Anesthetic administration system, method for determining anesthetic dose, and anesthesia method

Abstract

This anesthesia method for general anesthesia before surgery comprises: a binaural beat provision step of providing binaural beats for induction of general anesthesia; an anesthetic dose calculation step of calculating, on the basis of the weight of a subject to be anesthetized, a reduced anesthetic dose according to the provision of the binaural beats; an anesthetic provision step of providing the calculated anesthetic dose; and a real-time monitoring step of monitoring whether the subject being anesthetized loses consciousness from the binaural beat provision step to the anesthetic provision step.

Description

Anesthetic administration system, anesthetic dosage determination method, and anesthesia method

[0001] The present invention relates to an anesthetic administration system, a method for determining anesthetic dosage, and an anesthetic method using the same, for increasing the efficiency of drugs used during anesthesia induction and reducing side effects. More specifically, the invention relates to an anesthetic administration system, a method for determining anesthetic dosage, and an anesthetic method that can reduce the amount of anesthetic required and stabilize the anesthesia induction process by providing a patient with a specific frequency of binaural beats prior to surgery.

[0002] Remimazolam is a new benzodiazepine anesthetic with rapid action and recovery and excellent hemodynamic stability. However, the optimal dose for anesthesia induction varies from person to person, and there is a risk of side effects such as hypotension when high doses are administered.

[0003] Propofol is widely used for the induction of general anesthesia, but it has side effects that can cause hypotension and reduced systemic vascular resistance in proportion to the administered dose.

[0004] Meanwhile, binaural beats are an auditory stimulation technique that induces brainwave entrainment by delivering different frequencies to each ear. Although they are known to reduce anxiety and the need for anesthetic, there is a lack of research on the specific effects of binaural beats during the anesthesia induction process.

[0005] Accordingly, the technical problem of the present invention is conceived from this point, and the objective of the present invention is to provide an anesthetic administration system, a method for determining anesthetic dosage, and an anesthetic method for reducing patient anxiety in a non-invasive manner before surgery, significantly reducing the dosage of anesthetic required for anesthesia induction to minimize the risk of hypotension caused by medication, and maximizing the efficiency of anesthesia induction.

[0006] An anesthesia method for preoperative general anesthesia according to the concept of the present invention comprises a binaural beat providing step for providing binaural beats to induce general anesthesia, an anesthetic dose calculation step for calculating a reduced anesthetic dose based on the body weight of the subject to anesthesia according to the binaural beat providing step, an anesthetic administration step for providing the calculated anesthetic dose, and a real-time monitoring step for monitoring whether the subject to anesthesia loses consciousness from the binaural beat providing step to the anesthetic administration step.

[0007] In one embodiment, in the step of providing the binaural beat, the binaural beat is provided by providing a first sound having a first frequency and a second sound having a second frequency to each of the two ears of the anesthetized subject, the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz, and the provision of the binaural beat may continue for 10 minutes or more and 40 minutes or less.

[0008] In one embodiment, the first frequency may be 431 Hz and the second frequency may be 432 Hz.

[0009] In one embodiment, in the step of calculating the anesthetic dose, the anesthetic is remimazolam, and the dose per unit body weight of the subject to anesthesia is set to 0.23 ± 0.05 mg / kg or more and 0.28 mg / kg or less, and the appropriate anesthetic dose can be calculated by multiplying the dose per unit body weight and the body weight of the subject to anesthesia.

[0010] In one embodiment, in the step of calculating the anesthetic dose, the calculated appropriate anesthetic dose may be 15 to 20% less than the normal dose without the provision of binaural beats.

[0011] In one embodiment, in the step of calculating the anesthetic dose, the anesthetic is propofol, and the dose per unit body weight of the subject to anesthesia is set to 1.56 mg / kg or less, and the appropriate anesthetic dose can be calculated by multiplying the dose per unit body weight by the body weight of the subject to anesthesia.

[0012] In one embodiment, in the step of providing the anesthetic agent, the anesthetic agent is propofol or remimazolam, and the administration rate of the anesthetic agent is 3 to 6 mg / kg / h, and in the real-time monitoring step, the condition of the subject to anesthesia and whether anesthesia is progressing are determined and displayed, and after the administration of the anesthetic agent, the time until loss of consciousness (LoC) may be 160 seconds or less.

