WO2024052142A1

WO2024052142A1 - Controller for an extracorporeal circulatory support using bioimpedance

Info

Publication number: WO2024052142A1
Application number: PCT/EP2023/073431
Authority: WO
Inventors: Matthias Heinke
Original assignee: Xenios Ag; Hochschule für Technik, Wirtschaft und Medien Offenburg
Priority date: 2022-09-06
Filing date: 2023-08-25
Publication date: 2024-03-14
Also published as: DE102022003278A1

Abstract

The invention relates to a method for controlling/regulating an extracorporeal circulatory support for a patient while taking into consideration bioimpedance and to corresponding devices and systems. Correspondingly, a method for controlling/regulating an extracorporeal circulatory support for a patient has the steps of: receiving (10) an EKG signal (22) of a patient being supported over a specified duration and evaluating the EKG signal in order to identify (16) at least one change in amplitude for a respective cardiac cycle, said change characterizing a cardiac cycle phase; receiving (12) a cardiological bioimpedance measurement (24) of the patient being supported over a specified duration in parallel to the EKG signal (22) and evaluating the bioimpedance measurement (24) in order to determine (18) at least one physiological characteristic (26A- 26D) of the patient; and providing (20) a trigger signal for the extracorporeal circulatory support and for the respective cardiac cycle according to the identified at least one change in amplitude. According to the invention, the trigger signal is additionally provided while taking into consideration the determined at least one physiological characteristic (26A-26D).

Description

Applicant:

1. Xenios AG and

2. Offenburg University of Technology, Economics and Media

Control for extracorporeal circulatory support with bioimpedance

Technical area

The present invention relates to methods for controlling/regulating extracorporeal circulatory support for a patient, taking bioimpedance into account, as well as corresponding devices and systems.

State of the art

If the heart's pumping performance or pumping function fails, cardiogenic shock can occur. This can lead to reduced perfusion or blood flow to end organs such as the brain, kidneys, and the vascular system in general due to a reduction in cardiac output or cardiac output. Acute heart failure causes an acute lack of blood supply in the tissue and organs, accompanied by a lack of oxygen, also known as hypoxia, with the result of possible end organ damage.

In order to stabilize the patient's condition, circulatory support systems have been developed which provide mechanical support and can be quickly connected to the circulatory system. They can improve blood flow and perfusion of organs, including the coronary arteries, and avoid a hypoxic state. For example, a blood pump can be connected to a venous access using a venous cannula and an arterial access using an arterial cannula for sucking in or pumping the blood. This allows blood to flow from one side with a low pressure, for example via an oxygenator, to one side with a higher pressure and the patient's circulation can be supported.

However, the complexity and dynamics of the patient's own heart action require fine timing and fine-tuning of the extracorporeal support. For example, blood flow to the heart's coronary arteries, which normally supply the heart muscle with sufficient oxygen, generally occurs in diastole of the cardiac cycle. Appropriate emptying of the left ventricle is therefore necessary. If the filling pressure at the end of systole or at the beginning of diastole in the left ventricle is as low as possible, the coronary arteries can expand their lumen as much as possible. In this way, the blood flow rate and oxygen supply are increased. Accordingly, the extracorporeal circulatory support for perfusion of the coronary arteries should be controlled in such a way that perfusion preferably occurs at the beginning of diastole. Perfusion during systole should be avoided.

To control extracorporeal support, measurement signals from an electrocardiogram (ECG) can be recorded and used. In this way, corresponding characteristic amplitudes can be determined for different cardiac cycle phases. For example, an R wave or R wave that is characteristic of the systolic phase of the cardiac cycle can usually be easily distinguished from other phases of the cardiac cycle, for example in a QRS complex. The R wave can be used, with a predetermined latency period, to control a blood pump in a successive diastolic phase by means of a trigger signal.

In order to support the patient's heart action, one or more stimulation pulses can also be provided using a cardiac pacemaker. Atrial and ventricular stimulation pulses and also interventricular stimulation pulses can be output with a corresponding delay. The delay corresponds, for example, to an operating mode of the pacemaker and/or therapeutic specifications.

However, the pathophysiological conditions and/or the therapeutic process can change in the patient during the course of therapy. Finally, changes in one or more cardiac cycle phases of a respective cardiac cycle are not sufficiently taken into account with preset (fixed) parameters.

Accordingly, there is a need to further improve the timing of the patient's trigger signals provided and, if necessary, the stimulation pulses during cardiac stimulation. of the inventors

According to the invention, it was recognized that circulatory support provided can vary at a predetermined latency period for the trigger signal to be provided, even if a characteristic amplitude change is clearly identified between the cardiac cycles.

Based on the known prior art, it is therefore an object of the present invention to further improve the circulatory support to be provided and in particular to optimize the timing of the trigger signal to be provided in the light of the individual patient-specific circumstances.

The task is solved by the independent claims. Advantageous further developments result from the subclaims, the description and the figures.

Accordingly, a method for controlling/regulating extracorporeal circulatory support for a patient is proposed, comprising the steps:

Receiving an ECG signal from a supported patient over a predetermined period of time and evaluating the ECG signal to identify at least one amplitude change characteristic of a cardiac cycle phase for a respective cardiac cycle;

Receiving a cardiac bioimpedance measurement of the supported patient over the predetermined period of time in parallel with the ECG signal and evaluating the bioimpedance measurement to determine at least one physiological characteristic of the patient; and

Providing a trigger signal for the extracorporeal circulatory support and for the respective cardiac cycle based on the identified at least one amplitude change.

According to the invention, the trigger signal is further provided taking into account the specific at least one “physiological property”.

