JP7450915B2 - Anesthesia assistance program, anesthesia assistance device, anesthesia assistance system and anesthesia assistance method - Google Patents

Description

The present invention relates to an anesthesia assistance program, an anesthesia assistance device, an anesthesia assistance system, and an anesthesia assistance method.

In the field of medicine, it is important for anesthesiologists to administer sedation, analgesia, and muscle relaxation during surgery, and for anesthesiologists to understand the degree of sedation, analgesia, and muscle relaxation during surgery. This is very important to prevent drug overdose.

In this case, sedation refers to the patient's lack of consciousness or memory, analgesia refers to the patient not feeling pain, and muscle relaxation refers to the patient's muscle contraction weakening to the extent that it does not interfere with the surgery. Regarding sedation, it is known that the degree of sedation is measured based on information from a BIS (Bispectral Index) monitor, and for analgesia, it is known that the degree of sedation is measured based on information from a BIS (Bispectral Index) monitor. An anesthesia auxiliary method for estimating the effective site concentration of analgesic has been proposed (for example, see Patent Document 1).

The anesthesia auxiliary method disclosed in Patent Document 1 utilizes the fact that there is a correlation between the effective site concentration Cn of an analgesic and the effective site concentration (esTEC) of a sedative, and calculates the effective site of an analgesic plotted over time. Calculate the regression curve f(x) for the concentration Cn and esTEC, and calculate the analgesia at the intersection of f(x) and y=a+δ, which is obtained by adding a predetermined width δ to the asymptote y=a of f(x). The effective site concentration Cn of the drug is determined as the analgesic concentration (esMIC) sufficient to reduce the required concentration of the sedative, and the esMIC tailored to each patient is estimated in real time, and the inter-individual variation and intra-individual variation are Estimate quantitative indicators of sedatives and analgesics to be administered to patients, taking into account variability.

JP2019-17730A

However, although the anesthesia auxiliary device of Patent Document 1 described above estimates quantitative indicators of sedatives and analgesics, it cannot estimate the degree of muscle relaxation. It is necessary to attach a muscle relaxation monitor and monitor the number of contractions by stimulating the nerve using four electrical stimulations. Muscle relaxation monitors require calibration for each patient, but because electrical stimulation causes pain for the patient, general anesthesia is usually induced to induce unconsciousness before administering muscle relaxants. When general anesthesia is started, breathing stops and manual ventilation is required; however, there is a high risk of difficulty in ventilation until the airway is secured by tracheal intubation, which is performed after administering a muscle relaxant, and the muscle relaxant monitor must be calibrated. The problem is that it is dangerous.

In addition, when determining the dose of muscle relaxant antagonists, the conventional method is to use a muscle relaxation monitor after surgery to determine the dose according to the state of muscle relaxation, but this method temporarily However, over time, the muscle relaxant transfers from extravascular tissues into the blood, causing muscle relaxation to reappear and leading to respiratory arrest. Additionally, in order to prevent this, a muscle relaxant antagonist is additionally administered at the discretion of the doctor, but sometimes a higher dose than the prescribed dose is administered, and the muscle relaxant is canceled and the muscle relaxant is reinstated. It cannot necessarily be said that the necessary and sufficient amount of the muscle relaxant antagonist has been administered to prevent the appearance of symptoms.

Accordingly, an object of the present invention is to provide an anesthesia assistance program, an anesthesia assistance device, an anesthesia assistance system, and an anesthesia assistance method that estimate the effective site concentration of a muscle relaxant in consideration of administration history.

In order to achieve the above object, one aspect of the present invention provides the following anesthesia assistance program, anesthesia assistance device, anesthesia assistance system, and anesthesia assistance method.

[1] Computer,
Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient, An anesthesia auxiliary program for functioning as an estimation means for estimating a change over time in an effect site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed.
[2] The estimating means further performs a pharmacokinetic simulation after the administration of the muscle relaxant and after the muscle relaxant antagonist has been administered, thereby estimating the patient's muscle relaxant, muscle relaxant antagonist, and these. The anesthesia auxiliary program according to [1], wherein the amount of the complex in the blood and body tissues is estimated over time to estimate the change over time in the effective site concentration of the muscle relaxant in the patient.
[3] Muscle relaxant index setting means for setting an effective site concentration of the muscle relaxant whose value indicating the degree of muscle relaxation of the patient corresponds to a value indicating recovery from muscle relaxation as a recovery concentration index of the muscle relaxant; ,
The said [[ Anesthesia assistance program described in [2].
[4] The estimating means performs the pharmacokinetic simulation after the administration of the muscle relaxant to estimate the remaining amount of the muscle relaxant in the patient's body, and estimates the amount of the muscle relaxant remaining in the patient's body based on the remaining amount of the muscle relaxant. The anesthesia auxiliary program according to [2] or [3], which determines the dose of the muscle relaxant antagonist to be administered.
[5] Based on the value indicating the degree of muscle relaxation of the patient obtained over time during the administration of a muscle relaxant, and the value of the effective site concentration of the muscle relaxant of the patient obtained over time. further functions as a muscle relaxant index setting means for setting an effective site concentration value of the muscle relaxant corresponding to a value indicating the target degree of muscle relaxation as a concentration index of the muscle relaxant for the patient;
The estimating means determines the dose of the muscle relaxant to be administered to the patient so that the effective site concentration of the muscle relaxant in the patient becomes a concentration index of the muscle relaxant. ] Anesthesia assistance program described in any of the following.
[6] Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient. and estimating means for estimating a change over time in the concentration of the muscle relaxant at the effect site of the patient after the administration of the muscle relaxant is completed.
[7] An anesthesia machine having a syringe pump for administering a muscle relaxant to a patient;
Anesthesia machine control means that controls the operation of the anesthesia machine and records the administration history of the muscle relaxant administered by the anesthesia machine, and performs a pharmacokinetic simulation based on the history of the dose of the muscle relaxant. The effective site concentration of the muscle relaxant in the patient and the amount of the muscle relaxant in the blood and body tissues are estimated over time to determine the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed. an anesthesia auxiliary device having an estimation means for estimating changes over time;
Anesthesia support system.
[8] Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient. An anesthesia auxiliary method for estimating a change over time in an effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed.

