Therapeutic aspects for reducing the carbon dioxide content in the blood

Abstract

The present invention relates to various aspects of a procedure for reducing the carbon dioxide content in the blood during the treatment of a patient. A first aspect of the present invention relates to a buffer solution for reducing the carbon dioxide content in the blood when treating a patient suffering from pulmonary insufficiency or complete pulmonary failure, wherein the fluid exchanges gases with a portion of the patient's blood conveyed through an extracorporeal circuit. The first aspect of the present invention also relates to a device for extracorporeally reducing the carbon dioxide content in the blood using the buffer solution. A second aspect of the present invention relates to a system for extracorporeal blood treatment using the buffer solution and the device as well, and also relates to a treatment device for extracorporeal blood treatment comprising the above system. A third aspect of the present invention relates to a functional unit for performing extracorporeal blood treatment, a blood guiding device for interacting with the functional unit for performing extracorporeal blood treatment using the above buffer solution, the blood guiding device comprising a blood treatment element, wherein the blood treatment element is the above device for extracorporeally reducing the carbon dioxide content in the blood. In a fourth aspect, the present invention relates to a treatment system comprising the above device for extracorporeally reducing the carbon dioxide content in the blood and a balancing device. In a fifth aspect, the present invention relates to a treatment system comprising the above device for extracorporeally reducing the carbon dioxide content in the blood and a device for reducing the pressure of the above buffer solution used in the treatment system.

Description

Technical Field

[0001] The present disclosure relates to various aspects of a procedure for reducing the carbon dioxide content in the blood during the treatment of a patient. A first aspect of the present disclosure relates to a buffer solution for reducing the carbon dioxide content in the blood when treating a patient suffering from pulmonary insufficiency or complete pulmonary failure, wherein a fluid exchanges gases with a portion of the patient's blood transported through an extracorporeal circuit. The first aspect of the present disclosure also relates to a device for extracorporeally reducing the carbon dioxide content in the blood using the buffer solution. A second aspect of the present disclosure relates to a system for extracorporeal blood treatment using the buffer solution and the device as well, and further relates to a treatment device for extracorporeal blood treatment including the above system. A third aspect of the present disclosure relates to a functional unit for performing extracorporeal blood treatment, a blood guiding device for interacting with the functional unit for performing extracorporeal blood treatment using the above buffer solution, the blood guiding device including a blood treatment element, wherein the blood treatment element is the above device for extracorporeally reducing the carbon dioxide content in the blood. In a fourth aspect, the present invention relates to a treatment system including the above device for extracorporeally reducing the carbon dioxide content in the blood and a balancing device. In a fifth aspect, the present invention relates to a treatment system including the above device for extracorporeally reducing the carbon dioxide content in the blood and a device for reducing the pressure of the above buffer solution used in the treatment system. Background Art

[0002] The central task of the lungs is the gas exchange of oxygen (O2) and carbon dioxide (CO2). Thus, oxygen is absorbed and carbon dioxide is released, and in the normal state, the optimal state of the lungs prevails in this regard.

[0003] The diffusion of oxygen and carbon dioxide in the lungs occurs over a very large area of 80 to 120 m 2 , and the blood film thickness is low and the contact time is long enough. In the case of lung dysfunction, such as during cardiac surgery, or when the lungs are severely damaged so that they cannot fully perform their gas exchange function, such as in patients suffering from acute respiratory distress syndrome (ARDS), medical procedures are required to replace or assist the lacking or insufficient gas exchange function.

[0004] The device used today to assist or completely replace the gas exchange function of the lungs is a membrane oxygenator, wherein the extracorporeally guided blood is separated from the gas phase via a membrane. Oxygen is provided to saturate the blood via the membrane, and carbon dioxide is released from the blood into the gas phase. The basic structure and operating mode of the membrane oxygenator are known from the prior art and are explained in more detail, for example, in the patent specification EP0 465 506 81.

[0005] Combined with the described prior art and the present disclosure, the term "extracorporeally guided blood" or the expression "blood conveyed through an extracorporeal circuit" refers to a part of the patient's blood located in the extracorporeal circuit, with the aim of reducing the carbon dioxide content in order to enable gas exchange with the elimination medium there.

[0006] Modern oxygenators use microporous polypropylene hollow fibers (i.e., hollow fibers made of PP, polypropylene) or microporous hollow fibers made of PMP (polymethylpentene) for gas exchange between extracorporeal blood and the elimination medium. The blood flows through the outside of these hollow fibers in a countercurrent manner, while the oxygen / air mixture flows through the inside of the fibers. Some of these oxygenators have been further developed to achieve optimized effects in eliminating carbon dioxide from the patient's blood. For example, EP 2 777801A2 describes a device for at least partially eliminating CO2 from the patient's blood, in which a hollow fiber device with an active fiber length is provided in a housing, through which both gas and blood can flow, and the ratio of the active fiber length to the minimum blood passage distance through the hollow fiber device does not exceed a specific value.

[0007] Technical Problem

[0008] When reducing CO2 in the lungs, the normal physiological values on the arterial side / mixed venous side are as follows:

[0009] a) On the mixed venous side

[0010] · pH = 7.369

[0011] · Partial pressure of carbon dioxide pCO2 = 46 mmHg

[0012] · Partial pressure of oxygen pO2 = 40 mmHg

[0013] · Oxygen saturation sO2 = 73%

[0014] b) On the arterial side:

[0015] · pH = 7.4

[0016] · Partial pressure of carbon dioxide pCO2 = 40 mmHg

[0017] · Partial pressure of oxygen pO2 = 90 mmHg

[0018] · Oxygen saturation sO2 = 96%

[0019] After absorbing O2 at a rate of 250 ml / min, pCO2 decreased from 46 mmHg to 40 mmHg, while pO2 increased from 40 mmHg to 90 mmHg. In doing so, 212 ml of CO2 was removed at a pressure difference of ΔpCO2 = 6 mmHg.

[0020] The affinity of the elimination medium used for CO2 absorption on the elimination side is crucial for the diffusion of CO2 from the blood to the elimination side. The higher the affinity on the elimination side compared to the blood, the more successful the diffusion. The main storage capacity is crucial for the convection on the elimination side. The higher the capacity on the elimination side, the lower the flow rate required to remove CO2.

[0021] The gas (air or a mixture of air with oxygen, nitrogen, or an inert gas) that is commonly used as an elimination medium in a membrane oxygenator has a rather low affinity on the elimination side, and its performance can be comparable to the CO2 diffusion from the blood to the elimination side in the lungs. In addition, the storage capacity is too low to maintain the convection on the elimination side, and it must be compensated for by a high flow rate (high gas flow rate).

[0022] The pulmonary physiology uses a surface area of 80 - 120 m 2 and the optimal geometry of the gas exchange surface in the form of spherical alveoli with a diameter of 50 to 250 μm to compensate for all of these.

[0023] The disadvantage of using a membrane oxygenator to eliminate carbon dioxide from the blood, which is known in the prior art, is that these devices only imperfectly mimic the human lungs. In a membrane oxygenator, the blood layer is quite thick, and compared to the very large surface area of up to 120 m 2 in the lungs, there is only a diffusion surface of approximately 2 to 10 m 2 .

[0024] Therefore, there is a need for a device through which better CO2 diffusion and convection can be achieved in patients suffering from pulmonary insufficiency or complete pulmonary failure, thereby enabling more effective CO2 reduction. Summary of the Invention

[0025] It is obvious that replacing the gas that is commonly used as an elimination medium in a membrane oxygenator with a fluid having properties particularly suitable for this purpose has considerable advantages.

[0026] Therefore, the present disclosure proposes using a buffer solution to reduce the carbon dioxide content in the blood during the treatment of patients suffering from pulmonary insufficiency or complete pulmonary failure, wherein the buffer solution is an aqueous solution that exchanges gases with the blood transported in an extracorporeal circuit of the patient and contains buffer A and buffer B, wherein

[0027] · Buffer A consists of at least one buffer substance having a pK value of 7.9 ± 0.2 at 37 °C,

[0028] and

[0029] · Buffer B consists of at least one buffering substance having a pK value of 6.9 ± 0.2 at 37°C, and wherein

[0030] at a carbon dioxide partial pressure pCO2 = 0.2 mmHg ± 0.2, the post - titration pH value of the solution is in the range of 8.25 to 8.35.

[0031] It has become apparent that the desired high affinity for CO2 absorption and the capacity for CO2 removal required for the elimination side can best be provided by a fluid which should correspond as much as possible to the electrolytic buffering characteristics of blood.

[0032] The DE 33 212 00C2 patent specification describes the use of a synthetic fluid as a blood substitute or as a solution for organ preservation, wherein the solution largely corresponds to the electrolytic buffering characteristics of blood. This is achieved by a solution comprising at least one buffer having a pK value of about 7.9 and a buffer having a pK value of about 6.9. The known prior - art buffer solutions were developed at that time to simulate as optimally as possible the behavior of natural blood with respect to the ratio of the pH value of blood to the carbon dioxide partial pressure (pCO2). It can now be shown for the first time in the present disclosure that these buffer solutions can also be advantageously used in a completely different context.

[0033] In particular, it has been shown that when treating patients suffering from pulmonary insufficiency or complete pulmonary failure, the buffer solutions disclosed herein can be used with great advantage to reduce the carbon dioxide content in the blood when the buffer solution exchanges gases with the patient's blood transported through an extracorporeal circuit. The obvious reason is that the buffer solution used herein has a 6 - fold higher affinity for CO2 absorption compared to the gas usually used as the elimination medium and an 11 - fold higher affinity for water in this regard.

[0034] The new implementation underlying the present disclosure particularly includes the fact that the buffer solution used herein not only provides a very high CO2 affinity (ml / l / mmHg), but also has an extremely high CO2 transport capacity (ml / I). The CO2 transport capacity of the buffer solution used herein can even exceed that of natural blood.

[0035] For example, at a predetermined pH of 7.4 and a partial pressure of carbon dioxide (pCO2) of 40 mmHg, the buffer solution can transport 18.7% more CO2 than natural blood. At a hematocrit of 45%, the bicarbonate concentration is 20 mmol / l, consisting of 24 mmol / l bicarbonate in plasma and 15 mmol / l bicarbonate in red blood cells. If the free carbonic acid concentration of 1.2 mmol / l is included, the CO2 transport in natural blood is 475 ml / l. On the other hand, in the case of the buffer solution disclosed herein, 564 ml / l can be achieved.

[0036] According to the present disclosure, buffer A consists of at least one buffering substance having a pK value of 7.9 ± 0.2 at a temperature of 37 °C, and buffer B consists of at least one buffering substance having a pK value of 6.9 ± 0.2 at a temperature of 37 °C. By titration, the pH of the solution is adjusted to a range of 8.25 to 8.35 in the case of a partial pressure of carbon dioxide pCO2 = 0.2 mmHg ± 0.2. In a specific embodiment, by titration, the pH value is adjusted to a value of 8.285 ± 0.02 in the case of a partial pressure of carbon dioxide pCO2 = 0.2 mmHg ± 0.2. In a very specific embodiment, the pH value is adjusted to a value of 8.285.

[0037] The present disclosure also includes variants, in which the buffer combination is obtained by two components produced from a single buffering substance - for example, by a chemical reaction - which exhibit pK values according to the disclosure after being dissolved in water.

[0038] Furthermore, the present disclosure also includes a multi-component system in which the buffer solution consists of more than two buffering substances. An example of an embodiment of a multi-component system comprising three components includes an additional third buffering substance having a pK value between the pK values of the other two buffering substances.

[0039] In certain embodiments of the present disclosure, in addition to buffer A and buffer B, the buffer solution may further comprise at least one buffer C and at least one buffer D, where buffer C and buffer D each consist of at least one buffering substance, and their pK values are substantially equidistantly located between the pK values of 6.9 ± 0.2 and 7.9 ± 0.2 at 37 °C. Also in these embodiments of the present disclosure, in the case of a partial pressure of carbon dioxide pCO2 = 0.2 mmHg ± 0.2, the finished buffer solution has a post-titration pH value in the range of 8.25 to 8.35. In a specific embodiment, by titration, the pH value in the case of a partial pressure of carbon dioxide pCO2 = 0.2 mmHg ± 0.2 is adjusted to a value of 8.285 ± 0.02. In a very specific embodiment, the pH value is adjusted to a value of 8.285.

[0040] The buffer solution preferably has a particularly high effective carbon dioxide affinity. Particularly preferably, the effective carbon dioxide affinity is greater than that of natural blood. In certain embodiments, at a carbon dioxide partial pressure of 40 mmHg, the effective carbon dioxide affinity is at least 10 ml / l / mmHg, preferably greater than 15 ml / l / mmHg. In alternative embodiments, at a pCO2 of 10 mmHg, the effective carbon dioxide affinity is at least 20 ml / l / mmHg, preferably ≥25 ml / l / mmHg, even more preferably ≥30 ml / l / mmHg. In these embodiments, embodiments where the pCO2 of the buffer solution is in the range of 0 to 10 mmHg are preferred.

[0041] The buffer solution preferably has a particularly high carbon dioxide transport capacity. Particularly preferably, the effective carbon dioxide transport capacity is greater than that of natural blood. An advantage of the buffer solution used as disclosed herein relative to natural blood is in particular a buffer solution without red blood cells, while blood consists of CO2-rich plasma and low-CO2 red blood cells at a given pCO2. At a pCO2 of 40 mmHg, in certain embodiments of the buffer solution disclosed herein, the carbon dioxide transport capacity is at least 500 ml / l or higher, and in alternative embodiments, the carbon dioxide transport capacity at a pCO2 of 10 mmHg is at least 250 ml / l or higher.

[0042] In certain embodiments, the pCO2 of the buffer solution used as disclosed herein is at most 0.2 mmHg ± 0.2, and thus within the partial concentration range in inhaled air.

[0043] The main feature of the present disclosure is that the buffering substances used in the buffer solution have appropriate pK values. In particular, the buffer solution requires buffer A and buffer B, where buffer A consists of at least one buffering substance with a pK value of 7.9 ± 0.2 at 37 °C, and buffer B consists of at least one buffering substance with a pK value of 6.9 ± 0.2 at 37 °C.

[0044] All buffering substances with the above properties are in principle suitable for achieving the object of the present disclosure. For example, the buffering substances disclosed herein used in the buffer solution can be selected from: BICINE (N,N-bis-(2-hydroxyethyl)glycine), BES (N,N-bis-(2-hydroxyethyl)glycine)-2-aminoethanesulfonic acid), TAPS (N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid), TRICIN (N-tris(hydroxymethyl)methylglycine), TRIS (tris(hydroxymethyl)aminomethane), imidazole (1,3-diazole), HEPES (2-(4-(2-(hydroxyethyl)-1-piperazinyl)ethanesulfonic acid), and sodium phosphate (Na2HPO4), but the present disclosure is not limited in any way to these specific buffering substances.

[0045] In a specific embodiment of the present disclosure, the buffer solution used comprises the following components:

[0046] Buffer A Tris 36.0 mmol / l

[0047] Buffer B Na2HPO4 34 mmol / l

[0048] Titration HCl 12.0 mmol / l

[0049] The buffer solution disclosed herein described in the present application can be a component of a device for reducing the carbon dioxide content in blood in vitro as an elimination medium. Accordingly, the present disclosure also includes a device having a first defined region for receiving blood in vitro and a second defined region for receiving the buffer solution disclosed herein, wherein the first and second regions adjacent to each other in the contact region are separated only by a membrane, and gas exchange can occur between the blood and the buffer solution via the membrane.

[0050] In a particularly designed embodiment of the device disclosed herein, the first defined region for receiving blood in vitro has an inlet port and an outlet port for the blood and is configured such that the blood can flow from the inlet port through the region to the outlet port along a first flow direction. In this embodiment, the second defined region for receiving the buffer solution has an inlet port and an outlet port for the buffer solution and is configured such that the buffer solution can flow from the inlet port through the region to the outlet port along a second flow direction.

[0051] In certain embodiments of the present disclosure, the flow directions in the respective regions are oriented such that the first flow direction in the first region and the second flow direction in the second region are opposite to each other.

[0052] The device disclosed herein has an exchange surface through which gas exchange can occur via the membrane in the contact region. In certain embodiments, the exchange surface extends at least 0.3 m 2 , in particular at least 0.6 m 2 , in particular at least 1 m 2 , preferably at least 2 m 2 . In certain embodiments, the exchange surface extends up to 5 m 2 square meters, preferably up to 3 m 2 .

[0053] Preferably, the exchange surface is a gas permeable membrane known in the prior art. Such a membrane can consist of, for example, micropores (e.g., PP = polypropylene) or diffusive hollow fibers (e.g., PMP = polymethylpentene), as described in EP 2 777 801 A1. These hollow fibers can be arranged in a parallel-aligned mat, and the hollow fiber arrangement structure can have a cylindrical or approximately cuboid shape.

[0054] In a further embodiment, the device disclosed herein is characterized in that the membrane through which gas exchange occurs comprises polysulfone and optionally polyvinylpyrrolidone. In the context of the present disclosure, the term "polysulfone" should be understood as a general term for polymers characterized by sulfonic acid groups in the polymer chain. Polysulfone (PSU) and polyethersulfone (PES) are known polysulfone agents.

[0055] In a further embodiment, the device disclosed herein is characterized in that the membrane separating the first defined region and the second defined region from each other is formed by a plurality of hollow fibers. The term "hollow fiber" should be understood as a hollow fiber composed of a membrane material. The corresponding hollow fibers, especially those containing polysulfone and polyvinylpyrrolidone, are known to those skilled in the art in the field of therapeutic extracorporeal blood treatment. The hollow fibers are arranged such that the membrane (also referred to as "hollow fiber membrane") is formed by the hollow fibers separating the first and second regions from each other. In this regard, those skilled in the art are familiar with filters based on such hollow fiber membranes (also referred to as "hollow fiber membrane filters"). The end regions of such hollow fiber membranes in the hollow fiber membrane filter are fixed in the hollow fiber membrane filter by means of a potting compound. The hollow fiber membrane is thus open at the ends, such that the interior of the hollow fibers in the hollow fiber membrane filter and the intermediate space between the hollow fibers form the first and second defined regions, where blood can enter the first defined region and the buffer solution disclosed herein can enter the second defined region.

[0056] In particular, in the context of the present disclosure, a "device" is understood to be a blood treatment device that serves as a gas exchange device for extracorporeal blood treatment, especially for gas exchange of CO2, in order to reduce the carbon dioxide content in the extracorporeal treated blood.

[0057] To remove CO2 from the blood, one embodiment of the present disclosure utilizes a membrane based on silicone-coated hollow fibers that comprises polysulfone and optionally polyvinylpyrrolidone. Such hollow fiber membranes are described in DE 10034098. It can be seen that the advantage of using such hollow fiber membranes for extracorporeal treatment of blood to reduce the carbon dioxide content is that silicone has a higher CO2 permeability compared to alternative polymers that can be used to form the hollow fiber membrane. Therefore, the inner surface and / or outer surface of the hollow fibers can be coated with silicone.

[0058] The flow rate of blood through the first defined region is desirably at most 20% by volume, particularly desirably at most 15% by volume, of the patient's cardiac output, and the carbon dioxide content in the blood will be reduced extracorporeally with the device. In some embodiments, the flow rate of blood through the first defined region is at most 10% by volume of the cardiac output.

[0059] Based on the calculation basis for a patient weighing 75 kg, the flow rate of blood through the first defined region is in some embodiments at least 100 ml / min, preferably at least 200 ml / min, or at least 500 ml / min, or preferably at least 600 ml / min, or particularly preferably at least 750 ml / min. Based on the calculation basis for a patient weighing 7.5 kg, in some embodiments, the flow rate is at least 50 ml / min, preferably 60 ml / min, particularly preferably 75 ml / min.

[0060] Based on the calculation basis for a patient weighing 75 kg, the flow rate of blood through the first defined region is in some embodiments at most 1000 ml / min, or at most 800 ml / min, preferably at most 700 ml / min, particularly preferably at most 600 ml / min. Based on the calculation basis for a patient weighing 7.5 kg, the flow rate of blood through the first defined region is in some embodiments at most 80 ml / min, preferably at most 75 ml / min, particularly preferably at most 60 ml / min.

[0061] The flow rate of the buffer solution through the second defined region depends on its composition and is only 10 to 100% by volume or only 50 to 100% by volume of the flow rate of blood through the first defined region.

[0062] In some embodiments, the device has means for enriching the extracorporeally directed blood with oxygen. Thereby, the oxygenation of the blood can occur simultaneously with the CO2 reduction, so that the Christiansen-Douglas-Haldane effect can be utilized. The oxygenated blood can then better release CO2. Therefore, sO2 can increase in 10% of the blood exchanged, for example, from 50% to 100%.

[0063] Preferably, the device has means for regenerating the buffer solution, via which the carbon dioxide absorbed from the blood can be removed from the buffer solution again. Particularly preferably, this is achieved via an optional metered supply of concentrated acid, wherein 98% of the carbon dioxide is stored in the buffer solution in the form of bicarbonate and is increasingly converted into carbon dioxide and can be degassed in this form. Preferably, the means for regenerating the buffer solution consists of a device for supplying acid to the buffer solution to be regenerated.

[0064] In an alternative embodiment, the buffer solution can also be regenerated in another device. The other device is a regeneration device. It can consist of a first defined region and a second defined region, where the two defined regions are separated from each other only by a membrane or membranes (such as hollow fiber membranes), and the hollow fiber membranes form the membranes for defining the first defined region and the second defined region. The membrane is a membrane that enables the first defined region and the second defined region to form a gas exchange relationship. According to one of the embodiments described herein, the membrane or hollow fiber membrane of the regeneration device can be designed according to the membrane in a device for reducing the carbon dioxide content in blood. The regeneration device is operated with a buffer solution flowing through the first defined region, where a regeneration fluid or regeneration gas flows through the second defined region. The device for reducing the carbon dioxide content in blood and the regeneration device can be connected in series; that is, the buffer solution first flows through the second defined region of the device for reducing the carbon dioxide content in blood, and then through the first defined region of the regeneration device. The device for reducing the carbon dioxide content in blood and the regeneration device can also be configured together in one device, where the device for reducing the carbon dioxide content in blood then exhibits the characteristics of the regeneration device.

[0065] For the purpose of the initial disclosure, it is pointed out that all features, figures, forms of use, and embodiments described in this specification can also be derived by those skilled in the art, even if they have only been described in combination with specific other features, can be combined individually, or can be combined with other features or groups of features disclosed herein in any combination, as long as such combination is not explicitly excluded or technical circumstances make such combination impossible or meaningless. For the sake of brevity and readability of the description, a comprehensive and exhaustive presentation of all possible feature combinations is only omitted here.

[0066] It is further pointed out that it is obvious to those skilled in the art that the following exemplary embodiments and figures are only used to represent the exemplary embodiments of the present disclosure.

[0067] Accompanying Drawings

[0068] Figure 1 The dependence of the plasma pH on the corresponding respiratory load R (CO2 load) of the blood is shown (cHb = 159 g / l, BE = 0 mmol),

[0069] Figure 2 The comparison of the CO2 affinity and transport capacity of the buffer solution (synthetic blood) disclosed herein with the CO2 affinity and transport capacity of natural blood (blood) according to the corresponding carbon dioxide partial pressure is shown, and

[0070] Figure 3 The basic structure of a specific embodiment of the device for reducing the carbon dioxide content in blood disclosed herein is schematically shown.

[0071] For the purpose of illustrating the present disclosure, Figure 1 the dependence of the respiratory load R (CO2 load) of blood on the plasma pH value is depicted (cHb = 159 g / l, 35 BE = 0 mmol).

[0072] The parameters of curves A to F are the different concentrations of "non-volatile bases" present in the blood, which are basically the "PP fraction" (commonly referred to as BE) composed of proteins and phosphates remaining due to the non-respiratory load NR. This PP fraction almost completely determines the buffering characteristics of the blood because it necessarily generates the bicarbonate fraction from the correspondingly present CO2 concentration. This is particularly important because bicarbonate is mainly present in the plasma and the PP component is mainly present in the red blood cells (see also DE 31 13 797 C2).

[0073] The resulting bicarbonate in turn greatly improves the buffering effect: at a pCO2 value of 40 mmHg, the blood contains 20 ± 0.2 mmol / l of bicarbonate. This results in a pH value of 7.4. Thus, the respiratory buffering capacity is 25 ± 0.2 mmol / l / pH, and the non-respiratory buffering capacity is 65 ± 0.2 mmol / l / pH. Therefore, 40% of the non-respiratory buffering capacity is represented by the PP fraction, while 60% is represented by the bicarbonate fraction.

[0074] The buffering characteristics of human blood depend on the pH value, the partial pressure of CO2, and the type of electrolytes supplied. The UP region in the figure is non-physiological, the PAP region is pathophysiological, and the P region is the physiological range of variable pH-pCO2; therefore, the dependence of the buffering characteristics on the hemoglobin concentration or hematocrit is not considered.

[0075] Furthermore, it can be seen from Figure 1 that as the pCO2 decays, curve D, which also operates within the physiological range P when only non-volatile bases (PP fraction) are retained in the blood, intersects the abscissa at pH = 8.285. Therefore, the synthetic blood used as a buffer solution disclosed herein must exhibit this intersection point. The intersection point can be adjusted by appropriate titration with NaOH or HCl.

[0076] Figure 2 A comparison of the CO2 affinity and transport capacity of the buffer solution (synthetic blood) disclosed herein with those of natural blood (blood) according to the corresponding partial pressure of CO2 is depicted. Thus, at a given partial pressure of CO2, the buffer solution disclosed herein always has a higher CO2 affinity and transport capacity than natural blood.

[0077] Figure 3is a highly schematic depiction of the basic structure of the device for reducing the carbon dioxide content in blood in vitro disclosed herein. What is seen in the figure is a first defined region 1 for receiving blood in vitro and a second defined region 2 for receiving the buffer solution disclosed herein. The first and second regions adjacent to each other in the contact area are separated only by a membrane 3, through which gas exchange can occur between the blood and the buffer solution.

[0078] The first defined region 1 has a blood inlet port 4 and an outlet port 5 for receiving blood in vitro, and is designed such that blood can flow from the inlet port 4 through the region to the outlet port 5 along a first flow direction 6. The second defined region 2 has a buffer solution inlet port 7 and an outlet port 8 for receiving the buffer solution, and is designed such that the buffer solution can flow from the inlet port 7 through the region to the outlet port 8 along a second flow direction 9. The first flow direction of the first region and the second flow direction of the second region are thus oriented to run in opposite directions to each other.

