Improved methods and devices for assessing a patient's drug compound needs and related delivery devices

Abstract

The present invention relates to a method (100) for assessing a patient's need for a drug compound. The method includes a step (150) of determining the patient's need for a drug compound based on the MC and ML indices derived from the ANI index, their PC and PL slopes, and physiological data about the patient. Step (150) includes determining a fuzzy logic variable C MC and C PC and a substep (151) of determining a bolus including fuzzy logic for determining: if the sum of the first and second fuzzy logic variables is strictly greater than one, then the bolus is equal to a first predetermined amount of said compound; otherwise, the bolus is equal to zero. The present invention also relates to a device for assessing a patient's need for a drug compound, as well as a device (300) for delivering a drug compound comprising such an assessment device (200).

Description

[Technical Field]

[0001] The present invention relates to the field of pain management in patients.

[0002] More particularly, the present invention relates to an improved method for assessing a patient's need for a pharmaceutical compound. The present invention also relates to an improved device for assessing a patient's need for a pharmaceutical compound, and in particular to a device for delivering a pharmaceutical compound, comprising such an assessment device. The pharmaceutical compound is in particular an analgesic and / or hypnotic compound.

[0003] In particular, the invention finds application in pain management for patients undergoing surgery for patients under general or local anesthesia. Alternatively, the invention may find wider application in pain management for conscious or unconscious patients in hospitals, particularly in intensive care or palliative care units, nursing homes, or at home. [Background technology]

[0004] When managing a patient's pain, accurate and real-time assessment of pain levels is necessary so that medical responses can be tailored to the patient's needs.

[0005] For example, the medical response may involve injecting a patient with an analgesic, pain-relieving or pain-relieving compound.

[0006] However, the amount of compound injected into a patient must be individualized to the patient, depending on the patient's condition and physiological characteristics.

[0007] To assess a patient's pain level, it is known to determine the ANI (acronym for "Analgesia Nociception Index"), which is determined according to the patient's heart rate variability. Such determination of the ANI index is known in the art, in particular by the devices and methods described in patent documents FR2821460, FR2840187, FR2864388 and EP1804655 filed by the applicant.

[0008] In order to assess the need for analgesic and / or hypnotic compounds in real time, taking into account changes in a patient's pain level over time and the type of pain the patient is experiencing, Applicant has developed an apparatus and method for assessing analgesic and / or hypnotic compounds that takes into account the average values ​​of the short-term and long-term ANI index, as well as the slope of the ANI index over these periods.

[0009] In particular, these techniques are the subject of patents FR3006879 and FR3006880 by the applicant.

[0010] The above techniques allow for the determination of the amount of analgesic and / or hypnotic compound to be administered to a patient at a given time. Such an amount of compound, which is large compared to the amount of compound normally administered and is intended to be administered over a short period of time, is medically referred to as a "bolus."

[0011] However, there is a need for more stable and reproducible techniques for assessing the required dosage of drug compounds, particularly with respect to determining the bolus to be administered to a patient.

[0012] There is also a need to determine the amount of compound required by a patient in a more granular manner, i.e., more precisely, and in an amount that more closely matches the patient's instantaneous compound need, since some known techniques may underestimate or overestimate the need for the compound, thereby increasing the patient's risk of hypotension or hypertension. Summary of the Invention

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

[0014] To this end, the present invention relates to a method for assessing a patient's need for a pharmaceutical compound, intended to be implemented by an assessment device comprising means for measuring the patient's cardiac variability in the range of 0.15 Hz to 4 Hz, a data processing and recording unit and means for recording physiological data relating to the patient, the method comprising: measuring the patient's heart rate variability in the range of 0.15 Hz to 4 Hz; first determining an ANI index related to the patient's pain level from the measured heart rate variability data by a data processing and recording unit; a second determination step of determining, from the ANI index by the data processing and recording unit, an MC index representing an average value of the ANI index over a so-called short period, an ML index representing an average value of the ANI index over a so-called long period, and a PC slope and a PL slope of each of the MC index and the ML index, wherein the MC index and the ML index correspond to the patient's pain level, and the PC index and the PL index correspond to its changes over the short and long periods, respectively; recording physiological data about the patient by a means for recording physiological data about the patient; a third determination step of determining, by the data processing and recording unit, the patient's need for a pharmaceutical compound based on the MC index and ML index, their PC gradients and PL gradients, and physiological data related to the patient. The third determining step includes a substep of determining the amount of the compound to be administered to the patient, called a bolus, which substep comprises: · MC index membership function F MC to the first fuzzy logic variable C between 0 and 1. MC and determining · Membership function F of exponential PC PC to a second fuzzy logic variable C between 0 and 1PC and determining First fuzzy logic variable C MC and the second fuzzy logic variable C PC is strictly greater than 1, determining that the bolus is equal to a first predetermined amount of said compound, and otherwise determining that the bolus is equal to 0. The third determining step further includes the substep of determining a second amount of the compound to be administered that is less than the first predetermined amount, determined based on the MC and ML indices, their PC and PL slopes, and physiological data about the patient, which substep is performed by the method following the substep of determining the bolus if the bolus is equal to 0.

