A method and system for estimating the target drug concentration in inhaled anesthesia

Abstract

The present invention belongs to the technical field of anesthesia machines, and particularly relates to a method and system for estimating the target drug concentration of inhaled anesthesia. The method includes: obtaining the parameters set by an anesthesia ventilator; obtaining the basic information of a patient; inputting the above data into a pre-established kinetic equation, and using the Runge-Kutta algorithm to calculate the drug concentration inhaled at the patient's mouth end, the alveolar drug concentration, and the effect-site concentration, so as to achieve the estimation of the target drug concentration; the kinetic equation is based on the diffusion process of the breathing circuit of the anesthesia ventilator and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the patient's basic information and the parameters set by the anesthesia ventilator. The method of the present invention is applicable to anesthesia ventilators and volatile anesthetics; the established model parameters have physiological significance and can adapt to the individual attributes of patients; the present invention can predict the time when the drug reaches the equilibrium state in the anesthesia circuit and the patient's respiratory system, and obtain the alveolar concentration and effect-site concentration of the anesthetic drug.

Description

Technical Field

[0001] The present invention belongs to the technical field of anesthesia machines, and particularly relates to a method and system for estimating the target drug concentration of inhaled anesthesia. Background Art

[0002] An anesthesia machine delivers anesthetic drugs into the patient's alveoli through a mechanical circuit to form an anesthetic gas partial pressure. After diffusing into the blood, it directly inhibits the central nervous system, thereby producing the effect of general anesthesia. The anesthesia machine belongs to a semi-open anesthesia device. It mainly consists of components such as an anesthetic vaporizer, a flowmeter, a folding bellows ventilator, a breathing circuit (including inhalation and exhalation one-way valves and a manual airbag), and corrugated tubing.

[0003] During the process of inhaled general anesthesia, volatile drugs are delivered to the patient's lungs through the anesthesia machine. The drug concentration inhaled by the patient is determined by the fresh gas flow rate and the set drug concentration of the vaporizer. The time for the patient's alveolar gas drug concentration to reach the Minimal Alveolar Concentration (MAC) value is also affected by the ventilation frequency and tidal volume. Clinically, the maintenance of anesthesia requires an accurate judgment of the patient's anesthesia depth and drug target concentration first, and then manual adjustment of the drug administration concentration and ventilation parameter settings according to the needs of the anesthesia process. For inhaled anesthesia, this target is the alveoli, and the distribution of anesthetic drugs in the lungs cannot be monitored and known by any instrument. Therefore, this kind of evaluation often relies on the experience and knowledge of anesthesiologists. Although the traditional maintenance method can also meet the surgical needs, this process of empirical judgment + manual operation is a cumbersome task for doctors and will inevitably distract the doctor's energy in performing the surgery. To meet the intelligent requirements, it is necessary to develop a software tool for anesthesia ventilators, establish effective mathematical and physiological models, and calculate the absorption of anesthetic drugs in the patient's lungs, as well as the distribution and metabolism of drugs in the patient's body by receiving the settings and monitoring parameters of the anesthesia machine, so as to estimate the maintenance level of anesthesia and assist doctors in adjusting the drug dosage.

[0004] Clinically, anesthesiologists mostly rely on empirical knowledge and monitoring indicators such as heart rate, blood pressure, and bispectral index to infer the patient's consciousness level or anesthesia depth, and estimate the volatile drug concentration or supply rate based on this. To infer the target drug concentration, it is necessary to establish a mathematical model of the drug intake to metabolism process and solve it under the condition that the parameters have physiological significance. Currently, most of the automatic drug administration systems applied to control the anesthesia depth are based on the classical three-compartment pharmacokinetics / pharmacodynamics model. Such systems can only be used for intravenous anesthesia. This drug administration method is relatively stable and the model parameters are easy to calculate. However, the drug administration of inhaled anesthetics is affected by the parameter settings of the anesthesia ventilator, the patient's respiratory status, etc. The classical model is not applicable in this scenario. Summary of the Invention

[0005] The object of the present invention is to overcome the defects of the prior art and propose a method and system for estimating the target drug concentration of inhaled anesthesia.

