EP2825238A1

EP2825238A1 - Appliance for performing anaesthesia or analgosedation, and method for operating an appliance for performing anaesthesia or analgosedation

Info

Publication number: EP2825238A1
Application number: EP13719010.4A
Authority: EP
Inventors: Sascha KREUER; Thomas Volk; Joerg-Ingo BAUMBACH; Heiko Buchinger
Original assignee: Universitaet des Saarlandes; Korea Institute of Science and Technology Europe Forschungs GmbH
Current assignee: Universitaet des Saarlandes; Korea Institute of Science and Technology Europe Forschungs GmbH
Priority date: 2012-03-13
Filing date: 2013-03-13
Publication date: 2015-01-21
Also published as: CA2867067A1; JP2015512698A; DE102012203897A1; KR20140135818A; DE102012203897B4; CN104302342A; WO2013135240A1; US20150038940A1

Abstract

The invention relates to an appliance for performing anaesthesia or analgosedation, comprising a dosing device (5) for the intravenous administration of an adjustable dose of at least one anaesthetic to a patient (1), a measuring device (2) for determining the concentration of the at least one anaesthetic in the exhaled air of the patient (1), means (4) for determining the effect of the at least one anaesthetic on the patient (1), preferably in the form of a depth of anaesthesia or depth of analgosedation, and a data processing device (7), which communicates via interfaces with the dosing device (5), the measuring device (2) and the means (4) for determining the effect and which, on the basis of the determined values of the parameters dosage, concentration and effect of the at least one anaesthetic, establishes a pharmacological model individualized to the patient (1) and, using the individualized pharmacological model that is established, calculates an individual dosage, optimized to the patient (1), of the at least one anaesthetic.

Description

DEVICE FOR CARRYING OUT ANESTHESIA OR ANALGESEING AND METHOD FOR OPERATING A DEVICE FOR IMPLEMENTING ANESTHESIA OR ANALYZESEING

The invention relates to an apparatus for performing anesthesia or analgesic sedation and to a method for operating an apparatus for performing anesthesia or analgesic sedation.

In general anesthesia or anesthesia certain body functions are switched off for the purpose of tolerance of diagnostic or surgical procedures on or in the body. In general, the goal of adequate anesthesia is to realize a combined effect of hypnotic, analgesic, and muscle relaxant effects, so as to ensure that the patient is in a state of unconsciousness during the procedure and does not perceive the procedure accordingly and that he It is also insensitive to pain-sensitive stimuli during the procedure. In analgesic sedation, a graded form of anesthesia depth is sought which, without the action of muscle relaxants, is a combination of hypnotic and analgesic effects.

To achieve the stated objectives, the anesthetist usually administers a combination of anesthetic drugs having different effects on the brain, spinal cord, autonomic nervous system, and / or neuromuscular junctions. For example, narcotics / sedatives are commonly used for unconsciousness, sedation or sedation combined with analgesics for pain suppression. A commonly used drug from the group of narcotics is propofol (active ingredient: 2,6-diisopropylphenol), while as analgesics typically opioids, such as remifentanil, fentanyl or morphine, are used. For the anesthesiologist, in addition to the actual selection of suitable medicaments, it is a major difficulty to dose them adequately. In this context, on the one hand, it is important to avoid overdoses as far as possible, as these can lead to undesirable side effects, some of which have serious consequences. In addition, overdose would unnecessarily increase the burden on the patient as a whole and unduly prolong the anesthesia. On the other hand, the dosages must not be too low, as, for example, insufficiently deep anesthesia can cause the patient to consciously experience the procedure, which can lead to serious trauma. An adequate dosage must be guaranteed throughout the duration of a diagnostic or invasive surgical procedure.

The problem of adequate dosage is made more difficult by the fact that the anesthetist has only limited access to information about the concentration of the administered anesthetic at the actual site of action. With gaseous anesthetics it has been the state of the art for many years to determine the concentration at the end of the exhalation of the patient - end-tidal. This measurement, which provides a relatively reliable indicator of anesthetic assessment, is mandatory and will provide the anaesthesiologist with the dosage of anesthetic delivery. For the (non-volatile) intravenously administered anesthetics, there is currently no way to measure the concentration. For example, propofol can be dosed by computer-assisted syringes (Target Controlled Infusion, TCI) that infuse the drug based on pharmacokinetic data. The relationship between the propofol concentration in the patient's blood and the administered dose is calculated exclusively on the basis of demographic data of the patient, such as size, weight, age, gender. The pharmacological models stored in TCI syringe pumps, as found today in everyday clinical practice, have an accuracy of approximately 20% in healthy patients. Patients with organ dysfunction have an even greater deviation. Further restrictions exist, for example obese patients and children. Accordingly, anesthesia control based on these models is inevitably inaccurate.