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

[0016] Bolus determination by fuzzy logic substeps can significantly improve the stability and reproducibility of assessment of compound need compared to techniques known in the art.

[0017] The substep of determining the amount of compound to be administered to the patient at a particular time, i.e. the substep of determining the bolus, makes it possible to assess whether a bolus can be administered to the patient.

[0018] When a bolus can be administered to a patient taking into account the MC and PC thresholds, the bolus value corresponds to a predetermined amount of the compound, which may be fixed or may be defined prior to carrying out the method, for example, based on data about the patient.

[0019] If a bolus cannot be administered to the patient considering the MC and PC thresholds, the bolus value will be 0.

[0020] The calculation of the mean value of the ANI index can be performed over a sliding window, and especially in such cases the reproducibility of the method according to the invention is even more important compared to known techniques.

[0021] These aspects make it possible to provide a process that is efficient, safe and meets the requirements for bringing to market a process performed by a medical device.

[0022] It is specified herein that the method can operate in a loop, either real-time or periodically, i.e., the steps of the method are repeated continuously to determine the patient's need for pharmaceutical compounds in real-time or periodically.

[0023] In clinical trials of the method according to the invention, a reduction in the amount of analgesic and / or hypnotic compound administered to the patient, as well as an improvement in hemodynamic stability, i.e., a reduction in the patient's tendency to hypotension and hypertension, was observed compared to known methods.

[0024] According to a second aspect, the present invention also relates to an apparatus for assessing a patient's need for a pharmaceutical compound, the apparatus comprising means for measuring the patient's heart rate variability in the range of 0.15 Hz to 4 Hz, a data processing and recording unit, and means for recording physiological data relating to the patient. The processing and recording unit comprises a processor and a computer memory. The computer memory comprises: receiving data relating to the patient's heart rate variability in a range of 0.15 Hz to 4 Hz; determining an ANI index associated with the patient's pain level from the received heart rate variability data; determining, from the ANI index, an MC index representing the average value of the ANI index over a so-called short period, an ML index representing the average value of the ANI index over a so-called long period, and a PC slope and a PL slope of the MC index and the ML index, respectively, wherein the MC index and the ML index correspond to the patient's pain level, and the PC index and the PL index correspond to its progression over the short and long periods, respectively; receiving physiological data about the patient; determining a need for a drug compound to be administered to the patient based on the MC index and ML index, their PC gradients and PL gradients, and physiological data about the patient, which includes the substep of determining a first amount of the compound to be administered to the patient as a single dose, called a bolus, the substep comprising: · MC index membership function F MC from the first fuzzy logic variable C between 0 and 1 MC and determining · Membership function F of exponential PC PC to a second fuzzy logic variable C between 0 and 1 PC and determining First fuzzy logic variable C MC and the second fuzzy logic variable C PC is strictly greater than 1, determining that the bolus is equal to the first predetermined amount, and otherwise determining that the bolus is equal to 0; if bolus is equal to 0, following bolus determination, determining a second amount of the compound to be administered that is less than the first predetermined amount based on the MC index and ML index, their PC slopes and PL slopes, and physiological data related to the patient.

[0025] Such an apparatus has the technical advantages and effects of the method according to the invention described above.

[0026] The device for assessing a patient's need for a drug compound may take the form of a computer having input terminals connected to a heart rate variability sensor and at least one other sensor for physiological data of the patient.

[0027] The evaluation device may comprise a device for displaying data, in particular the amount of drug compound administered.

[0028] It is specified that the above method and device may be a method and device for assessing a patient's need for a drug compound or drug and / or paramedic care. Preferably, the drug compound is an analgesic compound and / or a hypnotic compound.

[0029] Other particularly advantageous and convenient features of the method according to the invention and of the evaluation device according to the invention are explained below.

[0030] According to one embodiment, in the evaluation method and device according to the present invention, the membership function F of the MC index is MC teeth, ·MC index is low threshold S MCLow Equals 1 if: ·MC index is high threshold S MCHigh If greater than or equal to 0, ·MC index is low threshold S MCLow and high threshold S MCHigh , and has a monotonically decreasing transition between 1 and 0, where the membership function of the PC exponent F PC teeth, ·PC index is low threshold S PCLow Equals 1 if: ·PC index is high threshold S PCHigh If greater than or equal to 0, ·PC index is low threshold S PCLow and high threshold S PCHigh If the value is between 1 and 0, then the transition between 1 and 0 is monotonically decreasing.

[0031] This type of selection of membership functions makes it possible to observe good performance of the method, which is particularly stable and reproducible.

[0032] The type of monotonic decreasing transition can be adjusted depending on the type of compound envisioned for administration and / or the clinical situation of the patient. Similarly, the high and low thresholds can be adjusted according to these same criteria.

[0033] According to one embodiment, in the method and evaluation device according to the invention, the membership function F of the MC index is MCis the expression: JPEG2025541932000002.jpg25170PC index F PC The membership function is expressed as: JPEG2025541932000003.jpg25170

[0034] In general, a decreasing linear transition allows for good performance of the method.

