Device for monitoring a patient during anesthesia and for determining the combined effect of several anesthetics

Abstract

Device (1) for determining a combined anesthetic effect on a patient anesthetized by means of a combination of at least two active substances characterized in that the device is set up to perform the following steps: Determining the concentration of each active ingredient at the site of action using pharmacokinetic and / or pharmacodynamic models; Summarizing the effect of all active ingredients within each class of active ingredients used, whereby the potency of the active ingredients is added if they act on the same receptor type; Determining the synergistic interaction between at least two active substances used in anesthesia by determining a combined potency N of the anesthetic effect of the applied active substances, based on a mean anesthetic efficacy of the active substances used and an interaction term. determining an NSRI index value NSRI = 100 ∗ ( 1 − ( N / N ' ) sl 1 + ( N / N ' ) sl ) , where - N is the combined power, - N' is a specific value at which an NSRI value of 50% is reached. - and sl is a slope factor for a transformation from N to NSRI; Display of the NSRI index value using a display device (29); and Display of at least one comparative value (67, 69) for anesthesia management and / or patient arousal by means of the display device (29).

Description

[0001] The present invention relates to a device for determining a combined anesthetic effect according to the preamble of claim 1.

[0002] The goal of adequate anesthesia is to ensure that the patient has no memory of the procedure, that reactions to painful stimuli are suppressed, and that circulation and respiration are maintained despite the necessary high-potency medications, thus guaranteeing the oxygen supply to the brain and other organs at all times. To achieve this, it is essential to ensure that the anesthetic drugs are present at their sites of action—for example, in the brain for centrally acting anesthetics such as sedatives or centrally acting analgesics such as opiates, or at the neuromuscular junction between motor nerves and skeletal muscles for paralytic drugs such as muscle relaxants—in appropriate concentrations. The required concentration can vary depending on the situation, for example, due to the surgical procedures being performed.For example, the pain stimulus triggered by a skin incision in the upper abdomen is significantly less than the pain stimulus due to incisions for kidney resection.

[0003] If the need for anesthetic effect changes during the course of, for example, an operation, adequate anesthesia should ensure that this need is met as quickly as possible.

[0004] Adequate anesthesia is also characterized by the fact that the anesthetic drugs are not administered in excessively high doses, in order to avoid, among other things, adverse effects. • to minimize undesirable side effects of the drugs used in anesthesia, such as acute weakening of the heart muscle's contractility or respiratory depression; and • to avoid unnecessarily high concentrations of anesthetic agents accumulating in the body's own storage sites or compartments such as fatty tissue, which would excessively delay the desired end of anesthesia due to backflow.

[0005] Achieving adequate anesthesia is particularly challenging for the anesthesiologist, among other reasons, because they have little or no knowledge of the concentrations of anesthetic agents in the blood or at the site of action, and the resulting anesthetic effects such as analgesia, sedation, and paralysis. This is especially true for drugs administered intravenously (IV). A further complication is that often more than one anesthetic drug is administered, and that analgesics (e.g., opiates) and sedatives (such as propofol) in particular interact synergistically. For example, the degree to which the effect of propofol is increased after increasing its concentration at the site of action depends on the presence of an opiate concentration at that site as well.

[0006] Technical solutions are known from the state of the art that can make it easier for the anesthesiologist to administer adequate anesthesia: a. The effect of muscle relaxants can be measured directly, albeit only on selected skeletal muscles (e.g., the thumb muscles) that are not always relevant to the specific procedure. b. The concentration of volatile anesthetic drugs can be measured in exhaled breath during exhalation. The end-expiratory concentration measured in this way reflects the concentration in the lungs. However, it only partially reflects the concentration in blood plasma and even less so the concentration in other tissues or at the site of action. c. Monitoring electrical voltages between specific points on the scalp (EEG) allows conclusions to be drawn about electrical activity in the brain. Devices are known that can interpret these voltage signals using highly sophisticated digital signal processing and, in some cases, modeling techniques, and aggregate them into a standardized value that is related—though not always strongly—to the depth of hypnosis experienced by the patient. One example of such a device is the BIS™ monitor from Aspect Medical. d. Methods are known by which the concentration profiles of anesthetic drugs can be determined and predicted using models based on knowledge of the drug amounts administered intravenously or via the lungs to the patient. These models are based on measurements from a large number of patients and allow for some adaptation to the actual patient by specifying the age, weight, etc., of the patient being treated. These methods fall within the field of pharmacokinetics. e. Furthermore, methods are known by which the anesthetic effects of the drugs used can be determined from the amounts of active ingredients administered. These effects are often expressed as the probability that a patient will react to a given stimulus (e.g., a skin incision or a response / shaking). These probabilities are based on statistical models derived from measurements on a large number of patients. These models can also describe the interaction of several anesthetic drugs. These methods fall within the field of pharmacodynamics. f. Furthermore, methods for the graphical representation of pharmacokinetically and pharmacodynamically determined concentration and effect profiles are known. These include representations on the time axis (time-based display), as well as representations of opiate concentrations versus sedative concentrations (concentration-based display, as described in patent DE 10 2004 050 717 B3).

