Comparison of Efficacy and Safety of Remimazolam and Midazolam in elderly Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study

Comparison of Efficacy and Safety of Remimazolam and Midazolam in elderly Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study | 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 Article Comparison of Efficacy and Safety of Remimazolam and Midazolam in elderly Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study Yan Zhou, Xiaohong Xu, Qing Xia, Guosheng Gao, Weihua Wang, Changzhen Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6507789/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Background Laparoscopic cholecystectomy (LC) is a widely performed minimally invasive procedure, with patients requiring to be given general anesthesia. Remimazolam and midazolam are two benzodiazepine drugs that have been extensively used for anesthesia induction and maintenance. Objective This study aimed to compare the efficacy and safety of remimazolam and midazolam in patients undergoing LC, focusing on recovery time, hemodynamic stability, and adverse event incidence. Methods A retrospective analysis was conducted on 184 patients who underwent LC under general anesthesia between January 2022 and January 2024. Patients were divided into remimazolam (n = 81) and midazolam (n = 103) groups. The primary outcome was extubation time, defined as the time from the end of anesthesia to successful extubation. Secondary outcomes included post-anesthesia care unit (PACU) stay duration, hemodynamic and respiratory parameters, and adverse events. Results The remimazolam group had significantly shorter extubation times (33 min [IQR 24.0–44.5] vs. 42 min [IQR 30.0–61.0], p = 0.0003) and PACU stay durations (55 min [IQR 45–65] vs. 65 min [IQR 55–80], p = 0.0001) compared to the midazolam group. Both groups achieved a 100% success rate in anesthesia. No significant differences were observed in hemodynamic and respiratory parameters between the two groups at predefined time points. Adverse event rates, including hypotension (13.6% vs. 15.5%) and bradycardia (8.6% vs. 13.6%), were lower in the remimazolam group, although not statistically significant (p > 0.05). No respiratory depression, nausea, or vomiting was observed in either group. Conclusion remimazolam demonstrated clear clinical advantages over midazolam in LC, including faster recovery and shorter PACU stays, with comparable hemodynamic stability and safety profiles. These findings suggest that remimazolam is a promising alternative for anesthesia in minimally invasive surgeries. Further multicenter studies are warranted to confirm these results and explore its utility in diverse surgical settings. Biological sciences/Drug discovery/Drug safety Health sciences/Diseases/Endocrine system and metabolic diseases remimazolam midazolam laparoscopic cholecystectomy safety efficacy Figures Figure 1 Figure 2 1. Introduction Laparoscopic cholecystectomy (LC) is a commonly performed minimally invasive surgical procedure, primarily indicated for the treatment of gallstone disease and cholecystitis. Its advantages, such as reduced postoperative pain, shorter hospital stays, and faster recovery, have made it the gold standard for gallbladder removal 1 , 2 . However, the success of LC relies heavily on the choice of anesthetic agents, as ensuring smooth endotracheal intubation, stable hemodynamics, and rapid recovery are crucial in optimizing patient outcomes. Benzodiazepines are among the most widely used sedatives in anesthesia due to their anxiolytic, amnestic, and muscle relaxant properties. Midazolam, a short-acting benzodiazepine, has been extensively employed in clinical practice for procedural sedation, premedication, and induction of general anesthesia. Its rapid onset and sedative effects make it particularly useful for short surgical procedures. Despite these advantages, midazolam has notable limitations, including dose-dependent respiratory depression, delayed recovery in elderly patients, and potential postoperative cognitive impairments 3 . To address these limitations, remimazolam, a novel ultra-short-acting benzodiazepine, has been developed. Unlike midazolam, remimazolam undergoes rapid metabolism by tissue esterases, leading to a shorter duration of action, faster recovery, and a more predictable pharmacokinetic profile 4 – 6 . Recent randomized controlled trials have demonstrated that remimazolam provides comparable sedation quality to midazolam and propofol while offering improved safety profiles, particularly in terms of hemodynamic stability and reduced respiratory depression 4 , 5 , 7 . For example, Luo et al. (2024) reported that remimazolam maintains more stable hemodynamics during induction and maintenance compared to propofol, with a lower incidence of hypotension and bradycardia in patients undergoing laparoscopic cholecystectomy 7 . Moreover, remimazolam has demonstrated advantages in elderly and high-risk patients. For instance, studies have shown that remimazolam results in faster recovery times and fewer postoperative cognitive impairments compared to midazolam 3 , 4 , 8 . In a randomized controlled trial, So et al. (2023) highlighted that remimazolam provides effective sedation with minimal impact on cardiac function, making it a safer alternative for elderly patients undergoing LC 5 . Despite these promising findings, the application of remimazolam in LC remains underexplored. While midazolam is widely used, its limitations highlight the need to evaluate alternative agents. Remimazolam, with its favorable pharmacological profile, has the potential to improve outcomes, especially in high-risk populations. However, the comparative efficacy and safety of remimazolam and midazolam in LC have not been fully elucidated. Therefore, further investigation is warranted to clarify their differences in terms of sedation quality, recovery profiles, hemodynamic effects, and adverse event rates. This study aims to comprehensively compare the efficacy and safety of remimazolam and midazolam in patients undergoing laparoscopic cholecystectomy. Specifically, this research seeks to evaluate key clinical outcomes, including sedation quality, hemodynamic stability, recovery time, and adverse event incidence. The findings aim to provide evidence-based guidance for the selection of sedative agents in LC, contributing to the optimization of anesthetic strategies and improved patient outcomes. 2. Methods 2.1 Study Population This study employed a retrospective design to assess the efficacy and safety of remimazolam and midazolam in elderly patients undergoing laparoscopic cholecystectomy. The research was conducted at Ningbo No.2 Hospital from January 2022 to January 2024. The study population was divided into two groups based on the anesthetic agent used: remimazolam and midazolam. The study included patients who underwent elective laparoscopic cholecystectomy during the study period. Eligibility criteria required patients to have an American Society of Anesthesiologists (ASA) physical status classification of II–III, aged 60 to 80 years, a body mass index (BMI) between 18 and 30 kg/m², and normal or mildly impaired liver and renal function. All participants provided informed consent for the use of anonymized data in research. Patients were excluded if they had a known allergy to remimazolam, midazolam, or other benzodiazepines. Other exclusion criteria included severe cardiopulmonary insufficiency, liver or kidney failure, advanced-stage malignant tumors, BMI outside the specified range, pregnancy or lactation, a history of substance abuse or psychiatric disorders, emergency surgeries, contraindications to laparoscopic procedures, or refusal to sign the informed consent form. 2.2 Materials Remimazolam tosilate for Injection was provided by Jiangsu Hengrui Pharmaceuticals Co., Ltd (China). Midazolam Injection and Sufentanil Citrate Injection were provided by Yichang Humanwell Pharmaceutical Co., Ltd (China). Remifentanil Hydrochloride for Injection was provided by Jiangsu Nhwa Pharmaceutical Co., Ltd (China). 