Measuring the change of intravascular blood volume during blood filtration

To determine in simple manner the change of the intravascular blood volume during filtration, in the extracorporeal blood circuit (2) of a blood purification apparatus at least one ultrasonic sensor (15) is arranged which is connected to an evaluating unit (18) which is configured in such a manner that at the start of the filtration a first ultrasonic signal is stored and during the filtration the change of the ultrasonic signals is determined. From the change of the ultrasonic signals the change of the hematocrit is determined and from this the change of the intravascular blood volume is deduced.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The invention proceeds from an apparatus for measuring the change of the 
intravascular blood volume as is known from EP 0 089 003. 
2. Description of the Related Art 
In blood purifying methods in which a fluid exchange or a withdrawal of 
fluid is provided it is necessary to control this liquid or fluid exchange 
in such a manner that undesired negative effects on the health of the 
patient are avoided. 
Methods in which this necessity exists are for example hemodialysis, 
hemofiltration and plasma filtration. 
The removal of fluid excess from the body of the patient requires a very 
precise control of the fluid balance and for this reason dialysis methods 
can only be carried out with fluid-balancing means. In spite of this 
precise balancing dialysis-typical unpleasant effects still occur in 
patients, such as headache, vomiting and muscular cramps. The probable 
reason for this is the too rapid extraction of sodium ions from the blood 
due to the concentration difference of sodium in the blood (extracorporeal 
circuit) and in the dialysis solution and in the too rapid fluid 
withdrawal. 
It is known in hemodialysis to carry out the so-called volumetric 
ultrafiltration control. The prior art of ultrafiltration control or 
monitoring in hemofiltration is the balancing of the ultrafiltrate and the 
substitution solution with the aid of one or two weighing devices or 
balances, cf. for example DE-OS 3,132,790. These methods, which have 
already been industrially employed, permit a fluid extraction in 
accordance with the direction of the physician or operator, i.e. in 
accordance with the input over a predetermined period of time, a certain 
amount of fluid is withdrawn from the patient. It is also known to 
prescribe a so-called "ultrafiltration profile", i.e. a time-dependent 
variation of the ultrafiltration rate. The objective of the variation of 
the ultrafiltration rate with time is the withdrawal of the predetermined 
ultrafiltration amount from the patient in the way causing the least 
possible detrimental effects, i.e. in particular avoiding blood pressure 
drops. 
In addition, by entering physiological and treatment parameters into such 
apparatuses for carrying out the ultrafiltration the change of the 
intracellular and extracellular volume can be predicted. Since these 
changes considerably influence the health of the patient the operator of 
the apparatus attempts to configure the ultrafiltration profile in such a 
manner that as uniform as possible a decrease of the extracellular volume 
takes place. Although this has led to an improvement of the otherwise 
unsatisfactory treatment result in the case of patients where the 
adjustment is difficult, this procedure is too complicated for a routine 
method. 
Aforementioned EP 0 089 003 discloses a blood purification apparatus in 
which in the extracorporeal blood circuit a hematocrit measuring device is 
arranged which is connected to a control and evaluating unit. This 
hematocrit measuring device is based on an electrical resistance 
measurement of the blood during the blood filtration. From the change of 
the resistance values of the blood the change of the hematocrit is 
determined and from the latter the intravascular blood volume is deduced. 
Such resistance measurements have however the disadvantage that the 
measured values are falsified by other influencing factors such as flow 
rate, erythrocyte orientation, etc. 
In DE-OS 3,640,089, which is based on the principle known from EP 0 089 
003, from the values obtained from a conductivity relative measuring 
arrangement and from the conductivity of the fresh dialysis solution and 
the blood flow, as well as the performance parameters of the dialyzer, the 
plasma conductivity and the change of the plasma and blood conductivity 
are determined. Thereafter the hematocrit is calculated during the 
dialysis and from the hematocrit the change in the intravascular blood 
volume is deduced and in dependence upon the change of the intravascular 
blood volume the ultrafiltration rate determined. 
A further apparatus for measuring the conductivity is known from 
EP-0029793. 
