method for differentiating changes in flow resistance in a blood treatment system and blood treatmen

专利摘要:
METHOD FOR DIFFERENTIATING FLOW RESISTANCE CHANGES IN A BLOOD TREATMENT SYSTEM AND BLOOD TREATMENT SYSTEM The present invention relates to a method and device for measuring pressure signals in a blood treatment system, through which changes of the system can be identified and thus additionally can be reliably differentiated between changes in the system in the direction of blood flow and transmembrane direction, in order to enable a specific action to be taken.
公开号:BR112013008706B1
申请号:R112013008706-4
申请日:2011-10-14
公开日:2021-01-05
发明作者:Henrik Wolff
申请人:B Braun Avitum Ag；
IPC主号:

专利说明:

The present invention relates to a method for recognizing system changes in a blood treatment device and to a blood treatment device.
In this case, the invention refers to the field of filtration, that is, tangential flow filtration (TFF). Here the fluid to be purified is separated from the purification solution by a semipermeable membrane. The purification solution usually has a low concentration of substances, less than the substances that must be removed from the fluid to be purified. With that, diffusion is generated. In order to be able to use diffusion optimally as a purifying force, tangential flow filters are normally operated with the countercurrent principle.
A dialysis filter consists essentially of hollow fibers, therefore cylindrical shaped fibers, which pass through a longitudinally stretched housing. The hollow fiber walls act as membranes, in this case, through partially permeable (semi-permeable) structures. At its ends, hollow fibers are incorporated into a casting compound. Hollow fibers can be combined, in dialysis filters, with modules with several square meters of filter area. During dialysis through tangential flow filtration, also known as cross flow filtration, blood / plasma is supplied to the hollow fibers through a first fluid circulation, which flows longitudinally through them. Through a second fluid circulation, dialysis fluid is normally supplied by the countercurrent principle, but, if possible, it is also supplied in parallel to the bloodstream. Thus, the housing has four doors, namely, two for each fluid stream, one for supply and removal, respectively. Inside the hollow fiber membrane is the bloodstream, and on the outside, dialysis fluid.
Another purification mechanism is convection. Here a pressure gradient is generated across the semipermeable membrane, through which the fluid to be purified is pressed onto the semipermeable membrane. In this way, the substances are washed at their current concentration. This purification process is not dependent on the concentration of substances in the purification solution. Decisive here are only the concentration in the liquid to be purified and the properties of the membrane, such as the sieving coefficient, permeability, etc. Thus, it is interesting to know the properties of the filter at the beginning, as well as during the treatment.
A specific area of filtration is the extracorporeal treatment of blood for chronic or acute renal failure. Here, the fluid to be purified is the patient's blood and the purification solution is the dialysis fluid. It is decisive, in this specific case of TFF, to replace the function of purifying the kidney blood in the treatments (in chronic cases, usually three times a week). To ensure this, the Kt / V value was established as a measure of the quality of the treatment. Kt / V is a parameter for determining the effectiveness of dialysis and a key element for assessing the effectiveness of dialysis. K is the distance, which is determined by the blood urea content before and after dialysis. The t value shows the effective dialysis time in minutes and V is the volume of distribution of urea. This refers to 60% of body mass (weight), in which blood can circulate (body water content). The goal of treatment is to obtain a Kt / V> 1.2. In some normal treatment processes the values are stored, which generally satisfy this criterion. However, adversities can occur in a treatment, which negatively affects the treatment process, as well as the treatment result. Therefore, it is important to monitor and control the parameters that influence during a treatment, in order to be able to react quickly to such adversities and, especially, to properly adjust the system parameters during dialysis.
A decisive process is the interaction of the filter membrane with the blood. Through this interaction the flow properties of the filter deteriorate both in the direction of the transmembrane and in the direction of the blood flow. These changes are caused, for example, by the binding of thrombocytes to the membrane, by the formation of a clot, by the chemical binding of blood components to the membrane or by the simple mechanical pressing (conditional flow) of blood components, including the membrane.
Transmembrane direction or transmembrane direction refers here to a flow of blood through the dialyzer membrane or the dialysis filter.
During the formation of the clot, a gelatinous aggregation of red blood cells (erythrocytes) appears, stabilized by means of fibrin threads. Unlike the term thrombus, a clot describes a blood clot, which is found outside a blood or lymphatic vessel (extravascular) and not inside (intravascular).
These and other changes in the properties of the system have several effects on the treatment process and on the quality of the treatment. Especially the treatment by hemodiafiltration is affected, since, here, it is focused on the convective transport of substance of medium molecular substances. Through deterioration of transmembrane flow properties or permeability, the sieving coefficient of uremic substances also deteriorates in the average molecular weight range, which leads to a result in which the same amount of fluid filtered by convection of less uremic substances is removed from the bloodstream. Another effect is the reduction of the effective flow area, both in the direction of blood flow and in the direction of the transmembrane. This results in a reduction in the active surface of the filter, which can lead to deterioration of diffuse purification. With new filters there is generally a buffering potential, which is greater than the maximum physiological filtration. In this way, a decrease in the effective flow area can be limited to a certain level. However, if this potential is exhausted, it leads to the effect described above.
Purge with saline solution for the "cleaning" of the dialyzer, the addition of heparin to prevent the formation of clots or to reduce the rate of ultrafiltration (UF), in order to reduce hemoconcentration, are generally accepted as contraindications. - appropriate actions or reactions to such changes. The permeability of the membranes is determined by measuring the volume of the fluid, which is carried out at a given pressure difference at a temperature of 37 ° C by means of a predetermined membrane surface across the membrane and which is normalized for general comparability in terms of area unit, time unit and pressure unit. Water is used as a fluid to determine the rate of ultrafiltration.
From the state of the art, attempts are already known, which aim to detect changes in the system and react to them. In US 2008/0215247 A1 it is considered that the linear relationship between the transmembrane pressure (TMP) and the ultrafiltration rate QUF = TMP * KUF (KUF = ultrafiltration coefficient) only takes place in a certain interval of the TMP. Thus, firstly, the QUF (TMP) function is estimated by gradually increasing the TMP and the measurement of the ultrafiltration rate is thus generated. After a certain amount, an increase in TMP results in an ever smaller increase in the rate of ultrafiltration. Hence the knee point (tangency point) of the QUF (TMP) function is selected as the working point. Since KUF deteriorates during treatment due to system change, WO 2006/011009 A2 describes the technical conditions that allow the relationship between TMP and QUF-
EP 1175917 A1 describes the adjustment of pre- and post-dilution proportions in the treatment process as another concept.
US 2006/157408 A1 discloses a method for detecting filter clots. To detect such filter clots, up to four different pressure sensors are used, which have pressure measurements of up to four different positions. For pressure changes in one of the pressure sensors, it is concluded that the filter obstruction is present, on which a reaction can be made with the addition of heparin. However, it has not been recognized that there are a plurality of combinations, in which the pressures in the system can be changed, without actually reaching a filter coagulation. Furthermore, it has not been recognized that these constellations can only be recognized by generating the time trend of the measured pressure signals and the quotients or differences of the measured pressure signals. In the present invention, it has been found that pressure differences are not always due to clogging of the filter, but can have a plurality of causes, which can be detected according to the invention and reduced locally. Although US 2006/157408 A1 reveals that up to four pressure measurement positions can be made in order to increase the safety of the yes-no instruction, the pressures, however, are not adjusted in relation to each other and trends are not observed for detect different patterns of change and to limit locally. Thus, the four measuring points only serve to make the declaration if the filter is clogged or not (yes-no declaration), which would have been found even with only the measurement at one measuring point. That is, the measurement carried out in US 2006/157408 A1 at up to four measurement points is not used to obtain more information, but only to increase the measurement accuracy, because, for example, during measurement, only one point of the measurement sensor can be damaged, which can be recognized by the measurement at several points. According to the invention, measuring at four measuring points does not serve to increase the measurement accuracy, but to obtain more information, in order to locally limit the source of the error and, additionally, describe the change qualitatively.
In addition, DE 10355042 B3 describes a method with which changes in blood flow can be detected, in which the phase angle of at least one harmonic component of an oscillating pressure signal of propagation in the extracorporeal blood circulation is determined. Also with this method, changes cannot be accurately detected in the system and cannot be limited locally and, as a single measure for eliminating a change, only the ultrafiltration rate control is indicated.
Accordingly, the aim of the present invention is to provide a method for recognizing system changes in a blood treatment device and a blood treatment device, suitable for measuring those system changes in the blood treatment device, which may not it only identifies system changes, but it can also, in addition, reliably differentiate between system changes in the direction of blood flow, flow direction of the dialysate and transmembrane direction, in order to enable a certain action.
This task is solved through the method and the devices, which are mentioned in the independent claims. Other advantageous configurations of the invention result from the dependent claims, the description, the figures as well as the examples.
The method for differentiating changes in flow resistance in a blood treatment system, which comprises the following steps:
The method according to the invention for recognizing system changes and especially for differentiating changes in flow resistance in a blood treatment system comprises the following steps, a) Measurement of at least two pressure signals selected from the group consisting of (PB1, PB2, PD1, PD2), which are measured on at least two pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], in that [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure measured in the pressure sensor [PB1], where [PB2] designates the pressure sensor in the bloodstream after the blood flow from the tangential flow filter TFF and PB2 designates the pressure measured in the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the flow filter tangential TFF and PD1 of means the pressure measured at the pressure sensor [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after the dialysate exits from the tangential flow filter TFF and PD2 designates the pressure measured at the pressure sensor [PD2] ; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2.PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of the time trend, if there was a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
Through the method according to the invention, one can preferentially find a statement, whether the flow properties have changed both in the direction of blood flow, in the direction of the dialysate flow, as well as in the transmembrane direction. Previous systems are not able to find such a differentiation. Furthermore, by means of the method according to the invention, changes can preferably be delimited not only on the spot, but it is also possible, in several cases, to qualitatively record the causes of the changes. This offers the advantage that, by assessing at least two signs of pressure, the type and location of the change are precisely determined in the blood treatment device, in order to subsequently perform a timely elimination of the cause for the change.
A costly and time-consuming search for the exact change is a problem that underlies the invention. General measures, such as washing the entire blood treatment device, can be replaced by one-off measures, in which, for example, only the tube system or only the filter is changed, in which a system change, for example , in the form of a clot formation, occurred.
This method can, ideally, additionally comprise the following steps: i) Elimination of the change in flow resistance in the transmembrane direction, direction of flow of the dialysate or direction of blood flow or indication of a possibility for eliminating the change.
The elimination of the change can, as long as it is not an exchange of system components, such as dialyzer or tube system, occur automatically, semi-automatically or manually. In addition, the display of the evaluation according to step h) and the indication of a possibility for eliminating the change according to step i) occur simultaneously with each other and immediately one after the other or both steps can also be identical. If the change is to be eliminated only by the complete change of a component of the system, the dialyser is changed manually, or if the change is to be automatically eliminated, the blood flow and, ideally, also the dialysate flow , is diverted to a replacing component that is next to or on the dialysis device.
