Improved method and device for assessing need of patient for drug compound, and related delivery device

Abstract

The present invention relates to a method (100) for assessing a patient's need for a pharmaceutical compound, comprising: performing a determination step (150) to determine a patient's need for a pharmaceutical compound based on MC and ML indices derived from an ANI index, their PC and PL slopes, and physiological data relating to the patient, the determination step comprising a sub-step (151) of determining a single bolus dose, the sub-step includes determining fuzzy logic variables CMC and CPC using fuzzy logic, the single bolus dose being equal to a first predetermined amount of the compound when the sum of the first and second fuzzy logic variables is strictly greater than 1, otherwise the single bolus dose being equal to zero.

Description

Technical Field

[0001] The field of this invention is patient pain management.

[0002] More specifically, the present invention relates to an improved method for assessing a patient's need for pharmaceutical compounds. The invention also relates to an improved apparatus for assessing a patient's need for pharmaceutical compounds, and a pharmaceutical compound delivery apparatus, particularly including such an assessment apparatus. The pharmaceutical compounds are, in particular, analgesic and / or hypnotic compounds.

[0003] In particular, the present invention can be applied to pain management in patients undergoing surgery under general or local anesthesia. Depending on other possibilities, the invention can be applied more broadly to pain management in conscious or unconscious patients in hospitals (especially in intensive care or palliative care), nursing facilities, or at home. Background Technology

[0004] When managing patient pain, it is necessary to accurately and in real time assess pain levels in order to provide medical responses that are tailored to the patient's needs.

[0005] For example, a medical response may include injecting analgesic, pain-relieving, or pain-soothing compounds into the patient.

[0006] However, the amount of compound injected into a patient should be proportionate to and tailored to the patient's condition and physiological characteristics.

[0007] To assess a patient's pain level, a method is known for determining the Analgesia Nociception Index (ANI) based on the variability of the patient's heart rate. The determination of this ANI index is known in the art, particularly through the methods and apparatus known in the patent documents filed by the applicant, FR 2821460, FR 2840187, FR 2864388, and EP 1804655.

[0008] To assess the need for analgesic and / or hypnotic compounds in real time, taking into account changes in patient pain levels over time and the types of pain experienced by the patient, the applicant has developed an apparatus and method for assessing the need for analgesic and / or hypnotic compounds, the method and apparatus taking into account the average ANI index over short and long periods, as well as the slope of the ANI index over these periods.

[0009] In particular, these technologies have become the subject of the applicant's patents FR 3006879 and FR 3006880.

[0010] The aforementioned techniques provide a way to determine the amount of analgesic and / or hypnotic compound to be administered to a patient at a specific point in time. Such a compound amount, which is significantly different from the amount usually administered and is intended to be administered over a short period of time, is referred to in medical terms as a "single bolus dose".

[0011] However, there has always been a need for a more stable and reproducible technique to assess the need for drug compounds, particularly in determining the single bolus dose to be administered to patients.

[0012] Furthermore, there is a need for more precise, closer-to-the-patient approach to determining the amount of compound a patient requires. This is because some known techniques may underestimate or overestimate the need for the compound, potentially increasing the patient's risk of hypotension or hypertension. Summary of the Invention

[0013] The present invention aims to overcome all or part of the above-mentioned disadvantages of the prior art.

[0014] Therefore, the present invention relates to a method for assessing a patient's need for a pharmaceutical compound, the method being implemented by an assessment device comprising means for measuring the patient's cardiac variability between 0.15 Hz and 4 Hz, a data processing and recording unit, and means for recording physiological data related to the patient, the method comprising the following steps: - Measurement steps, measuring the patient's cardiac variability between 0.15 Hz and 4 Hz; -In the first determining step, the data processing and recording unit determines the ANI index related to the patient's pain level based on the measured cardiac variability data; - The second determining step involves the data processing and recording unit determining, based on the ANI index, the MC index representing the average value of the ANI index in the so-called short term and the ML index representing the average value of the ANI index in the so-called long term, as well as the PC and PL slopes of the MC and ML indices, respectively. The MC and ML indices correspond to the patient's pain level in the short term and long term, respectively, and the PC and PL indices correspond to their changes in the short term and long term, respectively. - A recording step, wherein a device for recording physiological data related to the patient records physiological data related to the patient; - The third determination step involves the data processing and recording unit determining the patient's required drug compound needs based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient. This third determination step includes a sub-step for determining the amount of the compound to be administered to the patient, referred to as a single bolus dose, comprising: - based on the membership function F of the MC index.MC Determine a first fuzzy logic variable C between 0 and 1. MC , -Based on the membership function F of the PC index PC Determine a second fuzzy logic variable C between 0 and 1. PC When the first fuzzy logic variable C MC With the second fuzzy logic variable C PC If the sum is strictly greater than 1, the single injection dose is determined to be equal to a first predetermined amount of the compound; otherwise, the single injection dose is determined to be equal to zero. The third determining step further includes a sub-step for determining a second amount of the compound to be administered, which is less than the first predetermined amount, based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient. This second amount is performed after the sub-step of determining the single injection dose when the single injection dose is zero.

[0015] The method according to the present invention is based on fuzzy logic steps.

[0016] Compared to methods known in the prior art, determining the single bolus dose through fuzzy logic sub-steps can significantly improve the stability and repeatability of compound demand assessment.

