Preoperative binaural beats reduce remimazolam dosage and enhance safety in anaesthesia induction: a randomised controlled trial

Preoperative binaural beats reduce remimazolam dosage and enhance safety in anaesthesia induction: a randomised controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Preoperative binaural beats reduce remimazolam dosage and enhance safety in anaesthesia induction: a randomised controlled trial Hyun-Chang Kim, Jin Young Sohn, Myoung Hwa Kim, Yoon Jung Kim, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7368631/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Binaural beats, a form of auditory stimulation, reduce anxiety and anaesthetic requirements through brainwave entrainment. Remimazolam offers advantages in terms of rapid onset and offset of action and hemodynamic stability. However, the optimal remimazolam dose for anaesthesia induction remains unclear and there are concerns regarding variability in response and potential side effects at higher doses. This study investigated the effects of preoperative binaural beats on the remimazolam dose required for loss of consciousness (LoC) during general anaesthesia induction. Methods: In this randomised, prospective, single centre study, 72 patients undergoing general anaesthesia were allocated to two groups: the binaural sound (B group) or the control group. The B group listened to binaural sounds (1-Hz frequency difference) for 30 min preoperatively, while the control group did not. Results: The B group required a significantly lower remimazolam dose for LoC (15.0 ± 3.6 vs. 17.7 ± 4.5 mg, P=0.006) and achieved LoC faster (140 ± 29 vs. 168 ± 47 s, P=0.003) than the control group. The incidence of hypotension was lower in the B group than in the control group (6 vs. 28%, P=0.024). Electroencephalography spectral analysis revealed no significant between-group differences. Conclusion: Binaural beats significantly reduced the remimazolam dose required for LoC and shortened the time to LoC, while reducing the incidence of hypotension during anaesthesia induction. Binaural beats are an effective, non-invasive method of enhancing efficiency and safety in anaesthesia induction when using remimazolam infusion. Trial Registration: This study was registered at ClinicalTrials.gov (NCT06099977; November 1, 2023). auditory stimulation brainwave entrainment general anaesthesia induction loss of consciousness remimazolam dosage Figures Figure 1 Background The quest for safer and more efficient methods of anaesthesia induction remains a challenge. Anaesthesia induction requires precise dosing of anaesthetic agents to achieve optimal sedation, while minimizing the risks associated with higher doses. Remimazolam, a novel benzodiazepine derivative, is a promising candidate because of its rapid onset and offset of action, offering potential advantages in terms of hemodynamic stability and reduced respiratory depression [ 1 – 3 ]. However, the optimal remimazolam dose for anaesthesia induction is still unclear, with concerns regarding individual variability in response and potential side effects at higher doses [ 4 – 7 ]. Binaural beats, a form of auditory stimulation involving slightly different frequencies presented to each ear, may reduce anxiety and anaesthetic requirements, potentially through brainwave entrainment or psychological relaxation [ 8 – 10 ]. While some evidence suggests binaural beats engage the brainstem’s superior olivary complex to produce a coherent neural response [ 11 ], their exact mechanism, whether through neural entrainment or anxiety reduction, remains unclear due to limited direct comparative studies [ 12 ]. This study investigates the effects of preoperative binaural beats on the remimazolam dose required for loss of consciousness (LoC) during general anaesthesia induction, to explore their potential to optimise sedation and to determine their underlying mechanisms, such as anxiety reduction or neural entrainment. We also aimed to elucidate whether the incorporation of binaural beats into the preinduction phase could optimise the sedative properties of remimazolam, thereby reducing the required dosage and associated risks. Methods This randomised, prospective, double-blind, single-centre, two-arm study was approved by the Investigative Review Board of Yonsei University Gangnam Severance Hospital in Seoul, Korea (document number: 2023-0759-001) on October 6, 2023. The study was registered at ClinicalTrials.gov (NCT06099977; November 1, 2023). Written informed consent was obtained prior to patient enrolment. Participants Patients with an American Society of Anesthesiologists (ASA) physical status of 1–2, aged 20–60 years, with an ideal bodyweight of 50–80 kg, and scheduled for general anaesthesia in November and December 2023 were included. The ideal bodyweight was calculated as follows: for men, 50 + 0.91 × (height in cm − 152.4), and for women, 45.5 + 0.91 × (height in cm − 152.4) [ 13 ]. Patients were excluded if they had a hearing disability; had used opioids or sedatives within the past week; were dependent on alcohol or drugs; had hypersensitivity to remimazolam; or had arrhythmia, cardiovascular disease, heart failure, hypovolemia, or liver failure. Randomisation and Intervention Seventy-two patients were randomly allocated to two groups (the binaural sound [B group] or no sound group [control group]) in a 1:1 ratio based on a computer-generated randomisation list, which was placed in a sealed opaque envelope. Patients in the B group used headphones to listen to real-time binaural sounds for 30 min in the anaesthesia pretreatment room. Real-time binaural sounds with a frequency difference of 1 Hz (431 Hz on the left side and 432 Hz on the right) were used. We selected a 1-Hz frequency difference based on the observation that slow delta oscillations are prevalent during anaesthesia [ 14 ]. Patients in the control group used headphones but listened to no sound for 30 min. The application of headphones and binaural beats was performed by a nurse who was not involved in the investigation. Anaesthetic Procedure The patients were transferred to the operating room, where they were monitored using non-invasive blood pressure measurement, electrocardiography, and pulse oximetry. The depth of anaesthesia was assessed using the Patient State Index (PSI), which was measured using a SedLine® brain function monitor (Masimo, Irvine, CA, USA). After preoxygenation with 100% oxygen, remimazolam was infused continuously at a rate of 6 mg/kg/h. LoC during anaesthesia induction was defined as the absence of response to vocal stimuli. Following LoC, continuous infusion of remifentanil was initiated with a target concentration of 4 ng/mL effect site concentration using the Minto pharmacodynamic model (Agilia SP TIVA; Fresenius Kabi, Bad Homburg, Germany) [ 15 ]. Additionally, rocuronium was administered at a dosage of 0.8 mg/kg. Tracheal intubation was performed after confirmation of complete muscle relaxation. Anaesthesia was maintained using sevoflurane, along with a continuous infusion of remifentanil and rocuronium. Hypotension was defined as a mean arterial pressure of < 65 mmHg or a decrease in mean arterial pressure by 20% from baseline. During the first 30 min after anaesthesia induction, hypotension was managed with vasopressors or inotropes at the discretion of the attending anaesthesiologist. The incidence of hypotension requiring vasopressor or inotrope treatment was recorded during the first 30 min after anaesthesia induction. Assessment and Data Collection The anxiety score (0, no anxiety; 10, maximum anxiety) was assessed before and after the 30-min headphone application period. The remimazolam dose and the time to events, including the absence of response to vocal stimuli or the eyelash reflex and PSI ≤ 50, were evaluated. The time to LoC was defined as the time taken to achieve the absence of response to vocal stimuli. Hemodynamic variables during these events, as well as when the PSI dropped to ≤ 50, were also assessed. The PSI and relative power of electroencephalography (EEG) were recorded using a SedLine brain function monitor. Data on hemodynamic variables, PSI, spectral edge frequency (SEF), and relative power of the EEG were collected and analysed using open-source VitalRecorder software (version 1.13.9) [ 16 ]. Relative EEG power was calculated as the percentage of power in each frequency band (alpha: 8–12 Hz, beta: 12–30 Hz, delta: 0.5–4 Hz, gamma: 30–100 Hz, theta: 4–8 Hz) relative to the total EEG power, averaged from 10-second intervals recorded by the SedLine® monitor and analysed using VitalRecorder software (version 1.13.9). Measurements were collected for 10 min before anaesthesia induction and from the start of remimazolam infusion until LoC, with normalisation based on the total power during each 10-s interval. Changes in relative EEG power were calculated as the post-anaesthesia induction values minus the pre-anaesthesia induction values for each group (binaural beats [B] group and control group). Positive values indicated an increase in relative power post-induction compared with pre-induction, while negative values indicated a decrease. Between-group differences in these changes (B group value minus control group value) were analysed and reported with 95% confidence intervals and P-values. Statistical Analyses The primary outcome was the remimazolam dose required to achieve an absence of response to vocal stimuli. Based on a preliminary, unpublished pilot investigation, the remimazolam dose necessary for the absence of vocal stimuli was 17.8 ± 5.1 mg. Assuming that the requirement would be 20% lower in the binaural beats group than in the control group, a sample size of 36 patients per group was necessary to achieve 80% power, with a two-sided significance level of 0.05 and a dropout rate of 10%. The assumption of a 20% lower remimazolam dose in the binaural beats group was based on an unpublished pilot study by our team, which found a mean dose of 17.8 ± 5.1 mg for the absence of vocal stimuli in a control group, combined with evidence from prior studies suggesting that binaural beats reduce anaesthetic requirements [ 9 , 10 ]. This 20% reduction was chosen as a conservative estimate for sample size calculation to achieve 80% power with a two-sided significance level of 0.05 and a 10% dropout rate. For continuous variables, two-way analysis of variance (ANOVA) was used to assess the effects of time (before vs. after anaesthesia induction) and group (binaural beats vs. control), followed by post-hoc Student’s t-tests or Mann–Whitney U tests, depending on normality assessed using Shapiro–Wilk tests. Continuous variables were presented as the mean ± standard deviation. Categorical variables were compared using the chi-squared test or Fisher’s exact test. All analyses were conducted on an intention-to-treat basis. Statistical significance was set at P < 0.05. Statistical analyses were performed using SPSS (version 25; IBM, Armonk, NY, USA) and R software (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria). Results Seventy-five patients were screened for inclusion in this study. Two patients were excluded owing to hearing disorders and one refused to participate. Therefore, 72 patients were included