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EP-4052265-B1 - VECTORIAL CALCULATION APPLIED TO A DECISION-MAKING MATRIX FOR THE TITRATION OF THE ANAESTHESIA LEVELS

EP4052265B1EP 4052265 B1EP4052265 B1EP 4052265B1EP-4052265-B1

Inventors

  • TOGNOLI, Emiliano

Dates

Publication Date
20260506
Application Date
20201028

Claims (14)

  1. Method for the control of hypnotic and analgesic concentrations of an anaesthetic composition comprising the following steps: - supplying a memory unit configured to receive and record data; - supplying at least one data processing unit (101), in signal communication with the memory unit and configured to process and record data in the memory unit; - providing the bispectral index (P BIS ) and the mean arterial pressure (P MAP ) of a patient treated with a first anaesthetic composition comprising an initial hypnotic concentration and an initial analgesic concentration, and storing the patient's P BIS and P MAP data in said memory unit; the method being characterized in that it comprises the following steps: - providing a two-dimensional matrix defined, on the abscissa, by a MAP dimension relative to the variation of Mean Arterial Pressure and on the ordinate by a BIS dimension relative to the variation of the Bispectral Index; - defining in the matrix an optimal anaesthesia zone (OAZ) located between MAP values of 65 and 110 mmHg and BIS values of 40 and 60; - defining in the matrix an ISO-MAP axis and an ISO-BIS axis, orthogonal to ISO-MAP, whose intersection defines a point (A) of the optimal anaesthesia zone (OAZ); - localizing in the matrix the values of the P BIS and P MAP data, to define a position (B) of the patient in the matrix with respect to the optimal anaesthesia zone (OAZ); - providing an algorithm resident in said processing unit, configured to quantify the deviation of the patient's position (B) with respect to the optimal anaesthesia zone (OAZ) and transforming the deviation into a quantitative variation of the initial hypnotic concentration and the initial analgesic concentration of the first anaesthetic composition to define a target hypnotic concentration and a target analgesic concentration of a second anaesthetic composition; - processing the patient's P BIS and P MAP data using said algorithm to obtain the target hypnotic concentration and the target anaesthetic concentration of the second anaesthetic composition, the step of processing the patient's P BIS and P MAP data comprising the sub-steps of: - quantifying the deviation of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) by means of a vectorial calculation, the sub-step of quantifying comprising the sub-steps of - defining a vector (V) passing through point (A) of the optimal anaesthesia zone (OAZ) through the patient's position (B) and - calculating a percentage deviation (D%) of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) on the maximum deviation (C) of the MAP and BIS values along the vector (V), - decomposing the deviation of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) into a deviation from hypnosis (D H ) and/or into a deviation from analgesia (D S ) with respect to point (A) of the optimal anaesthesia zone (OAZ), and - calculating an increase or decrease in the initial hypnotic and/or analgesic concentration of the first anaesthetic composition based on said deviations (D H ; D S ), said sub-step of calculating comprising the sub-step of - modifying the hypnotic and analgesic concentration if the percentage deviation (D%) of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) is greater than 10%, - generating, by means of the algorithm, a datum relative to the target hypnotic and analgesic concentrations of the second anaesthetic composition, said datum being configured to induce the processing unit (101) to generate a receivable signal from a graphical interface device (102) configured to display target hypnotic and sedative concentrations processed by the algorithm, and/or from a machine configured for the delivery of one or more drugs (103).
  2. The method according to claim 1, wherein the step of defining the optimal anaesthesia zone (OAZ) involves localizing the optimal anaesthesia zone (OAZ) between MAP values of 65 and 85 mmHg and BIS values of 40 and 60.
  3. The method according to claim 1 or 2, wherein the matrix is defined by a MAP variation between 0 and 150 mmHg and by a BIS variation between 0 and 100, where the MAP and BIS dimensions orthogonally intersect each other at the zero point (0; 0).
  4. The method according to any one of claims from 1 to 3, wherein point (A) is defined by the intersection of the ISO-MAP axis at a MAP value of 75 mmHg and of the ISO-BIS axis at a BIS value of 50.
  5. The method according to anyone of claims from 1 to 4, wherein the percentage deviation (D%) of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ), on the maximum deviation (C) of the MAP and BIS values along the vector (V), is obtained with the expression: D% = A − B A − C ∗ 100
  6. The method according to any one of claims from 1 to 5, wherein the sub-step of decomposing the deviation of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) comprises a sub-step of calculating the deviation from hypnosis (D H ) by applying the percentage deviation (D%) of the patient's position (B) with respect to point (A) of the optimal anaesthesia zone (OAZ) at a hypnotic coefficient (H') obtained by dividing a hypnotic vector component (H), measured as the distance between the patient's position (B) and the ISO-BIS axis, by the sum of the hypnotic vector component (H) and an analgesic vector component (S) measured as the distance between the patient's position (B) and the ISO-MAP axis.
  7. The method according to any one of claims from 1 to 6, wherein the sub-step of calculating an increase or decrease in the hypnotic and/or analgesic initial concentration comprises the following sub-steps: - changing the hypnotic concentration if the deviation from hypnosis (D H ) is greater than 7.5%; and - changing the analgesic concentration if the deviation from analgesia (D S ) is greater than 7.5%.
  8. The method according to any one of claims from 1 to 7, wherein the sub-step of calculating an increase or decrease in the hypnotic and/or analgesic initial concentration comprises the following sub-steps: - modifying the hypnotic concentration if the percentage deviation (D%) of the patient's position (B) from point (A) of the optimal anaesthesia zone (OAZ) is greater than 10% and, at the same time, the deviation from hypnosis (D H ) is greater than 7.5%; - modifying the analgesic concentration if the percentage deviation (D%) of the patient's position (B) from point (A) of the optimal anaesthesia zone (OAZ) is greater than 10% and, at the same time, the deviation from analgesia (D S ) is greater than 7.5%.
  9. The method according to any one of claims from 1 to 8, wherein the increase in the hypnotic and analgesic initial concentration of the first anaesthetic composition as a function of said deviations (D H ; D S ) is obtained with the expression c target ↑ = c in + D H / S ∗ c max − c in
  10. The method according to any one of claims from 1 to 9, wherein the decrease in the hypnotic and analgesic initial concentration of the first anaesthetic composition as a function of said deviations (D H ; D S ) is obtained with the expression c target ↓ = c in − D H / S ∗ c in
  11. The method according to any one of claims from 1 to 10, further comprising the step of: - generating, by means of the processing unit (101), a signal as a function of the datum relative to the target hypnotic and analgesic concentrations and sending the signal to a graphical interface device (102) configured to display the target hypnotic and sedative concentrations processed by the algorithm; and/or - generating, by means of the processing unit (101), a signal as a function of the datum relative to the target hypnotic and analgesic concentrations to be used by a machine configured to deliver one or more drugs (103) as a function of the target hypnotic and sedative concentrations processed by the algorithm.
  12. The method according to claim 11, further comprising the step of approving the datum relative to the target hypnotic and analgesic concentration of the second anaesthetic composition by the anaesthesiologist by means of the graphical interface.
  13. Computer program configured to perform the method according to any one of the claims from 1 to 11 when performed by a computer.
  14. PID controller configured to implement the method according to any one of the claims from 1 to 11.