[0079] Embodiment

[0080] A. Various Embodiments of the Buffer Solution Disclosed herein

[0081] 1. Two-component buffer system

[0082] An embodiment of the buffer solution used according to the present invention is produced in the following manner:

[0083] Buffer A TRIS 36.0 mmol / I

[0084] Buffer B Na2HPO4 34.0 mmol / I

[0085] In the absence of CO2, it is weighed and titrated to a pH value of 8.285 using HCl as the titration degree (12.0 mmol / 1).

[0086] 2. Multicomponent system

[0087] If the buffer solution consists of more than two components, according to the present disclosure, the pK values of the other two buffer substances are set equidistantly between the pK values of 6.9 ± 0.2 and 7.9 ± 0.2.

[0088] An embodiment of the multicomponent system containing three components includes the following components:

[0089] Buffer A TRIS (pK = 7.9) 23.5 mmol / l

[0090] Buffer B HEPES (pK = 7.4) 19.5 mmol / l

[0091] Buffer C Phosphate (pK = 6.9) 17.0 mmol / l

[0092] In this variant of the present disclosure, the pK value of the additional third buffering substance lies in the middle between the pK values of the other two buffering substances.

[0093] Thus, a particularly advantageous combination of substances can be selected for the respective purpose. Thus, the combination of substances can also show pK values in accordance with the present disclosure after a single substance formed from multiple components - for example, by a chemical reaction - is dissolved in water.

[0094] B. Uses of the Buffer Solution Disclosed herein

[0095] In a membrane oxygenator, blood with a hemoglobin concentration of cHb = 159 g / l, an oxygen partial pressure of pO2 = 25 mmHg, and an oxygen saturation of sO2 = 50% is treated with a buffer solution according to the present disclosure.

[0096] Oxygenation is carried out simultaneously during CO2 reduction, and the Christiansen - Douglas - Haldane effect is partially utilized by adding oxygen to the blood led extracorporeally. Thus, in 10% of the exchanged blood, sO2 increases from 50% to 100%. The buffer solution used comprises the following components:

[0097] Buffer A TRIS 36.0 mmol / l

[0098] Buffer B Na2HPO4 34.0 mmol / l

[0099] Titration HCl 12.0 mmol / l

[0100] Example 1:

[0101] The partial pressure pCO2 of the venous blood to be treated is reduced from 50 mmHg to 10 mmHg in a counter - current with a 1:1 flow rate, thereby removing 300 ml / l of CO2 (see Figure 2 : blood). The buffer solution absorbs the same amount of CO2, and its CO2 partial pressure rises from 0 mmHg to 10.5 mmHg (see Figure 2 : synthetic blood). The required blood flow rate is 707 ml / min, and the HZV is 14%.

[0102] Example 2:

[0103] The partial pressure pCO2 of the venous blood to be treated is reduced from 50 mmHg to 10 mmHg in a countercurrent flow at a 1:1 flow rate, while the sO2 is oxygenated from 50% to 100%, thereby removing 321 ml / l of CO2. As a result, the buffer solution absorbs the same amount of CO2, and its CO2 partial pressure rises from 0 mmHg to 16 mmHg. The required blood flow rate is 660 ml / min, and the HZV is 13.2%.

[0104] Example 3:

[0105] The partial pressure pCO2 of the venous blood to be treated is reduced from 55 mmHg (pulmonary dysfunction) to 10 mmHg in a countercurrent flow at a 1:1 flow rate, while the sO2 is oxygenated from 50% to 100%, thereby removing 342 ml / l of CO2. The buffer solution absorbs the same amount of CO2, and its CO2 partial pressure rises from 0 mmHg to 18 mmHg. The required blood flow rate is 620 ml / min, and the HZV is 12.4%.

[0106] Example 4:

[0107] The partial pressure pCO2 of the venous blood to be treated is reduced from 70 mmHg (hypercapnia) to 10 mmHg in a countercurrent flow at a 1:1 flow rate, while the sO2 is oxygenated from 50% to 100%, thereby removing 403 ml / l of CO2. The buffer solution absorbs the same amount of CO2, and its CO2 partial pressure rises from 0 mmHg to 25 mmHg. The required blood flow rate is 526 ml / min, and the HZV is 10.5%.

[0108] Figures 1 to 3 List of reference numerals:

[0109] 1 First defined region

[0110] 2 Second defined region

[0111] 3 Membrane

[0112] 4 Inlet port for blood

[0113] 5 Outlet port for blood

[0114] 6 First flow direction

[0115] 7 Inlet port for buffer solution

[0116] 8 Outlet port for buffer solution

[0117] 9 Second flow direction

[0118] 10 Device for in vitro reduction of carbon dioxide content in blood

[0119] In a first aspect, the subject matter of the present disclosure is characterized by the following use forms 1 to 6 and the features of Examples 7 to 19:

[0120] Use form 1

[0121] Use of a buffer solution for reducing the carbon dioxide content in the blood during treatment of patients suffering from pulmonary insufficiency or complete pulmonary failure, wherein the buffer solution is an aqueous solution that exchanges gases with the blood transported in an extracorporeal circuit of the patient and contains buffer A and buffer B, wherein

[0122] - Buffer A consists of at least one buffer substance having a pK value of 7.9 ± 0.2 at 37 °C, and

[0123] - Buffer B consists of at least one buffer substance having a pK value of 6.9 ± 0.2 at 37 °C, and wherein

[0124] - At a carbon dioxide partial pressure pCO2 = 0.2 mmHg ± 0.2, the post-titration pH value of the solution is in the range of 8.25 to 8.35.

[0125] Use form 2

[0126] The use according to claim 1, characterized in that the buffer solution further contains at least one buffer C and / or at least one buffer D in addition to buffer A and buffer B, wherein

[0127] - Buffer C and buffer D each consist of at least one buffer substance,

[0128] - At 37 °C, the pK values of the buffer substances of buffer C and buffer D are arranged substantially equidistantly between the pK values of 6.9 ± 0.2 and 7.9 ± 0.2, wherein the distance of the pK value of the buffer substance of buffer C from the lower threshold is equal to the distance of the pK value of the buffer substance of buffer D from the upper pK threshold within a tolerance of ±0.1, and at a carbon dioxide partial pressure pCO2 = 0.2 mmHg ± 0.2, the post-titration pH value of the solution is in the range of 8.25 to 8.35.

[0129] Use form 3

[0130] The use according to claim 1 or 2, characterized in that the buffer solution has an effective carbon dioxide affinity of ≥ 10 ml / l / mmHg, preferably ≥ 15 ml / l / mmHg, at a pCO2 of 40 mmHg, and an effective carbon dioxide affinity of ≥ 20 ml / l / mmHg, preferably ≥ 25 ml / l / mmHg, even more preferably 30 ml / l / mmHg, at a pCO2 of 10 mmHg.

[0131] Use form 4

[0132] For the use according to any one of claims 1 to 3, characterized in that the buffer solution has an effective carbon dioxide transport capacity of ≥ 500 ml / l at a pCO2 of 40 mmHg and an effective carbon dioxide transport capacity of ≥ 250 ml / l at a pCO2 of 10 mmHg.

[0133] Use form 5

[0134] For the use according to any one of claims 1 to 4, characterized in that the carbon dioxide partial pressure pCO2 of the buffer solution is 0.2 mmHg ± 0.2.

[0135] Use form 6

[0136] For the use according to any one of claims 1 to 5, characterized in that the buffer solution comprises the following components:

[0137] Buffer A TRIS 36.0 mmol / l

[0138] Buffer B Na2HPO4 34.0 mmol / l

[0139] Titration HCl 12.0 mmol / l

[0140] Example 7

[0141] A buffer solution for reducing the carbon dioxide content in the blood of a patient suffering from pulmonary insufficiency or complete pulmonary failure, wherein the buffer solution has the characteristics of the buffer solution according to any one of claims 1 to 6.

[0142] Example 8

[0143] A device (10) for reducing the carbon dioxide content in blood in vitro, wherein the device has a first defined area (1) for receiving blood in vitro and a second defined area (2) for receiving a buffer solution, wherein the first area (1) and the second area (2) adjacent to each other in the contact area are separated only by a membrane (3), through which gas exchange can occur between the blood and the buffer solution, and wherein the buffer solution has the characteristics of the buffer solution used according to any one of claims 1 to 6.

[0144] Example 9

[0145] The device according to claim 8, characterized in that the membrane comprises at least one polymer selected from polypropylene (PP), polymethylpentene (PMP), polysulfone (PSU) and optionally PVP, or a mixture selected from the above polymers, in particular a mixture of polysulfone and polyvinylpyrrolidone.

[0146] Example 10

[0147] The device according to claim 8 or 9, characterized in that the membrane is formed by a plurality of hollow fibers.

[0148] Example 11

[0149] The device according to any one of claims 8 to 10, characterized in that the membrane is coated with silicone resin, preferably, the membrane is formed by hollow fibers coated with silicone resin.

[0150] Example 12

[0151] The device according to claim 11, characterized in that the inner surface and / or the outer surface of the hollow fiber is coated with silicone resin.

[0152] Example 13

[0153] The device (10) according to any one of claims 8 to 12, characterized in that

[0154] - The first defined region (1) for receiving extracorporeal blood has an inlet port (4) and an outlet port (5) for blood, and is configured such that blood can flow from the inlet port (4) through the first defined region to the outlet port (5) along a first flow direction (6), and

[0155] - The second defined region (2) for receiving a buffer solution has an inlet port (7) and an outlet port (8) for the buffer solution, and is configured such that the buffer solution can flow from the inlet port (7) through the second defined region to the outlet port (8) along a second flow direction (9), wherein the first flow direction (6) of the first region (1) and the second flow direction (9) of the second region (2) are oriented in opposite directions to each other.

[0156] Example 14

[0157] The device (10) according to any one of claims 8 to 13, characterized in that the exchange surface area in the contact zone through which gas exchange can occur through the membrane (3) reaches at least 0.3 m 2 、in particular at least 0.6 m 2 、in particular at least 1 m 2 、preferably at least 2 m 2 .

[0158] Example 15

[0159] The device (10) according to any one of claims 8 to 14, characterized in that the exchange surface area in the contact zone through which gas exchange can occur through the membrane (3) reaches at most 5 m 2 、preferably at most 3 m2 。

[0160] Example 16

[0161] The device (10) according to any one of claims 8 to 15, characterized in that the flow rate of the blood flowing through the first defined region (1) reaches at most 20% by volume, in particular at most 15% by volume, of the cardiac output of a patient for whom the device is to be used to reduce the carbon dioxide content in the blood outside the body.

[0162] Example 17

[0163] The device (10) according to any one of claims 8 to 16, characterized in that the flow rate of the blood flowing through the second defined region (2) reaches 10 - 100% by volume, in particular 50 - 100% by volume, of the flow rate of the blood flowing through the first defined region (1).

[0164] Example 18

[0165] The device (10) according to any one of claims 8 to 17, characterized in that the device comprises means for regenerating the buffer solution, via which the carbon dioxide extracted from the blood can be removed again from the buffer solution.

[0166] Example 19

[0167] The device (10) according to any one of claims 8 to 18, characterized in that the means for regenerating the buffer solution comprises means for supplying an acid to the buffer solution to be regenerated.

[0168] In a second aspect, the present disclosure relates to a system for extracorporeal blood treatment using a buffer solution and a device for extracorporeally reducing the carbon dioxide content in the blood according to the first aspect of the present disclosure, wherein the system has a first inlet for introducing a blood flow to be treated into the system, at least one blood treatment device, and a first outlet for extracting a treated blood flow from the system. The present disclosure also relates to a treatment device having such a system and a kit comprising the components of the system. In addition, the present disclosure also relates to a method for operating such a system and / or a treatment device with such a system. Furthermore, a method for extracorporeal blood treatment using such a system or such a treatment device is described.

[0169] Systems for extracorporeal blood treatment are in principle known from the prior art. Thus, systems that can combine two different blood treatments are also known. The corresponding methods of extracorporeal blood treatment using such systems are also known.

[0170] For example, a system for peritoneal dialysis using an oxygenator arranged in an extracorporeal circuit is known from WO 2015 / 067232 A1.

[0171] DE 196 22 184 A1 describes a multi-functional device for multi-functional extracorporeal blood treatment, by means of which gas exchange treatment and dialysis treatment can be carried out.

[0172] For example, it is further known from EP 2 735 326 A1 or EP 0 236 0 509 B1 to combine an extracorporeal dialysis treatment for continuous renal replacement therapy (CRRT) with an extracorporeal adsorption treatment for sepsis treatment in a common extracorporeal blood circuit.

[0173] EP 2 735 326 A1 discloses a system for blood treatment, which system comprises two dialyzers, each dialyzer containing hollow fiber membranes, which dialyzers are intended to be connected in series in an extracorporeal blood circuit for blood treatment and to be flowed through successively, wherein one of the two dialyzers comprises an adsorbent material.

[0174] EP 0 236 0 509 B1 likewise teaches arranging a dialyzer and an adsorber in series connection in an extracorporeal blood circuit for combining dialysis treatment and adsorption treatment.

[0175] It is further known to combine an extracorporeal dialysis treatment for continuous renal replacement therapy with an extracorporeal ventilation for removing CO2 from the blood (ECCO2R = extracorporeal CO2 removal) or for simultaneous oxygen enrichment (ECMO = extracorporeal membrane oxygenation) in a common extracorporeal blood circuit.

[0176] Furthermore, a blood treatment device with a gas exchange device is known from EP 2 461 847 B1, which blood treatment device is capable of carrying out adsorption treatment in addition to gas exchange treatment, wherein the gas exchange device comprises a carrier coated with a substance for this purpose for adsorptive removal of toxins, their metabolites and degradation products of biological and chemical / synthetic origin as present in blood, blood substitutes or solutions introduced into the blood circulation of humans and / or animals.

[0177] In this context, the task of the present invention is to provide an improved system for extracorporeal blood treatment, in particular a system that can expand the possibilities of extracorporeal blood treatment and provide additional treatment options, in particular to flexibly provide treatment options in each case according to the respective treatment, without the need for additional patient accesses to be cannulated or additional extracorporeal blood circuits to be established. A further task of the present invention is to provide a corresponding treatment device, a corresponding kit, a corresponding method for operating such a system and / or corresponding treatment device, and a corresponding method for extracorporeal blood treatment.

[0178] According to the present disclosure, these tasks are solved by a system for extracorporeal blood treatment having the features of embodiment 20, by a treatment device having the features of embodiment 36, by a kit having the features of embodiment 37, by a method for operating such a system and / or treatment device, and by a method for extracorporeal blood treatment using such a system or treatment device. Advantageous embodiments of the present disclosure form the subject matter of embodiments 21 to 35, the description and the drawings, and will be explained in more detail below.

[0179] The system for extracorporeal blood treatment according to the present disclosure includes a first inlet for introducing the blood to be treated into the system, at least one first blood treatment device, a second blood treatment device, a third blood treatment device, and a first outlet for extracting the treated blood flow from the system.

[0180] The first blood treatment device includes an adsorber device for removing at least one exogenous and / or at least one endogenous pathogen and / or a plasma separation device for separating plasma from other blood components, or is an adsorber device and / or a plasma separation device.

[0181] The second blood treatment device is designed as a dialysis device, in particular as a dialysis device for renal replacement therapy, preferably for continuous renal replacement therapy.

[0182] The third blood treatment device is designed as a device (10) for extracorporeally reducing the carbon dioxide content in the blood according to any one of embodiments 8 to 19, in particular as a gas exchange device for at least partially removing CO2 from the blood flow flowing through the first defined region of the gas exchange device and from the buffer solution according to at least one of the features of embodiments 1 to 6 flowing through the second defined region of the gas exchange device.

[0183] The first, second, and third blood treatment devices are thus connected in series in sequence with respect to the blood flow direction of the blood flow to be treated between the first inlet and the first outlet of the system in the functional application state of the system, and the blood flow to be treated can flow through the first, second, and third blood treatment devices outside the body in succession. Therefore, the sequential order of the arrangement of the blood treatment devices preferably depends on the respective application.

[0184] In vitro blood treatment in the context of the present disclosure is understood to be blood treatment that occurs outside the body of a human or animal, and such in vitro blood treatment is generally known from the prior art.

[0185] The blood flow in the context of the present disclosure is understood to include a mass flow of blood components.

[0186] A blood treatment device in the context of the present disclosure is understood to be a device by means of which the quality of blood, in particular a blood flow, can be treated, i.e., a device that modifies its components.

[0187] For in vitro blood treatment, the blood flow to be treated, in particular the blood to be treated; i.e., so-called whole blood containing all the components normally present in blood or a body fluid to be treated having blood components, such as plasma or the like, can be supplied to the system disclosed herein via the first inlet and can be discharged from the system via the first outlet of the system.

[0188] In an embodiment of the system according to the present disclosure, the blood flow to be treated can be supplied from a storage volume such as, for example, a storage bag; i.e., a blood bag or the like, and / or directly from the system supplied by the patient or animal to be treated.

[0189] The treated blood flow can be discharged into a storage volume, for example, also into a suitable storage bag or the like, and / or provided for supplying a separate transplant organ, and / or directly supplied to the patient or animal to be treated.

[0190] Particularly preferably, the system for in vitro blood treatment according to the present disclosure is designed to be introduced into the human and / or animal blood circuit and, in particular, to be connected to the in vivo blood circuit of the patient or animal to be treated, thereby creating an in vitro blood circuit.

[0191] In a preferred embodiment of the system disclosed herein, the system is designed to have a venous-venous (VV) connection or an arterio-venous (AV) connection to the in-vivo blood circuit of a patient or an animal. Depending on the application, a venous-venous or arterio-venous connection of the system disclosed herein to the in-vivo blood circuit of the patient or animal to be treated may be more advantageous. This depends in particular on the required blood treatment or combination of required blood treatments. In another embodiment, the system disclosed herein may also be connected to the in-vivo blood circuit of a patient or an animal via one or more than two artificial blood access points (e.g., fistulas or shunts).

[0192] In the system for extracorporeal blood treatment according to the present disclosure, all variants of the sequential order of the arrangement of individual blood treatment devices in the direction of blood flow are in principle possible, where there are a total of 3! = 6 arrangement possibilities, some of which have particular advantages and will be explained in more detail in the further course of this application.

[0193] Preferably, the first inlet and / or the first outlet of the system according to the present invention is formed by pipelines, each of which preferably has at least one corresponding connection, or correspondingly preferably includes one or more than two corresponding pipelines respectively, and each pipeline is particularly capable of being connected to the blood vessels and / or storage volume of the patient or animal to be treated via an appropriate passage. Therefore, the pipelines of the system disclosed herein can thus form a tube set, especially a replaceable tube set.

[0194] Preferably, the system for extracorporeal blood treatment disclosed herein includes a supply pipeline for introducing, in particular supplying, the blood flow drawn from a patient and / or the blood flow drawn from an animal and / or extracted from a storage volume into the system and / or a return pipeline for extracting, in particular removing, the treated blood flow from the system and / or returning the treated blood flow or a part thereof to the in-vivo blood circuit of the patient or animal to be treated and / or to a storage volume or to a separate transplanted organ.

[0195] In a preferred embodiment of the system disclosed herein, the system has at least one one-way valve in the return pipeline so as to be able to prevent the removal or corresponding extraction of the treated blood flow from the system, especially in order to be able to prevent the return to the in-vivo blood circuit of the patient or animal to be treated. The return pipeline may further include a protection device, such as a filter or a magnetic device, so as to retain unwanted particles, especially to prevent and / or inhibit the intrusion of said unwanted particles into the in-vivo blood circuit.

[0196] In the case of sepsis, in addition to continuous renal replacement therapy due to renal failure, respiration is usually indicated simultaneously, especially in intensive care patients. With the system according to the present disclosure, at least three blood treatments can be performed simultaneously and using only one extracorporeal blood circuit, which are dialysis treatment, adsorption treatment, and / or plasmapheresis and an extracorporeal treatment for reducing the carbon dioxide content in the blood, especially in combination with extracorporeal ventilation that replaces or combines with mechanical ventilation that requires intubation or tracheotomy.

[0197] The advantage of extracorporeal treatment for reducing the carbon dioxide content in the blood over mechanical ventilation is that it can also treat patients with pulmonary insufficiency or complete pulmonary failure. Therefore, especially in cases affecting the lungs, as often occurs in sepsis, extracorporeal treatment for reducing the carbon dioxide content in the blood is more advantageous than mechanical ventilation. When combined with mechanical ventilation, mechanical ventilation can become a less intensive process and less stressful for the patient.

[0198] The series connection of the adsorber device and / or plasmapheresis device, dialysis device, and gas exchange device (which is a device for extracorporeally reducing the carbon dioxide content in the blood) disclosed herein also enables the use of only one extracorporeal blood circuit. As a result, patients with insufficient stability to supply two extracorporeal blood circuits simultaneously or whose condition does not allow for a delay in extracorporeal blood treatment can also simultaneously receive extracorporeal blood treatment including adsorption treatment and / or plasmapheresis, especially plasma treatment, dialysis treatment, and gas exchange treatment, which is a treatment for extracorporeally reducing the carbon dioxide content in the blood using the system according to the present disclosure. In addition, only one extracorporeal blood circuit requires fewer accesses. Therefore, this reduces the stress on the patient and the risk of infection. In the context of the present disclosure, the gas exchange device is understood to be a device for extracorporeally reducing the carbon dioxide content in the blood according to the first aspect of the present disclosure, especially a device defined by at least one of Examples 8 - 19. In addition, in the context of the present invention, the treatment for extracorporeally reducing the carbon dioxide content in the blood is understood to be gas exchange treatment.

[0199] By means of the sequential arrangement of the adsorber device and / or plasmapheresis device, dialysis device, and gas exchange device, the system according to the present invention simultaneously achieves, for example, sepsis treatment, dialysis treatment for limited or failed renal function, and extracorporeal ventilation.

[0200] The adsorber device in the context of the present disclosure is a device designed to remove one or more components of the blood flow passing through the adsorber device from the blood flow by means of adsorption. Adsorber devices are generally known from the prior art.

[0201] In an advantageous embodiment of the system disclosed herein, the first blood treatment device is an adsorber device, in particular an adsorber device designed for endotoxin adsorption, cytokine adsorption, and / or immunoadsorption, or comprising such an adsorber device. In particular, the adsorber device is designed to remove at least one exogenous pathogen, such as removing at least one drug and / or at least one pharmaceutical substance and / or at least one phytotoxin and / or organic toxin and / or other toxic substances and / or bacteria, viruses, fungi, and / or other organisms, and / or removing at least one endogenous pathogen, such as removing immune complexes in the body and / or at least one immunoglobulin and / or at least one inflammatory mediator and / or antibody, and / or removing at least one so-called pathogen-associated molecular pattern (PAMP) and / or at least one so-called alarmin ("damage-associated molecular pattern" - DAMP).

[0202] The plasmapheresis device in the context of the present disclosure is a device by means of which the plasma in a certain volume of blood introduced into the plasmapheresis device can be at least partially separated from the other components of that volume of blood. The plasmapheresis device particularly includes a plasma filter and / or a centrifuge device, or is designed as a plasma filter or a centrifuge.

[0203] The dialysis device of the system for extracorporeal blood treatment disclosed herein is preferably designed to implement at least one method among a set of different blood purification methods, preferably for continuous renal replacement therapy; namely, CRRT treatment, in particular for hemodialysis, hemofiltration, hemodiafiltration, hemoperfusion, and / or CRRT treatment for peritoneal dialysis, wherein this type of dialysis device and the associated dialysis method are also known from the prior art.

[0204] The gas exchange device of the system disclosed herein is designed as a device for reducing the carbon dioxide content in blood extracorporeally.

[0205] In a preferred embodiment of the system disclosed herein, the system, in particular the gas exchange device, includes a membrane of hollow fibers coated with a silicone layer. In particular, in one embodiment, the gas exchange device can be designed as a (silicone-coated) hollow fiber membrane filter.

[0206] According to the present disclosure, a gas exchange device for reducing the carbon dioxide content in vitro includes a device according to the first aspect of the present disclosure, wherein the gas exchange device has a first defined region for receiving extracorporeal blood and a second defined region for receiving a buffer solution according to the first aspect of the present invention, wherein the first and second defined regions adjacent to each other in the contact region are separated only by a membrane, and gas exchange can occur between the blood and the buffer solution through the membrane. The buffer solution disclosed herein in this application can be a component of a gas exchange device for reducing the carbon dioxide content in blood in vitro as an elimination medium.

[0207] In a particularly designed embodiment of the device disclosed herein, the first defined region for receiving extracorporeal blood has an inlet port and an outlet port for blood and is designed such that blood can flow through the region from the inlet port to the outlet port in a first flow direction. In this embodiment, the second defined region for receiving the buffer solution has an inlet port and an outlet port for the buffer solution and is designed such that the buffer solution can flow through the region from the inlet port to the outlet port in a second flow direction.

[0208] Since in most applications, the pumping capacity of the heart or an implanted pump of the patient or animal to be treated is insufficient to pump the blood flow through the system, or a veno-venous access for establishing an extracorporeal blood circuit for extracorporeal blood treatment using the system disclosed herein is more advantageous; that is, the blood flow to be treated is extracted from a vein and the treated blood flow is also returned to the vein. In an advantageous embodiment, the system disclosed herein includes at least one first pump, particularly a first pump designed as a blood pump, for delivering at least a portion of the blood flow to be treated, wherein the first pump is preferably arranged in the blood flow direction between the first inlet and the first blood treatment device and is particularly designed to deliver the entire blood flow to be treated. In other words, in an advantageous embodiment of the system disclosed herein, the first pump is preferably connected in series with three blood treatment devices and is particularly arranged directly after the first inlet and before the first blood treatment device with respect to the direction of blood flow.

[0209] In some cases, in the functional use of the system disclosed herein, it may be more advantageous to arrange the first pump between the first blood treatment device and the second blood treatment device, or between the second blood treatment device and the third blood treatment device, or even after the third blood treatment device, in each case with respect to the direction of blood flow.

[0210] In a particularly preferred embodiment, the system disclosed herein includes a plurality of pumps, in particular a plurality of pumps each designed to convey a blood flow to be treated, which pumps are preferably connected in series with the treatment device in the direction of blood flow and are arranged, in particular in the direction of blood flow, such that the corresponding pressure conditions required for optimal treatment are established at one or more than two locations in the blood treatment device.

[0211] In a preferred embodiment, the system disclosed herein includes a peristaltic pump as the first pump. In a particularly preferred embodiment, the system disclosed herein includes a centrifugal pump as the first pump. This can be a diagonal pump configured as a rotor pump, wherein the pump preferably includes a blood guiding part decoupled from the drive part, and the rotor of the pump is particularly supported via ball bearings made of, in particular, ceramic or alumina, preferably supported on pins, and preferably includes a permanent magnet on its bottom side facing the drive part and can be driven by magnetic coupling. It is particularly preferred that at least one pump is designed such that when the blood flows through the pump, only low shear stress is generated, and the individual blood components, in particular red blood cells, are thus damaged as little as possible.