in the final analysis (Fig. 1 ). The demographic characteristics of patients in the B and control groups were comparable. No significant differences were observed in age, sex distribution, height, weight, body mass index, or ASA physical status between the two groups (Table 1 ). The anxiety scores before headphone application were similar between groups, but after headphone application, they were significantly lower in the B group than in the control group (3.0 ± 2.8 vs. 4.4 ± 2.5, P = 0.034). Table 1 Demographic characteristics B group (n = 36) Control group (n = 36) Age 47 ± 10 46 ± 12 Sex Male, % 13 (36%) 12 (33%) Height, cm 164 ± 7 164 ± 9 Weight, kg 66 ± 12 65 ± 14 Body mass index, kg/m 2 24 ± 4 24 ± 3 ASA physical status, 1/2 30 (83%)/6 (17%) 30 (83%)/6 (17%) Smoking, % 3 (8%) 3 (8%) Anxiety score Before headphone application 4.7 ± 2.7 4.7 ± 2.7 After headphone application 3.0 ± 2.8 4.4 ± 2.5 Surgery type Robotic prostatectomy 4 (11%) 5 (14%) Robotic cholecystectomy 6 (17%) 5 (14%) Robotic myomectomy 3 (8%) 6 (17%) Robotic gastrectomy 5 (14%) 3 (8%) Robotic ovarian cystectomy 7 (19%) 6 (17%) Robotic nephrectomy 4 (11%) 1 (3%) Others 7 (19%) 10 (28%) Anaesthesia time 174 ± 73 182 ± 76 B, binaural sound; ASA, American Society of Anesthesiologists. The B group received binaural sound through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction. The anxiety score was measured on a scale from 0 (no anxiety) to 10 (maximum imaginable anxiety). The dose of remimazolam required to achieve the absence of response to vocal stimuli was significantly lower in the B group than in the control group (15.0 ± 3.6 vs. 17.7 ± 4.5 mg, P = 0.006, Table 2 ). Similarly, the dose of remimazolam per unit bodyweight was significantly lower in the B group than in the control group (0.23 ± 0.05 vs. 0.31 ± 0.18 mg/kg, P = 0.014). The time to the absence of response to vocal stimuli was also shorter in the B group than in the control group (140 ± 29 vs. 168 ± 47 s, P = 0.003). Table 2 Variables of anaesthesia induction using remimazolam infusion B group (n = 36) Control group (n = 36) Difference (95% confidence interval) P value Cohen’s d Loss of consciousness (defined as absence of response to vocal stimuli) Remimazolam dose, mg 15.0 ± 3.6 17.7 ± 4.5 -2.7 (-4.6 to -0.8) 0.006 0.67 Remimazolam dose per unit bodyweight, mg/kg 0.23 ± 0.05 0.31 ± 0.18 -0.07 (-0.14 to -0.02) 0.014 0.60 Duration, s 140 ± 29 168 ± 47 -28 (-47 to -10) 0.003 0.73 Patient state index 76 ± 16 63 ± 16 12 (5–20) 0.002 0.76 Right spectral edge frequency 14 ± 6 15 ± 6 -1 (-4 to 2) 0.534 0.15 Left spectral edge frequency 14 ± 6 14 ± 5 0 (-3 to 2) 0.910 0.03 Mean blood pressure, mmHg 90 ± 19 88 ± 19 1 (-8 to 10) 0.785 0.06 Heart rate, bpm 79 ± 11 81 ± 13 -3 (-8 to 3) 0.372 0.21 In the absence of the eyelash reflex Remimazolam dose, mg 15.5 ± 3.7 18.4 ± 4.7 -2.6 (-4.9 to -0.9) 0.005 0.68 Remimazolam dose per unit bodyweight, mg/kg 0.24 ± 0.05 0.29 ± 0.07 -0.05 (-0.08 to -0.02) 0.001 0.82 Duration, s 146 ± 34 174 ± 45 -29 (-47 to -10) 0.003 0.73 Patient state index 73 ± 16 62 ± 15 12 (4–19) 0.003 0.72 Right spectral edge frequency 14 ± 6 15 ± 6 -1 (-4 to 2) 0.530 0.15 Left spectral edge frequency 14 ± 6 15 ± 5 0 (-3 to 2) 0.730 0.08 Mean blood pressure, mmHg 89 ± 19 87 ± 17 2 (-7 to 10) 0.645 0.11 Heart rate, bpm 79 ± 11 81 ± 14 -3 (-8 to 3) 0.395 0.20 In the patient state index ≤ 50 Remimazolam dose, mg 21.2 ± 6.1 22.2 ± 5.2 -1.0 (-3.7 to 1.6) 0.451 0.18 Remimazolam dose per unit bodyweight, mg/kg 0.32 ± 0.08 0.36 ± 0.10 -0.05 (-0.08 to -0.02) 0.142 0.35 Duration, s 228 ± 62 245 ± 101 -17 (-56 to 22) 0.389 0.20 Right spectral edge frequency 13 ± 5 15 ± 4 -2 (-4 to 0) 0.083 0.42 Left spectral edge frequency 13 ± 6 15 ± 4 -2 (-5 to 0) 0.089 0.41 Mean blood pressure, mmHg 89 ± 16 90 ± 15 -2 (-9 to 5) 0.618 0.12 Heart rate, bpm 77 ± 13 82 ± 14 -5 (-11 to 2) 0.137 0.36 At tracheal intubation Patient state index 42 ± 7 45 ± 7 -3 (-6 to 0) 0.079 0.42 Mean blood pressure, mmHg 106 ± 27 104 ± 23 2 (-10 to 14) 0.752 0.07 Heart rate, bpm 92 ± 11 95 ± 13 -3 (-9 to 3) 0.307 0.24 B, binaural sound. The B group received binaural sounds through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction. For the absence of eyelash reflex, the remimazolam dose was lower in the B group than in the control group (15.5 ± 3.7 vs. 18.4 ± 4.7 mg, P = 0.005), as was the dose per unit bodyweight (0.24 ± 0.05 vs. 0.29 ± 0.07 mg/kg, P = 0.001). The time to absence of eyelash reflex was shorter in the B group than in the control group (146 ± 34 vs. 174 ± 45 s, P = 0.003), and the PSI was higher (73 ± 16 vs. 62 ± 15, P = 0.003). No significant between-group differences were observed in the SEFs, mean blood pressure, or heart rate at this timepoint. When the PSI was ≤ 50, no significant difference was observed in the remimazolam dose between the two groups (21.2 ± 6.1 vs. 22.2 ± 5.2 mg, P = 0.451), although the dose per unit bodyweight tended to be lower in the B group than in the control group (0.32 ± 0.08 vs. 0.36 ± 0.10 mg/kg, P = 0.142). No significant differences were observed in the SEFs, mean blood pressure, or heart rate between the groups at this timepoint. During tracheal intubation, the PSI and hemodynamic variables (mean blood pressure and heart rate) did not differ significantly between the groups. Two-way ANOVA was conducted to evaluate the effects of time (before vs. after anaesthesia induction) and group (binaural beats vs. control) on relative EEG power across alpha, beta, delta, gamma, and theta bands. No significant interaction was observed between time and group for any frequency band (alpha: F(1,140) = 0.29, P = 0.589, η²ₚ = 0.002; beta: F(1,140) = 0.02, P = 0.896, η²ₚ = 0.0001; delta: F(1,140) = 0.001, P = 0.969, η²ₚ < 0.0001; gamma: F(1,140) = 0.40, P = 0.525, η²ₚ = 0.003; theta: F(1,140) = 0.41, P = 0.522, η²ₚ = 0.003). The main effect of time was significant for all bands (alpha: F(1,140) = 15.62, P < 0.001, η²ₚ = 0.10; beta: F(1,140) = 25.47, P < 0.001, η²ₚ = 0.15; delta: F(1,140) = 20.13, P < 0.001, η²ₚ = 0.13; gamma: F(1,140) = 8.92, P = 0.003, η²ₚ = 0.06; theta: F(1,140) = 5.67, P = 0.018, η²ₚ = 0.04), indicating changes in relative power post-induction. The main effect of group was not significant for any band (alpha: F(1,140) = 0.05, P = 0.821, η²ₚ = 0.0004; beta: F(1,140) = 0.09, P = 0.763, η²ₚ = 0.001; delta: F(1,140) = 0.03, P = 0.862, η²ₚ = 0.0002; gamma: F(1,140) = 0.02, P = 0.879, η²ₚ = 0.0001; theta: F(1,140) = 0.01, P = 0.920, η²ₚ = 0.0001). Post-hoc t-tests revealed no significant between-group differences in relative power before or after anaesthesia induction (Table 3 ). Before anaesthesia induction, the relative powers of the alpha, beta, delta, gamma, and theta waves did not differ significantly between the B and control groups. After induction of anaesthesia, no significant differences were observed in the relative power of these waves between groups. However, changes in the relative power before and after anaesthesia induction were significant for all wave types. The relative power difference before and after anaesthesia induction did not differ significantly between groups. The incidence of hypotension was significantly lower in the B group than in the control group (2 [6%] vs. 10 [28%], P = 0.024). The incidence of vasopressor use was lower in the B group than in the control group (2 [6%] vs. 10 [28%], P = 0.024). Table 3 Electroencephalography during anaesthesia induction B group (n = 36) Control group (n = 36) Difference (95% confidence interval) P value Cohen’s d Relative power before anaesthesia induction, % Alpha 3 ± 3 4 ± 5 -1 (-3 to 1) 0.346 0.24 Beta 4 ± 4 5 ± 5 -1 (-3 to 2) 0.614 0.14 Delta 77 ± 10 75 ± 12 2 (-4 to 7) 0.555 0.17 Gamma 2 ± 2 2 ± 2 0 (-1 to 1) 0.931 0.02 Theta 10 ± 3 10 ± 4 0 (-2 to 2) 0.954 0.01 Relative power after anaesthesia induction, % Alpha 8 ± 8 8 ± 8 -1 (-4 to 4) 0.956 0.01 Beta 17 ± 16 18 ± 17 0 (-8 to 7) 0.897 0.03 Delta 57 ± 25 58 ± 25 0 (-12 to 12) 0.965 0.01 Gamma 3 ± 2 2 ± 2 0 (-1 to 1) 0.546 0.17 Theta 9 ± 3 9 ± 3 0 (-1 to 2) 0.678 0.10 Relative power difference before and after anaesthesia induction Alpha 5 ± 7 4 ± 8 -3 to 5 0.589 0.13 Beta 13 ± 17 13 ± 18 -8 to 9 0.896 0.03 Delta -19 ± 25 -19 ± 28 -13 to 12 0.969 0.01 Gamma 1 ± 3 1 ± 3 -1 to 2 0.525 0.17 Theta -1 ± 3 -1 ± 4 -1 to 2 0.522 0.17 B, binaural sound. The B group received binaural sounds through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction. Discussion This study investigated the effects of preoperative binaural beats on the remimazolam dose required for LoC (absence of response to vocal stimuli) during general anaesthesia induction. Our results demonstrated that the preoperative application of binaural beats significantly reduced the dose of remimazolam required for LoC, as assessed by the response to vocal stimuli and the eyelash reflex. In addition, binaural beats reduced the incidence of hypotension during anaesthesia induction. Previous studies have demonstrated that binaural beats can reduce the requirements for anaesthetics and analgesics [ 9 , 10 , 12 ]. Our study extends these findings by being the first to investigate the effects of preoperative binaural beats on remimazolam, a novel ultra-short-acting benzodiazepine with rapid onset, offset, and favourable hemodynamic stability [ 1 – 3 ]. This is particularly significant given the limited data on optimizing remimazolam dosing during anaesthesia induction, where individual variability and potential side effects like hypotension remain concerns [ 4 – 7 ]. By demonstrating that binaural beats reduce the remimazolam dose required for LoC and the incidence of hypotension, our study introduces a non-invasive adjunct that enhances the safety and efficiency of remimazolam-based anaesthesia induction. Furthermore, while our EEG spectral analysis did not detect significant between-group differences in standard frequency bands (alpha, beta, delta, gamma, theta), the use of a 1-Hz binaural beat frequency suggests the potential for frequency-specific neural entrainment at 1 Hz, which was not explored in this study due to the focus on broader frequency bands [ 17 ]. Future investigations could incorporate targeted 1-Hz power analysis to assess whether binaural beats induce specific neural responses that further explain the observed reductions in remimazolam requirements, offering a novel avenue of examining brainwave entrainment mechanisms in anaesthesia. A practical challenge in using binaural beats during anaesthesia is the necessity for patients to wear headphones, which can be difficult if they are not supine. However, the application of binaural beats in the preoperative treatment room is relatively straightforward and practical. In our study, the administration of binaural beats before anaesthesia induction effectively reduced the required dose of remimazolam. Additionally, a reduction in the time to LoC of approximately 28 s could be clinically significant. Given that heightened anxiety during induction can prolong the process and adversely affect postoperative outcomes, including quality of life [ 8 , 18 ], this shorter induction time, combined with reduced preoperative anxiety, may contribute to a less stressful experience for patients. Furthermore, the preoperative use of binaural