Abstract:
A device and method for detecting recirculation for an extracorporeal blood treatment apparatus and an apparatus with a device for detecting recirculation are based on targeted haemodilution by administration of a substituate bolus, causing a pressure change in venous and arterial branches of the extracorporeal circuit due to a viscosity change of flowing fluid. Recirculation is detected based on detection of the pressure change. The device includes a control unit cooperating with a device for conveying blood and a device for supplying substituate. The control unit provides an operating mode for detecting recirculation, in which blood flow rate is reduced during administration of a substituate bolus. With simultaneous substituate bolus administration and reduction of blood flow rate, the composition of fluid flow is optimised for detection of recirculation, so that fairly large pressure changes result in venous and arterial branches, thereby improving sensitivity and reliability of the measurement method.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application claims priority to U.S. Provisional Patent Application No. 61/703,845, filed on Sep. 21, 2012, and claims priority to Application No. DE 10 2012 018 628.2, filed in the Federal Republic of Germany on Sep. 21, 2012, each of which is expressly incorporated herein in its entirety by reference thereto. 
     
    
     FIELD OF INVENTION 
       [0002]    The present invention relates to a device for detecting the recirculation for an extracorporeal blood treatment apparatus as well as an extracorporeal blood apparatus with a device for detecting the recirculation. Moreover, the present invention relates to a method for detecting the recirculation during an extracorporeal blood treatment. 
       BACKGROUND INFORMATION 
       [0003]    Various methods for extracorporeal blood treatment or cleaning are used to remove substances usually eliminated with urine and for fluid withdrawal. In haemodialysis, the patient&#39;s blood is cleaned outside the body in a dialyser. The dialyser comprises a blood chamber and a dialysing fluid chamber, which are separated by a semipermeable membrane. During the treatment, the patient&#39;s blood flows through the blood chamber. In order to clean the blood effectively from substances usually eliminated with urine, fresh dialysing fluid flows continuously through the dialysing fluid chamber. 
         [0004]    Whereas the transport of the lower-molecular substances through the membrane of the dialyser is essentially determined by the concentration differences (diffusion) between the dialysing fluid and the blood in the case of haemodialysis (HD), substances dissolved in the plasma water, in particular higher-molecular substances, are effectively removed by a high fluid flow (convection) through the membrane of the dialyser in the case of haemofiltration (HF). In haemofiltration, the dialyser functions as a filter. Haemodiafiltration (HDF) is a combination of the two processes. 
         [0005]    In haemo(dia)filtration, a part of the fluid removed from the blood through the membrane of the dialyser is replaced by a sterile substitution fluid, which is generally fed to the extracorporeal blood circuit either upstream of the dialyser or downstream of the dialyser. 
         [0006]    The supply of substitution fluid upstream of the dialyser is also referred to as pre-dilution and the supply downstream of the dialyser as post-dilution. 
         [0007]    Apparatuses for haemo(dia)filtration are known, wherein the dialysing fluid is prepared online from fresh water and concentrations and the substitution fluid is prepared online from the dialysing fluid. 
         [0008]    In the known haemo(dia)filtration apparatuses, the substitution fluid (substituate) is fed to the extracorporeal blood circuit from the fluid system of the machine via a substituate line. With pre-dilution, the substituate line leads to a connection point on the arterial blood line upstream of the dialyser or filter, whereas with post-dilution the substituate line leads to a connection point on the venous blood line downstream of the dialyser or filter. 
         [0009]    With the known methods of chronic blood cleaning therapy, such as haemodialysis, haemofiltration and haemodiafiltration, the vascular connection (shunt) is generally applied between an artery and vein in operative surgery as an access to the patient&#39;s blood vessel system. When mention is made in the following of a “fistula”, this is understood to mean any kind of connection between a vein and an artery of the patient. 