2.3 Interventions General anesthesia was administered using standardized protocols in both groups, with remimazolam or midazolam as the primary anesthesia agent. Remimazolam group: Upon entering the operating room, patients were connected to vital sign monitoring equipment to ensure real-time monitoring of heart rate, blood pressure, and oxygen saturation. During the induction phase, remimazolam was used for anesthesia induction at a dose of 0.3 mg/kg, delivered via slow intravenous injection over 2 minutes. To achieve effective analgesia and prevent pain-related stress responses caused by surgical stimuli, sufentanil was administered intravenously at a dose of 0.5 µg/kg, completed within 1–2 minutes. To facilitate endotracheal intubation, a muscle relaxant, rocuronium bromide, was administered at a dose of 0.9 mg/kg. During the maintenance phase of anesthesia, a continuous intravenous infusion of remifentanil at a rate of 0.2 µg/(kg·min) was administered. Simultaneously, remimazolam was infused intravenously at a rate of 0.2 mg/(kg·h). Midazolam group: The basic protocol was similar to the remimazolam group, except for the following adjustments: during the induction phase, midazolam was administered at a dose of 0.2 mg/kg. Throughout the procedure, oxygen was supplied at a rate of 6 L/min during induction, and oxygen saturation (SpO₂) was continuously monitored. 2.4 Outcome Measures The primary outcome of the study was the time from the end of anesthesia to extubation, by which time the patient had fully regained consciousness. Prior to extubation, the MOAA/S (Modified Observer’s Assessment of Alertness/Sedation) score was assessed, and extubation was performed only when the MOAA/S score reached 5. Secondary outcomes included hemodynamic parameters, such as systolic and diastolic blood pressure, heart rate, and SpO₂, measured at predefined time points: T1 (5 minutes before anesthesia induction), T2 (immediately after induction), T3 (5 minutes after induction), T4 (10 minutes after induction), and T5 (15 minutes after induction). Additional secondary outcomes included the time to intubation, measured from the start of induction to successful endotracheal intubation. Other recorded parameters included the time from extubation to leaving the post-anesthesia care unit (PACU) and the duration of PACU stay. These definitions were consistent with those used in previous studies 4 , 5 , 7 . Adverse events were recorded, including hypotension (systolic blood pressure < 90 mmHg or a decrease of more than 30% relative to baseline), bradycardia (heart rate < 50 bpm), hypoxemia (oxygen desaturation, SpO₂ < 94%), and the need for vasoactive medications. Respiratory depression was defined as a respiratory rate below 10 breaths per minute and was recorded accordingly. Additionally, nausea and vomiting were also documented. 2.5 Statistical Analysis All continuous variables were first tested for normality using the Shapiro-Wilk test. Continuous variables that followed a normal distribution were expressed as mean ± standard deviation (SD) and compared between groups using the t-test. For continuous variables that did not follow a normal distribution, data were expressed as median (interquartile range, IQR) and analyzed using the Mann-Whitney U test. Categorical variables were presented as frequencies and percentages and analyzed using the chi-square test or Fisher's exact test, as appropriate. A two-tailed p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS software (version 22.0, IBM Corp., Armonk, NY, USA). Data visualization and trend analysis were conducted using GraphPad Prism (version 9.0). 3. Results 3.1 Baseline Characteristics A total of 184 patients were included in the analysis, with 103 patients in the midazolam group and 81 patients in the remimazolam group (Fig. 1 ). The baseline characteristics of the patients in the two groups (midazolam group; remimazolam group) are presented in Table 1 . Statistical analyses were performed to evaluate the balance between the two groups in terms of demographic and clinical characteristics, including age, sex, weight (BW), BMI, ASA classification, and duration of surgery. No statistically significant differences were observed between the two groups in any of these baseline characteristics (p > 0.05 for all variables), indicating that the groups were well-balanced. Table 1 Baseline characteristics of patients Total (N = 184) Midazolam (N = 103) Remimazolam (N = 81) p_value Age, year, median (P25, P75) 63 (60, 69) 63 (61, 67) 64 (60, 70) 0.760 Female (%) 102 (55.43) 58 (56.31) 44 (54.32) 0.788 BW, Kg, median (P25, P75) 63.0 (56.25, 72.93) 62.00 (57.50, 70.50) 65.00 (56.00, 74.00) 0.638 BMI, median (P25, P75) 24.00 (21.90, 26.23) 24.00 (21.80, 26.05) 24.00 (21.90, 26.55) 0.57 Duration of surgery (min), median (P25, P75) 65.00 (50.00, 85.00) 68.00 (55.00, 85.00) 65.00 (46.50, 80.00) 0.229 ASA Classification II/III 117 (63.59) / 67 (36.41) 62 (60.19) / 41 (39.81) 55 (67.90) / 26 (32.10) 0.281 3.2 Efficacy Outcomes The time from the end of anesthesia to extubation was significantly shorter in the remimazolam group compared to the midazolam group (Table 2 ). The median time for the remimazolam group was 33 minutes (IQR 24.0, 44.5), whereas it was 42 minutes (IQR 30, 61) in the midazolam group (p = 0.0003), indicating that patients in the remimazolam group regained consciousness and achieved extubation faster than those in the midazolam group. The duration of stay in the PACU was also significantly shorter in the remimazolam group (Table 2 ). The median PACU time for the remimazolam group was 55 minutes (IQR 45, 65), compared to 65 minutes (IQR 55, 80) in the midazolam group (p = 0.0001). The time from the start of anesthesia to intubation was comparable between the two groups. The median time was 3 minutes (IQR 2, 5) for the midazolam group and 3 minutes (IQR 3, 5) for the remimazolam group (p = 0.6186). The median time from extubation to leaving the PACU was similar between groups (p = 0.2992): 30.0 minutes (IQR, 30.0–33.0) in remimazolam group and 31.0 minutes (IQR, 30.0–33.5) in midazolam group. Vital sign changes (Fig. 2 ), including SpO₂, DBP, SBP, and HR, were analyzed at five time points: T1 (5 minutes before anesthesia), T2 (immediately after induction), T3 (5 minutes after induction), T4 (10 minutes after induction), and T5 (15 minutes after induction). At each time point, there were no significant differences between remimazolam group and midazolam group. However, at T3, T4, and T5, following the injection of remimazolam or midazolam, significant changes in SpO₂, DBP, SBP, and HR were observed compared to T1. Specifically, SpO₂ levels significantly increased at T3, T4, and T5 compared to T1 in both groups. Conversely, DBP, SBP, and HR showed a significant overall downward trend following the administration of the anesthetic agents. Table 2 Comparison of the induction and recovery times between the remimazolam and midazolam groups. Total (N = 184) Midazolam (N = 103) Remimazolam (N = 81) p_value Time from the end of anesthesia to extubation (min) 40 (25.0, 54.5) 42 (30, 61) 33 (24.0, 44.5) 0.0003 Time to intubation (min) 3 (2, 5) 3 (2, 5) 3 (3, 5) 0.6186 Time from Extubation to leaving PACU 31 (30.0, 33.0) 31 (30.0, 33.5) 30 (30.0, 33.0) 0.2992 Duration of PACU stay (min) 60 (50, 75) 65 (55, 80) 55 (45, 65) 0.0001 3.3 Safety Outcomes Table 3 presents the comparison of adverse events between the midazolam and remimazolam groups. The study focused on hemodynamic and respiratory effects. The incidence of hypotension was higher in the midazolam group (15.5%) compared to the remimazolam group (13.6%), as was the incidence of bradycardia (13.6% vs. 8.6%); however, these differences were not statistically significant (p > 0.05). Hypoxemia occurred in approximately 1% of patients in the midazolam group, whereas it was not observed in the remimazolam group. Neither nausea nor vomiting was reported in either group. Table 3 Comparison of adverse events between groups Adverse events Midazolam (N = 103) Remimazolam (N = 81) p_value Hypotension (SBP < 90 mmHg) 16 (15.5) 11 (13.6) 0.7100 Hypoxemia (SpO₂ < 94%) 1 (1.0) 0 (0) 0.3739 Bradycardia (HR < 50 bpm) 14 (13.6) 7 (8.6) 0.2945 Respiratory depression (RR < 10 breaths/min) 0 (0) 0 (0) Nausea 0 (0) 0 (0) Vomiting 0 (0) 0 (0) 4. Discussion This study compared the efficacy and safety of remimazolam and midazolam for general anesthesia in LC. The primary outcome was extubation time, which reflects patient recovery and postoperative safety. Shorter extubation times