beats presents a non-invasive, user-friendly intervention that could improve patient outcomes by enhancing the efficiency and safety of anaesthesia induction. This approach aligns with ongoing efforts in anaesthesiology to minimise drug doses and enhance patient comfort and safety. Remimazolam is widely recognised for its safety profile, particularly its hemodynamic stability [ 2 , 3 ]. However, when administered at high doses, it can lead to significant hypotension, necessitating the use of vasopressors to maintain hemodynamic stability [ 1 ]. In our study, the preoperative application of binaural beats significantly reduced the incidence of hypotension requiring vasopressor intervention during anaesthesia induction. This reduction is likely attributable to the reduced dosage of remimazolam required when binaural beats are employed, as they have previously been shown to enhance the efficacy of anaesthesia agents, allowing for lower dosages. Vasopressors, which are effective in managing hypotension, are associated with risks and complications. Their use can lead to adverse effects, such as tachycardia, myocardial ischemia, and peripheral vasoconstriction, which pose significant risks, particularly in patients with pre-existing cardiovascular conditions [ 19 ]. Thus, minimizing the need for vasopressors through adjunctive measures such as binaural beats can be highly beneficial. Reduced hypotension may lessen the need for vasopressors and their associated risks, thereby enhancing overall safety and workflow efficiency. From this perspective, the incorporation of preoperative binaural beats into anaesthetic protocols holds promise for the enhancement of the safety of anaesthesia induction using remimazolam. Our analysis, which focused on standard frequency bands (alpha, beta, delta, gamma, theta), did not reveal significant between-group differences in EEG spectral power. Given this, the term “brainwave modulation”, which encompasses broader changes in neural activity or relaxation states without requiring specific frequency synchronisation, may more accurately describe the potential effects of binaural beats in our study. The lack of observed EEG changes could be attributed to the brief 30-min duration of binaural beat application, the focus on broad frequency bands rather than targeted 1-Hz power analysis, or insufficient statistical power to detect subtle variations [ 17 ]. While our EEG spectral analysis did not detect significant between-group differences in standard frequency bands (alpha, beta, delta, gamma, theta), a targeted analysis at the 1-Hz stimulation frequency could provide critical evidence for the hypothesised brainwave entrainment mechanism. Such an analysis was not performed in this study due to limitations in the EEG analysis configuration, which focused on broader frequency bands. Future studies should incorporate narrow-band spectral analysis or time-frequency decomposition targeting the 1-Hz frequency to determine whether binaural beats induce specific neural entrainment, potentially transforming our understanding of their role in optimizing anaesthesia induction. This could bridge a critical gap in the literature and establish a mechanistic foundation for the use of binaural beats in anaesthesiology. It is also possible that binaural beats primarily reduced remimazolam requirements through anxiety reduction, rather than direct neural entrainment. Future studies should extend the duration of binaural beat exposure and include frequency-specific analyses, such as 1-Hz power, to better elucidate the mechanisms by which binaural beats influence anaesthetic requirements. The lower anxiety scores in the binaural beats group suggest that anxiety reduction may reduce the required remimazolam dosage. A post-hoc correlation analysis (e.g., Pearson’s or Spearman’s) between post-headphone anxiety scores and the remimazolam dose could confirm this but was not conducted in this study. Future studies should explore this using our shared dataset (Mendeley Data, DOI: 10.17632/swxgj79jpy.2 ) to clarify the role of anxiety reduction in optimizing anaesthetic dosing. The absence of significant EEG changes in our study suggests that brainwave entrainment may not be the primary mechanism by which binaural beats reduce remimazolam requirements. This could be due to the brief 30-min exposure to 1-Hz binaural beats, which may be insufficient to induce detectable neural entrainment, or the lack of frequency-specific analysis targeting the 1-Hz stimulation frequency. Alternatively, the observed reduction in anxiety scores in the B group suggests that anxiety reduction may play a significant role in decreasing the required remimazolam dosage and time to LoC. Anxiety is known to increase anaesthetic requirements [ 8 ], and correlation of anxiety scores with remimazolam dosage in future studies could clarify this mechanism. Low-frequency binaural beats, such as the 1-Hz difference used in this study, have been shown to promote deep sleep or reduced consciousness [ 20 , 21 ]. It is possible that preoperative binaural beat exposure induced a sleep-like state, lowering the baseline level of consciousness and thus reducing the remimazolam dose required for LoC. This hypothesis warrants further investigation using objective sedation measures, such as the Ramsay Sedation Scale or polysomnography, to assess the depth of relaxation during the preoperative period. The current study had some limitations. First, we exclusively used binaural beats with a 1-Hz difference preoperatively. Given the variety of binaural beats and their varying effects, different types of binaural beats may exhibit distinct or even more potent effects on the induction of anaesthesia with remimazolam. Further research should explore the impact of other binaural-beat frequencies and patterns to identify potentially more effective options. Second, our study focused primarily on variables related to anaesthesia induction. It is plausible that preoperative binaural beats may also influence perioperative variables. However, this investigation specifically focused on the anaesthesia induction phase with remimazolam infusion. Future studies should assess the broader perioperative effects of binaural beats to provide a more comprehensive explanation of their effects. A third limitation is the lack of prioritised use of SEF in our analysis. Future studies should emphasise SEF as a primary metric for monitoring anaesthesia depth to better elucidate its role in optimizing remimazolam-based anaesthesia induction. Fourth, this study did not use the Ramsay Sedation Scale. Given the rapid progression of the study, its application was not feasible. In future studies conducted in settings with a slower pace, we plan to incorporate the Ramsay Sedation Scale for sedation assessment. Fifth, we were unable to compare the outcomes by sex and age. This should be addressed in future studies with larger sample sizes. Sixth, our findings are specific to the use of remimazolam and may not be generalizable to other anaesthetics. Further studies are warranted to confirm the benefits of binaural beats in patients receiving different anaesthetics for general anaesthesia induction. Seventh, we selected a 1-Hz frequency difference to align with the slow delta oscillations typically observed during anaesthesia [ 14 ]. However, other frequency differences might prove more effective in this context. Future studies comparing binaural beats to other auditory stimuli could help validate and refine this approach. Eighth, this study lacks a sham control, such as 0-Hz binaural beats, to account for general auditory input or placebo effects. While comparing binaural beats to no sound is informative, it does not fully isolate their specific effects. Previous studies suggest that binaural beats reduce anxiety, but without sham controls, placebo effects remain possible [ 8 , 22 ]. Future research should include sham conditions to confirm the unique effects of binaural beats on remimazolam dosage and hypotension. Ninth, our EEG spectral analysis focused on broader frequency bands (alpha, beta, delta, gamma, theta) and may not have been sensitive enough to detect frequency-specific neural responses at the 1-Hz stimulation frequency, as suggested by recent literature [ 17 ]. This could explain the lack of significant between-group differences in EEG patterns. Future studies should incorporate targeted analysis of spectral power at or around the stimulation frequency (e.g., 1 Hz) to better evaluate the neural entrainment hypothesis and elucidate the specific mechanisms underlying the observed effects of binaural beats on remimazolam dosage and anaesthesia induction outcomes. Tenth, we did not assess the participants’ ability to perceive the 1-Hz binaural beats. Low-frequency binaural beats, such as the 1-Hz difference used in this study, may not be uniformly perceptible, as reported by Fan et al [ 21 ]. Without verifying auditory perception, it is unclear whether the observed reductions in remimazolam dosage and time to LoC were directly attributable to brainwave entrainment or other mechanisms, such as relaxation or placebo effects. Future studies should incorporate subjective or electrophysiological measures (e.g., auditory steady-state responses) to confirm the perception of low-frequency binaural beats and validate their neural effects. Conclusions Our study suggests that the preoperative use of binaural beats may reduce the dose of remimazolam needed for LoC (the absence of response to vocal stimuli), shorten the time to achieve it, and potentially lower the incidence of hypotension during anaesthesia induction. These preliminary findings indicate that binaural beats could serve as a non-invasive adjunctive measure to support the efficiency and safety of anaesthesia induction, though further research with larger samples is needed to confirm these effects. Abbreviations LoC loss of consciousness ASA American Society of Anesthesiologists PSI Patient State Index EEG electroencephalography SEF spectral edge frequency ANOVA analysis of variance Declarations Ethics approval and consent to participate The studies involving human participants were approved by the Investigative Review Board of Yonsei University Gangnam Severance Hospital in Seoul, Korea (document number: 2023-0759-001). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Consent for publication Not applicable Availability of data and materials The datasets generated and/or analysed during the current study are available in Mendeley Data repository, https://data.mendeley.com/preview/swxgj79jpy?a=b175b9e4-0d0c-4863-9b02-2ae45b770356. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Department of Anesthesiology and Pain Medicine and Anesthesia and Pain Research Institute, Yonsei University College of Medicine. This research was supported by a special research grant funded by the Korean Society of Neuroscience in Anesthesiology and Critical Care (KSNACC-2024) and a new faculty research seed money grant from the Yonsei University College of Medicine for 2024 (2024-32-0075). Authors’ Contributions HCK: Conceptualization, formal analysis, funding acquisition, investigation, methodology, resources, software, supervision, validation, visualization, original draft, and review and editing. JYS: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing. MHK: Conceptualization, investigation, methodology, resources, visualization, original draft, and review and editing. YJK: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing. CHJ: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing. JHS: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, resources, software, supervision, validation, visualization, original draft, and review and editing. Acknowledgments We would like to thank Medical Illustration & Design (MID), a member of the Medical Research Support Services of Yonsei University College of Medicine, for providing excellent support with the medical illustrations. Authors’ information References Chae D, Kim HC, Song Y, Choi YS, Han DW. Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study. Br J Anaesth. 2022;129(1):49–57. Doi M, Hirata N, Suzuki T, Morisaki H, Morimatsu H, Sakamoto A. Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial. J Anesth. 2020;34(4):491–501. Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020;34(4):543–53. Monaco F, Bottussi A, Barucco G, D'Andria Ursoleo J. Remimazolam in Cardiac Anesthesia: Not So Ultra-short Acting After All. J Cardiothorac Vasc Anesth. 2025;39(1):327–8. D'Andria Ursoleo J, Bottussi A, Agosta VT, Monaco F. Letter to the editor regarding Effect of remimazolam versus propofol on hypotension after anesthetic induction in patients undergoing coronary artery bypass grafting: A randomized controlled trial. J Clin Anesth. 2024;99:111644. Pieri M, D'Andria Ursoleo J, Di Prima AL, Bugo S, Barucco G, Licheri M, Losiggio R, Frau G, Monaco F. Collaborators: Remimazolam for anesthesia and sedation in pediatric patients: a scoping review. J Anesth. 2024;38(5):692–710. D'Andria Ursoleo J, Licheri M, Barucco G, Losiggio R, Frau G, Pieri M, Monaco F. Remimazolam for anesthesia and sedation in cardiac surgery and for cardiac patients undergoing non-cardiac surgery: a systematic-narrative hybrid review. Minerva Anestesiol. 2024;90(7–8):682–93. Padmanabhan R, Hildreth AJ, Laws D. A prospective, randomised, controlled study examining binaural beat audio and pre-operative anxiety in patients undergoing general anaesthesia for day case surgery. Anaesthesia. 2005;60(9):874–7. Schmid W, Marhofer P, Opfermann P, Zadrazil M, Kimberger O, Triffterer L, Marhofer D, Klug W. Brainwave entrainment to minimise sedative drug doses in paediatric surgery: a randomised controlled trial. Br J Anaesth. 2020;125(3):330–5. Tani A, Vagheggini G, Moretti F, Del Colombo V, Lehle J, Campana S, Labate A, Tomaiuolo F. Binaural Beats Reduce Postoperative Morphine Consumption in Older adults After Total Knee Replacement Surgery. Altern Ther Health Med. 2021;27(2):27–30. Oster G. Auditory beats in the brain. Sci Am. 1973;229(4):94–102. Bae J, Yoo S, Kim H, Kim Y, Kim JT, Lim YJ, Kim HS. Effect of real-time binaural music on sedation with dexmedetomidine during spinal anesthesia: A triple-arm, assessor-blind, randomized controlled trial. J Clin Anesth. 2023;84:110997. Acute Respiratory Distress, Syndrome N, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–8. Bhattacharya S, Donoghue JA, Mahnke M, Brincat SL, Brown EN, Miller EK. Propofol Anesthesia Alters Cortical Traveling Waves. J Cogn Neurosci. 2022;34(7):1274–86. Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997;86(1):10–23. Lee HC, Jung CW. Vital Recorder-a free research tool for automatic recording of high-resolution time-synchronised physiological data from multiple anaesthesia devices. Sci Rep. 2018;8(1):1527. Ingendoh RM, Posny ES, Heine A. Binaural beats to entrain the brain? A systematic review of the effects of binaural beat stimulation on brain oscillatory activity, and the implications for psychological research and intervention. PLoS ONE. 2023;18(5):e0286023. Sadeghi A, Khaleghnejad Tabari A, Mahdavi A, Salarian S, Razavi SS. Impact of parental presence during induction of anesthesia on anxiety level among pediatric patients and their parents: a randomized clinical trial. Neuropsychiatr Dis Treat. 2017;12:3237–41. Cullen BF. Barash, Cullen, and Stoelting's clinical anesthesia, Ninth edition. edn. Philadelphia, PA: Wolters Kluwer; 2024. Jirakittayakorn N, Wongsawat Y. Brain Responses to a 6-Hz Binaural Beat: Effects on General Theta Rhythm and Frontal Midline Theta Activity. Front Neurosci. 2017;11:365. Fan Z, Zhu Y, Suzuki C, Suzuki Y, Watanabe Y, Watanabe T, Abe T. Binaural beats at 0.25 Hz shorten the latency to slow-wave sleep during daytime naps. Sci Rep. 2024;14(1):26062. Wahbeh H, Calabrese C, Zwickey H. Binaural beat technology in humans: a pilot study to assess psychologic and physiologic effects. J Altern Complement Med. 2007;13(1):25–32. Additional Declarations No competing interests reported. Supplementary Files FlowDiagram.jpg GraphicAbstractsBMC.tif CONSORT2010ChecklistBMC.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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for safer and more efficient methods of anaesthesia induction remains a challenge. Anaesthesia induction requires precise dosing of anaesthetic agents to achieve optimal sedation, while minimizing the risks associated with higher doses. Remimazolam, a novel benzodiazepine derivative, is a promising candidate because of its rapid onset and offset of action, offering potential advantages in terms of hemodynamic stability and reduced respiratory depression [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the optimal remimazolam dose for anaesthesia induction is still unclear, with concerns regarding individual variability in response and potential side effects at higher doses [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBinaural beats, a form of auditory stimulation involving slightly different frequencies presented to each ear, may reduce anxiety and anaesthetic requirements, potentially through brainwave entrainment or psychological relaxation [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. While some evidence suggests binaural beats engage the brainstem\u0026rsquo;s superior olivary complex to produce a coherent neural response [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], their exact mechanism, whether through neural entrainment or anxiety reduction, remains unclear due to limited direct comparative studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study investigates the effects of preoperative binaural beats on the remimazolam dose required for loss of consciousness (LoC) during general anaesthesia induction, to explore their potential to optimise sedation and to determine their underlying mechanisms, such as anxiety reduction or neural entrainment.\u003c/p\u003e\u003cp\u003eWe also aimed to elucidate whether the incorporation of binaural beats into the preinduction phase could optimise the sedative properties of remimazolam, thereby reducing the required dosage and associated risks.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This randomised, prospective, double-blind, single-centre, two-arm study was approved by the Investigative Review Board of Yonsei University Gangnam Severance Hospital in Seoul, Korea (document number: 2023-0759-001) on October 6, 2023. The study was registered at ClinicalTrials.gov (NCT06099977; November 1, 2023). Written informed consent was obtained prior to patient enrolment.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003ePatients with an American Society of Anesthesiologists (ASA) physical status of 1\u0026ndash;2, aged 20\u0026ndash;60 years, with an ideal bodyweight of 50\u0026ndash;80 kg, and scheduled for general anaesthesia in November and December 2023 were included. The ideal bodyweight was calculated as follows: for men, 50\u0026thinsp;+\u0026thinsp;0.91 \u0026times; (height in cm\u0026thinsp;\u0026minus;\u0026thinsp;152.4), and for women, 45.5\u0026thinsp;+\u0026thinsp;0.91 \u0026times; (height in cm\u0026thinsp;\u0026minus;\u0026thinsp;152.4) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients were excluded if they had a hearing disability; had used opioids or sedatives within the past week; were dependent on alcohol or drugs; had hypersensitivity to remimazolam; or had arrhythmia, cardiovascular disease, heart failure, hypovolemia, or liver failure.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRandomisation and Intervention\u003c/h3\u003e\n\u003cp\u003eSeventy-two patients were randomly allocated to two groups (the binaural sound [B group] or no sound group [control group]) in a 1:1 ratio based on a computer-generated randomisation list, which was placed in a sealed opaque envelope. Patients in the B group used headphones to listen to real-time binaural sounds for 30 min in the anaesthesia pretreatment room. Real-time binaural sounds with a frequency difference of 1 Hz (431 Hz on the left side and 432 Hz on the right) were used. We selected a 1-Hz frequency difference based on the observation that slow delta oscillations are prevalent during anaesthesia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Patients in the control group used headphones but listened to no sound for 30 min. The application of headphones and binaural beats was performed by a nurse who was not involved in the investigation.\u003c/p\u003e\n\u003ch3\u003eAnaesthetic Procedure\u003c/h3\u003e\n\u003cp\u003eThe patients were transferred to the operating room, where they were monitored using non-invasive blood pressure measurement, electrocardiography, and pulse oximetry. The depth of anaesthesia was assessed using the Patient State Index (PSI), which was measured using a SedLine\u0026reg; brain function monitor (Masimo, Irvine, CA, USA).\u003c/p\u003e\u003cp\u003eAfter preoxygenation with 100% oxygen, remimazolam was infused continuously at a rate of 6 mg/kg/h. LoC during anaesthesia induction was defined as the absence of response to vocal stimuli. Following LoC, continuous infusion of remifentanil was initiated with a target concentration of 4 ng/mL effect site concentration using the Minto pharmacodynamic model (Agilia SP TIVA; Fresenius Kabi, Bad Homburg, Germany) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Additionally, rocuronium was administered at a dosage of 0.8 mg/kg. Tracheal intubation was performed after confirmation of complete muscle relaxation. Anaesthesia was maintained using sevoflurane, along with a continuous infusion of remifentanil and rocuronium. Hypotension was defined as a mean arterial pressure of \u0026lt;\u0026thinsp;65 mmHg or a decrease in mean arterial pressure by 20% from baseline. During the first 30 min after anaesthesia induction, hypotension was managed with vasopressors or inotropes at the discretion of the attending anaesthesiologist. The incidence of hypotension requiring vasopressor or inotrope treatment was recorded during the first 30 min after anaesthesia induction.