According to the inventions according to claims 1, 6, 7, and 8, it is possible to estimate the effective site concentration of a muscle relaxant in consideration of the administration history.
According to the invention according to claim 2, it is possible to estimate the temporal change in the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed and after the muscle relaxant antagonist has been administered.
According to the invention according to claim 3, the effective site concentration of the muscle relaxant at which the value indicating the degree of muscle relaxation of the patient becomes the value indicating recovery from muscle relaxation is set as the recovery concentration index of the muscle relaxant, and The dose of the muscle relaxant antagonist administered to the patient from the anesthesia machine can be controlled such that the effect site concentration is lower than the recovery concentration index.
According to the invention according to claim 4, after the administration of the muscle relaxant is completed, a pharmacokinetic simulation is performed to estimate the remaining amount of the muscle relaxant in the patient's body, and the muscle relaxant is administered to the patient based on the remaining amount of the muscle relaxant. The dose of muscle relaxant antagonist to be administered can be determined.
According to the invention according to claim 5, the value of the effective site concentration of the muscle relaxant corresponding to the value indicating the target degree of muscle relaxation is set as a concentration index of the muscle relaxant for the patient, and the value indicating the degree of muscle relaxation of the patient is The dose of the muscle relaxant administered to the patient can be determined such that the effective site concentration of the drug is indicative of the concentration of the muscle relaxant.

FIG. 1 is a schematic diagram showing an example of the configuration of an anesthesia assistance system according to an embodiment. FIG. 2 is a block diagram showing a configuration example of the anesthesia assisting device according to the embodiment. FIG. 3 is a diagram showing an example of the structure of muscle relaxant administration history information. FIG. 4 is a diagram showing a configuration example of muscle relaxant concentration history information. FIG. 5 is a diagram showing an example of the configuration of monitor value information. FIG. 6 is a diagram illustrating a configuration example of index information. FIG. 7 is a schematic diagram showing the model configuration of pharmacokinetic simulation. FIG. 8 is a graph diagram for explaining the muscle relaxant administration operation of the anesthesia auxiliary device. FIG. 9 is a graph diagram for explaining the operation of administering a muscle relaxant antagonist by the anesthesia auxiliary device. FIG. 10 is a flowchart showing an example of the muscle relaxant administration operation of the anesthesia auxiliary device. FIG. 11 is a flowchart showing an example of the muscle relaxant antagonist administration operation of the anesthesia auxiliary device.

[Embodiment]
(Configuration of anesthesia support system)
FIG. 1 is a schematic diagram showing an example of the configuration of an anesthesia assistance system according to an embodiment.

When administering a muscle relaxant to a patient 6 for general anesthesia, this anesthesia support system 8 is designed to prevent variations due to individual differences in age, height, weight, gender, etc. This is for estimating and presenting a dosage suitable for the patient 6, taking into account variations in pharmacokinetics (intra-individual variation) such as water content and cardiac output. It is also used to assist in administering a muscle relaxant at an appropriate dose to the patient 6, or to administer an appropriate dose of a muscle relaxant to the patient 6.

Furthermore, when administering the muscle relaxant antagonist to the patient 6 after surgery, the anesthesia auxiliary system 8 takes into account the dose of the muscle relaxant administered to the patient 6 and the inter-individual variation and intra-individual variation of the patient 6. , for estimating and presenting an appropriate dosage for patient 6. It is also used to assist in administering a dose of the muscle relaxant antagonist suitable for the patient 6, or to administer a dose of the muscle relaxant antagonist suitable for the patient 6.

The anesthesia support system 8 includes an anesthesia support device 1 which is a specially designed device or an information processing device such as a PC or a tablet terminal, which processes information, and an anesthesia support device 1 that processes information and administers anesthetic to the patient 6 intravenously. An anesthesia machine 2 for assisting an anesthetized patient 6 by administering breathing, etc., a monitor 3 for indicating the degree of sedation, biological information, and muscle relaxation of the patient 6, and an information processing device such as a PC or a tablet terminal. It has a terminal 4 that processes information. The anesthesia auxiliary device 1, anesthesia machine 2, monitor 3, and terminal 4 are operated by an anesthesiologist 7.

Note that anesthetics include sedatives, analgesics, and muscle relaxants. As the sedative, an intravenous anesthetic propofol is used as an example, but an inhalation anesthetic (sevoflurane, desflurane, etc.) may also be used. As the analgesic, the opioid analgesic remifentanil is used as an example, but fentanyl, morphine, etc. may also be used. As the muscle relaxant, rocuronium, a non-depolarizing muscle relaxant, is used as an example, but vecuronium or the like may be used. As an example of the muscle relaxant antagonist, Sugammadesk is used for rocuronium, but neostigmine or the like may also be used.