[0017] The sub-step for determining the amount of compound to be administered to the patient at an isolated time point, i.e., the sub-step for determining a single bolus dose, enables the assessment of whether a single bolus dose can be administered to the patient.

[0018] If a single bolus dose can be administered to the patient based on MC and PC thresholds, then the value of the single bolus dose corresponds to a predetermined amount of compound. This predetermined amount of compound may be fixed or may be defined prior to implementation of the method, for example, based on patient-related data.

[0019] If a single bolus dose cannot be administered to the patient based on the MC and PC thresholds, the value of the single bolus dose is zero.

[0020] The average value of the ANI index can be calculated over a sliding window. In particular, the repeatability of the method according to the invention is even more important in this case compared to known techniques.

[0021] These aspects enable the provision of an efficient and safe process that meets the requirements for bringing such processes, performed by medical devices, to market.

[0022] This document indicates that the method can be operated in real time or cyclically, i.e., the steps of the method are repeated sequentially to determine the patient's drug compound requirements in real time or cyclically.

[0023] In clinical trials of the method according to the invention, compared with known methods, a reduction in the amount of analgesic and / or hypnotic compounds to be administered to patients was observed, as well as better hemodynamic stability, i.e., patients were less likely to experience hypotension and hypertension.

[0024] According to a second aspect, the present invention also relates to an apparatus for assessing a patient's need for a pharmaceutical compound, comprising means for measuring the patient's cardiac variability between 0.15 Hz and 4 Hz, a data processing and recording unit, and means for recording physiological data related to the patient, the processing and recording unit comprising a processor and a computer memory storing instructions configured to: - Receive data on the patient's cardiac variability between 0.15 Hz and 4 Hz; - Determine the ANI index related to the patient's pain level based on the received cardiac variability data; -Based on the ANI index, determine the MC index, which represents the average value of the ANI index in the so-called short term, and the ML index, which represents the average value of the ANI index in the so-called long term, as well as the PC and PL slopes of the MC and ML indices, respectively, which correspond to the patient's pain level in the short term and long term, and the PC and PL indices correspond to their changes in the short term and long term. - Receive physiological data related to the patient; - Based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient, determine the need for a drug compound to be administered to the patient. This step includes a sub-step for determining a first amount of the compound to be administered to the patient in a single dose, referred to as a single bolus dose, including: -Based on the membership function F of the MC index MC Determine the first fuzzy logic variable C between 0 and 1. MC - According to the membership function F of the PC index PC Determine the second fuzzy logic variable C between 0 and 1. PC , -When the first fuzzy logic variable C MC With the second fuzzy logic variable C PC If the sum is strictly greater than 1, the single injection dose is determined to be equal to the first predetermined amount; otherwise, the single injection dose is determined to be equal to zero. - After determining the single injection dose, when the single injection dose is equal to zero, a second amount of the compound to be administered is determined based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient, the second amount being less than the first predetermined amount.

[0025] Such a device possesses the technical advantages and effects of the method according to the present invention as described above.

[0026] Devices used to assess a patient’s need for drug compounds can, in particular, take the form of a computer with an input terminal, a cardiac variability sensor, and at least one other sensor for patient physiological data connected to the input terminal.

[0027] The evaluation equipment may include a device for displaying data, particularly the amount of the drug compound to be administered.

[0028] It should be noted that the method and the device described can also be used to assess a patient's needs for a pharmaceutical compound or drug and / or auxiliary medical care. Preferably, the pharmaceutical compound is analgesic and / or hypnotic.

[0029] The following describes other particularly advantageous and convenient features of the method according to the invention and the evaluation device according to the invention.

[0030] According to one embodiment, in the evaluation method and apparatus according to the present invention, the membership function F of the MC index is... MC For: - When the MC exponent is less than or equal to the low threshold S MCLow When, equal to 1, -When the MC exponent is greater than or equal to the high threshold S MCHigh When, equal to 0, -and when the MC index is between the low threshold S MCLow and high threshold S MCHigh Between these two points, there is a monotonically decreasing transition between 1 and 0, and the membership function F of the PC exponent is... PC for: -When the PC index is less than or equal to the low threshold S PCLow When, equal to 1, -When the PC index is greater than or equal to the high threshold S PCHigh When, it equals 0. -and when the PC index is between the low threshold S PCLow and high threshold S PCHigh Between 1 and 0, there is a monotonically decreasing transition.

[0031] Choosing this type of membership function allows us to observe the good performance of the method, which is particularly stable and repeatable.

[0032] The type of monotonically decreasing transition can be adjusted based on the type of compound intended for administration and / or the patient's clinical condition. Similarly, high and low thresholds can be adjusted according to these same criteria.

[0033] According to one embodiment, in the method and evaluation apparatus according to the invention, the membership function F of the MC index... MC Defined according to the following expression: And the membership function F of the PC index PC Defined according to the following expression:

[0034] Typically, a decreasing linear transition can give the method good performance.

[0035] This transition is particularly useful for patients undergoing surgery under general anesthesia.

[0036] According to one embodiment, in the evaluation method and apparatus of the present invention: -The threshold S MCLow Between 45 and 55, and preferably equal to 50. -The threshold S MCHigh Between 58 and 68, and preferably equal to 63. -The threshold S PCLow Between -40 and -30, and preferably equal to -35. -The threshold S PCHigh It is between -30 and -20, and preferably equal to -25.

