WO2011063879A1

WO2011063879A1 - Measuring device for registering the propagation speed of pulse waves and method for determining the volumetric flow of a discontinuously operational pump

Info

Publication number: WO2011063879A1
Application number: PCT/EP2010/006516
Authority: WO
Inventors: Raymond Glocker
Original assignee: Mhm Harzbecher Medizintechnik Gmbh
Priority date: 2009-11-24
Filing date: 2010-10-26
Publication date: 2011-06-03
Also published as: DE102009054319A1

Abstract

The invention describes a measuring device (1) with a sensor arrangement for extracorporeally registering dynamic blood pressure changes and for extracorporeally registering the propagation speed of pulse waves in the human or animal circulatory system, characterized by a partly perfused housing (2, 7, 18) with a wet area (3), enclosed by at least two membranes (6) and a separation wall within the housing (2, 7, 18), and a dry area (4), wherein the membranes (6) are arranged in the separation wall (2) and the centroids of the membranes (6) define a longitudinal axis (8), wherein the housing has a first opening (9) and a second opening (10), basically along the longitudinal axis (8), for connection to the circulatory system of the patient and/or of an infusion device, and wherein the membranes (6) have a distance of between approximately 20 mm and 60 mm between their centroids, and wherein a printed circuit (11, 12) is arranged in the dry area (4) for connecting the membranes (6) electrically and for establishing an electrical connection to a connection line for connecting the measuring device to an evaluation, display, storage and/or monitoring device, and also a method.

Description

Measuring device for registering the propagation speed of pulse waves and method for determining the volumetric flow of a discontinuously operational pump

The invention relates to a measuring device with a sensor arrangement for registering the propagation speed of pulse waves in the human or animal circulatory system and to a method for determining the volumetric flow of a discontinuously operational pump for pumping a non-Newtonian liquid through a branched, closed line network .

Field of the invention

Cardiovascular diseases constitute the largest proportion of diseases in humans in industrialized nations; more particularly, such diseases also constitute the most common cause of death. Measuring the blood pressure in this case constitutes the most common metrological measure in the diagnosis and therapy of cardiovascular diseases. A blood-pressure measurement with a high time-resolution over a relatively long period of time and the blood-pressure profiles registered thereby allow further information to be obtained about the state of the cardiovascular system.

Prior art

A large number of highly developed systems for extracorporeal metrological blood-pressure registration are known and are utilized. In the process, an access from the outside is typically laid into a blood vessel of the patient, by means of which access e.g. an infusion is supplied or blood of the patient is removed for haemodialysis and/or returned again. In the process, the liquid column is guided through a so- called pressure dome, which is connected to a pressure la transducer via a tight membrane, which converts the pressure in the pressure dome and, more particularly, the changes in the pressure into electrical signals, which can subsequently be displayed, stored and analysed by appropriate display or recording devices.

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Such measuring devices are described, for example, in DE 100 32 616 Al , DE 103 21 099 Al , DE 10 2004 027 044 Al and DE 198 02 615 Al . However, it is problematic to register the blood pressure over a relatively long period of time, for example one or more days or weeks, in patients who are recognized as patients at risk but the examination of whom in a medical practice or in a hospital does not supply sufficient information for reliable diagnosis or therapy settings and therefore at least the blood pressure needs to be registered over a relatively long period of time. The aforementioned apparatuses and methods can be eliminated in this case because the extracorporeal measurement can generally only be taken in a stationary manner in the medical practice or in the hospital. Transportable long-term blood measuring instruments are known, which are worn on the body by the patient and carry out a conventional blood-pressure measurement at predefined fixed time intervals using a permanently attached blood-pressure cuff. As a result of the size of the instruments and the negative effect on the patient due to regular squeezing of an upper arm and the noise and vibration disturbances due to the air pump, these devices only have very limited suitability because they cause the patient additional stress, more particularly these instruments do not allow normal sleep . Taking into account the fact that an estimated one million people in Germany suffer from high blood pressure (hypertension) that cannot be reliably regulated by conventional examination and therapy methods, and the fact that, although an increased myocardial infarction risk is known in very many patients, approximately 30% of patients suffering a myocardial infarction nevertheless pass away before reaching a clinic, work is currently being undertaken - 3 - on an intravascular implantable monitoring system for hypertensive patients (Hyper- IMS) , by means of which intracorporeal long-term monitoring for up to six months of the blood pressure, the pulse and the body temperature should be effected. The system consists of an implantable pressure and temperature sensor, which is inserted into a blood vessel by minimally invasive means, and the data therefrom is transmitted extracorporeally and wirelessly to a transmission station by means of inductive coupling, in which transmission station the obtained data is buffered or directly transmitted to a stationary evaluation station. A significant problem with this project has emerged as the electrical energy supply of the implanted elements, and so a capacitive pressure sensor with pressure cells having an upper cut-off frequency of more than 20 kHz will probably be used as a pressure sensor. Due to the low signal strength, direct amplification of the signals is necessary in order to obtain a signal-to-noise ratio that is suitable for the evaluation. The implanted circuit is supplied with energy by the transmission station, worn on the belt for example, using inductive coupling or by a co- implanted battery, the service life of which battery, however, limits the period of use.