The anesthesia auxiliary device 1 calculates an appropriate dose for a patient 6 to whom anesthetic is administered for surgery, etc., based on the effective site concentration of the anesthetic and information obtained from the monitor 3, and displays the calculated dose on the display of the terminal 4. A CPU (Central Processing Unit) or It is equipped with electronic components such as a HDD (Hard Disk Drive) and flash memory. Note that the anesthesia auxiliary device 1 is placed in an operating room where a surgery is performed on the patient 6, but when configured as a server device, it may be placed in a remote location.

The anesthesia machine 2 includes a sedative pump 20 that is a syringe pump that can control the flow rate of administering a sedative to the patient 6, an analgesic pump 21 that is a syringe pump that can control the flow rate of analgesic that is administered to the patient 6, and a patient 6. A muscle relaxant pump 22 is a syringe pump that can control the flow rate of muscle relaxant administered to the patient 6, a muscle relaxant antagonist pump 23 is a syringe pump that can control the flow rate of the muscle relaxant administered to the patient 6, and 6, and a respirator 24 that assists in breathing. The muscle relaxant pump 22 and the muscle relaxant antagonist pump 23 adjust the flow rates of the syringe pumps according to the target blood concentration based on the control of the anesthesia auxiliary device 1 to achieve TCI (Target-CI) of the sedative for the patient 6. Controlled Infusion) administration.

Note that instead of operating the muscle relaxant pump 22 and the muscle relaxant antagonist pump 23 based on the control of the anesthesia auxiliary device 1, a TCI pump capable of administering TCI is used as the muscle relaxant pump 22 and the muscle relaxant antagonist pump 23. May be used. In this case, the muscle relaxant pump 22 and the muscle relaxant antagonist pump 23 periodically transmit information on the effective site concentration of the muscle relaxant and the muscle relaxant antagonist to the anesthesia auxiliary device 1. Further, the sedative pump 20 and the analgesic pump 21 periodically transmit information on the administration flow rate of the sedative and analgesic to the anesthesia auxiliary device 1.

The monitor 3 includes a biological monitor 31 that measures biological information such as an electrocardiogram, a blood pressure monitor, a pulse oximeter, and a BIS monitor that measures BIS (Bispectral Index) values, and a biological monitor 31 that is attached to the patient 6 and is contracted by nerve stimulation using quadruple stimulation. It has a muscle relaxation monitor 32 that measures the number of times.

The anesthesia auxiliary device 1, the anesthesia machine 2, and the monitor 3 are connected to each other through a dedicated line so that they can communicate with each other, but they may also be connected through a network 5 that connects the anesthesia auxiliary device 1 and the terminal 4. The network 5 may be a wired or wireless communication network, or may be a communication network such as an intranet or a LAN (Local Area Network).

In the above configuration, the anesthesia auxiliary device 1 estimates the effective site concentration of the muscle relaxant in the patient 6 after the muscle relaxant is administered to the patient 6, regardless of whether or not the muscle relaxant monitor 32 is calibrated. The terminal sets the corresponding effect site concentration as an index when the output of the relaxation monitor 32 reaches a value necessary and sufficient to maintain the muscle relaxation state, and administers the muscle relaxant so as not to exceed the index. Display on display section 4. Further, when the surgery is completed, the anesthesia auxiliary device 1 controls the anesthesia machine 2 to administer a muscle relaxant antagonist (this may be done by the doctor 7), and administers a muscle relaxant, a muscle relaxant antagonist, and a complex thereof. The amount of muscle relaxant in the blood and body tissues of the person is estimated, taking into consideration the movement between the two, and the output of the muscle relaxation monitor 32 is determined to be the muscle relaxation level value at which it is determined that the muscle relaxation state has been recovered. The corresponding effect site concentration at the time of 0 is set as an index, and a message is displayed on the display section of the terminal 4 to instruct the administration of the muscle relaxant antagonist so that the concentration does not exceed the index.

The doctor 7 checks the information displayed on the display section of the terminal 4 and adjusts the dosage of the anesthetic and the like. Further, the anesthesia auxiliary device 1 may control the muscle relaxant pump 22 and the muscle relaxant antagonist pump 23 based on the set index as necessary to control the amount of anesthetic administered to the patient 6. good.

Note that all or part of the functions of the anesthesia auxiliary device 1, anesthesia machine 2, monitor 3, and terminal 4 may be integrated, or some or all of the functions of each device may be included in other devices. good. Further, all or part of the functions of the anesthesia auxiliary device 1, the anesthesia machine 2, and the monitor 3 may be operated by equipment located at a remote location. Alternatively, a plurality of anesthesia machines 2 and monitors 3 may be associated with the anesthesia auxiliary device 1, and the anesthesia auxiliary device 1 may simultaneously perform a plurality of anesthesia auxiliary operations. Alternatively, a plurality of anesthesia assisting devices 1 may be associated with the terminal 4, and a plurality of anesthesia assisting operations may be performed from the terminal 4 at the same time.

(Configuration of anesthesia auxiliary device)
FIG. 2 is a block diagram showing a configuration example of the anesthesia assisting device 1 according to the embodiment.

The anesthesia auxiliary device 1 includes a control unit 10 that is composed of a CPU and the like and controls each unit and executes various programs, a storage unit 11 that is composed of a storage medium such as an HDD or a flash memory and stores information, and an external It includes a communication section 12 that communicates with the device.