[0037] The threshold range and preferred threshold are particularly relevant during surgery when the patient is under general anesthesia.

[0038] These values ​​are particularly applicable when the drug compound is the analgesic and / or hypnotic compound remifentanil.

[0039] According to one embodiment, in the method according to the invention, the step of recording patient-related physiological data is a step of recording at least one systolic blood pressure (SBP) of the patient by means of a physiological data recording device configured to measure and record at least one systolic blood pressure (SBP), wherein the patient's systolic blood pressure (SBP) is greater than or equal to a first systolic blood pressure threshold S. SBP1 Second systolic blood pressure threshold S SBP2 When at least one of the following conditions is met, the method performs the sub-step of determining the single injection dose.

[0040] In the assessment device according to the invention, receiving patient-related physiological data includes receiving at least one systolic blood pressure (SBP) data of the patient, for example, acquired by a physiological data recording device configured to measure and record at least one systolic blood pressure (SBP), when the patient's systolic blood pressure (SBP) is greater than or equal to a first systolic blood pressure threshold S. SBP1 Second systolic blood pressure threshold S SBP2 When at least one of them is present, the operation of determining the single injection dose is performed.

[0041] According to one embodiment, in the evaluation method and apparatus according to the present invention, the first systolic blood pressure threshold S SBP1 Corresponding to a predetermined average value of systolic blood pressure, and the second systolic blood pressure threshold S SBP2 This corresponds to the patient's systolic blood pressure as previously measured and recorded.

[0042] Specifically, in the method according to the invention, the second systolic blood pressure threshold S SBP2 This corresponds to the patient's systolic blood pressure measured and recorded prior to performing the method.

[0043] By setting the threshold in this way, the proportional adjustment can be adjusted based on the generally accepted average systolic blood pressure and the patient's systolic blood pressure before the procedure.

[0044] According to one embodiment, in the method according to the invention, the systolic blood pressure of a patient previously measured and recorded corresponds to the systolic blood pressure of a patient previously measured and recorded during the previous execution of the method.

[0045] In the assessment device according to the invention, the previously measured and recorded systolic blood pressure of the patient corresponds to the systolic blood pressure of the patient obtained during the period when the assessment device previously received the patient's physiological data.

[0046] When the method according to the invention is performed cyclically, or when the equipment is evaluated cyclically, the scaling factor can take into account the systolic pressure measured and recorded during the previous method iteration or equipment operation, so that changes in systolic pressure can be tracked.

[0047] According to one embodiment, the method includes a proportioning step for adjusting the amount of the drug compound to be administered when the patient's systolic blood pressure (SBP) is strictly below a first threshold S. SBP1 and the second systolic blood pressure threshold S SBP2In both cases, the method performs the adjustment step upstream of the third determining step, the adjustment step including determining the amount of drug compound to be administered, which corresponds to the amount of drug compound previously administered, and subtracting an amount of drug compound from it, the subtracted amount of drug compound being proportional to the change in the measured and recorded patient systolic blood pressure (SBP) value relative to the patient's systolic blood pressure value measured and recorded before performing the method.

[0048] In the assessment device according to the invention, the instructions include proportionally adjusting the amount of the drug compound to be administered when the patient's systolic blood pressure (SBP) is strictly below the first threshold S. SBP1 and the second systolic blood pressure threshold S SBP2 In both cases, the adjustment is performed upstream of determining the compound requirement. The adjustment includes determining the amount of drug compound to be administered, which corresponds to the amount of drug compound previously administered, and subtracting an amount of drug compound from it. The amount of drug compound subtracted is proportional to the change in the measured and recorded patient systolic blood pressure (SBP) value compared to the patient systolic blood pressure value received by the assessment device during a previous assessment.

[0049] By adjusting the dosage proportional to the decrease in systolic blood pressure, the amount of compound to be administered can be reduced, thereby lowering the risk of hypotension in patients. Furthermore, the total amount of compound to be administered can be reduced, making it more suitable for the patient's condition.

[0050] Therefore, when a patient's systolic blood pressure drops too much, the amount of drug compound will decrease.

[0051] Here, this may be the amount of drug compound determined before using the method or before any evaluation by the evaluation device, or the amount of drug compound determined by the evaluation device during the third determination step of the method, during a previous execution of the method, or when the compound requirement was previously determined.

[0052] When the method is executed cyclically or the evaluation device is evaluated cyclically, it is understood that the determination of compound requirements and thus the determination of a single injection dose are performed only when a sufficient number of adjustments have been performed to verify that the systolic blood pressure is no longer lower than one of the two aforementioned systolic blood pressure thresholds.

[0053] This ensures the safety of the method or the evaluation device, guaranteeing that there is no risk of excessive compound, especially no single bolus dose, being administered to patients with hypotension.

[0054] According to a third aspect, the present invention also relates to an apparatus for delivering a pharmaceutical compound, comprising an apparatus for assessing a patient’s need for the pharmaceutical compound according to a second aspect of the invention, said apparatus being associated with a control device and, preferably, an electrically powered infusion system.

