{"paper_id":"2b4baf11-3107-438d-975b-181443d6ccf1","body_text":"Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical 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 Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial Jie Gao, Hong Yu, Zhao Xu, Yongqing Xu, Yuwei Wu, Peng Liang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6037634/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Apr, 2026 Read the published version in Trials → Version 1 posted 6 You are reading this latest preprint version Abstract Background : Procedural sedation for patients with end-stage renal disease (ESRD) is challenging due to impaired renal function, which affects drug metabolism and increases the risk of adverse events. Remimazolam, a novel, ultrashort-acting intravenous sedative-hypnotic, offers rapid onset and clearance independent of renal function, making it a potential alternative to dexmedetomidine for sedation in this patient population. This study aims to compare the efficacy and safety of remimazolam and dexmedetomidine in ESRD patients undergoing procedural sedation. The primary hypothesis is that remimazolam will demonstrate superior sedation efficacy and a better safety profile, with reduced hemodynamic instability and faster recovery. Methods : This is a single-center, prospective, double-blind, randomized controlled trial (RCT). A total of 88 ESRD patients aged ≥18 years scheduled for peritoneal dialysis catheter placement or removal will be randomly assigned to receive either remimazolam or dexmedetomidine. The primary outcome is the sedation success rate, defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤1 within 10 minutes of drug administration. Secondary outcomes include time to sedation, intraoperative movement, the duration of BIS values <60 or >80 during anesthesia maintenance, recovery time, incidence of adverse events (e.g., hypotension, bradycardia, hypoxemia), postoperative pain scores and incidence of postoperative nausea and vomiting. Discussion : This is the first RCT to directly compare remimazolam and dexmedetomidine for sedation in ESRD patients undergoing procedural sedation. The results of this study will provide valuable insights into optimizing sedation strategies in this high-risk population, potentially improving clinical outcomes by minimizing complications associated with drug metabolism and recovery. Trial registration: Chinese Clinical Trial Registry. chictr.org.cn ChiCTR2300075278. Registered on August 31, 2023. https://www.chictr.org.cn/showproj.html?proj=205061 Randomized controlled trial Remimazolam Dexmedetomidine End-stage renal disease Sedation Anesthesia Peritoneal dialysis Figures Figure 1 Administrative information Title {1} Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial Trial registration {2a and 2b} Chinese Clinical Trial Registry ID: ChiCTR2300075278, August 16, 2021 Protocol version {3} 6 July 2023, version 2.0 Funding {4} None. Author details {5a} Jie Gao, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] . Hong Yu, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] . Zhao Xu, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] . Yongqing Xu, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] . Yuwei Wu, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] Peng Liang, MD. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041. Day Surgery Center, General Practice Medical Center，West China Hospital, Sichuan University, Chengdu 610041, China. [email protected] . Corresponding author. Name and contact information for the trial sponsor {5b} The trial sponsor is the West China Hospital of Sichuan University, Chengdu, China. Postal address: No.37 Guoxue Alley, Chengdu 610041, Sichuan, China. Tel: +862885423592, Fax: 86-28-85423593. Role of sponsor {5c} The trial sponsor has a regulatory role and will play a part in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Introduction Background and rationale {6a} Dialysis is a key treatment for patients with end-stage renal disease (ESRD), who often requires procedures such as arteriovenous fistula (AVF) creations or placement and removal of peritoneal dialysis catheters[1]. To alleviate the discomfort and anxiety of patient, and facilitate a smooth procedure, regional anesthesia combined with sedation is often used. However, for patients with ESRD, the selection of sedatives needs to be cautious, as impaired renal function may cause altered pharmacokinetics, prolonged drug half-life, and difficulty in the clearance of drugs or their metabolites[2]. These increase the risk of anesthetic overdose and postoperative complications. Therefore, it’s important to develop a strategy that strikes a balance between efficacy, safety, and renal function. Dexmedetomidine, an α-2 adrenergic agonist, is widely used as it provides sedation without respiratory depression. It has been shown to reduce perioperative renal injury in cardiac surgery patients in several randomized controlled trials (RCTs)[3–5]. Midazolam also has analgesic effects, thereby reducing the use of analgesics. Dexmedetomidine is metabolized in the liver into inactive metabolites, and its renal clearance is unaffected by renal impairment[6]. However, its long onset time prevents it from achieving satisfactory sedation quickly. And increased dosage can result in adverse effects like bradycardia, hypotension, and delayed recovery, which potentially exacerbate complications in critically ill patients, including those with ESRD[7, 8]. Remimazolam, a novel benzodiazepine derivative, offers a possible alternative to dexmedetomidine due to its unique pharmacokinetics. Remimazolam bypasses the renal pathway and is metabolized to inactive metabolites by tissue esterases, so its plasma