Abstract:
A process and a device for improving the determination of the pulse transit time for non-invasive blood pressure measurement. A value, correlating with the blood density, is determined and its influence on the pulse transit time is compensated. In this manner more precise blood pressure data can be obtained. In a further development, a value, correlating with the blood density, is determined by a measuring device for the change in relative blood volume or hematocrit. The device can also be used as part of a hemotherapeutic arrangement such as a hemodialysis device and/or hemofiltration device, in which a blood pressure monitoring as continuous and precise as possible is desired, among other things, because of a blood volume change and thereby a blood density change inherent in the therapy.

Description:
BACKGROUND 
     1. Field of the Invention 
     The invention relates to the field of determining the pulse transit time of a patient or donor where a pulse transit time is measured for pulse waves propagating via the patient&#39;s or donor&#39;s vascular system and created by his/her heart contractions. 
     2. Description of the Related Art 
     A patient&#39;s or donor&#39;s blood pressure is typically measured by means of an inflatable rubber cuff according to the Riva-Rocci method. This method allows a measurement only at a defined time, at which the pressure of the cuff is varied over a certain period of time. Thus, continuous measurement is limited to time intervals that are determined by the measuring method. A quasi continuous measurement would be associated with a constantly alternating expansion and deflation of the rubber cuff, which would be accompanied by unreasonable stress on the patient. 
     As an alternative to the non-invasive Riva-Rocci method, there exists a method for determining the pulse transit time, which can also be carried out non-invasively. This method is based on the knowledge that the time that a pulse wave, produced by a heart contraction of a patient or donor, requires to make its way through the vascular system from a first point to a second place is a function of the blood pressure of the person examined. If the time is measured that passes between the occurrence of a heartbeat (detected, for example, by means of an electrocardiograph (EKG)) and the time of arrival of the related pulse wave at an area of the body at a distance from the heart (detected, for example, by an optical sensor on the ear lobe or finger), this pulse transit time represents a direct measure of the patient&#39;s or donor&#39;s blood pressure. Since the pulse transit time varies from person to person, a calibration by means of an initial Riva-Rocci measurement is necessary. However, a statement on relative changes can be obtained directly from the relative changes in the pulse transit time. The relation between the blood pressure and the pulse transit time is largely linear (Psychophysiology, Vol. 3,86 (1976)). Since one measurement is possible per heart beat, this measuring method represents a semi-continuous blood pressure measurement. 
     The WO 89/08424 describes a measurement process for determining the pulse transit time by means of an electrocardiograph EKG and an optoelectronic measuring sensor on skin areas with good circulation. However, since the circulation in the skin tissue and thus also the photoelectric profile itself can change over time due to vasomotoric and other adjustments without the blood pressure necessarily having changed, a repeated recalibration should follow the initial calibration according to the Riva-Rocci method, using the measured values of the optoelectronic measuring sensor. In this respect, a constant relationship between the pulse transit time and the blood pressure is assumed for each person. The recalibration serves the purpose of allowing absolute statements about the systolic as well as the diastolic pressure from the photoelectric profiles at later points in time. 
     Acute emergencies, e.g. during hemodialysis and/or hemofiltration, require careful action. A primary complication during such a hemotherapy is a decrease in blood pressure. The most frequent cause of such an incident is a hypovolemia as a result of an excessively intensive fluid withdrawal. In particular during extracorporeal hemotherapy, it is, therefore, necessary to constantly monitor the blood pressure of a patient or donor in order to recognize possible circulation complications at an early stage. 
     The EP-A 0 911 044, which is hereby incorporated by reference, describes, among other things, a hemodialysis and/or hemofiltration apparatus, in which a continuous blood pressure monitoring with only a slight negative effect on the patient is made possible by means of a pulse transit time measurement. Using the measurement signal of the pulse transit time, it is possible to recognize critical blood pressure conditions at an early stage and to then inform the staff without delay. If necessary, countermeasures can be carried out automatically on the hemodialysis and/or hemofiltration apparatus, e.g. by infusions or modifying concentrations. This prior art apparatus, like the teaching of the WO 89/08424, assumes a constant relationship between the blood pressure and the pulse transit time. This assumption is not sufficiently accurate in the case of hemotherapies that It change the blood density in particular. In particular due to fluid withdrawal during a hemodialysis and/or hemofiltration treatment, the blood density increases during the course of the treatment (blood density in this case refers to the density of blood as a fluid per se). Since blood density has a direct influence on the pulse wave velocity and thus the pulse transit time, the results are inaccurate measurement values. 
     SUMMARY OF THE INVENTION 
     The present invention is based on the technical problem of improving a process and/or a device for determining a patient&#39;s or donor&#39;s pulse transit time in such a manner that the changes in the blood count are taken into account during the course of time and thus a more precise monitoring of blood pressure is made possible. 
     According to the teaching of the invention, this problem is solved by means of a process for determining the pulse transit time where a pulse transmit time is measured for pulse waves propagating via the patient&#39;s or donor&#39;s vascular system and created by his/her heart contractions, in which a value, correlating with the blood density, is determined and then used to calculate from the measured pulse transit time a pulse transit time, for which the influence of blood density is compensated. 
     The problem is also solved by a device for determining the pulse transit time with means for determining the pulse transit time of pulse waves, which are propagated via the patient&#39;s or donor&#39;s vascular system and are created by heart contractions, according to which there are means for determining a value, correlating with the blood density, and an evaluation unit that compensates for the influence of blood density on the pulse transit time. 
     The invention builds on the knowledge that the influence of a variable blood density between the two measurements can be compensated by means of measurements of a value, correlating with the blood density, at the time of a first pulse transit time measurement and at the time of a second pulse transit time measurement. In this manner a compensated first or second pulse transit time can be obtained that is directly comparable with the second or the first pulse transit time, as if it had been measured with constant blood density. In this manner, emergency conditions can be indicated with significantly greater reliability. 
     The rate at which a disturbance along an elastic, cylindrical, sufficiently long tube spreads in a homogenous fluid, may be expressed (Y. C. Fung, in “Biomechanics Circulation”, 2nd edition, Springer, N.Y., Berlin, 1997, p. 140): 
     