[0035] Such a transition is particularly suitable during surgery when the patient is under general anesthesia.

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

[0037] The threshold ranges and preferred thresholds are particularly suitable during surgery when the patient is under general anesthesia.

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

[0039] According to one embodiment, in the method according to the invention, the step of recording physiological data about the patient is a step of recording at least one systolic blood pressure (SBP) of the patient by a physiological data recording means configured to measure and record at least one SBP. The sub-step of determining the bolus comprises determining whether the systolic blood pressure (SBP) of the patient is greater than or equal to a first systolic blood pressure threshold S SBP1 and the second systolic blood pressure threshold S SBP2 When at least one of the above is satisfied, the method is carried out.

[0040] In the evaluation device according to the present invention, the step of receiving physiological data about the patient includes, for example, receiving at least one systolic blood pressure (SBP) data of the patient obtained by a physiological data recording means configured to measure and record at least one systolic blood pressure (SBP), and determining whether the systolic blood pressure (SBP) of the patient is greater than or equal to a first systolic blood pressure threshold S SBP1 and the second systolic blood pressure threshold S SBP2 If at least one of the above is true, a bolus determination is performed.

[0041] According to one embodiment, the evaluation method and device according to the invention comprises determining a first systolic blood pressure threshold S SBP1 corresponds to a predetermined mean value of the systolic blood pressure, and the second systolic blood pressure threshold S SBP2 corresponds to the patient's previously measured and recorded systolic blood pressure.

[0042] In particular, in the method according to the invention, a second systolic blood pressure threshold S SBP2 corresponds to the patient's systolic blood pressure measured and recorded before carrying out the method.

[0043] Setting such a threshold allows the proportional control to be adapted according to the generally accepted average systolic blood pressure and the systolic blood pressure of the patient before the process is carried out.

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

[0045] In the evaluation 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 a previous reception of the patient's physiological data by the evaluation device.

[0046] If the method according to the invention is carried out in a loop or if the evaluation device evaluates the needs in a loop, the proportional control can take into account the systolic blood pressure measured and recorded during previous iterations of the method or evaluation device, thereby making it possible to follow changes in the systolic blood pressure.

[0047] According to one embodiment, the method comprises determining whether the patient's systolic blood pressure (SBP) is greater than or equal to the first threshold S SBP1 and the second systolic blood pressure threshold S SBP2 and a proportional control step of the amount of drug compound to be administered, performed by the method upstream of the third determining step if the measured and recorded value of the drug compound is strictly lower than both of the measured and recorded value of the drug compound. The adjusting step comprises determining an amount of drug compound to be administered depending on the amount of drug compound previously administered, from which an amount of drug compound is subtracted that is directly proportional to the change in the patient's measured and recorded value of systolic blood pressure (SBP) relative to the value of the patient's systolic blood pressure measured and recorded before performing the method.

[0048] In the evaluation device according to the invention, the instruction is to determine whether the patient's systolic blood pressure (SBP) is greater than or equal to the first threshold value S SBP1 and the second systolic blood pressure threshold S SBP2 and proportional control of the amount of pharmaceutical compound to be administered, performed upstream of the determination of the compound requirement, when the required amount is strictly lower than both of the above. The adjustment includes determining the amount of pharmaceutical compound to be administered according to the amount of pharmaceutical compound previously administered, from which is subtracted an amount of pharmaceutical compound that is directly proportional to the change in the patient's measured and recorded systolic blood pressure (SBP) value compared to the patient's systolic blood pressure value received during a previous evaluation by the evaluation device.

[0049] Such control, proportional to the reduction in systolic blood pressure, allows for a reduction in the amount of compound administered, which reduces the patient's risk of hypotension, and also allows for a reduction in the total amount of compound administered, which can be more tailored to the patient's condition.

[0050] Thus, if the patient's systolic blood pressure drops too much, the amount of drug compound decreases.

[0051] Here, the amount of drug compound may be an amount of drug compound determined prior to any use of the method or evaluation by the evaluation device, or may be an amount of drug compound determined during the third determination step of the method, during a previous run of the method, or prior to determining the need for the compound by the evaluation device.

[0052] It will be understood that if the method is performed in a loop or the evaluation device evaluates in a loop, the determination of the compound requirement, and therefore the bolus determination, is performed only if a sufficient number of adjustments have been performed to confirm the condition that the systolic blood pressure does not fall below one of the two aforementioned systolic blood pressure thresholds.

[0053] This makes the method or use of the evaluation device safe and ensures that there is no risk of administering excessive amounts of compound, especially boluses, to a patient in a hypotensive state.

[0054] According to a third aspect, the present invention also relates to a device for delivering a drug compound comprising a device for assessing a patient's need for a drug compound according to the second aspect of the invention, associated with control means and a preferably motorized injection system.