[0006] To achieve the above object, the present invention proposes a method for estimating the target drug concentration of inhaled anesthesia, the method comprising:

[0007] Obtaining the parameters set by the anesthesia ventilator;

[0008] Obtaining the basic information of the patient;

[0009] Inputting the above data into a pre-established dynamic equation, and using the Runge-Kutta algorithm to calculate the drug concentration inhaled at the patient's mouth end, the alveolar drug concentration and the effect concentration, so as to realize the estimation of the target drug concentration;

[0010] The dynamic equation is based on the diffusion process of the anesthesia ventilator breathing circuit and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the basic information of the patient and the parameters set by the anesthesia ventilator.

[0011] As an improvement of the above method, the parameters set by the anesthesia ventilator include:

[0012] Fresh gas flow rate Q0, unit: L / min; drug concentration C0 input into the breathing circuit, unit: vol%; respiratory rate f, unit: 1 / min, tidal volume V t , unit: L.

[0013] As an improvement of the above method, the basic information of the patient includes: the gender G of the patient, where, for male, G = 1, for female, G = 0; age y, height h, unit: meter, and weight m, unit: kilogram.

[0014] As an improvement of the above method, the dynamic equation satisfies the following formula:

[0015]

[0016] Wherein, C ins , C1, C eff respectively represent the drug concentration inhaled at the mouth end, the alveolar drug concentration and the effect concentration;

[0017] The subscript i takes values from 2 to 4, and C2, C3, and C4 respectively represent the residual concentrations of the drug in rich blood tissue, muscle and fat;

[0018] V0 represents the total volume of the anesthesia ventilator airway and the patient's lungs, which is a constant, and takes values from 7L to 8L;

[0019] ΔQ represents the flow rate lost due to the gas valve in the circuit, which is 0.1 times the fresh gas flow rate Q0, with the unit of L / min;

[0020] V d represents the dead space volume of the lung, with the unit of mL, and its value is 2.2 times the patient's body weight, where the unit of the patient's body weight is kg; V1 represents the functional residual capacity of the lung, estimated by BMI, with the unit of L;

[0021] Q2, Q3, and Q4 are the blood flow rates of the human rich blood tissue, muscle tissue, and adipose tissue respectively, with the unit of L / min; and they satisfy the following formula:

[0022] Q2 = 75% of the cardiac output

[0023] Q3 = 18% of the cardiac output

[0024] Q4 = 6% of the cardiac output

[0025] V2, V3, and V4 represent the total volumes of the human rich blood tissue, muscle tissue, and adipose tissue respectively, with the unit of L, and they satisfy the following formula:

[0026]

[0027]

[0028]

[0029] Among them, IBW is the ideal body mass index, and IBW = 22h 2 ;

[0030] λ0 represents the blood-gas partition coefficient of the inhaled anesthetic, which is determined by the drug type;

[0031] λ2 represents the liver / blood partition coefficient of the drug, λ3 represents the muscle / blood partition coefficient of the drug, and λ4 represents the fat

[0032] / blood partition coefficient of the drug, and they are all constants; k e0 is the drug elimination rate constant in the effect compartment; k 20 is a constant.

[0033] On the other hand, the present invention proposes a target drug concentration estimation system for inhaled anesthesia, and the system includes: a parameter acquisition module, an information acquisition module, and an output module; among them,

[0034] The parameter acquisition module is used to acquire the parameter settings of the anesthesia ventilator;

[0035] The information acquisition module is used to acquire the basic information of the patient;

[0036] The output module is used to input the above data into a pre-established dynamic equation, and calculate the drug concentration inhaled at the patient's mouth tip, the alveolar drug concentration, and the effect concentration by using the Runge-Kutta algorithm, so as to realize the estimation of the target drug concentration;

[0037] The dynamic equation is based on the diffusion process of the anesthesia ventilator breathing circuit and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the patient's basic information and the set parameters of the anesthesia ventilator.

[0038] As an improvement of the above system, the set parameters of the anesthesia ventilator include:

[0039] Fresh gas flow rate Q0, unit: L / min; drug concentration C0 input into the breathing circuit, unit: vol%; respiratory rate f, unit: 1 / min, tidal volume V t , unit: L.