The received bioimpedance measurement allows the patient's condition to be taken into account when providing the trigger signal. The cardiac bioimpedance measurement is received in parallel to the ECG signal, so that the specific “physiological property” can be taken into account as an indicator of the effectiveness of the extracorporeal circulatory support. For example, a predetermined latency period can be provided for providing a control and/or regulating signal of a blood pump after the at least one characteristic amplitude change. Even if a time interval between predetermined amplitude changes remains almost unchanged between successive cardiac cycles, changes in the at least one “physiological property” can become noticeable due to the set or provided extracorporeal circulatory support itself, but also due to a pathophysiological course and/or a therapeutic course . These make it possible to draw conclusions about the current efficiency and/or stability of the circulatory support provided. This applies in particular when a time interval between predetermined amplitude changes of successive cardiac cycles changes or the time interval varies.

A characteristic amplitude change from a QRS complex of the ECG signal is preferably identified, in particular an R wave or R wave, which can be used as a trigger signal for controlling the extracorporeal circulatory support. Alternatively, the characteristic amplitude change can also be, for example, a P wave, which was determined or identified from the ECG signal.

In order to take into account the effect of a previous trigger signal on the circulatory support, for example such as a previous activation of a blood pump when providing a trigger signal, for a current cardiac cycle, the at least one "physiological property" is preferably from a bioimpedance measurement after the provided trigger signal of a respective, at least a previous cardiac cycle is determined. The “physiological property” can therefore be determined in particular from an immediately preceding cardiac cycle. An early or late effect of the circulatory support provided on the physiological property can be recorded.

Alternatively, however, the “physiological property” can also be determined for a current cardiac cycle; this applies, for example, if the time for which the “physiological property” is determined in the current cardiac cycle, for example immediately before or after the QRS complex or in the QRS -Complex of the current cardiac cycle lies. A “physiological property” can therefore be provided for the current cardiac cycle. This is preferably determined at a predetermined period of time after the trigger signal of the previous cardiac cycle. The predetermined period of time is selected such that a sufficient predetermined period of time is required to provide the trigger signal for the current cardiac cycle is guaranteed after the time of determining the “physiological property”.

So the “physiological property” can be determined not only for the previous and/or current cardiac cycle, but also for a predetermined number of previous ones Cardiac cycles, whereby the corresponding at least one “physiological property” to be taken into account is evaluated for the selected number of cardiac cycles. In this way, individual outliers or incorrect values for individual cardiac cycles, for example due to a measurement error that occurs, can be identified when determining the at least one “physiological property " be taken into account. The “physiological property” can also be taken into account periodically. In this way, the required computing capacity can be reduced and/or temporally stabilized changes in the “physiological property” can be taken into account.

Preferably, the at least one “physiological property” is determined from a bioimpedance measurement before the characteristic amplitude change of a subsequent or current cardiac cycle. In this way, the “physiological property” can be determined either for the previous or the following, for example the current, cardiac cycle. On the one hand, a sufficient time period is made possible to provide the trigger signal. On the other hand, the probability can be increased that an effect of the trigger signal for the previous cardiac cycle on the extracorporeal circulatory support can also be taken into account. Any effects of the characteristic amplitude change, for example an R wave of a QRS complex, can thereby be avoided.

The specific "physiological property" can be taken into account, for example, based on an output signal. A visual signal can be shown on a display or monitor to indicate that there is a change or an absolute value of the "physiological property" which is a exceeds or falls below the specified threshold value. Such a signal can also be output if the “physiological property” is determined at a time that does not correspond to a predetermined cardiac cycle phase or does not (sufficiently) correlate with the corresponding ECG signal.

It is preferably provided, alternatively or additionally, that a target value is specified for the at least one “physiological property”. The time at which the trigger signal is provided is preferably changed if the specific “physiological property” deviates from the target value. Accordingly, the latency period can be adjusted according to the characteristic amplitude change, preferably automatically. In this way, a correction can be made that is tailored to the changing (patho)physiological conditions of the patient.

The target value can be determined based on a statistical evaluation of the “physiological property” from a predetermined number of previous cardiac cycles. For example, the corresponding values for the last 2 to 5 cardiac cycles, the last 5 to 10 cardiac cycles or even the last 1 or 10 to 50 cardiac cycles can be evaluated. The predetermined number is preferably selected based on a determined heart rate of the patient and/or an expected setting time or stabilization of the circulatory support.

In particular, the target value can include a maximum value or a minimum value of the “physiological property”. In this way, an optimum of the “physiological property” can be determined and the time of the trigger signal to be provided can be adjusted in order to (again) achieve this optimal value. As an alternative to the maximum value or minimum value, depending on which of these values is considered advantageous for the respective "physiological property" for supporting the patient, an average value or a value that is most frequently determined for the given number of cardiac cycles can also be selected as the target value .

The evaluation can include a correlation analysis of the bioimpedance measurement or the “physiological property” with the ECG signal present at the time and/or at least one further “physiological property”. In particular, a statistical evaluation can be carried out using a so-called Pearson correlation. In this way, a correlation coefficient, preferably at a predetermined confidence interval, can be used as a target value and, for example, falling below or exceeding the confidence interval can be used as an indicator of a necessary adjustment of the time of the trigger signal.

The target value may be based at least partially on data stored offline. In general, data stored offline as a basis for the target value allows validated data to be used as the basis for the target value and empirical values to be taken into account in the context of the patient's pathophysiological condition. For example, a correlation of the characteristic amplitude change or the latency period for the trigger signal with the “physiological property” can be determined in this way. The patient's own values can be compared with known or usual characteristic maps and / or expected values. An optimized latency period after the characteristic amplitude change can thus be determined be determined based on the validated data.