indicate faster recovery and lower risks of postoperative complications, making it a key metric for evaluating the efficacy and safety of anesthetic agents 9 . The results demonstrated that the extubation time was significantly shorter in the remimazolam group compared to the midazolam group (33 minutes vs. 42 minutes). This clinically significant difference may enhance surgical efficiency and patient throughput. Additionally, PACU stay was significantly shorter in the remimazolam group compared to the midazolam group (55 minutes vs. 65 minutes), further highlighting remimazolam’s potential to optimize postoperative resource utilization. These advantages are particularly relevant in outpatient or ambulatory surgery settings, where minimizing recovery time is a priority 10 . The findings of this study are consistent with previous research. Kim et al. conducted a study comparing the safety and efficacy of remimazolam and midazolam in bronchoscopy, demonstrating that the time from the end of surgery to full alertness and peak sedation was shorter in the remimazolam group 11 . Similarly, in Japan, Ichijima et al. investigated the use of remimazolam and midazolam in gastrointestinal endoscopy, showing that the median time to awakening was significantly shorter in the remimazolam group (0 minutes [0–5.0 minutes]) compared to the midazolam group (27.0 minutes [23.0–40.5 minutes]). Discharge time was also significantly shorter in the remimazolam group 12 . These differences are likely attributable to the distinct pharmacokinetic profiles of the two agents. remimazolam is an ultrashort-acting benzodiazepine that undergoes rapid metabolism via tissue-specific carboxylesterases 13 , 14 , resulting in predictable clearance and a shorter duration of action compared to midazolam, which relies on hepatic cytochrome P450 enzymes for metabolism 4 , 5 , 15 . This pharmacokinetic advantage allows remimazolam to facilitate faster recovery times and more stable sedation profiles, as evidenced by the shorter extubation time and reduced PACU stay in our study. Moreover, remimazolam's pharmacokinetics make it a safer alternative in patients with hepatic or renal impairment, as its metabolism is independent of these organ systems 9 , 16 . A key strength of this study lies in its focus on elderly and moderate-risk patients (ASA II–III), a population often underrepresented in anesthesia trials. The faster recovery times observed with remimazolam may be particularly advantageous for elderly patients, who are more susceptible to postoperative cognitive dysfunction and prolonged sedation 17 , 18 . Liu et al. compared remimazolam and midazolam regarding postoperative early cognitive recovery in elderly patients undergoing tooth extraction. Their results indicated that remimazolam facilitated faster recovery of postoperative cognitive function and reduced discharge time compared to midazolam 19 . Furthermore, the high patient satisfaction scores in the remimazolam group, though not quantitatively measured here, could be attributed to reduced postoperative drowsiness and quicker return to baseline function, factors known to influence patient-reported outcomes 11 . Previous studies have shown that, compared to midazolam, remimazolam is associated with more stable hemodynamics and less respiratory depression 20 . In cardiovascular surgery under general anesthesia, remimazolam caused significantly less reduction in mean arterial pressure (MAP) than midazolam, demonstrating superior hemodynamic stability 21 . However, in the current study, the effects of remimazolam and midazolam on hemodynamics and respiratory parameters were similar. Both remimazolam and midazolam led to decreases in SBP, DBP, and HR, with no significant differences between the two groups. Changes in SpO₂ were relatively stable. These findings are consistent with results observed in bronchoscopy, which showed similar fluctuations in hemodynamic and respiratory parameters for remimazolam and midazolam 11 . Such differences across studies may be attributed to variations in surgical type and patient baseline characteristics. Previous evaluations of benzodiazepines in surgical anesthesia have demonstrated comparable safety profiles for remimazolam and midazolam, particularly regarding hypotension and bradycardia. In bronchoscopy, the incidence of hypotension was 2% in both the remimazolam and midazolam groups, with no bradycardia observed 11 . In the present study, there was a trend toward lower rates of hypotension and bradycardia in the remimazolam group compared to the midazolam group (13.6% vs. 15.5% and 8.6% vs. 13.6%, respectively), although these differences were not statistically significant, indicating good safety. The higher incidence of hypotension and bradycardia in this study may be related to factors such as the older age of patients, the complexity of the surgeries, and longer operation times. Notably, the safety profiles of remimazolam and midazolam appear superior to other anesthetic agents, such as propofol. For example, in LC under general anesthesia, remimazolam demonstrated more stable hemodynamics and a lower incidence of hypotension compared to propofol 4 . Similarly, in endoscopic submucosal dissection for esophageal squamous cell carcinoma, the incidence of hypotension was significantly lower in the midazolam group compared to the propofol group (28.8% vs. 47.0%, p = 0.04), while the incidence of bradycardia was similar in both groups (19.7%) 22 . In this study, no respiratory depression (respiratory rate < 10 breaths/min), nausea, or vomiting was observed. The absence of hypoxemia in the remimazolam group further supports its respiratory safety, a critical consideration in procedures requiring controlled ventilation 23 . These findings underscore the broad applicability of remimazolam in a variety of surgical settings, particularly in high-risk populations such as the elderly or patients with comorbid conditions or hemodynamic instability 24 . Despite these advantages, our findings must be interpreted in light of several limitations. First, the retrospective design introduces potential selection bias and unmeasured confounding factors. Second, the single-center nature and modest sample size may limit generalizability. Future multicenter trials with larger sample sizes are needed to validate and expand upon these results. Finally, the study did not incorporate advanced monitoring techniques, such as bispectral index (BIS) or electroencephalographic monitoring, to assess sedation depth. Incorporating such tools in future research could provide more precise evaluations of anesthetic depth and recovery profiles. 5. Conclusion In summary, remimazolam offers distinct clinical advantages over midazolam in LC, including faster recovery and shorter PACU stays, potentially improving hospital resource utilization. Both remimazolam and midazolam demonstrated stable hemodynamic profiles and low respiratory depression, indicating high safety. These advantages make remimazolam a promising alternative for anesthesia in minimally invasive surgeries. Larger multicenter studies are needed to validate these findings and explore its roles in different surgical settings. Declarations Acknowledgements Not applicable. Author Contributions All authors contributed to this paper. YZ, XHX: Methodology, Investigation, Data collection, Writing—Original Draft. QX, GSG: Conceptualization, Formal analysis. WHW: Methodology, Data collection. CZZ: Supervision, Writing—Reviewing. All authors read and approved the final manuscript. Funding This study was supported by the Ningbo Natural Science Foundation (No. 2022J246). Data Availability The datasets used or analysed during the current study are available from the corresponding authors on reasonable request. Ethics Approval The present study followed the Declaration of Helsinki. This study was approved by the Human Research Ethics Committee, Ningbo No.2 Hospital (PJ-NBEY-KY-2025-076-01). Consent to Participate Informed consent was obtained from all subjects and/or their legal guardians. Conflict of Interest The authors declare no conflict of interest. References Majedi, M. A., Sarlak, S., Sadeghi, Y. & Ahsan, B. Comparison of the effects of thoracic epidural anesthesia with general anesthesia on hemodynamic changes and its complications in patients undergoing laparoscopic cholecystectomy. Adv Biomed Res 8 , 7 (2019). Bilgi, M., Alshair, E. E., Göksu, H. & Sevim, O. 