The control unit 10 executes an anesthesia auxiliary program 110, which will be described later, to control the anesthesia machine control means 100, the muscle relaxant concentration estimation means 101, the monitor value acquisition means 102, the muscle relaxant index setting means 103, the display processing means 104, etc. functions as

The anesthesia machine control means 100 controls the administration flow rate of each of the sedative pump 20, the analgesic pump 21, the muscle relaxant pump 22, and the muscle relaxant antagonist pump 23 of the anesthesia machine 2. In this embodiment, since the muscle relaxant pump 22 is a syringe pump, the anesthesia machine control means 100 estimates the administration flow rate from the target blood concentration of the muscle relaxant by pharmacokinetic simulation, and specifies the administration flow rate. to control the administration flow rate of the muscle relaxant. Note that when the muscle relaxant pump 22 has a function of determining the administration flow rate from the target blood concentration, the anesthesia machine control means 100 specifies the target blood concentration of the muscle relaxant, and any configuration may also be used. Furthermore, since the muscle relaxant antagonist pump 23 is a syringe pump, the anesthesia machine control means 100 estimates the administration flow rate from the target blood concentration of the muscle relaxant by pharmacokinetic simulation, and specifies the administration flow rate to induce muscle relaxation. Control the antagonist administration flow rate. Further, the anesthesia machine control means 100 records the dose of the administered muscle relaxant in the storage unit 11 as muscle relaxant administration history information 111. Note that the sedative pump 20 and the analgesic pump 21 are not essential components, and may be used to manually administer sedatives and analgesics.

The muscle relaxant concentration estimating means 101 calculates the blood concentration of the muscle relaxant and the effective site concentration Croc(es) from the administration flow rate of the muscle relaxant being administered by the muscle relaxant pump 22 of the anesthesia machine 2 through pharmacokinetic simulation. and the amount in the body tissue (second compartment, third compartment) is calculated. In addition, the muscle relaxant concentration estimating means 101 calculates the blood concentration of the muscle relaxant, the effective site concentration value Croc(es), and the amount in the body tissue (second compartment, third compartment) along with time. It is recorded in the history information 112.

The muscle relaxant concentration estimating means 101 calculates the blood concentration of the muscle relaxant antagonist in the body tissue (in body tissue 2 compartment, 3rd compartment). Furthermore, the muscle relaxant concentration estimating means 101 calculates the blood concentration and the amount in the body tissues (second compartment, third compartment) of the complex of the muscle relaxant and muscle relaxant antagonist by pharmacokinetic simulation.

The monitor value acquisition means 102 acquires a value output from the biological monitor 31 from the monitor 3 and a value output from the muscle relaxation monitor 32 (at least, a Train Of Four Count (TOFC), a Train Of Four Rate (TOFR)). , twitch ratio %T1) are periodically obtained. The monitor value acquisition means 102 records these values in the monitor value information 113 together with the acquisition time.

The muscle relaxant index setting means 103 determines the range (upper limit value and lower limit value) of the output value of the muscle relaxant monitor 32 that is necessary and sufficient as the degree of muscle relaxation and the range (lower limit value and lower limit value) of the corresponding concentration of the muscle relaxant at the effective site. upper limit value) and is recorded in the storage unit 11 as index information 114. Furthermore, the muscle relaxant index setting means 103 sets the output value (lower limit value) of the muscle relaxant monitor 32 necessary for recovery from muscle relaxation as an index of the effective site concentration value (upper limit value) of the corresponding muscle relaxant. , is recorded in the storage unit 11 as index information 114.

The display processing means 104 displays the dose of the muscle relaxant calculated by the muscle relaxant concentration estimating means 101, the effective site concentration value Croc(es), and the monitor value (twitch ratio %T1, All or an appropriately selected part of the four-reaction number TOFC, the four-reaction ratio TOFR, etc.) is displayed on the display unit of the terminal 4 in real time or including history and predicted values. The display method may be numerical, graphical, color, etc., but is not limited. Furthermore, the display processing means 104 may display all or all of the other values (values of the muscle relaxant, muscle relaxant antagonist, and complex) calculated by the muscle relaxant concentration estimating means 101.

The storage unit 11 stores an anesthesia auxiliary program 110 that causes the control unit 10 to operate as each of the above-mentioned means 100 to 104, muscle relaxant administration history information 111, muscle relaxant concentration history information 112, monitor value information 113, index information 114, etc. Remember.

FIG. 3 is a diagram showing an example of the structure of the muscle relaxant administration history information 111.

The muscle relaxant administration history information 111 includes a time and the amount of muscle relaxant administered at the time.

FIG. 4 is a diagram showing an example of the structure of the muscle relaxant concentration history information 112.

The muscle relaxant concentration history information 112 includes the time, the effective site concentration Croc(es) of the muscle relaxant at the time, the blood concentration, and the amount in the body tissue (second compartment, third compartment). In addition, the muscle relaxant concentration history information 112 includes the blood concentration of the muscle relaxant antagonist, the amount in the body tissues (second compartment, third compartment), and the blood concentration of the muscle relaxant and muscle relaxant antagonist complex. concentration, and amount in body tissues (second compartment, third compartment).

FIG. 5 is a diagram showing a configuration example of the monitor value information 113.

The monitor value information 113 includes the time, the number of quadruple reactions (TOFC) obtained by the muscle relaxation monitor 32, and the quadruple reaction ratio (TOFR).

FIG. 6 is a diagram showing a configuration example of the index information 114.

The index information 114 includes an index indicating the type of index and an effective site concentration value serving as the index.

(Operation of anesthesia auxiliary device)
Next, the action of this embodiment will be explained by dividing into (1) basic operation, (2) muscle relaxant administration operation, and (3) muscle relaxant administration operation.