The present invention is therefore based on the object, a device for performing anesthesia or Analgosedierung and a method for operating a device for performing anesthesia or Analgosedierung such and further, that anesthesia control with improved accuracy is possible. According to the invention the above object is solved by the features of claim 1. Thereafter, the device in question for performing anesthesia or analgesic sedation comprises a metering device for intravenous administration of an adjustable dose of at least one anesthetic agent to a patient, a measuring device for determining the concentration of the at least one anesthetic in the patient's exhalation air, means for determining the effect of at least one Anesthesia means on the patient, preferably in the form of an anesthetic or Analgosedierungstiefe, and a data processing device which communicates via interfaces with the metering device, the measuring device and the means for determining the effect, based on the determined values of the parameters dose, concentration and effect of the at least one Anesthetized with a patient-individualized pharmacological model, and based on the individualized pharmacological model calculated on the patient optimized dosage of at least one anesthetic agent.

In procedural terms, the above object is achieved by the features of claim 15. Hereinafter, the method for operating an apparatus for performing anesthesia comprises the steps:

Intravenous administration of an adjustable dose of at least one

Anesthetic agent to a patient;

Determining the concentration of the at least one anesthetic in the patient's exhalation air; Determining the effect of the at least one anesthetic on the patient, preferably in the form of anesthetic depth,

Preparation of a pharmacological model individualized for the patient on the basis of the respective values determined for the parameters dose, concentration and effect of the at least one anesthetic, and

Determination of an individual, patient-optimized dosage of the at least one anesthetic using the individualized pharmacological model created. In accordance with the invention, it has first been recognized that improved accuracy in terms of performing anesthesia or analgesic sedation can be achieved by integrating data obtained in real time or quasi real time during patient intervention into a pharmacological model. According to the invention, a measuring device for determining the concentration of an anesthetic in the exhaled air of the patient, means for determining the effect (anesthetic or analgosedation depth) of the administered anesthetic and a dosing device for the intravenous administration of an anesthetic via a data processing device. The measured concentration values, together with information on the effect, flow into an individualized pharmacological model tailored to each patient. Preferably, the pharmacological model is a complete PK / PD model that takes into account both pharmacokinetic and pharmacodynamic aspects. An individual patient-specific anesthesia or analgesic sedation control can be realized by the calculation of such a pharmacological model individualized for the respective patient in parallel with the intervention on the patient.

With a view to the most exact possible dosage of the anesthetic, it is provided within the scope of a specific embodiment that the metering device comprises a computer-controlled syringe pump. This allows the anesthesiologist according to the identified need for a simple and accurate replenishment of the anesthetic during the procedure. The syringe pump records the dosage of the patient administered during the procedure respective Anästhesiemittels continuously and transmits the data via a corresponding interface to the data processing device.

In a preferred embodiment, the measuring device for determining the concentration of the at least one Anästhesiemittels works continuously, wherein the discontinuous respiratory gas flow is transferred into a continuous sample gas flow and this is fed to a sensor system of the measuring device. As an alternative to a continuous examination of the exhaled air with corresponding concentration determinations, the measurements can also be carried out timed with short measuring intervals of less than 60 s, ideally of less than 30 s, and preferably in a range of 15-25 s, so that approx Every 3-5 breaths of the patient, a current concentration value, which can be incorporated into the PK / PD model, is available. In order to realize the mentioned short measuring distances, the measuring device is advantageously designed as an ion mobility spectrometer with upstream gas-chromatographic separation column, preferably a multi-capillary column. Through the separation column / multi-capillary column, an advance separation of the individual components contained in the respiratory gas can be carried out so that the individual components enter the drift tube of the ion mobility spectrometer at different times and / or have different drift times / mobilities. Accordingly, it is possible to determine the concentration of several different anesthetic agents independently of each other and almost in parallel with each other. For the significance of concentration measurements carried out in the exhaled air of a patient, the defined withdrawal of respiratory gas samples, both with regard to the respective volumes and with regard to the respective respiratory phases, is of crucial importance. Advantageously, therefore, the ion mobility spectrometer is coupled to a volume flow sensor (flow sensor) and / or to a CO 2 sensor. In this way, it is possible to remove constant breathing gas volumes as a function of a defined CO2 content, by means of which a specific breathing phase (eg expiration, end-tidal, etc.) is defined, and to feed it to the sensor system. By the Determining the volume of such a dosing loop, preferably between 1 ml and 50 ml, the concentration can be determined.