[0007] Furthermore, the technical solutions are known from patent specification US 6 186 977 B1 and application specification US 2007 / 0 118 075 A1.

[0008] In addition to administering adequate anesthesia, as described above, the anesthesiologist is also responsible for monitoring and, if necessary, safeguarding bodily functions that are impaired or compromised due to side effects of anesthetic medications, therapeutic or surgical procedures, or patient illness. These bodily functions include, among others, circulatory function, body temperature, and respiration.

[0009] To fulfill this task, the anesthesiologist has a range of interventional options at their disposal, such as hemodynamically active drugs, volume administration (e.g., physiological saline solution), warming or cooling techniques, and ventilators. To effectively control the use of these interventional options, the anesthesiologist has various measurement methods available to measure relevant physiological variables or their surrogates. These include, for example, end-expiratory CO2 partial pressure measurement, invasive or non-invasive blood pressure measurement, heart rate measurement, and the like.

[0010] Against this background, the task is to specify a method for monitoring an anesthetized patient that allows the anesthesiologist to better care for the patient during adequate anesthesia as discussed above, and in particular to administer more appropriate doses of anesthetics. Furthermore, a suitable device should be developed and an anesthesia machine specified.

[0011] The problem is solved by means of a method for monitoring a patient anesthetized by means of at least one anesthetic agent using a monitoring device which has a display unit for showing information relating to the anesthetic agent, characterized in that the display unit also shows changing physiological states (HR, MAP, etCO2) of the patient during anesthesia.

[0012] Thus, a method is proposed for monitoring a patient anesthetized with at least one anesthetic agent using a monitoring device that includes a display unit for showing current or relevant information concerning the anesthetic. Furthermore, the display unit indicates changing physiological states of the patient during the course of anesthesia.

[0013] Within the scope of the present invention, an anesthetic is understood to be any drug known as an anesthetic, or any active ingredient underlying such a drug, and also combinations thereof, regardless of whether it is a volatile drug or an intravenously administered drug. The term anesthetic, as used in the invention, also includes any drug not belonging to the class of anesthetics, which the anesthesiologist must nevertheless consider when administering anesthesia in the implementation of the present invention. The latter category of drugs and / or active ingredients includes, for example, sedatives. In particular, drugs that exhibit relevant interactions with the commonly used anesthetics are considered anesthetics in this context.

[0014] The “patient” of the present invention can be a human being, but the present invention can also be used on anesthetized animals.

[0015] The patient's physiological states, which are also displayed on the monitor, can be indicated by measured values ​​or their surrogates of selected hemodynamic, respiratory, or other parameters suitable for assessing the patient's status and relevant to the anesthesiologist. Depending on the type of therapeutic or surgical procedure, different physiological states can be displayed to the anesthesiologist via the monitor.

[0016] For a general surgical procedure on an otherwise healthy patient who is intubated and ventilated, the following measurements, which change over time, can be displayed, for example: heart rate, mean arterial pressure, end-expiratory CO2 partial pressure, and the BIS™ value (Bispectral Index Monitoring, or BIS™ index for short, a measure of "depth of anesthesia", measured using an EEG).

[0017] Depending on the therapeutic intervention and patient context (e.g., comorbidities), some parameters may be omitted or additional parameters may be important. For example, during a therapeutic intervention where the patient is breathing spontaneously, respiratory rate, oxygen saturation, and tidal volume can also be displayed. In another example, a surgical procedure where the oxygen supply to the heart muscle is relevant due to pre-existing coronary artery disease, the ST segment of the simultaneously recorded ECG (electrocardiogram) and the inspiratory oxygen concentration can also be displayed.