       
           c =[( A /ρ)( dp/dA )]  (1) 
       
     
     where 
     ρ: density of the fluid 
     A: cross section of the tube 
     dA: change in cross section 
     dp: change in pressure in the tube 
     If equation (1) is assumed to be valid for blood in arteries, this results in equation (2) for blood with a density ρ(t 0 ) at time t 0  compared to blood with a density of ρ(t) at time t at constant blood pressure p(t 0 ) for the pulse wave velocity c: 
     
       
         [ c ( t, p ( t   0 ), ρ( t ))]/[ c ( t   0 ,  p ( t   0 ), ρ( t   0 ))]=[ρ( t   0 )/ρ( t )]  (2) 
       
     
     For the pulse transit time PTT, which indicates the passage of the pulse waves at the pulse wave propagation velocity over a defined path L, a similar expression is obtained: 
     
       
           PTT ( t, p ( t   0 ), ρ( t ))/ PTT ( t   0 ,  p ( t   0 ), ρ( t   0 ))= L/c ( t, p ( t   0 ), ρ( t ))/ L/c ( t   0 ),  p ( t   0 ), ρ( t   0 ))=[ρ( t )/ρ( t   0 )]  (3) 
       
     
     By means of equation (3), it is possible to take into account the change in pulse transit time due to a change in blood density. For example, if at a time t 0  a first pulse transit time PTT (t 0 ,p(t 0 ),ρ(t 0 )) was measured and at a second time t a second pulse transit time PTT (t,p(t),ρ(t)) was measured using equation (3), the influence of the different blood densities can be compensated. Each of the two pulse transit times can be converted to the blood density of the other measurement and thus made comparable: 
     
       
           PTT ( t, p ( t ), ρ( t   0 ))= PTT ( t, p ( t ), ρ( t ))[ρ( t   0 )/ρ( t )]  (3a) 
       
     
     
       
           PTT ( t   0 , p( t   0 ), ρ( t ))= PTT ( t   0 ,  p ( t   0 ), ρ( t   0 ))[ρ( t )/ρ( t   0 )]  (3b) 
       