[0212] In a particularly preferred embodiment, the system disclosed herein includes a pump designed according to the blood pump described in DE 10 2010024 650A1. Preferably, the size of the blood pump, in particular its connection geometry, is selected to be suitable for the corresponding blood flow to be conveyed or correspondingly suitable for the blood volume of the patient or animal to be treated.

[0213] Since the effectiveness of blood filtration blood treatment depends on the pressure gradient applied to the blood filter, in particular on the hydrostatic pressure gradient between the two sides of the filter membrane, i.e., the so-called transmembrane pressure (TMP: Transmembrane Pressure), it is advantageous that, relative to optimal blood filtration blood treatment, an extracorporeal blood treatment system designed according to the present disclosure for blood filtration or hemodiafiltration and / or a dialysis device of the system disclosed herein for blood filtration or hemodiafiltration includes at least one blood pump for conveying at least a part of the blood flow to be treated, by means of which the change in the blood flow can be used to define the pressure established at least at one location in the blood treatment device and / or the generated set pressure gradient, in particular the transmembrane pressure generated on the dialysis membrane of the dialysis device.

[0214] Preferably, the system according to the present disclosure includes a plurality of correspondingly designed and controllable pumps for setting a defined transmembrane pressure, in particular various correspondingly designed and controllable pumps, such as one or more than two blood, dialysate, filtrate, and / or replacement pumps, by means of which the blood flow rate can be set in order to generate a desired defined transmembrane pressure on the blood filter of the dialysis device.

[0215] In another advantageous embodiment of the system disclosed herein, the system includes another, particularly a second inlet for adding a first component to the blood stream, particularly to the blood stream to be treated, wherein this another inlet is preferably arranged in the direction of blood flow such that the first component can be supplied to the blood stream in the direction of blood flow before the first pump and / or before the first of the three blood treatment devices, particularly before the adsorber device.

[0216] Preferably, this another, particularly the second inlet is thus designed for adding a liquid anticoagulant, particularly for adding an anticoagulant citrate solution. Thus, the system disclosed herein is particularly preferably designed such that the first component, particularly the anticoagulant, can be supplied to the blood stream no later than before the treatment section of the first treatment device, i.e., upstream of the first treatment device. Particularly advantageously, the second inlet is thus arranged such that the addition can occur upstream of the first pump; i.e., before the first pump in the direction of blood flow. Thus, the risk of blood clotting within the system, particularly within the more downstream adsorber device, can be reduced.

[0217] Blood clotting refers to the coagulation of blood components; i.e., clots of blood components.

[0218] The treatment section in the context of the present disclosure refers to the flow path along which the actual blood treatment takes place.

[0219] In some cases, it has proven advantageous for the system disclosed herein to include another, particularly a second separation pump for conveying the first component, particularly for pumping the first component out of a first storage volume in which the first component is accommodated into the blood stream to be treated. Preferably, the storage volume in which the first component is accommodated is particularly a storage bag for storing the first component or a suitably equivalently designed container, particularly a container capable of storing the component aseptically and having a sufficient shelf life.

[0220] Since hemofiltration and hemodiafiltration generally allow not only the molecules of the blood stream to be purified to pass through the filter membrane of the dialysis device, the so-called hemofilter, but also some of the plasma fluid to pass through the hemofilter and be discharged as effluent, in these cases, i.e., especially when the dialysis device is designed for hemofiltration or for hemodiafiltration, it is usually necessary to supply a replacement, usually a physiological replacement fluid, especially an electrolyte solution, to the blood stream to compensate for the resulting fluid loss. Thus, in principle, the replacement can be supplied before and / or after the dialysis treatment. In some of these applications, it is more advantageous to supply the replacement to the blood stream only after the dialysis treatment, i.e., especially only after the hemofilter, and thus, in some cases, it is particularly advantageous to supply the replacement only immediately before the treated blood mass flow returns to the in-vivo blood circuit of the patient or animal to be treated.

[0221] In hemodialysis, i.e., when the dialysis device is designed for hemodialysis or hemodiafiltration, especially when an anticoagulant citrate solution is added to the blood stream, the blood stream can be decalcified via the effluent, and compensation is likewise required, wherein the resulting calcium loss is preferably compensated downstream of the dialysis device, especially only after the last blood treatment device.

[0222] In another advantageous embodiment of the system disclosed herein, the system disclosed herein thus has another, especially a third inlet for adding a second component to the blood mass flow, especially for adding a second component to the treated blood mass flow, wherein the another inlet is preferably arranged in the blood flow direction such that the second component can be supplied to the blood mass flow in the direction of blood flow, downstream of the dialysis device, especially after the last blood treatment device.

[0223] Thus, the another, especially the third inlet is specifically designed for adding the second component in the form of a replacement to compensate for the fluid loss occurring during hemofiltration or hemodiafiltration and / or for adding the second component in the form of a liquid calcium solution to compensate for the calcium loss occurring during hemodialysis.

[0224] In other words, in a preferred embodiment of the system for extracorporeal blood treatment disclosed herein, the second component can preferably be supplied to the blood mass flow after the treatment section of the dialysis device and / or after the dialysis procedure. Particularly preferably, the second component can be supplied directly to the blood stream, especially directly introduced into the return line, before the blood stream returns to the in-vivo blood circuit.

[0225] In some cases, it has proven advantageous for the systems disclosed herein to have another pump, in particular a third pump, for delivering a second component, which pump is designed in particular to pump the second component from a second storage volume in which the second component is accommodated into the blood stream.

[0226] However, in some cases, it may also be advantageous to provide another, in particular a separate, inlet for supplying the required replacement fluid to compensate for the fluid or volume losses occurring in the dialysis device during hemofiltration or hemodiafiltration, in particular by correspondingly providing an additional inlet to the third inlet or to the inlet for compensating for calcium losses.

[0227] In some cases, it is advantageous for the corresponding inlet for supplying the replacement fluid to be arranged in the direction of blood flow such that the replacement fluid can be supplied to the blood stream in the direction of blood flow before gas exchange, wherein the associated inlet is arranged in particular directly before the gas exchange device with respect to the direction of blood flow in order to be able to compensate for any potential undesired CO2 loading of the replacement fluid via the gas exchange device. In some applications, it is even more advantageous to supply the replacement fluid to the blood stream only after dialysis and adsorption treatment in order to prevent a dilution effect that reduces the effectiveness of the adsorption treatment (generally speaking, the adsorption force depends on the concentration).

[0228] As previously mentioned, the adsorber device and / or the plasma separation device, the dialysis device and the gas exchange device can in principle be connected in series in any order in the systems disclosed herein, however, certain arrangements, namely a specific flow sequence through the individual treatment devices in the direction of blood flow, are particularly advantageous.

[0229] A particularly advantageous embodiment of the system for extracorporeal blood treatment disclosed herein results from the adsorber device and / or the plasma separation device being arranged in the direction of blood flow before the gas exchange device. Since a replacement fluid, which can sometimes be loaded with CO2, usually a physiological replacement fluid, preferably an electrolyte solution, is also usually supplied to the blood mass flow after adsorption treatment in order to compensate for the volume lost during treatment, it is advantageous for the adsorber device to be arranged in the direction of blood flow before the gas exchange device because the undesired CO2 loading caused by the replacement fluid can thereby be compensated for again by means of the gas exchange device. As a result, the removal of CO2 from the blood mass flow to be treated can be improved compared to an arrangement in which the gas exchange device is before the adsorber device.

[0230] In alternative, in some cases equally advantageous embodiments of the systems disclosed herein, the adsorber device and / or the plasma separation device are arranged behind the gas exchange device in the direction of blood flow. The advantage of this arrangement is that it is possible to achieve an increase in the pressure gradient in the gas exchange device, in particular across the gas exchange membrane, based on the back pressure generated at the adsorber device, thereby improving gas exchange.

[0231] To provide the required replacement fluid to compensate for the volume loss occurring in the adsorber device during the adsorption treatment, the system according to the present disclosure preferably has a further, in particular fourth, inlet to the blood mass flow, which is arranged in particular in the direction of blood flow such that replacement fluid can be supplied to the blood mass flow in the direction of blood flow after the absorption procedure, in particular after the treatment section in the adsorber device, wherein the fourth inlet is arranged directly behind the adsorber device with respect to the direction of blood flow.

[0232] However, in some cases, it may also be (more) advantageous to arrange the fourth inlet in front of the adsorber device, in particular upstream of the gas exchange device, in order to be able to compensate for the undesired CO2 loading of the blood flow via the gas exchange device caused by the replacement fluid required to compensate for the fluid losses occurring during the adsorption treatment. This is particularly the case when the adsorber device is arranged behind the gas exchange device in the direction of blood flow, i.e., downstream of the gas exchange device.

[0233] In a further advantageous embodiment of the systems disclosed herein, the adsorber device and / or the plasma separation device are arranged in front of the dialysis device in the direction of blood flow, in particular when the dialysis device is designed for hemodialysis or hemodiafiltration and in particular comprises a dialyzer. The upstream arrangement of the adsorber device, i.e., in front of the dialysis device in the direction of blood flow, has the advantage of not supplying the adsorber device with hemodiluted blood flow, thereby enabling a particularly high adsorption treatment efficiency.

[0234] Furthermore, the downstream arrangement of the dialysis device can compensate for non-specific ion binding or pH changes occurring in the absorber.

[0235] Furthermore, due to the structure of its (smallest) hollow fibers, the downstream arrangement of the blood flow of the dialysis device can act as a safety system against the undesired intrusion of particles from the adsorber device.

[0236] If the dialysis device of the system according to the present disclosure is designed for hemodialysis or hemodiafiltration and in particular comprises a dialyzer, the system according to the present disclosure, in particular the dialysis device, preferably has a fifth inlet for supplying dialysis fluid, i.e., dialysis liquid.

[0237] To remove the effluent generated in the dialysis device during dialysis treatment, the system according to the present disclosure preferably has a second outlet.

[0238] In an alternative embodiment of the system disclosed herein, the adsorber device is arranged downstream of the dialysis device in the direction of blood flow, particularly when the dialysis device is designed for hemofiltration or hemodiafiltration and preferably includes a hemofilter. Such an arrangement may be advantageous in certain applications, particularly when a particularly effective adsorption treatment is indicated, since in this case the blood flow to be treated can be concentrated in the dialysis device by hemofiltration, thereby increasing the effectiveness of the adsorption treatment in the downstream arranged adsorber device.

[0239] In this case, although the risk of blood clotting in the system, particularly in the adsorber device, increases compared to the previously described embodiments of the system disclosed herein, in many cases, the incipient clotting can be identified relatively reliably and quickly by appropriate monitoring measures, such as pressure sensor devices arranged upstream and downstream of at least one blood treatment device, and the state of the individual blood treatment devices can be inferred with the aid of these monitoring measures. Thus, particularly in combination with the additional use of anticoagulants, the risk of blood clotting can be well controlled in most cases.

[0240] In another advantageous embodiment of the system disclosed herein, the dialysis device is arranged upstream of the gas exchange device in the direction of blood flow, particularly when the dialysis device is designed for hemodialysis or hemofiltration and requires the supply of dialysis fluid for dialysis treatment. In this case, before the treated blood flow returns to the body blood circuit of the patient or animal to be treated, the undesired CO2 load of the potentially CO2-containing dialysis fluid in the dialysis device can be compensated via the gas exchange device arranged downstream of the dialysis device in the direction of blood flow, which is not the case for the arrangement of the dialysis device downstream of the gas exchange device.

[0241] In an alternative but in certain cases also advantageous embodiment of the system disclosed herein, the dialysis device is arranged downstream of the gas exchange device in the direction of blood flow, whereby in this case the dialysis device is preferably designed for hemofiltration and includes a hemofilter and is particularly not designed for hemodialysis.

[0242] By means of the hemofilter downstream of the gas exchange device, the pressure gradient between the blood side and the gas side on the gas exchange device can be increased, thereby increasing the efficiency of the gas exchange device.

[0243] If the dialysis device is only designed for hemofiltration and not for hemodialysis, and in particular not for hemodiafiltration, then there will be no disadvantage of an undesired CO2 load due to blood flow exchange with imaginable CO2-containing dialysis fluid in hemodialysis or hemodiafiltration. In the latter case, the replacement solution for volume compensation can preferably be added upstream of the gas exchanger so as to be able to at least partially, preferably completely, compensate for the potential CO2 load generated via the gas exchange device.

[0244] In another advantageous embodiment of the system disclosed herein, the system includes at least one pressure sensor device for determining the flow pressure of the blood flow at least at one defined point in the system, wherein the at least one pressure sensor device is preferably arranged directly before and / or after at least one treatment section of the blood treatment device in the blood flow direction.

[0245] If corresponding pressure sensor devices are provided before and after at least one treatment section, the pressure drop across the treatment section can thereby be detected, from which the state of the relevant blood treatment device can be inferred. In particular, the degree to which the blood treatment device is affected by clotting can thereby be evaluated, wherein a suddenly increased pressure drop indicates that the corresponding blood treatment device is affected by clotting.

[0246] In a preferred embodiment, the system according to the present disclosure includes control means, wherein the control means is particularly designed to control and / or regulate all system components in the system disclosed herein that can be controlled and / or regulated. That is to say, in other words, in a preferred embodiment, the system according to the present disclosure has a common controller for controlling all blood treatment devices. Thus, the controller is particularly designed to control one or more than two pumps, and / or control the inflow and / or outflow of substances and / or components, and / or evaluate the sensor data recorded by at least one sensor device and / or monitor the system disclosed herein, in particular control and / or regulate the blood flow to be treated.

[0247] Preferably, by means of one or more than two pressure sensor devices and corresponding measures triggered thereby, such as triggering an alarm or shutting down the system, in particular the pump delivering the blood flow, a blockage or interruption of the blood circuit can be detected.

[0248] Preferably, the system according to the present disclosure is designed such that the defined transmembrane pressure required for the highest possible effectiveness of the blood treatment is monitored with respect to at least one limit value in the blood treatment device, in particular for the dialysis device. Preferably, the flow rate of the blood flow can be adjusted according to at least one sensor signal detected by the pressure sensor device, so as to set or correspondingly generate the desired defined transmembrane pressure, thereby enabling improved blood treatment.

[0249] In another advantageous embodiment of the system disclosed herein, the system disclosed herein preferably includes at least one bubble detection device for detecting bubbles in the blood flow. Preferably, the system is thus designed such that when bubbles are detected by the bubble detection device, the one-way valve preferably arranged in the return line particularly before the first outlet can be closed to prevent the bubbles from returning to the body circuit with the treated blood flow of the patient or animal to be treated, especially the in-vivo blood circuit. Additionally, preferably, all pumps for delivering the blood flow can be additionally closed.

[0250] In another advantageous embodiment of the system disclosed herein, the treatment section of at least one blood treatment device is at least partially, preferably entirely, formed by a replaceable treatment module, especially a cassette-type treatment module. Such a configuration of the blood treatment device enables flexible replacement of the corresponding treatment module, especially enabling each treatment device to be simply and flexibly adapted to the respective required blood treatment.

[0251] For example, the endotoxin adsorber treatment module can thus be easily replaced with a cytokine adsorber treatment module having another functional adsorption layer or a special immunoadsorption treatment module used, or the hemofilter can be replaced with a dialyzer, etc. Therefore, the possible treatment range using the system according to the present disclosure is greatly increased, whereby the economic efficiency of the system according to the present disclosure can be significantly improved.

[0252] In another advantageous embodiment of the system according to the present disclosure, the system includes at least one switchable bypass device for bypassing at least one blood treatment device. Thus, if necessary, the system disclosed herein can also be used for blood treatment, where each blood treatment only requires the use of one or two of the three blood treatment devices of the system, but does not need to flow through all three blood treatment devices of the system disclosed herein. In this way, the required blood treatment that only requires adsorption treatment and / or only requires plasmapheresis and dialysis treatment, for example, can be performed while bypassing the gas exchange device. A dialysis treatment with subsequent gas exchange for CO2 removal can also be performed without simultaneous adsorption treatment. Therefore, the range of treatment options can be significantly increased using the system disclosed herein. Additionally, since all three treatment modules do not have to be fully employed in each case, the material consumption can be significantly reduced, and thus the treatment cost can be significantly reduced in many treatment cases. Furthermore, when a treatment device no longer performs its function, for example, due to coagulation or exhaustion (such as a fully loaded adsorber), it can be removed from the system.

[0253] Preferably, at least one bypass device includes at least one bypass valve and an associated bypass line, the associated bypass line being fluidly connected or connectable, in particular, to the main line, wherein the associated bypass line can be opened or closed, in particular, by means of the bypass valve such that the blood flow to be treated can be selectively directed along the associated bypass line or can be selectively directed through a subsequent blood treatment device or subsequent blood treatment section accordingly.

[0254] Preferably, at least one bypass valve is designed such that when the bypass valve is open, no flow passes through the downstream treatment section; that is, the subsequent blood treatment device can preferably be completely blocked, and all of the blood flow to be treated can be directed through the associated blood treatment device via the associated bypass line; that is, the blood treatment device can be bypassed.

[0255] In the sense of the present disclosure, "bypassing the blood treatment device" is particularly understood as a branch of the main line, in particular, a bypass line is arranged around the blood treatment device at a branch point upstream of the blood treatment device or in the blood treatment device, and the bypass line is reconnected to the main line downstream again, in particular, after the blood treatment device or in the blood treatment device again.

[0256] In contrast, when the bypass valve is closed, the bypass line is preferably blocked, in particular, completely blocked, so that all of the blood flow to be treated flows through the subsequent treatment section or subsequent blood treatment device accordingly.

[0257] In doing so, the flow only selectively flows through the required treatment devices. Thus, the possible uses of the system according to the present disclosure can be significantly increased. In particular, the utilization rate or utilization cycle of the system disclosed herein can be improved thereby, and the economic efficiency can be further increased thereby.

[0258] In order to set a defined flow rate of the blood flow on at least one of the blood treatment devices, in particular, for at least one associated treatment section, in particular, in order to cause a desired defined transmembrane pressure, the system disclosed herein can include at least one additional pump, which is particularly arranged in the section between the branch point to the main line and the subsequent junction point and / or in the bypass line.

[0259] By means of an appropriate number and design of individual pumps, independent regulation of the blood flow rate can thus be achieved in the individual treatment devices, wherein the system particularly includes one or more than two corresponding control devices for this purpose.

[0260] In an advantageous embodiment, at least one bypass device associated with the blood treatment device is designed such that a recirculating blood flow can be achieved via and / or through the associated device.

[0261] In a further advantageous embodiment of the system disclosed herein, at least one additional blood treatment device is arranged in an associated bypass line of at least one blood treatment device, in particular such that a recirculating blood flow is generated from the associated blood treatment device arranged in the main line and / or via another blood treatment device arranged in the bypass line.

[0262] In an alternative advantageous embodiment of the system disclosed herein, the first blood treatment device is a plasma separation device, which can preferably be bypassed by means of a bypass line, wherein another blood treatment device in the form of an adsorber device is particularly arranged in the bypass line. Thus, the adsorber device is preferably arranged downstream of a pump arranged in the bypass line.

[0263] Thus, the treated blood discharged from the adsorber device or the treated plasma discharged correspondingly from the adsorber device can be supplied to the main line after the plasma separation device or supplied to the plasma separation device in a recirculating manner.

[0264] In an alternative embodiment of the system disclosed herein, the separated plasma can be discharged from the plasma separation device particularly by means of a pump and supplied to a plasma disposal container, and fresh plasma, in particular fresh plasma from a storage device, is preferably supplied via another inlet, in particular the main line, by means of another pump.

[0265] In a further advantageous embodiment of the system disclosed herein, at least one component of the system comprises a biocompatible and preferably functional coating on a surface in contact with the blood flow to be treated, in particular an antibacterial, anticoagulant and / or anti-inflammatory coating. Preferably, at least one lumen of the system designed to allow the blood flow to be treated and / or the treated blood flow to pass through is provided with a biocompatible and preferably functional coating, in particular an antibacterial, anticoagulant and / or anti-inflammatory coating.

[0266] Preferably, at least one surface of the system disclosed herein thus has a coating comprising heparin and / or albumin and heparin. In some cases, it may be advantageous for the system to instead have only a heparin-free coating, since the system can thus also be used to treat heparin-intolerant patients or animals.

[0267] In an alternative and / or additional preferred embodiment of the system disclosed herein, at least one coating comprises defined antibodies and / or one or more enzymes. The use of antibacterial coatings can also be considered.

[0268] In a further advantageous embodiment of the system disclosed herein, at least one protective layer is applied to protect the functional coating, wherein the protective layer is preferably used to enable the individual coated components of the system to be sterilized and / or stored without any significant loss of the function of the functional coating.

[0269] In a particularly preferred embodiment of the system disclosed herein, the system includes at least one surface having a coating formed using the technology from Leukocare AG.

[0270] The treatment device for extracorporeal blood treatment disclosed herein includes a system for extracorporeal blood treatment designed according to the present disclosure, wherein the first, second, and third blood treatment devices of the system are particularly arranged in a common housing and / or accommodated by a common base, i.e., through a common carrier device.

[0271] Preferably, the three blood treatment devices are thus arranged in a common housing and / or accommodated by a common base, such as a common carrier device, etc. Particularly preferably, each individual blood treatment device is thereby removably fixed in and / or on the common housing and / or base, especially as a corresponding replaceable module. Thereby, a particularly compact system as disclosed herein can be provided, which can be flexibly customized and configured for each corresponding treatment situation simultaneously.

[0272] The kit and / or set for extracorporeal blood treatment disclosed herein has at least one first blood treatment device, a second blood treatment device, a third blood treatment device, and a tube set having a first inlet for introducing a blood flow to be treated and a first outlet for discharging the treated blood flow via one or more than two tubes, and in particular an installation and / or operation manual as components.

[0273] Thus, the first blood treatment device is an adsorber device for removing at least one exogenous and / or at least one endogenous pathogen and / or a plasma separation device for separating plasma from other blood components, or includes a corresponding adsorber device and / or plasma separation device. The second blood treatment device is designed as a dialysis device, particularly a dialysis device for renal replacement therapy, and the third blood treatment device is designed as a gas exchange device configured to be a device for extracorporeally reducing the carbon dioxide content in blood according to one of Embodiments 8 to 19, particularly a gas exchange device designed to at least partially remove CO2 from the blood flow flowing through the first defined region of the gas exchange device and a buffer solution designed according to at least one of the characteristics of Use Forms 1 to 6 flowing through the second defined region of the gas exchange device. The components of the kit can be connected to a system for extracorporeal blood treatment designed according to the present disclosure, particularly according to the installation and / or operation manual, as disclosed herein.

[0274] Thus, a particularly flexible system as disclosed herein can be easily provided, which enables the combination of an adsorber device and / or a plasma separation device, a dialysis device, and a gas exchange device specifically for the corresponding treatment situation.

[0275] That is to say, the system disclosed in this document can be provided either in the form of a common treatment device for three blood treatment devices of the system; namely, the adsorber device and / or the plasma separation device, the dialysis device, and the gas exchange device are part of the common device, or in the form of a kit and / or a complete set of equipment, where at least two of the three blood treatment devices are separate devices, although they can be connected to the system disclosed in this document by means of a suitable pipe system with one or more than two hoses, and can be connected in series sequentially as disclosed in this document, so that each individual blood treatment device can be flowed through sequentially in series.

[0276] A method for operating the system for extracorporeal blood treatment disclosed in this document and / or the treatment device disclosed in this document according to this disclosure, characterized by the following steps:

[0277] - Providing a certain amount of blood to be treated,

[0278] - Introducing the blood flow to be treated into the system via the first inlet of the system,

[0279] - Flowing through at least one of the blood treatment devices, and

[0280] - Extracting the treated blood flow via the first outlet of the system.

[0281] Preferably, if the system for extracorporeal blood treatment is designed and includes at least one switchable bypass device, the resulting flow only flows through the required blood treatment devices, and the uses of the blood treatment devices are indicated for the corresponding treatments.

[0282] In an advantageous embodiment of the method according to this disclosure for operating the system disclosed in this document, the blood quality to be treated is provided in a container, especially in a container or a bag, where the treated blood is preferably extracted into the container, especially into the container or the bag. Alternatively, the treated blood can also be supplied to a separated organ intended for transplantation or to the patient or animal to be treated.

[0283] A method for extracorporeal blood treatment using the system disclosed in this document or the treatment device disclosed in this document according to this disclosure is characterized by the following steps:

[0284] - Introducing the system into the blood circuit of the human or animal to be treated and establishing an extracorporeal blood circuit by connecting the first inlet of the system to the first blood vessel of the human or animal to be treated and connecting the first outlet of the system to the first blood vessel and / or the second blood vessel of the human or animal,

[0285] - Withdraw a blood stream to be treated from the in vivo blood circuit of a human or an animal, and introduce the blood stream to be treated into the system via a first inlet of the system,

[0286] - Flow through at least one of the blood treatment devices,

[0287] - Extract the treated blood stream via a first outlet of the system and return the treated blood stream to the in vivo blood circuit of the human or the animal.

[0288] Depending on the situation, the system disclosed herein can thus be connected to the in vivo blood circuit of the human or animal to be treated venovenously or arteriovenously, or alternatively via at least one artificial blood access point.

[0289] Particularly suitable for a venovenous connection of the system disclosed herein to the in vivo blood circuit of a human or animal to be treated is a double-lumen cannula having concentrically arranged inlets and outlets, such as the " twin" cannula sold by Novalung GmbH for adult patients, i.e., in the method for extracorporeal blood quality disclosed herein, the system is introduced into the blood circuit of the human or animal to be treated, and preferably a double-lumen cannula is used to establish the extracorporeal blood circuit.

[0290] In addition to being derived from Examples 20 to 37 and the description, these and further features of the present disclosure are also derived from the associated drawings and the description of the drawings, wherein, in the embodiments of the present disclosure, all the features and combinations of features cited and / or depicted can be implemented not only in the combinations indicated respectively but also in other combinations or individually, as long as it is technically feasible.