[0055] The delivery device may comprise control means arranged to control the flow rate of the drug compound in dependence on the determined amount of drug compound, in particular through action on the injection system. [Brief explanation of the drawings]

[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 of the present invention, which description refers to the accompanying drawings. [Figure 1] 1 shows a schematic representation of a delivery device equipped with an evaluation device according to the present invention; [Figure 2] 1 shows a schematic representation of an evaluation device according to the invention; [Figure 3] 1 is a flowchart of an evaluation method according to the present invention. [Figure 4] 1 is a flow chart of an evaluation method according to the present invention, including the optional step of proportional control. [Figure 5] The graph of the F_MC membership function of the MC index and the graph of the F_PC membership function of the PC index are shown. [Figure 6] 1 is a flowchart of an evaluation method according to one embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0057] The present description is given as a non-limiting example, and each feature of one embodiment can be advantageously combined with any other feature of any other embodiment.

[0058] It should be noted that the drawings are not plotted to scale.

[0059] FIG. 1 shows a schematic diagram of a compound-delivery device 300 .

[0060] The delivery device 300 comprises a device 200 for assessing the need for a drug compound, a control means 240 and an injection system 250 .

[0061] Preferably, the infusion system 250 is electrically powered and is operated by a control means 240 connected by a data link to the evaluation device 200. The infusion system is suitable for administering a medicinal compound, for example via a catheter of the infusion system 250, into the blood circuit of a patient in need of administration of the medicinal compound.

[0062] The drug compound is in particular an analgesic compound and / or a hypnotic compound.

[0063] In particular, the analgesic and / or hypnotic compound is an analgesic compound, such as an opioid compound, in particular morphine. For example, the compound is remifentanil. In other examples, the compound is a non-morphine compound, such as ketamine, or a compound of the alpha-2 agonist class, such as clonidine.

[0064] 2 shows only the evaluation device 200 in a schematic manner, i.e., not specifically associated with the control means 240 and the infusion system 250. The evaluation device 200 can in fact operate alone without the need for means to administer compounds, and can determine the need for analgesic and / or hypnotic and / or curarizing compounds and transmit this information to another device, or to a medical professional, etc.

[0065] The evaluation device 200 may in particular comprise means 210 for measuring the heart rate variability of the patient in the range of 0.15 Hz to 4 Hz, a data processing and recording unit 220 and means 230 for recording physiological data relating to the patient.

[0066] For example, the data processing and recording unit 220 comprises a microprocessor, or processor 221, and a computer memory 222 adapted to store instructions that configure the operation of the processor 221. For example, the computer memory 222 is a rewritable non-volatile storage computer memory, for example of the "EPROM" type.

[0067] The means 230 for recording physiological data about the patient may be physiological data sensors, in particular commercially available sensors, which may be configured to record patient physiological (or vital) data and transmit it via a data link to the data processing and recording unit 220. For example, the recording means 230 may comprise at least one blood pressure sensor, in particular a systolic blood pressure sensor, also called a blood pressure monitor.

[0068] The means 210 for measuring the patient's heart rate variability in the range of 0.15 Hz to 4 Hz may comprise various means known to those skilled in the art, such as an electrocardiograph (ECG) and / or an oximeter, through which the patient's heart rate variability in the range of 0.15 Hz to 4 Hz can be measured.

[0069] The evaluation device 200 may also include other peripheral devices such as means for displaying information, for example a computer screen.

[0070] The evaluation device 200 allows for the evaluation of a patient's need for analgesic and / or hypnotic compounds (hereinafter referred to as "compounds") based on the patient's physiological data, particularly when the patient is under anesthesia or sedation.

[0071] The need for the compound may in particular be a determination of the amount of compound required by the patient, and the evaluation device 200 may communicate such amount of compound to a medical professional, for example via a computer screen, or communicate the amount of compound to the control means 240 for administration by the infusion system 250.

[0072] Thus, the evaluation device 200 can make recommendations regarding the patient's required dosage of the compound, after which the appropriate amount of compound can be administered by medical staff or automatically by the infusion system, as determined by medical staff.

[0073] The need for the compound is assessed by the assessment device 200 based in particular on the ANI index, which is an index related to the pain level experienced by the patient. Thus, the need for the compound can be determined according to the perceived pain level, thereby enabling an assessment of the optimal amount of compound required for the patient to relieve pain without administering too little or too much of the compound.

[0074] To this end, the assessment device 200 is configured to perform the method 100 for assessing a patient's need for an analgesic and / or hypnotic compound.

[0075] More specifically, the computer memory 222 of the evaluation device 200 stores instructions that configure the processor 221 to perform the steps of the method 100 .

[0076] The method 100 intended to be implemented by the evaluation device 200 will now be described with particular reference to FIGS.

[0077] The method 100 includes a step 110 of measuring the patient's heart rate variability in the range of 0.15 Hz to 4 Hz.

[0078] Next, the method 100 includes a first determination step 120 in which the data processing and recording unit 220 determines, from the heart rate variability data measured during step 110, an ANI index related to the patient's pain level.