In another preferred mode, the time trend is generated from the measured pressure signals and the calculated differences and / or the pressure signal quotients, or only with the calculated differences and / or quotients. In this modality, step d) is replaced by the following step d '): d') Generation of at least one time trend from the measured pressure signals selected from the groups consisting of (PB1, PB2, PD1, PD2) and the calculated differences, and / or the quotient of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM), or the calculated differences and / or the quotients of the pressure signals PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM).
Step d ') reproduces the same as step d), only in a more detailed sense.
In another embodiment, the method according to the invention comprises the measurement of at least two pressure signals and, therefore, comprises the following steps: a) Measurement of at least two pressure signals selected from the group consisting of (PB1, PB2 , PD1, PD2), which are measured on at least two pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the blood pressure sensor before blood enters the TFF and PB1 tangential flow filter designates the pressure measured at the pressure sensor [PB1], where [PB2] designates the blood pressure sensor after blood flow from the TFF and PB2 tangential flow filter designates the pressure measured in the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF and PD1 tangential flow filter designates the pressure measured at the pressure sensor [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured in the pressure sensor [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
In an especially preferred embodiment, the method according to the invention comprises the measurement of four pressure signals and thus represents as follows. Method for differentiating changes and / or changes in flow resistance in a blood treatment system, which comprises the following steps: a) Measurement of four pressure signals (PB1, PB2, PD1, PD2), which are measured in four pressure sensors ([PB1], [PB2], [PD1] and [PD2]), where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure measured at the pressure sensor [PB1], where [PB2] designates the pressure sensor in the bloodstream after the blood exits from the tangential flow filter TFF and PB2 designates the pressure measured at the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the tangential flow filter TFF and PD1 designates the pressure measured in the pressure sensor [PD1] and [PD2] designates the pressure sensor in the circulation of the dialysate dialysate after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured at the pressure sensor [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals (PB1, PB2) and / or ( PB1, PD1) and / or (PB1, PD2) and / or (PB2.PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which four pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of the time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2 , PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
In this modality, four pressure signals PB1, PB2, PD1 and PD2 are measured in the blood treatment system. The measurement takes place on the pressure sensors ([PB1], [PB2], [PD1] and [PD2]), where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure measured at the pressure sensor [PB1], where [PB2] designates the pressure sensor in the bloodstream after the blood flows from the TFF tangential flow filter and PB2 designates the pressure measured at the pressure sensor [ PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF tangential flow filter and PD1 designates the pressure measured in the pressure sensor [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured in the pressure sensor [PD2];
From the measured pressure signals, each possible combination from the quotients and / or differences is calculated in the next step in a central processing unit, which combination is formed from the four pressure signals. This means, concretely, that the quotients and / or differences are calculated from the four pressure signals (PB1, PB2), (PB1, PD1), (PB1, PD2), (PB2, PD1), (PB2, PD2) , (PD1, PD2), (PB1, PDM), (PB2, PDM), (PD1, PBM), (PD2, PBM) and (PDM, PBM). Thus, all quotients and / or differences from the pressure signals are available for the first measurement.
In the next step, a new measurement is performed on the four pressure sensors, which happens with time lag in relation to the first measurement. This measurement takes place in the same way as the first, that is, on the same pressure sensors, with the same adjustments, except for the difference that the pressure signals are measured with a lag time compared to the first measurement. From the pressure signals measured over time, each possible combination from the quotients and / or differences is calculated with respect to the calculation described above in a central processing unit, which combinations can be measured from the four measured pressure signals with lagged time. This means, concretely, that the quotients and / or differences are calculated from the pressure signals measured with time lag (PB1, PB2), (PB1, PD1) (PB1, PD2), (PB2, PD1), (PB2, PD2), (PD1, PD2), (PB1, PDM), (PB2, PDM), (PD1, PBM), (PD2, PBM) and (PDM, PBM). As a result, the quotients and / or differences from the pressure signals measured over time are available for the second measurement.
In general, it should be noted that the method according to the invention requires, in the aforementioned combination of pressure signals, that, during similar and repeated measurements and calculations, the same measurement and calculation be carried out. Especially the formation of the quotients must comprise not only a / b and, when re-measuring, b / a, but continuously a / b. The same applies mutatis mutandis to the formation of differences; when the new measurement a- b is formed, a - b is also formed again in the new measurement, not b - a.
In other measurements with lagged time other pressure signals can be measured, and other quotients and / or differences from the pressure signals can be calculated; however, according to the invention the two measurements mentioned above are sufficient to carry out the method. In order to determine a trend, several measurements can theoretically be related to different times, in which the period selected for the determination of a trend must evidently be below one tenth (1/10) of the duration of the dialysis session, preferably below one fiftieth (1/50), more preferably below one eightieth, even more preferably below 1/100, most preferably still below 1/100, even more preferably below 1/110 and even more preferably below 1/120 the duration of the dialysis session. Within the period considered for the determination of a trend, there are 2 to 60.00 measurements with lagged time of the pressure signals, preferably from 3 to 20.00, more preferably from 4 to 10.00 and even more preferably from 5 to 5,000 measurements.
From the pressure signals measured from the first and second measurements and from all quotients and / or differences from the first measurement and second measurement, a time trend is calculated, that is, it is calculated that the quotient and / or difference from of the pressure signals (PB1, PB2) from the first measurement is compared with the quotient and / or the difference from the pressure signals (PB1, PB2) from the second measurement. This time trend is determined for each of the quotients and / or each of the differences from the pressure signals of the first measurement and from the quotients and / or differences from the pressure signals of the second measurement. In addition, the time trend for each of the pressure signals PB1, PB2, PD1 and PD2 is determined. This makes time trends available for the measured pressure signals and for each of the quotients and / or differences in the pressure signals from the first and second measurements. Each time trend is assessed taking into account whether a change has occurred beyond a margin of tolerance. In this sense, each of the trends can be classified taking into account if no changes occurred, which exceeds a margin of tolerance, if the trend is upward, that is, if it goes beyond the margin of tolerance to a greater limit or if the trend is downward, that is, it goes beyond the margin of tolerance to a lower limit. From the assessment of each time trend a pattern results, which can be attributed to a specific picture of change.
The measurement of pressure signals, for example, in the period t = Os and in other measurements with time lag in periods t = 60s, t = 120s, t = 180s, t = 240s and t = 300s could have resulted in the following values:

From the measured values, all possible quotients and / or differences are formed for each measurement with lagged time. For the period t = 0 this would mean that the quotients and / or differences are calculated from (PB1, PB2), (PB1, PD1), (PB1, PD2), (PB2, PD1), (PB2, PD2), (PD1, PD2), (PB1, PDM), (PB2, PDM), (PD1, PBM), (PD2, PBM) and (PDM, PBM). This would lead, for the period t = 0, to the following result for the formation of quotients: (120/50), (120/80), (120/70), (50/80), (50/70), ( 80/70), (120/75), (50/75), (80/85), (70/85) and (75/85). The calculation also occurs for the differences and is performed for each measurement with lagged time. From the calculated quotients and / or differences and / or measured absolute values, trends for absolute values and / or quotients and / or differences are determined. For the quotient from (PB1, PB2) the following time trends could result: (120/50), (125/49), (133/51), (139/48), (145/52) and (150 / 50). This time trend is determined for each of the quotients and / or each of the differences and / or each of the absolute values. From this it results, in the present example, that the time trend t = 0 to t = 300s is upward for the quotients from (PB1, PB2), (PB1, PD1), (PB1, PD2), (PB1, PDM ), (PBM, PD1), (PBM, PD2) and (PBM / PDM), in which the common time trends of the quotients remain unchanged. In addition, it is possible to determine trends within trends. This would mean, in the present example, that not only is a time trend between t = 0 to t = 300s determined, but that any number in time trends between t = 0 and t = 240s, or t = 60s and t = 180s and etc. . can also be determined. The determination of long-term trends is naturally better suited to the recording of changes, which occur gradually, in which with shorter trends changes can also be recognized, which are of a minor nature. The pattern constellation shown in this example based on trends in quotients and / or differences and / or absolute values is specific to secondary membrane formation. For all possible tables of change, there are specific pattern constellations, which can be formed from the formation of trends from quotients and / or from trends of differences and / or trends of absolute values. Such pattern constellations are shown, for example, in figures 6 and 7.
In another embodiment, the measurement of at least two pressure signals occurs simultaneously. In this modality, step a) is replaced by the following step a '): a') Measurement of at least two pressure signals selected from the group consisting of (PB1, PB2, PD1, PD2), which are measured in at least at least two pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor in the bloodstream before blood enters in the tangential flow filter TFF and PB1 designates the pressure measured in the pressure sensor [PB1], where [PB2] designates the pressure sensor in the blood circulation after the blood is released from the tangential flow filter TFF and PB2 designates the pressure measured at the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the tangential flow filter TFF and PD1 designates the pressure measured at the pressure sensor [PD1] and [ PD2] designates the pressure sensor in the dialysate circulation after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured in the pressure sensor [PD2];
As used here, "simultaneously" means that the pressure signals are measured simultaneously or immediately one after the other. That is, it means that no long pause is left between the measurement of one pressure signal and the other pressure signal (s). The measurement of the pressure signals occurs, preferably, within a period of 5 minutes, preferably within 1 minute, even more preferably within 45 seconds, most preferably within 30 seconds and, moreover, preferably within 15 seconds and even more preferably within periods of less than or equal to 1 second.
The method according to the invention can mainly be carried out with at least two pressure sensors, in which preferably three pressure sensors and, in addition, preferably four pressure sensors are used.
The tangential flow filter is one of the most common types of filter, which can be inserted into a blood treatment device. In principle, other types of filters can also be used, without compromising the method according to the invention in any way. For this reason, the invention concerns not only the dialysis device with a tangential flow filter, but also any type of dialyzer.
The pressure signals, according to the invention, are measured, and all possible ratios and / or differences from the measured pressure signals are calculated, that is, when using two pressure sensors, two pressure signals are measured, from which the quotient and / or the difference are formed. This means that when using the pressure sensors [PB1] and [PD1], the pressure signals PB1 and PD2 are measured and the quotients and / or differences from (PB1, PD1) are calculated. If three pressure sensors are used, then a pressure signal is measured in each of these pressure sensors, for which the quotients or differences are calculated with each of the other pressure signals. For example, pressure signals PB1, PB2 and PD1 could be measured, from which, then, the quotients and / or differences are calculated from (PB1, PB2), (PB1, PD1), (PB2, PD1 ) and (PBM, PD1). For the case where four pressure sensors are used, the quotient and / or the difference is calculated for each possible pair of the four pressure signals. In addition, average values are calculated for both pressure signals related to the dialysate and for both pressure signals related to blood, for which, then, the quotients and / or differences are recalculated with each pressure signal, that is, it concretely means that the quotients and / or the differences are calculated from (PB1, PB2), (PB1, PD1), (PB1, PD2), (PB2, PD1), (PB2, PD2), (PD1 , PD2), (PB1, PDM), (PB2, PDM), (PD1, PBM), (PD2, PBM) and (PDM, PBM). With PBM, the respective mean value is designated from the blood and dialysate signals.
