Improved method and device for assessing a patient's drug compound requirements, and associated delivery device

Abstract

The invention relates to a method (100) for assessing a patient's drug compound requirements, comprising a step (150) for determining, based on MC and ML indices derived from an ANI index, and their slopes PC and PL, and physiological data relating to the patient, the patient's drug compound requirement, comprising a substep (151) for determining a bolus, comprising fuzzy logic for determining fuzzy logic variables, the bolus being equal to a first predetermined quantity of said compound when the sum of the first and second fuzzy logic variables is strictly greater than 1, the bolus being equal to zero otherwise. The invention also relates to a device for assessing a patient's drug compound requirements, as well as a drug compound delivery device (300), comprising such an assessment device (200). (See Figure 3 for abbreviations.)

Description

Title of the invention: Improved method and device for assessing a patient's drug compound requirements, and associated delivery device TECHNICAL FIELD OF THE INVENTION

[0001] The field of the invention is that of the field of pain management for a patient.

[0002] More specifically, the invention relates to an improved method for assessing a patient's drug compound requirements. The invention also relates to an improved device for assessing a patient's drug compound requirements, as well as a drug compound delivery device comprising, in particular, such an assessment device. The drug compound is, in particular, an analgesic and / or hypnotic compound.

[0003] The invention finds particular applications in the management of a patient's pain during a surgical procedure performed under general or local anesthesia. According to other possibilities, the invention may find broader applications in the management of pain in conscious or unconscious patients in hospitals, particularly in intensive care or palliative care units, in healthcare facilities, or at home. STATE OF THE ART

[0004] In the context of managing a patient's pain, it is necessary to assess the level of pain precisely and in real time, so as to be able to provide a medical response adapted to the patient's needs.

[0005] For example, the medical response may consist of injecting an analgesic, analgesic or pain-relieving compound into the patient.

[0006] The amount of compound injected into the patient must, however, be proportionate and personalized for the patient according to his condition and physiological characteristics.

[0007] In order to assess a patient's pain level, it is known to determine an index called the ANI (acronym for "Analgesia Nociception Index"), which is determined based on the variability of the patient's heart rate. The determination of such an ANI index is known from the art, in particular by means of the devices and methods known from patent documents FR 2821460, FR 2840187, FR 2864388 and EP 1804655 filed by the Applicant.

[0008] In order to assess the need for analgesic and / or hypnotic compounds in real time and taking into account the evolution over time of the patient's pain level, as well as the type of pain experienced by the patient, the Applicant has developed a device and method for evaluating the needs for analgesic and / or hypnotic compounds which takes into account averages of the ANI index over short and long periods, as well as the slope of the ANI index over these periods.

[0009] These techniques have notably been the subject of patents FR 3006879 and FR 3006880 by the Applicant.

[0010] The aforementioned techniques involve determining a quantity of analgesic and / or hypnotic compound to be administered to the patient at a specific time. Such a quantity of compound, significant compared to the quantity normally administered, and intended to be administered over a short period, is called a "bolus" in medical terminology.

[0011] However, the need arose for a more stable and repeatable technique for assessing drug compound requirements, particularly with regard to determining a bolus to be administered to the patient.

[0012] The need also arose to determine more precisely, that is, more accurately and more closely to the patient's instantaneous compound requirements, the quantity of compound a patient needs. Indeed, some known techniques underestimate or overestimate compound requirements, resulting in an increased risk of hypotension or hypertension in the patient. Description of the invention

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

[0014] To this end, the invention relates to a method for assessing a patient's drug compound needs, intended to be implemented by an assessment device comprising means for measuring the patient's heart rate variability between 0.15Hz and 4Hz, a data processing and recording unit, and means for recording physiological data relating to the patient, the method comprising the following steps: • a step to measure the patient's heart rate variability between 0.15Hz and 4Hz; • a first determination step by the data processing and recording unit, from the measured heart rate variability data, of an ANI index related to the patient's pain level; • a second determination step by the data processing and recording unit, based on the ANI index, of an MC index, representing the average of the ANI index over a so-called short period, and of an ML index, representing the average of the ANI index over a so-called long period, as well as the slopes PC and PL respectively of said MC and ML indices ML, the MC and ML indices corresponding to a patient's pain level and the PC and PL indices to its evolution, respectively over a short period and a long period; • a step of recording physiological data relating to the patient, by means of recording physiological data relating to the patient; • a third determination step by the data processing and recording unit, based on the MC and ML indices, their PC and PL slopes, and the patient's physiological data, of the patient's need for the drug compound, said third determination step including a sub-step of determining a quantity of said compound to be administered to the patient at a timely dose, called a bolus, comprising • the determination of a first fuzzy logic variable CMC, between 0 and 1, from a membership function FMC of the index MC, • the determination of a second fuzzy logic variable Cpc, between 0 and 1, from a membership function FPC of the index PC, • the determination that the bolus is equal to a first predetermined quantity of said compound when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable Cpc is strictly greater than 1, and that the bolus is equal to zero otherwise; said third determination step further comprising a substep of determining a second quantity of said compound to be administered, less than said first predetermined quantity, determined according to the MC and ML indices, their slopes PC and PL, and physiological data relating to the patient, this substep being executed by the process following the substep of determining a bolus when the bolus is equal to zero.