     
     The PTT data, compensated for the influence of blood density, can be directly compared and evaluated. If a calibration was carried out beforehand with an absolute blood measuring apparatus, the pulse transit time should be converted to the blood density at the time of the calibration measurements. 
     Thus, it continues to be possible to make a precise conversion into absolute blood pressure values. 
     The inventive process and/or the inventive device of the present invention embrace(s) this finding. In this respect it is sufficient to determine a value, correlating with the blood density, as long as the square roots in equations (3a) or (3b) can be determined for blood density compensation. The evaluation unit of the inventive device, which compensates for the influence of blood density on the pulse transit time, is suitable for carrying out a compensation, according to equations (3a) or (3b). 
     An especially preferred embodiment of the process, according to the invention, is used in an embodiment of the device, according to the invention, whereby the means for determining a value, correlating with the blood density, comprise a measuring device for determining the relative blood volume or the relative change in blood volume. Assuming that the change in density according to equation (3) was caused only by volumetric changes, but not by measurement changes, the following results for the root term from equation (3) with volumes V(t 0 ) and V(t): 
     
       
         [ρ( t )/ρ( t   0 )]=[ m/V ( t )/ m/V ( t   0 )]=[ V ( t   0 )/ V ( t )]=[ V ( t   0 )/ V   0 / V ( t )/ V   0 ]=[ RBV ( t   0 )/ RBV ( t )]  (4) 
       
     
     where V 0  is a comparative volume for the relative blood volumes RBV. Thus, according to equation (4), it is sufficient to determine the relative change in blood volume; additional measurements for blood density or absolute data on blood volumes are not necessary. 
     In another embodiment of the invention, the means for determining a value correlating with the blood density are provided by a measuring apparatus for determining the hematocrit (HCT) and/or the relative change in hematocrit. If one assumes that during the measuring time, the number of red blood corpuscles and their size remain approximately constant, then the change in hematocrit is inversely proportional to the change in blood volume: 
     
       
           RBV ( t   0 )/ RBV ( t )= HCT ( t )/ HCT ( t   0 )  (5) 
       