\u003c/p\u003e\n\u003ch3\u003eAssessment and Data Collection\u003c/h3\u003e\n\u003cp\u003eThe anxiety score (0, no anxiety; 10, maximum anxiety) was assessed before and after the 30-min headphone application period. The remimazolam dose and the time to events, including the absence of response to vocal stimuli or the eyelash reflex and PSI\u0026thinsp;\u0026le;\u0026thinsp;50, were evaluated. The time to LoC was defined as the time taken to achieve the absence of response to vocal stimuli. Hemodynamic variables during these events, as well as when the PSI dropped to \u0026le;\u0026thinsp;50, were also assessed. The PSI and relative power of electroencephalography (EEG) were recorded using a SedLine brain function monitor. Data on hemodynamic variables, PSI, spectral edge frequency (SEF), and relative power of the EEG were collected and analysed using open-source VitalRecorder software (version 1.13.9) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Relative EEG power was calculated as the percentage of power in each frequency band (alpha: 8\u0026ndash;12 Hz, beta: 12\u0026ndash;30 Hz, delta: 0.5\u0026ndash;4 Hz, gamma: 30\u0026ndash;100 Hz, theta: 4\u0026ndash;8 Hz) relative to the total EEG power, averaged from 10-second intervals recorded by the SedLine\u0026reg; monitor and analysed using VitalRecorder software (version 1.13.9). Measurements were collected for 10 min before anaesthesia induction and from the start of remimazolam infusion until LoC, with normalisation based on the total power during each 10-s interval. Changes in relative EEG power were calculated as the post-anaesthesia induction values minus the pre-anaesthesia induction values for each group (binaural beats [B] group and control group). Positive values indicated an increase in relative power post-induction compared with pre-induction, while negative values indicated a decrease. Between-group differences in these changes (B group value minus control group value) were analysed and reported with 95% confidence intervals and P-values.\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the remimazolam dose required to achieve an absence of response to vocal stimuli. Based on a preliminary, unpublished pilot investigation, the remimazolam dose necessary for the absence of vocal stimuli was 17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 mg. Assuming that the requirement would be 20% lower in the binaural beats group than in the control group, a sample size of 36 patients per group was necessary to achieve 80% power, with a two-sided significance level of 0.05 and a dropout rate of 10%. The assumption of a 20% lower remimazolam dose in the binaural beats group was based on an unpublished pilot study by our team, which found a mean dose of 17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 mg for the absence of vocal stimuli in a control group, combined with evidence from prior studies suggesting that binaural beats reduce anaesthetic requirements [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This 20% reduction was chosen as a conservative estimate for sample size calculation to achieve 80% power with a two-sided significance level of 0.05 and a 10% dropout rate.\u003c/p\u003e\u003cp\u003eFor continuous variables, two-way analysis of variance (ANOVA) was used to assess the effects of time (before vs. after anaesthesia induction) and group (binaural beats vs. control), followed by post-hoc Student\u0026rsquo;s t-tests or Mann\u0026ndash;Whitney U tests, depending on normality assessed using Shapiro\u0026ndash;Wilk tests. Continuous variables were presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Categorical variables were compared using the chi-squared test or Fisher\u0026rsquo;s exact test. All analyses were conducted on an intention-to-treat basis. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analyses were performed using SPSS (version 25; IBM, Armonk, NY, USA) and R software (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSeventy-five patients were screened for inclusion in this study. Two patients were excluded owing to hearing disorders and one refused to participate. Therefore, 72 patients were included in the final analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe demographic characteristics of patients in the B and control groups were comparable. No significant differences were observed in age, sex distribution, height, weight, body mass index, or ASA physical status between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The anxiety scores before headphone application were similar between groups, but after headphone application, they were significantly lower in the B group than in the control group (3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 vs. 4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5, P\u0026thinsp;=\u0026thinsp;0.034).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (36%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight, cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e164\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e164\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight, kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA physical status, 1/2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (83%)/6 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (83%)/6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore headphone application\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter headphone application\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic prostatectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic cholecystectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic myomectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic gastrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic ovarian cystectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic nephrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (28%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnaesthesia time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e174\u0026thinsp;\u0026plusmn;\u0026thinsp;73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e182\u0026thinsp;\u0026plusmn;\u0026thinsp;76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eB, binaural sound; ASA, American Society of Anesthesiologists. The B group received binaural sound through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction. The anxiety score was measured on a scale from 0 (no anxiety) to 10 (maximum imaginable anxiety).\u003c/p\u003e\u003cp\u003eThe dose of remimazolam required to achieve the absence of response to vocal stimuli was significantly lower in the B group than in the control group (15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 vs. 17.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 mg, P\u0026thinsp;=\u0026thinsp;0.006, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, the dose of remimazolam per unit bodyweight was significantly lower in the B group than in the control group (0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 vs. 0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 mg/kg, P\u0026thinsp;=\u0026thinsp;0.014). The time to the absence of response to vocal stimuli was also shorter in the B group than in the control group (140\u0026thinsp;\u0026plusmn;\u0026thinsp;29 vs. 168\u0026thinsp;\u0026plusmn;\u0026thinsp;47 s, P\u0026thinsp;=\u0026thinsp;0.003).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eVariables of anaesthesia induction using remimazolam infusion\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDifference (95% confidence interval)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eLoss of consciousness (defined as absence of response to vocal stimuli)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose, mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2.7 (-4.6 to -0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose per unit bodyweight, mg/kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.07 (-0.14 to -0.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration, s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e168\u0026thinsp;\u0026plusmn;\u0026thinsp;47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-28 (-47 to -10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient state index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (5\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRight spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 (-4 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.534\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-3 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.910\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (-8 to 10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.785\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rate, bpm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3 (-8 to 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.372\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eIn the absence of the eyelash reflex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose, mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2.6 (-4.9 to -0.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose per unit bodyweight, mg/kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.05 (-0.08 to -0.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.82\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration, s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e146\u0026thinsp;\u0026plusmn;\u0026thinsp;34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e174\u0026thinsp;\u0026plusmn;\u0026thinsp;45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-29 (-47 to -10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient state index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4\u0026ndash;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.72\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRight spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 (-4 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.530\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-3 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.730\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (-7 to 10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.645\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rate, bpm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3 (-8 to 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.395\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eIn the patient state index\u0026thinsp;\u0026le;\u0026thinsp;50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose, mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.0 (-3.7 to 1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.451\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemimazolam dose per unit bodyweight, mg/kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.05 (-0.08 to -0.