[0015] The method according to the invention is based on a fuzzy logic step, also called "fuzzy logic" in English terminology.

[0016] Determining a bolus by means of a fuzzy logic substep greatly improves the stability and repeatability of the compound requirement assessment, compared with known techniques of the technique.

[0017] The substep of determining a quantity of the compound to be administered to the patient on an ad hoc basis, i.e. a substep of determining a bolus, makes it possible to evaluate whether a bolus can be administered to the patient or not.

[0018] If a bolus can be administered to the patient, taking into account the MC and PC threshold values, the bolus value corresponds to a predetermined quantity of compound. The predetermined quantity of compound may be fixed, or defined prior to the implementation of the process, for example, based on patient data.

[0019] If a bolus cannot be administered to the patient, in view of the MC and PC threshold values, the value of the bolus is zero.

[0020] The calculation of the average ANI index can be performed over a sliding window. In particular, in such a case, the repeatability of the method according to the invention is even greater compared with the known technique.

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

[0022] It is specified here that the process can operate in a loop, in real time or periodically, that is to say that the said steps of the process are repeated in succession so as to determine in real time or periodically the need for drug compounds of the patient.

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

[0024] According to a second aspect, the invention also relates to a device for assessing a patient's drug compound needs, comprising means for measuring the patient's heart rate variability between 0.15 Hz and 4 Hz, a data processing and recording unit, and means for recording physiological data relating to the patient, the processing and recording unit comprising a processor and computer memory storing instructions configuring the processor to: • receive patient heart rate variability data between 0.15Hz and 4Hz; • determine, from the received heart rate variability data, an ANI index related to the patient's pain level; • determine, from the ANI index, an MC index, representative of the average of the ANI index over a so-called short period, and an ML index, representative of the average of the ANI index over a so-called long period, as well as the slopes PC and PL respectively of said MC and ML indices, the MC and ML indices corresponding to the level of pain of a patient and the PC and PL indices to its evolution, respectively over a short period and a long period; • receive physiological data relating to the patient; • determine, based on the MC and ML indices, their PC and PL slopes, and the patient's physiological data, the need for the medicinal compound The compound to be administered to the patient, this step including a sub-step of determining an initial quantity of said compound to be administered to the patient on an ad hoc basis, called a bolus, comprising: • the determination of a first fuzzy logic variable CMC, between 0 and 1, from a membership function Fmc of the index MC, • the determination of a second fuzzy logic variable CpC, between 0 and 1, from a membership function FPC of the index PC, • the determination that the bolus is equal to a first predetermined quantity when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable Cpc is strictly greater than 1, and that the bolus is equal to zero otherwise • determine a second quantity of said compound to be administered, less than said first predetermined quantity, based on the MC and ML indices, their PC and PL slopes, and physiological data relating to the patient, following the determination of a bolus, when the bolus is equal to zero.

[0025] Such a device presents the advantages and technical effects of the process according to the invention described above.

[0026] The device for assessing a patient's drug compound needs may in particular take the form of a computer having inputs to which are connected a heart rate variability sensor and at least one other sensor for physiological data of the patient.

[0027] The evaluation device may include a data display device, in particular for a quantity of drug compound to be administered.

[0028] It is specified that the method, and the device, can also be a method, and a device, for assessing a patient's needs for a drug compound, or drugs, and / or for paramedical care. Preferably, the drug compound is an analgesic and / or 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 described below.

[0030] According to one embodiment, in the evaluation method and device according to the invention, the membership function F MC of the index MC is: • equal to 1 when the MC index is less than or equal to a low threshold value ^MCBas, • equal to 0 when the MC index is greater than or equal to a high threshold value ^MCHaut, • and exhibits a monotonically decreasing transition between 1 and 0, when the MC index is between the lower threshold value SMCBas and the upper threshold value SMCHauU, and in which the membership function FPC of the PC index is:

[0031]

[0032]

[0033]

[0034]

[0035]

[0036] • equal to 1 when the PC index is less than or equal to a low threshold value $ PC Low, • equal to 0 when the PC index is greater than or equal to a high threshold value F PC High, • and exhibits a monotonic decreasing transition between 1 and 0, when the PC index is between the low threshold values ​​SPCBas and high threshold values ​​SpCHaut. The choice of this type of membership function has allowed us to observe good performance of the process, which is particularly stable and repeatable. The type of monotonic decay transition can be adapted according to the type of compound to be administered, and / or according to the patient's clinical condition. Similarly, the upper and lower thresholds can be adapted according to these same criteria. According to one embodiment, in the evaluation method and device according to the invention, the membership function Pmc of the index MC is defined according to the expression: 1, if MC S MCBas F MC ~ ' S^ '-S^ t ' Sl $MCLow < MC < SMCHigh 0, if MC > S MCHaut and the membership function Fpc of the index PC is defined according to the expression: FPC~ 1, siPC PCBas PC-Spcu^ . „ _ „ „ SPr^ ~Speu P ^PCBas ^^PCHaut ^PCiicis ^PCilaut 0, if PC > S PCHaut In general, a linear decreasing transition allows for good process performance.​ Such a transition is particularly suitable during surgery in which the patient is under general anesthesia. According to one embodiment, in the evaluation method and device according to the invention: The SMCBas threshold value is between 45 and 55, and preferably equal to 50. the SMCHautest threshold value being between 58 and 68, and preferably equal to 63, The SPCBas threshold value is between -40 and -30 and preferably equal to -35. The SPCHaut threshold value is between -30 and -20, and preferably equal to -25.