[0055] The delivery device may specifically include a control device configured to adjust the flow rate of the drug compound according to the determined amount of the drug compound, which is achieved by acting on the infusion system. Attached Figure Description

[0056] Other specific advantages, objects, and features of the present invention will become apparent from the following non-limiting description of at least one specific embodiment of the apparatus and method to which the invention is subject, with reference to the accompanying drawings: - Figure 1 A conveying device including an evaluation device according to the invention is illustrated schematically; - Figure 2 An evaluation device according to the present invention is shown schematically; - Figure 3 This is a flowchart of the evaluation method according to the present invention; - Figure 4 This is a flowchart of the evaluation method according to the present invention, which includes an optional scaling step; - Figure 5 The graphs show the membership functions F_MC for the MC exponent and F_PC for the PC exponent. - Figure 6 This is a flowchart of an evaluation method according to one embodiment. Detailed Implementation

[0057] This specification is given by way of non-limiting example, and each feature of one embodiment can be advantageously combined with any other feature of any other embodiment.

[0058] From now on, it should be noted that the accompanying drawings are not drawn to scale.

[0059] Figure 1 The compound delivery device 300 is shown schematically.

[0060] The delivery equipment 300 includes equipment 200 for assessing drug compound requirements, a control device 240, and an infusion system 250.

[0061] Preferably, the infusion system 250 is electrically powered and driven by the control device 240, which is connected to the evaluation device 200 via a data link. The infusion system is suitable for dispensing drug compounds into the blood circuit of a patient requiring administration of the drug compound, for example, through a catheter of the infusion system 250.

[0062] The pharmaceutical compounds are particularly analgesic and / or hypnotic compounds.

[0063] Specifically, the analgesic and / or hypnotic compound is an analgesic compound, such as an opioid compound, particularly morphine. For example, the compound is remifentanil. According to other examples, the compound is a non-morphine compound such as ketamine, or an α-2-agonist compound such as clonidine.

[0064] Figure 2 A separate assessment device 200 is schematically shown, not specifically associated with the control device 240 and the infusion system 250. In fact, the assessment device 200 can operate independently without the device for administering the compound, determining the need for analgesic and / or hypnotic and / or muscle relaxant compounds, and transmitting this information to another device or, for example, a medical professional.

[0065] The assessment device 200 may specifically include a device 210 for measuring the patient’s cardiac variability between 0.15 Hz and 4 Hz, a data processing and recording unit 220, and a device 230 for recording physiological data related to the patient.

[0066] For example, the data processing and recording unit 220 includes a microprocessor or processor 221 and a computer memory 222 adapted to store instructions for configuring the processor 221 for its operation. For example, the computer memory 222 is a non-volatile memory, which may be rewritable, such as an "EPROM" type.

[0067] The device 230 for recording physiological data related to the patient can be a physiological data sensor, particularly a commercially available sensor. These sensors can be configured to record the patient's physiological or vital data and transmit it to the data processing and recording unit 220 via a data link. For example, the recording device 230 includes at least one blood pressure sensor, particularly a systolic blood pressure sensor, also known as a blood pressure monitor.

[0068] The device 210 for measuring the patient’s cardiac variability between 0.15 Hz and 4 Hz may include various devices known to those skilled in the art, such as an electrocardiograph (ECG) and / or a pulse oximeter, by which the patient’s cardiac variability between 0.15 Hz and 4 Hz can be determined.

[0069] The evaluation device 200 may also include other peripheral devices, such as information display devices, such as computer screens.

[0070] The assessment device 200 enables the assessment of a patient’s need for analgesic and / or hypnotic compounds (hereinafter “compounds”) based on the patient’s physiological data, particularly when the patient is under anesthesia or sedation.

[0071] The need for a compound may specifically involve determining the amount of the compound required by the patient. The assessment device 200 may enable the communication of such a compound amount to medical personnel, for example, via a computer screen, or to the control device 240 for administration by the infusion system 250.

[0072] Therefore, the assessment device 200 can make recommendations on the patient's need for the compound, and then the appropriate amount of the compound can be administered by a medical professional or automatically by the infusion system according to the medical professional's decision.

[0073] The need for the compound is specifically assessed by the assessment device 200 from the ANI index, which is an index related to the level of pain experienced by the patient. Therefore, the need for the compound can be determined based on the perceived level of pain, thereby assessing the optimal amount of compound required by the patient to relieve pain without resulting in underdosing or overdosing.

[0074] Therefore, the assessment device 200 is configured to implement a method 100 for assessing a patient's need for analgesic and / or hypnotic compounds.

[0075] More specifically, the computer memory 222 of the evaluation device 200 stores instructions for configuring the processor 221 to implement the steps of the method 100.

[0076] Now will be of particular reference Figure 3 and Figure 4 To describe the method 100 intended to be implemented by the evaluation device 200.

[0077] The method 100 includes step 110 of measuring the patient’s cardiac variability between 0.15 Hz and 4 Hz.

[0078] The method 100 then includes a first determining step 120, in which the data processing and recording unit 220 determines an ANI index related to the patient’s pain level based on cardiac variability data measured during step 110.

[0079] For example, the ANI index can be calculated according to the method described in application WO 2006 / 032739. The first determining step 120 may therefore include the steps of the method to determine the ANI index.

[0080] The method 100 further includes a second determining step 130, in which the data processing and recording unit 220 determines the sub-index or index MC and the sub-index or index ML.

[0081] The MC and ML indices are determined based on the ANI index, where the MC index represents the average value of the ANI index over the so-called short term, and the ML index represents the average value of the ANI index over the so-called long term.

[0082] Therefore, the MC and ML indices correspond to the patient's pain levels in the so-called short term and the so-called long term (which lasts longer than the short term), respectively.