DE 10 2007 030 163 Al has disclosed a measuring device with an implantable sensor arrangement for registering the propagation speed of pulse waves in the human or animal circulatory system, which more particularly is provided for being implanted outside of the bloodstream of a patient. The measuring device described is used for the purpose of allowing intracorporeal long-term monitoring of up to six months, with the measuring device continuously registering measured values, for example even during showering, and transmitting these values to an external readout station via a transponder circuit, time-buffered where necessary. The transponder - 4 - circuit is housed on a flexible chip. The diameter of the chip is approximately 1 to 2 cm in size; a sensor arrangement with three pressure sensors is arranged on its underside, i.e. the side of the transponder circuit facing away from the readout station. The three sensors 5 are arranged equidistantly on the film in the form of an equilateral triangle. When the sensors are arranged as an equilateral triangle, the operator need pay no further attention to the angular position of the implant with respect to the artery, which greatly simplifies the procedure.

The energy required to operate the circuit should be coupled into the transponder circuit from a readout instrument worn by the patient on a belt.

DT 2 314 336 describes a catheter for measuring the blood flow speed with the aid of an electromagnetic sensor, in which a prepared wire loop made of beryllium copper is introduced into a blood vessel and is excited by a magnetic field generated outside of the body of the patient. Here, the wire loop is embodied in an elongate narrow form, and so it can be compressed radially against the elastic material forces and can be introduced into the blood vessel through a catheter.

Due to the elastic restoring forces, the wire loop expands radially after being pushed out of a catheter until it rests against the walls of the blood vessel. A double phase-shift network can be used to set the apparatus by switching such that the pass of a pulse wave can be detected by indirect measurement of the change in the artery diameter.

WO 2007/067 690 A2 discloses an implantable system for measuring the blood pressure and the blood-pressure waveform. In that document, it is proposed to attach a plurality of force sensors under mechanical pretension to an artery using a mechanically rigid clamp. The - 5 - blood pressure can be established by the force measurement if the elastic behaviour of the artery wall and the clamp is known. For this purpose, various transfer functions are specified in the document. The pulse wave speed can be established by registering the time differences of the peak of the pulse wave passing between the sensors .

Summary of the invention

The invention is therefore based on the object of improving the application of measuring the pulse wave speed . According to the invention, the object is achieved by an extracorporeal measuring device, characterized by a partly perfused housing with a wet area, enclosed by at least two membranes and a separation wall within the housing, and a dry area, wherein the membranes are arranged in the separation wall and the centroids of the membranes define a longitudinal axis, wherein the housing has a first opening and a second opening, basically along the longitudinal axis, for connection to the circulatory system of the patient and/or of an infusion device, and wherein the membranes have a distance of between approximately 20 mm and 60 mm between their centroids, and wherein a printed circuit is arranged in the dry area for connecting the membranes electrically and for establishing an electrical connection to a connection line for connecting the measuring device to an evaluation, display, storage and/or monitoring device, and also a method with the following steps: arranging a measuring device with a sensor arrangement with at least two pressure-gradient sensors at a predetermined distance along the longitudinal extent of a line section arranged outside of the line network, fed by the pump, within the measuring device, which line section is - 6 - hydraulically connected to the line network directly or via an auxiliary liquid, registering at least the relative pressure profile at at least two sites spaced apart by a known distance along the longitudinal extent of the line section with the aid of the pressure- gradient sensors, establishing the time of the greatest pressure rise rate and/or the time of maximum pressure during the pass of a pressure wave at each of the pressure-gradient sensors, establishing the time of the pass of a pressure wave between the at least two spaced apart sites and determining the propagation speed of the wave from the pass time by forming the difference between the established times of the pass of a pressure wave between two pressure-gradient sensors, and determining a correction factor for correcting a reference value for the volumetric flow as a function of the propagation speed of a pressure wave.