[0018] According to the invention, it is possible for the first time to advantageously provide the anesthesiologist with the information required for the optimal management of anesthesia in such an easily accessible manner that the anesthesiologist can control and monitor the anesthesia with improved safety and precision. Since the anesthesiologist can, for the first time, recognize an interplay between information about the anesthetic(s) used and their effects on the patient, as well as those related to the procedure and / or anesthesia, the anesthesiologist can better determine the currently required dosage of the anesthetics used and the required depth of anesthesia.

[0019] The present invention further enables a reduced cognitive workload for the anesthesiologist by combining individually, jointly, and mutually relevant information in a display or indicator device. This can lead to less early fatigue of the anesthesiologist, as well as improved anesthetic outcomes and increased patient safety, compared to methods known from the prior art.

[0020] Combining information on the anesthetics used with information on the patient's current physiological state in a single display allows for the assessment of whether the drug models used to determine concentrations—which are always based on patient population statistics—are accurate in individual cases, or whether they need to be adjusted or verified based on the specific individual patient being treated. If necessary, adjustments to the anesthetic management can be made based on the identified deviations of the patient's behavior from the assumed model behavior, which in turn leads to improved anesthesia.

[0021] Advantageous embodiments of the invention are the subject of the dependent claims.

[0022] Furthermore, the task is to specify a method by which the combined anesthetic effect of a combination of active substances on the anesthetized patient can be determined. A further objective is to specify a suitable device for this purpose and to propose an anesthesia device.

[0023] This task is solved by a procedure for determining a combined anesthetic effect on a patient anesthetized by a combination of active substances, characterized by the following steps: Determining the concentration of each active ingredient at the site of action; Summarizing the effects of all active ingredients, particularly within each class of active ingredient used; and Determining the interaction between the active substances used in anesthesia.

[0024] Here, the concentration of each active ingredient at the site of action is determined. Of particular interest according to the invention is therefore knowledge of the actual effect of the administered active ingredient on the patient, as opposed to knowledge of the concentration at which the active ingredient is present in the blood alone. In cases where it is not possible to determine the actual concentration of one or more active ingredients at the site of action by measurement, this concentration can be replaced by the next most accurate concentration that can be measured. The concentration of each drug at the site of action can be determined using pharmacokinetic (and / or pharmacodynamic) models.

[0025] In this method, the effects of all active ingredients are combined, whereby each active ingredient can be considered individually, or a clustering process is used to group active ingredients of the same class. According to the invention, combination can be understood, for example, as the addition of their efficacy or potency if they act on the same receptor type or receptor. However, if they act via different mechanisms of action, the effects of the active ingredients are combined according to the type of interaction between these active ingredients, e.g., additively, synergistically, or antagonistically. The interaction between opiates, for example, is additive; the corresponding site concentrations of action of the opiates used can be added together, scaled according to their respective C50 or EC50 values ​​(corresponding to an average efficacy or potency).

[0026] The sedatives / hypnotics used (e.g., volatile anesthetics, intravenous anesthetics) are treated as described above in general terms. Volatile hypnotics, for example, can be "added" to each other with regard to their effectiveness using a scale based on the MAC value (minimal alveolar concentration).

[0027] The procedure also identifies synergistic interactions between several, i.e., at least two, active substances used in anesthesia. These interactions can be described using models such as those published by Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. In: Pharmacological Reviews (1995) Vol. 47, No. 2, 331-85; Minto CF, Schnider TW, Short TG, Gregg KM, Gentilini A, Shafer SL. Response surface model for anesthetic drug interactions. In: Anesthesiology 2000, 92: 1603-16; Bouillon TW, Bruhn J, Radulescu L, Andresen C, Shafer TJ, Cohane C, Shafer SL. Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy. In: Anesthesiology. 2004, Vol. 100, No. 6, pp. 1353-1372. ISSN 0003-3022 (P), 1528-1175 (E); and Bouillon TW, Schumacher PM, Leibundgut D, Shafer SL, Zbinden AM.A Novel Mechanistic Model Based on the MAC Reduction Paradigm Describes Hypnotic-Opioid Interaction for Suppression of Responses to Stimulation. In: Anesthesiology 2004, 101: A503. All related content of the aforementioned publications is incorporated by reference into this disclosure.