[0083] Furthermore, in the second determination step 130, the slopes PC and PL of the MC and ML indices are determined, which correspond to changes in the patient's pain level in the short and long term, respectively.

[0084] In other words, the MC and ML indices are calculated based on various values ​​of ANI over a given time period, which enables the limitation of the effects of transient variability in ANI measurements due to the calculation method, and also allows the derivation of trends in changes in patient pain.

[0085] More specifically, the MC and ML indices are preferably calculated based on the average value of the ANI index over two different periods (i.e., short-term and long-term).

[0086] Advantageously, the short period corresponds to a sliding window of 45 to 90 seconds, and preferably about 60 seconds, while the long period corresponds to a sliding window of 90 to 240 seconds, and preferably about 180 seconds.

[0087] Advantageously, the period used to calculate ML is generally 1.5 to 3 times the period used to calculate MC.

[0088] The PC slope, in degrees, is calculated from two independent MC values ​​for a given duration using the following formula: PC =

[0089] Advantageously, the time interval between t1 and t2 is approximately 15 to 45 seconds, and preferably equal to 30 seconds.

[0090] The slope of PL, in degrees, is calculated in a similar manner to PC using the following formula: PL =

[0091] Similarly, the time interval separating t1 and t2 is approximately 15 to 45 seconds, and preferably equal to 30 seconds.

[0092] In addition, the method 100 includes a step 140 of recording patient-related physiological data, performed by a device 230 for recording patient-related physiological data.

[0093] As previously described, the recording device 230 can measure, for example, heart rate (HR) and systolic blood pressure (SBP).

[0094] These parameters are not used directly to calculate the optimal amount of compound needed by the patient, but rather as a safety precaution, because the assessment device will not perform an assessment if certain thresholds corresponding to these parameters are exceeded.

[0095] Examples of safety procedures will be described later in this manual.

[0096] In other embodiments, other physiological parameters may be used to replace or supplement heart rate (HR) and systolic blood pressure (SBP).

[0097] Although this mode has the disadvantage of reduced safety, it is possible to use only one physiological parameter.

[0098] Other types of patient-related data, such as the patient's weight, height, age, or gender, can also be recorded via the recording device 230. For this purpose, the recording device 230 may advantageously include a keyboard or touch surface, not shown in the figures.

[0099] The method 100 further includes a third determining step 150, in which the data processing and recording unit 220 determines the patient's required drug compound (here, for example, analgesic and / or hypnotic compound).

[0100] The patient’s need for analgesic and / or hypnotic compounds is determined based on the MC and ML indices, their PC and PL slopes, and patient-related physiological data.

[0101] More specifically, during the third determination step 150, it is first determined whether the patient needs to receive the first dose q. p The compound is administered to the patient in a single dose. This relatively large amount of compound, intended for administration over a short period of time, is referred to as a "single bolus dose." A single bolus dose of the compound is required when the pain is severe, i.e., when the ANI index is close to 0.

[0102] Therefore, the third determining step 150 includes a sub-step 151 of determining a first amount of compound to be administered to the patient in a single dose, i.e., determining a single bolus dose.

[0103] Sub-step 151, which determines the single bolus dose, includes determining the membership function F based on the MC index. MC Determine the first fuzzy logic variable C between 0 and 1.MC .

[0104] Sub-step 151, which determines the single bolus dose, also includes determining the membership function F based on the PC index. PC Determine the second fuzzy logic variable C between 0 and 1. PC .

[0105] Sub-step 151, which determines the single injection dose, then includes: when the first fuzzy logic variable C... MC and the second fuzzy logic variable C PC When the sum is strictly greater than 1, the single injection dose is determined to be equal to the first predetermined amount q. p The compound, otherwise the single injection dose is determined to be zero.

[0106] In other words, when the first fuzzy logic variable C MC and the second fuzzy logic variable C PC When the sum is strictly greater than 1, the patient requires a single bolus dose; while when the first fuzzy logic variable C MC and the second fuzzy logic variable C PC When the sum is less than 1, the patient does not need a single bolus dose.

[0107] Therefore, the sub-step 151 of determining the single injection dose is the step of calling fuzzy logic to determine whether a single injection dose needs to be administered.

[0108] The membership function F of the MC exponent here MC and PC exponent membership function F PC It is a function bounded between 0 and 1. Therefore, the MC or PC exponent values ​​are represented by the image of their respective membership functions, which is a value C between 0 and 1. PC Or C MC This refers to a "fuzzy" Boolean value.

[0109] Figure 5 The membership function F of the MC exponent is shown. MC and PC exponent membership function F PC The image.

[0110] For example, the MC exponential membership function F MC yes:

[0111] -When the MC exponent is less than or equal to the low threshold S MCLow When, it equals 1;

[0112] -When the MC exponent is greater than or equal to the high threshold S MCHigh When, it equals 0;

[0113] -and when the MC index is within the low threshold S MCLowand high threshold S MCHigh Between 1 and 0, there is a monotonically decreasing transition.

[0114] Similarly, for example, the PC exponential membership function F PC yes:

[0115] -When the PC index is less than or equal to the low threshold S PCLow When, it equals 1;

[0116] -When the PC index is greater than or equal to the high threshold S PCHigh When, it equals 0;

[0117] -and when the PC index is between the low threshold S PCLow and high threshold S PCHigh Between 1 and 0, there is a monotonically decreasing transition.