[0037] Threshold ranges, as well as preferential thresholds, are particularly suitable during surgery in which 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 patient physiological data recording step is a patient systolic blood pressure (SBP) recording step, by physiological data recording means that are configured to measure and record at least one systolic blood pressure (SBP), the bolus determination substep being carried out by the method when the patient systolic blood pressure (SBP) is greater than or equal to at least one of a first threshold value SPASl of systolic blood pressure and a second threshold value SpAsi of systolic blood pressure.

[0040] In the evaluation device according to the invention, the reception of physiological data relating to the patient includes the reception of at least one systolic blood pressure (SBP) data from the patient, for example acquired by physiological data recording means which are configured to measure and record at least one systolic blood pressure (SBP), the determination of a bolus being carried out when the patient's systolic blood pressure (SBP) is greater than or equal to at least one of a first threshold value $pasi of systolic blood pressure and a second threshold value $PAS2 of systolic blood pressure.

[0041] According to one embodiment, in the method and the evaluation device according to the invention, the first threshold value $PAS} of systolic blood pressure corresponds to a predetermined average value of systolic blood pressure, and the second threshold value SPAS2 of systolic blood pressure corresponds to a previously measured and recorded systolic blood pressure of the patient.

[0042] In particular, in the process according to the invention, the second SPAS2 threshold value of systolic blood pressure corresponds to a systolic blood pressure of the patient measured and recorded prior to the execution of said process.

[0043] By such a setting of the thresholds, it is possible to adapt the proportional regulation according to a generally accepted average systolic blood pressure, and a systolic blood pressure of the patient preceding the execution of the process.

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

[0045] In the assessment device according to the invention, the patient's systolic blood pressure measured and recorded previously corresponds to an arterial pressure patient's systolic, obtained during a previous reception of the patient's physiological data by the evaluation device.

[0046] When the process according to the invention is executed in a loop, or when the evaluation device evaluates the needs in a loop, the proportional regulation can take into account the systolic blood pressure measured and recorded during a previous iteration of the process or the operation of the evaluation device, thus allowing the evolution of the systolic blood pressure to be monitored.

[0047] According to one embodiment, the method includes a proportional regulation step of a quantity of drug compound to be administered, carried out by the method upstream of the third determination step, when the patient's systolic blood pressure (SBP) is strictly less than both said first threshold value and said second threshold value SPAS2 of systolic blood pressure, said regulation step comprising the determination of a quantity of drug compound to be administered corresponding to a quantity of drug compound previously administered, from which is subtracted a quantity of drug compound directly proportional to a variation in the value of the patient's systolic blood pressure (SBP) measured and recorded, relative to a value of the patient's systolic blood pressure measured and recorded prior to the execution of said method.

[0048] In the assessment device according to the invention, the instructions include the proportional regulation of a quantity of drug compound to be administered, carried out upstream of the determination of the need for compound, when the patient's systolic blood pressure (SBP) is strictly less than both said first threshold value SPAS1 and said second threshold value SPAS2 of systolic blood pressure, said regulation including the determination of a quantity of drug compound to be administered corresponding to a quantity of drug compound previously administered, from which is subtracted a quantity of drug compound directly proportional to a variation in the value of the patient's systolic blood pressure (SBP) measured and recorded, relative to a value of the patient's systolic blood pressure received during a previous assessment by the assessment device.

[0049] By regulating the dose proportionally to the decrease in systolic blood pressure, the amount of compound to be administered can be reduced, thereby decreasing the risk of hypotension in the patient. Furthermore, the total amount of compound to be administered can be reduced and better adapted to the patient's condition.

[0050] Thus, when the patient's systolic blood pressure falls too low, the amount of drug compound is reduced.

[0051] This may refer to a specific quantity of drug compound prior to any use of the process or evaluation by the evaluation device, or of a quantity of drug compound determined during the third determination step of said process, during a previous execution of the process, or previous determination of the compound requirement by the evaluation device.

[0052] When the process is executed in a loop, or when the evaluation device evaluates in a loop, it is understood that the determination of the need for the compound, and therefore the determination of a bolus, is only carried out when the regulation, executed a sufficient number of times, has made it possible to verify the condition under which the systolic blood pressure is no longer below one of the two aforementioned systolic blood pressure thresholds.

[0053] This makes it possible to secure the process or the use of the evaluation device, by ensuring that no excessive amount of compound, and in particular no bolus, risks being administered to the patient who may be in a situation of hypotension.