Preferably, the time of the trigger signal to be provided is adjusted iteratively for a predetermined number of successive cardiac cycles based on the specific “physiological property”. The iterative adjustment enables a continuous or continuous optimization of the circulatory support provided. For example, an adjustment of the time of the Trigger signal or the latency period can be provided. However, periodic iterative adjustment can also take place. For example, an adjustment can be made for every second to fifth or every fifth to tenth or twentieth to thirtieth subsequent cardiac cycle.

An adjustment for every second to fifth cardiac cycle or every second to fifth cardiac action can be advantageous, for example, for a tachycardic, atrial heart rhythm, for steady and non-steady heart rhythms such as atrial tachycardia, for atrial flutter, or for atrial fibrillation. Accordingly, such a periodicity can also be advantageous for tachycardic, ventricular heart rhythms, for stable and non-steady heart rhythms such as ventricular tachycardia, for ventricular flutter or for asynchronous triggering until termination of the ventricular tachycardia.

Furthermore, when ventricular or supraventricular extrasystoles (VES or SVES) occur, in the case of single or two or three VES or SVES, for example bigeminus or trigeminal, correspondingly short adaptation periods can be provided. Such short adaptation periods for every second to fifth cardiac action may also be preferred in the case of right bundle branch block or left bundle branch block, complete or incomplete.

In this way, in particularly critical and/or changing pathophysiological conditions, the timing of the trigger signal or the latency period can be quickly adjusted and optimized.

A longer periodicity, for example between 5 and 10 cardiac actions, can provide a (sufficiently) therapeutically optimized result in, for example, a normofrequency and bradycardic sinus rhythm with supraventricular and/or ventricular extrasystoles. Similarly, but without supraventricular and/or ventricular extrasystoles, a periodicity between, for example, 20 and 30 cardiac actions and 5 to 10 cardiac actions can be selected. These longer adjustment periods enable sufficient adjustment, advantageously reduce the required computing capacity and can, if necessary, take into account a leveling off or long-term changes or conditions.

The periodicity can preferably be selected depending on time and/or heart rate. The periodicity can also be designed dynamically. The frequency of the adjustment is then preferably based on a percentage of deviation from the target value. For example, if there is initially a significant deviation, an adjustment can be made for every, every second cardiac cycle or every fifth cardiac cycle, i.e. at a high frequency. After entering a normal range, an adjustment can be made at low frequency, for example for every twentieth person cardiac cycle. The proposed number of cardiac cycles is not to be understood as limiting, but rather merely as an example of an advantageous embodiment.

The change in time can also take place after a predetermined partial period of the latency period between the characteristic amplitude change and the time of the provided trigger signal of the at least one previous cardiac cycle. This partial period is preferably short with regard to the duration of the latency period and is typically between 0.1% and 10% of the total latency period, in particular between 1% and 5% of the total latency period, i.e. that the change in time preferably occurs not later than after 1 /10 of the latency period occurs. In this way, only minor adjustments are preferably made, which on the one hand enable an improvement in the circulatory support provided and, on the other hand, do not impair the stability of the circulatory support. However, the adjustments can, additionally or alternatively, also be made in such a way that, for example, an atrial graft or similar situations can be avoided. The adjustment can also be negative with regard to hemodynamic optimization, for example.

The change in time is preferably between 1 ms and 50 ms, in particular between 5 ms and 20 ms. As explained above, such minor adjustments can have a particularly beneficial effect on the circulatory support provided. The temporal change can be based, for example, on the duration of a determined cardiac cycle phase. In particular, the temporal change can be selected depending on intermittent cardiac arrhythmias and/or conduction delays in the left atrium and left ventricle. However, as described above, the adjustments, additionally or alternatively, can also be made in such a way that, for example, an atrial graft or similar situations are avoided.

The trigger signal can still not only be adjusted using time correction. Alternatively or additionally, it can be provided that the characteristic amplitude change, which is used to provide the trigger signal, is selected in accordance with the specific at least one "physiological property". An R wave can initially be used as the starting point for providing the Trigger signal. If difficulties arise in determining the R wave, for example as a result of cardiac stimulation of the patient and/or due to measurement errors, an alternative characteristic amplitude change can be suggested and used, for example the P wave. A selection of an alternative characteristic amplitude change can be used also in the case of established bradycardia or tachycardia as well as in persistent and not persistent cardiac arrhythmias, each of which requires special hemodynamic optimization.

Furthermore, even after the cardiac cycle phases have been clearly identified, it could be recognized that circulatory support can be improved by using an alternative characteristic amplitude change. For example, this knowledge can result from a correlation analysis of the at least one “physiological property” with the respective cardiac cycle phases, preferably using appropriate algorithms which can be based on machine learning. An adapted, alternative characteristic amplitude change can be specified automatically. However, the setting is preferably made first after approval by the medical staff, for example in the form of a confirmation or rejection based on a correspondingly issued signal.

By taking into account the bioimpedance measurement or the at least one “physiological property” of the patient according to the invention, the actual effect of the set parameters of the extracorporeal circulatory support on the (patho)physiological state of the patient can be determined or measured. In this way, particularly efficient circulatory support is achieved also provided in the event of (unexpected) changes in the patient's condition or the course of therapy. The "physiological property" can serve as a benchmark for a potential correction of the circulatory support provided. In particular, particularly stable and circulation-optimized support can be made possible, which is tailored to the patient and his condition.

Accordingly, it can be provided that the trigger signal for a respective cardiac cycle is provided based on the specific "physiological property" of the respective cardiac cycle, provided that the characteristic amplitude change for the respective cardiac cycle could not be clearly identified. The trigger signal can therefore be provided based on the measured bioimpedance . A defined point in time of the specific "physiological property" in the respective or previous cardiac cycle can serve as the starting point of a predetermined latency for outputting the trigger signal. Based on the value of the “physiological property”, this latency period can then be adjusted accordingly if necessary.