[0013] In one embodiment, a binaural beat providing unit that provides binaural beats to both ears of an anesthetized subject;

[0014] An anesthetic administration system according to the concept of the present invention comprises a binaural beat providing unit that provides binaural beats to both ears of an anesthetic subject, an anesthetic dose calculation unit that calculates a reduced anesthetic dose based on the body weight of the anesthetic subject according to the provision of binaural beats, and a monitoring unit that monitors whether the anesthetic subject loses consciousness.

[0015] A method for determining an anesthetic dose according to the concept of the present invention comprises a binaural beat providing step for providing binaural beats to induce general anesthesia, and an anesthetic dose calculation step for calculating a reduced anesthetic dose based on the body weight of the subject to anesthesia according to the provision of binaural beats. In the step of providing binaural beats, the binaural beats are provided to each of the two ears of the subject to anesthesia, wherein the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz, and the provision of binaural beats is sustained for a period of 10 minutes or more and 40 minutes or less. In the step of calculating anesthetic dose, if the anesthetic is remimazolam, the dose per unit body weight of the subject to anesthesia is set to 0.23 ± 0.05 mg / kg or more and 0.28 mg / kg or less, and the appropriate anesthetic dose is calculated by multiplying the dose per unit body weight by the body weight of the subject to anesthesia. In the case where the anesthetic is propofol, the dose per unit body weight of the subject to anesthesia is set to 1.56 mg / kg or less, and the appropriate dose of the anesthetic is calculated by multiplying the dose per unit body weight by the body weight of the subject to anesthesia.

[0016] According to one aspect of the present invention, patient anxiety can be reduced by a non-invasive method prior to surgery, and the dose of anesthetic required during anesthesia induction can be significantly reduced, thereby minimizing the risk of hypotension caused by medication.

[0017] However, the effects of the present invention are not limited to the above effects and may be extended in various ways without departing from the spirit and scope of the present invention.

[0018] FIG. 1 is a schematic diagram showing an anesthetic administration system according to one embodiment of the present invention.

[0019] FIG. 2 is a flowchart illustrating an anesthesia method according to one embodiment of the present invention.

[0020] Figures 3a and 3b are diagrams showing the Integrated Standard for Clinical Trial Reporting (CSRT) flowcharts.

[0021] Figure 4 is a diagram showing the relative power of the delta (a), theta (b), alpha (c), and beta (d) bands before and 20 minutes after the application of binaural beats.

[0022] Figure 5 is a diagram comparing the patient characteristics of the binaural beats group and the control group with respect to the anesthetic propofol.

[0023] Figure 6 is a diagram comparing the results and effects related to general anesthesia in a group that applied binaural beats and a control group for the anesthetic propofol.

[0024] Figure 7 is a diagram comparing the patient characteristics of the group (B group) and the control group (Control group) that applied binaural beats to the anesthetic remimazolam.

[0025] Figure 8 is a diagram comparing the results and effects related to general anesthesia in a group that applied binaural beats and a control group for the anesthetic remimazolam.

[0026] Figure 9 is a diagram showing the results of electroencephalograms during anesthesia for the anesthetic remimazolam, the group to which binaural beats were applied, and the control group.

[0027] Terms including ordinal numbers, such as “first,” “second,” etc., may be used to describe various components, but said components are not limited by said terms, and said terms are used solely for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be named the second component, and similarly, the second component may be named the first component. The term “and / or” includes a combination of a plurality of related described items or any of a plurality of related described items.

[0028] In addition, terms such as "~part," "~unit," "~block," "~part," and "~module" may refer to a unit that processes at least one function or operation. For example, the above terms may refer to at least one piece of hardware such as an FPGA (field-programmable gate array) or ASIC (application specific integrated circuit), at least one piece of software stored in memory, or at least one process processed by a processor.

[0029] FIG. 1 is a schematic diagram showing an anesthetic administration system according to one embodiment of the present invention.