Therefore, at least one time-lapse measurement occurs, therefore, with the same number and the same pressure sensors, as in the case of the measurement carried out previously. Measurement with lagged time therefore occurs under the same conditions, that is, with the same determinations, with the only difference that it occurs with lagged time. With this, it is obtained, through the measurement with lagged time, for each of the pressure sensors, another pressure signal with lagged time. In practice, it has been proven that several time lag measurements are advantageous for detecting changes in flow resistance in a blood treatment system. They occur advantageously over the entire duration of treatment with the blood treatment system, in order to ensure that changes over the duration of the treatment can also be recognized in the system. In this sense, lagged time means that between each measurement there is a known period, which can be established individually. In this case, you can deal with very fast measurements, such as, for example, 20 times per second; however, it is also possible for measurements to be taken over a longer period, such as, for example, a measurement every 5 minutes, a measurement every 1 minute, a measurement every 30 seconds, a measurement every 10 seconds , one measurement every second or one measurement every tenth of a second.
Preferably, the measured pressure signals are normalized to eliminate normal pressure variations, which, for example, are caused by the pump.
The determination of the time trend includes the comparison of the measured pressure signals and / or the quotients and / or the differences from the measurements, considering whether the changes in the measured pressure signals and / or the quotients and / or the differences resulted over time. of time. For the generation of the time trend, according to the invention, at least two time-lapse measurements on the pressure sensors must occur. Time trends are thus generated for each of the measured pressure signals and / or each of the quotients and / or each of the differences, that is, with four pressure sensors and thus with four measured pressure signals, all possible quotients and / or differences are formed from the four measured pressure sensors. According to the invention, the four pressure signals are measured at least once with time lag in the four pressure sensors, from which new ratios and / or differences are formed. Each of the measured pressure signals and / or quotients and / or differences from the first measurement are compared with the measured pressure signals and / or with the quotients and / or with the differences from the lagged measurement, with the which results as a result of a time trend for each of the measured pressure signals and / or each quotient and / or each difference.
If several measurements occur with lagged time, according to the invention, for each of these periods, several measured pressure signals and / or several quotients and / or several differences are available. It is at the expert's discretion whether "short" time trends should preferably be recorded, which consist of only a few time-lagged measurements, or whether long-term time trends should be recorded, which consist of a plurality of time-lagged measurements. The generation of the time trend can occur mainly also by comparing the measured pressure signals and / or the quotients and / or the differences over time lagged measurements. However, it is also possible that the time trend is generated only for some of these time-lagged measurements. This means, concretely, that small variations can be better recognized, at first, through the generation of “short” trends, which consist only of some measurements with lagged time, in which gradual and continuous changes in the system can be better recognized by through the generation of long-term trends, which contain a plurality of pressure signals measured over time and / or quotients and / or differences. According to the invention, both short trends and long-term time trends can be generated and combined with each other.
In practice, it has been shown that, with the generation of temporal trends, one should start only after a preliminary period of about 1 to 5 minutes, since, regardless of hematocrit, ultrafiltration rate, specific filter, which are used, that is, especially the number of fibers in the filter, the flow rate and, in general, blood viscosity, it takes a while before stable pressure signals can be measured, from which, then, time trends for the measured pressure signals and / or quotients and / or differences can be generated.
The evaluation of time trends occurs in such a way that it is registered if a change in the time trend occurred beyond a margin of tolerance.
In this case, a distinction is made between time trends that increase rapidly (++), which increase (+), which remain unchanged (0), which decrease (-) and those which decrease rapidly (-).
The tolerance margin can, for example, be delimited in such a way that, in the case of a small time trend, consisting of measured pressure signals and / or quotients and / or differences of two measurements with lagged time, a change in measured pressure signals and / or quotients and / or differences is measured around 10%, in either direction, or as an increase (+) or a decrease (-) in the time trend. Conversely, each change within this tolerance range is assessed as "remained unchanged (0)". As a result, the tolerance margin indicates the range in which the values of the measured pressure signals and / or the quotients and / or differences can remain, in order to be evaluated as "remained unchanged (0)". Values that fall outside the tolerance range are changed with this, with which the time trend is then correspondingly evaluated. For a time trend to be assessed as rapidly increasing (++) or as rapidly decreasing an acute change must occur between the pressure signals measured and generated with lagged time and / or the quotients and / or differences, that is, the change does not it can develop over an extended period of time, but rather abruptly. This is especially the case when, for example, a pipe is pulled out. The threshold for delimiting between signals that increase or decrease as well as signals that increase rapidly or decrease rapidly can be determined individually according to the type of device, patient, preferred assessment parameters, etc.
The delimitation of the tolerance margin depends on a known number of factors, such as, for example, hematocrit, ultrafiltration rate, specific filter used, that is, it depends especially on the number of fibers in the filter, the flow speed and, general, blood viscosity. The tolerance margin can be delimited in such a way, for example, that the measured pressure signals and / or quotients and / or differences within the time trend cannot exceed or fall below an absolute value. On the other hand, the margin of tolerance can also be chosen in such a way that, for example, a known percentage change in the measured pressure signals and / or quotients and / or differences cannot be above. Naturally, several limits for tolerance margins can be combined with each other, with the result, for example, that the tolerance margin is delimited both by a higher absolute value and also by percentage changes in the measured pressure signals and / or quotients and / or differences. In such a case, a time trend could be assessed as increasing (+), with which it is above either the upper absolute limit or the limit of the percentage changes in the measured pressure signals and / or the quotients and / or differences. It is up to the specialist's skills to determine tolerance margins, without having to be related to the invention.
From the evaluation of time trends, a pattern is generated, which can be attributed to a specific change condition. Thus, it can happen, for example, that the quotient of PB1 / PD1 has a decreasing trend, in which the quotient from PB2 / PD2 has a constant trend. The totality of time trends assessed also results in a pattern. In figures 6 and 7 some pattern constellations are compiled for pressure changes that occur in the operation of a dialysis device and for the changes underlying them.
It is especially preferred when at least one pressure signal on the arterial side and at least one other pressure signal on the dialysate side are determined. Most preferred is when a pressure signal on the arterial side and two pressure signs on the dialysate side or two pressure signs on the arterial side and a pressure signal on the dialysate side are determined. In a particularly preferred embodiment, two signs of pressure on the arterial side and two signs of pressure on the dialysate side are determined. Pressure measurements are preferably taken or directly before the tangential flow filter (TFF) inlets and outlets.
In the case of the measured pressure signals, we can deal with absolute pressures, relative pressures, absolute pressure differences between two pressure measurement points, relative pressure differences between two pressure measurement points, absolute pressure ranges, relative amplitudes of pressure, of differences between the absolute pressure amplitudes at two pressure measurement points, or differences between the relative pressure amplitudes at two pressure measurement points or a combination of these, or the pressure frequency spectra.
The term "absolute pressure" or "absolute pressures", as used here, describes pressure in comparison to atmospheric pressure.
The term "relative pressure" or "relative pressures", as used herein, describes the relative change of a pressure signal in relation to a second pressure signal.
The term "pressure difference" or "pressure differences", as used here, describes the difference in two pressures.
The term "pressure range" or "pressure range", as used herein, describes the measured or determined value of pressure fluctuations. As a synonym for the term, pressure oscillation amplitude can be used.
The term "frequency spectrum" or "frequency spectra", as used here, describes all of the frequencies, which are generated by an oscillating system or are included in a signal.
It has been found that the measurement and analysis of pressure signals, for example, also generated by a blood P pump in the system, provides information on the flow properties of a device for treating blood through the formation of quotients and / or differences in relation to the measured pressure signals, from which a time trend is derived, which has a specific pattern of specific changing conditions. According to the invention, each of the pressure signals in the system can be used for analysis, regardless of their origin. For example, in one embodiment, the pressure signals that are generated by switching a BK balance chamber are determined and used for analysis.
The control of the properties of the system during the treatment is preferably implemented in such a way that the pressure signals generated by the blood pump P and its propagation are monitored. According to the invention, the pressure signals from a pump on the dialysate side or the pressure spikes produced by switching the valves are also monitored. It is also possible to monitor the combined signal pressure from both pumps, or to detect each unique pressure signal. Especially preferable is the monitoring of the four pressure signals at the tangential flow filter inlets and outlets.
Depending on the properties of the blood treatment system, the pressure signals in the system spread along the direction of blood flow and the transmembrane direction.
Thus, it is possible to record changes in flow conditions by monitoring the pressure signals on the arterial side and on the dialysate side, as well as by controlling the relationships of these pressures and differentiating between changes in the direction of blood flow, direction dialysate flow and transmembrane direction.
The term "blood treatment unit" thus describes a device that can be used for the purification and / or treatment of blood, the central point of which is a tangential flow filter. In particular, it can be a dialysis unit, which is capable of hemodialysis, hemoperfusion, hemofiltration or hemodiafiltration.
The term "system change", as used herein, includes, in particular, the interaction of components of the apparatus for treating blood, particularly the membrane filter with the blood. Through this interaction, the flow properties are deteriorated, both in the transmembrane direction and also in the direction of the blood flow. This is caused, for example, by thrombocyte binding, clot formation, chemical binding of blood components to the membrane or simply mechanical pressures (conditioned by the flow) of blood components and even the membrane, but it is not limited to this and can also occur in other positions within the blood treatment unit. In addition, changes are understood in the system, since they can occur, for example, due to the removal of a tube or due to a leak in the system. System alterations are also involved here, although there is no direct interaction of the device's components with the blood.
The determination of pressure signals is carried out by means of pressure sensors. For this, pressure sensors known from the state of the art can be used, such as piezoresistive, piezoelectric pressure sensors, frequency analogs, as well as the flow conversion elements, capacitive, inductive and / or combinations thereof. Pressure sensors, whose sample rate is at least 20 Hz, are preferred. The sample rate describes here the rate at which signal values are taken from a continuous signal.