In order to increase or ensure the stability of such provision of the trigger signal, the validity of the at least one “physiological property” as a trigger signal for extracorporeal circulatory support can first be determined within a predetermined time interval, for example, by means of a statistical evaluation (such as a correlation analysis). with regard to identified amplitude changes. In this way, time intervals between the times of the specific "physiological property" can be determined for successive cardiac cycles and these Time intervals are compared with the corresponding time intervals between characteristic amplitude changes. For example, if RR intervals correlate with the time intervals of the corresponding bioimpedance signals, sufficient temporal stability of the “physiological property” can be expected as a basis for providing the trigger signal.

The “physiological property” preferably includes at least one hemodynamic factor. The hemodynamic factor can, for example, the heart rate, the pre-ejection period, the velocity index, the cardiac ejection volume, the cardiac index, the cardiac period length, the left ventricular ejection time, the acceleration index and / or the stroke volume be.

Through the hemodynamic factor and in particular the heart-related "physiological properties", the therapeutic potential of the circulatory support provided on the circulatory system or the heart function of the patient being supported can be determined directly. According to the invention, a possible adjustment of the time of the trigger signal to be provided can be carried out with regard to the actual circulatory support or . the current condition of the patient can be beneficial.

In order to provide the trigger signal, several “physiological properties” determined from the bioimpedance measurements are preferably taken into account. In this way, in the event of a potential improvement of a “physiological property”, for example based on the specific corresponding value and a corresponding target value, the influence of one can be taken into account at the same time appropriate adjustment of the trigger signal to be provided to a different “physiological property” of the patient takes or would take. In particular, several hemodynamic parameters can advantageously be taken into account, preferably the cardiac output volume, the cardiac index and/or the velocity Index.

For example, an adjustment of the time at which the trigger signal is provided can only be done or suggested if this improves several “physiological properties” of the patient or in any case none of them deteriorates (significantly). In this way, both patients with cardiac stimulation and patients with bradycardic and/or tachycardic cardiac arrhythmias and/or bundle branch blockages, which may also occur intermittently, must be hemodynamically optimized taking appropriate conditions into account.

The invention is described above with regard to extracorporeal circulatory support. When optimizing the control of the extracorporeal circulatory system, cardiac arrhythmias, right bundle branch block, left bundle branch block and/or can also occur bifascicular bundle branch blocks and their intermittent occurrence are taken into account. It can, additionally or alternatively, also be provided that the patient is a heart-stimulated patient whose cardiac action is supported, for example, by a cardiac pacemaker.

Accordingly, it can be provided that a cardiac stimulation signal from the patient is detected for a respective cardiac cycle. In accordance with the determined at least one "physiological property", a signal for adjusting an interventricular stimulation delay can be output. In this way, in addition or as an alternative to providing a trigger signal for extracorporeal circulatory support, a signal for a pacemaker can be output in order to adjust an interventricular stimulation delay if necessary. In particular, an adaptation for the stimulation signal of a current cardiac cycle can take place taking into account the at least one “physiological property” which was determined from the bioimpedance signal of at least one previous cardiac cycle or before the QRS complex of the current cardiac cycle.

For example, with a corresponding pacemaker mode, a (change in) delay of the stimulation pulse between the left ventricle and the right ventricle can be suggested and/or set, a so-called VV delay. Accordingly, the stimulation pulse can be delivered, for example, between 5 ms and 30 ms, preferably between 10 ms and 20 ms, delayed for the right ventricle or left ventricle or, if necessary, simultaneously. A signal for setting an atrioventricular stimulation delay, a so-called AVp delay, can also be emitted. Such a stimulation delay can, for example, be in the range between 120 and 220 ms, with a change preferably being in the range between 10 ms and 30 ms and in particular 20 ms.

Such an adjustment of the stimulation delay can be particularly advantageous in the case of (possibly parallel) cardiac resynchronization therapy. The setting or adjustment or the corresponding suggestion is preferably carried out iteratively, as described above with regard to a trigger signal to be provided.

However, as a result of cardiac stimulation, signal interference can occur in the ECG signal provided, which makes it difficult to determine the corresponding amplitudes from the ECG signal. For example, as a result of a stimulation pulse, signal levels can be detected which mask the patient's own ECG signal and/or cause a corresponding change in amplitude. In both cases, synchronization may not be possible with sufficient security for the patient. Accordingly, it can be provided that, based on a detected slope height in the ECG signal which exceeds a predetermined threshold value, the patient's own cardiac stimulation signals are not detected and are suppressed for an immediately subsequent predetermined period of time in the respective ECG signal and/or bioimpedance signal.

By detecting the slope height, which can serve as an indicator for an output stimulation pulse, interference signals can be taken into account simultaneously in the ECG signal for determining the characteristic amplitude change and/or in the parallel bioimpedance signal for determining the at least one “physiological property”.

A characteristic amplitude change, which is used as a corresponding trigger signal for the control/regulation of the extracorporeal circulatory support, can therefore be determined more precisely. This is because the signal heights in the ECG signal can be taken into account at the time of the stimulation signal and immediately afterwards to determine the amplitude change. Any distortions in the ECG signal, which would otherwise be incorrectly recognized as a characteristic change in amplitude, but are actually attributable to the stimulation signal, can be recognized as such.

By suppressing or masking out the ECG signal and/or the bioimpedance signal for the subsequent times, the existing number of data points for determining the respective amplitude change or "physiological property" can be reduced if necessary. It is nevertheless ensured that the amplitude change or . “physiological property” is largely free of interference signals and the corresponding time and/or value in the respective cardiac cycle can be determined more precisely.