[0030] Referring to FIG. 1, the anesthetic administration system (100) may include a binaural beat providing unit (110), an anesthetic dosage calculation unit (120), an anesthetic providing unit (130), a monitoring unit (140), a control unit (150), an input unit (160), an output unit (170), a communication unit (180), and a storage unit (190).

[0031] The binaural beat providing unit (110) provides binaural beats to both ears of the subject under anesthesia. Here, binaural beats are a type of auditory stimulus that can reduce anxiety and the need for anesthetic through brainwave synchronization. Binaural beats are auditory stimuli that induce brainwave synchronization by presenting slightly different frequencies to both ears, and they serve to reduce anxiety and the need for anesthetic.

[0032] At this time, the binaural beat is provided by providing a first sound having a first frequency and a second sound having a second frequency to each of the two ears of the anesthetized subject, wherein the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz, and the provision of the binaural beat may continue for a period of 10 minutes or more and 40 minutes or less. In one embodiment, the first frequency may be 431 Hz and the second frequency may be 432 Hz.

[0033] The anesthetic dosage calculation unit (120) calculates a reduced anesthetic dosage based on the body weight of the subject to anesthesia and the provision of binaural beats. The anesthetic dosage calculation unit (120) can set the dosage per unit body weight of the subject to anesthesia according to the anesthetic used, and can calculate an appropriate dosage and an appropriate injection rate using the actual body weight of the subject to anesthesia and the ideal body weight calculated therefrom. For example, the anesthetic is remimazolam, and the dosage per unit body weight of the subject to anesthesia is set to 0.23 ± 0.05 mg / kg or more and 0.28 mg / kg or less, and the appropriate anesthetic dosage can be calculated by multiplying the dosage per unit body weight and the body weight of the subject to anesthesia. At this time, the calculated appropriate anesthetic dosage may be 15 to 20% less than the normal dosage without the provision of binaural beats. According to another embodiment, the anesthetic is propofol, and the dose per unit body weight of the subject to anesthesia is set to 1.56 mg / kg or less, and the appropriate dose of the anesthetic can be calculated by multiplying the dose per unit body weight by the body weight of the subject to anesthesia. At this time, the calculated appropriate dose of the anesthetic may be 15 to 20% lower than the normal dose without the provision of binaural beats.

[0034] The anesthetic supply unit (130) can control a device that physically injects an anesthetic according to a set protocol. For example, the anesthetic is propofol or remimazolam, the administration rate of the anesthetic is 3 to 6 mg / kg / h, and can be provided to the anesthetic subject in an appropriate anesthetic dose calculated by the anesthetic dose calculation unit (120).

[0035] The monitoring unit (140) monitors whether the anesthetized subject has lost consciousness. The monitoring unit (140) can monitor the condition of the anesthetized subject using non-invasive blood pressure measurement, electrocardiogram, and pulse oximeter. The depth of anesthesia can be evaluated by the Patient Status Index (PSI) measured using a SedLine® Brain Function Monitor (Masimo, Irvine, CA, USA), and loss of consciousness during anesthesia induction (LoC) can be determined by evaluating the response to a voice stimulus or eyelash reflex and PSI ≤ 50. Alternatively, it can be determined in combination through the event time required to achieve a state without an eyelash reflex and hemodynamic electroencephalogram (EEG) spectrum analysis.

[0036] The control unit (150) oversees the operation of the entire system and processes data between each component. The input unit (160) may be an interface through which medical staff input the patient's basic information and initial condition into the system. The output unit (170) may visually display the current progress status and analyzed result data in real time. The communication unit (180) may be responsible for data linkage and transmission with external medical devices (e.g., SedLine EEG devices). The storage unit (190) may store necessary audio files, patient data, anesthesia protocols, etc.

[0037] FIG. 2 is a flowchart illustrating an anesthesia method according to one embodiment of the present invention.

[0038] Referring to FIG. 2, the anesthesia method may include a binaural beat providing step (S100), anesthetic dose calculation step (S200), anesthetic providing step (S300), and a real-time monitoring step (S400).

[0039] In the binaural beat providing step (S100) above, binaural beats are provided for inducing general anesthesia. The binaural beats are provided by providing a first sound having a first frequency and a second sound having a second frequency to each of the two ears of the subject to anesthesia, wherein the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz, and the provision of the binaural beats may continue for a period of 10 minutes or more and 40 minutes or less.

