Hemodiafiltration method

Abstract

The invention relates to a device for hemodiafiltration with an extracorporeal circulation (10) for receiving blood to be purified and having a hemodialyzer and/or hemofilter (20) which is connected to the blood circulation (10), such that the blood circulation (10) has at least one inlet line (12, 14) for the supply of a replacement fluid upstream and downstream from the hemodialyzer and/or hemofilter (20), characterized in that the apparatus also comprises measurement apparatuses for recording the transmembrane pressure and/or hematocrit (HKT) and/or blood density, such that the measurement apparatuses are connected to a control unit (100) for controlling one or more of the transmembrane pressure and/or the hematocrit (HKT) and/or the blood density, the control unit (100) being constructed so that the control is implemented with the help of at least one of the infusion rates (Q.sub.spre, Q.sub.spost) of the replacement fluid (13, 15), and the blood to be purified is exposed to a high-frequency electromagnetic field and/or an electric DC field (70) before and/or during contact with the hemodialyzer and/or hemofilter (20).

Claims

1. A hemodiafiltration device comprising: a hemodialyzer/hemofilter separated by a membrane into a blood circulation chamber and dialysis fluid circulation chamber; an extracorporeal blood circulation line extending upstream and downstream of the blood circulation chamber and having at least one replacement-fluid inlet line upstream and at least one replacement-fluid inlet line downstream of said blood circulation chamber; at least one measurement apparatus for recording at least one of transmembrane pressure, difference between upstream and downstream hematocrit (HKT), and difference between upstream and downstream blood density; a control unit connected to the at least one measurement apparatus and constructed for control of at least one of the transmembrane pressure, the hematocrit, and the blood density by controlling the upstream and downstream infusion rates of the replacement fluid (Q.sub.spre, Q.sub.spost) based on input received from the at least one measurement apparatus; and a high-frequency electromagnetic field generator configured to generate a field having a frequency of 1 MHz to 1 GHz arranged to surround the hemodialyzer/hemofilter or a part of the extracorporeal blood circulation line extending upstream of the hemodialyzer/hemofilter and the hemodialyzer/hemofilter in order to expose blood during or before an during passing through the blood circulation chamber to a high-frequency electromagnetic field.

2. The device according to claim 1 further comprising f) a dialysis fluid circulation line extending upstream and downstream of the dialysis fluid circulation chamber, and g) pressure sensors arranged in the dialysis fluid circulation line upstream and downstream of the dialysis fluid circulation chamber, respectively.

3. The device according to claim 1, wherein the control unit is configured to control the infusion rates (Q.sub.spre, Q.sub.spost) of the replacement fluid so that Q.sub.spre is greater than or equal to Q.sub.spost during hemodiafiltration treatment.

4. The device according to claim 1, wherein the control unit is configured to control the infusion rates (Q.sub.spre, Q.sub.spost) of the replacement fluid so that the ratio of the infusion rates Q.sub.spre/Q.sub.spost is at least 1.2.

5. The device according to claim 1, wherein the control unit is configured to control the infusion rates (Q.sub.spre, Q.sub.spost) of the replacement fluid so that the ratio of the infusion rates Q.sub.spre/Q.sub.spost is at least 1.5.

6. The device according to claim 1, wherein the high-frequency electromagnetic field generator is a high-frequency coil, a high-frequency electrode, or a high-frequency capacitor.

7. The device according to claim 1, wherein the high-frequency electromagnetic field generator has an output power greater than 12 Db.

8. The device according to claim 1, wherein the high-frequency electromagnetic field generator is configured to generate a field having a frequency of 10 MHz-1 GHz.

9. The device according to claim 1, wherein the high-frequency electromagnetic field generator is configured to generate a field having a frequency of 20 MHz-1 GHz.

Description

(1) Additional details and advantages of the present invention are explained with reference to the following figures and embodiments. There are shown in the Figures:

(2) FIG. 1 a schematic diagram of a part of the extracorporeal circulation and of the dialysis fluid circulation with a hemodialyzer and a hemofilter as well as with inlet lines for the replacement fluid;

(3) FIG. 2: experimental results relating to the influence of high-frequency electromagnetic fields on the protein-bound portion of uremic toxins;

(4) FIG. 3; experimental results as proof of the lack of damage to the membrane by the high-frequency fields;

(5) FIG. 4: experimental results relating to the influences of an HF field in the frequency range 1 to 170 MHz on the protein-bound portion of uremic toxins;

(6) FIG. 5: experimental results relating to the influences of an HF field in the frequency range 110 to 115 MHz on the protein-bound portion of uremic toxins;

(7) FIG. 6: experimental results relating to the influences of an H field in the frequency ranges 1 to 6 MHz and 9 to 13 MHz on the protein-bound portion of the uremic toxins; and

(8) FIG. 7: experimental results relating to the influences of the field strength on the protein-bound portion of the uremic toxins.