[0054] According to a third aspect, the invention also relates to a device for delivering a medicinal compound, comprising a device for assessing the needs for a medicinal compound of a patient according to a second aspect of the invention, associated with control means and an infusion system, preferably electric.

[0055] The delivery device may include control means configured to regulate a flow rate of drug compound according to the quantity of drug compound determined, through an action on the infusion system. BRIEF DESCRIPTION OF THE FIGURES

[0056] Other advantages, purposes and particular features of the present invention will become apparent from the following non-limiting description of at least one particular embodiment of the devices and methods of the present invention, with reference to the accompanying drawings, in which: • Fig. 1 schematically represents a delivery device comprising an evaluation device according to the invention; • [Fig.2] schematically represents an evaluation device according to the invention; • [Fig.3] is a flowchart of the evaluation process according to the invention; • Figure 4 is a flowchart of the evaluation process according to the invention. including an optional proportional regulation step; • [Fig.5] represents the graph of the membership function F_MC of index MC and the graph of the membership function F_PC of index PC; • Figure 6 is a flowchart of the evaluation process, according to a method of implementation. lisation. DETAILED DESCRIPTION OF THE INVENTION

[0057] The present description is given by way of non-limiting grammar, each feature of an embodiment being able to be advantageously combined with any other feature of any other embodiment.

[0058] It should be noted from the outset that the figures are not to scale.

[0059] Fig. 1 schematically represents a compound delivery device 300.

[0060] The delivery device 300 includes a drug compound needs assessment device 200, control means 240 and an infusion system 250.

[0061] Preferably, the perfusion system 250 is electric, and is operated by the control means 240, connected by a data link to the evaluation device 200. The perfusion system is adapted to distribute a drug compound into the blood circulation circuit of a patient requiring administration of the drug compound, for example via a catheter of the perfusion system 250.

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

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

[0064] Figure 2 schematically represents a single 200 evaluation device, that is to say not associated in particular with control means 240 and a perfusion system 250. The evaluation device 200 can in fact operate alone without means of administration of the compound, by determining the needs for analgesic and / or hypnotic and / or curarizing compound and by transmitting this information to another device, or to medical personnel for example.

[0065] The evaluation device 200 may in particular include means for measuring 210 the patient's heart rate variability between 0.15Hz and 4Hz, a data processing and recording unit 220 and means for recording 230 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 configuring the processor 221 for its operation. For example, the computer memory 222 is a non-volatile, rewritable computer memory, for example of the "EPROM" type.

[0067] The means 230 for recording physiological data relating to the patient may be physiological data sensors, including commercially available sensors. These sensors may be configured to record physiological, or vital, data of the patient and transmit them via a data link to the data processing and recording unit 220. For example, the recording means 230 include at least one blood pressure sensor, including systolic pressure, also known as a sphygmomanometer.

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

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

[0070] The evaluation device 200 makes it possible to evaluate, from physiological data of the patient, a patient's need for an analgesic and / or hypnotic compound, hereinafter referred to as "compound", in particular when the patient is placed under anesthesia or sedation.

[0071] The need for the compound may, in particular, be the determination of the quantity of compound required by the patient. The assessment device 200 may allow such a quantity of compound to be communicated to medical personnel, for example via a computer screen, or the quantity of compound to be communicated to the control means 240 for administration by the infusion system 250.

[0072] Thus, the evaluation device 200 makes it possible to provide a recommendation on the compound needs of a patient, the appropriate quantity of compound can then be administered by medical staff, or automatically by the infusion system, at the decision of the medical staff.

[0073] The need for compounds is assessed by the assessment device 200, notably using an ANI index, which is an index related to the level of pain experienced by the patient. Thus, the need for compounds can be determined based on the level of pain experienced, and the optimal quantity of compound needed by the patient to alleviate pain can be assessed, without under- or over-dosing.

[0074] For this purpose, the evaluation device 200 is configured to implement a process 100 for evaluating a patient's needs for an analgesic and / or hypnotic compound.

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

[0076] The method 100, intended to be implemented by the evaluation device 200, will now to be described, with reference in particular to figures 3 and 4.

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

[0078] The process 100 then includes a first determination step 120 by the data processing and recording unit 220, from the heart rate variability data measured during step 110, of an ANI index relating to the patient's pain level.

[0079] For example, the ANI index can be calculated according to the process described in application WO 2006 / 032739. The first determination step 120 can thus include the steps of such a process in order to determine the ANI index.

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

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

[0082] The MC and ML indices therefore correspond to the level of pain of a patient, respectively over a so-called short period and a so-called long period, of duration greater than the short period.

[0083] In addition, in the second determination step 130, the slopes PC and PL respectively of said indices MC and ML are determined, corresponding to the evolution of the level of pain of a patient, respectively over the short period and the long period.

[0084] In other words, the MC and ML indices are calculated from the different values ​​of the ANI over a given period, and make it possible to limit the impact of the instantaneous variability of the ANI measurement due to the calculation method and also to identify trends in the evolution of the patient's pain.