[0040] As an improvement of the above system, the patient's basic information includes: the gender G of the patient, where for male, G = 1, and for female, G = 0; age y, height h, unit: meter, and weight m, unit: kilogram.

[0041] As an improvement of the above system, the dynamic equation satisfies the following formula:

[0042]

[0043] Among them, C ins , C1, C eff respectively represent the drug concentration inhaled at the mouth tip, the alveolar drug concentration, and the effect concentration; the subscript i represents the value range of 2 to 4, and C2, C3, and C4 respectively represent the residual drug concentrations in the rich blood tissue, muscle, and fat;

[0044] V0 represents the total volume of the anesthesia ventilator airway and the patient's lungs, which is a constant value, and the value range is 7L to 8L;

[0045] ΔQ represents the flow rate lost due to the air valve in the circuit, which is 0.1 times the fresh gas flow rate Q0, unit: L / min;

[0046] V d represents the dead space volume of the lungs, unit: mL, and the value is 2.2 times the patient's weight, and the patient's weight unit is kilogram; V1 represents the functional residual capacity of the lungs, estimated by BMI, unit: L;

[0047] Q2, Q3, and Q4 are the blood flow rates of the human rich blood tissue, muscle tissue, and fat tissue respectively, unit: L / min; and satisfy the following formula:

[0048] Q2 = 75% of the cardiac output

[0049] Q3 = 18% of cardiac output

[0050] Q4 = 6% of cardiac output

[0051] V2, V3, and V4 represent the total volumes of the well - vascularized tissue, muscle tissue, and adipose tissue of the human body, in liters, and satisfy the following formula:

[0052]

[0053]

[0054]

[0055] where IBW is the ideal body weight index, and IBW = 22h 2 ;

[0056] λ0 represents the blood - gas partition coefficient of the inhaled anesthetic, which is determined by the drug type;

[0057] λ2 represents the liver / blood partition coefficient of the drug, λ3 represents the muscle / blood partition coefficient of the drug, and λ4 represents the fat / blood partition coefficient of the drug, all of which are constants; k e0 is the drug elimination rate constant in the effect compartment; k 20 is a constant.

[0058] Compared with the prior art, the advantages of the present invention are as follows:

[0059] 1. The method of the present invention is applicable to anesthesia ventilators and volatile anesthetics;

[0060] 2. The model parameters established by this method have physiological significance and can adapt to the individual attributes of patients;

[0061] 3. The present invention can predict the time when the drug reaches equilibrium in the anesthesia circuit and the patient's respiratory system;

[0062] 4. The output of the present invention is the alveolar drug concentration of the patient, that is, the effective concentration of the anesthetic can be obtained. Brief Description of the Drawings

[0063] Figure 1 is a schematic diagram of the compartment model for the absorption and metabolism of inhaled anesthetic drugs involved in this method;

[0064] Figure 2 is the change trend of the inhaled concentration, alveolar concentration, and effective concentration throughout the process obtained by using the method of the present invention. Detailed Embodiments

[0065] ]Traditional methods for controlling the concentration of inhaled anesthetic drugs rely mostly on doctors' experience and intuition, and existing anesthesia drug delivery systems are only limited to intravenous anesthesia. In order to achieve precise target drug delivery of inhaled anesthetics, it is necessary to combine the diffusion process of inhaled anesthetics (such as isoflurane, sevoflurane, desflurane, etc.) in the breathing circuit of the anesthesia ventilator and the absorption and metabolism process in the human body, and establish a mathematical model that can accurately describe these two dynamic processes simultaneously. The input variables of this model are the tidal volume, respiratory rate, fresh gas flow rate, and set concentration of the vaporizer of the anesthesia ventilator, the model parameters are the patient's gender, age, height, and weight, and the output result of the model is the alveolar drug concentration or the effect-site concentration. The ultimate goal is to infer, through this model, the output that is instructive to anesthesiologists from the known input variables and parameters.

[0066] The technical solutions of the present invention will be described in detail below with reference to the accompanying drawings and embodiments.