(1) Basic operation First, after the patient 6 enters the operating room, the patient 6 is shown a BIS quattro sensor (manufactured by Govedien Japan, registered trademark) as a biological monitor 31, an electrocardiogram, a non-invasive blood pressure monitor, and a pulse monitor. Wear an oximeter. In addition, as the muscle relaxation monitor 32, a muscle relaxation monitor (AF-201P or AF-101P manufactured by Nihon Kohden Industries, Ltd.) capable of stimulating nerves by four-way electric stimulation is attached.

Next, an indwelling needle is inserted into the vein of the patient 6, and a sedative pump 20, an analgesic pump 21, a muscle relaxant pump 22, and a muscle relaxant antagonist pump 23 are connected, respectively. Additionally, a respirator 24 is attached to the patient 6.

(2) Muscle relaxant administration operation The doctor 7 operates the terminal 4 to start administering the anesthetic. The terminal 4 transmits a request to start administration of anesthetic to the anesthesia auxiliary device 1.

FIG. 10 is a flowchart showing an example of the muscle relaxant administration operation of the anesthesia auxiliary device.

The anesthesia machine control means 100 of the anesthesia auxiliary device 1 receives a request from the terminal 4 to start administration of anesthetic, controls the anesthesia machine 2 based on the set value, administers a sedative and an analgesic, and starts general anesthesia. (Step S1). Specifically, first, the anesthesia machine control means 100 controls the anesthesia machine 2 to administer oxygen at 6 l/min through the mask of the respirator 24 to perform oxygenation. Next, the anesthesia machine control means 100 controls the analgesic pump 21 to start administering remifentanil as an analgesic at 0.3-0.5 μg/kg/min, and then controls the sedative pump 20. , propofol is administered as a sedative at a target blood concentration of 3 μg/ml. After that, the anesthesia machine control means 100 applies the method described in Patent Document 1, for example, to appropriately control the sedative pump 20 and the analgesic pump 21 to administer the sedative and analgesic.

Next, after confirming that patient 6's name response has disappeared and the BIS value has become less than 70, doctor 7 administers rocuronium as an initial muscle relaxant, for example, 0.6 mg/kg ( Step S2, t=t ₁ in FIG. 8). Further, the anesthesia machine control means 100 records the dose of the muscle relaxant pump 22 together with the time in the muscle relaxant administration history information 111.

Thereafter, the muscle relaxant concentration estimating means 101 of the anesthesia auxiliary device 1 obtains the administration rate of the muscle relaxant pump 22 from the anesthesia machine control means 100 and calculates the effective site concentration Croc(es) of the muscle relaxant by pharmacokinetic simulation. The calculated effective site concentration value Croc(es) is recorded in the muscle relaxant concentration history information 112 along with the time (lower graph in FIG. 8). Further, the muscle relaxant concentration estimating means 101 estimates the concentration of the muscle relaxant in the blood (center compartment V1) and the amount in body tissues (second compartment V2, third compartment V3), and increases the concentration of the muscle relaxant with time. It is recorded in the history information 112. Note that the calculation operation of the muscle relaxant concentration estimating means 101 is performed as shown below.

FIG. 7 is a schematic diagram showing the model configuration for pharmacokinetic simulation.

As shown in FIG. 7, the muscle relaxant concentration estimation means 101 calculates the concentration of the muscle relaxant rocuronium in the blood (center compartment V1) and the amount in body tissues (second compartment V2, third compartment V3). The amount of the muscle relaxant rocuronium is calculated by taking into account the movement of the muscle relaxant rocuronium between Furthermore, the muscle relaxant concentration estimating means 101 takes into account the amount in the body tissue in the second compartment (V2) and the third compartment (V3), and is movable with the central compartment. Furthermore, the muscle relaxant concentration estimating means 101 calculates the blood concentration by the inflow (IV administration) of the muscle relaxant rocuronium, the combination (K1) or decomposition (K2) of the muscle relaxant antagonist sugammadex, and the excretion or decomposition. (excretion), the effective site concentration is calculated from the blood concentration.

In addition, in "(3) Muscle relaxant antagonist administration operation" described later, the muscle relaxant concentration estimating means 101 similarly calculates the blood concentration (center compartment V1), the body tissue (center compartment V1), and Regarding the amounts of the second compartment V2 and the third compartment V3), the amount of the muscle relaxant antagonist sugammadex is calculated by taking into account the movement of the muscle relaxant antagonist sugammadex between them. Furthermore, the muscle relaxant concentration estimating means 101 considers the amount in the body tissue in the second compartment V2 and the third compartment V3, and is movable with the central compartment. Furthermore, the muscle relaxant concentration estimating means 101 determines the blood concentration by the inflow (IV administration) due to administration of the muscle relaxant antagonist sugammadex, the combination (K1) or decomposition (K2) of the muscle relaxant rocuronium, and the excretion or decomposition (K2). (excretion).

In addition, in "(3) Muscle relaxant antagonist administration operation" described later, the muscle relaxant concentration estimating means 101 similarly calculates the blood concentration of the complex of the muscle relaxant rocuronium and the muscle relaxant antagonist sugammadex. Calculate the amount of the complex by considering the movement of the complex between (the central compartment V1), the amount in the body tissues (the second compartment V2, the third compartment V3), and excretion or decomposition (excretion). It is something.

Furthermore, the muscle relaxant concentration estimating means 101 considers K _e0 as excretion or decomposition regarding the effective site concentration.