The relations according to the invention are represented in detail, as shown in Figures 6 and 7:
If, for example, the filter membrane is clogged by coagulation, an increasing tendency of the measured pressure signal PB1 is shown on the pressure sensor [PB1], where the trends of the other pressure signals PB2, PD1 and PD2 remain unchanged . By further calculating the quotients and / or differences in the measured pressure signals and the generation of temporal trends, a much more differentiated image appears, which shows that the temporal tendencies of the quotients and / or differences in (PB1, PB2), ( PB1, PD1), (PB1, PD2), (PBM, PD1), (PDM, PD2), (PWM / PDM) increase, while the time trend of the quotients and / or differences of (PB2, PD1), (PB2, PD2), (PB2, PDM) and (PD1, PD2) remains unchanged. From the totality of the measured pressure signal trends and / or the quotient trends and / or the trends of the measured pressure signal differences, it results in a characteristic pattern constellation, which can be directly attributed to the coagulation change table .
The single value (pressure signal) itself is subject to various influences and, by observing the current value, little information is obtained. Therefore, according to the invention, it has been recognized that only through the formation of quotients and / or differences in pressure signals and the generation of a temporal evolution, changes can be detected in detail. Changes in this time trend are different under various conditions of change and result in a specific pattern, which can be attributed to the respective condition of change. For example, changes in the system due to treatment can be distinguished from those (changes), due to external influences.
The differentiation between the formation of quotients and differences in pressure signals, therefore, makes sense, since, in the case of a pressure change through a displacement, such as, for example, in an increased resistance at reflux, alter the pressure signals around the same absolute value causes the differences to remain constant, however, the quotients change, so these changes can also be detected according to the invention.
Other changes could, for example, occur in the form of an acute flow constriction before [PD1] or an acute flow constriction between [PD1] and the filter. According to the invention, here, one can distinguish between the two changes. With an acute flow constriction before [PD1], all pressure sensors quickly show a downward trend in the measured pressure signals. Only by calculating the quotient and the differences in the measured pressure signals and the generation of time trends, a more differentiated pattern of results shows that the temporal trends in the measured pressure signals quotient have a tendency to increase, with the result that trends in differences show no change. The total trends in the measured pressure signals and the trends in the quotients and the trends in the differences in the measured pressure signals now result from the characteristic standard constellation that can be directly attributed to the change in the acute constriction of the standard flow before [PD1] .
The change in the acute flow constriction between [PD1] and the filter, however, is characterized by the fact that in the case of an acute flow constriction between [PD1] and the filter in all pressure sensors, a trend is shown decreasing speed of the measured pressure signals, except for the pressure sensor [PD1], which remains unchanged. The additional calculation of the quotients and the differences between the measured pressure signals and the generation of time trends show, in this case, that the temporal trend of the quotients between the measured pressure signals (PB1, PB2), (PB1, PD2), ( PB2, PD2), (PBM, PD2) and (PD1, PD2) increases, while the time trend of the measured pressure signals quotient (PB1, PD1), (PB1, PDM), (PB2, PD1), ( PB2, PDM), (PBM, PD1) and (PBM, PDM) decreases. In this relationship, the time trends of the differences show another pattern. Here, the difference in time trends (PD1, PD2) increases rapidly, the differences between trends in (PB1, PB2), (PB1, PD2), (PB2, PD2) and (PBM, PD2) remain unchanged, while differences between time trends (PB1, PD1), (PB1, PDM), (PB2, PD1), (PB2, PDM), (PBM, PD1) and (PBM, PDM) decrease rapidly. From all the trends in the measured pressure signals and the trends in the quotients and trends in the differences in the measured pressure signals, they now result from the characteristic standard constellation that can be directly attributed to the change in the acute flow constriction between [PD1] and the filter .
According to the invention, not only are changes detected in the qualitative sense and evaluated, but it is also possible to detect and qualitatively evaluate results that are not a change. In the case of these discoveries, it is also, according to the invention, changes in the system, which do not represent changes, but which, however, may still make sense to detect these results and notify the operator of the treatment system. blood.
Such a conclusion deals, for example, if through a measure coagulation can be reduced. The reduction in coagulation represents, according to the invention, that, for the pressure sensor [PB1] a tendency to decrease the measured pressure signals is determined, while the measured pressure signals of the other pressure sensors have a tendency of time without changes. Through another calculation of the quotients and / or the differences between the measured pressure signals and the generation of temporal trends, a much more differentiated pattern results, which demonstrates that the tendencies of the quotients and / or differences of (PB1, PB2), (PB1, PD1), (PB1, PD2), (PBM, PD1), (PDM, PD2) and (PBM / PDM) decrease, while the time trends of the quotients and / or differences of (PB2, PD1), ( PB2, PD2), (PB2, PDM) and (PD1, PD2) remain unchanged. From all the trends in the measured pressure signals and trends in the quotients and / or trends in the differences in the measured pressure signals, it results in a characteristic standard constellation that can be directly attributed to the "reduced coagulation" conclusion.
Thus, such discoveries represent valuable information for the operator of the blood treatment system, since they can provide, among other things, information on whether a measure initiated has also been successful.
Resistance to transmembrane flow is determined from the difference in pressure signals measured from PB1 and PD2 and / or the ratio from
PB1 and PD2 and / or the difference between PB2 and PD2 and / or the ratio of PD2 and PB2. In addition, changes in pressure ranges APD2 θ / or the relationship between pressure ranges and APBI APD2 θ / or the relationship between pressure ranges and APB2 APD2 and / or the difference between PB1 and PD1 and / or the ratio of PB1 and PD1 and / or the difference of PB2 and PD1 and / or the ratio of PB2 and PD1 and / or the change in pressure range and APBI APD1 and / or the relationship between pressure ranges and APB1APDI and / or the reason that the pressure ranges APB2 and APDI serve as an indicator for resistance to transmembrane flow.
With [PB1] the pressure sensor in the blood circulation is described before the blood enters the TFF tangential flow filter and with PB1 the pressure measured in the pressure sensor [PB1]. With [PB2] the pressure sensor in the blood circulation is described after the blood has left the TFF tangential flow filter and with PB2 the pressure measured in the pressure sensor [PB2]. With [PD1] the pressure sensor in the dialysate circulation is described before the dialysate enters the TFF tangential flow filter and with PD1 the pressure measured in the pressure sensor [PD1]. With [PD2] the pressure sensor in the dialysate circulation is described after the dialysate outlet of the TFF tangential flow filter and with PD2 the pressure measured in the pressure sensor [PD2].
As the PBM or PDM the respective mean value of PB1 and PB2 or PD1 and PD2 is described.
Previous approaches could not differentiate between changes in the direction of blood flow, direction of dialysate flow and transmembrane direction, in which a targeted elimination of changes was not possible. By using a maximum of four pressure sensors and analyzing the pressure signals detected in each of these pressure sensors, all the proportions mentioned above can be monitored. From the total of the indicated pressure, a complete analysis can be performed, which allows to determine the type of target change of the system. Through an adequate analysis of the four pressure signals, the alteration situation can be minimally limited.
Preferably, the pressure signals are determined on the arterial side for the pressure sensor [PB1], as well as for the pressure sensor [PB2]. On the dialysate side, the pressure signals are determined, preferably for the pressure sensor [PD2] and for the pressure sensor [PD1],
In an alternative embodiment, however, it is sufficient if there are pressure signals PB1 and PB2 and one of the signals of PD1 PD2 or on the dialysate side.
The analysis of pressure signals is carried out by means of certain devices which are known to the person skilled in the art from the prior art. The device for analyzing the measured data can be, for example, a cup, which calculates changes in the measured pressure signals to the predetermined reference value and / or changes previously measured from initial values. The analysis can be carried out in the form of absolute and / or relative changes, differences in the measured values, changes in pressure ranges, for example, the height of the ranges and / or the frequency spectrum.
In a preferred embodiment, the analysis of the pressure signals is carried out in a central processing unit. This central processing unit comprises a CPU, an input for the measured pressure values and a display for the measured pressure values and / or the recommendations established for the actions.
The effectiveness of blood treatment depends mainly on four factors: treatment time, blood flow, clearance and dialysate flow. Especially long treatment times must be guaranteed and are an important factor for successful treatment. Numerous studies have shown that the higher the dose administered in dialysis, the lower the mortality of patients (over a wide range of correlation).
Failures due to changes in functioning quickly accumulate to several sessions per year. In extreme cases, sessions should even be interrupted. Much more often, however, are the cases in which the changes are not detected and, therefore, are not eliminated, which leads to a sub-ideal dialysis result. For a targeted elimination of changes, these waiting times are reduced to a minimum, and in some cases, even completely, can be avoided by starting the appropriate measure during the execution operation. The search for the cause of the change is omitted as far as possible and therefore also provides patients with an increased sense of security. Consequently, increases in dialysis efficiency and economic efficiency of dialysis are also improved.
The term "flow properties", as used herein, refers to the entire properties of the respective flowing fluid. The dynamic viscosity, the flow speed, the flow volume, the flow profile, the osmotic pressure, the surface tension, as well as the changes generated by the pumps used are of special interest, as well as the active control elements, such as such as electrical appliances and passive operating elements, such as the pipe system, the dialyzer and the artifacts.
The term "relation", as used here, is not necessarily limited to the quotients of two factors, but it can also understand the difference or other index, with which the "relation" between two elements is expressed.
The analysis of the frequency spectrum of the individual pressure signals also showed that a change in permeability affects the amplitudes of the harmonic frequencies. The same applies to changes in flow in the direction of blood flow.
In a preferred embodiment, the frequency spectrum of the individual signals, as well as the relative variation with respect to a second signal, is determined. By analyzing both frequency spectra, an indication can be made of the flow properties in the direction of the blood flow, the direction of the dialysate flow or the transmembrane direction, in which the blood flow direction and the transmembrane direction are preferred shares.
In another embodiment, the pressure signals of a blood pump are determined to differentiate changes in the system according to the invention.
In another embodiment, the pressure signals of a balance chamber are determined to differentiate the changes in the system according to the invention.
In another embodiment, the method for measuring pressure signals in a blood treatment system increases the efficiency of dialysis and the economic efficiency of dialysis by differentiating between system changes that occur in the direction of blood flow, or in the direction of transmembrane.
In all the methods described here, it is preferable to measure more than two pressure signals and, in particular, four pressure signals at the same time, or in time lagged at the inputs and outputs of the TFF tangential flow filter, as taken by the pressure sensors [PB1], [PB2], [PD1] and [PD2].
The invention also comprises, in addition, a device for measuring pressure signals in a blood treatment device, which increases the efficiency of dialysis and the economic efficiency of dialysis, by differentiating between the system changes that occur in the direction of blood flow, or in the transmembrane direction, which comprises at least two pressure sensors for the measurement of pressure signals.
All the above described modalities and advantages also advantageously refer to the method and device for measuring pressure signals in a blood treatment system, which increases the dialysis efficiency and the economic efficiency of dialysis, by differentiating between the system changes that occur in the blood flow direction or in the transmembrane direction.
The composition of the pressure signals is not significant for the process of the present invention. According to the invention, pressure signals can be used from individual sources, but also pressure signals that represent the sum of a plurality of sources.