[0028] In the case of interactions that are not (yet) known from the state of the art, the mean efficacy or potency between the drugs of each drug type (i.e., analgesics on the one hand or sedatives / hypnotics on the other) can be extrapolated.

[0029] In the case of volatile anesthetics, this can be done, for example, using the MAC values, while in the case of opiates, this can be done using their C50 or EC50 values.

[0030] Using such interaction models and knowledge of the respective concentrations of the active ingredients at the site of action, a summary of the effects of all active ingredients can be made, and a combined potency N can be described. This potency N is derived from the drug types scaled by their mean efficacy or potency and an interaction term. The combined potency N can be mapped to a range of, for example, 0 to 100, or 0 to 10, or a correspondingly different scale (e.g., by simple multiplication by a factor or division by it) using an inverted sigmoid function. The combined potency N can therefore be expressed, for example, as the NSRI (Noxious Stimulus Response Index). NSRI=100*(1−(N / N')sl1+(N / N')sl)

[0031] This NSRI index corresponds to the probability of a patient's reaction or response to a painful stimulus. By carefully selecting N' and sl (see below), a favorable working range can be defined with regard to, for example, the patient's tolerance of a painful stimulus or their arousability. The NSRI is 100 for an awake or non-anesthetized patient and 0 for deepest anesthesia, where the values ​​0 and 100 are purely illustrative. The possible range of values ​​can extend between other values: the representation is therefore not limited to a scale of 0 to 100. Other representations are also possible. In particular, the range of values ​​for the NSRI can be changed, for example, by linear transformation. The NSRI can be given as a dimensionless numerical value. It can also be displayed as a temporal trend with a forecast.In this embodiment, its representation is comparable to the representation of parameters for indicating the depth of anesthesia, such as the BIS™ achieved via EEG. In particular, it can be represented in a time-related manner – i.e., with reference to specific, future points in time.

[0032] To assist the anesthesiologist, several graphical comparative values ​​for anesthesia management and patient arousal can be integrated into the display, such as an NSRI where 50% of patients would tolerate laryngoscopy without response. These comparative values ​​can be based, for example, on known population data.

[0033] To estimate the interaction, the NSRI can also be plotted for comparison for just one drug, e.g., the sedative / hypnotic. For this purpose, N (according to the calculation rules of the chosen interaction model) is calculated as if no analgesic (e.g., an opiate) had been administered. The NSRI is then calculated as before using formula (1). From the difference between the reduced NSRI calculated in this way and the combined NSRI (also taking the analgesics into account), an analgesic effect – consisting of the direct effect of the analgesics and the gain in efficacy due to synergistic interaction with the sedatives / hypnotics – can be estimated. However, the calculation of, for example, only the analgesic component, or the component of other administered drugs such as the hypnotic or sedative, or an interaction term, is also possible and encompassed by the invention, as is evident to those skilled in the art.

[0034] The following model is suitable for representing the depth of anesthesia as a continuum from sedation to the absence of any response to harmful or disturbing stimuli on a time-based scale. This approach allows for the specification of a patient's response probability and the representation of a cumulative drug effect on an integrated scale.

[0035] The standard interaction surface model can be expressed as: P=Ng1+Ng with P Probability of enduring a particular stimulus; N Combination of the active ingredient concentrations, normalized using their corresponding C50 values ​​and corrected for the interaction effect; and g is the slope factor, which indicates the steepness of the concentration-response curve.

[0036] The following applies to the sequential interaction model: N=ChypC50hyp∗Aout with Aout=Ain∗(1−CopiC50opi+Copi)

[0037] A out indicates a stimulus intensity for effects caused by administered opioids, and A in indicates the stimulus intensity in the absence of opioids (A in = 1 yields the “calibration stimulus strength”), so the model describes the attenuation of the opioid stimulus.

[0038] C hyp and C opi C50 represents the concentrations of the hypnotic and the opioid, or their respective combinations. xxx for the corresponding C50 or EC50 values ​​according to the mean efficacy or potency. N is therefore a dimensionless value that indicates the combined "effective concentrations" and is obviously independent of the strength of the stimulus (A). in= 1). This may seem unintuitive at first glance, but it is important to remember that the relative attenuation of a stimulus is completely independent of the stimulus strength, and that the value N required for a stimulus tolerance is calculated taking the stimulus strength into account (see below).