[0085] More specifically, the calculation of the MC and ML indices is preferably carried out from an average of the values ​​of the ANI indices over two different periods, namely a short period and a long period.

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

[0087] Advantageously, the period taken into account for the calculation of ML is approximately 1.5 to 3 times the period used for the calculation of MC.

[0088] The slope PC is calculated in degrees from two MC values ​​separated by a given time interval according to the following formula: p(j _ / 180 \ grctan(MC ~ Y

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

[0090] The slope PL is calculated in degrees in a manner analogous to that of PC according to the following formula PL = { — ) arctanl ——— r

[0091] Here again the time interval separating t1 and t2 is on the order of 15 to 45 seconds and preferably equal to 30 seconds.

[0092] Furthermore, the method 100 includes a step 140 of recording physiological data relating to the patient, by means of recording physiological data 230 relating to the patient.

[0093] As presented earlier, the recording means 230 allow, for example, the measurement of heart rate (HR) and systolic blood pressure (SBP).

[0094] These parameters are not used directly in the calculation of the optimal quantity of compounds required by the patient, but are used in such a way as to constitute safeguards, the evaluation device not performing an evaluation when certain thresholds corresponding to these parameters are exceeded.

[0095] An example of a security step will be described later in this description.

[0096] In other embodiments, other physiological parameters could can be used as a replacement for, or in addition to, heart rate (HR) and systolic blood pressure (SBP).

[0097] It is also conceivable, although this mode would have the disadvantage of degraded safety, to use only one physiological parameter.

[0098] It is also possible to record other types of patient data, such as weight, height, age, or sex, using the recording means 230. For this purpose, the recording means 230 may advantageously include a keyboard or touch surface, not shown in the accompanying figures.

[0099] The process 100 also includes a third determination step 150 by the data processing and recording unit 220, of the need for a drug compound, here for example an analgesic and / or hypnotic compound, required by the patient

[0100] The need for analgesic and / or hypnotic compound required by the patient is determined according to the MC and ML indices, their PC and PL slopes, and physiological data relating to the patient.

[0101] More specifically, during the third determination step 150, it is first determined whether the patient requires the administration of an initial quantity of said compound, to be administered to the patient on an ad hoc basis. Such a relatively large quantity of compound, intended to be administered over a short period of time, is called "bolus". The patient requires the administration of a compound bolus when the pain felt is acute, i.e., when the ANI index is close to 0.

[0102] For this purpose, the third determination step 150 includes a sub-step 151 for determining a first quantity of the compound to be administered on an ad hoc basis to the patient, i.e. a sub-step 151 for determining a bolus.

[0103] Substep 151 of determining a bolus includes determining a first fuzzy logic variable CMC, between 0 and 1, from a membership function FMC of the index MC.

[0104] Substep 151 of determining a bolus also includes determining a second fuzzy logic variable Cpc, between 0 and 1, from a membership function FPC of the index PC.

[0105] Substep 151 of determining a bolus then includes determining that the bolus is equal to a first predetermined quantity Qp of said compound when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable Cpc is strictly greater than 1, and that the bolus is equal to zero otherwise.

[0106] In other words, the patient requires a bolus when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable CPC is strictly greater than 1, and does not require a bolus when the sum of the first fuzzy logic variable CMc and the second fuzzy logic variable CPC is less than 1.

[0107] Substep 151 of determining a bolus is thus a step using fuzzy logic to determine whether or not to administer a bolus.

[0108] The membership function FMC of index MC and the membership function FPC of index PC are here bounded functions between 0 and 1. Thus, the image of a value of index MC or PC by the respective membership function is a value Cpc or CMC between 0 and 1, that is to say a "fuzzy" Boolean value.

[0109] Figure 5 represents the graphs of the membership function FMC of index MC and the membership function FPC of index PC.

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

[0111] - Equal to 1 when the MC index is less than or equal to a low threshold value SMCBas

[0112] - Equal to 0 when the MC index is greater than or equal to a high threshold value ^MChaii J

[0113] - And exhibits a monotonically decreasing transition between 1 and 0, when the index MC is between the lower threshold value SMCBas and the upper threshold value SMCHauh

[0114] Similarly, for example, the membership function FPC of the index PC is:

[0115] - Equal to 1 when the PC index is less than or equal to a low threshold value SPCBas;