     
     Using equations (4) and (5), equation (3) can be easily converted into an expression in which, in addition to the pulse transit time measurement, it is then only necessary to indicate the relative change in hematocrit HCT(t)/HCT(t 0 ). 
     Furthermore, the device according to the present invention exhibits advantageously as part of the evaluation unit an evaluation step that examines the values compensated according to equation (3a) or (3b) for abnormal values, using predefined criteria. For example, simple alarm threshold values can be set absolute or relative. The increase in pulse transit time over time t can also represent an alarm criterion. Lastly, if a calibration has been carried out with an absolute blood pressure measuring device, the pulse transit time can first be converted into an absolute blood pressure value and the alarm criteria can be applied to this value. 
     A preferred embodiment of the device, according to the invention, contains a unit for providing an EKG. The evaluation unit determines from the EKG the first reference point, ta, of the pulse transit time PTT. In addition, at a point at a distance from the heart, a unit for detecting the pulse waves is provided. The evaluation unit determines from the signal of this system the second reference point, te, of the pulse transit time PTT. In a preferred embodiment the detection unit is a photoplethysmograph. The pulse transit time PTT is shown as the interval between the two reference points (PTT=te-ta). 
     In a particularly advantageous embodiment, the means for determining the pulse transit time comprise at the same time the means for determining a value correlating with the blood density. Thus, for example, a photoplethysmograph can be used at the same time to determine the hematocrit. 
     The evaluation unit can also handle input and output functions with respect to the operating personnel as they are sufficiently well-known in the state of the art. 
     At this point it should be pointed out that the concept of the claimed invention can also be reapplied to the effect that the pulse transit time is not measured, but rather the pulse wave propagation velocity is directly measured. As evident from the equation (2), the dependency of the measurement values on the blood density can also be transferred directly to the pulse wave propagation velocity without diverging from the core idea of the invention. This case is regarded as an equivalent implementation of the invention. 
     The present invention is also directed to the problem of improving a hemotherapeutic arrangement with an extracorporeal blood circulation and a device for determining the pulse transit time of a patient or donor in such a manner that the changes in the blood count are taken into consideration over time and a more accurate monitoring of the pulse transit time and thereby of the blood pressure is thus made possible. 
     According to the invention, this problem is solved by a hemotherapeutic arrangement with an extracorporeal blood circulation and having a blood supply line connected at one end to the intake of the hemotherapeutic arrangement and at the other end for connection to the patient&#39;s or donor&#39;s vascular system, a blood removal line connected at one end to the outlet of the hemotherapeutic arrangement and at the other end for connection to the patient&#39;s or donor&#39;s vascular system, in which the arrangement has a device for determining the pulse transit time with means for determining the pulse transit time of pulse waves, which are propagated via the patient&#39;s or donor&#39;s vascular system and are created by heart contractions, means for determining a value correlating with the blood density, and an evaluation unit that compensates for the influence of the blood density on the pulse transit time. 
     As already stated above, in particular for extracorporeal hemotherapy, a constant observation of values, like the patient&#39;s or donor&#39;s blood pressure, is helpful. At the same time the blood count is automatically modified during hemotherapy. In particular, in the case of hemodialysis and/or hemofiltration, a change in blood volume also takes place. These forms of treatment, which are intended to replace the functions of the human kidney or at least supplement them, have the purpose, among other things, of controlling a patient&#39;s fluid balance. At each treatment, a few liters of fluid are withdrawn from the patient during approximately 4-6 hours of treatment time. Hence there is a considerable change in blood density, even if fluid from other fluid compartments of the body flows in. 
     Integrating a device, for determining the pulse transmit time, as just summarized, into such a hemotherapeutic arrangement enables a continuous, precise blood pressure measurement. In addition, the actuator and sensor technology of the existing apparatus can be resorted to. As already described in EP-A 0 911 044, the unit for detecting the pulse waves at a point at a distance from the heart can comprise a measuring sensor that is already a part of the hemotherapeutic arrangement. 
     In an advantageous embodiment of the invention, this is the arterial pressure sensor, i.e., the pressure sensor that is attached to the blood supply line for a hemotherapeutic arrangement. 
     In the state of the art, there exist other sensors, by means of which blood volume and hematocrit changes can be determined extracorporeally. The EP-A 0 358 873 describes a system for determining the ultrasonic runtime that calculates from ultrasonic runtime the relative change in blood volume and/or hematocrit. There exist optical methods that determine with the optical direct light method the hematocrit concentration at the extracorporeal blood supply line, on the basis of which the hematocrit and relative blood volumes are derived. Such a process is the object of WO 94/27495, for example. A combination of an optical direct light method with a scattered light method, in which only a light wavelength needs to be used is proposed by WO 00/33053. 
     Other details and advantages of the invention are described in greater detail with reference to the embodiments illustrated in the drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic diagram of a device, according to the invention, for applying the inventive process for determining the pulse transit time in the sense of an independent monitor. 