[0040] In the above anesthetic dosage calculation step (S200), the reduced anesthetic dosage based on the binaural beat is calculated based on the body weight of the subject to anesthesia. At this time, the calculated appropriate anesthetic dosage may be 15 to 20% lower than the normal dosage without the binaural beat.

[0041] In the above anesthetic supply step (S300), the calculated anesthetic dose is provided. At this time, the administration rate of the anesthetic may be 3 to 6 mg / kg / h.

[0042] In the above real-time monitoring step (S400), the loss of consciousness of the subject to anesthesia is monitored from the binaural beat provision step to the anesthetic agent provision step. The state of the subject to anesthesia and whether anesthesia is progressing are determined and displayed, and the time until loss of consciousness (LoC) after administration of the anesthetic agent may be 160 seconds or less.

[0043] Figure 3A is a diagram showing the Comprehensive Standard for Clinical Trial Reporting (CSRT) flowchart for propofol. Figure 3B is a diagram showing the Comprehensive Standard for Clinical Trial Reporting (CSRT) flowchart for remimazolam. Figure 4 is a diagram showing the relative power of the delta (a), theta (b), alpha (c), and beta (d) bands before and 20 minutes after the application of binaural beats for the anesthetic propofol. Figure 5 is a diagram comparing the patient characteristics of the binaural beats group and the control group for the anesthetic propofol. Figure 6 is a diagram comparing the results and effects related to general anesthesia for the binaural beats group and the control group for the anesthetic propofol. Figure 7 is a diagram comparing the patient characteristics of the binaural beats group (B group) and the control group for the anesthetic remimazolam. Figure 8 is a diagram comparing the results and effects related to general anesthesia in a group that applied binaural beats and a control group for the anesthetic remimazolam. Figure 9 is a diagram showing the results of electroencephalogram (EEG) tests during anesthesia in a group that applied binaural beats and a control group for the anesthetic remimazolam.

[0044] Referring to Figures 3 through 9, the applicant randomly assigned patients scheduled for routine surgery under general anesthesia to listen to sounds through stereo headphones for 20 minutes in the pre-operative waiting room. During this time, the experimental group listened to binaural beats combining frequencies of 432 Hz and 431 Hz, while the control group listened to silence. Subsequently, 10 mg of propofol was administered every 15 seconds for anesthesia induction, and the loss of response to verbal commands (primary outcome variable), loss of eyelash reflex, and the attainment of a Patient Status Index (PSI) of 50 or less were observed. As a result of the study, the dose of propofol required for the loss of response to verbal commands was significantly lower in the binaural beat group than in the control group (average 87 mg vs. 105 mg), but no difference was found in the processed frontal lobe brainwaves or anxiety scores. In conclusion, binaural beats at a frequency of 1 Hz slightly reduced the dose of propofol required for general anesthesia induction but did not affect frontal lobe brainwaves or pre-operative anxiety levels.

[0045] This was a prospective, single-blind, randomized controlled trial involving patients aged 20 to 50 scheduled for routine surgery who met ASA physical grades 1-2. Patients were randomly assigned to a binaural beat group and a control group; the binaural beat group listened to a beat frequency of 1 Hz (a combination of 432 Hz and 431 Hz) to mimic the slow delta waves associated with propofol anesthesia, while the control group listened to a completely silent file for 20 minutes. Researchers attached a SedLine sensor to the forehead to monitor brainwave data and measured anxiety scores (VAS) before and after the intervention. Anesthesia induction was performed by administering 10 mg of propofol at 15-second intervals and monitoring the response.

[0046] A total of 69 patients (34 in the binaural beat group and 35 in the control group) were analyzed, and the baseline characteristics of the patients were similar between the two groups. The dose of propofol administered until the loss of response to verbal commands, the primary outcome variable, averaged 87 mg in the binaural beat group, which was statistically significantly lower than the 105 mg in the control group. The dose adjusted for actual body weight was also lower in the binaural beat group, but no statistically significant difference was observed when adjusted for ideal body weight (IBW). There were no differences between the groups regarding the secondary outcome variables of anxiety scores and relative electroencephalogram (EEG) power; however, the magnitude of the decrease in systolic blood pressure after tracheal intubation was greater in the binaural beat group than in the control group.