In some embodiments, it can be advantageous when, from the sum of the pressure signals, only one is determined or, from the sum of the signaling pressure, only one is filtered in order to determine a valid value for the remaining pressure signals . This can be, for example, the case when a very irregular pressure signal that overlaps the measurement of others, or when a signal of a certain pressure is especially suitable for measurement, due to its properties. Such devices for the correction of pressure signals are well known in the art.
In addition, the object of the present invention is solved by the method according to claim 1.
In a preferred embodiment, the blood on the side of a pressure sensor [PB1] P between a pump and a TFF filter and a pressure sensor plus [PB2] between the filter and the patient TFF 3 are installed on the dialysate side and one pressure sensor [PD2] behind the outlet of the TFF filter and a pressure sensor plus [PD1], before the entrance to the TFF filter are installed.
In another embodiment of the apparatus according to the invention, it comprises a device for analyzing the measured data. This can be a CPU that calculates the changes in the measured pressure signals with the predetermined reference values and / or changes previously measured in the initial values.
In a preferred embodiment, the blood treatment device comprises a TFF tangential flow filter, a P pump and at least two pressure sensors ([PB1], [PB2] or [PD1], [PD2] or [PB1 ], [PD1] or [PB1], [PD2] or [PB2], [PD1] or [PB2], [PD2]), where the pressure sensors ([PB1], [PB2] or [PD1], [PD2] or [PB1], [PD1] or [PB1], [PD2] or [PB2], [PD1] or [PB2], [PD2]) are located directly upstream and / or downstream directly to TFF tangential flow.
In another preferred embodiment, the blood treatment device comprises a TFF tangential flow filter, a P pump and at least three pressure sensors ([PB1], [PB2], [PD1] or [PB1], [ PB2], [PD2] or [PD1], [PD2], [PB1] or [PD1], [PD2], [PB2]), where the pressure sensors ([PB1], [PB2], [PD1] or [PB1], [PB2], [PD2] or [PD1], [PD2], [PB1] or [PD1], [PD2], [PB2]) are located directly upstream and / or downstream directly to the Tangential flow TFF.
Even more preferred is a blood treatment device comprising a TFF tangential flow filter, a P pump and four pressure sensors [PB1], [PB2], [PD1] and [PD2], where the pressure sensors [PB1], [PD1] are located directly upstream of the TFF tangential flow filter and the pressure sensors [PB2], [PD2] are located immediately downstream of the TFF tangential flow filter.
When at least one pressure signal is used, which must be registered in several successive periods of time, in order to relate them successively in the form of a quotient or in the form of a difference, and stop, in a second stage calculation, relate that specific sensor quotient or this difference with other sensor specific quotient or other differences, the following steps of the method are represented (method 2): a) Time-lapse measurement of the respective at least two pressure signals in at least two pressure sensors, where the pressure signals are selected from the group consisting of PB1, PB2, PD1 and PD2, the pressure sensors are selected from the group consisting of [PB1], [PB2], [ PD1] and [PD2], [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure signal measured in [PB1], [PB2] designates the pressure sensor in the bloodstream after After the blood flow from the TFF and PB2 tangential flow filter designates the pressure signal measured in [PB2], [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF tangential flow filter and PD1 designates the pressure signal measured in [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after the dialysate exits from the tangential flow filter TFF and PD2 designates the pressure signal measured in [PD2]; b) Calculation of at least two quotients and / or differences from the pressure signals measured with time lag in the same pressure sensor according to step a) in a central processing unit, in which the quotients calculated in such a way according to with the pressure sensor on which the measurement was performed they are designated as Q [PB1], Q [PB2], Q [PD1] and Q [PD2] and the differences as Δ [PB1], Δ [PB2], Δ [PD1 ] and Δ [PD2]; c) Calculation of at least one quotient and / or at least one difference in the central processing unit from the quotients and / or differences calculated according to step b), in which the quotients and differences are selected from the group consisting of (Q [PB1], Q [PB2]) and / or (Q [PB1], Q [PD1]) and / or (Q [PB1], Q [PD2]) and / or (Q [PB2], Q [PD1]) and / or (Q [PB2J, Q [PD2]) and / or (Q [PD1], Q [PD2]) and / or (Δ [PB1], Δ [PB2]) and / or ( Δ [PB1], Δ [PD1]) and / or (Δ [PB1], Δ [PD2]) and / or (Δ [PB2], Δ [PD1]) and / or (Δ [PB2], Δ [PD2 ]) and / or (Δ [PD1], Δ [PD2]) and / or (Q [PB1], (Δ [PB1]) and / or (Q [PB1], (Δ [PB2]) and / or ( Q [PB1], (Δ [PD1]) and / or (Q [PB1], (Δ [PD2]) and / or (Q [PB2], (Δ [PB1]) and / or (Q [PB2], (Δ [PB2]) and / or (Q [PB2], (Δ [PD1J) and / or (Q [PB2], (Δ [PD2]) and / or (Q [PD1], (Δ [PB1]) and / or (Q [PD1], (Δ [PB2]) and / or (Q [PD1], (Δ [PD1]) and / or (Q [PD1], (Δ [PD2]) and / or (Q [PD2], (Δ [PB1]) and / or (Q [PD2], (Δ [PB2]) and / or (Q [PD2], (Δ [PD1]) and / or (Q [PD2], ( Δ [PD2]) and / or (Q [PB1], Q [PBM]) and / or (Q [PB2], Q [PBM]) and / or (Q [PD1], Q [PBM]) and / or (Q [PD2], Q [PBM]) and / or (Δ [PB1], Q [P BM]) and / or (Δ [PB2], Q [PBM]) and / or (Δ [PD1], Q [PBM]) and / or (Δ [PD2], Q [PBM]) and / or (Q [PB1], Q [PDM]) and / or (Q [PB2], Q [PDM]) and / or (Q [PD1], Q [PDM]) and / or (Q [PD2], Q [PDM] ) and / or (Δ [PB1], Q [PDM]) and / or (Δ [PB2], Q [PDM]) and / or (Δ [PD1], Q [PDM]) and / or (Δ [PD2] ], Q [PDM]) and / or (Q [PB1], Δ [PBM]) and / or (Q [PB2], Δ [PBM]) and / or (Q [PD1], Δ [PBM]) and / or (Q [PD2], Δ [PBM]) and / or (Δ [PB1], Δ [PBM]) and / or (Δ [PB2], Δ [PBM]) and / or (Δ [PD1], Δ [PBM]) and / or (Δ [PD2], Δ [PBM]) and / or (Q [PB1], Δ [PDM]) and / or (Q [PB2], Δ [PDM]) and / or (Q [PD1], Δ [PDM]) and / or (Q [PD2], Δ [PDM]) and / or (Δ [PB1], Δ [PDM]) and / or (Δ [PB2], Δ [ PDM]) and / or (Δ [PD1], Δ [PDM]) and / or (Δ [PD2], Δ [PDM]) and / or (Q [PBMJ, Q [PDM]) and / or (Q [ PBM], Δ [PBM]) and / or (Q [PBM], Δ [PDM]) and / or (Q [PDM], Δ [PBM]) and / or (Q [PDM], Δ [PDM]) and / or (Δ [PBM], Δ [PDM]) and where Q [PBM] designates the average value from Q [PB1] and Q [PB2], Q [PDM] designates the average value from Q [PD1] and Q [PD2], Δ [PBM] designates the average value from Δ [PB1] and Δ [PB2], Δ [PDM] designates the average value from Δ [PD1] and Δ [PD2] ; d) At least one time-lapse repetition of steps a), b) c), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; e) Generation of at least one time trend from the measured pressure signals selected from the groups listed in c); f) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; g) Generation of a standard for the evaluation of at least one time trend; h) Assignment of the standard to a change table and i) Display of the change on a central processing unit display device. This embodiment is simply a complement to the main method previously described of the present invention. In this case, the calculation step of the method described above is preceded only by the measurement step with time lag in at least two pressure sensors. With this alternative method, some changes in the dialysis process, which can be located and detected using the first method, can be displayed more precisely, in case of doubt. For the sake of clarity, the quotients calculated in this additional calculation step according to the pressure sensor, in which they were generated, are designated as Q [PB1], Q [PB2], Q [PD1] and Q [PD2] and differences such as Δ [PB1], Δ [PB2], Δ [PD1] and Δ [PD2]. It is understood that only the combinations can be calculated, which are the most logical possible from the pre-selection of the number of measurement repetitions and the number of pressure sensors, in order to carry out the method according to the invention. Optionally, this method may additionally comprise the following step: j) Elimination of the change in flow resistance in the transmembrane direction, direction of flow of the dialysate or direction of blood flow or indication of a possibility for eliminating the change. Regarding steps i) and j), the same described above, similarly, applies to method 1.
Tolerance margins for assessing the time trends of the measured pressure signals and / or quotients and / or differences from the pressure signals can now be deposited in the central processing unit. These time trends in the measured pressure signals and / or quotients and / or differences in the pressure signals can come from one or more previous sessions of a given patient with this specific dialysis device. Eventually, however, this patient's measurement values can also be used by other dialysis devices. Likewise, measurement values for this specific dialysis device, which are not specific to the patient. This can also be, from the literature, known guideline values or typical specifications of the device of the dialysis device manufacturer.
By "directly" it is thought that there is no other component between the pressure sensor and the mentioned component. The actual distance between the pressure sensor and the mentioned component is not decisive here, but it does mean that the pressure sensor and the mentioned component are not separated by another component that is located between them. According to the invention, two pressure sensors are never directly behind each other, therefore, without another component between the pressure sensors. In addition, the present invention does not use a pressure sensor for blood circulation between patients (S and P pump, as pressure sensors of this nature are used to monitor the patient and are not suitable for monitoring system changes in the TFF tangential flow filter.
In other preferred embodiments, however, on the arterial side, a bubbler can be arranged between the pressure sensor and the component, and / or a filter can be arranged on the dialysate side. The basic principle described earlier, however, is not called into question.
The terms “upstream” and “downstream” must be understood in relation to the flow direction. If a pressure sensor is "upstream", it is located in the direction of flow in front of the component, that is, the blood or dialysate first through the pressure sensor and then through the component. If a pressure sensor is "downstream", then it is located in the direction of flow behind the component, that is, the blood or dialysate passes through the component first and then through the pressure sensor. The direction of flow can be in the blood circulation and the dialysate flow, contrary to each other.
The device according to the invention for the treatment of blood may additionally comprise a UFP ultrafiltration pump, a BK balance chamber system or BK balance chamber and / or a unit for analyzing the measured pressure signals. The ultrafiltration pump is required for continuous controlled ultrafiltration and removes a precise amount of fluid from the closed system. The same amount that is removed from the dialysate flow is removed in the TFF tangential flow filter from the blood by means of low pressure. The balance chamber is responsible for balancing the inflow and outflow circulations, so it is guaranteed that no fluid is removed from the patient or accidentally delivered to the patient. The balance chamber can be divided by a flexible separation wall into two chamber halves, which are alternately filled with the ultrafiltrate which is removed from the dialysate circulation, in which the contents of the respective other chamber half are discarded. Optionally, the device according to the invention additionally comprises a drip chamber. The drip chamber will help prevent air from entering the downstream tubes through a layer of fluid that acts as an air blocker at the bottom of the drip chamber.