Other methods for blood volume variation measurement are described for 
example in: 
R. N. Greenwood, C. Aldridge, W. R. Cattell, Clinical Science (1984) 66, 
575-583: "Serial blood water estimations and in-line blood viscometry: the 
continuous measurement of blood volume during dialysis procedures" 
and U. Schallenberg, S. Stiller, H. Mann, Life Support Systems (1987) 5, "A 
New Method of Continuous Haemoglobinometric Measurement of Blood Volume 
During Haemodialysis". 
However of these known methods has so far led to industrial use because 
firstly there are difficult to surmount measuring and method problems and 
secondly complicated and additional apparatuses are necessary, such as 
conductivity measuring devices. 
SUMMARY OF THE INVENTION 
The object of the invention is therefore to provide an apparatus with which 
these disadvantages are avoided and with which the change of the 
intravascular blood volume during the filtration can be determined in 
simple manner. 
The apparatus of the present invention comprises at least one ultrasonic 
sensor which is arranged in the extracorporeal blood circuit of the blood 
purifying apparatus and an evaluating unit which is connected to said 
ultrasonic sensor. The evaluating unit is constructed in such a manner 
that at the start of the filtration a first ultrasonic signal is stored 
and during the filtration the change of the ultrasonic signals is 
determined. From this change the variation of the hematocrit is determined 
and from the latter the change of the intravascular blood volume deduced. 
The ultrasonic sensor may be installed into the extracorporeal blood 
circuit of a hemodialysis apparatus, a hemofiltration apparatus or a 
plasma filtration apparatus. 
In the work by E. L. Bradley and Jose Sacerio ("The velocity of ultrasound 
in human blood under varying physiologic parameters", Journal of Surgical 
Research 12, 290-297, 1972) ultrasonic measurements on human blood are 
described and the relationships between the ultrasonic signals and the 
temperature, the hematocrit and the protein content explained. It is also 
apparent from this work that the measurements are made in the Megahertz 
range and it was found that the sound velocity is independent of the 
frequency. 
In K. Kirk Shung ("Tissue Characterization with Ultrasound", Chapter 10, 
page 230, 1986) an empirical formula is given based on the work of Bradley 
and Sacerio. According to this formula the relationship between the sound 
velocity c in m/sec, the temperature T in .degree. C., the hematocrit H in 
% and protein content w in g% is as follows: 
EQU c=1482.26+1.54 T+0.51 H+2.8 w (1) 
If the normal values specified by K. Kirk Shung are inserted the following 
is obtained 
EQU c=1482.26+56.98+20.4+16.8 (2) 
It is apparent from this that the hematocrit and the protein content enter 
in the same order of magnitude. 
In the case of a hyperhydrated patient whose condition is to be corrected 
by ultrafiltration the two values change proportionally. The order of 
magnitude of this change is 10-20%, corresponding to a change of the sound 
velocity of 3-6 m/sec which in turn is equivalent to the velocity change 
caused by a temperature change of 2.degree. C. This shows that as a rule, 
account must be taken of the temperature. 
Consequently, if the temperature T is additionally measured information on 
the hematocrit can be derived from the measured sound velocity. 
According to a particular embodiment of the apparatus according to the 
invention in the extracorporeal circuit at least one temperature measuring 
device is therefore arranged which is likewise connected to the evaluating 
unit which is constructed in such a manner that the hematocrit can be 
corrected with regard to the temperature. 
If in this manner with the aid of the ultrasonic sensor before starting the 
treatment the hematocrit H.sub.o is measured and during the treatment the 
particular hematocrit H, then the change of the blood volume dV can be 
determined as follows: 
##EQU1## 
The desired resolution of 1% change of the blood volume makes it necessary 
to measure a relative change of the ultrasonic velocity of about 0.4 
m/sec. This is about 0.03% of the ultrasonic velocity in serum. 
From this, the requirements of the size of the measuring path and the 
magnitude of the measuring frequency can be derived. For a travelling 
distance of 1 cm the travelling time is of the order of magnitude of 6 
.mu.sec and the desired resolution 2 nsec. This resolution lies within the 
range of that which can be achieved with conventional electronic circuits. 
To achieve this resolution in practice a frequency of the order of 
magnitude of MHz or more is necessary. The estimation of the wavelength 
gives for 1 MHz a wavelength of 1.5 mm. 