         [0010]    The blood flowing through the fistula is used only during the actual dialysis treatment. In the period free from dialysis, the blood flow in the fistula corresponds to a functional left/right shunt, wherein a part of the arterial blood is fed from the heart minute volume (HMV), bypassing a peripheral use, directly to the venous system and the heart. The fistula flow recirculates via the heart and lungs. The fractional part of the fistula flow in the heart minute volume is defined as the cardiopulmonary recirculation. 
         [0011]    The cardiopulmonary recirculation not only has effects on the patient&#39;s circulatory load, but also on the efficiency of the dialysis. Since the dialysed blood from the extracorporeal circuit is mixed with the venous backflow from the large body circulation thereby bypassing the systemic circulatory areas, a systematic reduction in the concentration of the dialysable constituents in the arterial blood results (D. Schneditz et al., Cardiopulmonary recirculation during haemodialysis, Kidney Int. 42: 1450-1456, 1992). 
         [0012]    Of importance for the functional capability of the fistula is its perfusion. If the fistula flow falls below a critical value, the risk of a fistula thrombosis then increases with the possible loss of the vascular access, which in dialysis treatment represents a considerable complication (W. Bay et al., Color Doppler flow predicts PTFE graft failure, J. Am. Soc. Nephrol. 5: 407 (1994)). If the fistula flow during the dialysis treatment is smaller than the extracorporeal blood flow(Q B ), local fistula recirculation occurs, wherein a fraction of the dialysed blood fed back to the fistula with the venous blood line is again fed to the dialyser via the arterial blood line. Fistula recirculation R A  causes a significant reduction in the dialysis efficiency (F. Gotch, “Models to predict recirculation and its effects on treatment time in single-needle-dialysis,” First Intl. Symposium on Single-Needle-Dialysis, S. Rignoir, R. Vanholder and P. Ivanovich, Cleveland, ISAO Press, 1984, page 305 ff.). The measurement of the quality of the vascular access is therefore an important means of quality assurance in dialysis treatment. 
         [0013]    International Patent Publication No. WO 98/32477 describes a method for measuring recirculation R, i.e., the sum of the fistula recirculation (R A ) and the cardiopulmonary recirculation R CP . With the known method, a physical or chemical characteristic variable of the dialysing fluid is changed in the dialysing fluid path upstream of the dialyser, which leads to a change in the physical or chemical characteristic variable on the blood side. The change in the characteristic variable on the blood side leads to a change in the characteristic variable of the dialysing fluid downstream of the dialysing fluid chamber of the dialyser. In order to determine the recirculation, the characteristic variable in the dialysing fluid path downstream of the dialyser is measured and recirculation R is determined from the time-related course of the change in the characteristic variable. The dialysing fluid ion concentration, for example the Na concentration of the dialysing fluid, or the temperature of the dialysing fluid, can be changed and measured as a physical or chemical characteristic variable. 
         [0014]    U.S. Pat. No. 5,830,365 describes a method for determining the cardiopulmonary recirculation, which is based on two measurements of the recirculation fraction following shortly after one another, which are carried out automatically before and after the reversal of the blood flow. The drawback is that the known method requires the reversal of the blood flow. 
         [0015]    European Application No. EP 1 595 560 describes a method for determining the recirculation, wherein the viscosity of the blood in the arterial or venous blood line is changed by switching on and/or switching off the substituate pump. The change in the viscosity of the blood leads to a drop in pressure or rise in pressure on the venous or arterial side of the extracorporeal blood circuit, which is picked up in order to detect a recirculation on the basis of the change in pressure. The known method provides for a change in the substituate rate by switching on and/or switching off the substituate pump, whilst the blood pump in the extracorporeal blood circuit continues to convey blood at the preset blood flow rate. 
       SUMMARY 
       [0016]    A problem underlying the present invention is to provide a device with which a recirculation can be detected quickly and reliably during an extracorporeal blood treatment, so that the checking of the state of the fistula during the extracorporeal blood treatment can be carried out routinely without great expense. 