The “predetermined immediately subsequent period of time” is preferably between 2 ms and 40 ms, particularly preferably between 6 ms and 10 ms. The “predetermined subsequent period of time” preferably corresponds to a period of time which hides an amplitude or a distorted signal level due to the stimulation signal. The ECG signal to be provided does not contain any significant interference signals. These can be filtered out accordingly so that "blanking" is provided. Furthermore, the "predetermined immediately following time period" is selected such that the characteristic amplitude change of an ECG signal or a specific cardiac cycle phase continues to occur in the ECG signal, i.e. not with it specified signal height is overwritten. For example, it can be ensured in this way that a QRS complex of an ECG signal, in particular an R wave or R wave, which can be used as a trigger signal for controlling the extracorporeal circulatory support, occurs in the ECG signal provided. By taking a stimulation signal or interference signal into account when identifying the amplitude change, the control signal or control signal for the extracorporeal circulatory support, which is based on the trigger signal, can be output or provided with increased temporal accuracy.

The threshold value for the gradient height is preferably specified based on offline evaluated ECG signals and/or stimulation signals which were previously validated. One or more data sets with evaluated and verified data can be provided, with the times of the respective stimulation pulses being clearly determined. Based on this data, for example, certain slope heights in the ECG signal that characterize the stimulation signal can be identified. These are taken into account for identification and make identification easier. This enables a clear assignment of the stimulation pulse to one or more specific times in the ECG signal.

In order to measure the bioimpedance, an electrode arrangement can be provided. This typically comprises at least two electrodes, with the electrode arrangement comprising two sections for coupling in an electrical signal and two sections for coupling out an electrical signal. In this way, for example, a measurement signal can be coupled out and detected by means of a coupled-in weak alternating current with a high frequency, for example approximately 50 kHz. The corresponding bioimpedance is determined by the arrangement of the sections across the cardiac area. Preferably, two sections are positioned in the neck area and two sections in the lower left thorax area below the patient's heart. The division of the sections ensures that a measurement signal can be provided that is largely free of interference signals. The measurement signal is patient-specific due to the individual arrangement. It can preferably be set specifically for the cardiac properties.

According to one embodiment, the electrode arrangement comprises two electrodes, each electrode comprising a section for coupling in the electrical signal and a section for coupling out the electrical signal. The electrodes therefore have areas that are separate from one another and are preferably not or only slightly connected to one another in an electrically conductive manner. This configuration enables a particularly compact electrode arrangement. The sections of a respective electrode can be arranged on the patient at a predetermined distance from one another.

Alternatively, it can also be provided that the electrode arrangement comprises three electrodes, with one electrode comprising a section for coupling in the electrical signal and a section for coupling out the electrical signal. An electrode is as Coupling electrode and an electrode designed as an outcoupling electrode. Three electrodes can therefore be provided. One electrode includes separate areas for coupling in and out, the other two can be provided as electrodes for bioimpedance measurement. In this way, an anatomical area for bioimpedance measurement can be chosen more freely or specifically. It can also be ensured that coupled-in and decoupled signals between the electrodes do not or only slightly influence each other.

Depending on the design, the electrode areas can be at least partially provided by one or more ECG electrodes, so that a function for detecting the ECG signal and a bioimpedance signal can be at least partially carried out by a respective electrode. In particular, an ECG lead that has already been provided can be used, for example, to decouple a measurement signal to determine or measure the bioimpedance. Corresponding frequency ranges that differ from one another can preferably be used in order to enable clear separation of the respective signals. Alternatively or additionally, a temporal separation can be provided. For example, the measurement signals can be recorded or received within different time windows.

The electrode arrangement preferably comprises four electrodes, with two electrodes each being designed as a coupling-in electrode and two electrodes each being designed as a coupling-out electrode. In this way, a clear bioimpedance measurement can be carried out. In this way, interference signals or mutual influence of the signals are largely avoided. By designing the sections as individual electrodes, complete electrically conductive separation or insulation can be made possible. The use of a larger number of electrodes enables even more precise and clear measurements of the bioimpedance. The acquisition can also be significantly simplified because no complex assignment in the frequency domain and/or the temporal domain is required. This configuration further enables more flexible positioning in the desired anatomical area of the patient.

With the two-, three- or four-electrode technology, at least one-channel measurement of the bioimpedance and preferably two-channel or multi-channel measurements of the bioimpedance can be made possible, which have an advantageous effect with regard to the hemodynamic optimization of the extracorporeal circulatory system.

The complex bioimpedance can optionally be viewed as a complex quantity, whereby the bioimpedance is composed of the real part as an ohmic resistance without phase shift and the imaginary part as an alternating current resistance with phase shift. Non-polarizable electrodes, for example silver-silver chloride electrodes, are preferably used to measure the bioimpedance.

In the method according to the invention, the steps of receiving the ECG signal and receiving the cardiac bioimpedance measurement can be made possible, for example, by means of an interface. The interface can be communicatively coupled to a control and/or regulating unit. Such a control and/or regulating unit can also be set up to evaluate the ECG signal and the bioimpedance measurement, with an evaluation unit preferably being provided for this purpose. The control and/or regulating unit can also be set up to output the trigger signal.

Accordingly, according to a further aspect of the invention, a device for controlling/regulating extracorporeal circulatory support for a patient is proposed. This device comprises an interface for receiving an ECG signal and a cardiac bioimpedance measurement of the supported patient in parallel to the ECG signal over a predetermined period of time, and furthermore an evaluation unit which is set up to detect at least one amplitude change of a respective cardiac cycle in the received one that is characteristic of a cardiac cycle phase Identify the ECG signal and determine at least one “physiological property” of the patient from the bioimpedance measurement. According to the invention, the device is set up to generate a trigger signal for the extracorporeal circulatory support for the respective cardiac cycle based on the identified at least one amplitude change and taking into account the at least to provide a “physiological property”.