     FIG. 2 is a schematic diagram of an extracorporeal hemotherapeutic arrangement, consisting of a hemodialysis unit with a device, according to FIG.  1 . 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
     The measuring device  28 , depicted in FIG. 1, for determining the pulse transit time for a patient or donor, has an electrocardiograph  45 , an absolute blood pressure measuring device  43 , designed as a pressure cuff, a photoplethysmograph  29  and an evaluation unit  34 . All sensor components are connected to the evaluation unit with corresponding lines  32 ,  33  and  44 . The electrocardiograph  45  provides the voltage signals using electrodes (not shown in greater detail). Said signals are generated by means of the heart stimulation (EKG) on the surface of the patient&#39;s or donor&#39;s body. These signals are made accessible via the line  32  of the evaluation unit  34 . It determines from the position of the R peak the first reference point, ta, for determining the pulse transit time. 
     The photoplethysmograph  29  has a sensor  30  that includes an infrared light source  31   a  and a light detector  31   b . In this embodiment the light source and the light detector are designed in such a manner that three LEDs and three photodiodes make measurements possible in the three wavelengths 805 nm, 970 nm and 1,310 nm. Such a photoplethysmograph is described in WO 94/23643, which is hereby incorporated by reference. 
     The photoplethysmograph  29  is attached to a part of the body, preferably to a finger or earlobe of the patient or donor in such a manner that the light at least partially penetrates the body part before it hits the photodiodes  31   b . This can take place in a direct light arrangement, but in principle also in a scattered light arrangement. The measurement signals are sent via the line  33  to the evaluation unit  34  that comprises means to determine from the curve the second reference point of the pulse transit time. This can take place according to the process mentioned in EP-A 0 911 044. For this, only the measurement with a wavelength is necessary at first. Pulse waves cause an expansion of the vessels in the blood vessels, thus leading to a modified absorption by the modified quantity of blood and thus also the blood constituents. In the described 3-wavelength photoplethysmograph, this applies to all three wavelengths 805 nm, 970 nm and 1,030 nm, whereby the measurements in the first two wavelengths are sensitive to the substances hemoglobin and oxyhemoglobin and whereby the measurement with the third wavelength concerns plasma water absorption. 
     The absolute blood pressure measuring apparatus  43  can be used to calibrate the pulse transit time measurements. Subsequent pulse transit time measurements can then be converted by the evaluation unit  43  directly into absolute blood pressure data and, if desired, they can be indicated. For greater details see also the EP-A 0 911 044. 
     For a pulse transit time measurement, compensated for blood density, the measuring device 28 works as follows. At a first time t 0 , the evaluation unit  34  determines from an incoming EKG signal (first reference point, ta) and a subsequent pulse signal of the photoplethysmograph  29  (second reference point, te) a first pulse transit time PTT (t 0 ,p(t 0 ),ρ(t 0 )). (Since the PTT values (≈0.15 . . . 0.3a) are small compared to the time periods of consecutive PTT measurements that concern significant changes in blood pressure, it is inconsequential whether for ta, te or a time between these two times is chosen for t 0 ). At the same time, with the help of the photoplethysmograph  29 , the hematocrit of the patient&#39;s or donor&#39;s blood is determined. For this, absorption measurements are carried out for all three of the aforementioned wavelengths and evaluated as described in WO 94/23643. An absolute value for the hematocrit HCT (t 0 ) at time t 0  is then obtained. 
     The initiation of this time t 0  can be brought about by an automatically running program or by a signal from outside-manually or via an interface connection. The same applies to the initiation of a second measurement at a time t with t&gt;t 0 , for which the pulse transit time PTT (t,p(t),ρ(t)) as well as a corresponding value HCT(t) are measured. 
     Then the means for blood density compensation of the pulse transit time in the evaluation unit  34  calculate the blood density-compensated pulse transit time PTT (t,p(t),ρ(t 0 )) and, respectively, PTT (t 0 ,p(t 0 ),ρ(t)). 
     The value obtained can then be indicated directly or after conversion into a blood pressure value, if a calibration was carried out using the absolute blood pressure measuring apparatus  43 , on a display unit  36  that is connected to the evaluation unit  34  via a line  35 . In addition, alarms  41  can be provided that are connected with a line  42  to the evaluation unit  34 . These are suitable for emitting acoustical or optical alarm signals, if the evaluation unit  34  gives a corresponding signal for this. This then occurs when the evaluation unit indicates an abnormal condition using the obtained blood pressure or pulse transit time values, e.g. when the threshold value is exceeded or falls below or when the value changes too quickly within a brief time. 
     FIG. 2 shows a hemotherapeutic arrangement with a hemodialyzer as the hemotherapy unit. This apparatus corresponds roughly to the device described in EP-A 0 911 044. The essential components are briefly described here nevertheless. The hemotherapeutic arrangement has a hemodialyzer  1  that is separated by a semipermeable membrane  2  into a blood chamber  3  and a dialyzer fluid chamber  4 . The intake of the blood chamber is connected to one end of a blood supply line  5 , into which a blood pump  6  is connected, while the outlet of the blood chamber  3  is connected to one end of a blood supply line  7 , into which a drip chamber  8  is connected. The extracorporeal blood circulation also has a unit  9  for automatic application of an infusion, in particular of a physiological NaCl solution (typically 200 ml) or also online filtered substitute solution at a substitution rate of typically 150 ml/min. The infusion, that usually takes place in bolus-like form, is fed to the patient via a feed line  10  that is connected upstream from the drip chamber  8  to the blood supply line  7 . 