         [0017]    The device according to the present invention and the method according to the present invention are based on a targeted haemodilution by the administration of a bolus of a substitution fluid (substituate). Due to a change in the viscosity of the fluid flowing in the extracorporeal circuit, the haemodilution leads to a change in the pressure conditions in the venous and arterial branch of the extracorporeal blood circuit. A recirculation is detected on the basis of the detection of the change in pressure in the extracorporeal circuit. The change in pressure can appear as an increase of the pressure in the arterial blood line or a reduction of the pressure in the venous blood line. 
         [0018]    The device according to the present invention and the method according to the present invention are characterised by a targeted reduction in the blood flow rate during the administration of the bolus of substituate. During the extracorporeal blood treatment, the blood flow rate within a preset time interval is reduced from a preset current blood flow rate, which is referred to below as the first blood flow rate, to a blood flow rate which is referred to below as the second blood flow rate. The second blood flow rate preferably corresponds to a minimum blood flow rate, which can be preset by the doctor. According to the present invention, the reduction in the blood flow rate is compensated again at least partially by the bolus administration of substituate. The reduced volume of blood in the preset time interval is preferably replaced completely by substituate. The bolus administration should take place simultaneously with the reduction in the blood flow rate, i.e., the preset time interval, in which the blood treatment takes place with a reduced blood flow rate, should correspond to the time interval in which the substituate bolus is administered. Certain time shifts between the time intervals of the reduction in the blood flow rate and the bolus administration can however also be preset. 
         [0019]    It has been shown that, with the simultaneous bolus administration of substituate and the reduction of the blood flow rate, the composition of the fluid flowing through the extracorporeal circuit, i.e., the blood diluted with substituate, is optimised for the detection of a recirculation. From the targeted change in the blood flow rate and substituate rate within the time interval, fairly large pressure changes result in the venous and arterial branch of the extracorporeal circuit, which can be picked up with a high degree of reliability for the detection of a recirculation. The sensitivity and reliability of the measurement method are thus improved overall. 
         [0020]    The device according to the present invention for the detection of the recirculation can form a separate assembly or can be a component of the extracorporeal blood treatment apparatus. 
         [0021]    The device according to the present invention for the detection of the recirculation is preferably a component of the blood treatment apparatus, which already comprises the main components for performing the method according to the present invention. 
         [0022]    The device for determining the recirculation comprises a measuring unit for measuring the pressure in the extracorporeal circuit in the arterial and/or venous blood line and an evaluation unit for detecting the recirculation on the basis of the pressure measurement. Moreover, the device for detecting the recirculation comprises a control unit, which cooperates with the device for conveying blood to the blood treatment apparatus and the device for supplying substituate to the blood treatment apparatus. The control unit provides an operating mode for detecting the recirculation, in which the device for conveying blood is controlled such that preset first blood flow rate Q b1  is reduced to second blood flow rate Q b2  in a preset time interval, and the device for supplying substituate is controlled such that substituate is supplied in the preset time interval at a preset substituate rate Q s  to the blood in the arterial blood line upstream of the dialyser or filter. The conveying rates can be constant or have a specific profile, for example rise and fall continuously or discontinuously, within the preset time interval. 
         [0023]    In a preferred exemplary embodiment, the control unit is constituted such that the device for supplying substituate in the preset time interval in the operating mode for detecting the recirculation is controlled such that the difference between preset substituate rate Q s  and the difference between first blood flow rate Q b1  and second blood flow rate Q b2  corresponds to a specific value. The reduction in the blood flow rate is thus at least partially compensated for by the supply of substituate. Preferably, however, the specific value is zero, so that a complete compensation takes place. 
         [0024]    A particularly preferred exemplary embodiment makes provision such that the evaluation unit generates a control signal signalling the presence of a recirculation when a pressure change is detected, wherein the device for determining the recirculation comprises an optical and/or acoustic signal unit receiving the control signal of the evaluation unit, said signal unit generating an acoustic and/or optical signal when the signal unit receives the control signal from the evaluation unit. 