[0079] For example, the ANI index can be calculated according to the method described in application WO2006 / 032739. The first determining step 120 can therefore comprise the steps of such a method for determining the ANI index.

[0080] The method 100 further comprises a second determination step 130 of determining, by the data processing and recording unit 220, a sub-index (or index) MC and a sub-index (or index) ML.

[0081] The MC index and the ML index are determined from the ANI index, with the MC index representing the average value of the ANI index over a so-called short period and the ML index representing the average value of the ANI index over a so-called long period.

[0082] Therefore, the MC index and the ML index correspond to the patient's pain level over a so-called short-term period and a longer period than the short-term period, so-called long-term, respectively.

[0083] Additionally, in a second determining step 130, the PC slope and PL slope of the MC index and ML index, respectively, are determined, which correspond to changes in the patient's pain level over the short and long term, respectively.

[0084] In other words, the MC index and ML index are calculated from various values ​​of ANI over a given period of time, which limits the influence of momentary fluctuations in ANI measurements due to the calculation method and allows for the derivation of trends in the patient's pain.

[0085] More specifically, the calculation of the MC and ML indices is preferably performed from the average of the values ​​of the ANI index over two different periods: short-term and long-term.

[0086] Preferably, the short term corresponds to a sliding window of 45 to 90 seconds, preferably around 60 seconds, and the long term corresponds to a sliding window of 90 to 240 seconds, preferably around 180 seconds.

[0087] Preferably, the period considered for calculating ML is about 1.5 to 3 times the period used for calculating MC.

[0088] The PC slope is calculated in degrees from two separate MC values ​​for a given period according to the following formula: JPEG2025541932000004.jpg17170

[0089] Preferably, the time interval between t1 and t2 is on the order of 15 to 45 seconds, preferably 30 seconds.

[0090] The PL slope, like the PC, is calculated in degrees according to the following formula: JPEG2025541932000005.jpg17170

[0091] The time interval between t1 and t2 is about 15 to 45 seconds, preferably 30 seconds.

[0092] Further, the method 100 includes a step 140 of recording physiological data about the patient by a means 230 for recording physiological data about the patient.

[0093] As mentioned above, the recording means 230 allows for example the measurement of 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 to constitute a safeguard, since the evaluation device will not perform the evaluation if certain thresholds corresponding to these parameters are exceeded.

[0095] Examples of safety steps are described later in this specification.

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

[0097] It is also possible to use only one physiological parameter, although this mode has the drawback of reduced safety.

[0098] The recording means 230 also allows for recording other types of data relating to the patient, such as the patient's weight, height, age, sex, etc. For this purpose, the recording means 230 is preferably equipped with a keyboard or touch surface, which are not shown in the accompanying figures.

[0099] The method 100 also comprises a third determining step 150 in which the data processing and recording unit 220 determines the patient's need for a pharmaceutical compound, here for example an analgesic compound and / or a 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 physiological data about the patient.

[0101] More specifically, in the third determination step 150, the patient first determines a first amount q of the compound to be administered to the patient in a single dose. pIt is determined whether a patient requires the administration of a compound bolus. Such a relatively large amount of compound intended to be administered over a short period of time is called a "bolus." If the pain is acute, i.e., the ANI index is close to 0, the patient requires a compound bolus.

[0102] To this end, the third determining step 150 comprises a substep 151 of determining a first amount of compound to be administered to the patient in a single dose, ie a determining bolus substep 151 .

[0103] The substep 151 for determining the bolus is based on the membership function F of the MC index. MC from the first fuzzy logic variable C between 0 and 1 MC This includes determining:

[0104] Substep 151 of determining the bolus also determines the membership function F of the exponential PC. PC to a second fuzzy logic variable C between 0 and 1 PC and determining:

[0105] Next, the substep 151 of determining the bolus is performed by calculating the first fuzzy logic variable C MC and the second fuzzy logic variable C PC is strictly greater than 1, the bolus contains a first predetermined amount q of the compound. p otherwise, determining the bolus to be equal to 0.

[0106] In other words, the patient is MC and the second fuzzy logic variable C PC If the sum of is strictly greater than 1, a bolus is required and the first fuzzy logic variable C MC and the second fuzzy logic variable C PC If the sum is less than 1, no bolus is required.

[0107] Thus, the sub-step 151 of determining the bolus is a step that uses fuzzy logic to determine whether or not a bolus needs to be administered.

[0108] MC index membership function F MC and the membership function F of the PC index PC is a function restricted here between 0 and 1. Therefore, the image of the index value MC or PC by the respective membership function is a value C between 0 and 1. PC or C MC , i.e., a "fuzzy" Boolean value.

[0109] Figure 5 shows the membership function F of the MC index. MC and the membership function F of the PC index PC The graph shows:

[0110] For example, the membership function F of the MC index MC teeth,

[0111] -MC index is low threshold S MCLow If it is less than or equal to 1,

[0112] -MC index is high threshold S MCHigh If it is greater than or equal to 0,

[0113] -MC index is low threshold S MCLow and high threshold S MCHigh If the value is between 1 and 0, then the transition between 1 and 0 is monotonically decreasing.