     The dialysis fluid system of the hemodialysis device also comprises a unit  11  for preparation of the dialysis fluid, whereby different compounds of the dialysis fluid (electrolytic administration) can be specified. The dialysis fluid preparation unit  11  has a temperature equalizing unit  12 , with which the temperature of the dialysis fluid can be set to various values and kept constant. It is connected via the first section  13  of a dialysis fluid feed line to the inlet of the first chamber half  14   a  of a balancing unit  15 . The second section  16  of the dialysis fluid feed line connects the outlet of the first balancing chamber half  14   a  to the intake of the dialysis fluid chamber  4 . The outlet of the dialysis fluid chamber  4  is connected via the first section  17  of a dialysis fluid removal line to the intake of the second balancing chamber half  14   b . A dialysis fluid pump  18  is connected into the first section  17   a  of the dialysis fluid removal line. The outlet of the second balancing chamber half  14   b  is connected via the second section  17   b  of the dialysis fluid removal line to the outlet  19 . Upstream from the dialysis fluid pump  18 , an ultrafiltrate line  20 , also leading to the outlet  19 , branches off from the dialysis fluid removal line  17 . An ultrafiltration pump  21  is connected into the ultrafiltrate line  20 . 
     The hemodialysis device also comprises a central control unit  22  that is connected via control lines  23  through  27  to the blood pump  6 , the dialysis fluid pump  18 , the ultrafiltration pump  21 , the unit  11  for preparation of the dialysis fluid and the unit  9  for automatic application of a bolus. 
     During the hemodialysis treatment, the patient&#39;s blood flows through the blood chamber  3 ; and the dialysis fluid flows through the dialysis fluid chamber  4  of the dialyzer  1 . Since the balancing unit  15  is connected into the dialysis fluid path, only as much dialyzer fluid can flow through the dialysis fluid supply line  16  as dialysis fluid can flow out through the dialysis fluid removal line  17 . Fluid can be removed from the patient with the ultrafiltration pump  21 . 
     The hemodialysis device also has a device  28  for continuous determination of the pulse transit time according to FIG.  1 . The reference numerals of these components are the same as in FIG.  1 . For practical reasons, the alarm  41  and the display unit  36  are illustrated in the present case by the already present simple elements  41 ′ and  36 ′ together with the control lines  42 ′ and  35 ′ of the hemotherapeutic arrangement, which are connected to the control unit  22 . The evaluation unit  34  is also connected via a line  37  to the control unit  22 . Both units can indeed represent physically separate units, but they can also be combined in a shared unit, practically the control unit for the hemotherapy device. The separation then has only a functional significance. 
     The operating mode of the device  28  has already been explained. In the case of the hemodialysis device, according to FIG. 2, the control unit  22  then also receives the blood density-compensated measurement values of the evaluation unit  34 . According to the stored alarm criteria, the control unit  22  can propose or, optionally, automatically carry out countermeasures to counteract a recognized critical blood pressure condition. 
     Owing to the ultrafiltration carried out during the hemodialysis treatment, the patient has considerable quantities of fluid withdrawn, a state that can lead to a decrease in blood pressure (hypotension). By semi-continuous measurement of the blood pressure by means of the pulse transit time method (approximately one measurement per second), a hypotension phase can already be recognized early before noticeable symptoms appear in the patient. 
     Owing to the evaluation unit  34 , these measurement values are then provided with increased accuracy, because the influence of the blood density, changing due to the ultrafiltration, is compensated. A decrease in the relative blood volume by 20% is not rare during hemodialysis. According to equations (3) and (4), the compensation of the blood pressure change results in approximately 20% more precise measurement value for a later measurement of the pulse transit time for a comparison with an earlier measurement. 
     Examples of countermeasures against a decrease in blood pressure can be introduced by the control unit by a change in the electrolytic concentration through the control line  23 , by an initiation of an infusion through the control line  26 , by reducing or even switching off the ultrafiltration through the line  24  or even by immediately stopping the treatment by stopping the blood pump  6 . 
     In another embodiment of the invention, an arterial pressure sensor  46  on the blood supply line  5 , usually present anyway, is used to detect the second reference point te for the pulse transit time measurement. In this case the pressure sensor  46  is connected via a line  47  to the evaluation unit  34 . In this embodiment there is no need for photoplethysmograph  28  for this function. 
     In a particularly advantageous embodiment the photoplethysmograph  29  can be dispensed with altogether. In this case the means for determining a value correlating with the blood density are provided extracorporeally. To this end, a blood volume monitor  48  can be attached in the manner described in EP-A 0 358 873 to the blood supply line  5 . This blood volume monitor consists of an ultrasonic transmitter  48   a  and an ultrasonic receiver  48   b  that determine the runtime of the ultrasonic signal through the blood supply line. The blood volume monitor  48  is connected via a line  49  to the evaluation unit  34  that determines from the signals a change in the relative blood volume or the hematocrit between the times t 0  and t. It is also conceivable to use other extracorporeal sensors that determine the hematocrit optically or using other measurement variables on the blood supply line, for example. 
     The handling of functions in the extracorporeal circulation can be divided differently. Thus, for certain situations it may be reasonable to integrate the means for determining a value, correlating with the blood density, into the extracorporeal circulation, but to leave the means for determining the pulse transit time completely directly on the patient&#39;s body. 
     The invention being thus described, it will be apparent that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be recognized by one skilled in the art are intended to be included within the scope of the following claims.