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Cite Share Download PDF Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 30 Nov, 2025 Reviews received at journal 19 Nov, 2025 Reviewers agreed at journal 19 Nov, 2025 Reviewers agreed at journal 07 Nov, 2025 Reviewers agreed at journal 14 Sep, 2025 Reviews received at journal 30 Jul, 2025 Reviewers agreed at journal 28 Jul, 2025 Reviewers invited by journal 27 Jun, 2025 Editor assigned by journal 27 Jun, 2025 Editor invited by journal 24 Apr, 2025 Submission checks completed at journal 24 Apr, 2025 First submitted to journal 22 Apr, 2025 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6507789","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":478285983,"identity":"c0f6b96a-9759-4f4f-8a9a-e322b6db7a43","order_by":0,"name":"Yan Zhou","email":"","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Zhou","suffix":""},{"id":478285984,"identity":"57999a5d-7e73-4f42-a4e5-6ea2a09841b2","order_by":1,"name":"Xiaohong Xu","email":"","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaohong","middleName":"","lastName":"Xu","suffix":""},{"id":478285985,"identity":"93020a9d-1e8b-4245-87fc-0b6cda3c2d7e","order_by":2,"name":"Qing Xia","email":"","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Xia","suffix":""},{"id":478285986,"identity":"361a4b80-7ee6-434c-8eb7-301c720276a9","order_by":3,"name":"Guosheng Gao","email":"","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Guosheng","middleName":"","lastName":"Gao","suffix":""},{"id":478285987,"identity":"3b368c3a-aa12-4a4f-9772-805fc17b23b1","order_by":4,"name":"Weihua Wang","email":"","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Weihua","middleName":"","lastName":"Wang","suffix":""},{"id":478285988,"identity":"8cbddb6d-7279-4e3e-9256-efcb528d509d","order_by":5,"name":"Changzhen Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIie3RMQ6CMBSA4UeaVIdH2EyJiVwBw+LAYcrCxKA3IDHBBXeIl+jIWNJEFz2BCwkXYGTTxsnJdnToP78vL30FcLn+Na9MkS6OUk6zPck3AV6zvq3tiUrCpkjUklpMR6fbQA4dyYQsJgUIUbCShgU156S9U00eQu13sG0v/DchDCTxK8xEfxaqQeDx00Ao80pNWCYUDgqpBUFGQJM4CSsEO8Iw1+TO9ZFprI/MzG/5XMzvXkijcZymOY2CtYHoFt9fzozjLpfL5bLoDeSAQenP4+RrAAAAAElFTkSuQmCC","orcid":"","institution":"Ningbo No.2 Hospital","correspondingAuthor":true,"prefix":"","firstName":"Changzhen","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-04-23 01:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6507789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6507789/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-41918-0","type":"published","date":"2026-03-04T15:58:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85829238,"identity":"d289b65e-38cc-42ad-9038-fab46eb4ed5c","added_by":"auto","created_at":"2025-07-02 07:35:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":142380,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient inclusion.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6507789/v1/144b68fdb95834e536916556.png"},{"id":85829239,"identity":"0b6ca358-064a-449d-b106-a2e9844c64ec","added_by":"auto","created_at":"2025-07-02 07:35:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":184040,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in patient vital signs before and after anesthesia. \u003csup\u003e**\u003c/sup\u003e p \u0026lt; 0.01，\u003csup\u003e***\u003c/sup\u003e p \u0026lt; 0.001 indicate significant differences in the values of midazolam group or remimazolam group at T2, T3, T4, and T5 compared to T1.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6507789/v1/3891a8a7cebec6f2e71a27c4.png"},{"id":104252241,"identity":"952d92bb-3d21-40e9-a76a-269179370ff6","added_by":"auto","created_at":"2026-03-09 16:17:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1005562,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6507789/v1/5c625dc9-a683-40c8-8d89-3876f235bda5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Efficacy and Safety of Remimazolam and Midazolam in elderly Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eLaparoscopic cholecystectomy (LC) is a commonly performed minimally invasive surgical procedure, primarily indicated for the treatment of gallstone disease and cholecystitis. Its advantages, such as reduced postoperative pain, shorter hospital stays, and faster recovery, have made it the gold standard for gallbladder removal\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, the success of LC relies heavily on the choice of anesthetic agents, as ensuring smooth endotracheal intubation, stable hemodynamics, and rapid recovery are crucial in optimizing patient outcomes.\u003c/p\u003e \u003cp\u003eBenzodiazepines are among the most widely used sedatives in anesthesia due to their anxiolytic, amnestic, and muscle relaxant properties. Midazolam, a short-acting benzodiazepine, has been extensively employed in clinical practice for procedural sedation, premedication, and induction of general anesthesia. Its rapid onset and sedative effects make it particularly useful for short surgical procedures. Despite these advantages, midazolam has notable limitations, including dose-dependent respiratory depression, delayed recovery in elderly patients, and potential postoperative cognitive impairments\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo address these limitations, remimazolam, a novel ultra-short-acting benzodiazepine, has been developed. Unlike midazolam, remimazolam undergoes rapid metabolism by tissue esterases, leading to a shorter duration of action, faster recovery, and a more predictable pharmacokinetic profile\u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Recent randomized controlled trials have demonstrated that remimazolam provides comparable sedation quality to midazolam and propofol while offering improved safety profiles, particularly in terms of hemodynamic stability and reduced respiratory depression\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. For example, Luo et al. (2024) reported that remimazolam maintains more stable hemodynamics during induction and maintenance compared to propofol, with a lower incidence of hypotension and bradycardia in patients undergoing laparoscopic cholecystectomy\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, remimazolam has demonstrated advantages in elderly and high-risk patients. For instance, studies have shown that remimazolam results in faster recovery times and fewer postoperative cognitive impairments compared to midazolam\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. In a randomized controlled trial, So et al. (2023) highlighted that remimazolam provides effective sedation with minimal impact on cardiac function, making it a safer alternative for elderly patients undergoing LC\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite these promising findings, the application of remimazolam in LC remains underexplored. While midazolam is widely used, its limitations highlight the need to evaluate alternative agents. Remimazolam, with its favorable pharmacological profile, has the potential to improve outcomes, especially in high-risk populations. However, the comparative efficacy and safety of remimazolam and midazolam in LC have not been fully elucidated. Therefore, further investigation is warranted to clarify their differences in terms of sedation quality, recovery profiles, hemodynamic effects, and adverse event rates.\u003c/p\u003e \u003cp\u003eThis study aims to comprehensively compare the efficacy and safety of remimazolam and midazolam in patients undergoing laparoscopic cholecystectomy. Specifically, this research seeks to evaluate key clinical outcomes, including sedation quality, hemodynamic stability, recovery time, and adverse event incidence. The findings aim to provide evidence-based guidance for the selection of sedative agents in LC, contributing to the optimization of anesthetic strategies and improved patient outcomes.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Population\u003c/h2\u003e \u003cp\u003eThis study employed a retrospective design to assess the efficacy and safety of remimazolam and midazolam in elderly patients undergoing laparoscopic cholecystectomy. The research was conducted at Ningbo No.2 Hospital from January 2022 to January 2024. The study population was divided into two groups based on the anesthetic agent used: remimazolam and midazolam.