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129] - Equal to 0 when the PC index is greater than or equal to a high threshold value SPCHau( - And exhibits a monotonic decreasing transition between 1 and 0, when the PC index is between the low threshold values ​​SPCBas and high threshold values ​​SPCHailt. Examples of monotonic decreasing transitions include linear, hyphenated, and hyphenated transitions. perbolic, including sigmoid, exponential or Gaussian. A linear decreasing transition is particularly preferred. For example, the FMC membership function of the MC index is defined according to the expression: F MC “ 1, if MC < S MCBas MC-SMCHmu c S.,rK / ^^MCBas MCBas JM Cilatti < MC < SMCHaut 0, if MC £ SMCHaut For example, the FPC membership function of the PC index is defined according to the expression: if PC < S PCBas Fpc = ■' ^pcb^PC^pch^ 0, if PC S PCHaut The high and low transition thresholds SMCBa^ SMCHaut, SPCBas and SPCHaut can The procedure can be freely adapted according to the conditions of use of process 100, particularly based on the patient's profile (including 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, the type of transition can be freely adapted according to these same criteria. For example, the values ​​of the SMCBai, S Menant, SpcBas and SPCHaut thresholds can be set as follows: - The SMCBas threshold value is between 45 and 55, and preferably equal to 50. - The SMCHautest threshold value is between 58 and 68, and preferably equal to 63. - The 5PCbm threshold value is between -40 and -30 and preferably equal to -35. - The SPCHaut threshold value is between -30 and -20, and preferably equal to -25. Such ranges of values, and preferred values, particularly those associated with a linear transition, are especially suitable for surgery under general anesthesia when remifentanil is to be administered to the patient. Indeed, repeatable and stable operation of the procedure has been observed in this context. Substep 151 of bolus determination, based on fuzzy logic, allows to obtain a particularly reliable and repeatable bolus determination, even when the MC index exhibits high variability, especially when determined over a sliding window. Indeed, fuzzy logic makes it possible to avoid bolus determination based on fixed thresholds, which is much more sensitive to variations in the MC index.

[0130] Specifically, with reference to [Fig.6] which shows a more detailed example of implementation of process 100 in the form of a flowchart, when a bolus is determined, and when the compound used is remifentanil with a concentration of 25pg / ml, a flow rate variable is for example increased according to the patient's weight by 0.12 pg / kg / min for 10 seconds.

[0131] In this example, a variable "Bolus" is set to 10, this variable being decremented during a subsequent execution of process 100, which can operate continuously or periodically in a loop. As long as the variable "Bolus" is not zero, no further steps for determining the quantity of compound are performed by process 100.

[0132] If, at the end of substep 151 of determining a bolus, the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable Cpc is less than 1, i.e. the bolus is zero, the process 100 executes a substep 152 of determining a second quantity of the compound to be administered, less than said first predetermined quantity p.

[0133] The second quantity of the compound is determined according to the MC and ML indices, their slopes PC and PL, and the physiological data relating to the patient.

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

[0135] In particular, as can be seen in Figure 6 at substep 152, the MC index is first compared successively to low thresholds Sb and high thresholds Sh, in order to determine whether the mean of the ANI index over a short period is low, medium, or high, i.e. whether the pain is severe, moderate, or mild.

[0136] Based on this initial determination, and taking into account the long-term trend in the average pain level and the short- and long-term evolution of the average pain level, process 100 determines the second quantity of compound. This second quantity of compound may be larger or smaller than a previously determined second quantity of compound, particularly one determined during a previous execution of process 100. It is also possible that the second quantity of compound may remain unchanged compared to a previously determined second quantity of compound.

[0137] Once substep 152 has been executed, and the second quantity of compound determined, Process 100 can be run again from the beginning. It is possible to delay a new execution of the process, for example by setting a value of the variable "Pref", here to 10 in the example of [Fig.6], this variable being decremented during each execution of the process, before the execution of the third determination step 150.

[0138] The specific implementation of substep 152, as well as the specific operation of the loops decrementing the variables “Bolus” and “Pref” of the algorithm illustrated in [Fig.6], are described in the Applicant’s patent documents FR 3006879 and FR 3006880, to which the person skilled in the art may refer for the implementation of method 100.

[0139] As mentioned earlier in this description, process 100 may include a safety step, aimed at preventing any determination of the quantity of compound to be administered when certain thresholds of patient physiological data are exceeded.

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

[0141] For this purpose, the patient physiological data recording step 140 is then a recording step of at least one systolic blood pressure (SBP) of the patient, by the physiological data recording means 230 which are then configured to measure and record at least one systolic blood pressure (SBP).

[0142] The optional step of comparing systolic blood pressure (SBP) to two systolic blood pressure thresholds includes comparing systolic blood pressure (SBP) to:

[0143] - A first Spasi threshold of systolic blood pressure which may be a value a predetermined average systolic blood pressure, for example a systolic blood pressure of 120 mmHg which can be considered a minimum systolic blood pressure threshold for a healthy person, and at:

[0144] - A second SPAS2 systolic blood pressure threshold which may be a value of the patient's systolic blood pressure (SBP), measured and recorded prior to the execution of process 100. For example, the patient's systolic blood pressure (SBP) may have been measured and recorded during a previous execution of process 100.

[0145] When the patient's systolic blood pressure (SBP) is greater than or equal to at least one of the first threshold value SPAS1 of systolic blood pressure and the second threshold value $pas2 of systolic blood pressure, substep 151 of determining a bolus is performed by method 100.

[0146] Indeed, when the patient's systolic blood pressure (SBP) is not below the first threshold, and does not decrease compared to a previous systolic blood pressure, it is possible to consider that the risk of hypotension of the patient is low, and that a quantity of compound to be administered can be determined without endangering the patient's health.