The object is furthermore achieved by a data storage medium containing a program for carrying out the method, and achieved by a measuring arrangement formed with the measuring device.

The embodiment of a measuring device or of a method according to the invention with an extracorporeal sensor arrangement for registering the propagation speed of pulse waves in the human or animal circulatory system affords the possibility of registering, without an invasive intervention, in an easily manageable, reliable and cost-effective fashion, a further important parameter for at-risk patients that provides indications for a threatening heart failure, namely the stroke volume of the heart, i.e. the volume pumped per heart beat, or the cardiac output.

Compared to the prior art, the invention is advantageous in that surgery on the human body can be dispensed with. Even minimally invasive surgery, let - 7 - alone surgery required for applying the system known from WO 2007/067 690 A2 , requires anaesthetization of the patient and harbours the risk of an infection. Infections in the region of the blood vessel walls harbour a high risk of complications.

These risks to the patient can be avoided by the apparatus according to the invention and the method according to the invention.

Furthermore, the requirement is dispensed with for implanting an energy source for operating an implantable measuring device and/or an additional extracorporeally affixed device for irradiating the body for excitement, energy supply and/or wireless data exchange with an implanted measuring device .

In addition to the simple and cost-effective design, a further advantage of the apparatus according to the invention is a high measurement precision in registering dynamic parameters, because errors as a result of the blood vessels changing properties with a direct effect thereof on the measuring system are ruled out. Such changes in the properties can, e.g. in the arrangement proposed in DT 2 314 336, come about as a result of a change in the blood-vessel diameter due to a change in the position of the patient body or a movement of the patient. There can be changes in the properties in the solution proposed in WO 2007/067 690 A2 as a result of a deviation or change in the mechanical-elastic properties of the vessel walls compared to the applied model, or else changes in time. Furthermore, there is uncertainty when measuring the pass speed of the pulse wave due to the fact that the precise distance between the individual implanted sensors along the flow path must be known. Exact positioning of the sensors during the operation for the implantation will not be possible; furthermore, the - 8 - distance can change over time as a result of the longitudinal elasticity and/or change in length of the blood vessel. Due to the simple design of the measuring device according to the invention, and the low weight of the measuring device resulting therefrom, it is possible in the process to design the use to be patient-friendly, and so such a measuring device can be used permanently whilst the vital parameters of the patient are monitored, without this being associated with significant limitations or adverse effects for the patient beyond what is given anyway. The stroke volume or the cardiac output of the heart cannot be measured directly without relatively large interventions. Cardiac output determination, e.g. using the dye-thinning or thermodilution method, is very complicated and cannot be carried out continuously either. In principle, the volumetric flow can be determined by the pressure as a function of time in a line section, with the flow resistances being influenced by the geometric parameters of the vessel and the viscosity of the medium. However, in blood vessels in a human and an animal, the geometric parameters of the vessel are not constant because the artery wall is flexible and the diameter of the vessel varies accordingly as a function of pressure. However, the flexibility of the wall of blood vessels likewise cannot be determined in the patient without large-scale intervention or removing samples of arteries including surrounding tissue.