[0047] Specifically, at least 20 minutes prior to surgery, the patient arrived at the pre-operative waiting room. This waiting room was quiet, had a temperature of 23–24°C, was softly lit, and had no partitions. After gently wiping the patient's forehead with an alcohol swab, a SedLine® sensor (Sedline Inc., San Diego, CA, USA) was attached symmetrically to the forehead. Pre-anesthetic anxiety scores were evaluated using a Visual Analog Scale (VAS; 0–100 mm, unmarked scale; 0 = not anxious, 100 = very anxious). After having the patient wear stereo headphones (Bose QuietComfort® 45 Headphones, Bose Corporation, Framingham, MA, USA), a clinician unrelated to the invention played an audio file to the patient according to group assignment. For the binaural beat group, binaural beat files were generated at a beat frequency of 1 Hz using 432 Hz and 431 Hz. The applicant selected 1 Hz based on the fact that slow delta oscillations occur during propofol anesthesia.

[0048] A complete silent file was generated for the control group. Both the binaural beat file and the silent file were provided for 20 minutes. During the intervention period in the preoperative waiting room, raw data of the frontal lobe electroencephalogram (EEG) processed using a SedLine® device was monitored. The applicant used a SedLine EEG sensor equipped with six gel-coated electrodes consisting of four active channels, one reference channel, and one ground channel. The electrodes were attached to the forehead, and the ground and reference channels were positioned over the patient's nose. The raw data was received and analyzed as EDF files. The relative power of the alpha (8-12 Hz), theta (4-8 Hz), and delta (<4 Hz) bands in the processed EEG data was calculated using power spectrum analysis with Python 3.10.4 (Python Software Foundation, Wilmington, DE).

[0049] Headphones were removed when the patient arrived in the operating room. The anxiety score was then re-measured. Monitoring was initiated using an electrocardiogram, pulse oximeter, neuromuscular monitoring device, and non-invasive blood pressure and heart rate monitors. SedLine monitoring continued during anesthesia induction and surgery, but was reconnected to the operating room equipment. At this point, only Patient Status Index (PSI) values ​​were collected, and raw data was not collected. A venous catheter was inserted into the patient's forearm one day prior to surgery. A three-way valve was connected to the most proximal end of the venous catheter inserted in the patient's forearm to administer propofol as close as possible. The anxiety score was assessed using a Visual Analog Scale (VAS).

[0050] All patients received pre-oxygenation with oxygen at FiO2 1.0. To reduce venous irritation, 30 mg of 1% lidocaine was administered prior to the propofol injection. For anesthesia induction, 10 mg of propofol was administered via a 3-way valve at 15-second intervals for 5 seconds. Propofol was administered until three clinical signs were observed, including loss of response to the verbal command "open your eyes," loss of the eyelash reflex, and a PSI ≤50. If insufficient spontaneous breathing or loss of consciousness was confirmed, the anesthesiologist performed mechanical ventilation using a bag-valve mask system.

[0051] After three clinical signs were confirmed, remifentanil 3 ng ml-1, rocuronium 0.6 mg kg-1, and sevoflurane 3 vol% were administered at effective site concentrations in a Minto pharmacokinetic model (Agilia® SP TIVA; Fresenius Kabi, Bad Homburg, Germany). Tracheal intubation was performed when the PSI was ≤50 and the train-of-four count was 0. The anesthesia procedure was identical for both groups, and the anesthetic concentrations were adjusted to maintain the PSI between 25 and 50.

[0052] The dose of propofol administered until the response to the verbal command "Open your eyes" was lost was evaluated (primary outcome variable). The propofol dose was adjusted according to actual body weight and ideal body weight. Anxiety scores before and after the intervention and the difference between the two scores were measured. The relative power of the delta, theta, alpha, and beta bands of the frontal lobe EEG before and after the intervention was analyzed using two-way repeated measures ANOVA. Heart rate, systolic, diastolic, and mean blood pressure were measured before propofol administration and after tracheal intubation.