In a preferred embodiment, the means for determining the effect of the at least one anesthetic agent on the patient comprises a device for deriving an EEG, referred to below as an EEG module.

In a preferred embodiment, demographic data of the patient are integrated into the individualized PK / PD model in addition to the values of the parameters dosage, concentration and effect with a view to a more extensive individualization. The demographic data of the patient, in particular age, weight, height, gender and BMI (body mass index), can either be entered manually into the data processing device with the aid of appropriate input means or read directly from a patient database into the data processing device.

In the case of the at least one anesthetic, for which an individualized patient-specific PK / PD model is created taking into account measured concentration values in the exhaled air of the patient, it may be, for example, a narcotic, in particular propofol. Additionally or alternatively, the at least one anesthetic agent may comprise an analgesic, in particular an opiod. On the basis of individually measured concentration values and their integration into a PK / PD model, interaction models between, for example, propofol and an opiod can be generated. This is of particular advantage since in the vast majority of surgical interventions propofol is used as a hypnotic opiode as an analgesic. Using such interaction models, it can be taken into account that most analgesics, including in particular the most common opiod, in addition to the analgesic active component also have a hypnotizing active component. It should be noted at this point that for the preparation of the interaction models, the time intervals for determining the concentration values of the narcotics and the opiod need not necessarily be identical, but may well differ from one another. In addition, it is also possible that the at least one anesthetic, for which an individualized patient-specific PK / PD model is created taking into account measured concentration values in the exhaled air of the patient, comprises a muscle relaxant.

In the context of a specific embodiment it is provided that the device is designed in the sense of an "open loop" system For this purpose, for example, a display device can be provided, on which the calculated, optimized for the patient dosage of the administered or anesthetic (s) The anesthetist may then decide whether to follow the recommendation and to adjust the dosage accordingly, taking into account the overall anesthetic situation.

Alternatively, the device may be designed in the sense of a "closed loop" system In this variant, the patient-specific optimized dosage of the anesthetic agent calculated on the basis of the created individualized PK / PD model is used to generate corresponding control signals which are sent to the metering device automatic adjustment of the dosage to be transmitted.

In an advantageous embodiment, the data processing device is set up to carry out a correlation analysis between EEG index values determined by means of the EEG module and the measured concentration of the at least one anesthetic in the exhaled air of the patient.

There are now various possibilities for designing and developing the teaching of the present invention in an advantageous manner. For this purpose, on the one hand to the claims subordinate to claim 1 and on the other hand to refer to the following explanation of preferred embodiments of the invention with reference to the drawings. In conjunction with the explanation of the preferred embodiments of the invention with reference to the drawings, also generally preferred embodiments and developments of the teaching are explained. In the drawing show Fig. 1 is a schematic representation of an embodiment of an inventive device for performing anesthesia, and

2 is a schematic representation of a method for creating an individual patient-specific PK / PD model according to an exemplary embodiment of the invention.

Fig. 1 shows a schematic representation of a preferred embodiment of a device according to the invention for performing anesthesia, which could be transferred directly to the implementation of a Analgosedierung. Shown are the patient 1 and the essential components of the device. Specifically, the illustrated device comprises a measuring device 2 for determining the concentration of an anesthetic in the exhaled air of the patient 1 in the form of an ion mobility spectrometer (IMS) 3 with multi-capillary column (MCC), an EEG module 8, a metering device 5 for intravenous Administration of an adjustable dose of anesthetic to a patient in the form of a TCI syringe pump 6 and a data processing device 7. The mode of operation of the individual modules is described in more detail below, it being assumed by way of example that they are intravenously administered during the anesthesia described Propofol, since propofol is the most widely used anesthetic in general anesthesia and sedation worldwide. However, the following remarks may, of course, be applied to other drugs administered as part of anesthesia. In particular, the following remarks are applicable to a number of different drugs administered in parallel to the patient during the procedure, in which case interaction models may be established for the individual drugs, for example to describe the interaction of propofol with an opiod and / or a muscle relaxant Drug.

The IMS 2 measures continuously or at regular intervals the current propofol concentration in the exhaled air of the patient 1. In the case of temporally These measurements are carried out with a maximum time interval of approx. 30 s. These short measurement intervals ensure that the measurements virtually represent real-time measurements. The measured values are therefore immediately available online during the procedure.

To measure the propofol concentration, an unillustrated respiratory gas sensor is provided in addition to the IMS 2, which is embodied in particular as a CC sensor or as a flow sensor and measures the CO 2 concentration in the exhalation phase. The respiratory gas sensor is used to control the sample gas removal from the respiratory gas flow. As soon as the respiratory gas sensor detects a CO2 concentration in the expiration phase which exceeds a first predetermined value, the sample gas withdrawal is started. As soon as the CO 2 concentration falls below a second predetermined value, the sample gas withdrawal is ended. In this way, reproducible samples are generated, which always result from the same defined respiratory phase. The samples thus generated are then fed to the IMS 2 to determine the exact propofol concentration.