[0114] Similarly, for example, the membership function F of the PC index PC teeth,

[0115] -PC index is low threshold S PCLow If it is less than or equal to 1,

[0116] -PC index is high threshold S PCHigh If it is greater than or equal to 0,

[0117] -PC index is low threshold SPCLow and high threshold S PCHigh If the value is between 1 and 0, then the transition between 1 and 0 is monotonically decreasing.

[0118] Examples of monotonically decreasing transitions are linear, hyperbolic, especially sigmoid, exponential and even Gaussian transitions.

[0119] A linear decrease transition is particularly preferred.

[0120] For example, the membership function F of the MC index MC is defined by the following formula: JPEG2025541932000006.jpg29170

[0121] For example, the membership function F of the PC index PC is defined according to the following formula: JPEG2025541932000007.jpg28170

[0122] High and low transition thresholds S MCLow , S MCHigh , S PCLow and S PCHigh can be freely adapted according to the conditions of use of the method 100, in particular the patient profile (in particular 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. Likewise, the type of transition can also be freely adapted according to these same criteria.

[0123] For example, the threshold S MCLow , S MCHigh , S PCLow and S PCHigh can be set as follows:

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

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

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

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

[0128] This range of values, especially the preferred values ​​associated with the linear transition, is particularly suitable for surgery under general anesthesia when remifentanil is administered to patients as a compound. Indeed, reproducible and stable operation of the method has been observed in this situation.

[0129] The substep 151 of determining the bolus based on fuzzy logic makes it possible to obtain a particularly reliable and reproducible bolus determination even when the MC index is highly variable, especially when determined over a sliding window, since the fuzzy logic makes it possible to dispense with a bolus determination based on a fixed threshold that is very sensitive to the variations in the MC index.

[0130] Specifically, referring to FIG. 6, which shows a more detailed example implementation of method 100 in the form of a flow chart, if a bolus is determined and the compound used is remifentanil at a concentration of 25 μg / ml, the flow rate variable will increase depending on the patient's weight, for example, by 0.12 μg / kg / min over 10 seconds.

[0131] In this example, the "bolus" variable is set to 10 and is decremented the next time method 100 is executed, which can be executed in a continuous or periodic loop. Unless the variable "bolus" is 0, method 100 will not execute a new step of determining the amount of compound.

[0132] At the end of the bolus determination substep 151, the first fuzzy logic variable C MC and the second fuzzy logic variable C PC is less than 1, i.e., the bolus is 0, the method 100 pA substep 152 is performed in which a second amount of compound is administered that is less than the first amount.

[0133] The second amount of the compound is determined based on the MC and ML indices, their PC and PL slopes, and physiological data about the patient.

[0134] For example, the substep 152 of determining the second amount of the compound includes a series of successive comparisons of the MC index, the ML index, the PC index and the PL index with predetermined thresholds.

[0135] In particular, as seen in FIG. 6, in substep 152, to determine whether the average ANI index over a short period of time is low, moderate, or high, i.e., whether the pain is severe, moderate, or mild, the MC index is first calculated based on the low S b and high S h It is continuously compared with the threshold.

[0136] Based on this first determination, the trend in average pain levels over time, and changes in primary pain levels over short and long periods, method 100 determines a second amount of the compound. The second amount of the compound may be greater or less than a previously determined second amount of the compound, particularly a second amount determined during a previous performance of method 100. Alternatively, the second amount of the compound may remain unchanged compared to a previously determined second amount of the compound.

[0137] Once sub-step 152 has been performed and the second amount of compound has been determined, method 100 can be performed again from the beginning. For example, it is possible to delay a new run of the method by setting the value of the variable "Pref", here set to 10 in the example of Figure 6. This variable is decremented for each run of the method before the third determination step 150 is performed.

[0138] A specific implementation of sub-step 152 and a specific implementation of the decrementing of the variables "Bolus" and "Pref" of the algorithm shown in Figure 6 are described in the applicant's patent documents FR3006879 and FR3006880, which those skilled in the art can refer to for the implementation of method 100.

[0139] As previously described herein, method 100 may include a safety step intended to prevent a determination of the amount of compound to be administered if a certain threshold value of the patient's physiological data is exceeded.

[0140] For example, with reference to FIGS. 4 and 6, the method 100 includes the optional step of comparing the systolic blood pressure (SBP) to two systolic blood pressure thresholds.

[0141] To this end, the step 140 of recording physiological data about the patient is a step of recording at least one systolic blood pressure (SPB) of the patient by a means 230 for recording physiological data configured to measure and record at least one systolic blood pressure (SPB).

[0142] The optional step of comparing the systolic blood pressure (SBP) to two systolic blood pressure thresholds is to compare the SBP with the first systolic blood pressure threshold S SBP1 and the second systolic blood pressure threshold S SBP2 This includes comparing with.

[0143] - First systolic blood pressure threshold S SBP1 may be a predetermined mean value of systolic blood pressure, for example a systolic blood pressure of 120 mmHg, which is considered the minimum systolic blood pressure threshold for a healthy person.