However, due to its long-standing activity in the field of medical technology, the applicant has learnt that the flexibility of blood vessels is substantially dependent on the hardening of the vessel wall, i.e. the flexibility of the vessel wall reduces as sclerotic - 9 - deposits on the vessel wall increase. This reduction in the elasticity of the vessel wall is also associated with internal bleeding in arteriosclerosis patients. It was additionally found that there is a connection between the flexibility of the vessel walls, and hence a degree of hardening of the vessels, and the propagation speed of the pulse waves in the arteries. Thus, an average pulse wave speed of approximately 500 cm/s was determined in young, healthy humans, one of approximately 1000 cm/s was determined in average 40- to 50-year-olds and one of approximately 1500 cm/s was determined in the elderly between 70 and 80 years old. Using appropriate reference values therefore affords the possibility of establishing the flexibility of the vessel wall from the propagation speed of the pulse wave. Moreover, significant changes in the propagation speed can be used directly as an indicator for unusual changes to the vessels. However, using the measuring device according to the invention and the method according to the invention allows the stroke volume or the cardiac output to be established in real time; in particular, changes in these values can now be recognized quickly and reliably. Recognizing a change of stroke volume or cardiac output beyond boundaries that can be defined in advance allows a critical change in the state of a patient, e.g. after a bypass operation, to be recognized long before this change can be recognized by a critical change in the blood-pressure values or e.g. the oxygen content in the blood. As a result of this, precious time for initiating stabilizing medical measures can be gained and the risk of a lethal progress of the complication or permanent damage due to insufficient oxygen supply can thereby be reduced significantly. For this purpose, the method according to the invention is expediently characterized by sounding an alarm as soon as the value, obtained from - 10 - determining the volumetric flow, falls below and/or exceeds a predefined upper and/or lower absolute or relative threshold. It is particularly expedient for the membranes each to form pressure-gradient sensors and to be piezoelectric sensors, more particularly from a film of piezoelectric material such as polyvinylidene fluoride (PVDF) . The PVDF material supplies a particularly strong output signal in the case of a change in length, which signal is approximately 10 times stronger than that of conventional ceramic piezoresistive pressure sensors, and so an energy supply for amplifiers or the like can be dispensed with. The membranes can expediently also consist of a PVDF copolymer or a laminate containing a layer of a PVDF or a PVDF copolymer. In order to achieve the highest possible sensitivity of the pressure-gradient sensors formed in this fashion, it is expedient to pretension the membrane or to arc it in a cup-shaped fashion, such that a pressure force acting on the surface of the membrane causes a change in membrane length at least in a direction across its thickness . Accordingly, it is advantageous if an electrical pickup on each membrane is brought about by electrical pickups on sides of the membrane that lie opposite one another along their greatest longitudinal extent, with the electrical pickups preferably being arranged approximately along the longitudinal axis.

It is preferred if the centre-to-centre distance of the membranes lies between 25 and 52 mm, preferably between 30 and 50 mm. Furthermore, it is advantageous if the measuring device has an upper cut-off frequency of at least approximately 10 kHz, preferably 20 kHz, more preferably of 36 kHz and particularly preferably of over 40 kHz. - 11 -

In the method according to the invention, it is particularly advantageous to determine the correction factor by correlating the propagation speed with an associated value for the flexibility of the wall of the line network section, or directly with the established propagation speed, which serves as a measure for the flexibility of the wall. More precise determination of the volumetric flow is possible if the correction factor is adapted by correlating typified parameters with an adaptation value. Such additional parameters can be the sex and/or the body mass index of a patient when determining the cardiac output . In the case of the measuring arrangement according to the invention, it is advantageous for a simple, reliable application, which does not adversely affect the patient much, if the connection element for the fluid connection of the measuring device is embodied with a cannula, a catheter port or an insertion valve of a catheter for insertion into a blood vessel of a patient and/or the flow path has a length of no more than 0.15 m, preferably no more than 11 cm, more preferably no more than 7 cm. The inventor has discovered that in the case of the conventional application of PVC tubings as connection elements, a change in the propagation speed of the pressure wave can be observed at relatively long lengths, and this can undesirably have an influence on the measurement results.