[0291] Some of the features or characteristics cited and / or depicted separately in the present disclosure relate both to the system disclosed herein, the treatment device disclosed herein, the kit disclosed herein, the method for operating the system disclosed herein and / or the treatment device disclosed herein, and the method for extracorporeal blood treatment using the system disclosed herein or the treatment device disclosed herein, wherein some of these features and characteristics are described only once, for example, only in combination with the system disclosed herein, although still applicable to the system disclosed herein, the treatment device disclosed herein, the kit disclosed herein, the method for operating such a system and / or the treatment device disclosed herein, and the method for extracorporeal blood treatment using such a system or the treatment device disclosed herein within the scope of technically possible embodiments. Description of the Drawings

[0292] The present disclosure will be defined in more detail below with reference to the accompanying drawings based on a plurality of exemplary embodiments, wherein components having the same function are denoted by the same reference numerals unless the context clearly indicates or otherwise. Shown are:

[0293] Figure 4 is a schematic diagram of the basic structure of a first exemplary embodiment of a system according to the present disclosure,

[0294] Figure 5 is a schematic diagram of the basic structure of a second exemplary embodiment of a system according to the present disclosure,

[0295] Figure 6 is a schematic diagram of the basic structure of a third exemplary embodiment of a system according to the present disclosure,

[0296] Figure 7 is a schematic diagram of the basic structure of a fourth exemplary embodiment of a system according to the present disclosure,

[0297] Figure 8 is a schematic diagram of the basic structure of a fifth exemplary embodiment of a system according to the present disclosure,

[0298] Figure 9 is a schematic diagram of the basic structure of a sixth exemplary embodiment of a system according to the present disclosure,

[0299] Figure 10 is a schematic diagram of the basic structure of a seventh exemplary embodiment of a system according to the present disclosure,

[0300] Figure 11 is a schematic diagram of the basic structure of an eighth exemplary embodiment of a system according to the present disclosure,

[0301] Figure 12 is a schematic diagram of the basic structure of a ninth exemplary embodiment of a system according to the present disclosure, and

[0302] Figure 13 is a schematic diagram of the basic structure of a tenth exemplary embodiment of a system according to the present disclosure. Detailed Description

[0303] Figure 4 shows a schematic diagram of the basic structure of a first exemplary embodiment of a system B100 for extracorporeal blood treatment disclosed herein, wherein the system B100 includes a first inlet formed by a supply line B1 for introducing a blood stream to be treated into the system B100, three blood treatment devices A, D, and G, and a first outlet formed by a return line B2 for extracting the treated blood stream from the system B100.

[0304] The first blood treatment device A is thus an adsorber device A designed for endotoxin adsorption. The second blood treatment device D is designed as a dialysis device D, in particular for hemodialysis. The third blood treatment device G is a gas exchanger designed as a device for reducing the carbon dioxide content from a blood stream to be treated according to the first aspect of the present disclosure.

[0305] Figure 4 The system B100 disclosed herein depicted in is thus designed to be introduced into a human or animal blood circuit to establish an extracorporeal blood circuit, whereby the supply line B1 can be connected for this purpose to a first blood vessel, in particular a vein or artery, of the patient or animal to be treated for withdrawing the blood stream to be treated, and the return line B2 is connected to the first blood vessel or a second blood vessel, in particular a vein, for returning the treated blood stream into the in-vivo blood circuit of the patient / animal.

[0306] To create an extracorporeal blood circuit, in particular connected to the in-vivo blood circuit of the patient or animal to be treated, the system can preferably be connected to a double-lumen cannula that allows the establishment of a veno-venous extracorporeal blood circuit with only one vascular access. This thus results in extremely low pressure for the patient or animal to be treated, since two separate inlets into two separate blood vessels do not need to be positioned. In addition, the risk of infection is also reduced.

[0307] According to the present disclosure, as Figure 4 shown by the arrows in Figure 4 , the three blood treatment devices A, D, and G are thus connected in series, i.e., successively, with respect to the blood flow direction of the blood stream flowing through the system B100. Thereby, the individual blood treatment devices A, D, and G are part of a common treatment device according to the present disclosure and are accommodated by a common base, in particular fixed to a common carrier, wherein the individual components of the system B100 are interconnected by corresponding hoses so as to be able to be successively, i.e., sequentially, flowed through.

[0308] The series connection of the adsorber device A, dialysis device D, and gas exchange device G disclosed herein enables a combined blood treatment, in particular a combination of adsorption treatments, in this case a combination of sepsis treatment, dialysis treatment, and removal of CO2 from the blood in a single common extracorporeal blood circuit. This can thus avoid having to create multiple extracorporeal circuits for blood treatment and having to position a corresponding plurality of inlets in the patient or animal to be treated. Thus, the system B100 according to the present disclosure enables simultaneous blood treatment by means of adsorption, dialysis, and gas exchange with the volume of blood of only one extracorporeal blood circuit.

[0309] The adsorber device A in this exemplary embodiment of the system B100 disclosed herein is designed for sepsis treatment. Adsorber devices for this purpose are in principle known from the prior art. Since a partial volume is extracted from the blood mass flow during blood treatment using the adsorber device A, another inlet, in particular a fourth inlet, is connected downstream of the adsorber device A in the blood flow direction to supply replacement fluid to compensate for this volumetric loss, so that in particular a liquid replacement fluid, in particular an electrolyte solution, can be supplied.

[0310] In Figure 4 the system B100 disclosed herein depicted, the dialysis device D includes a dialyzer for hemodialysis, to which dialysate or dialysis fluid can be supplied via a fifth inlet B6 accordingly, and the effluent formed during dialysis treatment can be discharged via a second outlet B5. Dialysis devices of this type are also generally known from the prior art.

[0311] The gas exchange device G is Figure 4 schematically depicted in the system B100 disclosed herein as a device having a first defined region for receiving extracorporeal blood and a second defined region for receiving the buffer solution described herein. The first region and the second region are adjacent to each other in a contact zone and are separated from each other only by a membrane via which gas exchange can take place between the blood and the buffer solution disclosed herein. The buffer solution disclosed herein described in this application can be an elimination medium component of a gas exchange device for reducing the carbon dioxide content in blood extracorporeally.

[0312] In a particularly designed embodiment of the device disclosed herein, the gas exchanger G of the system 100 has a first defined region for receiving extracorporeal blood, an inlet port and an outlet port for the blood, and is designed such that the blood can flow through this region from the inlet port to the outlet port in a first flow direction. In this embodiment, the second defined region for receiving the buffer solution has an inlet port B8 and an outlet port B7 for the buffer solution, and is designed such that the buffer solution can flow through this region from the inlet port to the outlet port in a second flow direction.

[0313] To convey the blood flow to be treated through the system B100, a first pump P1 designed as a blood pump is provided, whereby the first blood pump P1 can be actuated by means of a control device (not shown here) which is also part of the system B100 disclosed herein to control and / or regulate the blood flow.

[0314] Thus, the first blood pump P1 can be a peristaltic pump. In a particularly preferred embodiment, the system disclosed herein has a centrifugal pump as the first pump. This can be a diagonal pump designed as a rotor pump, preferably as described in DE 10 2010024 650 A1. The size of the blood pump P1, in particular its connection cross-section, is selected based on the blood volume of the patient or animal to be treated.

[0315] In order to be able to establish an optimal blood flow for optimal treatment success and for monitoring purposes in at least one of the three blood treatment devices A, D, and / or G, the system includes a plurality of pressure sensor devices (not shown here), wherein, in the present exemplary embodiment of the system B100 disclosed herein, the corresponding pressure sensor devices are arranged directly before and after the blood treatment devices A, D, or G.

[0316] This enables the determination of the corresponding pressure gradients generated on the associated blood treatment devices A, D, or G. The device can help deduce the state of each blood treatment device A, D, or G. In particular, the determined pressure gradient allows conclusions to be drawn about the degree to which each blood treatment device A, D, or G is affected by coagulation.

[0317] Furthermore, the given transmembrane pressure in each of the blood treatment devices A, D, and / or G can be determined in this way. Since the efficiency of each blood treatment essentially depends on the transmembrane pressure applied respectively, and the treatment efficiency should be within a specific range for optimal treatment success for each blood treatment device, the blood flow can be set at least for at least one of the three blood treatment devices A, D, and G such that in each case, a favorable transmembrane pressure is established, especially by the corresponding actuation of the blood pump P1.

[0318] In Figure 4 The system B100 disclosed herein depicted also includes a bubble detection device B14 arranged downstream of the three blood treatment devices A, D, and G in the blood flow direction for detecting bubbles in the blood flow and a check valve B3 arranged downstream of the bubble detection device B14 in the return line 2. When the bubble detection device 14 detects bubbles in the blood flow, the check valve B3 is closed, the first blood pump P1 is shut down, and an alarm is triggered. Thus, this can prevent bubbles from returning to the patient's or animal's in-vivo blood circuit with the blood flow, resulting in life-threatening conditions or even death.

[0319] Therefore, the system B100 disclosed herein described here is designed for a blood flow in the range of 0.05 to 5 l per minute, especially in the range of 0.1 to 3 l per minute, especially in the range of 0.2 to 1 l per minute, especially in the range of 0.2 to 0.5 l per minute.

[0320] To avoid complications, the surface of the cavity of system B100 that comes into contact with the blood flow can be biocompatible and at least partially have at least one functional coating, in particular an antibacterial, anticoagulant, and / or anti-inflammatory coating.

[0321] In the Figure 4 first exemplary embodiment of the system B100 for extracorporeal blood treatment disclosed herein depicted in, the adsorber device A is arranged upstream of the dialysis device D in the blood flow direction, where the dialysis device D is in turn arranged upstream of the gas exchange device G in the blood flow direction. The advantage of this arrangement is that an undiluted blood flow can be supplied to the adsorber device A, thus ensuring high efficiency of the adsorption treatment. Furthermore, in the case of the given sequence of the respective blood treatment devices A, D, and G as depicted in Figure 4 , undesired non-specific ion binding or pH changes may occur in the adsorber device A, which can be compensated for by the dialysis treatment of the dialysis device D performed downstream in the blood flow.

[0322] Furthermore, this arrangement of the dialysis device D downstream of the adsorber device A in the blood flow direction can act as another safety system to prevent the undesired intrusion of particles from the upstream adsorber device A.

[0323] The arrangement of the gas exchange device G downstream of the adsorber device A in the blood flow direction has the following advantages: The gas exchange device G can compensate for the carbon dioxide (CO2) accumulated in the blood flow due to the supply of the replacement (which can be via the fourth inlet B4 after the adsorber device and before the dialysis device in the exemplary example shown in Figure 4 ) and due to the potential carbon-containing (CO2) dialysis fluid (which can be supplied to the system B100 via the fifth inlet B6 in this exemplary example) before the treated blood flow is correspondingly returned to the in-vivo blood circuit of the patient or animal.

[0324] If the dialysis device D in the system for extracorporeal blood treatment disclosed herein is designed for hemodiafiltration instead of hemodialysis, and the blood treatment devices in the system are arranged as described in Figure 4 , the replacement, in particular an additional amount of replacement, can preferably also be supplied to the blood flow via the inlet B4 to compensate for the fluid loss in the dialysis device D. Alternatively or additionally, the system can also include another inlet downstream of the dialysis device D in the blood flow direction for adding replacement to compensate for the fluid and / or volume loss in the adsorber device A and / or the dialysis device D.

[0325] To enable the system B100 disclosed herein to flexibly adapt to the respective blood treatment requirements, each of the blood treatment devices A, D, and G of the system 100 disclosed herein has a replaceable treatment module, and each treatment module includes the entire treatment section and can be easily replaced as a replacement part. In this way, the system B100 disclosed herein can be easily and quickly adapted to the respective treatments required. Thus, for example, the adsorber device A can be quickly and easily reconfigured from an adsorber device A for endotoxin adsorption, for example, into an adsorber device A for cytokine adsorption, for which an adsorber treatment module is specially designed according to the application requirements.

[0326] Correspondingly, by changing the respective dialysis treatment module, the dialysis device D of the system B100 disclosed herein can be reconfigured from a dialysis device D designed for hemodialysis into a dialysis device D designed for hemofiltration or hemodiafiltration.

[0327] The gas exchange device G of the system B100 disclosed herein can also be adapted in the same way, where, depending on the treatment required, a gas exchange treatment module designed to remove CO2 from the blood stream can be used.

[0328] Preferably, the respective inlets and outlets can likewise be adapted and / or reconfigured, especially with regard to their arrangement within the system, especially relative to their arrangement before and / or after the respective blood treatment devices.

[0329] Thus, the system B100 can be specifically configured for each treatment. In addition, when coagulation or a similar situation occurs, individual treatment modules can be quickly and easily replaced. In addition, it is possible to ensure in a particularly simple manner that a sterile system B100 for blood treatment is provided, since all components in contact with the blood stream, especially the respective blood treatment modules and their hose fittings, can be easily replaced separately before starting treatment of a new patient or new animal.

[0330] Figure 5 A second exemplary embodiment of the system B200 for extracorporeal blood treatment disclosed herein is shown, where components having the same function have the same reference numerals.

[0331] Similarly only in Figure 5 The structure of the second exemplary embodiment of the second system B200 for extracorporeal blood treatment schematically shown in is mainly similar to the first exemplary embodiment of the system 100 for extracorporeal blood treatment described according to Figure 4 Although different from the system B100 described with reference to Figure 4 The difference lies in that Figure 5The order of the three blood treatment devices A, D, and G in the system B200 depicted is different. In addition, the dialysis device D is not designed for hemodialysis and thus does not have a dialyzer but is only used for hemofiltration and thus has a hemofilter.

[0332] For this reason, the system B200 does not have a fifth inlet B6 for supplying dialysate because hemofiltration does not require the supply of additional dialysate fluid, and only one kind of effluent generated by hemofiltration will be discharged, which can also be discharged via Figure 5 the second outlet B5 in the system depicted.

[0333] Figure 5 An embodiment of the system B200 for extracorporeal blood treatment depicted - in which the dialysis device D is arranged before the adsorber device A in the blood flow direction, so that the blood flow to be treated flows through the dialysis device D before flowing through the adsorber device A - has the advantage that the blood flow is concentrated by removing the filtration volume (effluent) in the hemofilter of the dialysis device D. Therefore, compared with Figure 4 the system B100, a more concentrated blood flow can be supplied to the adsorber device A. Therefore, a higher adsorption treatment efficiency can be achieved. Therefore, using Figure 5 the system B200 depicted can achieve an improved adsorption treatment.

[0334] In Figure 5 a second exemplary embodiment of the system depicted, the downstream arrangement of the gas exchange device G in the blood flow direction can also compensate for the undesired load generated due to the addition of a load (CO2) replacement via the fourth inlet B4 before returning to the in-vivo blood circuit of the patient or animal to be treated or the corresponding enrichment of the blood mass flow with carbon dioxide ((CO2).

[0335] Since a more concentrated blood flow is supplied to the adsorber device A, the risk of coagulation may increase, especially in the adsorber device A. However, coagulation can be detected quickly and reliably by the respective pressure sensor devices provided immediately before and after the three blood treatment devices A, D, and G, especially by adding an anticoagulant additionally to the blood flow, for example, by adding citrate via the inlet B9 (see Figure 7 ), and coagulation is largely avoided. In addition, if coagulation occurs, the respective adsorber device A affected by coagulation or the corresponding blood treatment devices A, D, and / or G, or the corresponding treatment modules of the blood treatment devices A, D, and / or G forming the treatment section can be replaced separately.

[0336] Figure 6Shows a third exemplary embodiment of a system B300 for extracorporeal blood treatment, wherein the system B300 has a substantially similar structure to the two previously described systems B100 and B200, although the sequential arrangement of the individual blood treatment devices A, G, and D is different from the two exemplary embodiments of the previously described systems B100 and B200 for extracorporeal blood treatment, respectively.

[0337] In Figure 6 the third exemplary embodiment of the system 300 for blood treatment shown in, as in Figure 4 the system B100 depicted in, the blood mass flow to be treated also first flows through the adsorber device A. However, thereafter, the mass flow first flows through the gas exchange device G until downstream, and only then flows through the dialysis device D.

[0338] Since in Figure 6 the exemplary embodiment of the system B300 depicted in the dialysis device D is also only designed for hemofiltration and not for hemodialysis, the blood flow can now no longer be loaded through the gas exchange device G due to the exchange with the CO2-loaded dialysate, because since hemofiltration does not require dialysate, no dialysate is supplied to the dialysis device.

[0339] The arrangement of the gas exchange device G after the adsorber device A ensures that a possible undesired CO2 load of the blood mass flow caused by the supply of the CO2-loaded replacement via the fourth inlet B4 can be compensated. Similarly, with the dialysis device D arranged downstream of the adsorber device A in the blood flow direction, the dialysis device D can also act as a safety-related filtration stage against the undesired intrusion of particles in the adsorber device A arranged upstream of the blood flow. In addition, the undesired, non-specific additional ion binding and / or pH changes potentially occurring in the adsorber device A can also be compensated by means of the dialysis device D in this arrangement or correspondingly through the system B300. Furthermore, the hemofilter downstream of the gas exchange device G generates a backpressure in the gas exchanger G, which has a beneficial effect on the function of the gas exchanger G.

[0340] Figure 7 Shows a fourth exemplary embodiment of a system B400 for extracorporeal blood treatment, wherein this exemplary embodiment represents a particularly preferred embodiment of a system for extracorporeal blood treatment and is also based on the first exemplary embodiment of the system B100 as described with reference to Figure 3 Furthermore, additionally to the system B100 described according to Figure 3 the system B400 also includes a second inlet B9 and a third inlet B11, via which components can be supplied to the blood flow in each case.

[0341] Thus, the first component, which is preferably accommodated in the bag B10, can be supplied to the blood flow to be treated via the second inlet B9 by means of the second pump P2, where, in this case, the system B400 is designed such that the first component can be supplied to the blood flow immediately after the blood flow has been withdrawn from the in-vivo blood circuit of the patient or animal to be treated, in particular still in front of the first blood pump P1 in the blood flow direction, in particular in front of the first blood treatment device through which the blood flow to be treated flows.

[0342] In particular, the system B400 is hereby designed to supply a liquid citrate solution as an anticoagulant to the blood flow to be treated via the second pump P2 and the second inlet B9.

[0343] The second component, in particular a calcium solution, can be supplied to the system via the third pump P3 and the third inlet B11 to compensate for the calcium loss occurring in the dialysis device D during hemodialysis. Thus, in Figure 7 this fourth exemplary embodiment of the system B400 for extracorporeal blood treatment depicted in, the second component is hereby supplied directly via the third inlet B11, in particular after the one-way valve B3, before the treated blood flow returns to the patient. Of course, the third inlet can also be arranged in front of the one-way valve B3 in the blood flow direction.

[0344] Figure 7 The system B400 depicted in is particularly suitable for the treatment of an extracorporeal blood circuit with a venous-venous access, i.e., in particular for CVVHD, where the blood flow to be treated is withdrawn from the vein of the patient or animal to be treated and the treated blood flow returns to the vein.

[0345] If, as described in accordance with Figure 7 the dialysis device D in a system for extracorporeal blood treatment of a blood treatment device is designed for hemodiafiltration instead of hemodialysis, the replacement fluid can preferably be supplied to the blood flow via an additional inlet B4 after the adsorber device A and before the dialysis device D in the blood flow direction to compensate for the fluid loss in the adsorber device A and / or the dialysis device D. Alternatively or additionally, the system can also include an inlet B4 located after the dialysis device D in the blood flow direction for adding replacement fluid to compensate for the fluid and / or volume loss in the adsorber device A and / or the dialysis device D. Such a system is particularly suitable for post-CVVHDF.

[0346] Figure 8 shows a fifth exemplary embodiment of the system B500 for extracorporeal blood treatment, which is also based on Figure 4 the system B100 depicted in, although different from Figure 4The system B100 is different in that the adsorber device A is arranged behind the gas exchange device G, in particular behind the gas exchange device G and behind the dialysis device D. The advantage of this arrangement is that due to the increased back pressure generated at the adsorber device A, the pressure gradient across the gas exchange membrane in the gas exchange device G increases, thereby enabling improved gas exchange.

[0347] Figure 8 It is shown that the replacement for compensating for the volume loss in the adsorber device A is preferably added to the blood stream before the gas exchange device G via the inlet B4. Alternatively or additionally, it can also be advantageously added before the dialysis device D. Thus, the subsequently arranged gas exchange device G can compensate for the undesired CO2 load caused by the replacement.

[0348] Figure 9 It is shown based on Figure 8 A sixth exemplary embodiment of the system B600 for extracorporeal blood treatment of the system B500 as shown, although different from the Figure 8 system B500 in that in this case the gas exchange device G is arranged before the adsorber device D, and in this case the adsorber device D is only designed for hemofiltration and not for hemodialysis.

[0349] The advantage of this arrangement is that the back pressure before the dialysis device D and before the adsorber device A has a corresponding increasing effect on the pressure gradient across the gas exchange membrane in the gas exchange device G, whereby the efficiency of gas exchange can be increased.

[0350] Preferably, the replacement for compensating for the volume loss in the adsorber device A is also added to the blood stream before the gas exchange device G via the inlet B4, so that the undesired CO2 load caused by the replacement can be compensated by the subsequently arranged gas exchange device G.

[0351] Since the dialysis device D is designed for hemofiltration and does not require dialysis fluid, the undesired CO2 load caused by the replacement can be prevented.

[0352] Figure 10 A seventh exemplary embodiment of the system B700 for extracorporeal blood treatment is shown, and this system 700 is also based on Figure 4System B100 depicted, but additionally provided with a bypass device B13 having a bypass line B13A and a bypass valve B13B, which allows the blood flow to be treated to bypass the adsorber device A. System B700 has the advantage that blood treatment can be carried out with or without adsorptive treatment. As a result, since adsorptive treatment is not indicated in all blood treatment cases, or coagulated or almost fully loaded or saturated adsorbers can be avoided, the flexibility in terms of possible applications of the systems disclosed herein is significantly increased.

[0353] Therefore, preferably, the bypass valve B13B is designed such that in each case the blood flow to be treated is completely guided through the adsorber device downstream of the bypass valve B13B in the direction of blood flow, or completely bypasses the adsorber device A via the bypass line B13A.

[0354] In a particularly advantageous embodiment of the systems disclosed herein, the system includes a bypass device suitably designed for each of the blood treatment devices A, D, G, in order to be able to carry out adsorptive treatment and / or gas exchange and / or dialysis treatment alternatively using the systems disclosed herein.

[0355] Figure 11 Shows the Figure 4 Eighth exemplary embodiment of the system B800 disclosed herein based on the system B100, wherein in this exemplary embodiment, instead of the adsorber device A, the first blood treatment device is a plasma separation device PT in the form of a plasma filter PT, by means of which the separated plasma can be supplied to the plasma disposal container W via a line B16 forming a fourth outlet for removing the separated plasma, with the aid of another, in particular a third pump P3.

[0356] Fresh plasma can be supplied to the blood flow via a line B17 forming a seventh inlet B17, in particular with the aid of another, in particular a fourth pump P4, as an alternative to the amount of plasma discharged.

[0357] Figure 12 Shows the Figure 11 Ninth exemplary embodiment of the system B900 based on the system B800, wherein in this exemplary embodiment, the separated plasma is not supplied to the plasma disposal container W, but instead, via a hose line, in particular via a bypass line, through a blood treatment device in the form of an adsorber device A, where the treated plasma returns to the rest of the blood flow, in particular to the main line, after the adsorptive treatment.

[0358] Figure 13 Shows the Figure 12Tenth exemplary embodiment of system B900 and system B1000, wherein in this exemplary embodiment, the separated plasma is not supplied to the rest of the blood flow after the adsorption treatment, but is supplied to the plasma separation device PT in a bypass circuit for recirculation. Thus, improved plasma separation and / or adsorption treatment can be achieved.

[0359] Figures 4 to 13 List of reference numerals:

[0360] B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000

[0361] System for extracorporeal blood treatment

[0362] B1 supply line (first inlet)

[0363] B2 return line (first outlet)

[0364] B3 one-way valve

[0365] B4 fourth inlet for supplying replacement to the blood flow

[0366] B5 second outlet for removing effluent from the dialysis device

[0367] B6 fifth inlet for supplying dialysate to the dialysis device

[0368] B7 third outlet for removing the buffer solution containing CO2 from the gas exchange device

[0369] B8 sixth inlet for supplying the buffer solution disclosed herein for reducing the CO2 content in the blood to the gas exchange device

[0370] B9 second inlet for supplying the first component to the blood flow

[0371] B10 bag filled with the first component

[0372] B11 third inlet for supplying the second component to the blood flow

[0373] B12 bag filled with the second component

[0374] B13 bypass device

[0375] 13A bypass line

[0376] 13B bypass valve

[0377] 14 bubble detection device

[0378] 15 bag filled with fresh plasma

[0379] The fourth outlet for removing separated plasma

[0380] The seventh inlet for supplying fresh plasma

[0381] An adsorber device

[0382] A dialysis device

[0383] A gas exchange device

[0384] A plasma separation device (PT)

[0385] P1 The first pump, a blood pump

[0386] P2 The second pump

[0387] P3 The third pump

[0388] P4 The fourth pump

[0389] P5 The fifth pump

[0390] A plasma disposal container (W)

[0391] In a second aspect, the subject matter of the present disclosure is characterized by the features of the following Examples 20 to 37: Example 20

[0392] A system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) for extracorporeal blood treatment, wherein the system (B100, B200, B300, B400, B500,

[0393] - A first inlet (B1) for introducing a blood stream to be treated into the system (B100, B200, B300, B400, B500,

[0394] B600, B700, B800, B900, B1000),

[0395] - At least one first blood treatment device (A, PT),

[0396] - A second treatment device (D),

[0397] - A third blood treatment device (G), and

[0398] - A first outlet (B2) for extracting a treated blood stream from the system (B100, B200, B300, B400, B500, B600, B700, B800,

[0399] B900, B1000),

[0400] Among them, the first blood treatment device (A, PT) is or includes an adsorber device (A) for removing at least one exogenous and / or at least one endogenous pathogen and / or a plasma separation device (PT) for separating plasma from other blood components.

[0401] Among them, the second blood treatment device (D) is designed as a dialysis device (D), in particular a dialysis device (D) for renal replacement therapy, and

[0402] Among them, the third blood treatment device (G) is a gas exchange device, which is designed as a device (10) for in vitro reducing the carbon dioxide content in blood according to any one of claims 8 to 19, in particular a gas exchange device (G) for at least partially removing CO2 from the blood flow flowing through the first defined region of the gas exchange device (G) and the buffer solution having the features of at least one of claims 1 to 6 flowing through the second defined region of the gas exchange device.

[0403] Among them, the three blood treatment devices (A and / or PT, D, G) are connected in series in sequence with respect to the blood flow direction of the blood flow to be treated between the first inlet (B1) and the first outlet (B2) of the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) in the functional application state of the system, and the blood flow to be treated flows through the three blood treatment devices successively in vitro.