Next, the monitor value acquisition means 102 acquires the BIS value from the monitor 3, the value output by the biological monitor 31, and the value output by the muscle relaxation monitor 32 (quadruple reaction number TOFC, quadruple reaction ratio TOFR), and The number of continuous reactions (TOFC) is defined as the muscle relaxation level (step S4). Further, the monitor value acquisition means 102 records these values together with the acquisition time in the monitor value information 113 (upper graph in FIG. 8).

FIG. 8 is a graph diagram for explaining the muscle relaxant administration operation of the anesthesia auxiliary device.

As shown in FIG. 8, in the upper graph, the horizontal axis represents time, and the vertical axis represents the magnitude of the response of the patient 6 to the muscle stimulation of the muscle relaxation monitor 32. The lower graph shares the same scale as the upper graph, with the horizontal axis representing time, and the effective site concentration Croc(es) of patient 6's muscle relaxant is shown on the vertical axis.

Next, the muscle relaxant index setting means 103 determines the range of the effective site concentration of the muscle relaxant ( lower limit value and upper limit value) and is recorded in the storage unit 11 as index information 114. Specifically, after the first administration of the muscle relaxant (t=t ₁ ), when the muscle relaxation level has recovered from %T1=0 to %T1=3% (t=TR1(t ₂ )), the muscle relaxant The effective site concentration Croc(es) is defined as an index Cr1 (for example, Cr1=1.4 μg/ml) (step S5). That is, the upper limit of the output value of the muscle relaxant monitor 32 is %T1=3%, and the lower limit of the effective site concentration of the muscle relaxant is Cr1. Note that %T1 is the rate of response to the first stimulus of the four consecutive stimuli.

Next, the anesthesia machine control means 100 controls the dose of the muscle relaxant pump 22 so as to maintain the effective site concentration of the muscle relaxant with the index Cr1 as the target value (S6). As a specific method for maintaining the muscle relaxant index setting means 103, the muscle relaxant index setting means 103 sets the effective site concentration of the muscle relaxant Croc when the number of quadruple reactions (TOFC) changes from 1 to 2 (t=TR2) as the muscle relaxation level. (es) is defined as the index Cr2 (upper limit) (for example, Cr2 = 0.5 μg/ml), and the anesthesia machine control means 100 controls the muscle relaxant so that the effective site concentration of the muscle relaxant is between Cr1 and Cr2. Controls the dosage of drug pump 22.

Under the control of the administration of sedatives and analgesics and muscle relaxants described above, doctor 7 administers sedatives, analgesics and muscle relaxants to patient 6, and doctor 7 or another doctor performs surgery on patient 6. I do.

(3) Muscle relaxant antagonist administration operation When the patient 6's surgery is completed, the doctor 7 finishes administering the sedative, analgesic, and muscle relaxant, and administers a muscle relaxant antagonist for the muscle relaxant. Operate the terminal 4 to prepare. The terminal 4 transmits to the anesthesia auxiliary device 1 the end of administration of the anesthetic and the start of administration of the muscle relaxant antagonist.

FIG. 11 is a flowchart showing an example of the muscle relaxant antagonist administration operation of the anesthesia auxiliary device.

The anesthesia machine control means 100 of the anesthesia auxiliary device 1 receives a request from the terminal 4 to end the administration of the anesthetic and to start administration of the muscle relaxant antagonist, and first, the muscle relaxant antagonist pump 23 is activated in order to administer the first muscle relaxant antagonist. (Step S11). The initial dose of the muscle relaxant antagonist is set to, for example, the recommended dose based on existing knowledge according to the muscle relaxant level of the patient 6 as a target value. Here, sugammadex is administered at 2 mg/ml as a muscle relaxant antagonist. In addition, the initial dose of the muscle relaxant antagonist is determined by the muscle relaxant concentration estimating means 101 performing a pharmacokinetic simulation based on the muscle relaxant administration history information 111, and determining the blood concentration of the muscle relaxant (center compartment V1), The amount in the body tissues (second compartment V2, third compartment V3) may be estimated, and the determination may be made based on the remaining amount of the muscle relaxant in each part.

Thereafter, the muscle relaxant concentration estimating means 101 of the anesthesia auxiliary device 1 acquires the administration rate of the muscle relaxant antagonist pump 23 from the anesthesia machine control means 100, and also obtains the administration rate of the muscle relaxant administered so far obtained from the muscle relaxant administration history information 111. A pharmacokinetic simulation is performed based on the administration history of the muscle relaxant, the muscle relaxant concentration history information 112 calculated so far by pharmacokinetic simulation, and the dose of the muscle relaxant antagonist being administered. The effect site concentration Croc(es) is calculated (step S12). Further, the muscle relaxant concentration estimating means 101 estimates the concentration of the muscle relaxant in the blood (center compartment V1) and the amount in the body tissues (second compartment V2, third compartment V3), and increases the concentration of the muscle relaxant with time. It is recorded in the history information 112. In addition, the muscle relaxant concentration estimating means 101 estimates the concentration of the muscle relaxant in the blood (center compartment V1) and the amount in the body tissues (second compartment V2, third compartment V3), and estimates the muscle relaxant antagonist with time. It is recorded in the density history information 112. In addition, the muscle relaxant concentration estimating means 101 estimates the concentration in the blood (center compartment V1) and the amount in body tissues (second compartment V2, third compartment V3) of a complex of a muscle relaxant and a muscle relaxant antagonist. and record it in the muscle relaxant concentration history information 112 along with the time.