Parallel to the measurement of the propofol concentration, an EEG of the patient 1 is derived by means of the EEG module 4. The EEG is displayed to the anesthesiologist at a corresponding EEG monitor. In addition, index values, for example so-called BIS values (Bispectral Index Monitoring), are transmitted from the EEG monitor and also displayed. These EEG index values are dimensionless and usually defined on a scale of 0 to 100 and represent a measure of hypnosis depth.

As shown in FIG. 1, the EEG values, the measured propofol concentrations and the dose of propofol administered to the patient 1 are transmitted via corresponding interfaces to a data processing device 7. According to the invention, a pharmacological model individualized for the patient 1-PK / PD model-is created on the basis of these values. On the basis of this PK / PD model, an individual propofol dosage optimized for the respective patient 1 is then calculated. The optimized propofol dosage can then the anaesthesiologist via appropriate Ausgabebzw. Display means are provided in the sense of a recommendation. Alternatively, a control loop can be realized, in which case the optimized propofol dosage is transmitted directly to the syringe pump 6 as a corresponding control signal. 2 schematically illustrates the creation of an individualized PK / PD model according to an embodiment of the invention. The illustrated embodiment is based on a conventional three-compartment model. This type of model has so far best proven in practice for describing and interpreting pharmacokinetic processes occurring within the body. In the three-compartment model, the organism is divided into a central (V _zen trai) and two parallel peripheral (V2 and V3) compartments. The central compartment V _ze ntrai corresponds to the blood volume and the organs with a high proportion of the cardiac output, in particular the brain, heart and lungs. One of the peripheral compartments (V2) corresponds to the musculature and the other organs, while the other of the peripheral compartments (V3) describes the fatty and connective tissue. In addition, the elimination of the considered drug is taken into account, which in the case of propofol essentially takes place via the liver. Conventional three-compartment models, as known in the art and used in clinical practice today, have as inputs only the demographic data of the patient, which is typically the age, weight, height, gender and the BMI. For healthy patients, these models have an inaccuracy of approximately 20%. Consequently, the dosage of the anesthetic agent to be administered based on the models for the invalid patient is correspondingly inaccurate.

In contrast, according to an exemplary embodiment of the present invention, an individual patient-specific PK / PD model is calculated during the anesthesia, taking into account not only the demographic data of the patient but additionally concentration values of the administered anesthetic agent measured in real time or virtually in real time and additionally measured EEG Index values integrated into the model calculation become. In this way, an individualized anesthesia or Analgosedierungssteuerung be made, which allows both a detailed statements about the current state of anesthesia or Analgosedierung as well as predictions about their future course.

In concrete terms, the size of the central compartment V _ze ntrai is not simply determined on the basis of the demographic data of the patient, but is calculated individually from the concentrations of the administered anesthetic agent actually measured by means of the IMS. This result, together with the dosage administered, is used in the calculation of the exchange process with the peripheral compartments V2 and V3 as well as the elimination process. The effect of the administered anesthetic agent is modeled on the basis of the determined size of the central compartment V _ze ntrai in combination with the recorded EEG index values. In an expanded embodiment, the conventional three-compartment model is extended by additional compartments to calculate the individual patient-specific PK / PD model.

According to one exemplary embodiment of the invention, an anesthesia monitor is implemented which enables anesthesiologists who are anesthetized on the basis of a pharmacological model optimized for the individual patient to have optimized anesthesia or analgesic administration. The anesthesiologist can make all relevant information available to the anesthesiologist. Thus, for example, by the already described connection of an EEG monitor system for measuring the effect of the administered anesthetic during anesthesia, the dose-response curve of the patient can be calculated. By integrating the quantity supplied and the demographic data of the patient, a prediction of the further course can be made. In addition, a comparison with pharmacological averages can be made. This allows a statement as to whether the individual patient has a normal, a faster or a slower metabolism (metabolization) of the administered anesthetic, in particular propofol. With a view to maximizing the simplification of the anesthetic or analgosedierungsführung for the Anesthetists are preferably given the following values / parameters via the anesthesia monitor:

^■ Measured end-tidal concentration of propofol

■ Individually calculated propofol blood concentration

^■ Individually calculated propofol concentration

^■ Dose-response curve Propofol / EEG Index value

^■ Metabolism rate of Propofol To further optimize and improve the predictive value of PK / PD models based on concentrations actually measured in patient exhaled air, different correlation analyzes may be performed. For example, a correlation analysis between a subsequently measured propofol blood concentration in the laboratory and the end-tidal propofol concentration measured during the procedure could help to incorporate more accurate information regarding the actual propofol blood concentration into the models. Correlation analysis between clinical endpoints (eg, loss of consciousness) and measured end-tidal propofol concentrations, as well as correlation analyzes between EEG index values and the measured end-tidal propofol concentration, could also contribute to further improvement.