The pressure sensors [PB1], [PB2], [PD1] and [PD2] are advantageously characterized by the fact that they have a sample rate of at least 20 Hz. A sample rate of 20 Hz means that a measurement of pressure by pressure sensor is performed 20 times per second.
The terms "on the dialysate side" and "on the arterial side" describe the two circulations that are passed along one another in the tangential flow filter, usually through the countercurrent principle; however, if necessary, together and parallel to the blood flow. They are introduced into the hollow fibers of the filter membrane, through a first circulation of blood / plasma fluid, which passes through them slowly. Through a second fluid circulation, the dialysate is supplied to the outside of the hollow fibers. Both circulations are separated from each other and are in contact with each other through the filter membrane.
The term “tolerance margin” refers to a range around an assumed desired value of a pressure signal, at a given pressure measurement point, at a given time during treatment, within which deviations from the expected value can be tolerated. This margin of tolerance is determined before the start of the dialysis session, but it can also be determined as a manufacturer-specific brand. Here, these can be absolute values, or a percentage or absolute range around an expected value, where the expected value is determined during the dialysis session, retrieved from the data stored in the central processing unit or supplied in advance. Measured values that fall within such a determined tolerance range are described as "remained unchanged".
The term "standard", as used here, refers to a form of mathematical, electronic and / or graphical representation of the trend of various quotients and / or differences and / or absolute values of pressure signals over time. From these standards, the assessment “increases rapidly”, “increases”, “remains unchanged”, “decreases” or “decreases rapidly” can be derived directly.
The term “any possible pattern” means that only a few of these patterns can occur through changes in the operation in a blood treatment unit. Other standards cannot occur due to logical reasons or would be caused by a failure in the system, which is unrelated to the invention, such as the malfunction of a pressure measuring device. Such a constellation should not be covered by the term "any possible pattern" and do not require, in the present invention, any consideration.
The term “pattern table” refers to a mathematical, electronic and / or graphical record or a corresponding matrix, in which for each conceivable combination of evaluations “increases”, “remains unchanged” or “decreases” to up to four measurement points, an indication of the discovery of the change and a proposed measure for its elimination are stored. In preferential modalities, not only a qualitative indication of the possible change is mentioned in the table of standards, but also a measure or a formula to calculate, from the measurement values, the pressure signals whose scope the variable parameters must be readjusted. in the blood treatment unit. In other preferred modalities, after an alignment of the pattern generated from the current pressure signals with the pattern table, the recommended qualitative and / or quantitative adjustment is performed automatically. For this, it is necessary to transmit the adjustment measurement from the central processing unit to at least one actuator in the blood treatment unit, in order to fulfill the necessary adjustment measurement.
The elimination of a change in resistance to flow in the direction of the transmembrane may consist of regulation of blood flow, regulation of the flow of dialysate, coordinated control of the flow of blood and dialysate, a process of transmembrane purging, a process of purge on the arterial side, a change in the treatment time, a regulation of the ultrafiltration rate, a combination of the above or a change of the filter module. The filter module can be changed only by interruption or after the end of the dialysis session. All other measures can be induced online during the dialysis session.
The elimination of a change in flow resistance in the direction of blood flow may consist of a regulation of blood flow, a regulation of the flow of dialysate, a coordinated control of the flow of blood and dialysate, a dilution of blood before the filter ( pre-dilution), an arterial side purge, a transmembrane purge, anticoagulant addition, a change in treatment time, a regulation of the ultrafiltration rate, a combination of the above or an exchange of at least one tube or a pipe system.
Changing a tube or tube system can be done only by interruption or after the end of the dialysis session. Occasionally, a change may consist of the flexing or collapse of one or more tubes. These errors can generally be eliminated relatively easily, depending on the type of dialysis device. As in the previous case, however, most other measures can be induced online, during the dialysis session.
A schematic flow system with the following components is shown in Figure 1. The P pump, preferably a peristaltic pump, generates the expected flow in the extracorporeal circulation. In the bloodstream, as shown in broken lines, the patient's blood at 3 passes through the P pump first, then through the pressure sensor on the first arterial side [PB1], the TFF tangential flow filter and before it flows back to patient 3 via another pressure sensor [PB2]. By the countercurrent principle, the dialysate is pumped through the TFF filter. In dialysis practice, as shown in the solid lines, there is no first dialysate pressure sensor [PD1] in the flow direction, before the TFF filter and the second pressure sensor [PD2] after the TFF filter. For the balance of the inflows and outflows of the BK balance chamber, it is provided, thus, it is ensured that no liquid is removed from the patient or that it is provided unintentionally. The weight loss prescribed for the therapy is produced by the UFP ultrafiltration pump, which bypasses the BK balance chamber.
The pressure progress of pressure PB1, PB2 and PD2, under different treatment conditions can be understood from Figure 2. A and B are the pressure curves of a high permeability dialyzer at UF = 0 (A) and UF> 0 (B). C and D are the pressure curves of a dialyzer with low permeability at UF = 0 (C) and UF> 0 (D). The dialyzer geometry (length of the fibers, the inner diameter of the fiber and the number of fibers) remains constant. A signal at PB1 the pressure is shown before the dialyzer. It is in amplitude and the absolute value of the strongest signal. PB2 and PD2 are in their amplitude and the absolute value is less than the latter. It is also shown that the signals are phase shifted against PB1, but have no phase shift between them.
Comparing the signs of A with those of B, it is shown that the phase has not changed. The pressure situation PB1 and PB2 is unchanged. The absolute value of PD2 is, however, lower and the amplitude of PB1 is reduced, which can be explained by the increase in the UF rate. The change impressed with the pressure signal PD2 is generated, in this case, by the UF pump, a gear pump.
Comparing C and D with each other, it is shown that the increase in UF rate has the same effects. High frequency pulses occur at PD2, especially at UF> 0, and are, in turn, caused by the UF pump.
Comparing the different permeabilities and the same UF rates, it is shown that the amplitudes of the arterial side (in PB1 and PB2) are greater in less permeability. The reason is that the lack of transfer to the dialysate side, which is caused by an increase in resistance to transmembrane flow, must be compensated for by an increase in pulse amplitudes on the arterial side.
The pressure progress for PB1, PB2 and PD1 pressures at a blood flow of 100 ml / min. is shown in figure 3. The pressure curves were, in each case, compared to a sine function, whose minima coincide with the minima of the pressure signal. Thus, the periodicity, the basis for calculating the phase shift, as well as the frequency analysis are clear.
The function with which the sine function has been adjusted is: G = A ■ sin (2 • π • f -t + q>) + B (A: amplitude in mm Hg, f. Frequency in Hz, t: time, cp : initial phase in rad, B: Offset).
The frequency analysis is shown, for example, in a pressure signal from PB1 (Fig. 4). The progress of the pressure signal corresponds to that of Figures 2 AD. In the graph above the progress over time 60 s is shown. The graph of an average section of the corresponding frequency spectrum is plotted. The graph below shows the relationship between the amplitude of the pressure signal spectrum for different PBE permeabilities. The reduction in permeability increases the frequency range of the pressure receiver [PB1] on the arterial side. This is particularly evident for the base oscillation, as well as for the first higher orders.
The invention also relates to a device that is capable of carrying out the above-described method of measurement and adjustment measures. Such a device is a blood treatment system.
A "blood treatment system", as used herein, comprises a blood treatment unit, the central point of which is a TFF tangential flow filter with at least two pressure sensors, which are selected from the group consisting of in [PB1], [PB2], [PD1] and [PD2], and a central processing unit, in which at least two pressure sensors are connected with the central processing unit for the transmission of the measured values and the unit central processing is able to analyze and present the measured input values in such a way that a differentiation of resistance flow changes in transmembrane direction, dialysate flow direction and blood flow direction is possible in the blood treatment system.
Thus, the invention also relates to a device that comprises the following:
The blood treatment unit and at least two pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] represents the pressure sensor in the blood circulation before the blood enters the TFF tangential flow filter, [PB2] represents the pressure sensor in the blood circulation after the blood exits from the TFF tangential flow filter, [PD1] represents the dialysate circulation pressure sensor before the dialysate entry for the TFF tangential flow filter and [PD2] represents the circulation pressure sensor after the TFF dialysate flow and a central processing unit filter, where the device is suitable for performing a method for differentiating changes in flow resistance from a blood treatment with a TFF tangential flow filter unit, which comprises the following steps; a) Measurement of at least two pressure signals selected from the group consisting of (PB1, PB2, PD1, PD2), which are measured on at least two pressure sensors, which are selected from the group consisting of [ PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure measured at the pressure sensor [ PB1], where [PB2] designates the pressure sensor in the bloodstream after the blood flows from the TFF tangential flow filter and PB2 designates the pressure measured at the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF and PD1 tangential flow filter designates the pressure measured in the pressure sensor [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after leaving the dialysate a from the tangential flow filter TFF and PD2 designates the pressure measured in the sens pressure value [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2.PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
In addition, the invention also relates to a device, which comprises the following: a blood treatment unit and at least three pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor into the bloodstream before blood enters the TFF tangential flow filters, [PB2] designates the pressure sensor into the bloodstream after blood is drawn out. from the TFF tangential flow filter, [PD1] designates the dialysate circulation pressure sensor before the dialysate enters the TFF tangential flow filter and [PD2] designates the dialysate flow pressure sensor after the dialysate circulation a from the TFF tangential flow filter and consists of a central processing unit, where the device is suitable for carrying out a method for differentiating changes in flow resistance in a blood treatment unit with a TF tangential flow filter F, which comprises the following steps: a) Measurement of at least two pressure signals selected from the group consisting of (PB1, PB2, PD1, PD2), which are measured on at least two pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF and PB1 tangential flow filter designates the pressure measured at the pressure sensor [PB1], where [PB2] designates the pressure sensor in the bloodstream after the blood flows from the tangential flow filter TFF and PB2 designates the pressure measured at the pressure sensor [PB2 ], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF tangential flow filter and PD1 designates the pressure measured in the pressure sensor [PD1] and [PD2] designates the pressure sensor in the circulation of the dialysate after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured at the pressure sensor [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
In addition, the invention also relates to a device, which comprises the following: a blood treatment unit and four pressure sensors [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the blood pressure sensor before the blood enters the TFF tangential flow filters, [PB2] designates the blood pressure sensor after the blood exits from the TFF tangential flow filter, [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF tangential flow filter and [PD2] designates the pressure sensor in the dialysate circulation after the dialysate exits from the TFF tangential flow filter and consists of a central unit process, in which the device is suitable for carrying out a method for differentiating changes in flow resistance in a blood treatment unit with a TFF tangential flow filter, which comprises the following steps: a) Measurement of at least qu pressure signals (PB1, PB2, PD1, PD2), which are measured in four pressure sensors [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor in the blood circulation before blood enters the tangential flow filter TFF and PB1 designates the pressure measured in the pressure sensor [PB1], where [PB2] designates the pressure sensor in the blood circulation after the blood flows from the filter tangential flow TFF and PB2 designates the pressure measured at the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the tangential flow filter TFF and PD1 designates the pressure measured at the sensor pressure [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after the dialysate exits from the tangential flow filter TFF and PD2 designates the pressure measured in the pressure sensor [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2.PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least two pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
In preferred embodiments, said blood treatment system further comprises an ultrafiltration pump and / or a balance chamber system.