Next, the monitor value acquisition means 102 acquires the BIS value, the value output by the biological monitor 31, etc. from the monitor 3, as well as the values output by the muscle relaxation monitor 32 (the number of quadruple reactions, the quadruple reaction ratio), and The reaction ratio is defined as a muscle relaxation level (step S13). Further, the monitor value acquisition means 102 records these values together with the acquisition time in the monitor value information 113 (the right vertical axis of the graph in FIG. 9).

FIG. 9 is a graph diagram for explaining the muscle relaxant antagonist administration operation of the anesthesia auxiliary device.

As shown in FIG. 9, the graph shows the effect site concentration Croc(es) of patient 6's muscle relaxant on the left vertical axis, with time on the horizontal axis. Furthermore, the quadruple response ratio of the patient 6 to muscle stimulation by the muscle relaxation monitor 32 is shown on the right vertical axis.

Next, the muscle relaxant index setting means 103 sets the output value of the muscle relaxant monitor 32 corresponding to the state recovered from the muscle relaxant state and the value of the corresponding effective site concentration of the muscle relaxant as an index (recovery concentration index, upper limit value) and is recorded in the storage unit 11 as index information 114. Specifically, after the first administration of the muscle relaxant antagonist (t=t _i (t ₃ )), when the muscle relaxation level has recovered to TOFR=100% (t=t _j (t ₄ )), the muscle relaxant The effective site concentration Croc(es) is defined as an index Cr3 (for example, Cr1=0.15 μg/ml) (step S14).

Next, the anesthesia machine control means 100 controls the dose of the muscle relaxant pump 23 so that the effective site concentration Croc(es) of the muscle relaxant is maintained as a target value without exceeding the index Cr3 (step S16). . As a specific method for maintaining the concentration, the muscle relaxant concentration estimating means 101 performs a pharmacokinetic simulation to determine the concentration of the muscle relaxant, muscle relaxant antagonist, and their complex in the blood (central compartment V1), in body tissues ( The effective site concentration Croc(es) is set as the target value by taking into account the amount of the second compartment V2, the third compartment V3) and the transition between these (seepage from body tissues, absorption into body tissues, etc.) and the index Cr3. The anesthesia machine control means 100 calculates the amount of the muscle relaxant antagonist such that the amount does not exceed , and causes the muscle relaxant pump 23 to administer the calculated amount of the muscle relaxant antagonist.

The muscle relaxant concentration estimating means 101 always performs pharmacokinetic simulations and calculates the concentration of muscle relaxants, muscle relaxant antagonists, and complexes thereof in blood (center compartment V1) and in body tissues (second compartment V2). , third compartment V3) and the movement between them (seepage from body tissues, absorption into body tissues, etc.) to calculate the effect site concentration Croc(es), Even before step S11 in which the antagonist is administered, the temporal change in the effective site concentration Croc(es) is estimated. That is, the attenuation curve of the effective site concentration Croc(es) before t=t _i shown in FIG. 9 and the attenuation curve of the effective site concentration Croc(es) shown by the broken line after t=t _i are estimated.

Under the administration control of the muscle relaxant antagonist described above, the doctor 7 administers the muscle relaxant antagonist to the patient 6, and when the muscle relaxant effect on the patient 6 disappears, the administration is finished, and the biological monitor 31, the muscle relaxant monitor 32, The ventilator 24 is removed from the patient 6, and the intravenous indwelling needles to which the sedative pump 20, analgesic pump 21, muscle relaxant pump 22, and muscle relaxant antagonist pump 23 are connected are removed to administer sedatives, analgesics, and muscle relaxants. Administration of drugs and muscle relaxant antagonists is discontinued.

According to the embodiment described above, the administration history of the muscle relaxant administered by the anesthesia machine control means 100 is recorded as the muscle relaxant administration history information 111, and the muscle relaxant concentration estimating means 101 records not only the effective site concentration but also Since the amount of the muscle relaxant in the blood and body tissues was estimated and recorded as the muscle relaxant concentration history information 112, changes over time in the concentration of the muscle relaxant at the effective site after the administration of the muscle relaxant in the blood, It can be estimated by considering the amount of muscle relaxant in body tissues. In addition, since information can be obtained about each case's sensitivity to muscle relaxants from the administration history and the course of muscle relaxation, the required amount of muscle relaxant antagonist can be calculated according to the relationship between body concentration and muscle recovery for each case. Ru.

In addition, since the muscle relaxant concentration estimating means 101 estimates the amount of muscle relaxants, muscle relaxant antagonists, and complexes thereof in the blood and body tissues, taking into account the movement between them, After administration of the muscle relaxant, the effect site concentration of the muscle relaxant after administration of the muscle relaxant antagonist can be estimated. Furthermore, by setting the effective site concentration at the time when the muscle relaxation level that is determined to be recovered from the muscle relaxation state by the muscle relaxation monitor as the index Cr3, the muscle relaxant in not only the blood but also the body tissues, Taking into consideration the muscle relaxant antagonist and their complexes, it becomes possible to estimate and control the administration of an appropriate amount of the muscle relaxant antagonist without excess or deficiency. Furthermore, since it is possible to antagonize muscle relaxants remaining in the body, the risk of delayed respiratory arrest due to relapse after muscle relaxant antagonism is suppressed.