[0039] Plotting N over time yields the corresponding time course. The relationship between concentrations and their effect(s) is represented as follows: The effect(s) or selected endpoints can be represented as bands of tolerance probabilities (50% - 90%) over time on an "effect" scale. This requires calculating the required effect for given probabilities.

[0040] The general surface equation (equation (2)) can be solved for N. This leads to N=(P1−P)1 / g

[0041] Substituting equation (3) and simplifying due to the absence of opioids, we obtain Aout=Ain,N=ChypC50hyp∗Ain

[0042] An N' can now be determined depending on the stimulus strength A in , the desired tolerance probability P and the known slope factor g can be calculated: N'=(P1−P)1 / g∗Ain

[0043] Examples of tolerance to shaking and loud speaking (TOSS) with an A in = 1 by definition and a tolerance of a laryngoscopy (TOL) of A in = 2.83 (corresponding to the C50 ratio of propofol for tolerance of laryngoscopy as well as tolerance of shaking and loud response according to Bouillon TW, Schumacher PM, Leibundgut D, Shafer SL, Zbinden AM. A Novel Mechanistic Model Based on the MAC Reduction Paradigm Describes Hypnotic-Opioid Interaction for Suppression of Responses to Stimulation. Anesthesiology 2004; 101: A50).

[0044] The use of a slope factor g of 3.46 - as estimated by sequential interaction modeling of propofol and remifentanil (see reference above) - leads to the N' values ​​in N units of the following Table 1. Probabilities [ N -units] P50% TOSS 1 P90% TOSS 1,89 P50% TOL 2,83 P90% TOL 5,34

[0045] Rescaling of N – especially when achieving high anesthetic concentrations – and the associated necessary rescaling of the axis labels as well as the rescaling of the calibration lines of the TOL and TOSS ranges can be advantageously avoided by means of a transformation using a sigmoid function of the following form: NSRI=100∗(1−(N / N')sl1+(N / N')sl) with N' specific N' value at which an NSRI of 50 is achieved; and sl is the slope factor for the transformation from N to NSRI.

[0046] With a definition like in equation (8), the NSRI in its exemplary calculation is 100*(1-(N / 2,83)sl / (1+(N / 2.83) sl ) in an awake patient 100 (i.e. without the use of drugs), and the NSRI approaches 0 in deepest anesthesia (i.e. with high concentrations of drugs).

[0047] This scaling described above, with values ​​between 0 and 100, has the further advantage that the anesthesiologist is usually experienced in dealing with indicators whose values ​​range between 0 and 100, with 0 for the deepest anesthesia and 100 for the awake patient (e.g. BIS™, entropy).

[0048] If, as in the example above, N' = 2.83, then an NSRI of 50 would correspond to a laryngoscopy tolerance of 50% of patients (see Table 1), which is a reasonable choice. The slope factor should be set such that a good working range is achieved for both the anesthetic and recovery phases. If sl = 2.18, then the 90% tolerance of laryngoscopy will be mapped to an NSRI of (exactly) 20, and the recovery range (90% to 50% TOSS) is mapped to an NSRI of approximately 70 to 90.

[0049] For a conventional pharmacokinetic / pharmacodynamic display used in clinical routine, the following configuration is proposed to implement the present invention: 1. Display of NSRI over time with predictions for the future based on current drug dosages; 2. Display of the NSRI only with hypnotic drugs (assuming that no opioids have been administered and there is no interaction), combined in the display as in the point above (same axes); 3. Display of the concentration of hypnotic agents (blood / end tidal and site of action) in separate axes over time with predictions about the future; 4. Displaying the concentration of one or more opioids (blood and drug site) in different axes over time with predictions about the future; 5. Providing the option to insert markers, bars and / or lines for individualization of the drug display; and 6. Displaying a wake-up prediction (especially displaying the expected wake-up time).

[0050] The possible combinations can also be very helpful: 1. Display of hemodynamic status over time (pulse rate, blood pressure); 2. Displaying processed EEG parameters over time (e.g., BIS, entropy); and 3. Display of further anesthesia-relevant parameters of the multidimensional patient status over time.

[0051] The methods can each be implemented with the device as well as the anesthesia device, which can, for example, be configured as a ventilator. Since the advantages described above can also be achieved without any loss with the device according to the invention, reference is expressly made here to the discussion above to avoid repetition. Advantageous further developments are again the subject of the dependent claims.