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration, s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e228\u0026thinsp;\u0026plusmn;\u0026thinsp;62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e245\u0026thinsp;\u0026plusmn;\u0026thinsp;101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-17 (-56 to 22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.389\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRight spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2 (-4 to 0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft spectral edge frequency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2 (-5 to 0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e89\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2 (-9 to 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.618\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rate, bpm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e82\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-5 (-11 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAt tracheal intubation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient state index\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3 (-6 to 0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106\u0026thinsp;\u0026plusmn;\u0026thinsp;27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e104\u0026thinsp;\u0026plusmn;\u0026thinsp;23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (-10 to 14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.752\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rate, bpm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3 (-9 to 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eB, binaural sound. The B group received binaural sounds through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction. For the absence of eyelash reflex, the remimazolam dose was lower in the B group than in the control group (15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 vs. 18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7 mg, P\u0026thinsp;=\u0026thinsp;0.005), as was the dose per unit bodyweight (0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 vs. 0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 mg/kg, P\u0026thinsp;=\u0026thinsp;0.001). The time to absence of eyelash reflex was shorter in the B group than in the control group (146\u0026thinsp;\u0026plusmn;\u0026thinsp;34 vs. 174\u0026thinsp;\u0026plusmn;\u0026thinsp;45 s, P\u0026thinsp;=\u0026thinsp;0.003), and the PSI was higher (73\u0026thinsp;\u0026plusmn;\u0026thinsp;16 vs. 62\u0026thinsp;\u0026plusmn;\u0026thinsp;15, P\u0026thinsp;=\u0026thinsp;0.003). No significant between-group differences were observed in the SEFs, mean blood pressure, or heart rate at this timepoint.\u003c/p\u003e\u003cp\u003eWhen the PSI was \u0026le;\u0026thinsp;50, no significant difference was observed in the remimazolam dose between the two groups (21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 vs. 22.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 mg, P\u0026thinsp;=\u0026thinsp;0.451), although the dose per unit bodyweight tended to be lower in the B group than in the control group (0.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 vs. 0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 mg/kg, P\u0026thinsp;=\u0026thinsp;0.142). No significant differences were observed in the SEFs, mean blood pressure, or heart rate between the groups at this timepoint.\u003c/p\u003e\u003cp\u003eDuring tracheal intubation, the PSI and hemodynamic variables (mean blood pressure and heart rate) did not differ significantly between the groups.\u003c/p\u003e\u003cp\u003eTwo-way ANOVA was conducted to evaluate the effects of time (before vs. after anaesthesia induction) and group (binaural beats vs. control) on relative EEG power across alpha, beta, delta, gamma, and theta bands. No significant interaction was observed between time and group for any frequency band (alpha: F(1,140)\u0026thinsp;=\u0026thinsp;0.29, P\u0026thinsp;=\u0026thinsp;0.589, η\u0026sup2;ₚ = 0.002; beta: F(1,140)\u0026thinsp;=\u0026thinsp;0.02, P\u0026thinsp;=\u0026thinsp;0.896, η\u0026sup2;ₚ = 0.0001; delta: F(1,140)\u0026thinsp;=\u0026thinsp;0.001, P\u0026thinsp;=\u0026thinsp;0.969, η\u0026sup2;ₚ \u0026lt; 0.0001; gamma: F(1,140)\u0026thinsp;=\u0026thinsp;0.40, P\u0026thinsp;=\u0026thinsp;0.525, η\u0026sup2;ₚ = 0.003; theta: F(1,140)\u0026thinsp;=\u0026thinsp;0.41, P\u0026thinsp;=\u0026thinsp;0.522, η\u0026sup2;ₚ = 0.003). The main effect of time was significant for all bands (alpha: F(1,140)\u0026thinsp;=\u0026thinsp;15.62, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, η\u0026sup2;ₚ = 0.10; beta: F(1,140)\u0026thinsp;=\u0026thinsp;25.47, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, η\u0026sup2;ₚ = 0.15; delta: F(1,140)\u0026thinsp;=\u0026thinsp;20.13, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, η\u0026sup2;ₚ = 0.13; gamma: F(1,140)\u0026thinsp;=\u0026thinsp;8.92, P\u0026thinsp;=\u0026thinsp;0.003, η\u0026sup2;ₚ = 0.06; theta: F(1,140)\u0026thinsp;=\u0026thinsp;5.67, P\u0026thinsp;=\u0026thinsp;0.018, η\u0026sup2;ₚ = 0.04), indicating changes in relative power post-induction. The main effect of group was not significant for any band (alpha: F(1,140)\u0026thinsp;=\u0026thinsp;0.05, P\u0026thinsp;=\u0026thinsp;0.821, η\u0026sup2;ₚ = 0.0004; beta: F(1,140)\u0026thinsp;=\u0026thinsp;0.09, P\u0026thinsp;=\u0026thinsp;0.763, η\u0026sup2;ₚ = 0.001; delta: F(1,140)\u0026thinsp;=\u0026thinsp;0.03, P\u0026thinsp;=\u0026thinsp;0.862, η\u0026sup2;ₚ = 0.0002; gamma: F(1,140)\u0026thinsp;=\u0026thinsp;0.02, P\u0026thinsp;=\u0026thinsp;0.879, η\u0026sup2;ₚ = 0.0001; theta: F(1,140)\u0026thinsp;=\u0026thinsp;0.01, P\u0026thinsp;=\u0026thinsp;0.920, η\u0026sup2;ₚ = 0.0001). Post-hoc t-tests revealed no significant between-group differences in relative power before or after anaesthesia induction (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Before anaesthesia induction, the relative powers of the alpha, beta, delta, gamma, and theta waves did not differ significantly between the B and control groups. After induction of anaesthesia, no significant differences were observed in the relative power of these waves between groups. However, changes in the relative power before and after anaesthesia induction were significant for all wave types. The relative power difference before and after anaesthesia induction did not differ significantly between groups.\u003c/p\u003e\u003cp\u003eThe incidence of hypotension was significantly lower in the B group than in the control group (2 [6%] vs. 10 [28%], P\u0026thinsp;=\u0026thinsp;0.024). The incidence of vasopressor use was lower in the B group than in the control group (2 [6%] vs. 10 [28%], P\u0026thinsp;=\u0026thinsp;0.024).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eElectroencephalography during anaesthesia induction\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDifference (95% confidence interval)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCohen\u0026rsquo;s d\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eRelative power before anaesthesia induction, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlpha\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 (-3 to 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.346\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 (-3 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.614\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e77\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (-4 to 7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.555\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-1 to 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.931\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTheta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-2 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.954\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eRelative power after anaesthesia induction, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlpha\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 (-4 to 4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.956\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e17\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-8 to 7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.897\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e57\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-12 to 12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.965\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-1 to 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.546\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTheta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (-1 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.678\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eRelative power difference before and after anaesthesia induction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlpha\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3 to 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.589\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-8 to 9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.896\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e-19\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-19\u0026thinsp;\u0026plusmn;\u0026thinsp;28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-13 to 12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.969\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 to 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTheta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e-1\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-1\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1 to 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.522\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eB, binaural sound. The B group received binaural sounds through headphones prior to anaesthesia induction. The control group received no sound through headphones prior to anaesthesia induction.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the effects of preoperative binaural beats on the remimazolam dose required for LoC (absence of response to vocal stimuli) during general anaesthesia induction. Our results demonstrated that the preoperative application of binaural beats significantly reduced the dose of remimazolam required for LoC, as assessed by the response to vocal stimuli and the eyelash reflex. In addition, binaural beats reduced the incidence of hypotension during anaesthesia induction.\u003c/p\u003e\u003cp\u003ePrevious studies have demonstrated that binaural beats can reduce the requirements for anaesthetics and analgesics [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our study extends these findings by being the first to investigate the effects of preoperative binaural beats on remimazolam, a novel ultra-short-acting benzodiazepine with rapid onset, offset, and favourable hemodynamic stability [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This is particularly significant given the limited data on optimizing remimazolam dosing during anaesthesia induction, where individual variability and potential side effects like hypotension remain concerns [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. By demonstrating that binaural beats reduce the remimazolam dose required for LoC and the incidence of hypotension, our study introduces a non-invasive adjunct that enhances the safety and efficiency of remimazolam-based anaesthesia induction. Furthermore, while our EEG spectral analysis did not detect significant between-group differences in standard frequency bands (alpha, beta, delta, gamma, theta), the use of a 1-Hz binaural beat frequency suggests the potential for frequency-specific neural entrainment at 1 Hz, which was not explored in this study due to the focus on broader frequency bands [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Future investigations could incorporate targeted 1-Hz power analysis to assess whether binaural beats induce specific neural responses that further explain the observed reductions in remimazolam requirements, offering a novel avenue of examining brainwave entrainment mechanisms in anaesthesia.