[0404] Example 21

[0405] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to claim 20, characterized in that the first blood treatment device (A) is or includes an adsorber device (A) designed for endotoxin adsorption, cytokine adsorption and / or immunoabsorption, wherein the adsorber device (A) is particularly designed to remove at least one drug and / or medicinal substance and / or at least one phytotoxin and / or at least one organic toxin and / or at least one other toxic substance and / or remove bacteria, viruses, fungi and / or other organisms and / or at least one immune complex and / or at least one immunoglobulin and / or at least one inflammatory reaction substance and / or antibody and / or at least one pathogen-associated molecular pattern and / or at least one so-called alarmins in the body.

[0406] Example 22

[0407] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to claim 20 or 21, characterized in that the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) comprises at least one first pump (P1), in particular a pump (P1) designed as a blood pump, for conveying at least a part of the blood flow to be treated, wherein the first pump (P1) is preferably arranged in the blood flow direction between a first inlet (1) and the first of the three blood treatment devices (A, PT, D, G), and is particularly designed to convey the entire blood flow to be treated.

[0408] Example 23

[0409] The system (B400) according to any one of claims 20 to 22, characterized in that the system (B400) comprises another, in particular a second inlet (B9), for adding a first component to the blood flow, in particular to the blood flow to be treated, wherein this other inlet (B9) is preferably arranged in the blood flow direction such that the component can be supplied to the blood flow in the blood flow direction before the first pump (P1) and / or before the first of the three blood treatment devices (A, PT, D, G).

[0410] Example 24

[0411] The system (B400) according to any one of claims 20 to 23, characterized in that the system (B400) comprises another, in particular a third inlet (B11), for adding a second component to the blood flow, in particular to the treated blood flow, wherein this other inlet (B11) is preferably arranged in the blood flow direction such that the component can be supplied to the blood flow in the blood flow direction after the dialysis device (D), in particular after the last of the blood treatment devices (A, PT, D, G).

[0412] Example 25

[0413] The system (B100, B200, B300, B400, B700, B800, B900, B1000) according to any one of claims 20 to 24, characterized in that the adsorber device (A) and / or the plasma separation device (PT) are arranged in the blood flow direction before the gas exchange device (G).

[0414] Example 26

[0415] The system (B500, B600) according to any one of claims 20 to 25, characterized in that the adsorber device (A) and / or the plasma separation device (PT) are arranged behind the gas exchange device (G) in the blood flow direction.

[0416] Example 27

[0417] The system (B100, B400, B700, B800, B900, B1000) according to any one of claims 20 to 26, characterized in that the adsorber device (A) and / or the plasma separation device (PT) are arranged in front of the dialysis device (D) in the blood flow direction, wherein the dialysis device (D) is preferably designed for hemodialysis and particularly includes a dialyzer.

[0418] Example 28

[0419] The system (B200, B500, B600) according to any one of claims 20 to 27, characterized in that the adsorber device (A) and / or the plasma separation device (PT) are arranged behind the dialysis device (D) in the blood flow direction, wherein the dialysis device (D) is preferably designed for hemofiltration and particularly includes a hemofilter.

[0420] Example 29

[0421] The system (B100, B200, B400, B500, B800, B900, B1000) according to any one of claims 20 to 28, characterized in that the dialysis device (D) is arranged in front of the gas exchange device (G) in the blood flow direction.

[0422] Example 30

[0423] The system (B300, B600, B700) according to any one of claims 20 to 29, characterized in that the dialysis device (D) is arranged behind the gas exchange device (G) in the blood flow direction, wherein the dialysis device (D) is preferably designed for hemofiltration and includes a hemofilter.

[0424] Example 31

[0425] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to any one of claims 20 to 30, characterized in that the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) comprises at least one pressure sensor device for determining the flow pressure of the blood flow at a defined point in the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000), wherein the at least one pressure sensor device is preferably arranged directly in front of and / or behind at least one treatment section of the blood treatment device (A, PT, D, G) in the blood flow direction.

[0426] Example 32

[0427] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to any one of claims 20 to 31, characterized in that the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) comprises at least one bubble detection device (B14) for detecting bubbles in the blood flow.

[0428] Example 33

[0429] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to any one of claims 20 to 32, characterized in that the treatment section of at least one blood treatment device (A, PT, D, G) is at least partially, preferably completely, formed by a replaceable treatment module, in particular by a cassette treatment module.

[0430] Example 34

[0431] The system (B700) according to any one of claims 20 to 33, characterized in that the system (B700) comprises at least one switchable bypass device (B13) for bypassing at least one blood treatment device (A, D, G).

[0432] Example 35

[0433] The system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) according to any one of claims 20 to 34, characterized in that at least one component of the system (B100, B200, B300, B400, B500, B500, B600, B700, B800, B900, B1000) comprises a biocompatible and preferably functional coating on the surface in contact with the blood flow to be treated, in particular an antibacterial, anticoagulant and / or anti-inflammatory coating.

[0434] Example 36

[0435] A treatment device for extracorporeal blood treatment, characterized in that the treatment device comprises a system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) designed according to any one of claims 20 to 35, wherein the first, second and third blood treatment devices (A, PT, D, G) of the system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) are particularly arranged in a common housing and / or accommodated by a common base.

[0436] Example 37

[0437] A kit for extracorporeal blood treatment, wherein the kit at least comprises the following as components:

[0438] - at least one first blood treatment device (A, PT),

[0439] - a second blood treatment device (D),

[0440] - a third blood treatment device (G), and

[0441] - a tube set having a first inlet (1) for introducing the blood flow to be treated and a first outlet (2) for discharging the treated blood flow via one or more than two tubes, and

[0442] - in particular an installation and / or operation manual,

[0443] wherein the first blood treatment device (A, PT) is or comprises an adsorber device (A) for removing at least one exogenous and / or at least one endogenous pathogen and / or a plasma separation device (PT) for separating plasma from other blood components,

[0444] wherein the second blood treatment device (D) is designed as a dialysis device (D), in particular a dialysis device (D) for renal replacement therapy, and

[0445] Among them, the third blood treatment device (G) is designed as a device (A10) for reducing carbon dioxide in blood in vitro according to any one of claims 8 to 19, in particular as a gas exchange device (G) for at least partially removing carbon dioxide from the blood flow flowing through the gas exchange device (G) with a buffer solution having at least one of the features described in claims 1 to 6.

[0446] It is characterized in that the components of the kit can be connected to a system (B100, B200, B300, B400, B500, B600, B700, B800, B900, B1000) for extracorporeal blood treatment according to any one of claims 19 to 33, in particular according to the installation and / or operation manual.

[0447] In a third aspect, the present disclosure relates to a functional unit for performing extracorporeal blood treatment, a blood guiding device for interacting with the functional unit for performing extracorporeal blood treatment, the blood guiding device including a blood treatment element, wherein the blood treatment element is a device for reducing the carbon dioxide content in blood in vitro according to an embodiment of the first aspect of the present disclosure, and an arrangement structure including a functional unit for extracorporeal blood treatment and a blood guiding device used in each case together with a buffer solution according to the first aspect of the present disclosure.

[0448] In the field of extracorporeal blood treatment, it is known to combine different therapies into a single therapy that can be performed, for example, using individual medical treatment devices or individual medical treatment systems separately. In other words, at least two separate blood treatment elements in a common extracorporeal blood circuit thus preferably affect the drawn blood in different ways. This kind of treatment is called combined treatment. Usually, therapies with causally related medical indications and thus often present together are combined. When the treatment technology requires such a combination due to favorable synergistic effects, the combination of treatments for different indications is also appropriate.

[0449] Therefore, for example, in the field of extracorporeal blood treatment, renal replacement therapy is combined with other extracorporeal blood therapies. For example, treatments for acute dialysis (CRRT), such as hemodialysis (HD), hemodiafiltration (HDF), hemofiltration (HF), hemoperfusion (HP), or ISO-UF, are respectively combined with extracorporeal membrane oxygenation or CO2 removal treatment and used in a common extracorporeal blood circuit. Usually, a dialyzer and a blood treatment element, such as a gas exchanger, for further extracorporeal blood treatment are arranged in series in the common extracorporeal blood circuit for this purpose.

[0450] It is further known that with increasing flow rate, the effectiveness of gas exchange increases, especially for removing CO2 from the blood or for enriching O2 in the blood.

[0451] The inventors have recognized that the forced flow rate coupling in both the dialyzer and the gas exchanger due to the series arrangement of the two components, regardless of their sequential arrangement, is problematic for operating a treatment device with efficient gas exchange. For example, the flow rates used in continuous renal replacement therapy (CRRT) treatments typically do not exceed 200 - 300 ml / min. In contrast, the efficiency of the cited lung assist therapies depends to a large extent on the blood flow rate. When reducing the carbon dioxide content of the blood in an extracorporeal blood circuit, from a medical perspective, a blood flow rate of at least 500 ml / min is provided. Thus, in the prior art, in terms of reducing CO2 in the blood, the combination of these renal replacement therapies and lung assist therapies is always associated with one of the potential indications for treatment with reduced efficiency.

[0452] The current task is to overcome the above - mentioned drawbacks and to be able to perform extracorporeal blood treatment (combined treatment) with a combination of a dialyzer and another blood treatment element for reducing the carbon dioxide content in the blood within the optimal efficiency range for each part of the treatment.

[0453] The present invention solves this task by means of Examples 38, 44, and 50. Advantageous embodiments of the present invention are represented by Examples 39 to 43 and 45 to 49.

[0454] A functional unit for performing extracorporeal blood treatment according to the present disclosure, in which blood is guided in a blood - guiding device having a main blood line and at least one secondary line fluidly connected to the main blood line, and wherein the main blood line includes a dialyzer and a blood treatment element downstream of the dialyzer, wherein the blood treatment element (C103) is a device (C10) for extracorporeal reduction of the carbon dioxide content in the blood according to any one of Examples 8 to 19, the functional unit including a control device and a pump assembly configured to be able to generate a blood flow in the main blood line and at least one secondary line, wherein the control device is configured to be able to operate the pump assembly such that a first blood flow rate (dialyzer flow rate) in the dialyzer is decoupled from a second blood flow rate in the blood treatment element.

[0455] In the context of the present application, a "blood treatment element" or "gas exchanger" is understood to be a device for reducing the carbon dioxide content in blood in vitro according to the first aspect of the present disclosure, in particular as defined in Examples 8 to 19. The device for reducing the carbon dioxide content in blood in vitro is characterized in that it operates together with a buffer solution according to the first aspect of the present disclosure, in particular as defined by the features of at least one of Use Forms 1 to 6. Thus, according to the first aspect of the present disclosure, the blood treatment element has a first defined region for receiving blood in vitro and a second defined region for receiving the buffer solution disclosed herein, wherein the first and second regions adjacent to each other in the contact region are separated from each other only by a membrane, through which gas exchange can occur between the blood and the buffer solution.

[0456] The blood guiding device disclosed herein for interacting with a functional unit for performing extracorporeal blood treatment disclosed herein includes: a main blood line for fluid connection to a dialyzer and fluid connection to a blood treatment element downstream of the dialyzer, wherein the main blood line has a blood sampling port for connection to a blood sampling access of a patient at one end and a blood return port for connection to a blood return access of the patient at the other end; at least one sub-line that branches off from the main blood line at a first branch point and rejoins the main blood line at a second branch point; and one or more pump assembly sections that are designed to act on the pump assembly of the blood treatment device.

[0457] The arrangement for blood treatment disclosed herein includes a functional unit for performing extracorporeal blood treatment and the blood guiding device disclosed herein.

[0458] In other words, the functional unit for performing extracorporeal blood treatment disclosed herein, the blood guiding device disclosed herein, and the arrangement for blood treatment disclosed herein all allow extracorporeal blood treatment to be carried out using a common extracorporeal blood circuit with a series connection of a dialyzer and a treatment element for reducing the carbon dioxide content in blood arranged downstream of the dialyzer, in order to improve the treatment efficiency. Therefore, a higher blood flow rate than that in dialyzer treatment is meaningful for further extracorporeal blood treatment.

[0459] The blood treatment element for further extracorporeal treatment is a gas exchanger for removing CO2.

[0460] In the sense of this specification, "treatment" can cover not only cure, but also at least include alleviation, symptomatic treatment, delay, dehabituation, and diagnosis. In particular, blood treatment can be understood as any influence on blood or changes in blood, such as adding substances to blood or extracting substances from blood, in order to be able to cause one of the above-mentioned effects or corresponding effects.

[0461] In the sense of a combined treatment, a common extracorporeal blood circuit for the two treatments is desirable, since for both treatments the invasive steps of withdrawing and returning blood need only be carried out once and the patient is thus also only exposed to the accompanying treatment risks once.

[0462] In a series arrangement of a dialyzer and a blood treatment element in an extracorporeal blood circuit, in principle both sequential arrangements are possible. If the blood first flows through a gas exchanger during CO2 removal and then through the dialyzer, after flowing through the gas exchanger, the blood, which already has a low CO2 content, may be re-enriched with CO2 in the dialyzer. This is due to the concentration gradient across the dialysis fluid membrane, since the dialysis solution usually contains bicarbonate in which CO2 is buffered. If the blood only passes through the gas exchanger after the dialyzer, this re-enrichment does not occur.

[0463] The functional unit for performing extracorporeal blood treatment can form the reusable machine side of the blood treatment arrangement. The blood guiding device can form a blood tube set or a cartridge with blood lines or a combination of a blood tube and at least one cartridge with blood lines for equipping the blood treatment device. The blood treatment device can thus be designed as a medical disposable device that is discarded after each treatment for hygienic reasons. In particular, in addition to the blood guiding member, the blood guiding device can also include one or more additional fluid guiding members, such as a dialysis fluid circuit or line for guiding a buffer solution for reducing the carbon dioxide content in the blood as described in the first aspect of the present disclosure, in particular as defined by the features of use forms 1 to 6, for operating the gas exchanger or blood treatment element as described above.

[0464] The main blood line of the blood guiding device can include corresponding suitable connectors or connections for connecting to the dialyzer and / or to the blood treatment element. The design of these connectors, in particular the connectors for connecting to the dialyzer, can include, for example, a cylindrical shape with an outer diameter in the range of 10.5 - 12.8 mm and a tapered fluid channel with an inner diameter of 6.33 mm at the distal end of the connector. However, other designs that meet the expected flow requirements can also be envisaged according to the knowledge of those skilled in the art. Furthermore, if the dialyzer and / or the blood treatment element are firmly attached to the main blood line, for example by gluing or welding, the blood guiding device can also incorporate the dialyzer and / or the blood treatment element.

[0465] The devices for blood treatment and for blood guiding disclosed herein can be provided to act together and can together form the arrangement for treating blood disclosed herein. The blood treatment arrangement can also have other components in addition to the functional unit and the blood guiding device.

[0466] The functional unit and the blood guiding device can each include mating components designed to interact with each other. Thus, the functional unit has a pump assembly, while the blood guiding device has one or more than two pump assembly sections designed to act on the pump assembly of the blood treatment device.

[0467] Optionally, in some embodiments, the functional unit can include one or more than two pressure sensors, while in some embodiments, the blood guiding device can optionally include one or more than two pressure measurement sections, which can be designed to measure pressure by means of the pressure sensors of the functional unit cited for measuring pressure. The pressure measurement section can be a flexible membrane or lead that can transmit the pressure in the blood guiding device to the pressure sensor via a compressible air column.

[0468] Furthermore, in some embodiments, the functional unit can optionally include one infusion pump for supplying a medical fluid or two infusion pumps for supplying a medical fluid or three infusion pumps for supplying a medical fluid or four or more infusion pumps for supplying a medical fluid, while in some embodiments, the main blood line of the blood guiding device can optionally include one or more than two addition ports for a medical anticoagulant liquid and one or more than two additional optional addition ports for a dilution liquid.

[0469] Therefore, the addition port can be understood both as a normal connection or connector, such as a Luer lock design, on the main blood line of the blood guiding device, and as a detachable or firmly attached access line to the main blood line. Thus, an infusion pump of the above-described blood treatment device can be provided to have a pumping action when connected to the addition port access line. Thus, the access lines can each be connected to a fluid reservoir with the fluid to be added to pump the fluid into the main blood line by means of the infusion pump.

[0470] In one embodiment, the inventors propose to branch the main blood line of the common extracorporeal blood circuit at a first branch point upstream of the dialyzer, guide a secondary line around the dialyzer, and recombine it into the main blood line only at a branch point downstream of the dialyzer and upstream of the gas exchanger. Thus, the inventors arrange the dialyzer in the main blood line upstream of the gas exchanger. This may mean that the previously described CO2 re-enrichment can be avoided.

[0471] Furthermore, a pump assembly can be arranged on the extracorporeal blood circuit, and the pump assembly is configured to generate a blood flow in the main blood line and in the secondary line. For this purpose, the pump assembly can be connected to a control device. The control device is configured to be able to control the operation of the pump assembly by means of appropriate signals. Throughout the description, the term "control" can also include regulation as an alternative.

[0472] The control device is configured to be able to operate the pump assembly such that the first blood flow rate in the dialyzer is decoupled from the second blood flow rate in the blood treatment element. Here, "decoupled" is to be understood as meaning that, by means of this control, any desired flow rates can be generated in the dialyzer and the blood treatment element without the specification of one flow rate being restricted to the choice of the other flow rate.

[0473] In another embodiment, the pump assembly can be designed to generate mutually independent blood flow rates in the main blood line and the secondary line. Here, "independent" is to be understood as meaning that the specification of one of the two flow rates has no influence on the choice of the other flow rate for the pump assembly setting.

[0474] Those skilled in the art recognize that the pump assembly can be implemented in various ways to function in the above-described manner.

[0475] Generally, the pump assembly has at least two elements acting on the flow in two line sections. Thus, at least one of these elements is usually an active element, such as a pump, capable of causing flow in the line element. The second element of the at least two elements can likewise be an active element for generating flow or can be a passive element, the function of which can be to make the flow through the element definable or adjustable. The second element can be, for example, a throttling member or a valve.

[0476] For example, the pump assembly can consist of an occluding blood pump upstream of the first branch point in the main blood line and another occluding blood pump downstream of the first branch point and upstream of the dialyzer. Other exemplary embodiments of the pump assembly are indicated in the drawings and the description of the drawings. However, in addition to the described exemplary embodiments, the present invention also encompasses all other pump assemblies capable of transporting blood through the main blood line and / or at least one secondary line.

[0477] In other embodiments of the present disclosure, the pump assembly can also be equipped to generate a blood flow in a second secondary line. In this case, the control device can be configured to be able to operate the pump assembly such that the blood flow rate in at least one section of the main blood line is independent of at least one of the blood flow rates in the secondary line.

[0478] In another embodiment, the main blood line of a common extracorporeal blood circuit branches at a first branch point downstream of the blood treatment element for additional extracorporeal blood treatment, and the secondary line leads around the blood treatment element and rejoins the main blood line again upstream of the blood treatment element and downstream of the dialyzer. In this case, the pump assembly enables the recirculation of the blood flow via the blood treatment element by means of the blood flow in the secondary line. Compared with the blood flow rate in the dialyzer, the blood flow rate in the blood treatment element increases by the amount of the blood flow in the secondary line, which decouples the two flow rates and thus solves the task.

[0479] In the case of CO2 removal, extracorporeal blood is initially mainly reduced by the CO2 provided free in the plasma as it passes through the gas exchanger. Then, the free CO2 is subsequently released again from the blood's natural CO2 buffer system into the plasma. Thus, after some time, the initially reduced partial pressure of free CO2 will be compensated again. The inventors have recognized that the blood that has already been treated in the gas exchanger can thus be re-treated after a very short time, and thus it is worthwhile to perform the above-mentioned recirculation through the gas exchanger.

[0480] In other embodiments of the present disclosure, the blood can also be guided in two secondary pipelines, wherein the first secondary pipeline deviates from the main blood pipeline at a first branch point upstream of the dialyzer and rejoins the main blood pipeline again at a second branch point downstream of the dialyzer and upstream of the treatment element. The second secondary pipeline can deviate from the main blood pipeline at a recirculation branch point downstream of the blood treatment element and merge into the recirculation return port. Thus, the recirculation return port can be arranged in the main blood pipeline upstream of the connection point of the blood treatment element and downstream of the connection point of the dialyzer. In addition, the recirculation return port can also be arranged in the first secondary pipeline upstream of the second branch point. In these embodiments, the second secondary pipeline can recirculate the blood through the blood treatment element for further blood treatment therapies, thereby contributing to improving the efficiency of this part of the therapy. In these embodiments, the pump assembly can also be equipped to generate a blood flow in the second secondary pipeline. In addition, the control device can be configured to be able to operate the pump assembly such that the blood flow rate in at least one section of the main blood pipeline is independent of at least one of the secondary pipeline blood flow rates.

[0481] Measures can be taken in extracorporeal blood treatment to counteract blood clotting. For this purpose, the patient is systematically treated regularly with an anticoagulant substance, such as heparin, or local anticoagulation occurs in the extracorporeal blood circuit, for example by means of heparin or by adding citrate and calcium (CiCa anticoagulation). Anticoagulant coatings of the blood guiding components of the extracorporeal blood circuit are also common. The CiCa anticoagulation method has been established in the field of acute dialysis for many years, and the dosage has been optimized and deeply reviewed in long-term studies. Normally, adding citrate in the extracorporeal blood circuit upstream of the dialyzer reduces blood clotting by binding calcium ions in the so-called calcium citrate chelate. When the blood returns, some of these calcium citrate chelates are re-infused into the patient, where the citrate part is metabolized in the liver and calcium is released again. Another part of the chelate is removed and discarded from the extracorporeal blood circulation via the dialysis membrane.

[0482] Since this process causes the patient to lose a large amount of calcium, it can be replaced by artificially adding calcium before the blood is reinfused. The rate of citrate addition is usually related to the blood flow rate in order to provide sufficient anticoagulation for the corresponding volume of blood that comes into contact with the components of the extracorporeal blood circuit. The rate of calcium addition can be selected so as to equally compensate for the calcium loss via the dialysis membrane. Therefore, it depends on the blood flow rate through the dialyzer, but also on a number of other parameters, such as the rate of citrate addition and the nature specific to the treatment, such as the choice of the dialyzer membrane and the corresponding transmembrane pressure, etc.

[0483] Therefore, the concentration of calcium ions can be regularly monitored by sampling during CiCa CRRT, and the addition rate can be adjusted accordingly. On the other hand, however, the experience of the above-mentioned research can also be utilized, and these experiences are processed using the standard CiCa dosage regimens available to the user. For this purpose, a control device for controlling the corresponding addition of anticoagulants can be provided. This control can be based on, for example, at least one or more than two of the above-mentioned calcium ion concentration, blood flow rate, dialyzer membrane, transmembrane pressure variables stored in the device and / or the standard regimen.

[0484] If another extracorporeal blood treatment is added to the common extracorporeal blood circuit for acute dialysis, it may lead to completely new boundary conditions for the citrate and calcium dosages in CiCa anticoagulation. In particular, the dosage regimens determined in the long-term research results do not necessarily have to be used for further extracorporeal treatments in the series connection of the dialyzer and the blood treatment element, because the influence of the blood treatment element on coagulation induction is not considered, nor is any calcium loss other than the known calcium loss in the dialyzer considered.

[0485] The pipeline route disclosed herein optionally provides an arrangement of an addition port for adding a first medical fluid, such as citrate, for anticoagulation in a section of the main blood pipeline upstream of the dialyzer. Then, all the blood flow in the section of the main blood pipeline will also pass through the dialyzer. Therefore, although a combined treatment is carried out, the known dosage regimen for CiCa anticoagulation can still be continued because only the coagulation initially passing through the dialyzer needs to be considered. The components of the blood treatment element can be anticoagulated by means of a coating.

[0486] The pipeline route also optionally provides an arrangement of an addition port for adding a second medical fluid, such as calcium, for anticoagulation in the main blood pipeline downstream of the blood treatment element.

[0487] In another embodiment of the present disclosure - where the first branch point is arranged upstream of the dialyzer, and thus the first addition port for the first medical fluid for anticoagulation is located downstream of the first branch point, another addition port for a third medical fluid for anticoagulation, such as citrate, can be arranged in the main blood line upstream of the first branch point. When needed throughout the extracorporeal blood circuit, additional addition of citrate, preferably a small amount of citrate, via this line can rapidly produce an enhanced anticoagulant effect. For a small amount of citrate, it is preferred to make an additional addition via the addition port upstream of the first branch point because the maximum tolerable amount of citrate is metabolically limited and a greater impact on the dialyzer, which is usually not coated with an anticoagulant, is desired. Thus, in this case, there is also no need to deviate from the known calcium dosage algorithm, even if a small amount of citrate is additionally added via this line.

[0488] The first and / or second and / or third medical fluid for anticoagulation can also be heparin or another medical fluid with anticoagulant action in each case.

[0489] The pump section for the infusion pump can be arranged in, for example, the above-mentioned single or all additional ports for calcium or citrate. Via the infusion pump, the corresponding medical fluid to be added can be conveyed from the reservoir through the addition line to the main blood line. In an embodiment where the same medical fluid is conveyed through multiple addition lines, especially in the case of citrate, a common pump and / or the same medical fluid can also be conveyed from a common reservoir.

[0490] As mentioned above, the blood treatment device can include a pressure sensor for determining the transmembrane pressure, especially for measuring the pressure in the main blood line between the dialyzer and the blood treatment element. In some embodiments of the blood guiding device, a corresponding pressure measurement section can be arranged for capturing the pressure via the pressure sensor.

[0491] As mentioned above, the blood treatment device can include another pressure sensor for determining the transmembrane pressure, especially for measuring the pressure in the main blood line between the first branch point and the dialyzer. A corresponding pressure measurement section can be arranged in the blood guiding device at the cited point for capturing the pressure via the pressure sensor.

[0492] Two or more pressure sensors can also be provided for measuring the pressure at the above two points or additionally at other points. This enables the transmembrane pressure to be determined particularly precisely via a threshold window of the corresponding pressure values and better monitoring of the treatment process.

[0493] To measure the transmembrane pressure, one or more than one pressure sensor can be arranged on the dialysate side. Thus, the pressure upstream and / or downstream of the dialyzer can be measurable on the dialysate side.