(9) FIG. 1 shows a part of the extracorporeal circulation 10 through which blood is circulated at the flow rate QB by means of a blood pump 11 in the direction of the arrow. A pressure sensor 40 and a sensor 50 are arranged upstream from the hemodialyzer or hemofilter 20 in the extracorporeal circulation 10 for detecting the arterial blood pressure P.sub.art and hematocrit HKT.sub.in before purification of the blood.

(10) Appropriate measuring devices 40, 50 for detecting the corresponding values P.sub.ven and HKT.sub.out after the purification of the blood are arranged downstream from the hemodialyzer and/or hemofilter 20.

(11) Dialysis fluid flows in countercurrent with the bloodstream in the direction of the arrow at flow rate QD through the hemodialyzer or hemofilter 20. The dialysis fluid line 30 has pressure sensors 40 upstream and downstream from the hemodialyzer or hemofilter for the respective pressure PD.sub.in and PD.sub.out of the dialysis fluid. Circulation of the dialysis fluid is controlled by pumping means and/or balancing means 31 and 32.

(12) The hemodialyzer and/or hemofilter is/are subdivided by a semipermeable membrane 21 into a blood chamber 22 and a dialysis fluid chamber 23.

(13) The hemodialyzer and/or hemofilter 20 is/are surrounded by means for generating a high-frequency electromagnetic field and/or an electric DC field 70.

(14) In another embodiment, in addition to the hemodialyzer and/or hemofilter 20, a part of the extracorporeal blood circulation 10 upstream therefrom is surrounded by means for generating a high-frequency electromagnetic field and/or an electric DC field 70. Upstream and downstream from the hemodialyzer and/or hemofilter 20 there are inlet lines 12, 14 with liquid pumps 13 and/or 15 which are provided for supplying replacement fluid to the blood flowing in the extracorporeal circulation 10 during the treatment. The respective flow rates are labeled as Q.sub.spre and Q.sub.spost.

(15) The two infusion rates Q.sub.spre and Q.sub.spost of the replacement fluid may be varied according to the invention with the help of the control unit 100. The control unit 100 is connected to all the actuators and sensors shown here by connections (not shown). The infusion rates are varied according to the measured values of the control values to be controlled. In the embodiment illustrated in FIG. 1, the measured values of the arterial and venous blood pressure P.sub.art, P.sub.ven as well as the pressures of the dialysis fluid P.sub.Din and P.sub.Dout before and after passing through the hemodialyzer and hemofilter 20 are shown. The resulting transmembrane pressure TMP is set or kept at the desired target level according to the present invention through a suitable modification of the flow rates Q.sub.spre and Q.sub.spost at the desired target value. Instead of the transmembrane pressure TMP, hematocrit values HKT.sub.in, HKT.sub.out may also be used as control values. TMP may also be approximated by using fewer than the four pressure sensors shown here. With the dialysis machines that are customary currently pressure sensors are normally used for P.sub.ven and P.sub.Dout.

(16) The effect achieved with the help of the apparatus claimed here is that the limitation membrane, which is built up on the side of the membrane of the hemodialyzer or hemofilter opposite the chamber in which the blood is present, can be kept in a stationary state, which results in a constant purification spectrum and a constant degree of purification during the treatment. At the same time, the transmembrane pressure can be kept constant during treatment because the pressure drop caused by the membrane and the limitation membrane also remains constant.

(17) Due to the limitation of the transmembrane pressure to a predeterminable level, the risk an extensive loss of albumin through the membrane due to high convective forces can be prevented. When using high-flow membranes, the limitation of the transmembrane pressure is especially important.

(18) Especially in patients with severe coagulation problems, the combination of pre- and postdilution contributes toward a reduction in the consumption of heparin, which is normally infused into the blood to prevent blood from coagulating in the extracorporeal circulation. When blood is diluted upstream from the hemodialyzer and/or hemofilter, less anticoagulant fluid is necessary to reduce the risk of blood coagulating in the hemodialyzer and/or hemofilter because the latter is the most significant potential for blood coagulation in the extracorporeal circulation.

(19) Apart from the aforementioned advantages of a constant operating behavior, a good purification performance for protein-bound uremic toxins can be achieved through the combination of predilution and postdilution and through the action of a high-frequency electromagnetic field and/or an electric DC field.

(20) The following experimental results serve as experimental proof of the effect of an electric field on the separation of protein-bound toxins during the dialysis.