         [0025]    A pressure drop in the venous branch of the extracorporeal blood circuit first arises on account of the haemodilution due to the bolus administration with the reduction in the blood flow. If a recirculation is present, a part of the blood volume passes directly into the arterial branch of the blood circuit, which leads to a time-shifted pressure rise in the arterial branch of the blood circuit, since the pressure drop at the arterial cannula is reduced on account of the reduction in the viscosity. The recirculation can consequently be detected by a pressure rise in the arterial branch of the blood circuit. 
         [0026]    In a particularly preferred exemplary embodiment, the evaluation unit is constituted such that the amount of the change in pressure in the arterial or venous blood line is compared with a preset threshold value, wherein the evaluation unit generates a control signal indicating the presence of a recirculation when the amount of the change in pressure is greater than the preset threshold value. Other evaluation methods can however also be used to detect a recirculation. The only important point is that the pressure rise due to the recirculation is detected. 
         [0027]    In general, it is sufficient when a recirculation is detected for information to be obtained concerning the state of the vascular access. The device according to the present invention for detecting the recirculation, however, also permits a determination of the recirculation. For the calculation of the percentage fraction of the recirculation, the evaluation unit is preferably constituted such that the ratio between the amount of the change in the pressure measured in the arterial blood line and the pressure measured in the venous blood line is calculated. The integrals of the pressure signals measured with the pressure measuring units are preferably put into a relationship with one another. 
         [0028]    The recirculation can also be precisely determined with the other methods known in the prior art, as soon as the device according to the present invention has detected a recirculation. 
         [0029]    For the rapid initiation of a recirculation test, a further particularly preferred exemplary embodiment provides an actuation unit for the control unit, which is constituted such that, after actuation of an actuation element, the control unit selects the operating mode for detecting the recirculation, so that the process steps required for this are carried out automatically. The recirculation test can thus be initiated quickly and then carried out automatically. The actuation unit can be a mechanical switch or pushbutton or an operator panel of a touch-screen. 
         [0030]    Exemplary embodiments of the present invention are explained in detail below with reference to the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0031]      FIG. 1  shows an extracorporeal blood treatment apparatus with a device for detecting the recirculation in a very simplified diagrammatic representation. 
           [0032]      FIG. 2  shows a diagram to illustrate the flow rates in the extracorporeal blood circuit during the bolus administration. 
           [0033]      FIG. 3  shows a first exemplary embodiment of the time-related course of the pressure in the arterial and venous branch of the extracorporeal blood circuit during the bolus administration in the presence of a recirculation. 
           [0034]      FIG. 4  shows a second exemplary embodiment of the time-related course of the pressure in the arterial and venous branch of the extracorporeal blood circuit during the bolus administration in the presence of a recirculation. 
           [0035]      FIG. 5  shows the time-related course of the pressure in the arterial and venous branch of the extracorporeal blood circuit during the bolus administration when no recirculation is taking place. 
       
    
    
     DETAILED DESCRIPTION 
       [0036]      FIG. 1  shows in a simplified diagrammatic representation only the main components of an extracorporeal blood treatment apparatus, which comprises a device for detecting the recirculation. 
         [0037]    The present blood treatment apparatus is a haemo(dia)filtration apparatus, which comprises a dialyser  1 , which is separated by a semipermeable membrane  2  into a first chamber  3  through which blood flows, which is referred to in the following as a blood chamber, and a second chamber  4  through which dialysing fluid flows, which is referred to as a dialyser fluid chamber. First chamber  3  is incorporated into an extracorporeal blood circuit  5 A, whilst second chamber  4  is incorporated into dialysing fluid system  5 B of the haemo(dia)filtration apparatus. 
         [0038]    Extracorporeal blood circuit  5 A comprises an arterial blood line  6 , which leads from an arterial cannula  6   a  to inlet  3   a  of blood chamber  3 , and a venous blood line  7 , which leads away from outlet  3   b  of blood chamber  3  of dialyser  1  and leads to a venous cannula  7   a.  The arterial and venous cannulas are connected to the fistula (shunt) of the patient, said fistula not being represented. The patient&#39;s blood is delivered through blood chamber  3  of dialyser  1  by an arterial blood pump  8 , which is disposed on arterial blood line  6 . Blood pump  8  feeds blood at a preset blood flow rate Q b , referred to as the first blood flow rate, to blood chamber  3  of the dialyser. The first blood flow rate can be changed during the blood treatment. Blood lines  6 ,  7  and dialyser  1  form a disposable intended for one-off use, which is inserted into the dialysis apparatus for the dialysis treatment. In order to eliminate air bubbles, air separators (drip chambers) can be incorporated into the arterial and venous blood line. 