Further, by setting the effective site concentration necessary and sufficient to maintain a muscle relaxation state as the index Cr1, and administering the muscle relaxant so as not to exceed the index Cr1, calibration of the muscle relaxation monitor becomes unnecessary. Conventionally, muscle relaxation monitors were calibrated during the time period from falling asleep to tracheal intubation when the risk of ventilation difficulties was high, so this time period can be omitted. Further, even if a muscle relaxant monitor is attached after administering a muscle relaxant, the estimation and control of this embodiment can be performed, and even if the muscle relaxant monitor is once removed, the present embodiment can be performed. estimation and control can be resumed.

[Other embodiments]
Note that the present invention is not limited to the embodiments described above, and various modifications can be made without departing from the spirit of the present invention.

In the embodiment described above, the functions of each means 100 to 104 of the control unit 10 are realized by a program, but all or part of each means may be realized by hardware such as an ASIC. Further, the programs used in the above embodiments can also be provided by being stored in a recording medium such as a CD-ROM. Further, the above steps explained in the above embodiments can be replaced, deleted, added, etc. without changing the gist of the present invention.

1: Anesthesia support device 2: Anesthesia machine 3: Monitor 4: Terminal 5: Network 6: Patient 7: Doctor 8: Anesthesia support system 10: Control unit 11: Storage unit 12: Communication unit 20: Sedative pump 21: Analgesic Pump 22 : Muscle relaxant pump 23 : Muscle relaxant antagonist pump 24 : Artificial ventilator 31 : Biological monitor 32 : Muscle relaxant monitor 100 : Anesthesia machine control means 101 : Muscle relaxant concentration estimation means 102 : Monitor value acquisition means 103 : Muscle relaxant index setting means 104: Display processing means 110: Anesthesia support program 111: Muscle relaxant administration history information 112: Muscle relaxant concentration history information 113: Monitor value information 114: Index information

Claims (7)

computer,
Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient, Estimating the change over time in the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed, and further administering the drug after the administration of the muscle relaxant is completed and the muscle relaxant antagonist is administered. By performing a dynamic simulation, the amount of the patient's muscle relaxant, muscle relaxant antagonist, and their complex in the blood and body tissues can be estimated over time, and the effective site concentration of the muscle relaxant in the patient can be estimated. Anesthesia auxiliary program to function as an estimator to estimate changes over time . computer,
muscle relaxant index setting means for setting, as a recovery concentration index of the muscle relaxant, an effective site concentration of the muscle relaxant whose value indicating the degree of muscle relaxation of the patient corresponds to a value indicating recovery from muscle relaxation;
Claim further configured to function as anesthesia machine control means for controlling the dose of the muscle relaxant antagonist administered to the patient from the anesthesia machine so that the effect site concentration estimated by the estimation means is lower than the recovery concentration index. The anesthesia assistance program described in 1 . The estimating means performs the pharmacokinetic simulation after completion of administration of the muscle relaxant to estimate the remaining amount of the muscle relaxant in the patient's body, and administers the muscle relaxant to the patient based on the remaining amount of the muscle relaxant. The anesthesia auxiliary program according to claim 1 or 2 , further comprising determining the dose of the muscle relaxant antagonist to be administered. computer,
During the administration of a muscle relaxant, a target is determined based on the value indicating the degree of muscle relaxation of the patient obtained over time and the value of the effective site concentration of the muscle relaxant of the patient obtained over time. further functioning as a muscle relaxant index setting means for setting the value of the effective site concentration of the muscle relaxant corresponding to the value indicating the degree of muscle relaxation as a concentration index of the muscle relaxant for the patient;
4. The estimating means determines the dose of the muscle relaxant to be administered to the patient such that the effective site concentration of the muscle relaxant in the patient is a concentration index of the muscle relaxant. or the anesthesia assistance program described in paragraph 1. Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient, Estimating the change over time in the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed, and further administering the drug after the administration of the muscle relaxant is completed and the muscle relaxant antagonist is administered. By performing a dynamic simulation, the amount of the patient's muscle relaxant, muscle relaxant antagonist, and their complex in the blood and body tissues can be estimated over time, and the effective site concentration of the muscle relaxant in the patient can be estimated. An anesthesia auxiliary device having an estimation means for estimating changes over time . an anesthesia machine having a syringe pump for administering a muscle relaxant to a patient;
Anesthesia machine control means that controls the operation of the anesthesia machine and records the administration history of the muscle relaxant administered by the anesthesia machine, and performs a pharmacokinetic simulation based on the history of the dose of the muscle relaxant. The effective site concentration of the muscle relaxant in the patient and the amount of the muscle relaxant in the blood and body tissues are estimated over time to determine the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed. After the administration of the muscle relaxant has been completed and the muscle relaxant antagonist has been administered, pharmacokinetic simulation is further performed to estimate the time course of the muscle relaxant, muscle relaxant antagonist, and combination thereof in the patient. an anesthesia auxiliary device having an estimation means for estimating the amount of blood and body tissue in the body over time to estimate a change over time in the concentration of the muscle relaxant at the effective site of the patient ;
Anesthesia support system equipped with Estimating the effective site concentration of the muscle relaxant and the amount of the muscle relaxant in the blood and body tissues of the patient over time by performing a pharmacokinetic simulation based on the history of the dose of the muscle relaxant to the patient, Estimating the change over time in the effective site concentration of the muscle relaxant in the patient after the administration of the muscle relaxant is completed, and further administering the drug after the administration of the muscle relaxant is completed and the muscle relaxant antagonist is administered. By performing a dynamic simulation, the amount of the patient's muscle relaxant, muscle relaxant antagonist, and their complex in the blood and body tissues can be estimated over time, and the effective site concentration of the muscle relaxant in the patient can be estimated. Anesthesia-assisted method for estimating changes over time .

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