The measuring device is advantageously connected by an electrical connection to a connection line for connecting the measuring device to an evaluation, display, storage and/or monitoring device for carrying out the method according to the invention. Here, it is particularly advantageous for the safety of the patient if the storage device is arranged separately from the - 12 - evaluation, display and/or monitoring device and connected to the measuring device such that the signals from the measuring device are looped through to the evaluation, display and/or monitoring device independently of the operating state of the storage device. Firstly, this affords the possibility of e.g. separately connecting the storage device to a PC for reading out and evaluating the stored data without interrupting the ongoing monitoring via a conventional patient monitoring system; furthermore, the monitoring and display function of the evaluation, display and/or monitoring device is maintained should the storage device be switched off, be faulty or have failed. This provides additional safety for the patient.

Hereinbelow, the invention is intended to be explained in more detail with the aid of an exemplary embodiment illustrated in the drawings, in which:

Figure 1 shows a schematic exploded view of measuring device according to the invention

Figure 2 shows a schematic exploded view of a plug arrangement for a measuring device according to the invention, and

Figure 3 shows a graph of a correction factor for correcting a reference value for the volumetric flow as a function of the propagation speed of a pressure wave as per a method according to the invention.

Figure 1 shows a perspective exploded view of a measuring device according to the invention, referred to by 1 in its entirety. The measuring device comprises a main housing part 2, which simultaneously forms a separation wall between a wet area 3 and a dry area 4. Here, the wet area 3 is understood to be that part of - 13 - the housing of the measuring device 1 through which blood from a human or animal circulatory system or an auxiliary liquid perfuses during proper use. By way of example, the auxiliary liquid can consist of an infusion solution.

Two cut-outs 5 for holding respectively one membrane 6 are provided in the separation wall section of the main housing part 2. Each of the membranes 6 consists of a PVDC film. The membranes 6 can also consist of a PVDF copolymer or a laminate containing a layer of a PVDF or a PCDF copolymer. The membranes 6 are expediently attached to the separation wall section of the main housing part 2 by adhesive bonding, ultrasonic welding or any other suitable connection technique allowing a liquid-tight connection. The wet area 3 is furthermore closed off by a cover 7 lying opposite the separation wall section of the main housing part 2, which cover is likewise connected to the main housing part 2 in a liquid-tight fashion by adhesive bonding, ultrasonic welding or any other suitable connection technique allowing a liquid-tight connection. The cover 7 preferably consists of a transparent material and thus allows visual monitoring of a bubble- free filling of the wet area 3 when the measuring device 1 is used.

Bubble-free filling is important for good functioning of the measuring device because gas bubbles are compressible and falsify the measurement of the dynamic pressure changes due to their damping effect.

The centres of the membranes 6, which simultaneously form the centroids of the membranes 6 in this case, form a longitudinal axis that is indicated by the line 8. Along the longitudinal axis 8, the main housing part 2 has a first opening 9 and a second opening 10 for hydraulically connecting the wet area 3 to e.g. the circulatory system of a patient and, possibly, of an infusion device (not illustrated) . - 14 -

The centres of the membranes are expediently arced in advance in a cup- shaped fashion with respect to the membrane edge, and so exerting a pressure force on the membrane 6 leads directly to a longitudinal strain of the membrane in the longitudinal extent. This is particularly expedient because PVDF films subjected to a mechanical load in the frequency range in question here have a many times higher sensitivity to the piezoelectric effect along their longitudinal extent than over their thickness.

The centres of the membranes 6 have a distance along the longitudinal axis 8 of approximately 20 mm to 60 mm, preferably between 25 and 52 mm, particularly preferably between 30 and 50 mm, in this case approximately 40 mm.

In the case of a pulse wave speed of 1800 cm/s, the pulse wave covers the path between the membrane centres in just over 2 ms . In order to register the dynamic pressure change as precisely as possible for registering the pulse wave contour, it is advantageous for the illustrated measuring device to have an upper cut-off frequency of more than 40 kHz, with however an upper cut-off frequency of at least approximately 20 kHz also already supplying good results. For the advantages according to the invention, the upper cutoff frequency should be at least approximately 10 kHz.