         [0039]    The fresh dialysing fluid is prepared in a dialysing fluid source  9 . From dialysing fluid source  9 , a dialysing fluid supply line  10  leads to inlet  4   a  of dialysing fluid chamber  4  of dialyser  1 . A dialysing fluid discharge line  11  leads from outlet  4   b  of dialysing fluid chamber  4  to a drain  12 . A dialysing fluid pump  13  is incorporated into dialysing fluid discharge line  11 . 
         [0040]    During the dialysis treatment, substitution fluid (substituate) can be fed from a substituate source  15  via a substituate line  14  to extracorporeal blood circuit  5 A. Substitution line  14  is connected to a line segment of arterial blood line  6  downstream of blood pump  8  and upstream of blood chamber  3  of dialyser  1 . The substituate is conveyed with a substituate pump  16 , which feeds substituate at a preset substituate rate Q s  to arterial blood line  6 . The substituate can be a fluid prepared from the dialysing fluid during the treatment. The substituate can however also be a fluid prepared in the substituate source, for example a cooking salt solution. 
         [0041]    The device for detecting a recirculation comprises a control unit  17 , which can be a component of the central control and computing unit of the blood treatment apparatus. Blood pump  8  and substituate pump  16  are connected via control lines  8 ′,  16 ′ to control unit  17  of the device for detecting the recirculation. The control unit switches pumps  8 ,  16  on and off and presets specific flow rates for the pumps. 
         [0042]    Moreover, the device for detecting the recirculation comprises a measuring unit  18  with an arterial pressure sensor  18 A for measuring the pressure in arterial blood line  6  upstream of blood pump  8  and a venous pressure sensor  18 B for measuring the pressure in venous blood line  7  downstream of the blood chamber of the dialyser. Arterial and venous pressure sensors  18 A,  18 B are connected via data lines  18 A′,  18 B′ to measuring unit  18 , and measuring unit  18  is connected via a data line  18 ′ to an evaluation unit  19  of the device for detecting a recirculation, said evaluation unit being connected via a data line  19 ′ again to control unit  17 . 
         [0043]    Furthermore, the device for detecting the recirculation comprises an actuation unit  20  with an actuation element  20 A, for example a pushbutton, and a signal unit  21 , which comprises an optical and/or acoustic signal transmitter  21 A. Actuation unit  20  and signal unit  21 , which can also be a component of the blood treatment apparatus, are connected via control and data lines  20 ′,  21 ′ to control unit  17 . 
         [0044]    Control unit  17  can be a data processing unit (microprocessor), on which a data processing program runs in order to execute the steps required for the performance of the method according to the present invention. The mode of functioning of the control unit is described in detail below. The control unit is configured (programmed) such that the individual components of the blood treatment apparatus are controlled as follows. 
         [0045]    During the blood treatment, blood pump  8  conveys the blood at a preset first blood flow rate Q b1 , which can vary during the blood treatment. To initiate the recirculation test, actuation element  20 A is actuated, for example the pushbutton is pressed. After pressing of the pushbutton, control unit  17  selects the operating mode for detecting the recirculation, so that blood pump  8  and substituate pump  16  are controlled for the administration of a substituate bolus with a reduced blood flow. Control unit  17  is configured (programmed) such that blood pump  8  conveys the blood within a preset time interval ΔT at a reduced second blood flow rate Q b2 . Control unit  17  calculates the difference between first blood flow rate Q b1  and second blood flow rate Q b2  and presets a rate for substituate rate Q s  which corresponds to the difference between first and second blood flow rates Q b1 , Q b2 . 