[0118] Examples of monotonically decreasing transitions are linear, hyperbolic (especially S-shaped), exponential, and even Gaussian transitions.

[0119] A linear decreasing transition is particularly preferred.

[0120] For example, the MC exponential membership function F MC Defined by the following expression:

[0121] For example, the PC exponential membership function F PC Defined according to the following expression:

[0122] The high and low transition thresholds S MCLow S MCHigh S PCLow and S PCHigh Method 100 can be freely adjusted according to the conditions of use, particularly based on the patient profile (especially their age, weight, sex, etc.), and / or the type of compound to be administered to the patient, and / or the patient's clinical condition, i.e., their medical care needs. Similarly, transitional types can be freely adjusted according to these same criteria.

[0123] For example, the threshold S MCLow S MCHigh S PCLow and S PCHigh The following settings can be made:

[0124] Threshold S MCLow It is between 45 and 55, and preferably equal to 50.

[0125] Threshold S MCHigh It is between 58 and 68, and preferably equal to 63.

[0126] Threshold S PCLow It is between -40 and -30, and preferably equal to -35.

[0127] Threshold S PCHigh It is between -30 and -20, and preferably equal to -25.

[0128] Such ranges and preferred values, particularly when associated with linear transitions, are especially applicable during surgery under general anesthesia when remifentanil, as a compound, is to be administered to the patient. Indeed, repeatable and stable operation of the method can be observed in this context.

[0129] The sub-step 151 for determining the single bolus dose based on fuzzy logic enables particularly reliable and repeatable single bolus dose determination, even when the MC index is highly variable, especially when determined over a sliding window. This is because fuzzy logic eliminates the need for single bolus dose determination based on a fixed threshold, which is much more sensitive to changes in the MC index.

[0130] Specifically, refer to Figure 6 It shows a more detailed embodiment of method 100 in the form of a flowchart, in which, when a single bolus dose is determined and the compound used is remifentanil at a concentration of 25 μg / ml, the flow rate variable is increased by 0.12 μg / kg / min for 10 seconds, for example, based on the patient’s weight.

[0131] In this example, the "Bolus" variable is set to 10, and this variable is decremented during the next execution of method 100, which can operate continuously or periodically. As long as the "Bolus" variable is not zero, method 100 will not execute a new step to determine the amount of compound.

[0132] If at the end of substep 151, which determines the single bolus dose, the first fuzzy logic variable C MC Second fuzzy logic variable C PC If the sum is less than 1, i.e., the single injection dose is zero, then method 100 performs sub-step 152 to determine a second amount of compound to be administered, which is less than the first predetermined amount q. p .

[0133] The second compound was determined based on the MC and ML indices, their PC and PL slopes, and patient-related physiological data.

[0134] For example, sub-step 152, which determines the amount of the second compound, includes making a series of successive comparisons of indices MC, ML, PC, and PL with predetermined thresholds.

[0135] In particular, such as in Figure 6 As can be seen in sub-step 152, the MC exponent is first compared with the low threshold S. b and high threshold S h Continuous comparisons are made to determine whether the average ANI index over a short period is low, moderate, or high, i.e., whether the pain is severe, moderate, or mild.

[0136] Based on this initial determination, and based on the long-term trend of the average pain level and the changes in the main pain level in the short and long term, method 100 determines a second amount of compound. This second amount of compound may be greater than or less than the previously determined second amount of compound, particularly those determined during previous executions of method 100. The second amount of compound may also remain unchanged relative to the previously determined second amount of compound.

[0137] Once substep 152 has been executed and the second amount of compound has been determined, method 100 can be executed again from the beginning. A new execution of the method can be delayed, for example, by setting the value of the variable "Pref". Figure 6 In the example, this value is 10, and the variable is decremented during each execution of the method, before the execution of the third determination step 150.

[0138] The specific implementation of sub-step 152, and Figure 6 The specific operation of the decrementing loop of variables “Bolus” and “Pref” in the algorithm shown is described in the applicant’s patent documents FR 3006879 and FR 3006880. Those skilled in the art can refer to these documents to implement method 100.

[0139] As discussed earlier in this specification, method 100 may include safety steps designed to prevent the determination of any amount of the compound to be administered when certain thresholds of the patient’s physiological data are exceeded.

[0140] For example, refer to Figure 4 and Figure 6 Method 100 includes an optional step of comparing systolic blood pressure (SBP) with two systolic blood pressure thresholds.

[0141] Therefore, step 140 of recording physiological data related to the patient is the step of recording at least one systolic blood pressure (SBP) of the patient, which is performed by device 230 for recording physiological data, the device being configured to measure and record at least one systolic blood pressure (SBP).

[0142] Optional steps for comparing systolic blood pressure (SBP) to two systolic blood pressure thresholds include comparing systolic blood pressure (SBP) to the following:

[0143] First systolic blood pressure threshold S SBP1This can be a predetermined average systolic blood pressure, such as a systolic blood pressure of 120 mmHg, which can be considered as the lowest systolic blood pressure threshold for healthy individuals, and related to:

[0144] Second systolic blood pressure threshold S SBP2 This could be the patient's systolic blood pressure (SBP) value measured and recorded prior to performing method 100. For example, the patient's systolic blood pressure (SBP) may have been measured and recorded during a previous execution of method 100.