According to the invention, the pressure sensors [PB1], [PB2], [PD1] and [PD2] have, in the case of the present blood treatment system, respectively, a sampling rate of at least 20 Hz. DESCRIPTION OF THE FIGURES
Figure 1: Scheme for a flow system of the type according to the invention Figures 2 AD: Pressure progress of pressures PB1, PB2 and PD2 under different treatment conditions: 2A: Pressure behavior at high permeability and UF = 0 2B: Pressure behavior at high permeability and UF> 0 2C: Pressure behavior at low permeability and UF = 0 2D: Pressure behavior at low permeability and UF> 0 Figure 3: Pressure progress for pressures PB1, PB2 and PD1 in a flow of blood of 100 ml / min. Sine function adjusted to it. Figure 4: Frequency analysis of pressure signal PB1 Figure 5: Signal PD2 at high permeability (above). Comparison of the frequency spectrum at high and low permeability (below). Figure 6: Pattern constellations for pressure changes that occur (absolute and quotient pressures) + increases ++ increases rapidly - decreases - decreases rapidly 0 remains unchanged Figure 7: Constellations of patterns for pressure changes that occur (absolute pressures and differences ) + increases ++ increases rapidly - decreases - decreases rapidly 0 remains unchanged EXAMPLES Example 1:
Analysis of the pressure pulse amplitudes: A periodic pressure progress is divided into individual pressure pulses and the amplitude of each pulse is determined from the minimum and maximum value. For this purpose, the periodic minimums of pressure progress are generated. As a pressure pulse a section of one minimum is considered for the next. The amplitude of the periodic pressure pulses is determined by the structure of the blood pump and the blood flow (BF). The pulse amplitude is the same for all pressures and ultrafiltration rates (UF rates) in fixed CR, which, however, increase with increasing CR. The maximum and minimum pressure are read for each pulse. The amplitude is given by the difference of these extreme values. The APDI / APBI and APD2 / APBI relationships, as well as APDI / APB2θ APD2 / APB2 show an evident increase with increasing fiber permeability. This is quite clearly recognized in Figure 2. With increasing BF the pressure pulses increase, but the relationships remain essentially constant. An increase in the UF rate has the same effects on the pressure ratio, as does the permeability described above. In both cases the amount of transmembrane transfer is improved. A change in resistance in the direction of blood flow is reflected, as expected, in a decrease in amplitude behavior from APB2 / APB2- Once the attenuation in the direction of flow is increased, APB2 falls. As expected, the amplitudes thus increase on the dialysate side, just like the dependent behaviors mentioned. The same behavior is shown in the reverse direction, when pulses are generated on the dialysate side, for example, through a balance system to compensate for ultrafiltration. Thus, even these pulses can be used to characterize the system, both in the direction of transmembrane flow and also in the direction of flow of the dialysate. Example 2:
Analysis of the phase shift of pressure signals
The pressure progress can be very close to the minimum positions through a sine function with fixed frequency and phase shift. The frequency is identical for the respective pressures and is determined by the blood flow and the blood pump that periodically works, as a rule, a peristaltic pump. The inverse value of the frequency corresponds to the time span of an individual pressure pulse. Among the individual pressure advances, a phase shift is available, which depends, among others, on permeability. The fill level of the bubbler and the length of the pipe system also have an influence and must therefore be kept constant during measurements. In decreasing permeability the phase shift from PB1 to PD1 and PD2 becomes greater, while decreasing from PB1 to PB2.
When using a high-flow dialyzer (dialysis filters) with a hydraulic permeability of 275 ml / (h m2 mm Hg), both PB2 and PD2 are displaced around 0.53 rad against PB1 (see figure 3) . If the permeability is changed to that of a low flow dialyzer (14 ml / (h m2mmHg)), PB2 is displaced against PB1 around 0.38 rad and PD2 is displaced in phase against PB1 around 0.65 rad . This comes about as a result of the changed flow resistances in the respective directions. Example 3:
Analysis of the frequency spectra of pressure signals
The bases of the calculation are the values of the complex amplitudes | cn | of individual Fourier terms for the different frequencies as
(i = imaginary unit, n = numerical parameter, f = frequency, t = time).
The amplitude values are standardized on the vector length, proportionally in relation to the recording duration of the signal to be transformed, in order to produce a comparability.
The frequency spectra have a steady progress and show the maximum amplitude in base frequency and in its multiple integers. The frequencies depend on the blood flow. A doubling of blood flow from 100 ml / min to 200 ml / min leads, for example, to a doubling of the base frequency from about 0.27 Hz to 0.54 Hz. The amplitude value | cn | it is higher for BP1 and PB2 pressures on the arterial side with decreasing permeability and behave inversely for pressures (PD1 and PD2) on the dialysate side.
Figure 4 shows how the permeability change described in example 2 acts on the spectrum of the pressure signal PB1. This is represented in an analogous way in figure 5 for PD2. Example 4:
Detection of a change in the form of a constriction in the tube system between [PB 11 and the filter in a blood treatment system
After starting treatment with a dialysis device, after 5 minutes of session time, the following pressure signals PB1 = 148 mmHg, PB2 = 61 mmHg, PD1 = 90 mmHg and PD2 = 83 mmHg can be measured on the sensors [PB1] , [PB2], [PD1] and [PD2], Measurement takes place with pressure sensors that have a sampling rate of 20 Hz.
After 30 minutes, the pressure signal in [PB1] suddenly increases within seconds at 207 mmHg, while all other pressure signals remain constant. This also reflects an increase in transmembrane pressure (TMP) from 18 to 48. This could be misinterpreted by the specialist as an evident worsening of the filter's permeability, for example, as the formation of a secondary membrane, as he trusts in the TMP.
Consideration of the totality of the measured pressure signals and of the quotients and / or of the differences of the time trends shows, in contrast, that all pressure sensors present an unaltered trend of the measured pressure signals, except the pressure sensor [PB1], the which has a rapidly increasing trend, from 148 mmHg to 207 mmHg. The other calculation of the quotients and differences in the measured pressure signals and the generation of time trends show, in this case, that the temporal trends of the measured pressure signals quotients (PB1, PB2), (PB1, PD1), (PB1, PD2), (PB1, PDM), (PBM, PD1), (PBM, PD2) and (PBM, PDM) increase rapidly, while the time trends of the measured pressure signal quotients (PB2, PD1), (PB2 , PD2), (PB2, PDM) and (PD1, PD2) remained unchanged.
From this pattern, comprising the trends in the measured pressure signals and the trends in the quotients and / or differences in the measured pressure signals, it becomes immediately clear that the change in the permeability of the filter cannot be the cause for the change, but rather that there must have been a constriction in the pipe system between [PB1] and the filter. A change in the permeability of the filter can be ruled out, since especially the trends in the pressure signal quotients measured from (PB2, PD1), (PB2, PD2) and (PB2, PDM) should also have increased and that this it should occur additionally and as a whole for a rapid increase in all trends. This, however, is not the case in the present change, in which a change in the form of a secondary membrane formation can be excluded. This avoids a misinterpretation of the change, and the change is detected in the right place and is determined qualitatively. Example 5:
Detection of a change in the form of a venous needle constriction After starting treatment with a dialysis device, after 5 minutes of session time, the following pressure signs PB1 = 155 mmHg, PB2 = 68 mmHg, PD1 = 88 mmHg and PD2 = 77 mmHg can be measured on the pressure sensors [PB1], [PB2], [PD1] and [PD2]. The measurement takes place with pressure sensors that have a sampling rate of 20 Hz.
During treatment, pressure signs increase on the arterial side PB1, from 155 mmHg to 178 mmHg, and PB2, from 68 mmHg to 91 mmHg. The signs also increase on the dialysate side. PD1, from 88 mmHg to 111 mmHg, and PD2, from 77 mmHg to 100 mmHg.
The other calculation of the quotients and the differences in the measured pressure signals and the generation of time trends shows, in this case, that the temporal trends of the quotients of all the pressure signals have a decreasing trend, whereas the temporal trends of the differences in pressure all pressure signals have a trend that remains unchanged. This alteration picture corresponds to a constriction in the venous needle and is detected according to the invention.