The device preferably comprises a control and regulation unit, which can be communicatively coupled to an ECG device of the patient being supported and is set up to provide the trigger signal, preferably by means of the interface. The device can, for example, be communicatively coupled directly to at least one ECG lead or also to an ECG device by means of the interface in order to receive recorded ECG signals. The device is preferably designed as (part of a) control and regulation unit and includes an EKG device or is designed as part of an EKG device, the device preferably together with an EKG device or a sensor box together in a housing of a system is installed for extracorporeal circulatory support. The device can be coupled to an extracorporeal circulatory support or a corresponding system, for example via the same interface.

In particular, the device can be set up to carry out the method according to the invention described above. Although the bioimpedance signal can be detected and received using different approaches, the device preferably comprises an electrode arrangement for detecting the bioimpedance measurement, which, as described above, comprises at least two electrodes. The electrode arrangement includes two sections for coupling in an electrical signal and two sections for coupling out an electrical signal.

The ECG measurement signals have a recorded signal height and accordingly form data points which can be processed or evaluated using the evaluation unit. The evaluation unit can be designed, for example, as an integrated computing module. It can include logic to evaluate the received signals and to determine at least one characteristic amplitude change. The signals can be recorded by the evaluation unit at least for a specific time period or for the entire predetermined period of time or longer, for example by means of a coupled or integrated storage medium or in a volatile main memory.

Furthermore, a circulatory support device is proposed, which includes the device described above for controlling/regulating extracorporeal circulatory support and further components, for example an oxygenator, an ECG device, a blood pump and two cannulas for withdrawing venous blood or for supplying possibly oxygenated blood through one includes arterial access. The circulatory support device therefore typically comprises a blood pump, which is fluidly connectable to a venous patient access and an arterial patient access and is designed to provide a blood flow from the venous patient access to the arterial patient access. The circulatory support device as such or the device for controlling/regulating the extracorporeal circulatory support as a component thereof preferably comprises an ECG device.

The control/regulation device is communicatively coupled to the circulatory support device and is set up to output a control and regulation signal for adjusting the blood pump at a predetermined point in time after the at least one characteristic amplitude change. The control device operates, actuates, controls, regulates and monitors the blood pump and enables the blood pump to be synchronized with the cardiac cycle of the respective patient.

Issuing the control signal or control signal for the extracorporeal circulatory support can also cause an immediate setting of a corresponding parameter or operating parameter of a coupled extracorporeal circulatory support device. For example, one or more pump drives or pump heads for blood pumps, for example non-occlusive blood pumps, present in a system for extracorporeal circulatory support can be controlled or regulated in this way. Thus A desired blood flow rate in the desired cardiac cycle phase can be provided based on the ECG signal, wherein the ECG signal can be processed and spectrally corrected based on the detected stimulation signal.

The blood pump may be connectable to a venous access via a venous cannula and to an arterial access via an arterial cannula for suction or delivery of blood to provide blood flow from a side with a low pressure to a side with a higher pressure. The blood can be passed through a membrane oxygenator to prepare the blood accordingly. The blood pump is preferably designed as a disposable or disposable item and is preferably fluidly separated from the respective pump drive and can be easily coupled, for example via a magnetic coupling. The control device actuates the motor of the pump drive by outputting the corresponding signal and can thus cause a change in the speed of the blood pump.

Short description of the characters

Preferred further embodiments of the invention are explained in more detail by the following description of the figures.

Figure 1 shows a schematic representation of a process sequence according to the invention;

Figure 2 shows an electrocardiographic course and a parallel recording of a cardiac bioimpedance;

Figure 3 shows an alternative electrocardiographic course and a parallel recording of a cardiac bioimpedance;

Figure 4 shows a point cloud as a basis for a correlation analysis between a received ECG signal and a bioimpedance measurement received in parallel;

Figure 5 shows a point cloud as a basis for a correlation analysis between different specific physiological properties;

Figure 6 shows a course of a bioimpedance measurement with changes in a stimulation delay of a heart-stimulated patient; and

Figures 7A and 7B show a spectro-temporal evaluation of the bioimpedance measurement for certain time intervals. Detailed

preferred version

Preferred exemplary embodiments are described below with reference to the figures. The same, similar or identical elements are given identical reference numbers in the different figures, and a repeated description of these elements is partly omitted in order to avoid redundancies.

1 shows a schematic representation of a method sequence according to the invention for controlling/regulating extracorporeal circulatory support for a patient. Accordingly, in step 10 an ECG signal or an ECG measurement signal from one or more ECG leads is received, for example for a predetermined period of time or continuously for successive cardiac cycles. The ECG signal contains signal heights for each data point, so that a corresponding measurement value is provided for each subsequent time in the ECG signal. The signal levels together form an electrocardiogram, which makes it possible to graphically depict and, if necessary, monitor the different cardiac cycle phases for each heart action of the patient.

Furthermore, in step 12, a cardiac bioimpedance measurement or a bioimpedance signal is received in parallel to the ECG signal. The bioimpedance measurement can take place simultaneously or can be recorded and received with a slight delay and assigned to the corresponding measurement time of the ECG signal.