[0494] In order to also enable a combined treatment of renal replacement therapy with hemofiltration or hemodiafiltration, the blood guiding device may optionally have one or more addition ports for dilution liquid on the main blood line. The corresponding infusion pumps on the blood treatment device side can convey dilution liquid, such as replacement solution or dialysis solution, into the main blood line through these addition ports. According to the present disclosure, the dilution liquid can be stored in one or more reservoirs, such as disposable bags. Alternatively, the blood treatment device can be configured to prepare replacement solution or dialysis solution separately. For this purpose, the blood treatment device can include a water treatment device having, for example, a degassing device and a concentrate port for connecting a concentrate source. The addition ports for dilution liquid can be arranged on the main blood line upstream of the dialyzer for pre-dilution. For post-dilution, addition ports for dilution liquid can be arranged on the main blood line downstream of the dialyzer and upstream of the blood treatment element. There is also another possibility of post-dilution for the combined treatment with a dialyzer and a blood treatment element disclosed herein. Addition ports for dilution liquid for post-dilution can also be arranged in the main blood line downstream of the blood treatment element. Introducing the replacement, which usually contains calcium, downstream of the blood treatment element has the advantage that the anticoagulant effect of citrate occurs in as many parts of the extracorporeal blood circuit as possible.

[0495] The user can also selectively connect the replacement line to one or more of the above-mentioned addition ports for dilution liquid. The dilution liquid can also be pumped from a common reservoir and / or through a common infusion pump.

[0496] In another embodiment of the present disclosure, the dialyzer can be arranged in a secondary line, and the blood treatment element for reducing the carbon dioxide content can be arranged in the main line. Thus, it is also possible to decouple the blood flow through the dialyzer and the blood treatment device and set significantly different flow rates. Therefore, a blood flow with a flow rate significantly lower than that of the blood in the main blood line can be guided from the secondary line via a branch point in the main blood line downstream of the blood treatment element. The blood can flow through the dialyzer in the secondary line, be treated by mass transfer, and join the main blood line via a branch point upstream of the blood treatment element. Therefore, the flow rate of the blood in the treatment element for reducing the carbon dioxide content in the blood is the sum of the flow rate of the blood drawn from the patient and the flow rate of the blood set in the secondary line.

[0497] Accordingly, the blood guiding device for interacting with the aforementioned functional units disclosed herein is characterized in that: a main blood pipeline for fluid connection to a blood treatment element, wherein the blood treatment element is a device for reducing the carbon dioxide content in blood in vitro according to any one of Embodiments 8 to 19; and a secondary blood pipeline for fluid connection to a dialyzer, wherein the main blood pipeline has a blood sampling port for connecting to a patient's blood sampling passage at one end and a blood return port for connecting to a patient's blood return passage at the other end, wherein the secondary pipeline (C130) preferably branches off from the main blood pipeline (C101) at a first branch point (C104) downstream of the blood treatment element for reducing carbon dioxide content, and preferably rejoins the main blood pipeline (C101) again at a second branch point (C105) upstream of the blood treatment element for reducing carbon dioxide content.

[0498] In addition, according to this embodiment, an addition port for adding a first and / or second medical fluid for anticoagulation can also be arranged on the blood guiding device. Accordingly, an addition port for a first medical fluid for anticoagulation, such as a citrate solution, can be arranged in the secondary pipeline (C130) upstream of the dialyzer. In addition, another addition port (C111) for a second medical fluid for anticoagulation, such as a calcium solution, can be arranged in the main blood pipeline downstream of the connection point of the treatment element.

[0499] A more detailed further description is made based on the exemplary embodiments and the drawings.

[0500] The drawings show:

[0501] Figure 14 A schematic diagram showing an embodiment of the arrangement for treating blood disclosed herein.

[0502] Figure 15 A schematic diagram showing an embodiment of the blood guiding device disclosed herein with a connected dialyzer and a connected blood treatment element.

[0503] Figure 16a A flowchart of the blood guiding device disclosed herein is shown in the schematic diagram.

[0504] Figure 16b Shown in the schematic diagram is Figure 16a a flowchart of the blood guiding device shown in, with other optional components.

[0505] Figure 17a An example of an alternative embodiment variant of a pump assembly represented by a pump assembly section is shown in the schematic diagram of the flowchart.

[0506] Figure 17bAn example of another alternative embodiment variant of the pump assembly, represented by a pump assembly section, is shown in the schematic of the flow chart.

[0507] Figure 17c An example of another alternative embodiment variant of the pump assembly, represented by a pump assembly section, is shown in the schematic of the flow chart.

[0508] Figure 17d An example of another alternative embodiment variant of the pump assembly, represented by a pump assembly section, is shown in the schematic of the flow chart.

[0509] Figure 18a The flow chart of the blood guiding device disclosed herein in an alternative embodiment is shown in the schematic.

[0510] Figure 18b Shown in the schematic is the Figure 18a flow chart of the blood guiding device shown in

[0511] Figure 19a The flow chart of another alternative embodiment of the blood guiding device disclosed herein is shown in the schematic.

[0512] Figure 19b Shown in the schematic is the Figure 19a flow chart of the blood guiding device shown in an alternative arrangement with a recirculation return port.

[0513] Figure 20 Shown in the schematic is the Figure 19a flow chart of the blood guiding device shown in

[0514] Figure 21 The flow chart of another embodiment of the blood treatment device is shown in the schematic, where the dialyzer is arranged in the secondary pipeline.

[0515] Figure 22 The treatment system of the present invention for reducing the carbon dioxide content in the blood is shown in the schematic.

[0516] Figure 23 The treatment system of the present invention for reducing the carbon dioxide content in the blood is shown in the schematic.

[0517] As Figure 14 shown, the arrangement structure C1000 for blood treatment includes the functional unit C10 and the blood guiding device C100. Figure 14 Shown is the functional unit C10 in the form of a dialysis machine for acute dialysis, which is equipped with the blood guiding device C100 designed as a cartridge. The blood treatment device includes the control device C30 and the pump assembly C7.Figure 14 Also shown is the main blood line C101 of the blood guiding device C100, to which a dialyzer C102 and a blood treatment element C103 in the form of a gas exchanger are connected. The main blood line C101 may further include one or more than two pressure measurement sections at which pressures can be captured by means of a pressure sensor C17 optionally provided in the functional unit C10.

[0518] As disclosed herein, the blood guiding device C100 may be designed as a medical disposable device in the form of a blood cartridge ( Figure 15 ). The blood guiding device C100 may include one or two pump assembly sections C107 on which the pump assembly C7 of the blood treatment device C10 may act to convey fluid in the respective line sections of the blood guiding device C100. Figure 15 Shown is the main blood line C101, which leads out from the cartridge body of the blood guiding device C100, successively passes through the dialyzer C102 and the blood treatment element C103 in the form of a gas exchanger, and then is guided back into the cartridge body in which the pump assembly C107 may be arranged. The first branch point C104 for leading out the first secondary line C106 may be arranged upstream of the dialyzer C102. The second branch point C105 at which the first secondary line C106 rejoins the main blood line C101 may be arranged downstream of the dialyzer C102 and upstream of the blood treatment element C103. An addition port C108 for a first medical fluid for anticoagulation, such as citrate, may be further arranged upstream of the dialyzer C102. The recirculation branch point C119 for leading out the second secondary line C120 may be arranged downstream of the blood treatment element C103. The second secondary line C120 leads to a recirculation return port C121 which may be arranged in the main blood line C101 upstream of the blood treatment element C103 and downstream of the dialyzer C102.

[0519] The blood guiding device C100 has a main blood line C101, wherein the main blood line C101 has a blood sampling port C127 for connection to the blood sampling passage of a patient at one end and a blood return port C128 for connection to the blood return passage of the patient at the other end. As Figure 16a schematically shown in the flowchart of, the blood drawn from the patient can be extracorporeally guided in the main blood line C101 to the dialyzer C102 and the blood treatment element C103 for further extracorporeal blood treatment and then reinfused back into the patient.

[0520] The dialyzer C102 is arranged in the main blood line. Generally, the dialyzer has a blood chamber and a dialysate chamber (not shown here), where the two chambers are separated by a semipermeable membrane through which the blood can interact permeably with the dialysate solution flowing in the dialysate circuit. As disclosed herein, the dialyzer can also be used for other common renal replacement or renal support therapies in dialysis, such as hemodiafiltration, hemodialysis, hemoperfusion, hemofiltration, ISO-UF, etc., and in particular can also be used for treatment methods where no dialysate solution is delivered on the dialysate side.

[0521] Downstream of the dialyzer C102, the main blood line C101 passes through a blood treatment element C103, which is configured here as a gas exchanger. It has a blood chamber and a gas chamber (not shown here), where the two chambers are separated by a semipermeable membrane through which the blood can interact permeably with the gas flowing in the gas line.

[0522] Thus, both the dialyzer C102 and the gas exchanger C103 can each have a large number of individual membranes in the form of hollow fibers. In the context of the present disclosure, the respective chambers for blood, dialysate, or gas can thus also each consist of a large number of individual volumes located inside the hollow fibers, which volumes are fluidly connected to each other at the ends of the fibers.

[0523] The main blood line C101 has a first branch point C104 upstream of the dialyzer C102. A first secondary line C106 leads from this first branch point C104 to a second branch point C105 of the main blood line C101.

[0524] The blood guiding device further includes a pump assembly section C107 at which the blood can be pumped through the main blood line C101 and through the first secondary line C106 by means of the pump assembly C7 of the functional unit C10. In Figure 16a the exemplary embodiment, the first pump assembly C7 is implemented in the form of two occluding blood pumps, one of which is arranged in the main blood line C101 upstream of the first branch point C104, and the second of which is arranged in the main blood line 101 downstream of the first branch point C104 and upstream of the dialyzer C102. In this exemplary embodiment, the first pump pumps, for example, at 500 ml / min, while the second pump pumps only at 200 ml / min. Thus, a flow rate of 300 ml / min is set in the secondary line C106. A blood flow rate of 200 ml / min is established at the dialyzer C102, and the gas exchanger C103 is flowed through at a rate of 500 ml / min, since the two flow components of 200 ml / min and 300 ml / min recombine again at the second branch point 105.

[0525] As in Figure 16aFurther visible in [description] is that the gas exchanger C103 for reducing the carbon dioxide content of the blood has an inlet port C103a and an outlet port C103b. The buffer solution according to the first aspect of the present disclosure, in particular the buffer solution defined by the features of using at least one of Forms 1 to 6, is introduced into and discharged from the second defined region of the gas exchanger via the inlet port and the outlet port. Thus, the gas exchanger C103 corresponds in its function and design to the device for reducing the carbon dioxide content in the blood according to the embodiment of the first aspect of the present disclosure, particularly as Figure 3 shown, and further particularly as defined by at least one of Examples 8 to 19.

[0526] As schematically depicted in Figure 16b , the blood guiding device may optionally include an addition port for a medical anticoagulant liquid. Thus, the addition port C108 for the citrate solution may be arranged downstream of the first branch point C104 and upstream of the dialyzer C102. This may also be configured as a citrate line C108 connected to a citrate reservoir C109. In addition, the functional unit C10 may also have an infusion pump C110 designed to convey citrate from the reservoir 109 to the main blood line C101 via the addition port C108. The addition port C111 for the calcium solution may be arranged downstream of the blood treatment element C103. This may also be configured as a calcium line C111 connected to a calcium reservoir C112. In addition, the functional unit C10 may also have another infusion pump C113 designed to convey calcium from the reservoir C112 to the main blood line C101 via the addition port C111.

[0527] Figure 16b Another alternative possibility for citrate addition is further shown. For this purpose, a third addition port C114 for a medical anticoagulant liquid is arranged in the main blood line upstream of the first branch point C104. The addition port C114 may also be configured as a citrate line connected to a citrate reservoir C115. In addition, the functional unit C10 may have another infusion pump C116 designed to convey citrate from the reservoir C115 to the main blood line C101 via the addition port C114. Alternatively (not shown here), the third addition line C114 may also be supplied from the first reservoir C109. Further alternatively, if the pressure generated by the first infusion pump C110 is used in the subsequently branched third addition line, the third infusion pump C116 may also be omitted. Thus, the third addition line may have a valve or throttle member for adjusting the pressure accordingly.

[0528] Figures 17a to 17dSchematically shows sections of the main blood line C101 of the blood guiding device C100 in the regions around the first branch point C104 and the second branch point C105. In this embodiment, the sections include two flow paths on the secondary line C106 and sections of the main blood line 101 passing through the dialyzer C102. Figures 17a to 17d Shows various possible exemplary embodiments of the pump assembly represented by the pump assembly sections C207, C307, C407, C507 for the operation of the pump assembly C7 of the functional unit C10.

[0529] Although the pump assembly of the embodiment shown by the pump assembly section C107 Figure 16a has an occlusive blood pump in the main blood line C101 upstream of the first branch point C104 and another occlusive blood pump in the main blood line C101 between the dialyzer C102 and the first branch point C104, Figure 17a shows a variant of the pump assembly represented by the pump assembly section C207, which also has a first blood pump in the main blood line C101 upstream of the first branch point C104, but an alternative arrangement with another occlusive blood pump in the secondary line C106.

[0530] In Figure 17b and 17c in the pump assembly examples represented by the pump assembly sections C307, C407 shown, another blood pump in the secondary line C106 or correspondingly in the main blood line C101 between the dialyzer C102 and the first branch point C104 is replaced by a throttling element respectively.

[0531] Figure 17d Shows another exemplary embodiment of the first pump assembly represented by the pump assembly section C507, which has two occlusive blood pumps, one arranged in the secondary line C106 and the other in the main blood line C101 between the dialyzer C102 and the first branch point C104.

[0532] All pump assemblies according to the present disclosure can generate blood flow in the main blood line C101 and can also direct a partial flow with a defined flow rate on the secondary line C106, so that the ratio between the total flow in the main blood line C101 upstream of the first branch line C104 or downstream of the second branch line C105 and the total flow in the region of the dialyzer C102 is adjustable. The present disclosure is not limited to Figures 17a to 17dAn embodiment of the pump assembly C7 as shown. As recognized by those skilled in the art, in the prior art, there are many other possibilities to control the flow rate ratio in the two pipeline sections. In some embodiments, the pump assemblies C7 can control the flow rates of the two pipeline sections independently of each other. The pump assembly C7 can include various fluid components, including occlusive pumps, non-occlusive pumps, clamps, valves, throttling components, etc. The components of the pump assembly C7 can be arranged at other points within the extracorporeal blood circuit or function at other points within the extracorporeal blood circuit.

[0533] As shown schematically in Figure 18a the blood guiding device C100 can also exhibit an alternative flow path. In this example, the first branch point C104 where the secondary pipeline C106 branches off from the main blood pipeline C101 is arranged downstream of the blood treatment element C103. In this example, the second branch point C105 where the secondary pipeline C106 rejoins the main blood pipeline C101 again is further arranged upstream of the blood treatment element C103 and downstream of the dialyzer C102.

[0534] As Figure 18b shown schematically in, the blood guiding device can optionally have an addition port for a medical anticoagulant liquid. Thus, the addition port C108 for the citrate solution can be arranged upstream of the dialyzer C102. This can also be configured as a citrate pipeline C108 connected to the citrate reservoir C109. In addition, the functional unit C10 can also have an infusion pump C110 designed to deliver citrate from the reservoir C112 to the main blood pipeline C101 via the addition port C108. The addition port C111 for the calcium solution can be arranged downstream of the blood treatment element C103. This can also be configured as a calcium pipeline C111 connected to the calcium reservoir C112. The functional unit 10 can also have another infusion pump C113 designed to deliver calcium from the reservoir C112 to the main blood pipeline C101 via the addition port C111.

[0535] Figure 19a Another alternative embodiment of the blood guiding device disclosed herein is schematically shown based on a flowchart, where in addition to the Figure 16a features, a second branch line C120 is provided here for the repeated recirculation of blood through the blood treatment element C103 designed as a gas exchanger here. The second secondary pipeline C120 branches off from the main blood pipeline C101 at the recirculation branch point C119 and leads to the recirculation return port C121. In the Figure 19a example, the recirculation return port C121 is arranged in the first secondary pipeline C106 upstream of the second branch point C105. Figure 19b The example of Figure 19aThe difference shown is that the recirculation return port C121 is directly arranged in the main blood line C101 downstream of the dialyzer C102 and upstream of the blood treatment element C103. In Figure 19a and 19b in these embodiments, the pump assembly C7 of the functional unit C10 can be further equipped to generate blood flow in the second secondary line C120. For this purpose, Figure 19a and 19b the pump assembly C7 of the functional unit 10 in Figure 19a and 19b —represented here by the pump assembly section C107—has another occlusion pump in the second secondary line C120. In addition, the control device C30 of the functional unit C10 can be configured to be able to operate the pump assembly C7 such that the blood flow rate in at least one section of the main blood line C101 is independent of at least one of the blood flow rates in the secondary lines C106, C120.

[0536] Figure 20 schematically shows an embodiment of the blood guiding device with additional optional components of Figure 19a The additional ports C108, C111, C114, the corresponding infusion pumps C110, C113, C116 and the reservoirs C109, C112, C115 already described with respect to the exemplary embodiments of Figure 19b can also be provided in the embodiment with two secondary lines C106, C120.

[0537] In addition, Figure 20 two optional pressure measurements C117, C118 in the main blood line C101 are also shown downstream and upstream of the dialyzer C102. On the one hand, the pressures downstream of the dialyzer and optionally also upstream of the dialyzer contribute to determining the transmembrane pressure. This represents an important parameter, for example, which provides information about an impending filter blockage during the dialysis treatment. The transmembrane pressure can also be taken into account when determining the calcium addition rate via the second addition port C111. On the other hand, the pressures in the corresponding flow sections also contribute to monitoring the treatment via a threshold window.

[0538] In addition, Figure 20Also shown are optional components that also allow hemofiltration and / or hemodiafiltration on the renal replacement therapy side. For this purpose, the extracorporeal blood circuit may include one or more than two addition ports C124, C125, C126 for dilution fluid, optionally also designed as replacement lines, through which replacement fluid can be added from a reservoir C122 to the main blood line C101 by means of another infusion pump 123. Thus, the replacement line may be connected in pre-dilution C124 and then merge into the main blood line C101 upstream of the dialyzer C102. The replacement line may also be connected in post-dilution. The blood circuit according to the present disclosure provides two possible connection locations in post-dilution. In the first option, the post-dilution line C125 may lead to the main blood line C101 between the dialyzer C102 and the blood treatment element C103. In the second option, the post-dilution line C126 may also lead to the main blood line C101 downstream of the gas exchanger. Thus, the latter variant C126 provides the advantage that the replacement solution, which usually contains calcium, only reduces the anticoagulant effect of citrate in the posterior part of the extracorporeal blood circuit.

[0539] Alternatively, the user may also selectively connect the replacement line to one or more than two of these locations. In a combination of pre-dilution and post-dilution, two independently delivered infusion pumps (not shown) may also be selectively selected for the dilution fluid.

[0540] Figure 21 An embodiment of a blood guiding device is schematically shown, in which a dialyzer is arranged in a secondary line C130. The secondary line C130 branches from the main blood line C101 at a branch point C104 downstream of a blood treatment element C103 for reducing the carbon dioxide content in the blood and rejoins the main blood line C101 at a branch point C105 upstream of the blood treatment element C103. A dialyzer C102 and a pump assembly section C107 are arranged in the secondary line C130, and the pump assembly section C107 is adjusted in combination with an adjustable blood flow in the secondary line C130 and the pump assembly C7. In addition, an addition port for a first medical anticoagulant fluid, in particular a citrate solution, is also located in the secondary blood line C130, through which the first medical fluid, in particular a citrate solution, can be infused from a reservoir C109 into the blood flow of the secondary line C130 by means of an infusion pump C110 for anticoagulation.

[0541] According to Figure 21In an embodiment, the pump assembly section C107 is arranged in the main blood pipeline upstream of the branch point C105 and the blood treatment element C103. With the pump assembly section C107, blood can be drawn from a patient via the blood sampling port 127 in combination with the pump assembly C7, and the blood flow in the main blood pipeline can be adjusted. The blood guiding device has an addition port for a second medical anticoagulant liquid C111, in particular a calcium solution, located downstream of the blood treatment element C103. Via the addition port, the second medical fluid, in particular a calcium solution, can be infused from the reservoir C112 into the blood flow in the main blood pipeline. In addition, the main blood pipeline C130 has a blood return port through which the treated blood can return to the patient.

[0542] In addition, the blood treatment element C103 includes an inlet port C103a and an outlet port C103b. A buffer solution for reducing the carbon dioxide content in the blood according to an embodiment of the first aspect of the present disclosure can flow through a second defined area (not shown) of the blood treatment element C103 via the inlet port C103a and the outlet port C103b.

[0543] According to Figure 21 The blood guiding device has the following advantages: It can decouple the blood flows to be treated in the dialyzer C102 and the treatment element C103, which is necessary for the combined treatment of blood by dialysis and reducing the carbon dioxide content from a medical and therapeutic perspective. In a preferred extracorporeal blood treatment of a patient using the blood guiding device schematically shown in Figure 21 various required blood flows can be set and adjusted in the respective different sections of the secondary pipeline C130 and the main blood pipeline C101. In particular, a blood flow of 500 ml / min can be set in the main blood pipeline C101 upstream of the blood treatment element C103, while a blood flow of 200 ml / min can be set in the secondary pipeline. The blood flows in the main blood pipeline C101 and the secondary pipeline C130 are combined via the branch point C105, thereby establishing a blood flow of 700 ml / min in the section of the main blood pipeline between the branch point C105 upstream of the blood treatment element C103 and the branch point C104 downstream of the blood treatment element C103. Therefore, from a therapeutic perspective, the blood treatment element C103 is flowed through with the required high blood flow, while from a therapeutic perspective, the dialyzer C102 is flowed through with the required lower blood flow. By setting the blood flows in the main blood pipeline and the secondary pipeline as cited, a blood flow of 500 ml / min is established downstream of the branch point C104 and downstream of the blood treatment element C103.

[0544] The functional device C10 includes a control device C30. The control device C30 can be configured to be capable of controlling and regulating a treatment method. According to one method covered by the present disclosure, in all exemplary embodiments, the pump assembly C7 can generate a blood flow rate between 0 and 300 ml / min in the main blood line C101 in the region of the dialyzer C102. Additionally, a blood flow rate greater than 500 ml / min can be generated in the region of the blood treatment element C103. In Figure 16a and 16b example, the flow rate in the main blood line C101 before the first branch point C104 corresponds to the flow rate in the blood treatment element C103. The desired dialyzer flow rate can be set by means of the pump assembly C7. Thus, this results in the flow rate in the secondary line C106 being the difference between the flow rates in the blood treatment element C103 and the dialyzer.

[0545] In all embodiments of the present disclosure, the flow rate in the blood treatment element C103 can also be greater than 800 ml / min, greater than 1 l / min, or greater than 2 l / min. According to the present disclosure, all these flow rates and even greater flow rates can be within the range of using the blood treatment element C103.

[0546] In all embodiments, the flow rate of the dialyzer can also be in the range between 100 and 250 ml / min. It can also be in the range of 175 to 225 ml / min, or exactly equal to 200 ml / min.

[0547] The flow rate of the first medical fluid, such as citrate, for anticoagulation delivered to the main blood line C101 by means of the first infusion pump C110 can be adjusted by the control device C30 according to the dialyzer flow rate.

[0548] The flow rate of the second medical fluid, such as calcium, for anticoagulation delivered to the main blood line C101 by means of the second infusion pump C113 can be adjusted by the control device C30 according to the dialyzer flow rate. This adjustment can additionally take into account other dependencies, such as the flow rate of the first medical anticoagulation fluid, the flow rate of the third medical anticoagulation fluid, the transmembrane pressure (TMP), the type of dialyzer, and / or other parameters that may optionally also be selected or provided by the user.

[0549] The flow rate of the third medical fluid, such as citrate, for anticoagulation can be controlled by direct user selection. It can also be adjusted according to the flow rate in the blood treatment element C103 or the difference between the flow rates in the blood treatment element 103 and the dialyzer.

[0550] In a third aspect, the subject matter of the present disclosure is characterized by the features of the following embodiments 38 to 50:

[0551] Embodiment 38

[0552] A functional unit (C10) for performing extracorporeal blood treatment, wherein blood is guided in a blood guiding device (C100) having a main blood pipeline (C101) and at least one secondary pipeline (C106, C130) fluidly connected to the main blood pipeline (C101), and wherein the main blood pipeline (C101) includes a dialyzer (C102) and a blood treatment element (C103) downstream of the dialyzer (C102), or

[0553] wherein the main blood pipeline (C101) includes a blood treatment element (C103), and the secondary pipeline (130) includes a dialyzer,

[0554] wherein the blood treatment element (C103) includes a device (10) for extracorporeally reducing the carbon dioxide content in blood according to any one of claims 8 to 19, and wherein the functional unit (C10) includes:

[0555] a control device (C30); and

[0556] a pump assembly (C7) configured to be able to generate blood flow in the main blood pipeline (C101) and the at least one secondary pipeline (C106),

[0557] wherein the control device (C30) is configured to be able to operate the pump assembly (C7) such that a first blood flow rate in the dialyzer (C102) is decoupled from a second blood flow rate in the blood treatment element (C103).

[0558] Example 39

[0559] The functional unit (C10) according to claim 38,

[0560] wherein the pump assembly (C7) is designed to generate independent blood flow rates in the main blood pipeline (C101) and the at least one secondary pipeline (C106).

[0561] Example 40

[0562] The functional unit (C10) according to claim 38 or 39, wherein the extracorporeal blood treatment device (C100) further includes a second secondary pipeline (C120) fluidly connected to the main blood pipeline (C101).

[0563] wherein the pump assembly (C7) is further equipped to generate blood flow in the second secondary pipeline (C120), and

[0564] Wherein, the control device (C30) is configured to operate the pump assembly (C7) such that the blood flow rate in at least one section of the main blood line (C101) is independent of at least one of the blood flow rates in the secondary blood lines (C106, C120).

[0565] Example 41

[0566] The functional unit (C10) according to any one of claims 38 to 40, wherein the functional unit (C10) comprises:

[0567] An infusion pump (C110) for supplying a medical fluid into the main blood line (C101) or a secondary line (130),

[0568] Two infusion pumps (C110, C113) for supplying a medical fluid into the main blood line (C101), or for supplying a medical fluid into the main blood line (C101) and a secondary line (C130),

[0569] Three infusion pumps (C110, C113, C116) for supplying a medical fluid into the main blood line (C101), or

[0570] Four or more infusion pumps (C110, C113, 116, C123) for supplying a medical fluid into the main blood line (C101).

[0571] Example 42

[0572] The functional unit (C10) according to claim 41, wherein the control device (C30) is configured to be able to adjust the supply rate of at least one of the infusion pumps according to the blood flow rate in the dialyzer (C102), in particular, the control device (C30) is configured to be able to adjust the respective supply rates of at least two of the infusion pumps according to the blood flow rate in the dialyzer (C102).