\u003c/p\u003e\u003cp\u003eA practical challenge in using binaural beats during anaesthesia is the necessity for patients to wear headphones, which can be difficult if they are not supine. However, the application of binaural beats in the preoperative treatment room is relatively straightforward and practical. In our study, the administration of binaural beats before anaesthesia induction effectively reduced the required dose of remimazolam. Additionally, a reduction in the time to LoC of approximately 28 s could be clinically significant. Given that heightened anxiety during induction can prolong the process and adversely affect postoperative outcomes, including quality of life [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], this shorter induction time, combined with reduced preoperative anxiety, may contribute to a less stressful experience for patients. Furthermore, the preoperative use of binaural beats presents a non-invasive, user-friendly intervention that could improve patient outcomes by enhancing the efficiency and safety of anaesthesia induction. This approach aligns with ongoing efforts in anaesthesiology to minimise drug doses and enhance patient comfort and safety.\u003c/p\u003e\u003cp\u003eRemimazolam is widely recognised for its safety profile, particularly its hemodynamic stability [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, when administered at high doses, it can lead to significant hypotension, necessitating the use of vasopressors to maintain hemodynamic stability [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In our study, the preoperative application of binaural beats significantly reduced the incidence of hypotension requiring vasopressor intervention during anaesthesia induction. This reduction is likely attributable to the reduced dosage of remimazolam required when binaural beats are employed, as they have previously been shown to enhance the efficacy of anaesthesia agents, allowing for lower dosages. Vasopressors, which are effective in managing hypotension, are associated with risks and complications. Their use can lead to adverse effects, such as tachycardia, myocardial ischemia, and peripheral vasoconstriction, which pose significant risks, particularly in patients with pre-existing cardiovascular conditions [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Thus, minimizing the need for vasopressors through adjunctive measures such as binaural beats can be highly beneficial. Reduced hypotension may lessen the need for vasopressors and their associated risks, thereby enhancing overall safety and workflow efficiency. From this perspective, the incorporation of preoperative binaural beats into anaesthetic protocols holds promise for the enhancement of the safety of anaesthesia induction using remimazolam.\u003c/p\u003e\u003cp\u003eOur analysis, which focused on standard frequency bands (alpha, beta, delta, gamma, theta), did not reveal significant between-group differences in EEG spectral power. Given this, the term \u0026ldquo;brainwave modulation\u0026rdquo;, which encompasses broader changes in neural activity or relaxation states without requiring specific frequency synchronisation, may more accurately describe the potential effects of binaural beats in our study. The lack of observed EEG changes could be attributed to the brief 30-min duration of binaural beat application, the focus on broad frequency bands rather than targeted 1-Hz power analysis, or insufficient statistical power to detect subtle variations [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. While our EEG spectral analysis did not detect significant between-group differences in standard frequency bands (alpha, beta, delta, gamma, theta), a targeted analysis at the 1-Hz stimulation frequency could provide critical evidence for the hypothesised brainwave entrainment mechanism. Such an analysis was not performed in this study due to limitations in the EEG analysis configuration, which focused on broader frequency bands. Future studies should incorporate narrow-band spectral analysis or time-frequency decomposition targeting the 1-Hz frequency to determine whether binaural beats induce specific neural entrainment, potentially transforming our understanding of their role in optimizing anaesthesia induction. This could bridge a critical gap in the literature and establish a mechanistic foundation for the use of binaural beats in anaesthesiology. It is also possible that binaural beats primarily reduced remimazolam requirements through anxiety reduction, rather than direct neural entrainment. Future studies should extend the duration of binaural beat exposure and include frequency-specific analyses, such as 1-Hz power, to better elucidate the mechanisms by which binaural beats influence anaesthetic requirements. The lower anxiety scores in the binaural beats group suggest that anxiety reduction may reduce the required remimazolam dosage. A post-hoc correlation analysis (e.g., Pearson\u0026rsquo;s or Spearman\u0026rsquo;s) between post-headphone anxiety scores and the remimazolam dose could confirm this but was not conducted in this study. Future studies should explore this using our shared dataset (Mendeley Data, DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.17632/swxgj79jpy.2\u003c/span\u003e\u003cspan address=\"10.17632/swxgj79jpy.2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) to clarify the role of anxiety reduction in optimizing anaesthetic dosing. The absence of significant EEG changes in our study suggests that brainwave entrainment may not be the primary mechanism by which binaural beats reduce remimazolam requirements. This could be due to the brief 30-min exposure to 1-Hz binaural beats, which may be insufficient to induce detectable neural entrainment, or the lack of frequency-specific analysis targeting the 1-Hz stimulation frequency. Alternatively, the observed reduction in anxiety scores in the B group suggests that anxiety reduction may play a significant role in decreasing the required remimazolam dosage and time to LoC. Anxiety is known to increase anaesthetic requirements [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and correlation of anxiety scores with remimazolam dosage in future studies could clarify this mechanism. Low-frequency binaural beats, such as the 1-Hz difference used in this study, have been shown to promote deep sleep or reduced consciousness [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. It is possible that preoperative binaural beat exposure induced a sleep-like state, lowering the baseline level of consciousness and thus reducing the remimazolam dose required for LoC. This hypothesis warrants further investigation using objective sedation measures, such as the Ramsay Sedation Scale or polysomnography, to assess the depth of relaxation during the preoperative period.\u003c/p\u003e\u003cp\u003eThe current study had some limitations. First, we exclusively used binaural beats with a 1-Hz difference preoperatively. Given the variety of binaural beats and their varying effects, different types of binaural beats may exhibit distinct or even more potent effects on the induction of anaesthesia with remimazolam. Further research should explore the impact of other binaural-beat frequencies and patterns to identify potentially more effective options. Second, our study focused primarily on variables related to anaesthesia induction. It is plausible that preoperative binaural beats may also influence perioperative variables. However, this investigation specifically focused on the anaesthesia induction phase with remimazolam infusion. Future studies should assess the broader perioperative effects of binaural beats to provide a more comprehensive explanation of their effects. A third limitation is the lack of prioritised use of SEF in our analysis. Future studies should emphasise SEF as a primary metric for monitoring anaesthesia depth to better elucidate its role in optimizing remimazolam-based anaesthesia induction. Fourth, this study did not use the Ramsay Sedation Scale. Given the rapid progression of the study, its application was not feasible. In future studies conducted in settings with a slower pace, we plan to incorporate the Ramsay Sedation Scale for sedation assessment. Fifth, we were unable to compare the outcomes by sex and age. This should be addressed in future studies with larger sample sizes. Sixth, our findings are specific to the use of remimazolam and may not be generalizable to other anaesthetics. Further studies are warranted to confirm the benefits of binaural beats in patients receiving different anaesthetics for general anaesthesia induction. Seventh, we selected a 1-Hz frequency difference to align with the slow delta oscillations typically observed during anaesthesia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, other frequency differences might prove more effective in this context. Future studies comparing binaural beats to other auditory stimuli could help validate and refine this approach. Eighth, this study lacks a sham control, such as 0-Hz binaural beats, to account for general auditory input or placebo effects. While comparing binaural beats to no sound is informative, it does not fully isolate their specific effects. Previous studies suggest that binaural beats reduce anxiety, but without sham controls, placebo effects remain possible [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Future research should include sham conditions to confirm the unique effects of binaural beats on remimazolam dosage and hypotension. Ninth, our EEG spectral analysis focused on broader frequency bands (alpha, beta, delta, gamma, theta) and may not have been sensitive enough to detect frequency-specific neural responses at the 1-Hz stimulation frequency, as suggested by recent literature [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This could explain the lack of significant between-group differences in EEG patterns. Future studies should incorporate targeted analysis of spectral power at or around the stimulation frequency (e.g., 1 Hz) to better evaluate the neural entrainment hypothesis and elucidate the specific mechanisms underlying the observed effects of binaural beats on remimazolam dosage and anaesthesia induction outcomes. Tenth, we did not assess the participants\u0026rsquo; ability to perceive the 1-Hz binaural beats. Low-frequency binaural beats, such as the 1-Hz difference used in this study, may not be uniformly perceptible, as reported by Fan et al [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Without verifying auditory perception, it is unclear whether the observed reductions in remimazolam dosage and time to LoC were directly attributable to brainwave entrainment or other mechanisms, such as relaxation or placebo effects. Future studies should incorporate subjective or electrophysiological measures (e.g., auditory steady-state responses) to confirm the perception of low-frequency binaural beats and validate their neural effects.