[0052] The invention is explained in more detail below with reference to the accompanying drawing, where identical reference numerals denote identical structures and / or components. In the drawing, the following applies: Fig.Figure 1 shows a schematically simplified representation of a device according to the invention with a display device; Fig. 2 represents the content of a display device of an exemplary embodiment according to the invention; Fig. Figure 3 shows a representation according to the invention; and Fig. Figure 4 shows values ​​of the NSRI according to the invention for certain intraoperative events.

[0053] Fig.Figure 1 schematically simplifies a device 1 according to the invention for monitoring a patient. This device 1 is configured by way of example as an anesthesia device, although the invention is not limited to a device for monitoring anesthesia. The device 1 has two IV pumps 3 and 5 for two anesthetics, wherein at least one of the pumps 3 and 5 for intravenous administration can also be configured as a device for administering a volatile anesthetic. The device 1 further has an interface 7 by means of which input can be made via a keyboard (not shown), a mouse, or the like. The device 1 also has an information management system 9 by means of which a connection can be established between the anesthesia device, a hospital information system, a network, and the like for the provision of data relevant in individual cases.Data from the IV pumps 3 and 5, as well as from the interface 7, also flow into this information management system 9. Information or data 11 about the dosage of a first anesthetic using the IV pump 3 are stored in the device 1 according to the invention. Fig.Information 1 is transmitted to a first pharmacokinetic model 13. Information or data 15 about the dosage of a second anesthetic administered by the IV pump 5 is forwarded to a second pharmacokinetic model 17. A pharmacodynamic model 19 receives information or data about the name, type, or ID of the first anesthetic administered by the IV pump 3, as well as comparable data 23 about the second anesthetic administered by the IV pump 5. The two pharmacokinetic models 13 and 17, as well as the pharmacodynamic model 19, can also receive demographic data 25 about the anesthetized patient. This demographic data 25 can be entered via interface 7 or stored and retrieved in the information management system 9.Furthermore, clinical observations 27 and other events can be forwarded to a display 29 via interface 7 and / or the information management system 9. For this purpose, display 29 has a device 31 for marking or indicating the occurrence of events. A storage device 33 and a playback device 35 are attached to display 29. Using the first pharmacokinetic model 13 and the second pharmacokinetic model 17 (which can be supplemented by further models), calculated or predicted data 37, 39 concerning the site concentrations of action of the administered drugs can be forwarded to display 29 for presentation in a concentration-based display 41 and / or in a time-based display 43. The pharmacodynamic model 19, which receives data from models 13 and 17 – see the respective data stream indicated by dashed lines in the figure – Fig.1 -, data 45 passed to the display 29 serve to display isobols in the display 29, as they are related to Fig. 2 will be explained below.

[0054] Fig. Figure 2 shows a possible, inventive representation on the display device 29 of a monitoring device according to the invention. In an upper section of the representation, designated I. Fig. 2, the pulse rate (HR, heart rate), the mean arterial pressure (MAP) and the end-expiratory CO2 partial pressure (etCO2) are plotted over time (see section VI).

[0055] In Section II, the BIS™ is presented as a measure of the depth of hypnosis over time. The NSRI index proposed according to the invention is presented as a measure of the depth of anesthesia in Section III on a scale between 0 and 100. The concentration of sevoflurane over time is shown in Section IV, and the concentration of remifentanil in Section V, in a manner readily apparent to the anesthesiologist at all times, with the indication of Ce in [Vol%] or [ng / ml] corresponding to the concentration at the respective site of action.

[0056] The presentation of Fig. Section VI. lists further events marked with reference numbers 51, 53, and 55, which can represent different events during anesthesia, such as skin incision, intubation, etc. Their display in the context of other information, such as time course, medication dosage, etc., can provide the anesthesiologist with further important information and explanations.