[0147] When the patient's systolic blood pressure (SBP) is strictly less than both the first threshold value i and the second threshold value SPAS2 of systolic blood pressure, a step 145 of proportional regulation of a quantity of analgesic and / or hypnotic compound to be administered is carried out by the process upstream of the third determination step 150. The third determination step 150, and thus in particular the determination of a bolus, is then not carried out by the process 100 during the same iteration of the process 100.

[0148] Step 145 of proportional regulation includes the determination of a quantity of analgesic and / or hypnotic compound to be administered, this quantity corresponding to a quantity of analgesic and / or hypnotic compound previously administered, from which is subtracted a quantity of analgesic and / or hypnotic compound directly proportional to a variation in the value of the patient's systolic blood pressure (SBP) measured and recorded, relative to a value of the patient's systolic blood pressure measured and recorded prior to the execution of process 100.

[0149] Specifically, with reference to the algorithm illustrated in [Fig.6], a "Flow Rate" variable for compound flow rate setpoint can be updated in a manner directly proportional to the variation in the patient's measured and recorded systolic blood pressure (SBP) value, relative to a patient's measured and recorded systolic blood pressure value prior to the execution of process 100.

[0150] For example, a new flow rate setpoint can be defined as follows: Flow rate = Flow rate - Flow rate . , where SPASmin is a predetermined threshold value- PAS-SPASMil completed systolic blood pressure, for example corresponding to 80 mmHg.

[0151] In other words, the "Flow Rate" variable is overwritten and updated so as to reduce the compound flow rate setpoint proportionally to the change in the patient's systolic blood pressure (SBP).

[0152] Step 145 of proportional regulation is executed in a loop until the patient's systolic blood pressure is no longer below either of the two threshold values ​​SpAS1 and SPAS2, i.e., the risk of hypotension in the patient can be considered low. This constitutes a safety measure, avoiding the assessment of excessive compound requirements for a patient experiencing hypotension, or a drop in blood pressure.

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

[0154] In addition, step 145 of proportional regulation allows for better adaptation of the administration of the compound according to the patient's needs, and also allows for a reduction in the total amount of compound to be administered to the patient, which is advantageous both clinically and economically.

[0155] Although the optional step of comparing systolic blood pressure (SBP) to two systolic blood pressure thresholds, followed if necessary by a proportional regulation step 145, is particularly advantageous as described above, it is also conceivable to provide a more conventional safety step as described in the Applicant's patent documents FR 3006879 and FR 3006880. The safety step described therein provides for a cessation of compound flow when the patient is hypotensive or bradycardia.

[0156] According to one embodiment, the process 100, and / or the evaluation device 200, and / or the delivery device 300 can be intended for the evaluation of a patient's paramedical care needs, as an alternative or complement to the evaluation of the need for a medicinal compound.

[0157] In other words, as a complement to or alternative to determining the quantity of compound required by the patient, it is possible to similarly assess, i.e., on the basis of fuzzy logic relying on an ANI index and its sub-indices, a patient's paramedical care needs. For example, determining a paramedical care need includes determining that paramedical care is required by the patient, and may, for example, include determining the duration and / or intensity of the paramedical care.

[0158] The term “paramedical care” means all care that can be provided to a patient with the exception of medical and surgical treatments; it includes, but is not limited to, care in pediatrics, physiotherapy, neonatology, neurophysiology, or more broadly, care based on modifying the environment to improve the patient’s well-being.

[0159] It is more generally recalled that the invention is not limited to the examples described and illustrated.

Claims

Claims

1. Method (100) for evaluating the needs of a patient for medicinal compound, intended to be implemented by an evaluation device (200) comprising means for measuring (210) the cardiac variability of the patient between 0.15Hz and 4Hz, a data processing and recording unit (220), and means for recording (230) physiological data relating to the patient, the method comprising the following steps: a measurement step (110) of the patient's cardiac variability between 0.15Hz and 4Hz; a first determination step (120) by the data processing and recording unit (220), from the measured cardiac variability data, of an ANI index relating to the patient's pain level; a second determination step (130) by the data processing and recording unit (220), from the ANI index, of an MC index, representative of the average of the ANI index over a so-called short period, and of an ML index, representative of the average of the ANI index over a so-called long period, as well as the PC and PL slopes respectively of said MC and ML indices, the MC and ML indices corresponding to the level of pain of a patient and the PC and PL indices to its evolution, respectively over a short period and a long period; a step (140) of recording physiological data relating to the patient, by the means (230) of recording physiological data relating to the patient; a third determination step (150) by the data processing and recording unit (220), as a function of the MC and ML indices, their PC and PL slopes, and the physiological data relating to the patient, the need for medicinal compound required by the patient, said third determination step comprising a sub-step (151) of determining a first quantity of said compound to be administered punctually to the patient, called a bolus, comprising: • the determination of a first fuzzy logic variable CMC, between 0 and 1, from a