\u003c/p\u003e \u003cp\u003eThe study included patients who underwent elective laparoscopic cholecystectomy during the study period. Eligibility criteria required patients to have an American Society of Anesthesiologists (ASA) physical status classification of II\u0026ndash;III, aged 60 to 80 years, a body mass index (BMI) between 18 and 30 kg/m\u0026sup2;, and normal or mildly impaired liver and renal function. All participants provided informed consent for the use of anonymized data in research.\u003c/p\u003e \u003cp\u003ePatients were excluded if they had a known allergy to remimazolam, midazolam, or other benzodiazepines. Other exclusion criteria included severe cardiopulmonary insufficiency, liver or kidney failure, advanced-stage malignant tumors, BMI outside the specified range, pregnancy or lactation, a history of substance abuse or psychiatric disorders, emergency surgeries, contraindications to laparoscopic procedures, or refusal to sign the informed consent form.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Materials\u003c/h2\u003e \u003cp\u003eRemimazolam tosilate for Injection was provided by Jiangsu Hengrui Pharmaceuticals Co., Ltd (China). Midazolam Injection and Sufentanil Citrate Injection were provided by Yichang Humanwell Pharmaceutical Co., Ltd (China). Remifentanil Hydrochloride for Injection was provided by Jiangsu Nhwa Pharmaceutical Co., Ltd (China).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Interventions\u003c/h2\u003e \u003cp\u003eGeneral anesthesia was administered using standardized protocols in both groups, with remimazolam or midazolam as the primary anesthesia agent. Remimazolam group: Upon entering the operating room, patients were connected to vital sign monitoring equipment to ensure real-time monitoring of heart rate, blood pressure, and oxygen saturation. During the induction phase, remimazolam was used for anesthesia induction at a dose of 0.3 mg/kg, delivered via slow intravenous injection over 2 minutes. To achieve effective analgesia and prevent pain-related stress responses caused by surgical stimuli, sufentanil was administered intravenously at a dose of 0.5 \u0026micro;g/kg, completed within 1\u0026ndash;2 minutes. To facilitate endotracheal intubation, a muscle relaxant, rocuronium bromide, was administered at a dose of 0.9 mg/kg. During the maintenance phase of anesthesia, a continuous intravenous infusion of remifentanil at a rate of 0.2 \u0026micro;g/(kg\u0026middot;min) was administered. Simultaneously, remimazolam was infused intravenously at a rate of 0.2 mg/(kg\u0026middot;h).\u003c/p\u003e \u003cp\u003eMidazolam group: The basic protocol was similar to the remimazolam group, except for the following adjustments: during the induction phase, midazolam was administered at a dose of 0.2 mg/kg. Throughout the procedure, oxygen was supplied at a rate of 6 L/min during induction, and oxygen saturation (SpO₂) was continuously monitored.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcome Measures\u003c/h2\u003e \u003cp\u003eThe primary outcome of the study was the time from the end of anesthesia to extubation, by which time the patient had fully regained consciousness. Prior to extubation, the MOAA/S (Modified Observer\u0026rsquo;s Assessment of Alertness/Sedation) score was assessed, and extubation was performed only when the MOAA/S score reached 5.\u003c/p\u003e \u003cp\u003eSecondary outcomes included hemodynamic parameters, such as systolic and diastolic blood pressure, heart rate, and SpO₂, measured at predefined time points: T1 (5 minutes before anesthesia induction), T2 (immediately after induction), T3 (5 minutes after induction), T4 (10 minutes after induction), and T5 (15 minutes after induction).\u003c/p\u003e \u003cp\u003eAdditional secondary outcomes included the time to intubation, measured from the start of induction to successful endotracheal intubation. Other recorded parameters included the time from extubation to leaving the post-anesthesia care unit (PACU) and the duration of PACU stay. These definitions were consistent with those used in previous studies\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAdverse events were recorded, including hypotension (systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg or a decrease of more than 30% relative to baseline), bradycardia (heart rate\u0026thinsp;\u0026lt;\u0026thinsp;50 bpm), hypoxemia (oxygen desaturation, SpO₂ \u0026lt; 94%), and the need for vasoactive medications. Respiratory depression was defined as a respiratory rate below 10 breaths per minute and was recorded accordingly. Additionally, nausea and vomiting were also documented.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical Analysis\u003c/h2\u003e \u003cp\u003eAll continuous variables were first tested for normality using the Shapiro-Wilk test. Continuous variables that followed a normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared between groups using the t-test. For continuous variables that did not follow a normal distribution, data were expressed as median (interquartile range, IQR) and analyzed using the Mann-Whitney U test. Categorical variables were presented as frequencies and percentages and analyzed using the chi-square test or Fisher's exact test, as appropriate. A two-tailed p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. All statistical analyses were performed using SPSS software (version 22.0, IBM Corp., Armonk, NY, USA). Data visualization and trend analysis were conducted using GraphPad Prism (version 9.0).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Baseline Characteristics\u003c/h2\u003e \u003cp\u003eA total of 184 patients were included in the analysis, with 103 patients in the midazolam group and 81 patients in the remimazolam group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The baseline characteristics of the patients in the two groups (midazolam group; remimazolam group) are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Statistical analyses were performed to evaluate the balance between the two groups in terms of demographic and clinical characteristics, including age, sex, weight (BW), BMI, ASA classification, and duration of surgery. No statistically significant differences were observed between the two groups in any of these baseline characteristics (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all variables), indicating that the groups were well-balanced.\u003c/p\u003e \u003cp\u003e \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\u003eBaseline characteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eTotal (N\u0026thinsp;=\u0026thinsp;184)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMidazolam (N\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRemimazolam (N\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep_value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year, median (P25, P75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (60, 69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (61, 67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (60, 70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.760\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102 (55.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (56.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (54.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBW, Kg, median (P25, P75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.0 (56.25, 72.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.00 (57.50, 70.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.00 (56.00, 74.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, median (P25, P75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.00 (21.90, 26.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.00 (21.80, 26.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.00 (21.90, 26.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of surgery (min), median (P25, P75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.00 (50.00, 85.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.00 (55.00, 85.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.00 (46.50, 80.