion concentration into bicarbonate conductivity or vice versa, c bic，0 is the bicarbonate ion concentration of the dilute alkaline fluid and c acid，0 is the acid concentration of the dilute acid fluid.

10. The method according to any one of the preceding claims, characterized in that The parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa is determined according to the following formula (4): in Λ m，acid，kor is the parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa, is the sodium ion concentration of the dilute acid fluid resulting in a conductivity of the dilute acid fluid of 11 mS / cm, and is the acid concentration of the dilute acid fluid having a sodium ion concentration resulting in a conductivity of the dilute acid fluid of 11 mS / cm.

11. The method according to claim 10, characterized in that The sodium ion concentration of the dilute acid fluid that results in a dilute acid fluid conductivity of 11 mS / cm is determined according to the following formula (5): in is the sodium ion concentration of the dilute acid fluid resulting in a conductivity of the dilute acid fluid of 11 mS / cm, and Λ m，acid is an uncorrected parameter used to convert the sodium ion concentration into the conductivity of the dialysis fluid or vice versa.

12. The method according to claim 11, characterized in that The uncorrected parameter Λ for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa m，acid Determined according to the following formula (6): in Λ m，acid is the uncorrected parameter for converting the sodium ion concentration into the conductivity of the dialysis fluid or vice versa, is the sodium ion concentration of the dilute acid fluid, is the potassium ion concentration of the dilute acid fluid, is the magnesium ion concentration of the dilute acid fluid and is the calcium ion concentration of the dilute acid fluid.

13. The method according to claim 10, characterized in that The acid concentration of the dilute acid fluid having a sodium ion concentration that results in a dilute acid fluid conductivity of 11 mS / cm is determined according to the following formula (7): in is the acid concentration of the dilute acid fluid having a sodium ion concentration resulting in a conductivity of the dilute acid fluid of 11 mS / cm, c bic，0 is the bicarbonate ion concentration of the dilute alkaline fluid, c acid，0 is the acid concentration of the dilute acid fluid, is the sodium ion concentration of the dilute acid fluid and is the sodium ion concentration of the dilute acid fluid that results in a conductivity of the dilute acid fluid of 11 mS / cm.

14. The method according to any one of the preceding claims, characterized in that The concentrations of the alkaline fluid and the acidic fluid are stored on an extracorporeal blood treatment device, in particular a hemodialysis device.

15. The method according to any one of the preceding claims, characterized in that At least a part of the method, in particular only a part of the method or the entire method, is performed by an extracorporeal blood treatment apparatus, in particular a hemodialysis apparatus.

16. A method according to any one of the preceding claims, characterised in that Depending on the bicarbonate ion concentration determined according to step i), a further addition of the dilute alkaline fluid to the pre-dialysis fluid is performed and / or depending on the sodium ion concentration determined according to step i), a further addition of the dilute acid fluid to the dialysis fluid is performed.

17. Use of the method according to any of the preceding claims for preparing or proportioning the dialysis fluid, in particular a dialysis fluid for hemodialysis.

18. Use of an extracorporeal blood treatment apparatus, in particular a hemodialysis apparatus, for carrying out the method according to any one of claims 1 to 16.

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