[0053] Categorical variables were presented as counts (percentages), while continuous variables were presented as the mean (standard deviation) or median (interquartile range) depending on the normality of the data distribution. Fisher's exact test was used to compare categorical variables. The Student t-test was used to compare continuous variables following a normal distribution, and the Mann-Whitney U test was used to compare variables following a non-normal distribution. Frontal lobe EEG data before and after binaural beat stimulation were analyzed using two-way repeated measures ANOVA.

[0054] All statistical analyses were performed using R software (version 4.1.3; R Foundation for Statistical Computing, Austria). A p-value less than 0.05 was considered statistically significant. When comparing two measurements of blood pressure and anxiety scores, Bonferroni correction was applied, with a significance level of p < 0.05 / 2. However, changes in blood pressure or anxiety scores themselves were considered significant if the p-value was less than 0.05.

[0055] In previous studies, the mean (standard deviation) of propofol doses that caused loss of response to verbal commands was 124 (23) mg. In the present invention, the sample size was calculated using the Student t-test. To detect a 15% difference (18.6 mg) in propofol dose, i.e., an effect size of 0.8, 34 patients were required in each group based on a significance level α=0.05 and a power of 0.9 in a two-sided test. Considering a dropout rate of 10%, it was planned to enroll 38 patients in each group.

[0056] After screening 150 patients, 76 suitable patients were identified, and 69 of them were analyzed. 34 patients were included in the binaural beat group and 35 in the control group. The characteristics of the patients were similar between the two groups (Fig. 6).

[0057] The propofol dose inducing loss of response to verbal commands, the primary outcome variable, was lower in the binaural beat group than in the control group (mean[standard deviation] 86

[0024] mg vs. 105

[0032] mg, mean difference -18 mg, 95% confidence interval -32–-5, P=0.009, Table 2). Even after adjusting for actual body weight, the propofol dose inducing loss of response to verbal commands remained lower in the bilateral beat group. However, after adjusting for ideal body weight, no statistically significant difference was observed between the two groups (Fig. 7).

[0058] There was no difference between groups in anxiety scores before and after intervention (Fig. 7). The decrease in systolic blood pressure after tracheal intubation was greater in the bilateral beat group than in the control group (mean [standard deviation] -26

[0020] mmHg vs. -16

[0020] mmHg; mean difference, -10; 95% confidence interval, -20–-1; P = 0.04, Fig. 7). No difference between groups was found in the relative power of the delta, theta, alpha, and beta bands in the treated frontal lobe EEG (Fig. 5).

[0059] Meanwhile, regarding remimazolam, the following experiments were conducted.

[0060] Seventy-two patients scheduled for general anesthesia were randomly assigned to a binaural sound group (Group B) and a control group. Group B listened to binaural sounds with a 1 Hz frequency difference for 30 minutes prior to surgery, while the control group did not. The results showed that Group B required a significantly lower dose of remimazolam for loss of consciousness compared to the control group (15.0 vs. 17.7 mg) and had a faster time to loss of response to verbal commands (140 vs. 168 seconds). Additionally, the incidence of hypotension was lower in Group B (6% vs. 28%), although there was no significant difference in electroencephalogram (EEG) analysis. In conclusion, binaural beats are an effective and non-invasive method for reducing the dose required for loss of consciousness, shortening the time required, and minimizing the occurrence of hypotension during anesthesia induction using remimazolam.

[0061] This was a randomized, prospective, double-blind, single-center study involving 72 patients aged 20–60 years with ASA physical grades 1–2. Patients were randomly divided into a binaural sound group (Group B) and a control group; Group B listened to binaural sounds with a 1 Hz frequency difference (431 Hz on the left, 432 Hz on the right) for 30 minutes in the pre-anesthesia treatment room. This was intended to mimic the slow delta waves commonly observed during anesthesia. Anesthesia induction was performed using a continuous infusion of remimazolam at a rate of 6 mg / kg / h, and verbal stimulation, loss of the eyelash reflex, and the attainment of a Patient Status Index (PSI) of 50 or less were evaluated. The primary outcome variable was the dose of remimazolam required for the loss of response to verbal stimulation.