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.229\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA Classification II/III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 (63.59) / 67 (36.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (60.19) / 41 (39.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (67.90) / 26 (32.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Efficacy Outcomes\u003c/h2\u003e \u003cp\u003eThe time from the end of anesthesia to extubation was significantly shorter in the remimazolam group compared to the midazolam group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median time for the remimazolam group was 33 minutes (IQR 24.0, 44.5), whereas it was 42 minutes (IQR 30, 61) in the midazolam group (p\u0026thinsp;=\u0026thinsp;0.0003), indicating that patients in the remimazolam group regained consciousness and achieved extubation faster than those in the midazolam group.\u003c/p\u003e \u003cp\u003eThe duration of stay in the PACU was also significantly shorter in the remimazolam group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median PACU time for the remimazolam group was 55 minutes (IQR 45, 65), compared to 65 minutes (IQR 55, 80) in the midazolam group (p\u0026thinsp;=\u0026thinsp;0.0001). The time from the start of anesthesia to intubation was comparable between the two groups. The median time was 3 minutes (IQR 2, 5) for the midazolam group and 3 minutes (IQR 3, 5) for the remimazolam group (p\u0026thinsp;=\u0026thinsp;0.6186). The median time from extubation to leaving the PACU was similar between groups (p\u0026thinsp;=\u0026thinsp;0.2992): 30.0 minutes (IQR, 30.0\u0026ndash;33.0) in remimazolam group and 31.0 minutes (IQR, 30.0\u0026ndash;33.5) in midazolam group.\u003c/p\u003e \u003cp\u003eVital sign changes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), including SpO₂, DBP, SBP, and HR, were analyzed at five time points: T1 (5 minutes before anesthesia), T2 (immediately after induction), T3 (5 minutes after induction), T4 (10 minutes after induction), and T5 (15 minutes after induction). At each time point, there were no significant differences between remimazolam group and midazolam group. However, at T3, T4, and T5, following the injection of remimazolam or midazolam, significant changes in SpO₂, DBP, SBP, and HR were observed compared to T1. Specifically, SpO₂ levels significantly increased at T3, T4, and T5 compared to T1 in both groups. Conversely, DBP, SBP, and HR showed a significant overall downward trend following the administration of the anesthetic agents.\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\u003eComparison of the induction and recovery times between the remimazolam and midazolam groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eTotal (N\u0026thinsp;=\u0026thinsp;184)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMidazolam (N\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRemimazolam (N\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep_value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from the end of anesthesia to extubation (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (25.0, 54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (30, 61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (24.0, 44.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to intubation (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.6186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from Extubation to leaving PACU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (30.0, 33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (30.0, 33.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (30.0, 33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2992\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of PACU stay (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (50, 75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (55, 80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (45, 65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0001\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\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Safety Outcomes\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the comparison of adverse events between the midazolam and remimazolam groups. The study focused on hemodynamic and respiratory effects. The incidence of hypotension was higher in the midazolam group (15.5%) compared to the remimazolam group (13.6%), as was the incidence of bradycardia (13.6% vs. 8.6%); however, these differences were not statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Hypoxemia occurred in approximately 1% of patients in the midazolam group, whereas it was not observed in the remimazolam group. Neither nausea nor vomiting was reported in either group.\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\u003eComparison of adverse events between groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse events\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMidazolam (N\u0026thinsp;=\u0026thinsp;103)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRemimazolam (N\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep_value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension (SBP\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoxemia (SpO₂ \u0026lt; 94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradycardia (HR\u0026thinsp;\u0026lt;\u0026thinsp;50 bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2945\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory depression (RR\u0026thinsp;\u0026lt;\u0026thinsp;10 breaths/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study compared the efficacy and safety of remimazolam and midazolam for general anesthesia in LC. The primary outcome was extubation time, which reflects patient recovery and postoperative safety. Shorter extubation times indicate faster recovery and lower risks of postoperative complications, making it a key metric for evaluating the efficacy and safety of anesthetic agents\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe results demonstrated that the extubation time was significantly shorter in the remimazolam group compared to the midazolam group (33 minutes vs. 42 minutes). This clinically significant difference may enhance surgical efficiency and patient throughput. Additionally, PACU stay was significantly shorter in the remimazolam group compared to the midazolam group (55 minutes vs. 65 minutes), further highlighting remimazolam\u0026rsquo;s potential to optimize postoperative resource utilization. These advantages are particularly relevant in outpatient or ambulatory surgery settings, where minimizing recovery time is a priority\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe findings of this study are consistent with previous research. Kim et al. conducted a study comparing the safety and efficacy of remimazolam and midazolam in bronchoscopy, demonstrating that the time from the end of surgery to full alertness and peak sedation was shorter in the remimazolam group\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Similarly, in Japan, Ichijima et al. investigated the use of remimazolam and midazolam in gastrointestinal endoscopy, showing that the median time to awakening was significantly shorter in the remimazolam group (0 minutes [0\u0026ndash;5.0 minutes]) compared to the midazolam group (27.0 minutes [23.0\u0026ndash;40.5 minutes]). Discharge time was also significantly shorter in the remimazolam group\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThese differences are likely attributable to the distinct pharmacokinetic profiles of the two agents. remimazolam is an ultrashort-acting benzodiazepine that undergoes rapid metabolism via tissue-specific carboxylesterases\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, resulting in predictable clearance and a shorter duration of action compared to midazolam, which relies on hepatic cytochrome P450 enzymes for metabolism\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. This pharmacokinetic advantage allows remimazolam to facilitate faster recovery times and more stable sedation profiles, as evidenced by the shorter extubation time and reduced PACU stay in our study. Moreover, remimazolam's pharmacokinetics make it a safer alternative in patients with hepatic or renal impairment, as