2. membership function FMC of the MC index, • the determination of a second fuzzy logic variable Cpc^ between 0 and 1, from a membership function FPC of the PC index, • determining that the bolus is equal to a first predetermined quantity of said compound when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable CPC is strictly greater than 1, and that the bolus is equal to zero otherwise; said third determination step (150) further comprising a sub-step (152) of determining a second quantity of said compound to be administered, less than said first predetermined quantity, determined as a function of the MC and ML indices, their PC and PL slopes, and physiological data relating to the patient, this sub-step (152) being executed by the method following the sub-step (151) of determining a bolus when the bolus is equal to zero. Method (100) according to claim 1, wherein the membership function FMC of the index MC is: • equal to 1 when the MC index is less than or equal to a low threshold value SMCBas> • equal to 0 when the MC index is greater than or equal to a high threshold value SMCHaMh and presents a monotonically decreasing transition between 1 and 0, when the MC index is between the low threshold values ​​SMCBas and high ^Leading, and in which the membership function FPC of the PC index is: • equal to 1 when the PC index is less than or equal to a low threshold value SpcBas, • equal to 0 when the PC index is greater than or equal to a high threshold value SPCHauh and presents a monotonically decreasing transition between 1 and 0, when the PC index is between the low threshold values ​​SPCBas and high SpCHaut- ^Claim 3] Method (100) according to claim 2, wherein the membership function FMC of the index MC is defined according to the expression: 1, if MC < SMCBas P — .......... ' Ç < W / ' < Ç 0, if MC > SMCHa[it and the membership function FPC of the index PC is defined according to the expression: 1, ifPC<spcbas fpc~ spcb -spch ’ $i spcbas < pc < spchaut 0, si pc 2: spchaut ^revendication 4] procédé (100) selon l’une quelconque des revendications 2 ou 3, dans lequel : •        la valeur seuil smcbas est comprise entre 45 et 55, préféren tiellement égale à 50, ^mchautesi 58 68, préfé rentiellement 63, spcbas -40 -30 -35, spchaut -20, -25. 5] 1 4, l’étape d’enregistrement (140) de données physiologiques relatives au patient une étape moins d’une pression artérielle systolique (pas) du patient, par les moyens (230) qui sont configurés pour mesurer enregistrer (pas), la sous-étape (151) détermination d’un bolus étant réalisée le procédé lorsque supérieure parmi première •spasi deuxième $pas2 systolique. 6] revendication 5, spasi correspond valeurpredetermined average systolic blood pressure, and the second threshold value SPAS2 of systolic blood pressure corresponds to a systolic blood pressure of the patient measured and recorded previously to the execution of said method.

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

8. Method (100) according to any one of claims 5 to 7, further comprising a step of proportional regulation (145) of an amount of medicinal compound to be administered, carried out by the method upstream of the third determination step (150), when the patient's systolic blood pressure (SBP) is strictly lower than both said first threshold value and said second threshold value $pas2 of systolic blood pressure, said regulation step (145) comprising the determination of an amount of medicinal compound to be administered corresponding to an amount of medicinal compound previously administered, from which is subtracted an amount of medicinal compound directly proportional to a variation in the value of the patient's systolic blood pressure (SBP) measured and recorded,compared to a value of the patient's systolic blood pressure measured and recorded previously to the execution of said method.,

9. Device (200) for evaluating the needs of a patient in medicinal compound, comprising means (210) for measuring the patient's cardiac variability between 0.15Hz and 4Hz, a data processing and recording unit (220), and means (230) for recording physiological data relating to the patient, the processing and recording unit comprising a processor (221) and a computer memory (222) storing instructions configuring the processor to: • receive data on the patient's cardiac variability between 0.15Hz and 4Hz; • determine, from the received cardiac variability data, an ANI index relating to the patient's pain level • determine, from the ANI index, an MC index, repre- representative of the average of the ANI index over a so-called short period, and of an ML index, representative of the average of the ANI index over a so-called long period, as well as the PC and PL slopes respectively of said MC and ML indices, the MC and ML indices corresponding to the level of pain of a patient and the PC and PL indices to its evolution, respectively over a short period and a long period; • receive physiological data relating to the patient; • determine, based on the MC and ML indices, their PC and PL slopes, and the physiological data relating to the patient, the need for medicinal compound to be administered to said patient, this step comprising a sub-step of determining a quantity of said compound to be administered punctually to the patient, called a bolus, comprising: • the determination of a first fuzzy logic variable CMC, between 0 and 1, from a membership function FMC of the MC index, • the determination of a second fuzzy logic variable Cp^ between 0 and 1, from a membership function FPC of the index PC, • determining that the bolus is equal to a first predetermined quantity when the sum of the first fuzzy logic variable CMC and the second fuzzy logic variable Cpc is strictly greater than 1, and that the bolus is equal to zero otherwise • determine a second quantity of said compound to be administered, less than said first predetermined quantity, based on the MC and ML indices, their PC and PL slopes, and the physiological data relating to the patient, following the determination of a bolus, when the bolus is equal to zero.

10. Delivery device (300) of a medicinal compound, comprising an evaluation device (200) according to claim 9, associated with control means (240) and with an infusion system (250), preferably electrical.< / spcbas>

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