After receiving the ECG signal (step 10) and the bioimpedance measurement (step 12), the measurement signals can optionally be processed, as shown in the corresponding steps 14A and 14B and with the dashed lines. For example, interference signals, such as cardiac stimulation pulses, can be determined and the corresponding data points and the data points immediately following them can be hidden or overwritten with a predetermined value or signal curve. In this way, any distortions in the respective signal can be avoided or reduced, so that the validity of the signals can be increased during further processing.

From the processed ECG signal, an amplitude change characteristic of a specific cardiac cycle phase is then identified in step 16. This is preferably the so-called R wave in the QRS complex of the cardiac cycle, which fundamentally enables a clear and temporally stable assignment of the corresponding point in time to the systolic phase.

The identified, characteristic amplitude change, in particular the R wave, serves as the basis for providing a trigger signal for extracorporeal circulatory support according to step 20. As explained above, the trigger signal can, for example, provide a control and/or regulation signal for an extracorporeal circulatory support device with temporal stability.

Accordingly, the control and/or regulation signal can be output with a predetermined latency period, for example to activate a blood pump in a specific cardiac cycle phase and to promote extracorporeal blood flow. In this way, for example, improved blood flow to the coronary arteries can be provided within a diastolic phase. For example, one or more amplitude changes can be determined which are characteristic of an R wave in the respective cardiac cycle, whereby the control and regulation signal can be output accordingly as an R trigger signal. Hiding or “blanking” the stimulation signals or interference signals makes it possible for control to be provided even when signal levels are present, which would otherwise, for example, cause a reset and prevent detection of an amplitude change.

When providing the trigger signal (step 20), at least one "physiological property" of the patient is also taken into account, which was previously determined based on the bioimpedance measurement (step 18). The bioimpedance measurement and the corresponding "physiological property" are preferably based on the trigger signal of an immediately previous cardiac cycle and recorded or determined before the time of the specific characteristic amplitude change of the current cardiac cycle.

In this way, the effect of the time of the previously provided trigger signal and thus, for example, the effect of activating a blood pump for circulatory support on the patient's condition can be taken into account. Accordingly, the time of the trigger signal to be provided can now be adjusted based on the specific “physiological property” in order to optimize at least this “physiological property” for subsequent cardiac cycles and to improve the patient's condition.

2 and 3 show curves of electrocardiographic signals 22 and cardiac bioimpedance measurements 24 recorded in parallel in different representations and for successive cardiac cycles. It can be seen that the signal height in the cardiac bioimpedance measurement 24 can vary even if the ECG signal 22 is relatively stable. According to the invention, the occurrence of such fluctuations is used to achieve the best possible value of the respective “physiological property” and/or a further improvement in the stability of the circulatory support. The at least one “physiological property” is preferred through a temporal correction or adjustment of the set Latency period between the time of the specific characteristic amplitude change and the time of provision of the trigger signal is optimized, in particular iteratively for successive cardiac cycles or periodically.

In particular, a statistical evaluation of the bioimpedance signal 24 can be used as the basis for such an iterative optimization. As shown in Figure 4, a point cloud with a confidence interval can be provided for this purpose. This makes it possible, for example, to calculate an expected value and statistical values, such as an average value or median value, which can be provided as a target value for the time adjustment of the trigger signal to be provided.

A corresponding statistical evaluation is shown in Figure 5 for the “physiological properties” 26A to 26D determined from the bioimpedance signal 24. In this advantageous but optional example, the cardiac index 26A, the stroke volume 26B, the heart frequency or heart rate 26C and the cardiac period length 26D are described .

For example, a correlation analysis can be carried out using the statistically evaluated data to determine a Pearson coefficient or correlation coefficient. As explained above, this analysis can be carried out for each subsequent cardiac cycle or periodically, for example for every fifth cardiac cycle, after appropriate averaging.

6 shows a further example of a course of a bioimpedance measurement 24, with changes 28 being made to a stimulation delay in a heart-stimulated patient at different times. In the present, non-limiting example, the cardiac period length 26A, the left ventricular ejection time 26B, the acceleration index 26C and the stroke volume 26D were determined as physiological properties 26A to 26D.

Cardiac pacing was administered for cardiac resynchronization therapy with right atrial, right ventricular, and left ventricular pacing. At the time points of change 28, different atrioventricular and interventricular pacing delays were set. This was done in an iterative manner, first hemodynamically optimizing the atrioventricular pacing delay and then the interventricular pacing delay. The AVp delay values were chosen in a range between 140 ms and 200 ms and VV delay values between -20 ms and +20 ms. In this way, for example, an optimum in stroke volume, cardiac cycle duration and cardiac index could be achieved at a stable and slightly lower heart rate value. 7A and 7B show the bioimpedance measurement 24 in the time and spectral domain, with the time axis shown in line numbers. It can be seen from the illustration that a higher frequency with sufficient stability could be achieved at different times. These times correspond to corresponding changes in the stimulation delay, as shown, for example, in Figure 6. While the temporal hemodynamic trend is shown in Figure 6, the spectral hemodynamic trend is shown in Figure 7. Accordingly, the spectral trend of different hemodynamic parameters can be used in intermittent cardiac arrhythmias and/or cardiac stimulations for hemodynamic optimization of the triggering of the control of extracorporeal circulatory support. The temporal and spectral hemodynamic trend can therefore be used for the hemodynamic assessment of cardiac rhythm, cardiac pacing and cardiac arrhythmias as well as various ventricular bundle branch blocks.

Accordingly, an evaluation in the spectral range, taking into account sufficient patient safety, can serve as the basis for an adjusted time of the trigger signal or stimulation pulse to be provided.

To the extent applicable, all individual features shown in the exemplary embodiments can be combined and/or exchanged with one another without departing from the scope of the invention.