         [0046]      FIG. 2  illustrates the selection of substituate rate Q s  during the bolus administration for different flow rates. The blood flow rate is reduced from a value Q b1  to a minimum value Q b2 =Q min , for example 50 ml/min. For a blood flow rate Q b1  before the bolus administration of 400 ml/min, a value of 350 ml/min results for example for substituate rate Q s  during the bolus administration, from which the value of 400 ml again results as the sum Q G =Q s +Q b2 . 
         [0047]    In the operating mode for recirculation detection, arterial and venous pressure sensor  18 A,  18 B of measuring unit  18  measures the pressure in arterial and venous blood line  6 ,  7 , wherein evaluation unit  19  evaluates the pressure signals. 
         [0048]      FIG. 3  shows the measured time-related course of venous and arterial pressure p v  (mbar) and p a  (mbar). After the substituate bolus with a reduced blood flow, a pressure drop I by a specific amount is detected in venous blood line  7  and a pressure rise II is detected in arterial blood line  6  on account of the haemodilution, the latter being denoted by the symbols I and II. In this exemplary embodiment, the recirculation amounts to 20%. For comparison,  FIG. 4  shows the time-related course of venous and arterial pressure p v  (mbar) and p a  (mbar) with a recirculation of 40%, whilst  FIG. 5  shows the time-related course of venous and arterial pressure p v  (mbar) and p a  (mbar) when no recirculation is present. It can clearly be seen that an arterial pressure rise can be noted only in the case of the recirculation. 
         [0049]    The characteristic course of the pressure signal shown in  FIGS. 3 to 5  is due to the changed viscosity of the blood. On account of the bolus administration, the viscosity of the blood in venous blood line  7  downstream of the blood chamber is increased on account of the supply of substituate. Consequently, a smaller pressure drop occurs at venous cannula  7   a.  The venous pressure thus drops. After the bolus administration, the viscosity of the blood in venous blood line  7  is reduced again, so that the venous pressure increases again. On account of the fistula recirculation, a part of the diluted blood passes via the fistula directly into arterial blood line  6 , which leads to a reduction in viscosity, for which reason the pressure in the arterial blood line increases. Evaluation unit  19  concludes from the arterial pressure rise or venous pressure drop that a fistula recirculation is present. In this regard, evaluation unit  19  determines the amount of the pressure rise in arterial blood line  6  and compares the amount with a preset threshold value. Alternatively, evaluation unit  19  can also determine the amount of the pressure drop in venous blood line  7  and compares the amount with a preset threshold value. If the threshold value is exceeded with a significant change in the pressure, evaluation unit  19  generates a control signal which signals a recirculation. Signal unit  21  receives the control signal of evaluation unit  19  via control unit  17 , so that signal transmitter  21 A generates an acoustic and/or optical alarm. The doctor performing treatment can then take the necessary measures. 
         [0050]    The device according to the present invention also permits the determination of the recirculation. The ratio between the amount of the maximum change in the arterial pressure signal of the arterial pressure sensor and the amount of the maximum change in the venous pressure signal of the venous pressure sensor serves as a measure for the recirculation. The recirculation Rez [%] is calculated by the evaluation unit according to the following equation. 
         [0051]    The relationship between the obtained haematocrit change ΔHkt and the measured pressure change (Δp a  and Δp v ) on the venous and arterial side is however not linear. Moreover, there is a dependence on blood flow Q b , the geometry of the cannula, in particular its diameter, and the absolute haematocrit value. The device according to the present invention therefore preferably provides for a measurement under defined conditions, wherein Q b  and Q s  are constant, so that the recirculation Rez [%] can be determined according to the above equation with sufficient accuracy. 
         [0052]    In contrast with a measurement on the basis of a thickening instead of a thinning of the blood, the problem does not arise that the dialyser may become clogged up or blood clots may form in the hose system. Moreover, no effects from the cardiopulmonary recirculation on the measurement result appear with the measurement method according to the present invention due to the detection of the pressure change immediately after the haemodilution.