[0062] A total of 72 patients were included in the final analysis, and demographic characteristics were similar between the two groups. Anxiety scores after wearing headphones were significantly lower in Group B than in the control group. The dose of remimazolam required for the loss of response to verbal stimuli was significantly lower in Group B (15.0 mg) compared to the control group (17.7 mg), and the dose per body weight was also lower in Group B. The time taken to loss of consciousness was also shorter in Group B than in the control group (140 seconds vs. 168 seconds). At the time of loss of the eyelash reflex, a lower dose of remimazolam was required in Group B, and the time was also shortened. The incidence of hypotension was significantly lower in Group B (6%) than in the control group (28%), and the frequency of antihypertensive drug use was also lower.

[0063] The application of preoperative binaural beats significantly reduced the dose of remimazolam required for loss of consciousness during anesthesia induction. It also shortened the time to loss of consciousness and reduced the frequency of hypotension during anesthesia induction. These dose-reducing effects are consistent with previous study results. In particular, shortening the anesthesia induction time by approximately 20 to 30 seconds may be clinically significant in alleviating patient anxiety. The reduction in remimazolam dosage enhanced patient safety by decreasing the occurrence of hypotension and the need for antihypertensive agents.

[0064] Specifically, no significant differences were observed between the two groups in age, gender distribution, height, weight, body mass index (BMI), and ASA physical condition score (Fig. 8). Anxiety scores were similar between the two groups before wearing headphones, but after wearing headphones, the anxiety score of Group B was significantly lower than that of the control group (3.0 ± 2.8 vs. 4.4 ± 2.5, P = 0.034).

[0065] The remimazolam dose required until no response to a voice stimulus occurred was significantly lower in group B than in the control group (15.0 ± 3.6 mg vs. 17.7 ± 4.5 mg, P = 0.006). Similarly, the remimazolam dose per unit of body weight was significantly lower in group B than in the control group (0.23 ± 0.05 mg / kg vs. 0.31 ± 0.18 mg / kg, P = 0.014).

[0066] The time to loss of consciousness was also shorter in group B than in the control group (140 ± 29 seconds vs. 168 ± 47 seconds, P = 0.003). Although the PSI at the time of loss of consciousness was higher in group B (76 ± 16 vs. 63 ± 16, P = 0.002), no significant difference was observed between the two groups in spectral edge frequency, mean blood pressure, or heart rate at this time.

[0067] Anxiety scores (0: no anxiety, 10: maximum anxiety) were evaluated before and after wearing headphones for 30 minutes. The remimazolam dosage and time to event (including absence of response to vocal stimulus or eyelash reflex, PSI ≤ 50) were evaluated.

[0068] Hemodynamic variables were also evaluated at the time of such events and when PSI dropped below 50. The relative power of PSI and electroencephalogram (EEG) was recorded using a SedLine brain function monitor. Data on hemodynamic variables, PSI, and relative power of EEG were collected and analyzed using open-source VitalRecorder software (version 1.13.9).

[0069] The primary outcome variable was the dose of remimazolam required to prevent a response to the negative stimulus.

[0070] According to a preliminary study, the dose of remimazolam required to prevent a response to a voice stimulus was 17.8 mg ± 5.1 mg. Assuming that the dose required in the binaural beat stimulation group would be 20% lower than in the control group, 36 patients per group were needed to achieve a power of 80%, considering a two-sided significance level of 0.025 and a dropout rate of 10%.

[0071] For continuous variables, comparisons between groups were performed using the Student t-test or Mann-Whitney U test based on the results of the normality test.

[0072] Categorical variables were compared using the chi-square test or Fisher's exact test. All analyses were performed using the intention-to-treat method. The statistical significance level was set at P < 0.05. Statistical analyses were performed using SPSS version 25 (IBM Corp., Armonk, NY, USA) and R software (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria).

[0073] Specific embodiments have been illustrated and described above. However, the invention is not limited to the embodiments described above, and those skilled in the art may make various modifications without departing from the essence of the technical concept of the invention as described in the following claims.