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

[0145] If the patient's systolic blood pressure (SBP) exceeds the first systolic blood pressure threshold S SBP1 and the second systolic blood pressure threshold S SBP2 If so, the method 100 performs a substep 151 of determining a bolus.

[0146] This is because if the 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 is considered to be low, and therefore it is possible to determine the amount of compound to be administered without harming the patient's health.

[0147] If the patient's systolic blood pressure (SBP) exceeds the first threshold S SBP1 and the second systolic blood pressure threshold S SBP2 If α is strictly lower than both α and β, then a step 145 of proportional control of the amount of analgesic and / or hypnotic compound administered is performed by the method upstream of a third decision step 150. The third decision step 150, and therefore the determination of the bolus in particular, is not performed by the method 100 during the same iteration of the method 100.

[0148] The proportional control step 145 involves determining an amount of analgesic and / or hypnotic compound to be administered, which corresponds to the amount of analgesic and / or hypnotic compound previously administered, minus an amount of analgesic and / or hypnotic compound that is directly 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 execution of method 100.

[0149] Specifically, with reference to the algorithm shown in FIG. 6, the compound flow rate setpoint variable "Flow" may be updated in direct proportion to the change in the patient's measured and recorded systolic blood pressure (SBP) value relative to the patient's measured and recorded systolic blood pressure value prior to execution of method 100.

[0150] For example, a new flow setpoint can be defined as: JPEG2025541932000008.jpg22170SSBPmin is a predetermined cutoff value for systolic blood pressure, for example, equivalent to 80 mmHg.

[0151] In other words, the "Flow Rate" variable is overridden and updated to decrease the compound flow set point in proportion to changes in the patient's systolic blood pressure (SBP).

[0152] The proportional control step 145 determines whether the patient's systolic blood pressure is greater than or equal to two thresholds S SBP1 and S SBP2 or 0.5, i.e., the patient can be considered at low risk for hypotension. This is a safety measure to avoid assessing an excessively high compound requirement for a patient who is hypotensive or has low blood pressure.

[0153] For example, the interval between two repetitions, i.e., between two measurements of the patient's systolic blood pressure, is 2 to 5 minutes.

[0154] Additionally, the proportional control step 145 allows for better adaptation of compound delivery according to the patient's needs and may also allow for a reduction in the total amount of compound administered to the patient, which is both clinically and economically advantageous.

[0155] While the optional step of comparing the systolic blood pressure (SBP) to two systolic blood pressure thresholds and, if appropriate, implementing a proportional control step 145 is particularly advantageous as described above, it is also contemplated that more conventional safety steps may be provided, as described in applicant's patent documents FR3006879 and FR3006880, which allow the flow of compound to be stopped in the event of patient hypotension or bradycardia.

[0156] According to one embodiment, the method 100, and / or the evaluation device 200, and / or the delivery device 300 may be intended to assess a patient's need for paramedicinal care as an alternative to, or as a complement to, assessing the need for a drug compound.

[0157] In other words, in addition to or instead of determining the amount of compound required by the patient, it is possible to assess the patient's need for paramedic care in a similar manner, i.e., based on fuzzy logic based on the ANI index and its sub-indexes. For example, determining the need for paramedic care includes determining that the patient needs paramedic care, and may include, for example, determining the duration and / or intensity of the paramedic care.

[0158] "Medical paramedical care" means all care that can be provided to a patient, excluding medical and surgical treatment, including, but not limited to, pediatric care, physical therapy, neonatology, neurophysiology, or more broadly, care based on modifying the patient's environment to improve their health.

[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 drug compound, intended to be implemented by an assessment device (200) comprising means (210) for measuring the patient's heart rate variability in the range of 0.15 Hz to 4 Hz, a data processing and recording unit (220), and means (230) for recording physiological data relating to the patient, said method comprising: measuring (110) the patient's heart rate variability in the range of 0.15 Hz to 4 Hz; a first determination step (120) of determining, from the measured heart rate variability data by said data processing and recording unit (220), an ANI index related to the patient's pain level; a second determination step (130) in which the data processing and recording unit (220) determines from the ANI index an MC index representing the average value of the ANI index over a so-called short period, an ML index representing the average value of the ANI index over a so-called long period, and a PC slope and a PL slope of the MC index and the ML index, respectively, wherein the MC index and the ML index correspond to the patient's pain level and the PC index and the PL index correspond to its changes over the short and long periods, respectively; - recording (140) physiological data about the patient by means (230) of recording physiological data about the patient; a third determination step (150) of determining, by the data processing and recording unit (220), the patient's need for a pharmaceutical compound based on the MC index and ML index, their PC slopes and PL slopes, and physiological data relating to the patient, The third determining step includes a substep (151) of determining a first amount of the compound to be administered to the patient in a single dose, called a bolus, comprising: o The membership function F of the MC index ＭＣ from a first fuzzy logic variable C between 0 and 1 ＭＣ and determining o The membership function F of the PC index ＰＣ to a second fuzzy logic variable C between 0 and 1 ＰＣ and determining o The first fuzzy logic variable C ＭＣ and the second fuzzy logic variable C ＰＣ is strictly greater than 1, determining that the bolus is equal to a first predetermined amount of the compound, otherwise determining that the bolus is equal to 0; The method (100) further comprises a substep (152) of determining a second amount of the compound to be administered that is less than the first predetermined amount, the second amount being determined based on the MC and ML indices, their PC and PL slopes, and physiological data about the patient, and this substep (152) is performed by the method following the substep (151) of determining a bolus if the bolus is 0.