A printed circuit in the form of a printed circuit board 11 with conductor tracks 12 attached thereon is arranged on the main housing part 2 in the dry area 4. The conductor tracks 12 lead from connection spots 13 to a section of the printed circuit board 11 embodied as a plug 14. In the region of the plug 14, the conductor tracks 12 terminate in connection surfaces 15, which can interact with corresponding spring - 15 - contacts in a modified socket element 16. The connection spots 13 are arranged such that they are arranged, under the opposing sides of the membrane 6 and along the greatest longitudinal extent thereof, along the longitudinal axis 8. In the part of the main housing part 2 arranged around the cut-out 5 and covered by the edge region of the membrane 6, breakthroughs (not illustrated) in the main housing part 2 are respectively provided level with the connection spots 13, which breakthroughs respectively hold connection pins 17 that are elastic in the longitudinal direction and electrically connect the edge of the membrane 6 to the respective connection spot 13. Finally, the dry area 4 is closed off by a base 18, which can be connected to the main housing part 2 like the cover 7. In the region of the plug 14 of the printed circuit board 11, the main housing part 2 and the base 18 respectively have overhangs 19, which protectively cover the plug 14 of the printed circuit board 11 from above and below. Finally, the part of the printed circuit board 11 embodied as a plug 14 still has projections 20, which can be used for latching to a socket element 16 in order to prevent inadvertent detachment of an electrical connection to a connection line for connecting the measuring device 1 to an evaluation, display, storage and/or monitoring device (not illustrated) .

Figure 2 illustrates a corresponding counterpart, in which a plug- socket element 16 is provided with contacts corresponding to the connection surfaces 15 of the region of the printed circuit board 11 forming a plug 14 for connecting it to an electrical connection cable (not illustrated) attached to the plug-socket element 16, and in which said plug-socket element is in each case encompassed by an upper plug housing part 21 and a lower plug housing part 22, which can, in a conventional manner, have a cable outlet opening 23 - 16 - and, if necessary, a conventional strain relief. Furthermore, the upper plug housing part 21 has a spring-elastic tongue 24, which is also preferably integrally moulded onto the upper plug housing part 21 and has a hook- shaped projection (not illustrated in more detail) , which latches to the projections 20 when the socket plug 16 with the upper and lower plug housing part 21 and 22 is pushed onto the plug section 14 of the printed circuit board 11 and which can be brought out of engagement with the projections 20 by hand against the elastic pretension force of the spring-elastic tongue 24, such that the plug-socket element 16 can again be separated from the measuring device 1, but inadvertent detachment is avoided.

The ends of the main housing part 2 surrounding the first opening 9 and the second opening 10 can be provided as a conventional connection element in invasive medical technology, for example in the form of Luer-lock connectors. A hydraulic connection of the wet area 3 of the measuring device 1 for example with a circulatory system of a patient can be undertaken by a direct connection with a cannula, a catheter port or an insertion valve of a catheter, or provision can be made for a connection element, for example in the form of a conventional PVC connection tubing (not illustrated) . According to the invention, it is expedient for the flow path between the entry site into a blood vessel of a patient and the measuring device 1 to have a length of no more than 0.15 m, preferably no more than 11 cm, more preferably no more than 7 cm, preferably around 5 cm. This affords the possibility of obtaining a particularly precise registration of the dynamic pressure changes by the heart as a discontinuously operational pump. The respective other opening of the first opening 9 and second opening 10 can expediently be connected to an extracorporeal circulatory-system section, for example within the scope of extracorporeal - 17 - haemodialysis, or to an infusion device, with the measuring device 1 in that case not being directly perfused by blood of the patient, but there being a hydraulic connection to the circulatory system via the infusion liquid as auxiliary liquid. The latter arrangement moreover is advantageous in that infusion liquids usually basically consist of water, and good transmission of pressure changes in the circulatory system is obtained due to the incompressibility of water.

In addition to an evaluation, display and/or monitoring device, the measuring device 1 can also be connected to a storage device (not illustrated either) in the form of a data logger, with it being possible for the storage device either to be structurally integrated in the other devices or to be arranged separately therefrom. In the process, the measuring device 1 is connected to the evaluation, display and/or monitoring device such that the signals from the measuring device 1 are transmitted on to the evaluation, display and/or monitoring device independently of the operating state of the storage device. This refinement affords the possibility of equipping the storage device for example with a removable data storage medium, for example in the form of an SD card, and so the collected data can be removed during an ongoing operation and fed for further evaluation on a PC without this interrupting the evaluation, display and monitoring of the data currently registered by the measuring device 1.