With regard to further advantageous embodiments of the device according to the invention, reference is made to avoid repetition to the general part of the specification and to the appended claims.

Finally, it should be expressly understood that the above-described embodiments of the device according to the invention are only for the purpose of discussion of the claimed teaching, but do not limit these to the exemplary embodiments. Reference numeral l iste

1 patient

2 fair inspection

3-ion mobility spectrometer

4 means for determining the effect

5 metering device

6 TCI syringe pump

7 data processing device

8 EEG module

Claims

Patent claims

1. Apparatus for performing anesthesia or analgesic sedation, comprising

a metering device (5) for the intravenous administration of an adjustable dose of at least one anesthetic to a patient (1), a measuring device (2) for determining the concentration of the at least one anesthetic in the exhaled air of the patient (1),

Means (4) for determining the effect of the at least one anesthetic agent on the patient (1), preferably in the form of an anesthesia or analgosedation depth, and

a data processing device (7) which communicates via interfaces with the metering device (5), the measuring device (2) and the means (4) for effect determination based on the determined values of the parameters dosage, concentration and effect of the at least one Anästhesiemittels a customized for the patient (1) pharmacological model and calculated on the basis of the individualized pharmacological model created an individual, on the patient (1) optimized dosage of the at least one anesthetic.

2. Device according to claim 1, characterized in that the metering device (5) comprises a, preferably microprocessor-controlled, syringe pump (6).

3. Apparatus according to claim 1 or 2, characterized in that the measuring device (2) for determining the concentration of the at least one Anästhesiemittels continuously or with measuring intervals of less than 30 s, preferably in a range of 15-25 s works.

4. Device according to one of claims 1 to 3, characterized in that the measuring device (2) comprises an ion mobility spectrometer (3) with multi-capillary column.

5. Apparatus according to claim 4, characterized in that the ion mobility spectrometer (3) is coupled to a flow or CC sensor.

6. Device according to one of claims 1 to 5, characterized in that the means (4) for determining the effect of the at least one anesthetic on the patient (1) comprises a device for deriving an EEG - EEG module (8) -.

7. Device according to one of claims 1 to 6, characterized in that demographic data of the patient (1) in the

Data processing device (7) can be entered and incorporated into the creation of the individualized pharmacological model.

8. Device according to one of claims 1 to 7, characterized in that the at least one anesthetic agent is a narcotic, in particular

Propofol, includes.

9. Device according to one of claims 1 to 8, characterized in that the at least one anesthetic agent comprises an analgesic, in particular an opiod.

10. Device according to one of claims 1 to 9, characterized in that the at least one anesthetic comprises a muscle relaxant.

11. Device according to one of claims 1 to 10, characterized in that the data processing device (7) is adapted to calculate interactions between a narcotic administered to the patient (1) and an analgesic administered to the patient (1).

12. Device according to one of claims 1 to 11, characterized by a display device on which the calculated, on the patient (1) optimized dosage of the at least one Anästhesiemittels is presented as a recommendation.

13. Device according to one of claims 1 to 1 1, characterized in that the data processing device (7) generates control signals and transmits them to the metering device (5) for automatically adjusting the calculated, on the patient (1) optimized dosage of the at least one anesthetic agent ,

14. Device according to one of claims 6 to 13, characterized in that the data processing device (7) is adapted to a correlation analysis between by means of the EEG module (8) determined EEG index values and the measured concentration of the at least one Anästhesiemittels in the Exhalation air of the patient (1).

15. A method for operating an apparatus for carrying out anesthesia, in particular according to one of claims 1 to 14, comprising the steps:

Intravenous administration of an adjustable dose of at least one anesthetic agent to a patient (1);

Determining the concentration of the at least one anesthetic in the exhaled air of the patient (1);

Determination of the effect of at least one anesthetic on the

Patients (1), preferably in the form of anesthesia depth,

Preparation of a pharmacological model individualized for the patient (1) on the basis of the values respectively determined for the parameters dosage, concentration and effect of the at least one anesthetic agent, and

Determination of an individual, optimized to the patient (1)

Dosing of the at least one anesthetic agent based on the individualized pharmacological model produced.