[0573] Example 43

[0574] The functional unit (C10) according to any one of claims 38 to 42, wherein the functional unit (C10) comprises a pressure sensor (C17) for determining the pressure in the main blood line (C101) downstream of the dialyzer (C102) and upstream of the blood treatment element (C103).

[0575] Example 44

[0576] A blood guiding device (C100) for interacting with the functional unit (C10) according to any one of claims 38 to 43, comprising:

[0577] A main blood pipeline (C101) for fluidly connecting to a dialyzer (C102) and for fluidly connecting to a blood treatment element (C103) downstream of the dialyzer (C102), wherein the blood treatment element (C103) is a device (10) for extracorporeally reducing the carbon dioxide content in blood according to any one of claims 8 to 19, wherein the main blood pipeline (C101) has a blood sampling port (C127) for connecting to a blood sampling passage of a patient at one end and a blood return port (C128) for connecting to a blood return passage of the patient at the other end; and at least one secondary pipeline (C106) that branches off from the main blood pipeline (C101) at a first branch point (C104) and rejoins the main blood pipeline (C101) at a second branch point (C105); or

[0578] A main blood pipeline (C101) for fluidly connecting to a blood treatment element (C103), wherein the blood treatment element (C103) is a device (10) for extracorporeally reducing the carbon dioxide content in blood according to any one of claims 8 to 19, and the blood guiding device (C100) includes a secondary blood pipeline (C130) for fluidly connecting to a dialyzer, wherein the main blood pipeline (C101) has a blood sampling port (C127) for connecting to a blood sampling passage of a patient at one end and a blood return port (C128) for connecting to a blood return passage of the patient at the other end, wherein the secondary pipeline (C130) branched off from the main blood pipeline (C101) at a first branch point (C104) rejoins the main blood pipeline (C101) again at a second branch point (C105);

[0579] And one or more than two pump assembly sections (C107) that are designed to act on the pump assembly (C7) of the blood treatment device (C10).

[0580] Example 45

[0581] The blood guiding device (C100) according to claim 44, wherein the first branch point (C104) is arranged upstream of the connection point for the dialyzer (C102), and

[0582] The second branch point (C105) is arranged downstream of the connection point for the dialyzer (C102) and upstream of the connection point for the blood treatment element (C103); or

[0583] Wherein the first branch point (C104) is arranged downstream of the connection point for the blood treatment element (C103), and

[0584] The second branch point (C105) is arranged upstream of the connection point for the blood treatment element (C103) and downstream of the connection point for the dialyzer (C102).

[0585] Example 46

[0586] The blood guiding device (C100) according to claim 44

[0587] comprises a second sub-line (C120) which branches off from the main blood line (C101) at a recirculation branch point (C119) and leads to a recirculation return port (C121),

[0588] wherein the first branch point (C104) is arranged upstream of the connection point for the dialyzer (C102), and

[0589] wherein the second branch point (C105) is arranged downstream of the connection point for the dialyzer (C102) and upstream of the connection point for the blood treatment element (C103), and

[0590] wherein the recirculation branch point (C119) is arranged downstream of the connection point for the blood treatment element (C103), and

[0591] wherein the recirculation return port (C121) in the main blood line (C101) is arranged upstream of the connection point for the blood treatment element (C103) and downstream of the connection point for the dialyzer (C102), or

[0592] wherein the recirculation return port (C121) in the first sub-line (C106) is arranged upstream of the second branch point (C105).

[0593] Example 47

[0594] The blood guiding device (C100) according to any one of claims 44 to 46,

[0595] wherein the main blood line (C101) comprises:

[0596] a port (C108) for adding a first medical anticoagulant liquid upstream of the connection point (C102) for the dialyzer; and / or

[0597] a port (C111) for adding a second medical anticoagulant liquid downstream of the connection point for the treatment element (C103); or

[0598] wherein the main blood line (C101) comprises:

[0599] An addition port (C108) for a first medical anticoagulant liquid downstream of the first branch point (C104) and upstream of the connection point for the dialyzer (C102); and / or

[0600] An addition port (C111) for a second medical anticoagulant liquid downstream of the connection point for the treatment element (C103);

[0601] Or

[0602] An addition port (C108) for a first medical anticoagulant liquid upstream of the dialyzer (C102) in the sub-pipeline (C130), and

[0603] An addition port (C111) for a second medical anticoagulant liquid downstream of the connection point for the treatment element (C103);

[0604] And / or

[0605] An addition port (C114) for a third medical anticoagulant liquid upstream of the first branch point (C104).

[0606] Example 48

[0607] A blood guiding device (C100) according to an embodiment of any one of claims 44 to 47,

[0608] Wherein, the main blood pipeline (C101) includes a pressure measurement section (C117) downstream of the connection point for the dialyzer (C102) and upstream of the connection point for the blood treatment element (C103) for determining the pressure in the main blood pipeline (C101).

[0609] Example 49

[0610] A blood guiding device (C100) according to an embodiment of any one of claims 45 or 48,

[0611] Wherein, the main blood pipeline (C101) includes:

[0612] An addition port (C124) for a dilution liquid upstream of the connection point for the dialyzer (C102); and / or

[0613] An addition port (C125) for a dilution liquid downstream of the connection point for the dialyzer (C102) and upstream of the connection point for the blood treatment element (C103); and / or

[0614] An addition port (C126) for a dilution liquid downstream of the connection point for the blood treatment element (C103).

[0615] Example 50

[0616] An arrangement (C1000) for blood treatment, comprising:

[0617] A functional unit (C10) according to any one of claims 38 to 43; and

[0618] A blood guiding device (C100) according to any one of claims 44 to 49.

[0619] In a fourth aspect, the present disclosure relates to a treatment system for reducing the carbon dioxide content in blood in an extracorporeal blood circuit, comprising

[0620] A device for extracorporeal reduction of the carbon dioxide content in blood, the device comprising a first defined region (1) for receiving extracorporeal blood and a second defined region (2) for receiving a buffer solution, wherein the first (1) and second regions (2) adjacent to each other in the contact zone are separated only by a membrane (3), through which gas exchange can occur between the blood and the buffer solution, and wherein the buffer solution is an aqueous solution that exchanges gases with the blood transported in the extracorporeal circuit of the patient and contains buffer A and buffer B, wherein

[0621] Buffer A consists of at least one buffer substance having a pK value of 7.9 ± 0.2 at 37 °C, and

[0622] Buffer B consists of at least one buffer substance having a pK value of 6.9 ± 0.2 at 37 °C, and wherein

[0623] At a carbon dioxide partial pressure pCO2 = 0.2 mmHg ± 0.2, the post-titration pH value of the solution is in the range of 8.25 to 8.35.

[0624] - A first inlet for introducing a blood stream to be treated into the treatment system, wherein the first inlet is in fluid communication via a fluid line with a first inlet port at the first defined region of the device for extracorporeal reduction of the carbon dioxide content in blood,

[0625] - A first outlet for extracting the treated blood stream from the blood treatment system, wherein the first outlet is in fluid communication via a fluid line with an outlet port at the first defined region of the device for extracorporeal reduction of the carbon dioxide content in blood,

[0626] - A source of buffer solution according to at least one of the features of usage forms 1 to 6, wherein the source of buffer solution is in fluid communication via a fluid line with an inlet port at the second defined region of the device for extracorporeal reduction of the carbon dioxide content in blood,

[0627] - A container for collecting the used buffer solution, wherein the container for collecting the used buffer solution is in fluid communication via a fluid line with an outlet port at a second defined region of a device for reducing the carbon dioxide content in blood in vitro, or

[0628] - A recycling device, which replaces the container for collecting the used buffer solution, wherein the recycling device includes a fluid line for returning the used buffer solution to the source of the buffer solution,

[0629] Characterized in that the treatment system includes a balancing device by means of which the amount of buffer solution introduced from the source of the buffer solution and the amount of used buffer solution can be balanced.

[0630] As previously defined, in the context of the present disclosure, a "gas exchanger" is understood to be a device for reducing the carbon dioxide content in blood in vitro according to at least one of embodiments 8 to 19.

[0631] In one embodiment, the treatment system according to the fourth aspect is characterized in that the balancing device is a weight balancing device, in particular in that the balancing device includes a scale for weighing the amount of buffer solution used from the buffer solution source and the balancing device includes a scale for weighing the amount of buffer solution used from the container for collecting the used buffer solution.

[0632] In a further embodiment, the treatment system according to the fourth aspect is characterized in that the balancing device is a volume balancing device which uses a balance chamber to balance the volume of buffer solution used from the buffer solution source and the volume of used buffer solution, or uses a flow meter to balance the used volume of buffer solution extracted from the buffer solution source and the amount of used buffer solution.

[0633] The treatment system of the present invention can be used together with a dialysis machine used in acute dialysis. Therefore, the blood treatment system of the present invention provides the advantage of being able to operate with a conventional dialysis machine. Such a dialysis machine already has a protection system required by known standards for detecting air and blood loss in the extracorporeal blood circuit. For example, the treatment system and associated method for reducing carbon dioxide in a patient's blood in vitro of the present invention can be used in combination with and operated with the well-known "multiFiltratPRO" or "multiFiltrate" dialysis machines of Fresenius MedicalCare Deutschland GmbH.

[0634] The treatment system of the present invention utilizes a gas exchanger which, as defined above, exhibits the characteristics of a device for reducing the carbon dioxide content in blood as defined in Examples 8 to 19. Such a gas exchanger includes a gas permeable membrane, particularly a gas selective membrane. Such membranes are described, for example, in EP 277 801 A2 or DE 100 34098 A1. A buffer solution is guided along the second bounding region of the gas exchanger. The patient's blood is pumped countercurrently in the first bounding region of the gas exchanger.

[0635] The treatment system of the present invention is substantially unchanged compared to a treatment system for dialysis. The pump used on the machine side can be operated at a pumping rate of 10 ml / min to 600 ml / min to an effective degree of treatment to guide the buffer solution through the second bounding region of the device for reducing carbon dioxide in blood or the gas exchanger. The buffer solution used is the buffer solution according to the first aspect of the present invention, and thus particularly a buffer solution having the characteristics of at least one of Use Forms 1 to 6.

[0636] To prevent the buffer solution from entering the patient's blood via the membrane of the gas exchanger, the fourth aspect of the present disclosure provides for balancing the buffer solution supplied to and discharged from the gas exchanger. The buffer solution supplied to the gas exchanger corresponds to the buffer solution withdrawn from the source of the buffer solution. The buffer solution discharged from the gas exchanger corresponds to the used buffer solution collected in the container for collecting the used buffer solution. Known dialysis machines for acute dialysis have two scales which measure the dialysis fluid supplied to and discharged from the dialyzer during dialysis treatment and accordingly adjust the pumps for supplying and discharging the dialysis fluid.

[0637] The advantage of this treatment system is that it can balance the volume of the buffer solution introduced and used in the gas exchanger during extracorporeal blood treatment, and the extracorporeal blood treatment reduces the carbon dioxide content in the patient's blood by means of the buffer solution for CO2. In particular, the buffer solution for treatment must not have any physiological components that are prohibited from entering the patient's blood circulation, because they may cause conditions harmful to the patient's health. In particular, membrane defects may allow the buffer solution to invade the extracorporeal blood circuit and ultimately enter the patient's body. The balance can determine the loss of the buffer solution that can invade the extracorporeal blood circuit. This balance can also be achieved by means of a balance chamber or by flow meters appropriately arranged in the treatment system instead of scales. Therefore, the treatment system of the present invention has a safety system by which it can be determined whether the buffer solution has damaged the patient's blood circuit. If the balance device of the treatment system of the present invention correspondingly determines that the used buffer solution discharged from the gas exchanger is less than the buffer solution introduced into the gas exchanger, an alarm can be triggered by the electronic control unit of the treatment system of the present invention, and for example, further extracorporeal treatment can be stopped.

[0638] Reference will be made to Figure 22 explain further details and embodiments of the treatment system of the present invention. Figure 22 The treatment system schematically shown in should not be construed as a definitive embodiment. On the contrary, it will be apparent to those skilled in the art that, in the context of the fourth aspect of the present disclosure, further embodiments can be derived from the schematic diagram of by adding or omitting individual features. Figure 22 of the schematic diagram.

[0639] Figure 22 The treatment system (D100) of the present invention for reducing the carbon dioxide content in the blood is shown schematically. The depicted treatment system consists of components that can be arranged on a dialysis machine and a treatment product. In certain embodiments, scales D8, D15, occlusion devices D1, D7, blood leak detectors D11, optical detectors D5, bubble detectors D6, pumps D13, D10, D2, and heating device D12 are arranged on the dialysis machine. A gas exchanger 10, a drip chamber D4, a container D9 for the buffer solution, a source D14 for the buffer solution, and fluid lines D16 to D20 can be arranged on the treatment product. According to the treatment system of the present invention, the components on the machine side and the components of the treatment product are designed to act together to reduce the carbon dioxide in the patient's blood in vitro.

[0640] In particular, pumps D2, D10, and D13 are designed to interact with fluid lines D16, D19, and D18 in order to effect the delivery of blood from patient B in to the treatment system and back to patient B out and to effect the delivery of the buffer solution from the source D14 of the buffer solution to the gas exchanger 10 and from the gas exchanger 10 to the container D9 for collecting the used buffer solution. In one embodiment, the fluid lines consist of flexible plastic tubes. Such fluid tubes are known in dialysis technology. They are characterized in that they can be squeezed together by applying a force such that no fluid can flow through the lumen of the flexible plastic tube. Such tubes are also characterized in that they have a restoring force so that, after the plastic tube is occluded, fluid can flow through the lumen again. These pumps can be designed as gear pumps, membrane pumps, or peristaltic pumps. In one embodiment, pumps D2, D10, and D13 are designed as peristaltic pumps.

[0641] In addition, the heating device D12 interacts with the fluid line D18 leading from the buffer solution source D14 to the gas exchanger 10 by heating the buffer solution flowing through the fluid line D18.

[0642] In addition, scales D8 and D15 for balancing the buffer solution interact with the source D14 of the buffer solution and the container for collecting the used buffer solution, so that the buffer solution in the buffer solution source D14 and the buffer solution in the container for collecting the buffer solution are weighed, and can be balanced by means of an electronic control or processing unit in a dialysis machine ( Figure 22 not shown). In one embodiment, the buffer solution source D14 is a fluid bag containing the buffer solution. In another embodiment, the container for collecting the used buffer solution is also a fluid bag. In the context of the fourth aspect of the present disclosure, the term "used buffer solution" refers to the buffer solution that has passed through the second defined region 2 of the gas exchanger for reducing carbon dioxide in the patient's blood. In a preferred embodiment where the membrane 3 of the gas exchanger 10 is gas-permeable but fluid-sealed, a volume memory ( Figure 22 not shown) can be arranged in the fluid line D18 and / or the fluid line D19 in each case. The volume memory is used to compensate for volume differences caused by potential process-related different supply rates of the pumps D13 and D10. The provided membrane 3 of the gas exchanger 10 has no membrane defects during the treatment operation of the treatment system D100, and the volume of the part of the treatment system through which the buffer solution flows is constant.

[0643] In addition, the occlusion device interacts with the fluid lines D16 and D17 by occluding the fluid lines to prevent blood from flowing through the fluid lines. This is particularly necessary when the electronic monitoring unit of the dialysis machine identifies an alarm during the treatment of reducing the carbon dioxide content in the patient's blood and needs to terminate or interrupt the treatment so as not to endanger the patient's health. In one embodiment, the occlusion device is a mechanically or electromagnetically operated hose clamp on the machine, which interacts with the fluid lines D16 and D17 designed as flexible plastic pipes, so as to be able to block or unblock the fluid lines D16 and D17, especially for the flow of blood.

[0644] In addition, the optical detector D5 and the bubble detector D6 interact with the fluid line D17. The interaction between the fluid line D17 and the detectors D5 and D6 is arranged such that the detectors D5 and D6 can detect potential blood clots and bubbles in the treated blood returned to the patient via the outlet B out . The electronic monitoring unit of the dialysis machine can evaluate the signals of the detectors D5 and D6 and trigger an alarm, so as to enable, for example, the occlusion devices D1 and D7, so as to be able to stop applying blood clots and / or bubbles to the patient via the outlet B out .

[0645] In addition, a blood leak detector D11 interacts with a fluid line D19. The interaction between the fluid line D19 and the blood leak detector is arranged such that the detector D1 can detect blood components in the buffer solution transported from the gas exchanger 10 through the fluid line D19 to the container D9 for collecting the used buffer solution. The detection of blood components in the buffer solution in the fluid line D19 can be monitored and evaluated by the electronic monitoring unit of the dialysis machine so that the occlusion devices D1 and D7 can be activated when necessary and the treatment can be stopped. The presence of blood components in the fluid line D19 indicates a defective membrane in the gas exchanger D10, and thus the dialysis machine can trigger an alarm via the signal from the blood leak detector D11.

[0646] In a method for reducing carbon dioxide in a patient's blood using a treatment system according to the present invention, blood is drawn from the patient and introduced into the treatment system D100 via an inlet B in Thereafter, the blood drawn from the patient is transported via a pump D1 that interacts with a fluid line D16 to transport the blood from the patient to the first defined region of the gas exchanger. The blood flowing into the first defined region 1 of the gas exchanger 10 via the inlet port 4 flows along the membrane 3 of the gas exchanger and forms a gas exchange relationship with the buffer fluid flowing through the second defined region 2 of the gas exchanger 10. The buffer solution containing the buffer substance as described in the first aspect of the present disclosure compensates for the carbon dioxide diffusing across the membrane into the second defined region. The blood with reduced carbon dioxide is discharged via the outlet port 5 at the first defined region 1 of the gas exchanger 10 and flows into the drip chamber D4 via the fluid line D17 to separate any potential bubbles in the blood. The blood then continues to flow through the fluid line D17 to the patient outlet B out and is checked for blood clots and bubbles via an optical detector D5 and a bubble detector D6.

[0647] Meanwhile, in a method for reducing carbon dioxide in a patient's blood using a treatment system of the present invention, the buffer solution as described in the first aspect of the present disclosure flows from a source of the buffer solution into the second defined region 2 of the gas exchanger through a fluid line D18 via a pump D13 that interacts with the fluid line D18. The carbon dioxide diffusing from the blood in the first defined region 1 across the membrane wall 3 of the gas exchanger 10 into the second defined region 2 of the gas exchanger 10 is compensated by the buffer solution in the second defined region and removed via the outlet port 8. A pump D10 helps to discharge the used buffer solution from the second defined region 2 of the gas exchanger 10 to the container D9 or a recycling device. The used buffer solution is checked for blood components by a blood leak detector and evaluated by the electronic monitoring unit of the dialysis machine.

[0648] In an alternative embodiment, the used buffer solution can be recycled. This means that if the buffer capacity for carbon dioxide has not been reached, the buffer solution can be returned to source D14. If the used buffer has been recycled to source D14, the buffer solution can be reused. Another pump for conveying the buffer solution back to the buffer solution source D14 for this purpose can be arranged in fluid line D20 ( Figure 22 not shown). The reduction of CO2 in the patient's blood can be adjusted by correspondingly adjusting the supply and discharge pumps D13, D10 and the pump in fluid line D20 ( Figure 21 not shown).

[0649] The treatment system D100 of the present invention includes a balancing device. According to Figure 22 , scales D8 and D15 are part of the balancing device. During the method of reducing carbon dioxide in a patient's blood using the treatment system according to the present invention, the amount of buffer solution extracted from source 14 and the amount of buffer solution collected in container D9 are weighed. The amounts of buffer solution measured by scales D8 and D15 are compared. The result of the weighing is evaluated by the electronic monitoring unit of the dialysis machine. If the result of the weighing determines that in successive weighings in a predetermined order, the amount of buffer solution collected in container D9 is less than the amount of buffer solution drawn from source D14 within a specific tolerance range, an alarm can be triggered via the dialysis machine. In this way, it can be checked whether the buffer solution is entering the blood circuit during treatment of the patient.

[0650] The pH sensor can be fixed to fluid line D18 before the inlet port 7 of the gas exchanger 10 in the flow direction of the buffer solution and to fluid line D19 after the outlet port 8 of the gas exchanger 10 in the flow direction of the buffer solution. By means of the pH sensor, the pH values of the buffer solution flowing into the gas exchanger and the buffer solution flowing out of the gas exchanger are determined ( Figure 22 not shown). These pH sensors are used for monitoring and can be used to adjust the flow rate of the buffer solution. In particular, the reduction process of carbon dioxide in the patient's blood can be tracked and monitored by measuring the pH value during treatment and the change in the pH value of the buffer solution. In addition, it can be monitored whether the buffer solution provided in source D14 still has sufficient buffer capacity to effectively reduce the carbon dioxide content in the patient's blood during treatment. This monitoring of the pH value of the buffer solution may be particularly relevant in the previously described buffer solution recycling. For precise pH measurement, a temperature sensor for measuring the temperature of the buffer solution in the pH measurement area can be further provided. The measured temperature and the measured pH value can be processed by the electronic monitoring or evaluation unit of the dialysis machine in order to predetermine further treatment procedures.

[0651] In addition, the pH sensor can be arranged in the fluid line D16 before the inlet port 4 of the gas exchanger 10 in the blood flow direction, and in the fluid line D17 after the outlet port of the gas exchanger in the blood flow direction ( Figure 22 not shown in). In addition, the pCO2 pressure sensor for measuring the partial pressure of CO2 can also be arranged there ( Figure 22 not shown in). For precise pH measurement, a temperature sensor can be arranged in the pH measurement area. The measurement results of the pH sensor, temperature sensor, and pCO2 sensor can be processed by the monitoring or evaluation unit of the dialysis machine, so as to be used for controlling further treatment processes.

[0652] Figure 22 List of reference numerals:

[0653] D1 Occlusion device for blocking / enabling blood flow through the fluid line D16 to the gas exchanger 10

[0654] D2 Pump for delivering blood to the gas exchanger through the fluid line D16

[0655] 10 Gas exchanger for reducing the carbon dioxide content in the patient's blood

[0656] D4 Drip chamber for separating air bubbles in the blood in the fluid line D17 for returning the treated blood to the patient

[0657] D5 Optical detector for detecting blood clots in the blood in the fluid line D17 for returning the treated blood to the patient

[0658] D6 Air bubble detector for detecting air bubbles in the blood in the fluid line D17 for returning the treated blood to the patient

[0659] D7 Occlusion device for blocking / enabling blood flow through the fluid line D17 for returning the treated blood to the patient

[0660] D8 Scale for weighing the volume of the used buffer solution in the container D9 for collecting the used buffer solution

[0661] D9 Container for collecting the used buffer solution

[0662] D10 Pump for delivering the buffer solution from the gas exchanger to the container D9 for collecting the buffer solution through the fluid line D19

[0663] D11 Blood leakage detector for detecting membrane defects in the gas exchanger 10

[0664] Heating device D12 for heating the buffer solution in fluid line D18 before the buffer solution enters the gas exchanger

[0665] Pump D13 for delivering the buffer solution to the gas exchanger

[0666] Source D14 for the buffer solution

[0667] Scale D15 for determining the volume extracted from source D14 of the buffer solution

[0668] D16 Fluid line for delivering blood from a patient to the first defined region 1 of the gas exchanger 10 via blood inlet B in

[0669] D17 Fluid line for delivering blood from the first defined region 1 of the gas exchanger 10 to the patient via outlet B out

[0670] D18 Fluid line for delivering the buffer solution from source 14 of the buffer solution to the second defined region of the gas exchanger 10

[0671] D19 Fluid line for delivering the used buffer solution from the second defined region of the gas exchanger to a container for collecting used fluid or to a recycling device for delivering the used buffer solution back to the source of the buffer solution

[0672] D20 Fluid line for delivering the used buffer solution from a recycling device for delivering the used buffer solution back to the source of the buffer solution

[0673] Therapy system D100 for reducing the carbon dioxide content of blood in an extracorporeal blood circuit

[0674] In a fifth aspect, the present invention relates to a therapy system according to the present invention for reducing the carbon dioxide content of blood in an extracorporeal blood circuit, comprising

[0675] Device for reducing the carbon dioxide content of blood extracorporeally, said device comprising a first defined region (1) for receiving extracorporeal blood and a second defined region (2) for receiving a buffer solution, wherein the first (1) and second regions (2) adjacent to each other in the contact zone are separated only by a membrane (3) through which gas exchange can occur between the blood and the buffer solution, and wherein the buffer solution is an aqueous solution that exchanges gas with the patient's blood transported in the extracorporeal circuit and contains buffer A and buffer B, wherein

[0676] ​​Buffer A consists of at least one buffering substance having a pK value of 7.9 ± 0.2 at 37 °C, and buffer B consists of at least one buffering substance having a pK value of 6.9 ± 0.2 at 37 °C, and wherein

[0677] at a partial pressure of carbon dioxide pCO2 = 0.2 mmHg ± 0.2, the pH value of the solution after titration is in the range of 8.25 to 8.35,

[0678] - a first inlet for introducing a blood stream to be treated into the treatment system (E100), wherein the first inlet is in fluid communication via a fluid line with a first inlet port at a first defined region of a device for reducing the carbon dioxide content in blood extracorporeally,

[0679] - a first outlet for extracting treated blood from the treatment system, wherein the first outlet is in fluid communication via a fluid line with an outlet port at a first defined region of a device for reducing the carbon dioxide content in blood extracorporeally,

[0680] - a source of a buffer solution for reducing the carbon dioxide content in blood, wherein the source is in fluid communication via a fluid line with an inlet port at a second defined region of a device for reducing the carbon dioxide content in blood extracorporeally,

[0681] - a container for collecting the used buffer solution, wherein the container for collecting the used buffer solution is in fluid communication via a fluid line (E19) with an outlet port at a second defined region of a device for reducing the carbon dioxide content in blood extracorporeally, or

[0682] characterized in that a device for reducing the pressure in the fluid line in fluid communication with the inlet port at the second defined region of the device for reducing the carbon dioxide content in blood extracorporeally is arranged in the fluid line in fluid communication with the inlet port at the second defined region of the device for reducing the carbon dioxide content in blood extracorporeally, before the inlet port.

[0683] As previously defined, in the context of the present disclosure, "gas exchanger" is understood to mean a device for reducing the carbon dioxide content in blood extracorporeally according to at least one of embodiments 8 to 19.

[0684] When operating a treatment device of the above type for reducing the CO2 content in the blood, a buffer solution is guided along the gas permeable membrane of the gas exchanger and forms a gas exchange relationship with the blood to be treated via said membrane. During treatment, the pressure in the first defined region through which the blood flows in the gas exchanger is higher than the pressure in the second defined region through which the buffer solution flows. Thus, the flow directions of the buffer solution and the blood are preferably opposite. Conceivable buffer solutions for reducing the carbon dioxide content in the blood are buffer solutions capable of binding CO2, also including those with non-physiological components. Therefore, safety precautions must be taken to prevent non-physiological buffer solutions from entering the blood circuit via the membrane wall of the gas exchanger. In particular, if a membrane defect occurs, there is a risk that the buffer solution will reach the blood side of the extracorporeal blood circuit and be injected into the patient's body.