The blood density can be measured with an ultrasonic sensor which is 
arranged in the arterial part of the extracorporeal blood circuit. 
To follow the relative change of the blood density during the blood 
purification in accordance with a further embodiment in the extracorporeal 
blood circuit two ultrasonic sensors are installed, one being arranged in 
the arterial part of the blood circuit and the second in the venous part 
of the blood circuit. Both the ultrasonic sensors are connected to the 
evaluating unit which is designed in such a manner that precisely this 
additional relative change of the ultrasonic signals during the filtration 
is detected and from it the relative change of the intravascular blood 
volume can be determined. 
The advantage of the apparatus claimed further resides in that the 
ultrasonic sensors can be combined with the measurement of other 
parameters which are likewise measured with ultrasound, thus enabling the 
apparatus expenditure to be kept within limits. 
Thus, according to a further embodiment the evaluating unit is equipped 
with a means for detecting air. 
Furthermore, the ultrasonic sensor can be integrated into a drip chamber 
and the evaluating unit constructed for detecting the fluid level. 
Preferably, the drip chamber in this case is provided with a measuring 
mark which reflects ultrasonic waves and is arranged at a defined 
distance, i.e. unalterable during the measurement, beneath the fluid level 
to be expected. The signal transmitted by the transmitter is then 
reflected twice, once at the measuring mark and again at the fluid 
surface. From the first signal, if the spacing is known, the sonic 
velocity can be derived and from the result and the travelling time of the 
second signal the level of the fluid surface determined. 
Furthermore, the apparatus can be combined with a Doppler flow measuring 
device. These possible combinations show that a change of the blood volume 
can be determined without great additional technical expenditure as was 
necessary in the prior art. 
The ultrasonic sensor can be equipped in known manner with a transmitter 
and an oppositely disposed receiver but can also operate by employing the 
reflection. For this purpose the receiver is not arranged opposite but 
corresponding to the angle of reflection which may for example be 
&lt;90.degree. or&gt; 270.degree.. With a reflection angle of 180.degree. the 
receiver is identical to the transmitter.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The hemodialysis apparatus consists essentially of a dialysis solution part 
1 and an extracorporeal blood circuit 2 between which a dialyzer 3 is 
disposed which has a dialysis solution compartment 4 and a blood 
compartment 5. The dialysis solution compartment 4 is connected upstream 
of the dialyzer 3 via a dialysis solution conduit 6 to a dialysis solution 
source 7. Downstream of the dialyzer 3 the dialysis solution compartment 4 
is followed by a further conduit 10 which has a dialysis solution pump 12. 
In the extracorporeal blood circuit 2 in the blood conduit 13 upstream of 
the dialyzer 3 a first temperature measuring device 21 and a first 
ultrasonic sensor 15 are disposed. 
Connected to the blood compartment 5 downstream of the dialyzer 3 is a 
further blood conduit 16 which additionally comprises a second ultrasonic 
sensor 17 and a further temperature measuring device 22. The latter 
temperature measuring device 22 is necessary to enable account to be taken 
of temperature losses occurring in the dialysis. 
The dialysis solution pump 12 and the blood pump 14 as well as the 
ultrasonic sensors 15 and 17 and the temperature measuring devices 21 and 
22 pass their delivery signals or measured values to an evaluating unit 18 
in which the determination of the blood volume is carried out. The 
evaluating unit 18 is further connected to an input unit 19 and a control 
unit 20 which passes its signals to the dialysis solution mixing means 7, 
the dialysis solution pump 12 and the blood pump 14. 
In the dialysis solution mixing means 7 a concentrate pump, not shown in 
detail, and a corresponding water inlet are arranged, the dialysis 
solution being made up in accordance with the output signal of the control 
unit 20. 
By determining the change of the blood volume continuously during the 
treatment with the aid of the ultrasonic sensors 15 and 17 a continuous 
monitoring of the fluid amount extracted is possible. If deviations occur 
in the predetermined fluid extraction rate, which is entered via the input 
unit 19, the evaluating unit 18, taking account of the delivery rates of 
the pumps 14 and 12, determines whether these delivery rates must be 
changed or the dialysis solution mixing means driven differently. This is 
done by corresponding signals which are sent to the control unit 20.