In the case of a constriction in the venous needle, the characteristics of the filter do not change, however, the dialysis machine still adjusts the pressures on the dialysate side around the same value, since the ultrafiltration flow must be kept constant. The TMP also remains constant. Likewise, all other relationships, which result from the differentiation framework, since all values change equally in absolute terms. However, since the relative changes are of different sizes for each of the pressure signals, the quotients increase, which are formed from the pressure signals. This becomes especially evident when considering the TMP (PBM - PDM) and the quotients from the pressure on the arterial side and on the dialysate side. TMP (anterior) = The difference from PBM - PDM = 29 mmHg TMP (posterior) = The difference from PBM - PDM = 29 mmHg
The quotient from PBM (previous) I PDM (previous) = 1.35
The quotient from PBM (posterior) I PDM (posterior) = 1.27 By observing the quotient trends and differences, the constriction in the venous needle is identified early enough as a coagulation of the return blood flow to the patient, in which an imminently critical situation can be avoided by means of a tightly closed return flow, which, otherwise, would have remained ignored. List of reference codes: PB1 Pressure measured at the pressure sensor (PB1) PB2 Pressure measured at the pressure sensor (PB2) PD1 Pressure measured at the pressure sensor (PD1) PD2 Pressure measured at the pressure sensor (PD2) [PB1, PB2 , PD1, PD2]: Pressure sensors [PB1] Pressure sensor on the arterial side in front of the tangential flow filter [PB2] Pressure sensor on the arterial side behind the tangential flow filter [PD1] Pressure sensor on the dialysate side in front of the tangential flow filter [PD2] Pressure sensor on the dialysate side behind the tangential flow filter APBI Pressure range PB1 measured at the pressure sensor (PB1) APB2 Pressure range PB2 measured at the pressure sensor (PB2) APDI Pressure range PD1 measured at the pressure sensor (PD1) APD2 Pressure range PD1 measured at the pressure sensor (PD2) UFP Ultrafiltration pump P TFF pump Tangential flow filter © Patient BK Balance chamber

权利要求:
Claims (9)
[0001]
1. Method for differentiating changes in flow resistance in a blood treatment system, characterized by the fact that it comprises the following steps: a) Measurement of at least three pressure signals selected from the group consisting of (PB1, PB2, PD1, PD2), which are measured on at least three pressure sensors, which are selected from the group consisting of [PB1], [PB2], [PD1] and [PD2], where [PB1] designates the pressure sensor in the blood circulation before blood enters the TFF and PB1 tangential flow filter designates the pressure measured in the pressure sensor [PB1], where [PB2] designates the pressure sensor in the blood circulation after blood is flowing out from the tangential flow filter TFF and PB2 designates the pressure measured in the pressure sensor [PB2], where [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the tangential flow filter TFF and PD1 designates the pressure measured at the pressure sensor [PD1] and [ PD2] designates the pressure sensor in the dialysate circulation after leaving the dialysate from the tangential flow filter TFF and PD2 designates the pressure measured in the pressure sensor [PD2]; b) Calculation of the quotients and / or differences from the pressure signals measured according to step a), in which the quotients and / or differences are calculated from the pressure signals selected from the group consisting of (PB1 , PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM ) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM) in a central processing unit, where the respective average value is designated with PBM or PDM from (PB1, PB2) or (PD1, PD2); c) At least one time-lapse repetition of steps a) and b), in which at least three pressure sensors, as in the previous measurement, are measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; d) Generation of at least one time trend from the measured pressure signals, selected from the group consisting of (PB1, PB2, PD1, PD2) and / or the calculated differences and / or quotients of the pressure signals (PB1, PB2) and / or (PB1, PD1) and / or (PB1, PD2) and / or (PB2, PD1) and / or (PB2, PD2) and / or (PD1, PD2) and / or (PB1, PDM) and / or (PB2, PDM) and / or (PD1, PBM) and / or (PD2, PBM) and / or (PDM, PBM); e) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; f) Generation of a standard for the evaluation of at least one time trend; g) Assigning the standard to a change table and h) Displaying the change on a display device of the central processing unit.
[0002]
2. Method according to claim 1, characterized by the fact that the at least three pressure signals can be, respectively, absolute pressures, relative pressures, absolute pressure differences between two pressure measurement points, relative pressure differences between two pressure measurement points, absolute pressure ranges, relative pressure ranges, differences between the absolute pressure ranges at the two pressure measurement points or differences between the relative pressure ranges at the two pressure measurement points or a combination of these.
[0003]
3. Method according to claim 1, characterized by the fact that the at least three pressure signals, respectively, are determined from the analysis of the frequency spectrum of the blood flow.
[0004]
4. Method for differentiating changes in flow resistance in a blood treatment system, characterized by the fact that it comprises the following steps: a) Time-lapse measurement of the respective at least three pressure signals (PB1, PB2, PD1 or PD2 ) on at least three pressure sensors (PB1], [PB2], [PD1] or [PD2]), where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filter and PB1 designates the pressure measured at the pressure sensor [PB1], [PB2] designates the pressure sensor in the bloodstream after the blood flows out of the tangential flow filter TFF and PB2 designates the pressure measured at the pressure sensor [PB2] , [PD1] designates the pressure sensor in the dialysate circulation before the dialysate enters the TFF tangential flow filter and PD1 designates the pressure measured in the sensor [PD1] and [PD2] designates the pressure sensor in the dialysate circulation after the dialysate output from the tan flow filter TFF and PD2 designates the pressure measured at the pressure sensor [PD2]; b) Calculation of at least two quotients and / or differences from the pressure signals measured with time lag in the same pressure sensor according to step a) in a central processing unit, in which the quotients calculated in such a way according to with the pressure sensor on which the measurement was performed they are designated as Q [PB1], Q [PB2], Q [PD1] and Q [PD2] and the differences as Δ [PB1], Δ [PB2], Δ [PD1 ] and Δ [PD2]; c) Calculation of at least one quotient and / or at least one difference in the central processing unit from the quotients and / or differences calculated according to step b), in which the quotients and / or differences are selected from of the group consisting of (Q [PB1], Q [PB2]) and / or (Q [PB 1], Q [PD1]) and / or (Q [PB1], Q [PD2]) and / or (Q [ PB2], Q [PD1]) and / or (Q [PB2], Q [PD2]) and / or (Q [PD1], Q [PD2]) and / or (Δ [PB1], Δ [PB2]) and / or (Δ [PB 1], Δ [PD1]) and / or (Δ [PB1], Δ [PD2]) and / or (Δ [PB2], Δ [PD1]) and / or (Δ [PB2 ], Δ [PD2]) and / or (Δ [PD1], Δ [PD2]) and / or (Q [PB1], (Δ [PB 1]) and / or (Q [PB1], (Δ [PB2] ]) and / or (Q [PB1], (Δ [PD1]) and / or (Q [PB1], (Δ [PD2]) and / or (Q [PB2], (Δ [PB1]) and / or (Q [PB2], (Δ [PB2]) and / or (Q [PB2], (Δ [PD1]) and / or (Q [PB2], (Δ [PD2]) and / or (Q [PD1] , (Δ [PB1]) and / or (Q [PD1], (Δ [PB2]) and / or (Q [PD1], (Δ [PD1]) and / or (Q [PD1], (Δ [PD2] ]) and / or (Q [PD2], (Δ [PB 1]) and / or (Q [PD2], (Δ [PB2]) and / or (Q [PD2], (Δ [PD1]) and / or (Q [PD2], (Δ [PD2]) and / or (Q [PB 1], Q [PBM]) and / or (Q [PB2], Q [PBM]) and / or (Q [PD1] , Q [PBM]) and / or (Q [PD2], Q [PBM]) and / or (Δ [P B 1], Q [PBM]) and / or (Δ [PB2], Q [PBM]) and / or (Δ [PD1], Q [PBM]) and / or (Δ [PD2], Q [PBM] ) and / or (Q [PB1], Q [PDM]) and / or (Q [PB2], Q [PDM]) and / or (Q [PD1], Q [PDM]) and / or (Q [PD2] ], Q [PDM]) and / or (Δ [PB 1], Q [PDM]) and / or (Δ [PB2], Q [PDM]) and / or (Δ [PD1], Q [PDM]) and / or (Δ [PD2], Q [PDM]) and / or (Q [PB1], Δ [PBM]) and / or (Q [PB2], Δ [PBM]) and / or (Q [PD1] , Δ [PBM]) and / or (Q [PD2], Δ [PBM]) and / or (Δ [PB1], Δ [PBM]) and / or (Δ [PB2], Δ [PBM]) and / or (Δ [PD1], Δ [PBM]) and / or (Δ [PD2], Δ [PBM]) and / or (Q [PB1], Δ [PDM]) and / or (Q [PB2], Δ [PDM]) and / or (Q [PD1], Δ [PDM]) and / or (Q [PD2], Δ [PDM]) and / or (Δ [PB1], Δ [PDM]) and / or ( Δ [PB2], Δ [PDM]) and / or (Δ [PD1], Δ [PDM]) and / or (Δ [PD2], Δ [PDM]) and / or (Q [PBM], Q [PDM] ]) and / or (Q [PBM], Δ [PBM]) and / or (Q [PBM], Δ [PDM]) and / or (Q [PDM], Δ [PBM]) and / or (Q [ PDM], Δ [PDM]) and / or (Δ [PBM], Δ [PDM]) and where Q [PBM] designates the mean value from Q [PB1] and Q [PB2], Q [PDM] designates the average value from Q [PD1] and Q [PD2], Δ [PBM] designates the average value from Δ [PB1] and Δ [PB2], Δ [PDM] designates the average value from Δ [PD1] and Δ [PD2]; d) At least one time-lapse repetition of steps a), b) and c), in which at least two pressure sensors, as in the previous measurement, as measured, and, from the measured pressure signals, the same quotients and / or differences are calculated; e) Generation of at least one time trend from the measured pressure signals selected from the groups listed in c); f) Evaluation of at least one time trend, if there has been a change in at least one time trend beyond a margin of tolerance; g) Generation of a standard for the evaluation of at least one time trend; h) Assignment of the standard to a change table and i) Display of the change on a central processing unit display device.
[0005]
5. Method according to claim 4, characterized by the fact that the at least three pressure signals are, respectively, absolute pressures, relative pressures, absolute pressure differences between two pressure measurement points, relative pressure differences between two pressure measurement points, absolute pressure ranges, relative pressure ranges, a difference between the absolute pressure ranges at two pressure measurement points or a difference between the relative pressure ranges at two pressure measurement points or one combination of these.
[0006]
6. Method according to claim 4 or 5, characterized by the fact that the at least three pressure signals are determined from the analysis of the frequency spectrum of the blood flow.
[0007]
7. Blood treatment system, characterized by the fact that it consists of a blood treatment unit and at least three pressure sensors [PB1], [PB2] and a pressure sensor is selected from [PD1] and [PD2], where [PB1] designates the pressure sensor in the bloodstream before blood enters the TFF tangential flow filters, [PB2] designates the pressure sensor in the bloodstream after blood exits from the filter TFF tangential flow, [PD1] designates the dialysate circulation pressure sensor before the dialysate enters the TFF tangential flow filter and [PD2] designates the dialysate circulation pressure sensor after the dialysate flow from the dialysate flow tangential flow TFF and consists of a central processing unit, in which the at least three pressure sensors are connected to the central processing unit for transmission of the measured values, and the central processing unit is capable of displaying and analyzing the s measured values received in such a way that a differentiation of changes in flow resistance in the transmembrane direction and direction of blood flow in the blood treatment unit is possible according to one of the methods according to one of claims 1 to 6.
[0008]
Blood treatment system according to claim 7, characterized in that it additionally comprises an ultrafiltration pump and a balance chamber system.
[0009]
9. Blood treatment system according to claim 7 or 8, characterized by the fact that the pressure sensors [PB1], [PB2], [PD1] and [PD2], respectively, have a sampling rate at least 20 Hz.

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EP3833411A1|2018-08-09|2021-06-16|Gambro Lundia AB|Method for detection of flow obstruction in an extracorporeal circuit, apparatus and computer program|

法律状态:
2018-12-26| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2019-09-10| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|

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2020-11-10| B09A| Decision: intention to grant|

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2021-01-05| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 14/10/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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DE102010048771A|DE102010048771A1|2010-10-14|2010-10-14|Method and device for measuring and correcting system changes in a device for treating blood|

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DE102010048771.6|2010-10-14|

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PCT/DE2011/001847|WO2012051996A2|2010-10-14|2011-10-14|Method and device for the measurement and the elimination of system changes in a device for the treatment of blood|

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