(21) The effect of an HF field in the frequency range from 1 to 20 MHz is described in embodiment 1. Embodiment 2 shows the effect of the HF field in the frequency range from 1 to 170 MHz on the separation of phenylacetic acid. The separation rate for phenylacetic acid was able to be increased by at least 45.3% under the influence of the HF field. The effect was particularly pronounced at 54.6% in the subband from 110 to 120 MHz. The subband from 110 to 120 MHz is looked at more closely in embodiment 3. Embodiment 4 shows the influence of an H field in the ranges 1-6 MHz and 9-13 MHz. Embodiment 5 shows the influence of the field strength on the separation of phenylacetic acid.

(22) The temperature was kept constant in all embodiments 1 to 5 so that the observed changes are based on the properties of the electric field and not on a heating.

EMBODIMENT 1

(23) The influence of high-frequency electromagnetic fields on the protein-bound portion of the uremic toxins was examined in a series of in vitro experiments.

(24) A dialysis module was set up for this purpose in that conventional hemofiltration capillaries were cast as loops using silicone into a syringe receiving neck. An aqueous albumin solution was introduced into the respective module in the presence of the uremic toxins phenylacetic acid, p-hydroxyhippuric acid and indoxyl sulfate. This solution was filtered with the dialysis module using a syringe pump for 10 min. A high-frequency electromagnetic field was subsequently induced in the solution by using a high-frequency electrode (HF electrode). The electromagnetic field is incremented by means of a high-frequency voltage source over a period of 10 minutes from 1 to 20 MHz in steps of 1 MHz. The concentration of the uremic toxins phenylacetic acid, p-hydroxyhippuric acid and indoxyl sulfate previously added to the artificial plasma was determined in the resulting filtrates. The effect of the HF field on the bond between the proteins and the uremic toxins was able to be evaluated by a comparison of the uremic toxin concentration in the resulting filtrates.

(25) The quantitative determination of the uremic toxin concentration in the resulting filtrates showed that high-frequency electromagnetic fields significantly increase the filtration rates of the protein-bound uremic toxins (FIG. 2). The protein concentration in the filtrate was determined using Bradford protein dyeing to check whether high-frequency electromagnetic fields damage the dialysis membranes. The results show that no significant changes of the protein concentration can be detected in dialysis modules without and with the influence of high-frequency electromagnetic fields (FIG. 3). Macroscopic damage to the membrane can be precluded on the basis of these data.

EMBODIMENT 2

(26) Examination of the HF field effect in the frequency range 1 to 170 MHz.

(27) An aqueous solution of bovine serum albumin (BSA, 60 mg/ml) was introduced into the dialysis module of Example 1 in the presence of the uremic toxin phenylacetic acid (1 mmol/l in 0.9% NaCl solution). The HF field was varied in subbands of 10 MHz in the frequency range 1-170 MHz and was compared with a control experiment without an HF field.

(28) The quantitative determination of the phenylacetic acid was performed using HPLC.

(29) The results of the experiments are collected in FIG. 4. The separation rate for phenylacetic acid was able to be increased by at least 45.3% under the influence of the HF field. The effect was particularly pronounced at 54.6% in the subband from 110 to 120 MHz.

EMBODIMENT 3

(30) This embodiment follows on from the examinations in accordance with Embodiment 2 which showed that the effect was particularly pronounced in the subband from 110 to 120 MHz.

(31) In the continuing examinations in accordance with Embodiment 3, the frequency range about 110 to 115 MHz was in particular able to be identified as an effective frequency range for the release of protein-bound uremic toxins. FIG. 5 shows the respective effect on the corresponding release and the subsequent separation of phenylacetic acid.

(32) According to the current status, the frequency ranges named summarily in Table 1 are suitable for the separation of protein-bound uremic toxins.

(33) TABLE-US-00001 TABLE 1 Suitable frequencies in the HF field Frequencies E Field PAA IDS pCRS 80-120 MHz 110 110 110 110-111 110-111 110-111 111 111 111 120-170 MHz 140-141 140-141 140-141 148-149 151-152 160-161

(34) The respective frequency ranges are the ranges at which the maximum separation effect was determined. An increased separation was determined in part in the non-named frequency ranges in comparison with the control; however, it was smaller than in the named frequency ranges.

EMBODIMENT 4

(35) An increased release and thus separation of the protein-bound uremic toxins was furthermore also able to be determined in the range of the H field.

(36) It can be seen from FIG. 6 that the H field range from 1-6 MHz and the range 9-13 MHz are suitable to release protein-bound uremic toxins from the protein bond and consequently to separate them dialytically. The effect on phenylacetic acid is shown in FIG. 6.

EMBODIMENT 5

(37) In addition to the frequency of the field used, its field strength is also relevant to the resulting release and separation. As the field strength increases, the respective uremic toxins are increasingly released from the protein bond and are subsequently separated.

(38) FIG. 7 shows the effect of an increasing field strength on the content of protein-bound uremic toxins in the retentate for the example of phenylacetic acid.