its metabolism is independent of these organ systems\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA key strength of this study lies in its focus on elderly and moderate-risk patients (ASA II\u0026ndash;III), a population often underrepresented in anesthesia trials. The faster recovery times observed with remimazolam may be particularly advantageous for elderly patients, who are more susceptible to postoperative cognitive dysfunction and prolonged sedation\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Liu et al. compared remimazolam and midazolam regarding postoperative early cognitive recovery in elderly patients undergoing tooth extraction. Their results indicated that remimazolam facilitated faster recovery of postoperative cognitive function and reduced discharge time compared to midazolam\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Furthermore, the high patient satisfaction scores in the remimazolam group, though not quantitatively measured here, could be attributed to reduced postoperative drowsiness and quicker return to baseline function, factors known to influence patient-reported outcomes\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePrevious studies have shown that, compared to midazolam, remimazolam is associated with more stable hemodynamics and less respiratory depression\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. In cardiovascular surgery under general anesthesia, remimazolam caused significantly less reduction in mean arterial pressure (MAP) than midazolam, demonstrating superior hemodynamic stability\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, in the current study, the effects of remimazolam and midazolam on hemodynamics and respiratory parameters were similar. Both remimazolam and midazolam led to decreases in SBP, DBP, and HR, with no significant differences between the two groups. Changes in SpO₂ were relatively stable. These findings are consistent with results observed in bronchoscopy, which showed similar fluctuations in hemodynamic and respiratory parameters for remimazolam and midazolam\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Such differences across studies may be attributed to variations in surgical type and patient baseline characteristics.\u003c/p\u003e \u003cp\u003ePrevious evaluations of benzodiazepines in surgical anesthesia have demonstrated comparable safety profiles for remimazolam and midazolam, particularly regarding hypotension and bradycardia. In bronchoscopy, the incidence of hypotension was 2% in both the remimazolam and midazolam groups, with no bradycardia observed\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In the present study, there was a trend toward lower rates of hypotension and bradycardia in the remimazolam group compared to the midazolam group (13.6% vs. 15.5% and 8.6% vs. 13.6%, respectively), although these differences were not statistically significant, indicating good safety. The higher incidence of hypotension and bradycardia in this study may be related to factors such as the older age of patients, the complexity of the surgeries, and longer operation times. Notably, the safety profiles of remimazolam and midazolam appear superior to other anesthetic agents, such as propofol. For example, in LC under general anesthesia, remimazolam demonstrated more stable hemodynamics and a lower incidence of hypotension compared to propofol\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Similarly, in endoscopic submucosal dissection for esophageal squamous cell carcinoma, the incidence of hypotension was significantly lower in the midazolam group compared to the propofol group (28.8% vs. 47.0%, p\u0026thinsp;=\u0026thinsp;0.04), while the incidence of bradycardia was similar in both groups (19.7%)\u003csup\u003e22\u003c/sup\u003e. In this study, no respiratory depression (respiratory rate\u0026thinsp;\u0026lt;\u0026thinsp;10 breaths/min), nausea, or vomiting was observed. The absence of hypoxemia in the remimazolam group further supports its respiratory safety, a critical consideration in procedures requiring controlled ventilation\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. These findings underscore the broad applicability of remimazolam in a variety of surgical settings, particularly in high-risk populations such as the elderly or patients with comorbid conditions or hemodynamic instability\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite these advantages, our findings must be interpreted in light of several limitations. First, the retrospective design introduces potential selection bias and unmeasured confounding factors. Second, the single-center nature and modest sample size may limit generalizability. Future multicenter trials with larger sample sizes are needed to validate and expand upon these results. Finally, the study did not incorporate advanced monitoring techniques, such as bispectral index (BIS) or electroencephalographic monitoring, to assess sedation depth. Incorporating such tools in future research could provide more precise evaluations of anesthetic depth and recovery profiles.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn summary, remimazolam offers distinct clinical advantages over midazolam in LC, including faster recovery and shorter PACU stays, potentially improving hospital resource utilization. Both remimazolam and midazolam demonstrated stable hemodynamic profiles and low respiratory depression, indicating high safety. These advantages make remimazolam a promising alternative for anesthesia in minimally invasive surgeries. Larger multicenter studies are needed to validate these findings and explore its roles in different surgical settings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to this paper. YZ, XHX: Methodology, Investigation, Data collection, Writing\u0026mdash;Original Draft. QX, GSG: Conceptualization, Formal analysis. WHW: Methodology, Data collection. CZZ: Supervision, Writing\u0026mdash;Reviewing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Ningbo Natural Science Foundation (No. 2022J246).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used or analysed during the current study are available from the corresponding authors on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study followed the Declaration of Helsinki. This study was approved by the Human Research Ethics Committee, Ningbo No.2 Hospital (PJ-NBEY-KY-2025-076-01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all subjects and/or their legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMajedi, M. A., Sarlak, S., Sadeghi, Y. \u0026amp; Ahsan, B. Comparison of the effects of thoracic epidural anesthesia with general anesthesia on hemodynamic changes and its complications in patients undergoing laparoscopic cholecystectomy. \u003cem\u003eAdv Biomed Res\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 7 (2019).\u003c/li\u003e\n\u003cli\u003eBilgi, M., Alshair, E. E., G\u0026ouml;ksu, H. \u0026amp; Sevim, O. 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Opioid-free anesthesia improves postoperative recovery quality of small and medium-sized surgery: a prospective, randomized controlled study. \u003cem\u003eMinerva Anestesiol\u003c/em\u003e \u003cstrong\u003e90\u003c/strong\u003e, 759\u0026ndash;768 (2024).\u003c/li\u003e\n\u003cli\u003eLuo, L. et al. Comparative study about different doses of remimazolam in short laparoscopic surgery: a randomized controlled double-blind trial. \u003cem\u003eTher Clin Risk Manag\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 829\u0026ndash;837 (2023).\u003c/li\u003e\n\u003cli\u003eGu, J. et al. Comparison of remimazolam-flumazenil and propofol on psychomotor function and emergence following general anesthesia in surgical abortion: a randomized controlled trial. \u003cem\u003eDrug Des Devel Ther\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 6447\u0026ndash;6457 (2024).\u003c/li\u003e\n\u003cli\u003eKim, S. H. et al. Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 20498 (2023).\u003c/li\u003e\n\u003cli\u003eIchijima, R. et al. Comparative study of remimazolam and midazolam during sedated upper gastrointestinal endoscopy: a propensity score matching analysis. \u003cem\u003eJGH Open\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, e70100 (2025).\u003c/li\u003e\n\u003cli\u003eKim, K. M. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. \u003cem\u003eAnesth Pain Med (Seoul)\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 1\u0026ndash;11 (2022).\u003c/li\u003e\n\u003cli\u003ePaton, D. M. Remimazolam: a short-acting benzodiazepine for procedural sedation. \u003cem\u003eDrugs Today (Barc)\u003c/em\u003e \u003cstrong\u003e57\u003c/strong\u003e, 337\u0026ndash;346 (2021).\u003c/li\u003e\n\u003cli\u003eMorimoto, Y. Efficacy and safety profile of remimazolam for sedation in adults undergoing short surgical procedures. \u003cem\u003eTher Clin Risk Manag\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 95\u0026ndash;100 (2022).\u003c/li\u003e\n\u003cli\u003eHuang, X. D. et al. The impact of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients: an up-and-down sequential allocation trial. \u003cem\u003eDrug Des Devel Ther\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 3729\u0026ndash;3737 (2024).\u003c/li\u003e\n\u003cli\u003eZhang, L., Qiu, Y., Zhang, Z. F., Zhao, Y. F. \u0026amp; Ding, Y. M. Current perspectives on postoperative cognitive dysfunction in geriatric patients: insights from clinical practice. \u003cem\u003eFront Med (Lausanne)\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1466681 (2024).\u003c/li\u003e\n\u003cli\u003ePatel, D., Lunn, A. D., Smith, A. D., Lehmann, D. J. \u0026amp; Dorrington, K. L. Cognitive decline in the elderly after surgery and anaesthesia: results from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. \u003cem\u003eAnaesthesia\u003c/em\u003e \u003cstrong\u003e71\u003c/strong\u003e, 1144\u0026ndash;1152 (2016).\u003c/li\u003e\n\u003cli\u003eLiu, B. et al. Effect of remimazolam vs midazolam on early postoperative cognitive recovery in elderly patients undergoing dental extraction: a prospective randomized controlled study. \u003cem\u003eDrug Des Devel Ther\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 5895\u0026ndash;5904 (2024).\u003c/li\u003e\n\u003cli\u003eLi, X., Tian, M., Deng, Y., She, T. \u0026amp; Li, K. Advantages of sedation with remimazolam compared to midazolam for the removal of impacted tooth in patients with dental anxiety. \u003cem\u003eJ Oral Maxillofac Surg\u003c/em\u003e \u003cstrong\u003e81\u003c/strong\u003e, 536\u0026ndash;545 (2023).\u003c/li\u003e\n\u003cli\u003eShintani, R. et al. Comparison of hemodynamic effects of remimazolam and midazolam during anesthesia induction in patients undergoing cardiovascular surgery: a single-center retrospective and exploratory study. \u003cem\u003eCureus\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, e72032 (2024).\u003c/li\u003e\n\u003cli\u003eOminami, M. et al. Comparison of propofol with midazolam in endoscopic submucosal dissection for esophageal squamous cell carcinoma: a randomized controlled trial. \u003cem\u003eJ Gastroenterol\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 397\u0026ndash;406 (2018).\u003c/li\u003e\n\u003cli\u003eLiu, F. et al. Effect of remimazolam tosilate on the incidence of hypoxemia in elderly patients undergoing gastrointestinal endoscopy: a bi-center, prospective, randomized controlled study. \u003cem\u003eFront Pharmacol\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 1131391 (2023).\u003c/li\u003e\n\u003cli\u003eTian, Y. et al. Procedural sedative effect of remimazolam in ICU patients on invasive mechanical ventilation: a randomised, prospective study. \u003cem\u003eAnn Intensive Care\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 8 (2025).\u003c/li\u003e\n\u003c/ol\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"remimazolam, midazolam, laparoscopic cholecystectomy, safety, efficacy","lastPublishedDoi":"10.21203/rs.3.rs-6507789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6507789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLaparoscopic cholecystectomy (LC) is a widely performed minimally invasive procedure, with patients requiring to be given general anesthesia. Remimazolam and midazolam are two benzodiazepine drugs that have been extensively used for anesthesia induction and maintenance.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to compare the efficacy and safety of remimazolam and midazolam in patients undergoing LC, focusing on recovery time, hemodynamic stability, and adverse event incidence.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted on 184 patients who underwent LC under general anesthesia between January 2022 and January 2024. Patients were divided into remimazolam (n\u0026thinsp;=\u0026thinsp;81) and midazolam (n\u0026thinsp;=\u0026thinsp;103) groups. The primary outcome was extubation time, defined as the time from the end of anesthesia to successful extubation. Secondary outcomes included post-anesthesia care unit (PACU) stay duration, hemodynamic and respiratory parameters, and adverse events.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe remimazolam group had significantly shorter extubation times (33 min [IQR 24.0\u0026ndash;44.5] vs. 42 min [IQR 30.0\u0026ndash;61.0], p\u0026thinsp;=\u0026thinsp;0.0003) and PACU stay durations (55 min [IQR 45\u0026ndash;65] vs. 65 min [IQR 55\u0026ndash;80], p\u0026thinsp;=\u0026thinsp;0.0001) compared to the midazolam group. Both groups achieved a 100% success rate in anesthesia. No significant differences were observed in hemodynamic and respiratory parameters between the two groups at predefined time points. Adverse event rates, including hypotension (13.6% vs. 15.5%) and bradycardia (8.6% vs. 13.6%), were lower in the remimazolam group, although not statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No respiratory depression, nausea, or vomiting was observed in either group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eremimazolam demonstrated clear clinical advantages over midazolam in LC, including faster recovery and shorter PACU stays, with comparable hemodynamic stability and safety profiles. These findings suggest that remimazolam is a promising alternative for anesthesia in minimally invasive surgeries. Further multicenter studies are warranted to confirm these results and explore its utility in diverse surgical settings.\u003c/p\u003e","manuscriptTitle":"Comparison of Efficacy and Safety of Remimazolam and Midazolam in elderly Patients Undergoing Laparoscopic Cholecystectomy: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-02 07:27:35","doi":"10.21203/rs.3.rs-6507789/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-01T04:26:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-19T20:04:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321927591579949834079470295184842101078","date":"2025-11-19T12:01:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"114354261883378126258375207762093018542","date":"2025-11-07T16:45:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"112966657581793693183512088297717369804","date":"2025-09-15T00:06:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-30T10:39:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"119651424696687233490540540933891256961","date":"2025-07-28T09:27:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-27T16:20:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-27T16:19:42+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-24T13:15:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-24T08:03:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-23T00:58:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e6372a67-5761-429b-949b-8609c3098783","owner":[],"postedDate":"July 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":50776461,"name":"Biological sciences/Drug discovery/Drug safety"},{"id":50776462,"name":"Health sciences/Diseases/Endocrine system and metabolic diseases"}],"tags":[],"updatedAt":"2026-03-09T16:15:11+00:00","versionOfRecord":{"articleIdentity":"rs-6507789","link":"https://doi.org/10.1038/s41598-026-41918-0","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-03-04 15:58:17","publishedOnDateReadable":"March 4th, 2026"},"versionCreatedAt":"2025-07-02 07:27:35","video":"","vorDoi":"10.1038/s41598-026-41918-0","vorDoiUrl":"https://doi.org/10.1038/s41598-026-41918-0","workflowStages":[]},"version":"v1","identity":"rs-6507789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6507789","identity":"rs-6507789","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}