[0685] For safety and medical treatment reasons, it is therefore advantageous to have a higher pressure in the fluid line conveying the blood of the treatment system than in the fluid line conveying the buffer solution. In the case of a defective membrane, for example when using a hollow fiber membrane filter as the gas exchanger and the fibers of the hollow fiber membrane rupture, it is most obvious that blood leaks from the first defined region into the second defined region of the gas exchanger. Then, the infiltrated blood can be detected by means of a blood leak detector in a fluid line in fluid communication with the outlet port at the second defined region of the gas exchanger for reducing the carbon dioxide content in the extracorporeal blood. In addition, a higher gas exchange rate is achieved by means of the higher pressure in the fluid line conveying the blood compared to the fluid line conveying the buffer solution, thus improving the reduction of the carbon dioxide content in the blood.

[0686] To prevent the buffer solution from entering the patient's blood via the membrane of the gas exchanger, a fifth aspect proposes reducing the pressure in the fluid line through which the buffer solution flows in order to achieve a higher pressure in the fluid line through which the blood flows. The pressure in the fluid line through which the buffer solution flows is achieved by means of a pressure reducing device arranged in the fluid line in fluid communication with the inlet port at the second defined region of the gas exchanger.

[0687] The pressure reducing device can be a throttling element, such as a check valve.

[0688] The advantage of this treatment system according to the fifth aspect of the present disclosure is that, due to the arrangement of a device for reducing the pressure during extracorporeal blood treatment for reducing the carbon dioxide content in the patient's blood by means of a buffer solution, non-physiological buffer solutions cannot penetrate into the blood circuit and the patient's body. In addition, the pressure difference between the first defined region and the second defined region of the gas exchanger increases, so that the CO2 gas exchange rate increases.

[0689] Reference will be made to Figure 23Explain further details and embodiments of the treatment system of the present invention. Figure 22 The treatment system schematically shown in Figure 22 should not be construed as a definitive embodiment. In the context of this fifth aspect of the present disclosure, further embodiments can be derived by adding or omitting individual features from Figure 23 it.

[0690] Figure 23 The treatment system (E100) of the present invention for reducing the carbon dioxide content in the blood is shown in the schematic diagram. The depicted treatment system consists of interacting machine-side components and components of the treatment product. Thus, the occlusion devices E1, E7, the pressure sensors E11a, E11b, E11c and E21, the pumps E2 and E10, and the heating device E12 components can be arranged on the dialysis machine. The gas exchanger 10, the drip chamber E3, the container E9 for collecting the buffer solution, the source E14 for the buffer solution, the fluid lines E16 to E19, and the pressure reduction device E22 components can be arranged on the treatment product. According to the treatment system of the present invention, the components of the machine and the components of the treatment system are designed to interact functionally to reduce carbon dioxide in the patient's blood in vitro.

[0691] In particular, the pumps E2 and E10 are designed to interact with the fluid lines E16 and E18 in order to effect the conveyance of blood from the patient B in into the treatment system and back to the patient B out and to effect the conveyance of the buffer solution from the source E14 of the buffer solution to the gas exchanger 10 and from the gas exchanger 10 to the container E9 for collecting the used buffer solution. In one embodiment, the fluid lines consist of flexible plastic tubes. Such fluid tubes are known in dialysis technology. They are characterized in that they can be squeezed together by applying a force such that no fluid can flow through the lumen of the flexible plastic tube. Such tubes are also characterized in that they have a restoring force so that the lumen of the plastic tube opens after occlusion and fluid can flow through the lumen. When using flexible plastic tubes, the pumps can be designed as peristaltic pumps. Alternatively, gear pumps or membrane pumps can also be used. In one embodiment, the pumps E2 and E10 are designed as peristaltic pumps.

[0692] Furthermore, the heating device E12 interacts with the fluid line E18 by heating the buffer solution flowing through the fluid line E18 from the source E14 of the buffer solution to the gas exchanger 10. The heating device can include a machine-side heating element serving as a heat energy source. In addition, the treatment product can include a flexible bag section in the area of the heating device so that the heat energy provided by the machine can act on the buffer solution on a larger surface section.

[0693] In addition, the occlusion device interacts with the fluid lines E16 and E17 by occluding the fluid lines to prevent blood from flowing through the fluid lines E16 and E17. This is particularly necessary when the electronic monitoring unit of the dialysis machine identifies an alarm during a treatment for reducing the carbon dioxide content in the patient's blood and it is necessary to terminate or interrupt the treatment so as not to endanger the patient. In one embodiment, the occlusion device is a mechanically or electromagnetically operated hose clamp on the machine side, which interacts with the fluid lines E16 and E17 that can be designed as flexible plastic tubes, so as to be able to block or unblock the fluid lines E16 and E17, especially with respect to the flow of blood.

[0694] In addition, an optical detector and a bubble detector ( Figure 23 not shown in the figure) can interact with the fluid line E17. The interaction between the fluid line E17 and the detector is arranged such that the detector can detect potential blood clots and bubbles in the treated blood returned to the patient via the outlet B out The electronic monitoring unit of the dialysis machine can evaluate the signals of the detectors described above and trigger an alarm, for example, enabling the occlusion devices E1 and E7, so as to be able to stop applying blood clots and / or bubbles to the patient via the outlet B out to the patient.

[0695] In addition, a blood leak detector ( Figure 23 not shown in the figure) can interact with the fluid line E19. The interaction between the fluid line E19 and the blood leak detector is arranged such that the blood leak detector can detect blood components in the buffer solution transported from the gas exchanger 10 to the container E9 for collecting the used buffer solution through the fluid line E19. The detection of blood components in the buffer solution in the fluid line D19 can be monitored and evaluated by the electronic monitoring unit of the dialysis machine, so that the occlusion devices E1 and E7 can be enabled when necessary and the treatment can be stopped. The presence of blood components in the fluid line E19 indicates a defective membrane in the gas exchanger 10, so the dialysis machine can trigger an alarm via the blood leak detector signal.

[0696] In a method for reducing carbon dioxide in a patient's blood using the treatment system of the present invention according to the fifth aspect, blood is drawn from the patient and passed through the inlet B inIt is introduced into the treatment system E100. The blood drawn from the patient is conveyed via a pump E2 that interacts with a fluid line E16 to convey the blood from the patient into the first defined region of the gas exchanger 10. The blood flowing into the first defined region 1 of the gas exchanger 10 via the inlet port 4 flows along the membrane 3 of the gas exchanger and forms a gas exchange relationship with the buffer fluid flowing through the second defined region 2 of the gas exchanger 10. A buffer solution containing a buffer substance as described in the first aspect of the present disclosure compensates for the carbon dioxide diffusing across the membrane into the second defined region. The blood with reduced carbon dioxide is discharged via the outlet port 5 at the first defined region 1 of the gas exchanger 10 and flows into the drip chamber E4 via the fluid line E17 to separate any potential bubbles in the blood. The blood continues to flow through the fluid line E17 to the patient outlet B out , and is checked for blood clots and bubbles via an optical detector and / or a bubble detector D6 if necessary.

[0697] Meanwhile, in a method for reducing carbon dioxide in a patient's blood using the treatment system of the present invention, a buffer solution as described, for example, in the first aspect of the present disclosure flows from a source of the buffer solution into the second defined region 2 of the gas exchanger via a fluid line E18 by a pump E13 that interacts with the fluid line E19. The pressure of the buffer solution in the fluid line E18 is reduced as it passes through a device for reducing pressure, so that there is a lower fluid pressure in the second defined region 2 of the gas exchanger 10 than in the first defined region of the gas exchanger through which the blood flows. In one embodiment, the pressure reducing device is a one-way valve. The pressure in the fluid line E18 is reduced in the direction of the buffer solution flowing towards the gas exchanger by the opening pressure of the one-way valve. In an alternative embodiment, the device for reducing pressure can also be designed as a peristaltic pump that interacts with the fluid line E18.

[0698] Furthermore, a pressure sensor E21 that interacts with a fluid line E21 can be arranged between the pressure reducing device E22 and the inlet port 7 at the second defined region of the gas exchanger 10. The measured value recorded at the pressure sensor E21 can be evaluated via the electronic monitoring and control unit of the dialysis machine. The dialysis machine can, for example, adjust the pump output of the pump E2 or E10 based on the measured pressure value of the sensor E21. Pressure monitoring can help compare and set the pressure determined at the pressure sensor E21 with the blood pressure in one of the regions of the fluid lines E16, E17 or in the first defined region 1 of the gas exchanger 10 such that the pressure in the fluid lines E16 and E17 and in the first defined region 1 of the gas exchanger is higher than the pressure measured at the pressure sensor E21.

[0699] In particular, another pressure sensors E11a, E11b, and E11c can be arranged in the treatment device of the present invention to monitor and adjust the required pressure in the treatment device E100. In one embodiment, the pressure sensor E11a is arranged on the fluid line E16 between the pump E2 and the occlusion device E1 to measure the blood pressure in the inlet area of the treatment device. In another embodiment, the pressure sensor E11b is arranged between the gas exchanger 10 and the pump E2 to measure the blood pressure in the fluid line E16 before the gas exchanger. In another embodiment, the pressure sensor E11c is arranged on the fluid line E19 between the pump E9 and the gas exchanger.

[0700] Carbon dioxide diffusing from the blood in the first defined region 1 through the membrane wall 3 of the gas exchanger 10 into the second defined region 2 of the gas exchanger 10 is compensated by the buffer solution in the second defined region and removed via the outlet port 8. Thus, the used buffer solution is discharged from the second defined region 2 of the gas exchanger 10 to the container E9 via the pump E10. The used buffer solution is checked for blood components by a blood leakage detector and evaluated by the electronic monitoring unit of the dialysis machine.

[0701] According to an embodiment of the fourth aspect of the present disclosure, the treatment system E100 of the present invention can include a balancing device. Thus, the amount of buffer solution extracted from the source E14 and the amount of buffer solution collected in the container E9 can be determined and balanced by weighing or by a flow sensor.

[0702] The pH sensor can be fixed to the fluid line E18 before the inlet port 7 of the gas exchanger 10 in the flow direction of the buffer solution and to the fluid line D19 (not shown in Figure 23 ) after the outlet port 8 of the gas exchanger 10 in the flow direction of the buffer solution. With the aid of the pH sensor, the pH values of the buffer solution flowing into the gas exchanger and the buffer solution flowing out of the gas exchanger (not shown in Figure 22 ) are determined. These pH sensors are used for monitoring and can be used to adjust the flow rate of the buffer solution. In particular, the reduction process of carbon dioxide in the patient's blood can be tracked and monitored by measuring the pH value during treatment and the change in the pH value of the buffer solution. In addition, it can be monitored whether the buffer solution provided in the source D14 still has sufficient buffering capacity to effectively reduce the carbon dioxide content in the patient's blood during treatment. For accurate pH measurement, a temperature sensor for measuring the temperature of the buffer solution in the pH measurement area can be further provided. The measured temperature and the measured pH value can be processed by the electronic monitoring or evaluation unit of the dialysis machine to predetermine a further treatment process.

[0703] In addition, the pH sensor can be arranged in the fluid line E16 before the inlet port 4 of the gas exchanger 10 in the blood flow direction, and in the fluid line E17 after the outlet port of the gas exchanger in the blood flow direction ( Figure 23 not shown in Figure 23 ). In addition, a pCO2 pressure sensor can also be arranged there to measure the partial pressure of CO2 (

[0704] not shown in Figure 23 ). For precise pH measurement, a temperature sensor can be arranged in the pH measurement area. The measurement results of the pH sensor, temperature sensor, and pCO2 sensor can be processed by the monitoring / evaluation unit of the dialysis machine and used to control further treatment processes.

[0705] Figure 23 List of reference numerals:

[0706] E1 Occlusion device for blocking / enabling blood flow through the fluid line E16 to the gas exchanger 10

[0707] E2 Pump for delivering blood to the gas exchanger through the fluid line E16

[0708] 10 Gas exchanger for reducing the carbon dioxide content in the patient's blood

[0709] E3 Drip chamber for separating air bubbles in the blood in the fluid line E17 for returning the treated blood to the patient

[0710] E7 Occlusion device for blocking / enabling blood flow through the fluid line E17 for returning the treated blood to the patient

[0711] E9 Container for collecting the used buffer solution

[0712] E10 Pump for delivering the buffer solution from the gas exchanger to the container E9 for collecting the buffer solution E through the fluid line E19

[0713] E12 Heating device for heating the buffer solution in the fluid line E18 before the buffer solution enters the gas exchanger 10

[0714] E14 Source for the buffer solution

[0715] E16 Fluid line for delivering blood from the patient to the first defined area 1 of the gas exchanger 10 via the blood inlet B in

[0716] E17 is for transporting blood from the first defined region of the gas exchanger 10 to the patient via outlet B out in a fluid line

[0717] E18 is for transporting a buffer solution from a source 14 for buffer solution to a fluid line in the second defined region 2 of the gas exchanger 10,

[0718] E19 is for transporting used buffer solution from the second defined region 2 of the gas exchanger 10 to a container for collecting used fluid or to a fluid line for transporting used buffer solution to a recycling device for returning used buffer solution to the source 14 of buffer solution

[0719] E11a is for measuring the pressure in fluid line E16 after blood inlet B in and before pump E2 for transporting blood in fluid line E16 with a pressure sensor

[0720] E11b is for measuring the pressure in fluid line E16 before the inlet port 4 of the gas exchanger 10 in the first defined region 1 of the gas exchanger and after pump E2 for transporting blood in fluid line E16 with a pressure sensor

[0721] E11c is for measuring the pressure in fluid line E19 between the inlet port 8 of the second defined region of the gas exchanger 10 and pump E10 for transporting buffer solution in fluid line E19 with a pressure sensor

[0722] E21 is for measuring the pressure in fluid line E18 between the inlet port 7 of the second defined region of the gas exchanger and device E22 for reducing the pressure in fluid line E18 with a pressure sensor

[0723] E22 is a device for reducing the pressure in fluid line E18

[0724] E100 is a treatment system for reducing the carbon dioxide content of blood in an extracorporeal blood circuit

[0725] In a fourth and fifth aspect, the subject matter of the invention is characterized by the features of embodiments 51 to 58 below:

[0726] Embodiment 51

[0727] A treatment system (D100) for reducing the carbon dioxide content of blood in an extracorporeal blood circuit, comprising

[0728] - a device (10) for extracorporeally reducing the carbon dioxide content of blood according to at least one of claims 8 to 19,

[0729] - A first inlet (B) for introducing a blood flow to be treated into a treatment system (D100), in wherein the first inlet is in fluid communication via a fluid line (D16) with a first inlet port (4) at a first defined region (1) of a device (10) for reducing the carbon dioxide content in blood extracorporeally,

[0730] in fluid communication,

[0731] - A first outlet (B) for extracting a treated blood flow from the treatment system (D100), out wherein the first outlet is in fluid communication via a fluid line (D17) with an outlet port (5) at a first defined region (1) of a device (10) for reducing the carbon dioxide content in blood extracorporeally,

[0732] in fluid communication,

[0733] - A source (D14) of a buffer solution for reducing the carbon dioxide content in blood, wherein,

[0734] the source (D14) is in fluid communication via a fluid line (D18) with an inlet port (7) at a second defined region (2) of a device (10) for reducing the carbon dioxide content in blood extracorporeally,

[0735] - A container (D9) for collecting the used buffer solution, wherein the container (D9) for collecting the used buffer solution is in fluid communication via a fluid line (D19) with an outlet port (8) at a second defined region (2) of a device (10) for reducing the carbon dioxide content in blood extracorporeally,

[0736] in fluid communication, or

[0737] - A recycling device that replaces the container for collecting the used buffer solution, wherein the recycling device includes a fluid line (D20) for returning the used buffer solution to the source of the buffer solution,

[0738] characterized in that the treatment system includes a balancing device by means of which the amount of buffer solution used from the source of the buffer solution and the amount of used buffer solution can be balanced.

[0739] Example 52

[0740] The treatment system according to claim 51, characterized in that the balancing device is a weight balancing device, in particular, characterized further in that the balancing device includes a scale (D15) for weighing the amount of buffer solution in the source of the buffer solution, and the balancing device includes a scale (D8) for weighing the amount of used buffer solution in the container for collecting the used buffer solution; or

[0741] Characterized in that the balancing device is a volume balancing device which uses a balance chamber to balance the volume of the buffer solution used from the buffer solution source (D14) and the volume of the used buffer solution, or uses a flow meter to balance the volume of the buffer solution extracted from the source for the buffer solution used and the amount of the used buffer solution.

[0742] Example 53

[0743] A treatment system (E100) for reducing the carbon dioxide content in blood in an extracorporeal blood circuit, comprising

[0744] - An apparatus (10) for extracorporeal reduction of the carbon dioxide content in blood according to at least one of claims 8 to 19,

[0745] - A first inlet (B in ) for introducing a blood stream to be treated into the treatment system (E100), wherein the first inlet is in fluid communication via a fluid line (E16) with a first inlet port (4) at a first defined region (1) of the apparatus (10) for extracorporeal reduction of the carbon dioxide content in blood

[0746] in fluid communication,

[0747] - A first outlet (B out ) for extracting the treated blood stream from the treatment system (E100), wherein the first outlet is in fluid communication via a fluid line (E17) with an outlet port (5) at a first defined region (1) of the apparatus (10) for extracorporeal reduction of the carbon dioxide content in blood

[0748] in fluid communication,

[0749] - A source (E14) of buffer solution for reducing the carbon dioxide content in blood, wherein

[0750] the source (E14) is in fluid communication via a fluid line (E18) with an inlet port (7) at a second defined region (2) of the apparatus (10) for extracorporeal reduction of the carbon dioxide content in blood

[0751] - A container (E9) for collecting the used buffer solution, wherein the container (E9) for collecting the used buffer solution is in fluid communication via a fluid line (E19) with an outlet port (8) at a second defined region (2) of the apparatus (10) for extracorporeal reduction of the carbon dioxide content in blood

[0752] in fluid communication, or

[0753] It is characterized in that the device for reducing the pressure (E22) in the fluid pipeline (E18) that is in fluid communication with the inlet port (7) at the second defined region (2) of the device (10) for reducing the carbon dioxide content in the blood in vitro is arranged on the fluid pipeline (E18) that is in fluid communication with the inlet port (7) at the second defined region (2) of the device for reducing the carbon dioxide content in the blood in vitro, before the inlet port (7).

[0754] Example 54

[0755] The treatment device according to claim 53, characterized in that the device (E22) for reducing the pressure is a valve that opens at a predetermined pressure in the fluid pipeline (E18), and in particular, the device for reducing the pressure is a one-way valve.

[0756] Example 55

[0757] The treatment device according to claim 53 or 54, characterized in that a pressure sensor is arranged between the inlet port (7) and the device (E22) for reducing the pressure in the fluid pipeline (E18) that is in fluid communication with the inlet port (7) at the second defined region (2) of the device (10) for reducing the carbon dioxide content in the blood in vitro.

[0758] Example 56

[0759] The treatment system according to any one of claims 51 to 55, characterized in that the pH sensor is arranged on the fluid pipelines (D18, E18) that are in fluid communication with the inlet port (7) at the second defined region (2) of the device (10) for reducing the carbon dioxide content in the blood in vitro, before the inlet port (7), and on the fluid pipelines (D19, E19) that are in fluid communication with the outlet port (8) at the second defined region of the device (10) for reducing the carbon dioxide content in the blood in vitro, after the outlet port (8).

[0760] Example 57

[0761] The treatment system according to at least one of claims 51 to 56, characterized in that the pH sensor is arranged on the fluid pipelines (D16, E16) that are in fluid communication with the inlet port (4) at the first defined region (1) of the device (10) for reducing the carbon dioxide content in the blood in vitro, before the inlet port (4), and on the fluid pipelines (D17, E17) that are in fluid communication with the outlet port (5) at the first defined region of the gas exchanger, after the outlet port (5).

[0762] Example 58

[0763] The treatment system according to at least one of claims 51 to 57, characterized in that the buffer solution is designed to reduce the carbon dioxide content in the blood as described in at least one of claims 1 to 6.

Claims

1. A treatment system (E100) for reducing the carbon dioxide content in blood in an extracorporeal blood circuit, comprising Device (10) for reducing the carbon dioxide content in blood in vitro, said device (10) comprising a first defined region (1) for receiving blood in vitro and a second defined region (2) for receiving a buffer solution, wherein, a first defined region (1) and a second defined region (2) adjacent to each other in a contact zone, separated only by a membrane (3) through which gas exchange can occur between blood and a buffer solution, and wherein the buffer solution is an aqueous solution that exchanges gases with the patient's blood transported in the extracorporeal circuit and contains buffer A and buffer B, where buffer A consists of at least one buffer substance having a pK value of 7.9 ± 0.2 at 37 °C, and buffer B consists of at least one buffer substance having a pK value of 6.9 ± 0.2 at 37 °C, and where at a carbon dioxide partial pressure pCO2 = 0.2 mmHg ± 0.2, the post-titration pH value of the solution ranges from 8.25 to 8.35, - The first inlet (B) for introducing the blood flow to be treated into the treatment system (E100) in ) wherein the first inlet is in fluid communication via a fluid line (E16) with a first inlet port (4) at the first defined region (1) of a device (10) for extracorporeally reducing the carbon dioxide content in blood, - A first outlet (B) for extracting treated blood flow from a treatment system (E100) out ) wherein the first outlet is in fluid communication via a fluid line (E17) with an outlet port (5) at the first defined region (1) of a device (10) for extracorporeally reducing the carbon dioxide content in blood, - a source (E14) of buffer solution for reducing the carbon dioxide content in blood, where the source (D14) is in fluid communication via a fluid line (E18) with an inlet port (7) at the second defined region (2) of a device (10) for extracorporeally reducing the carbon dioxide content in blood, - a container (E9) for collecting the used buffer solution, where the container (E9) for collecting the used buffer solution is in fluid communication via a fluid line (E19) with an outlet port (8) at the second defined region (2) of a device (10) for extracorporeally reducing the carbon dioxide content in blood in fluid communication, characterized in that a device (E22) for reducing the pressure in a fluid line (E18) in fluid communication with the inlet port (7) at the second defined region (2) of a device for extracorporeally reducing the carbon dioxide content in blood is arranged on the fluid line (E18) in fluid communication with the inlet port (7) of the second defined region (2) of the device for extracorporeally reducing the carbon dioxide content in blood, before the inlet port (7), and the device (E22) for reducing the pressure includes a throttling element.

2. The treatment system according to claim 1, characterized in that, The device (E22) for reducing the pressure is a valve that opens at a predetermined pressure in the fluid line (E18).

3. The treatment system according to claim 1 or 2, characterized in that, The membrane comprises at least one polymer selected from polypropylene PP, polymethylpentene PMP, and polysulfone PSU, or a mixture selected from the above polymers.

4. The treatment system according to claim 1 or 2, characterized in that, The membrane comprises at least one polymer selected from polypropylene PP, polymethylpentene PMP, polysulfone PSU, and polyvinylpyrrolidone PVP, or a mixture selected from the above polymers.

5. The treatment system according to claim 1 or 2, characterized in that, The membrane comprises a mixture of polysulfone PSU and polyvinylpyrrolidone PVP.

6. The treatment system according to claim 1 or 2, characterized in that, The membrane is formed by a plurality of hollow fibers.

7. The treatment system according to claim 1 or 2, characterized in that The membrane is coated with silicone.

8. The treatment system according to claim 1 or 2, characterized in that, The membrane is formed by hollow fibers coated with silicone.

9. The treatment system according to claim 6, wherein The inner surface and / or outer surface of the hollow fiber is coated with silicone resin.

10. The treatment system according to any one of claims 1, 2, 9, characterized in that - The first defined region (1) for receiving extracorporeal blood has an inlet port (4) and an outlet port (5) for blood, and is configured such that blood can flow from the inlet port (4) through the first defined region to the outlet port (5) along the first flow direction (6), and - The second defined region (2) for receiving the buffer solution has an inlet port (7) and an outlet port (8) for the buffer solution, and is configured such that the buffer solution can flow from the inlet port (7) through the second defined region to the outlet port (8) along the second flow direction (9), wherein the first flow direction (6) of the first defined region (1) and the second flow direction (9) of the second defined region (2) are oriented in opposite directions to each other.

11. The treatment system according to any one of claims 1, 2, and 9, characterized in that, The exchange surface in the contact zone through which gas exchange can occur via the membrane (3) is at least 0.3 m 2 .

12. The treatment system according to any one of claims 1, 2, and 9, characterized in that The exchange surface area in the contact zone through which gas exchange can occur through the membrane (3) is at least 0.6 m 2 .

13. The treatment system according to any one of claims 1, 2, and 9, characterized in that, The exchange surface in the contact zone, through which gas exchange can occur via the membrane (3), is at least 1 m 2 .

14. The treatment system according to any one of claims 1, 2, and 9, characterized in that, The exchange surface that enables gas exchange through the membrane (3) in the contact zone reaches at least 2 m 2 .

15. The treatment system according to any one of claims 1, 2, and 9, characterized in that The exchange surface area in the contact zone where gas exchange can occur through the membrane (3) is at most 5 m 2 .

16. The treatment system according to any one of claims 1, 2, and 9, characterized in that, The exchange surface area in the contact zone through which gas exchange can occur through the membrane (3) is at most 3 m 2 .

17. The treatment system according to any one of claims 1, 2, and 9, characterized in that, The pH sensor is arranged upstream of the inlet port (7) on fluid lines (D18, E18) in fluid communication with the inlet port (7) at the second defined region (2) of the device (10) for reducing the carbon dioxide content in extracorporeal blood, and downstream of the outlet port (8) on fluid lines (D19, E19) in fluid communication with the outlet port (8) at the second defined region of the device (10) for reducing the carbon dioxide content in extracorporeal blood.

18. The treatment system according to claim 10, wherein The pH sensor is arranged upstream of the inlet port (4) on fluid lines (D16, E16) in fluid communication with the inlet port (4) at the first defined region (1) of the device (10) for reducing the carbon dioxide content in extracorporeal blood, and downstream of the outlet port (5) on fluid lines (D17, E17) in fluid communication with the outlet port (5) at the first defined region of the gas exchanger.

19. The treatment system according to any one of claims 1, 2, 9, and 18, characterized in that, The buffer solution is designed to reduce the carbon dioxide content in blood.

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