[0067] Embodiment 1

[0068] Embodiment 1 of the present invention proposes a method for estimating the target drug concentration of inhaled anesthesia.

[0069] As Figure 1 shown, it is a compartment model of the absorption and metabolism of inhaled anesthetic drugs involved in this method, where each box represents different human tissues, mainly including the alveoli, rich-blood tissues (such as the liver, kidneys, etc.), muscle, fat, and the effect site (the brain). Inhaled anesthetic drugs mainly enter the human blood circulation through the alveoli, and then are distributed to various tissues, and also enter the alveolar gas through the blood circulation and are excreted from the human body. Therefore, the lung is the center of the entire compartment model. There is drug transfer between each tissue and the lung, and the transfer rates of each part are affected by multiple factors and vary greatly. The main purpose of this model is to describe this dynamic process and estimate the drug concentration in the alveoli or the effect site.

[0070] The specific steps are as follows:

[0071] Obtain the parameters set by the anesthesia ventilator; including: fresh gas flow rate Q0, unit: L / min; drug concentration C0 input into the breathing circuit, unit: vol%; respiratory rate f, unit: 1 / min, tidal volume V t , unit: L.

[0072] Obtain the basic information of the patient; including: the patient's gender (G, male: G = 1, female: G = 0), age (y), height (h, in meters), and weight (m, in kilograms),

[0073] Based on the diffusion process in the breathing circuit of the anesthesia ventilator and the absorption and metabolism process in the human body, establish a kinetic equation;

[0074] Combined with the parameters set by the anesthesia ventilator and the patient's basic information, the Runge-Kutta algorithm is used to perform a single-step solution of the kinetic equation to obtain the inhaled drug concentration at the patient's mouth end, the alveolar drug concentration, and the effect concentration, thereby realizing the estimation of the target drug concentration.

[0075] The following is a specific analysis:

[0076] First, establish the kinetic equation of the entire system model as follows:

[0077]

[0078] Secondly, obtain the input variables of the model. The meanings and determination methods of these input variables are as follows:

[0079] Q0: Fresh gas flow rate, set through the anesthesia machine interface, unit: L / min;

[0080] C0: Drug concentration input to the breathing circuit, set by the doctor operating the drug evaporation tank of the anesthesia machine, unit: vol%;

[0081] f: Respiratory rate, set through the anesthesia machine interface, unit: 1 / min;

[0082] V t : Tidal volume, set through the anesthesia machine interface, unit: L;

[0083] Then, obtain the parameters of the model. The parameters of this model are actually the patient's gender (G, male: G = 1, female: G = 0), age (y), height (h, in meters), and weight (m, in kilograms), and the parameters of the above differential equations are all calculated from these four items. The meanings and calculation methods of the parameters in the equations are as follows:

[0084] V0: Total volume of the entire respiratory system (including the airway of the anesthesia ventilator and the patient's lungs), usually a constant, about 7L to 8L;

[0085] ΔQ: Flow rate loss in the circuit due to valves, etc., generally 0.1 times the fresh gas flow rate Q0, unit: L / min;

[0086] Vd: Dead space volume of the lungs, which can be estimated by 2.2 times the body weight (kg), unit: mL;

[0087] V1: Functional residual capacity of the lungs, which can be estimated through the BMI index (Body Mass Index, BMI = m / h 2 ), unit: L;

[0088] Q2, Q3, and Q4 are the blood flow rates of blood-rich tissue, muscle tissue, and adipose tissue, respectively, measured in L / min. Q2, Q3, and Q4 account for approximately 75%, 18%, and 6% of cardiac output, respectively. Cardiac output can be estimated using age, gender, height, and weight (cardiac output = 5.84 + 0.08 BMI - 0.03y - 0.62g). V2, V3, and V4 represent the total volume of blood-rich tissue, muscle tissue, and adipose tissue, respectively, measured in L. Their relationship to IBW is:

[0089]

[0090]

[0091]

[0092] Among them, IBW is the ideal quality index, IBW = 22h 2 ;

[0093] λ0: blood gas partition coefficient of inhaled anesthetics, a constant determined by the type of drug;

[0094] λ2, λ3, λ4: Tissue / blood distribution coefficients of inhalation anesthetics, which are generally known constants.