2. The membership function F of the MC index ＭＣ teeth, The MC index is a low threshold S ＭＣＬｏｗ Equals 1 if: The MC index is a high threshold S ＭＣＨｉｇｈ If greater than or equal to 0, The MC index is the low threshold S ＭＣＬｏｗ and high threshold S ＭＣＨｉｇｈ and has a monotonically decreasing transition between 1 and 0 if The membership function F of the PC index ＰＣ teeth, The PC index is a low threshold S ＰＣＬｏｗ Equals 1 if: The PC index is a high threshold S ＰＣＨｉｇｈ If greater than or equal to 0, The PC index is the low threshold S ＰＣＬｏｗ and high threshold S ＰＣＨｉｇｈ 2. The method (100) of claim 1, wherein the transition has a monotonically decreasing transition between 1 and 0 if the transition is between 1 and 0.

3. The membership function F of the MC index ＭＣ is defined according to the following formula: The PC index membership function F ＰＣ 3. The method (100) of claim 2, wherein is defined according to the following formula:

4. The threshold value S ＭＣＬｏｗ is between 45 and 55, preferably equal to 50, The threshold value S ＭＣＨｉｇｈ is between 58 and 68, preferably equal to 63, The threshold value S ＰＣＬｏｗ is between −40 and −30, preferably equal to −35, The threshold value S ＰＣＨｉｇｈ Method (100) according to claim 2 or 3, characterized in that is between -30 and -20, preferably equal to -25.

5. The step (140) of recording physiological data about the patient is a step of recording at least one systolic blood pressure (SBP) of the patient by the means (230) for recording physiological data configured to measure and record at least one SBP, and the sub-step (151) of determining a bolus is a step of determining a bolus by determining at least one SBP of the patient when the SBP of the patient is greater than or equal to a first systolic blood pressure threshold S ＳＢＰ１ and the second systolic blood pressure threshold S ＳＢＰ２ 5. The method (100) according to any one of claims 1 to 4, characterized in that said method is carried out when at least one of

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

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

8. The patient's systolic blood pressure (SBP) is ＳＢＰ１ and the second systolic blood pressure threshold S ＳＢＰ２ and (b) a step (145) of proportionally controlling the amount of drug compound to be administered, performed by the method upstream of the third determining step (150) if the measured value of the drug compound is strictly lower than both of (a) and (b), wherein the adjusting step (145) comprises determining an amount of drug compound to be administered depending on an amount of drug compound previously administered, from which is subtracted an amount of drug compound that is directly 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 before the method was performed.

9. 1. An apparatus (200) for assessing a patient's need for a drug compound, comprising: means (210) for measuring the patient's heart rate variability between 0.15 Hz and 4 Hz; a data processing and recording unit (220); and means (230) for recording physiological data relating to the patient, said processing and recording unit comprising a processor (221) and a computer memory (222), said computer memory (222) comprising: receiving data relating to the patient's heart rate variability in the range of 0.15 Hz to 4 Hz; - determining an ANI index related to the patient's pain level from the received heart rate variability data; - determining from the ANI index an MC index representing the average value of the ANI index over a so-called short period, an ML index representing the average value of the ANI index over a so-called long period, and a PC slope and a PL slope of the MC index and the ML index, respectively, wherein the MC index and the ML index correspond to the pain level of the patient, and the PC index and the PL index correspond to its progression over the short and long periods, respectively; receiving physiological data relating to the patient; determining the need for a drug compound to be administered to the patient based on the MC and ML indices, their PC and PL slopes, and physiological data about the patient, which step includes a sub-step of determining the exact amount of the compound to be administered to the patient, called a bolus, which sub-step comprises: o The membership function F of the MC index ＭＣ from a first fuzzy logic variable C between 0 and 1 ＭＣ and determining o The membership function F of the exponent PC ＰＣ to a second fuzzy logic variable C between 0 and 1 ＰＣ and determining o The first fuzzy logic variable C ＭＣ and the second fuzzy logic variable C ＰＣ is strictly greater than 1, determining that the bolus is equal to a first predetermined amount, and otherwise determining that the bolus is equal to 0; - if the bolus is equal to 0, following bolus determination, determining a second amount of the compound to be administered that is less than the first predetermined amount based on the MC index and ML index, their PC slopes and PL slopes, and physiological data about the patient.

10. A device (300) for delivering a drug compound, comprising an evaluation device (200) according to claim 9, associated with control means (240) and a preferably motorized injection system (250).

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