[0057] As the right side of the illustration shows Fig.As can be seen below marking VII., future-oriented representations can also be considered in the display according to the invention. For example, in a concentration-based diagram VIII., the concentrations of sevoflurane and remifentanil are shown in an isobolate representation. Values ​​that lie in the past are marked in bold and bear the reference numeral 57. The current concentration ratio of the two anesthetics (sevoflurane and remifentanil) is marked by the dot with reference numeral 59. A forecast of the anesthetic concentrations and stimulus tolerances that will be present in the near future (5 minutes and 10 minutes, respectively) is clearly illustrated for the anesthesiologist by the less boldly marked curve 61 and the trend indicated by arrow 63. With regard to diagram VIII., reference is also made to the patent application pending before the German Patent and Trademark Office with application number 10 2006 053 856.Reference is made to document 0-32 of the same applicant. Its entire content in this regard is therefore incorporated by reference into the present disclosure.

[0058] Fig. Figure 3 shows two related displays of indications that appeared during the anesthesia of the patient anonymized under the designation "T01G0300". The upper display of the Fig. Figure 3 corresponds to a representation as it is the subject of the aforementioned patent application of the present applicant, number 10 2006 053 856.0-32. For further explanation, reference is therefore made to the aforementioned application. The representation below in Fig. 3 indicates the course (65) of the NSRI over the duration of the anesthesia.

[0059] The lower illustration also shows two hatched bands, 67 and 69. Band 67 extends from an NSRI level of 20 to an NSRI level of 50. Band 69 extends from an NSRI level of 70 to an NSRI level of 90. The area labeled 67 represents a range in which 90 to 50% of patients tolerate laryngoscopy in this embodiment. Area 69 represents a range in which 90 to 50% of patients do not respond to shaking and loud calls.

[0060] Fig. Figure 4 shows a representation of the NSRI according to the invention for certain intraoperative events, namely intubation 71, skin incision 73 and extubation 75 from anesthesias of 35 patients in whom propofol was administered together with remifentanil and fentanyl.

[0061] A first, hatched area 77 (which corresponds to area 69 of the Fig.3) is limited by the 90% and 50% TOSS (tolerance to shaking and loud noise) and is prominently displayed (e.g., in color) on the display or indicator device for easier orientation by the anesthesiologist. The same applies to a second, also hatched, area 79 (which corresponds to area 67 of the Fig. 3), which is limited by the 90% and 50% TOL (tolerance of a laryngoscopy).

[0062] Reference numbers 81, 83 and 85 indicate the distributions of NSRI for three events 71, 73 and 75 across the 35 patients.

[0063] Figure 87 shows the NSRI course 65 of a patient anonymized with “T24G0300” over time.

[0064] A method for monitoring an anesthetized patient and a method for determining the combined effect of various anesthetics are described. The present invention provides a device for carrying out these methods.

Claims

Device (1) for determining a combined anesthetic effect on a patient anesthetized by a combination of at least two active substances, characterized in that the device is configured to perform the following steps: determining the concentration of each active substance at the site of action using pharmacokinetic and / or pharmacodynamic models; summarizing the effect of all active substances within each class of active substances used, wherein the potency of the active substances is added if they act on the same receptor type;Determining the synergistic interaction between at least two active substances used in anesthesia by determining a combined potency N of the anesthetic effect of the applied active substances, based on a mean anesthetic efficacy of the active substances used and an interaction term, determining an index value NSRI to NSRI = 100 ∗ ( 1 − ( N / N ' ) sl 1 + ( N / N ' ) sl ) ,; where - N is the combined power, - N' is a specific value at which an NSRI value of 50% is reached. - and sl is a slope factor for a transformation from N to NSRI; Display of the NSRI index value using a display device (29); and Display of at least one comparative value (67, 69) for anesthesia management and / or patient arousal by means of the display device (29). Device (1) according to claim 1, characterized in that the device (1) is configured to perform the following step: Determining the synergistic interaction by means of extrapolation. Device (1) according to at least one of claims 1 or 2, characterized in that the device (1) is configured to perform the following step: Specifying the determined synergistic interaction as a value in a range from 0 to 100. Device (1) according to at least one of claims 1 to 3, characterized in that the device (1) comprises a technical device or a computer for carrying out the steps. Device (1) according to at least one of claims 1 to 4, characterized in that the device (1) is configured to perform the following step: Displaying all time-varying parameters over the time course (VI.) by means of the display device (29). Device (1) according to at least one of claims 1 to 5, characterized in that the device (1) is configured to perform the following step: Displaying a forecast (61) of future values ​​by means of the display device (29). Device (1) according to at least one of claims 1 to 6, characterized in that the device (1) is configured to perform the following step: Displaying a trend (63) for the development of calculated values ​​by means of the display device (29).

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