[0095] λ2 represents the drug's liver / blood partition coefficient, λ3 represents the drug's muscle / blood partition coefficient,

[0096] λ4 represents the lipid / blood partition coefficient of the drug.

[0097] k 20 : Constant, when sevoflurane or isoflurane is used, the value is 0.009;

[0098] Finally, the Runge-Kutta algorithm is used to solve the above differential equations in a single step, and finally C is obtained. ins , C1, C eff These three results, which are of great significance to anesthesiologists, represent the patient's oral inhaled drug concentration, alveolar drug concentration, and effect concentration (in the brain). C2, C3, and C4 in the equations represent the residual drug concentrations in blood-rich tissues, muscle, and fat, respectively. These three variables are considered intermediate variables in the overall system and are not outputs.

[0099] Drug metabolism processes may require more sophisticated physiological modeling.

[0100] Figure 2These are the simulation results of the model for sevoflurane anesthesia. The fresh gas flow rate is set at 4 L / min, the initial drug administration concentration is 3%, the respiratory rate is 12 breaths per minute, the tidal volume is 0.5 L, and the drug administration concentration is set to 0 at the 15th minute. The curves in the figure show the changing trends of the inhaled concentration, alveolar concentration, and effect concentration throughout the process.

[0101] Example 2

[0102] Example 2 of the present invention proposes a target drug concentration estimation system for inhaled anesthesia, which is implemented based on the method of Example 1. The system includes: a parameter acquisition module, an information acquisition module, and an output module; wherein,

[0103] The parameter acquisition module is used to acquire the parameter settings of the anesthesia ventilator;

[0104] The information acquisition module is used to acquire the basic information of the patient;

[0105] The output module is used to input the above data into a pre-established dynamic equation, and use the Runge-Kutta algorithm to calculate the drug concentration inhaled at the patient's mouth end, alveolar drug concentration, and effect concentration, so as to achieve the estimation of the target drug concentration;

[0106] The dynamic equation is based on the diffusion process of the anesthesia ventilator breathing circuit and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the patient's basic information and the parameter settings of the anesthesia ventilator.

[0107] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the embodiments, those of ordinary skill in the art should understand that any modification or equivalent replacement of the technical solutions of the present invention does not depart from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the claims of the present invention.

Claims

1. A method for estimating the target drug concentration of inhaled anesthesia, the method comprising: Obtaining the parameters set by the anesthesia ventilator; Obtaining the basic information of the patient; Inputting the above data into a pre-established dynamic equation, and using the Runge-Kutta algorithm to calculate the drug concentration inhaled at the patient's mouth end, the alveolar drug concentration, and the effect concentration, so as to achieve the estimation of the target drug concentration; The dynamic equation is based on the diffusion process of the anesthesia ventilator breathing circuit and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the patient's basic information and the parameters set by the anesthesia ventilator; The parameters set by the anesthesia ventilator include: Fresh gas flow rate Q0, unit: L / min; drug concentration C0 input into the breathing circuit, unit: vol%; breathing frequency f, unit: 1 / min, tidal volume V t , unit: L; The basic information of the patient includes: the gender G of the patient, where for male, G = 1, and for female, G = 0; age y, height h in meters, and weight m in kilograms; The dynamic equation satisfies the following formula: Among them, C ins , C1, C eff respectively represent the drug concentration inhaled at the mouth end, the alveolar drug concentration, and the effect concentration; the subscript i takes values from 2 to 4, and C2, C3, and C4 respectively represent the residual concentrations of the drug in the blood-rich tissue, muscle, and fat; V0 represents the total volume of the anesthesia ventilator airway and the patient's lungs, which is a constant value, taking values from 7 L to 8 L; V t is the tidal volume, which is set through the anesthesia machine interface, with the unit of L; ΔQ represents the flow rate lost due to the air valve in the circuit, which is 0.1 times the fresh gas flow rate Q0, with the unit of L / min; V d represents the dead space volume of the lungs, with the unit of mL, taking a value of 2.2 times the patient's body weight, and the unit of the patient's body weight is kilograms; V1 represents the functional residual capacity of the lungs, which is estimated through BMI, with the unit of L; Q2, Q3, and Q4 are the blood flow rates of the human blood-rich tissue, muscle tissue, and fat tissue respectively, with the unit of L / min; the following formula is satisfied: Q2 = 75% of the cardiac output Q3 = 18% of the cardiac output Q4 = 6% of the cardiac output V2, V3, and V4 respectively represent the total volumes of the rich-blood tissue, muscle tissue, and adipose tissue in the human body, in liters, and satisfy the following formula: wherein, IBW is the ideal body weight index, and IBW = 22h 2 ; BMI is the body mass index; λ0 represents the blood-gas partition coefficient of the inhaled anesthetic, which is determined by the drug type; λ2 represents the liver / blood partition coefficient of the drug, λ3 represents the muscle / blood partition coefficient of the drug, and λ4 represents the fat / blood partition coefficient of the drug, all of which are constants; k e0 is the drug elimination rate constant in the effect compartment; k 20 is a constant.