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study suggests that the preoperative use of binaural beats may reduce the dose of remimazolam needed for LoC (the absence of response to vocal stimuli), shorten the time to achieve it, and potentially lower the incidence of hypotension during anaesthesia induction. These preliminary findings indicate that binaural beats could serve as a non-invasive adjunctive measure to support the efficiency and safety of anaesthesia induction, though further research with larger samples is needed to confirm these effects.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLoC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eloss of consciousness\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eASA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAmerican Society of Anesthesiologists\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePSI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePatient State Index\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eelectroencephalography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSEF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003espectral edge frequency\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eANOVA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eanalysis of variance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were approved by the Investigative Review Board of Yonsei University Gangnam Severance Hospital in Seoul, Korea (document number: 2023-0759-001). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available in Mendeley Data repository, https://data.mendeley.com/preview/swxgj79jpy?a=b175b9e4-0d0c-4863-9b02-2ae45b770356.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Department of Anesthesiology and Pain Medicine and Anesthesia and Pain Research Institute, Yonsei University College of Medicine. This research was supported by a special research grant funded by the Korean Society of Neuroscience in Anesthesiology and Critical Care (KSNACC-2024) and a new faculty research seed money grant from the Yonsei University College of Medicine for 2024 (2024-32-0075).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHCK: Conceptualization, formal analysis, funding acquisition, investigation, methodology, resources, software, supervision, validation, visualization, original draft, and review and editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eJYS: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing.\u003c/p\u003e\n\u003cp\u003eMHK: Conceptualization, investigation, methodology, resources, visualization, original draft, and review and editing.\u003c/p\u003e\n\u003cp\u003eYJK: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing.\u003c/p\u003e\n\u003cp\u003eCHJ: Conceptualization, investigation, methodology, supervision, visualization, original draft, and review and editing.\u003c/p\u003e\n\u003cp\u003eJHS: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, resources, software, supervision, validation, visualization, original draft, and review and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Medical Illustration \u0026amp; Design (MID), a member of the Medical Research Support Services of Yonsei University College of Medicine, for providing excellent support with the medical illustrations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChae D, Kim HC, Song Y, Choi YS, Han DW. Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study. Br J Anaesth. 2022;129(1):49\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoi M, Hirata N, Suzuki T, Morisaki H, Morimatsu H, Sakamoto A. Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial. J Anesth. 2020;34(4):491\u0026ndash;501.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth. 2020;34(4):543\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMonaco F, Bottussi A, Barucco G, D'Andria Ursoleo J. Remimazolam in Cardiac Anesthesia: Not So Ultra-short Acting After All. J Cardiothorac Vasc Anesth. 2025;39(1):327\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eD'Andria Ursoleo J, Bottussi A, Agosta VT, Monaco F. Letter to the editor regarding Effect of remimazolam versus propofol on hypotension after anesthetic induction in patients undergoing coronary artery bypass grafting: A randomized controlled trial. J Clin Anesth. 2024;99:111644.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePieri M, D'Andria Ursoleo J, Di Prima AL, Bugo S, Barucco G, Licheri M, Losiggio R, Frau G, Monaco F. Collaborators: Remimazolam for anesthesia and sedation in pediatric patients: a scoping review. J Anesth. 2024;38(5):692\u0026ndash;710.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eD'Andria Ursoleo J, Licheri M, Barucco G, Losiggio R, Frau G, Pieri M, Monaco F. Remimazolam for anesthesia and sedation in cardiac surgery and for cardiac patients undergoing non-cardiac surgery: a systematic-narrative hybrid review. Minerva Anestesiol. 2024;90(7\u0026ndash;8):682\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePadmanabhan R, Hildreth AJ, Laws D. A prospective, randomised, controlled study examining binaural beat audio and pre-operative anxiety in patients undergoing general anaesthesia for day case surgery. Anaesthesia. 2005;60(9):874\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmid W, Marhofer P, Opfermann P, Zadrazil M, Kimberger O, Triffterer L, Marhofer D, Klug W. Brainwave entrainment to minimise sedative drug doses in paediatric surgery: a randomised controlled trial. Br J Anaesth. 2020;125(3):330\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTani A, Vagheggini G, Moretti F, Del Colombo V, Lehle J, Campana S, Labate A, Tomaiuolo F. Binaural Beats Reduce Postoperative Morphine Consumption in Older adults After Total Knee Replacement Surgery. Altern Ther Health Med. 2021;27(2):27\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOster G. Auditory beats in the brain. Sci Am. 1973;229(4):94\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBae J, Yoo S, Kim H, Kim Y, Kim JT, Lim YJ, Kim HS. Effect of real-time binaural music on sedation with dexmedetomidine during spinal anesthesia: A triple-arm, assessor-blind, randomized controlled trial. J Clin Anesth. 2023;84:110997.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAcute Respiratory Distress, Syndrome N, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhattacharya S, Donoghue JA, Mahnke M, Brincat SL, Brown EN, Miller EK. Propofol Anesthesia Alters Cortical Traveling Waves. J Cogn Neurosci. 2022;34(7):1274\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMinto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997;86(1):10\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee HC, Jung CW. Vital Recorder-a free research tool for automatic recording of high-resolution time-synchronised physiological data from multiple anaesthesia devices. Sci Rep. 2018;8(1):1527.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIngendoh RM, Posny ES, Heine A. Binaural beats to entrain the brain? A systematic review of the effects of binaural beat stimulation on brain oscillatory activity, and the implications for psychological research and intervention. PLoS ONE. 2023;18(5):e0286023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSadeghi A, Khaleghnejad Tabari A, Mahdavi A, Salarian S, Razavi SS. Impact of parental presence during induction of anesthesia on anxiety level among pediatric patients and their parents: a randomized clinical trial. Neuropsychiatr Dis Treat. 2017;12:3237\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCullen BF. Barash, Cullen, and Stoelting's clinical anesthesia, Ninth edition. edn. Philadelphia, PA: Wolters Kluwer; 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJirakittayakorn N, Wongsawat Y. Brain Responses to a 6-Hz Binaural Beat: Effects on General Theta Rhythm and Frontal Midline Theta Activity. Front Neurosci. 2017;11:365.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFan Z, Zhu Y, Suzuki C, Suzuki Y, Watanabe Y, Watanabe T, Abe T. Binaural beats at 0.25 Hz shorten the latency to slow-wave sleep during daytime naps. Sci Rep. 2024;14(1):26062.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWahbeh H, Calabrese C, Zwickey H. Binaural beat technology in humans: a pilot study to assess psychologic and physiologic effects. J Altern Complement Med. 2007;13(1):25\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"auditory stimulation, brainwave entrainment, general anaesthesia induction, loss of consciousness, remimazolam dosage","lastPublishedDoi":"10.21203/rs.3.rs-7368631/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7368631/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Binaural beats, a form of auditory stimulation, reduce anxiety and anaesthetic requirements through brainwave entrainment. Remimazolam offers advantages in terms of rapid onset and offset of action and hemodynamic stability. However, the optimal remimazolam dose for anaesthesia induction remains unclear and there are concerns regarding variability in response and potential side effects at higher doses. This study investigated the effects of preoperative binaural beats on the remimazolam dose required for loss of consciousness (LoC) during general anaesthesia induction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this randomised, prospective, single centre study, 72 patients undergoing general anaesthesia were allocated to two groups: the binaural sound (B group) or the control group. The B group listened to binaural sounds (1-Hz frequency difference) for 30 min preoperatively, while the control group did not.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The B group required a significantly lower remimazolam dose for LoC (15.0 ± 3.6 vs. 17.7 ± 4.5 mg, P=0.006) and achieved LoC faster (140 ± 29 vs. 168 ± 47 s, P=0.003) than the control group. The incidence of hypotension was lower in the B group than in the control group (6 vs. 28%, P=0.024). Electroencephalography spectral analysis revealed no significant between-group differences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Binaural beats significantly reduced the remimazolam dose required for LoC and shortened the time to LoC, while reducing the incidence of hypotension during anaesthesia induction. Binaural beats are an effective, non-invasive method of enhancing efficiency and safety in anaesthesia induction when using remimazolam infusion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration:\u003c/strong\u003e This study was registered at ClinicalTrials.gov (NCT06099977; November 1, 2023).\u003c/p\u003e","manuscriptTitle":"Preoperative binaural beats reduce remimazolam dosage and enhance safety in anaesthesia induction: a randomised controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-29 20:00:36","doi":"10.21203/rs.3.rs-7368631/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"800a22e0-4678-411a-b678-0d787a17e5f3","owner":[],"postedDate":"September 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-14T08:09:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-29 20:00:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7368631","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7368631","identity":"rs-7368631","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}