[0145] When a patient's systolic blood pressure (SBP) is greater than or equal to the first systolic blood pressure threshold S... SBP1 Second systolic blood pressure threshold S SBP2 When at least one of them is present, method 100 performs sub-step 151 to determine the single bolus dose.

[0146] This is because when a patient's systolic blood pressure (SBP) is not lower than the first threshold and has not decreased compared to the previous systolic blood pressure, the patient's risk of hypotension can be considered low, and the amount of compound to be administered can be determined without endangering the patient's health.

[0147] When a patient's systolic blood pressure (SBP) is strictly below the first threshold S SBP1 Second systolic blood pressure threshold S SBP2 In both cases, the method performs a proportioning step 145 of the amount of analgesic and / or hypnotic compound to be administered upstream of the third determination step 150. Then, during the same iteration of method 100, method 100 does not perform the third determination step 150, and therefore, in particular, does not perform the determination of the single bolus dose.

[0148] The proportional adjustment step 145 includes determining the amount of analgesic and / or hypnotic compound to be administered, which corresponds to the amount of analgesic and / or hypnotic compound previously administered, and subtracting the amount of analgesic and / or hypnotic compound from the amount of analgesic and / or hypnotic compound that is proportional to the change in the measured and recorded value of the patient's systolic blood pressure (SBP) relative to the value of the patient's systolic blood pressure measured and recorded prior to performing method 100.

[0149] Specifically, refer to Figure 6 The algorithm shown allows the compound flow rate setpoint variable "Flow" to be updated directly proportionally to the changes in the patient's measured and recorded systolic blood pressure (SBP) values ​​relative to the changes in the patient's systolic blood pressure values ​​measured and recorded prior to the execution of method 100.

[0150] For example, a new flow rate setpoint can be defined as follows: Where S SBPmin It is a predetermined systolic blood pressure cutoff value, for example, corresponding to 80 mmHg.

[0151] In other words, the "Flow" variable is overridden and updated so that the compound flow setpoint is reduced proportionally to changes in the patient's systolic blood pressure (SBP).

[0152] The proportional adjustment step 145 is repeated until the patient's systolic blood pressure is no longer lower than two thresholds S. SBP1 and S SBP2 One of the factors considered is that the patient's risk of hypotension is considered low. This is a safety measure to avoid assessing excessive compound requirements for patients who are in a state of hypotension or decreased blood pressure.

[0153] For example, the time interval between two iterations, that is, the time interval between two measurements of the patient's systolic blood pressure, is between 2 and 5 minutes.

[0154] Furthermore, the proportioning step 145 allows for better adjustment of compound delivery according to the patient's needs, and also enables a reduction in the total amount of compound to be administered to the patient, which is both clinically and economically beneficial.

[0155] While the optional step of comparing systolic blood pressure (SBP) to two systolic blood pressure thresholds and subsequently performing proportional adjustment step 145 as described above is particularly advantageous, a more conventional safety procedure, as described in the applicant's patent documents FR 3006879 and FR 3006880, is also conceivable. The safety procedure described therein specifies stopping the flow of the compound when the patient is in a state of hypotension or bradycardia.

[0156] According to one embodiment, method 100 and / or assessment device 200 and / or delivery device 300 can be used to assess a patient’s need for complementary medical care as an alternative to or supplement to assessing the need for pharmaceutical compounds.

[0157] In other words, in addition to determining the amount of compound a patient needs, or as an alternative, a patient's need for ancillary medical care can be assessed in a similar manner, based on fuzzy logic based on the ANI index and its sub-indices. For example, determining the need for ancillary medical care includes determining that the patient requires it, and may include, for example, determining the duration and / or intensity of the ancillary medical care.

[0158] "Assisted care" refers to all care that can be provided to a patient, in addition to medical and surgical treatments, including but not limited to pediatric care, physical therapy, neonatology, neurophysiology, or more broadly, care based on environmental changes to improve the patient's well-being.

[0159] More generally, it should be noted that the invention is not limited to the examples described and shown.

Claims

1. A method (100) for assessing a patient's need for a pharmaceutical compound, the method being intended to be performed by an assessment device (200) comprising means (210) for measuring the patient's cardiac variability between 0.15 Hz and 4 Hz, a data processing and recording unit (220), and means (230) for recording physiological data related to the patient, the method comprising the steps of: ○ Measurement step (110): Measure the patient's cardiac variability between 0.15 Hz and 4 Hz; ○ First determination step (120): The data processing and recording unit (220) determines the ANI index related to the patient's pain level based on the measured cardiac variability data; ○ Second determination step (130): The data processing and recording unit (220) determines, based on the ANI index, the MC index representing the average value of the ANI index in the so-called short term and the ML index representing the average value of the ANI index in the so-called long term, as well as the PC and PL slopes of the MC and ML indices respectively, the MC and ML indices corresponding to the patient's pain level in the short term and long term respectively, and the PC and PL indices corresponding to their changes in the short term and long term respectively; ○ Recording step (140): Physiological data related to the patient is recorded by a device (230) for recording physiological data related to the patient; The third determination step (150) involves the data processing and recording unit (220) determining the patient's required drug compound needs based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient. This third determination step includes a sub-step (151) for determining a first amount of the compound to be administered to the patient in a single dose, referred to as a single bolus dose, comprising: ■Based on the membership function F of the MC index MC Determine the first fuzzy logic variable C between 0 and 1. MC , ■Based on the membership function F of the PC index PC Determine the second fuzzy logic variable C between 0 and 1. PC , ■When the first fuzzy logic variable C MC With the second fuzzy logic variable C PC If the sum is strictly greater than 1, the single injection dose is determined to be equal to a first predetermined amount of the compound; otherwise, the single injection dose is determined to be equal to zero. The third determining step (150) further includes a sub-step (152) for determining a second amount of the compound to be administered, based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient, the second amount being less than the first predetermined amount, and the sub-step (152) being performed by the method after the sub-step (151) for determining the single injection dose when the single injection dose is zero.