2. A target drug concentration estimation system for inhaled anesthesia, characterized in that, The system includes: a parameter acquisition module, an information acquisition module, and an output module; wherein, The parameter acquisition module is used to acquire the parameter settings of the anesthesia ventilator; The information acquisition module is used to acquire the basic information of the patient; The output module is used to input the above data into a pre-established dynamic equation, and use the Runge-Kutta algorithm to calculate the drug concentration inhaled at the patient's mouth end, the alveolar drug concentration, and the effect concentration, so as to achieve the estimation of the target drug concentration; The dynamic equation is based on the diffusion process of the anesthesia ventilator breathing circuit and the absorption and metabolism process in the human body, and is a relational expression of three concentrations to be solved with the patient's basic information and the parameters set by the anesthesia ventilator; The parameters set by the anesthesia ventilator include: Fresh gas flow rate Q0, unit: L / min; drug concentration C0 input to the breathing circuit, unit: vol%; respiratory rate f, unit: 1 / min, tidal volume V t , unit: L; The basic information of the patient includes: the gender G of the patient, where for male, G = 1, and for female, G = 0; age y, height h in meters, and weight m in kilograms; The dynamic equation satisfies the following formula: Among them, C ins , C1, C eff respectively represent the drug concentration inhaled at the mouth end, the drug concentration in the alveoli, and the effect concentration; the subscript i represents the values from 2 to 4, and C2, C3, and C4 respectively represent the residual concentrations of the drug in the blood-rich tissue, muscle, and fat; V0 represents the total volume of the airway of the anesthesia ventilator and the patient's lungs, which is a constant value, and the value ranges from 7 L to 8 L; V t is the tidal volume, which is set through the anesthesia machine interface, and the unit is L; ΔQ represents the flow rate lost due to the air valve in the circuit, which is 0.1 times the fresh gas flow rate Q0, and the unit is L / min; V d represents the dead space volume of the lungs, and the unit is mL, and the value is 2.2 times the patient's body weight, and the unit of the patient's body weight is kilograms; V1 represents the functional residual capacity of the lungs, which is estimated by BMI, and the unit is L; Q2, Q3, and Q4 are respectively the blood flow rates of the human blood-rich tissue, muscle tissue, and fat tissue, and the unit is L / min; the following formula is satisfied: Q2 = 75% of the cardiac output Q3 = 18% of the cardiac output Q4 = 6% of the cardiac output V2, V3, and V4 respectively represent the total volumes of the rich-blood tissue, muscle tissue, and adipose tissue in the human body, in liters, and satisfy the following formula: Among them, IBW is the ideal body weight index, and IBW = 22h 2 ; BMI is the body mass index; λ0 represents the blood-gas partition coefficient of the inhaled anesthetic, which is determined by the drug type; λ2 represents the liver / blood partition coefficient of the drug, λ3 represents the muscle / blood partition coefficient of the drug, and λ4 represents the fat / blood partition coefficient of the drug, all of which are constants; k e0 is the drug elimination rate constant in the effect compartment; k 20 is a constant.

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