[0074] (Explanation of symbols)

[0075] 100: Anesthetic administration system 110: Bionic acoustic provider

[0076] 120: Dose calculation unit 130: Anesthetic dispensing unit

[0077] 140: Monitoring unit 150: Control unit

[0078] 160: Input section 170: Output section

[0079] 180: Communications Unit 190: Storage Unit

Claims

1. Regarding the anesthesia method for preoperative general anesthesia, A binaural beat providing step for providing binaural beats to induce general anesthesia; Anesthetic dosage calculation step for calculating a reduced anesthetic dosage based on the body weight of the anesthetic subject and the provision of binaural beats; A step of providing an anesthetic agent that provides a calculated dose of anesthetic agent; and An anesthesia method comprising a real-time monitoring step for monitoring whether the subject of anesthesia has lost consciousness from the binaural beat provision step to the anesthetic provision step.

2. In Paragraph 1, In the step of providing the binaural beats mentioned above, The binaural beat is provided by providing a first sound having a first frequency and a second sound having a second frequency to each of the two ears of the anesthetized subject, wherein the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz. An anesthesia method characterized by the provision of the above binaural beat lasting for 10 minutes or more and 40 minutes or less.

3. In Paragraph 2, An anesthesia method characterized in that the first frequency is 431 Hz and the second frequency is 432 Hz.

4. In Paragraph 1, In the above anesthetic dosage calculation step, The above anesthetic is remimazolam, and An anesthesia method characterized by setting the dose per unit body weight of the anesthesia subject to be 0.23 ± 0.05 mg / kg or more and 0.28 mg / kg or less, and calculating the appropriate anesthetic dose by multiplying the dose per unit body weight and the body weight of the anesthesia subject.

5. In Paragraph 4, In the above anesthetic dosage calculation step, An anesthesia method characterized in that the calculated appropriate anesthetic dose is 15 to 20% less than the normal dose without the provision of binaural beats.

6. In Paragraph 1, In the above anesthetic dosage calculation step, The above anesthetic is propofol, and An anesthesia method characterized by setting the dose per unit body weight of the subject to anesthesia to 1.56 mg / kg or less, and calculating the appropriate dose of anesthetic as the product of the dose per unit body weight and the body weight of the subject to anesthesia.

7. In Paragraph 6, In the above anesthetic dosage calculation step, An anesthesia method characterized in that the calculated appropriate anesthetic dose is 15 to 20% less than the normal dose without the provision of binaural beats.

8. In Paragraph 1, In the step of providing the anesthetic agent mentioned above, The above anesthetic is propofol or remimazolam, and The administration rate of the above anesthetic is 3 to 6 mg / kg / h, and In the above real-time monitoring step, It determines and displays the condition of the anesthesia subject and whether anesthesia is progressing, and An anesthesia method characterized by the time until loss of consciousness (LoC) after administration of the above anesthetic being 160 seconds or less.

9. A binaural beat providing unit that provides binaural beats to both ears of an anesthetized subject; An anesthetic dosage calculation unit that calculates a reduced anesthetic dosage based on the body weight of the anesthetic subject and the provision of binaural beats; and An anesthetic administration system comprising a monitoring unit for monitoring whether the anesthetic subject loses consciousness.

10. A binaural beat providing step for providing binaural beats for inducing general anesthesia; and It includes an anesthetic dosage calculation step that calculates a reduced anesthetic dosage based on the body weight of the anesthetic subject and the provision of binaural beats, and In the step of providing the binaural beats mentioned above, The binaural beat is provided by providing a first sound having a first frequency and a second sound having a second frequency to each of the two ears of the anesthetized subject, wherein the first frequency and the second frequency have a difference of 0.8 to 1.2 Hz. The provision of the above binaural beats continues for a period of 10 minutes or more and 40 minutes or less, and In the above anesthetic dosage calculation step, If the above anesthetic is remimazolam, The dose per unit body weight of the anesthetic subject is set to 0.23 ± 0.05 mg / kg or more and 0.28 mg / kg or less, and the appropriate anesthetic dose is calculated by multiplying the dose per unit body weight by the body weight of the anesthetic subject. If the above anesthetic is propofol, A method for determining an anesthetic dosage by setting the dosage per unit body weight of the anesthetic subject to 1.56 mg / kg or less, and calculating the appropriate anesthetic dosage by multiplying the dosage per unit body weight by the body weight of the anesthetic subject.

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