The determination of the volumetric flow of a discontinuously operational pump for pumping a non- Newtonian liquid through a branched line network with an at least partly flexible wall, for example a heart in a human or animal circulatory system, can be obtained by connecting the measuring device 1 with the membranes 6 designed as pressure-gradient sensors at - 18 - their known distance along the longitudinal extent of the wet area 3 of the measuring device 1 to the circulatory system in a direct hydraulic fashion or via an auxiliary liquid, such as an infusion solution.

Pressure changes in the wet area 3 of the measuring device 1 are directly converted proportionally over a broad frequency range into an electrical voltage signal in the millivolt range by the pressure-gradient sensors formed by the membrane 6, and so the pressure profile can be registered in real time at the membranes 6 arranged at a known distance from one another. The measurement signal can be fed to an evaluation, display and/or monitoring device and, optionally, to a storage device. The propagation speed of the wave can be established by forming the difference in the time offset of the pass of a pressure wave between the two membranes 6. In the process, it is expedient, for increased accuracy, for the time of the pressure wave pass not to be fixed at the highest value of the pressure (crest value of the pressure wave) , but alternatively, or in addition thereto, for use to be made of the time of greatest pressure rise rate in order to obtain a more precise registration. The time of the greatest pressure rise rate can be obtained by simple differentiation of the measurement signal with respect to time and from the maximum value of the derivative obtained in this fashion. Conclusions can be drawn about the flexibility of the walls in the line network using the established propagation speed of the wave. Specifically in the case of a discontinuously operational pump, this has a significant influence on the volumetric flow because the reflection of the pulse wave in the line network has a significant influence on the augmentation and hence the overall pump power. In accordance with the propagation speed, this can lead to the reflected pulse wave completely increasing the pump power, but in the case of a corresponding phase shift - 19 - with respect to the pumping stroke, the reflected pulse wave can also correspondingly reduce the pump power because the pump must then work against the reflected pressure wave. Therefore the method according to the invention comprises the determination of a correction factor, as illustrated in Figure 3 for example, as a function of the propagation speed of the pressure wave. The correction factor established with the aid of the propagation speed is multiplied by a reference value, for example from the Helmholtz circulatory model from the FDA, in order to calculate the volumetric flow from the registered pressure values.

For further refinement and increasing the accuracy of the absolute values of the volumetric flow, the correction factor can be adapted by correlating typified parameters with an adaptation value. Such typified parameters can comprise the sex of a patient and/or their body mass index.

The method is expediently embodied such that an alarm is sounded as soon as the value obtained from determining the volumetric flow falls below and/or exceeds a predefined upper and/or lower absolute or relative threshold. This immediately affords the possibility of detecting a performance drop in the circulatory system for example of a patient, even before a collapse in the blood pressure or a drop in the oxygen content of the blood can be noticed, and thereby gaining precious time for initiating suitable countermeasures .

In this case, the measuring device according to the invention is easily assembled from a few parts that can be produced in a cost-effective fashion, and so the costs resulting from the single use of the measuring device can be significantly reduced compared to the previously utilized measuring devices, in particular - 20 - transducer systems, and hence corresponding vitals monitoring can be beneficial to a greater number of people worldwide .

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List of reference signs:

1 Measuring device

2 Main housing part

3 Wet area

4 Dry area

5 Cut-out in 2

6 Membrane

7 Cover

8 Longitudinal axis

9 First opening

10 Second opening

11 Printed circuit board

12 Conductor track

13 Connection spots

14 Plug

15 Connection surface

16 Plug element

17 Connection pin

18 Base

19 Overhangs

20 Projections in 14

21 Upper plug housing part

22 Lower plug housing part

23 Cable outlet opening

24 Spring-elastic tongue

Claims

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Patent claims

Measuring device (1) with a sensor arrangement for extracorporeally registering dynamic blood pressure changes and for extracorporeally registering the propagation speed of pulse waves in the human or animal circulatory system, characterized by a partly perfused housing (2, 7, 18) with a wet area (3) , enclosed by at least two membranes (6) and a separation wall within the housing (2, 7, 18), and a dry area (4), wherein the membranes (6) are arranged in the separation wall (2) and the centroids of the membranes (6) define a longitudinal axis (8) , wherein the housing has a first opening (9) and a second opening (10) , basically along the longitudinal axis (8) , for connection to the circulatory system of the patient and/or of an infusion device, and wherein the membranes (6) have a distance of between approximately 20 mm and 60 mm between their centroids, and wherein a printed circuit (11, 12) is arranged in the dry area (4) for connecting the membranes (6) electrically and for establishing an electrical connection to a connection line for connecting the measuring device to an evaluation, display, storage and/or monitoring device .