Reference symbol list

10 Receiving an ECG signal

12 Receive a bioimpedance measurement

14A Processing the ECG signal 14B Processing the bioimpedance measurement

16 Identify a characteristic amplitude change

18 Determining a physiological characteristic

20 Providing a trigger signal

22 ECG signal 24 Bioimpedance signal

26A-D physiological property

28 Pacing delay change

Claims

Claims Method for controlling/regulating extracorporeal circulatory support for a patient, comprising the steps:

Receiving (10) an ECG signal (22) from a patient over a predetermined period of time and evaluating the ECG signal (22) to identify (16) at least one amplitude change characteristic of a cardiac cycle phase for a respective cardiac cycle;

Receiving (12) a cardiac bioimpedance measurement (24) of the patient over the predetermined period of time parallel to the ECG signal (22) and evaluating the bioimpedance measurement to determine (18) at least one physiological property (26A-26D) of the patient; and

Providing (20) a trigger signal for the extracorporeal circulatory support and for the respective cardiac cycle, based on the identified at least one amplitude change and taking into account the determined at least one physiological property (26A-26D). Method according to claim 1, wherein the at least one physiological property (26A-26D) is determined from a bioimpedance measurement (24) according to the provided trigger signal of a respective, at least one previous cardiac cycle. The method according to claim 2, wherein the at least one physiological property (26A-26D) is determined from a bioimpedance measurement (24) before the characteristic amplitude change of a subsequent cardiac cycle. Method according to one of the preceding claims, wherein a target value is specified for the at least one physiological property (26A-26D) and the time at which the trigger signal is provided is changed when the specific physiological property (26A-26D) deviates from the target value. The method of claim 4, wherein the target value is determined based on a statistical evaluation of the physiological characteristic (26A-26D) from a predetermined number of previous cardiac cycles. A method according to claim 4 or 5, wherein the target value comprises a maximum value or a minimum value of the physiological property (26A-26D). Method according to one of claims 4 to 6, wherein the target value is based at least partially on data stored offline. Method according to one of claims 4 to 7, wherein the timing of the trigger signal to be provided is iteratively adjusted for a predetermined number of successive cardiac cycles based on the determined physiological characteristic (26A-26D). Method according to one of claims 4 to 8, wherein the change in time takes place after a predetermined partial period of the latency period between the characteristic amplitude change and the time of the provided trigger signal of the at least one previous cardiac cycle, the partial period preferably being between 0.1% and 10% of the Latency period is, particularly preferably between 1% and 5%. Method according to one of claims 4 to 9, wherein the change in time is between 1 ms and 50 ms, preferably between 5 ms and 20 ms. A method according to any preceding claim, wherein the characteristic amplitude change used to provide the trigger signal is selected based on the determined at least one physiological characteristic (26A-26D). Method according to one of the preceding claims, wherein the trigger signal for a respective cardiac cycle is provided based on the specific physiological property (26A-26D) of the respective cardiac cycle if the characteristic amplitude change for the respective cardiac cycle could not previously be clearly identified. Method according to one of the preceding claims, wherein the physiological characteristic (26A-26D) comprises at least one hemodynamic factor. Method according to claim 13, wherein the hemodynamic factor is selected from the heart rate, the pre-ejection period, the velocity index, the cardiac ejection volume, the cardiac index, the cardiac period length, the left ventricular ejection time, the acceleration index and / or the stroke volume. Method according to one of the preceding claims, wherein several physiological properties (26A-26D) determined from the bioimpedance measurements (24) are taken into account for providing (20) the trigger signal. Method according to one of the preceding claims, wherein a cardiac stimulation signal from the patient is detected for a respective cardiac cycle and, in accordance with the determined at least one physiological characteristic (26A-26D), a signal for setting an interventricular stimulation delay is output. Method according to one of the preceding claims, wherein based on a detected slope height in the ECG signal (22), which exceeds a predetermined threshold value, the patient's own cardiac stimulation signals are not detected and for an immediately subsequent predetermined period of time in the respective ECG signal (22) and / or Bioimpedance signal (24) can be suppressed. Method according to one of the preceding claims, wherein the bioimpedance is measured by means of an electrode arrangement which comprises at least two electrodes, the electrode arrangement comprising two sections for coupling in an electrical signal and two sections for coupling out an electrical signal. Method according to claim 18, wherein the electrode arrangement comprises two electrodes, each electrode comprising a section for coupling in the electrical signal and a section for coupling out the electrical signal. Method according to claim 18, wherein the electrode arrangement comprises three electrodes, wherein a first electrode comprises a section for coupling in the electrical signal and a section for coupling out the electrical signal, and wherein a second electrode is designed as a coupling-in electrode and a third electrode is designed as a coupling-out electrode. Method according to claim 18, wherein the electrode arrangement comprises four electrodes, two electrodes each being designed as a coupling-in electrode and two electrodes each being designed as a coupling-out electrode. Device for controlling/regulating extracorporeal circulatory support for a patient, comprising an interface for receiving an ECG signal (22) and a cardiac bioimpedance measurement (24) of the supported patient in parallel to the ECG signal (22) over a predetermined period of time, and an evaluation unit which is set up to identify at least one amplitude change of a respective cardiac cycle in the received ECG signal (22) that is characteristic of a cardiac cycle phase and to determine at least one physiological property (26A-26D) of the patient from the bioimpedance measurement (24), where the device is set up to provide a trigger signal for the extracorporeal circulatory support for the respective cardiac cycle in accordance with the identified at least one amplitude change and taking into account the at least one physiological property (26A-26D). Device according to claim 22, comprising an electrode arrangement for detecting the bioimpedance measurement. Device according to claim 22 or 23, which is designed to carry out the method according to one of claims 1 to 21. Circulation support device, comprising a device according to one of claims 22 to 24.