2. The method (100) according to claim 1, wherein the membership function F of the MC index... MC for: ○ When the MC exponent is less than or equal to the low threshold S MCLow When, equal to 1, ○ When the MC exponent is greater than or equal to the high threshold S MCHigh When, it equals 0. And when the MC index is between the low threshold S MCLow and high threshold S MCHigh Between these, there is a monotonically decreasing transition between 1 and 0, and the membership function F of the PC exponent is... PC for: ○ When the PC index is less than or equal to the low threshold S PCLow When, equal to 1, ○ When the PC index is greater than or equal to the high threshold S PCHigh When, it equals 0. ○ And when the PC index is between the low threshold S PCLow and high threshold S PCHigh Between 1 and 0, there is a monotonically decreasing transition.

3. The method (100) according to claim 2, wherein the membership function F of the MC index MC Defined according to the following expression: And the membership function F of the PC index PC Defined according to the following expression:

4. The method (100) according to any one of claims 2 or 3, wherein ●The threshold S MCLow Between 45 and 55, and preferably equal to 50. ●The threshold S MCHigh Between 58 and 68, and preferably equal to 63. ●The threshold S PCLow Between -40 and -30, and preferably equal to -35. ●The threshold S PCHigh It is between -30 and -20, and preferably equal to -25.

5. The method (100) according to any one of claims 1 to 4, wherein the step (140) of recording patient-related physiological data is a step of recording at least one systolic blood pressure (SBP) of the patient by means of the physiological data recording device (230) configured to measure and record at least one systolic blood pressure (SBP), wherein the patient's systolic blood pressure (SBP) is greater than or equal to a first systolic blood pressure threshold S. SBP1 Second systolic blood pressure threshold S SBP2 When at least one of them is present, the method performs the sub-step (151) of determining the single injection dose.

6. The method (100) according to claim 5, wherein the first systolic blood pressure threshold S SBP1 Corresponding to a predetermined average value of systolic blood pressure, and the second systolic blood pressure threshold S SBP2 This corresponds to the patient's systolic blood pressure measured and recorded prior to performing the method.

7. The method (100) of claim 6, wherein the previously measured and recorded systolic blood pressure of the patient corresponds to the systolic blood pressure of the patient previously measured and recorded during the previous performance of the method.

8. The method (100) according to any one of claims 5 to 7, further comprising when the patient's systolic blood pressure (SBP) is strictly below the first threshold S SBP1 and the second systolic blood pressure threshold S SBP2 At the same time, upstream of the third determining step (150), a proportional adjustment step (145) of the amount of drug compound is performed, the adjustment step (145) including determining the amount of drug compound to be administered, which corresponds to the amount of drug compound previously administered, and subtracting the amount of drug compound that is proportional to the change in the measured and recorded value of the patient's systolic blood pressure (SBP) relative to the systolic blood pressure value of the patient measured and recorded before performing the method.

9. An apparatus (200) for assessing a patient's need for a drug compound, comprising means (210) for measuring the patient's cardiac variability between 0.15 Hz and 4 Hz, a data processing and recording unit (220), and means (230) for recording physiological data associated with the patient, the processing and recording unit comprising a processor (221) and a computer memory (222), the computer memory storing instructions configuring the processor to: ● Receive data on the patient's cardiac variability between 0.15 Hz and 4 Hz; ●Based on the received cardiac variability data, determine the ANI index related to the patient's pain level; ●Based on the ANI index, determine the MC index, which represents the average value of the ANI index in the so-called short term, and the ML index, which represents the average value of the ANI index in the so-called long term, as well as the PC and PL slopes of the MC and ML indices, respectively, where the MC and ML indices correspond to the patient's pain level in the short term and long term, respectively, and the PC and PL indices correspond to their changes in the short term and long term. ● Receive physiological data related to the patient; ● Based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient, determine the need for the drug compound to be administered to the patient. This step includes a sub-step for determining the amount of the compound to be administered to the patient immediately, referred to as a single bolus dose, including: ○ Based on the membership function F of the MC index MC Determine the first fuzzy logic variable C between 0 and 1. MC , ○ Based on the membership function F of the PC index PC Determine the second fuzzy logic variable C between 0 and 1. PC , ○ When the first fuzzy logic variable C MC With the second fuzzy logic variable C PC If the sum is strictly greater than 1, the single injection dose is determined to be equal to the first predetermined amount; otherwise, the single injection dose is determined to be equal to zero. ●After determining the single injection dose, when the single injection dose is equal to zero, a second amount of the compound to be administered is determined based on the MC and ML indices, their PC and PL slopes, and physiological data related to the patient. This second amount is less than the first predetermined amount.

10. An apparatus (300) for delivering a pharmaceutical compound, comprising an evaluation device (200) according to claim 9, the evaluation device being associated with a control device (240) and an infusion system (250), the infusion system (250) preferably being electrically powered.

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