Description

FIELD OF THE INVENTION The present invention relates to a method for controlling the concentrations of drugs used in anaesthesia. In particular, the method of the present invention implements a series of steps which allow to optimize the modulation of the anaesthesia concentration for the induction and maintenance of a balanced anaesthesia, as well as for the cessation of the anaesthesia in the awakening step. STATE OF THE ART General anaesthesia mainly includes two components: hypnosis and control of the stress response to surgical trauma; in this sense, anaesthesia can be maintained by the systemic administration of a hypnotic and an analgesic so that the therapeutic objectives of the anaesthesia are achieved by the combined action of the two drugs1,2. This anaesthetic technique is generally referred to as "balanced anaesthesia". Both the hypnotic agent and the analgesic agent contribute, at least in part, to obtaining the two components of the anaesthesia and interact synergistically for the creation of the anaesthetic state3,4,5. The synergistic interaction allows the use of lower doses of each drug to achieve a balanced anaesthesia, potentially reducing the occurrence of side effects. Several studies have been designed to identify the optimal concentration of hypnotic and opioid combinations suitable for ensuring an adequate anaesthesia, ensuring the lowest patient exposure to the anaesthetic agents. One issue which is still unresolved in this clinical context concerns the method to be applied to modulate the level of anaesthesia during the induction, maintenance and awakening steps, whenever the selected target concentrations are inappropriate to control the patient's reaction to procedure-related stress. To control the level of a balanced anaesthesia it is necessary to answer two questions: which drug needs to be adjusted and how the concentration thereof needs to be modulated. The mathematical model describing the pharmacodynamic interactions between the analgesic agent and the hypnotic agent makes it possible to identify infinite combinations of concentrations which produce the same effect, so that different titration strategies can be put into practice when the patient deviates from an optimal anaesthesia state. Figure 1 graphically depicts the approaches taken over time by anaesthesiologists, consistent with what has been disclosed in the literature and what has been introduced in clinical practice: studies on the synergy of hypnotics and opioids indicate that a certain level of anaesthesia, measured as a response to increasing stressful stimuli or as a level of intensity of hypnosis, can be obtained by employing (X) high concentrations of hypnotics and low concentrations of opioids, (Y) low concentrations of both, (Z) minimum concentrations of hypnotics and high concentrations of opioids. By the same token, the separate monitoring of the distinct pharmacodynamic signals of the two drugs cannot solve the dilemma. An alternative approach consists in combining vital parameters identifying the level of hypnosis or stress response in a matrix, such as that proposed by G.M. Gurman in a publication of 19946 (Figure 2). This matrix is based on an electroencephalogram and blood pressure signal as control variables; for both parameters, a range of values can be defined which identifies an optimal anaesthesia region. In relation to that region, Gurman identifies nine different clinical conditions characterized by the combination of an appropriate increase or decrease of one or both vital parameters, in response to which an increase or decrease of one or both anaesthetic agents is planned. Problems of the background art The Gurman matrix allows, in view of the patient's vital parameters, to understand on which drug to intervene to balance the anaesthesia, but does not indicate how to intervene on hypnotic and/or analgesic concentrations to obtain the balanced anaesthesia. State-of-the-art approaches to modulating the hypnotic and analgesic concentration during anaesthesia are based on the experience of the anaesthesiologist and an unstructured approach, which results in an uncoordinated management of the hypnotic and analgesic component of anaesthesia. US 2012/095437 A1 relates to an automatic control system and method for the control of anaesthesia . Parameters that can be used to monitor the hypnotic component of anaesthesia include the bi-spectral index (BIS), the so-called analgoscore, a score based on the processing of mean arterial pressure (MAP) and heart rate. However, said document only considers these parameters in isolation. SUMMARY OF THE INVENTION The invention is defined by the appended claims. The Applicant has now found that it is possible to solve the problems of the known art by introducing a vectorial calculation which quantifies the deviation of the anaesthesia induced in the patient with respect to the values expected from a balanced anaesthesia and, through an algorithm, transforms the