2. Measuring device (1) according to Claim 1, in which each of the membranes (6) respectively forms a pressure-gradient sensor and consists of a polyvinylidene fluoride (PVDF) , a PVDF copolymer or a laminate containing a layer of a PVDF or a PVDF copolymer.

3. Measuring device (1) according to Claim 2, characterized in that an electrical pickup on each membrane (6) is brought about by electrical pickups on sides of the membrane (6) that lie - 23 - opposite one another along their greatest longitudinal extent, with the electrical pickups preferably being arranged approximately along the longitudinal axis (8) .

Measuring device (1) according to one of the preceding claims, characterized in that the centre-to-centre distance of the membranes (6) lies between 25 and 52 mm, preferably between 30 and 50 mm.

Measuring device (1) according to one of the preceding claims, characterized in that the measuring device (1) has an upper cut-off frequency of at least approximately 10 kHz, preferably 20 kHz, more preferably of 36 kHz and particularly preferably of over 40 kHz.

Method for determining the volumetric flow of a discontinuously operational pump for pumping a non-Newtonian liquid through a branched, closed line network, the line network having an at least partly flexible wall, with the following steps: arranging a measuring device (1) with a sensor arrangement with at least two pressure-gradient sensors (6) at a predetermined distance along the longitudinal extent of a line section (3) arranged outside of the line network, fed by the pump, within the measuring device (1) , which line section is hydraulically connected to the line network directly or via an auxiliary liquid, registering at least the relative pressure profile at at least two sites spaced apart by a known distance along the longitudinal extent of the line section (3) with the aid of the pressure-gradient sensors (6) ,

establishing the time of the greatest pressure rise rate and/or the time of maximum pressure - 24 - during the pass of a pressure wave at each of the pressure-gradient sensors (6) ,

establishing the time of the pass of a pressure wave between the at least two spaced apart sites and determining the propagation speed of the wave from the pass time by forming the difference between the established times of the pass of a pressure wave between two pressure-gradient sensors (6) , and

determining a correction factor for correcting a reference value for the volumetric flow as a function of the propagation speed of a pressure wave .

Method according to Claim 6, furthermore characterized by one or more steps selected from: determining the correction factor by correlating the propagation speed with an associated value for the flexibility of the wall of the line network section,

adapting the correction factor by correlating typified parameters with an adaptation value, sounding an alarm as soon as the value, obtained from determining the volumetric flow, falls below and/or exceeds a predefined upper and/or lower absolute or relative threshold.

Data storage medium containing a program for carrying out the method according to one of Claims 6 to 7 in an evaluation, display, storage and/or monitoring device.

Measuring arrangement, characterized by a measuring device (1) according to one of Claims 1 to 5 and a connection element for the liquid connection of the measuring device with a blood vessel of a patient, the connection element containing a flow path for the liquid connection. - 25 -

Measuring arrangement according to Claim 9, characterized in that the connection element for the fluid connection of the measuring device (1) is embodied with a cannula, a catheter port or an insertion valve of a catheter for the insertion into a blood vessel of a patient and/or the flow path has a length of no more than 0.15 m, preferably no more than 11 cm, more preferably no more than 7 cm, and/or the measuring device (1) is connected by an electrical connection to a connection line for connecting the measuring device (1) to an evaluation, display, storage and/or monitoring device for carrying out the method according to one of Claims 6 to 7 , wherein, optionally, the storage device is arranged separately from the evaluation, display and/or monitoring device and connected to the measuring device (1) such that the signals from the measuring device (1) are looped through to the evaluation, display and/or monitoring device independently of the operating state of the storage device.