clearance is comparable in patients with renal insufficiency and healthy individuals[9]. It has a rapid onset (1–3 minutes) and fast metabolism (terminal half-life of 0.75 hours), enabling more predictable and faster awakening[10]. Due to its short-acting properties, it is a promising sedative for procedures that require sedation but not deep anesthesia, such as local anesthesia in patients with ESRD. Phase II trials have demonstrated sufficient sedation depth for endoscopic procedures, with a faster awakening than midazolam[11, 12]. Studies suggest that its unique pharmacokinetics allow its use in patients with hepatic or renal impairment without dosage adjustments[9]. Additionally, remimazolam's sedative effects can be rapidly reversed by flumazenil, further enhancing its safety profile[13]. Remimazolam may have certain advantages in safety and efficacy under specific clinical circumstances. For example, in patients undergoing flexible bronchoscopy, remimazolam demonstrated non-inferiority to dexmedetomidine with better time metrics, enhanced hemodynamic stability, fewer procedure interruptions and reduced need for rescue medications[14–17]. In patients undergoing spinal anesthesia for orthopedic surgery, remimazolam similarly demonstrated faster induction and onset of sedation, without significant differences in hemodynamics and hypoventilation[18]. Considering its faster onset and offset, remimazolam may be particularly advantageous in reducing sedation time and minimizing recovery delays, critical for patients requiring kidney protection. Objectives {7} In summary, remimazolam may be a potentially superior sedative to dexmedetomidine for ESRD patients. However, no studies have specifically compared the efficacy and safety of these two drugs in sedating ESRD patients. This study aims to provide evidence to guide anesthesiologists in making safer and more effective sedation choices for ESRD patients, especially those requiring peritoneal dialysis. By directly comparing remimazolam and dexmedetomidine, this study seeks to fill gaps in the current literature and offer valuable insights for optimizing sedation protocols in one of the most challenging patient populations in anesthesiology. Trial design {8} This is a single-center, randomized, parallel-controlled clinical trial conducted to compare the efficacy and safety of remimazolam versus dexmedetomidine for sedation in patients with ESRD. Methods Study Setting {9} This study is being conducted at West China Hospital of Sichuan University. Ethical approval has been obtained from the hospital’s Ethics Committee. All participants will provide written informed consent prior to enrollment. The study adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Additional file 1). Eligibility Criteria {10} Inclusion criteria Patients meeting all of the following criteria will be included in this trial: (1) Adults aged ≥18 years. (2) American Society of Anesthesiologists (ASA) classification III or IV. (3) Diagnosed with ESRD (eGFR 25–60 ml/min/1.73 m²) requiring peritoneal dialysis catheter placement or removal. (4) Signed informed consent. Exclusion criteria Patients meeting one or more criteria listed below will be excluded from this trial: (1) Severe arrhythmias, including resting heart rate ≤50 bpm, conduction block (e.g., second- or third-degree atrioventricular block), frequent ventricular ectopy, or prolonged QTc (male ≥450 ms, female ≥470 ms) (2) Cardiovascular instability, including acute heart failure, unstable angina, or myocardial infarction within the last 6 months (3) Current heart failure (NYHA class III and IV) or severe valvular heart disease (4) Uncontrolled hypertension [Sitting systolic blood pressure (SBP) ≥160 mmHg and/or sitting diastolic blood pressure (DBP) ≥100 mmHg] or severe hypotension (Sitting SBP ≤90 mmHg). (5) Known contraindications to benzodiazepines or dexmedetomidine. (6) Pregnant or lactating women. (7) Psychiatric disorders requiring long-term psychotropic medications, or cognitive impairment. Who will take informed consent? {26a} Trained study investigators will explain the purpose, methods, risks, and benefits of the study to potential participants during preoperative visits. Written informed consent will be obtained from participants or their legal representatives before any study-related procedures. Additional Consent Provisions for Collection and Use of Participant Data and Biological Specimens {26b} The study does not involve the collection or storage of biological specimens for future research. Data collected will be used solely for the purposes of this study. Interventions Explanation for the choice of comparators {6b} Remimazolam is a novel benzodiazepine with rapid onset and offset and minimal respiratory or hemodynamic effects. It is being compared to dexmedetomidine, a commonly used sedative in patients with renal dysfunction, due to its potential renal protective effects and stable sedation. Intervention description {11a} Study Drug Administration Both patients in the two groups will be administered with an intravenous injection of sufentanil at a dose of 0.1 µg/kg for pre-sedation. Subsequently, participants in the remimazolam group will receive a bolus dose of remimazolam at 0.15–0.2 mg/kg over 3 minutes. Additional doses of 0.1 mg/kg will be administered as needed to achieve a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of ≤1. Continuous intravenous infusion of remimazolam at a rate of 0.1–0.3 mg/kg/h will be maintained to achieve a bispectral index (BIS) of 60–80. Participants in the dexmedetomidine group will then receive a loading dose of dexmedetomidine at 0.5 μg/kg over 10 minutes, followed by a maintenance infusion of dexmedetomidine at a rate of 0.2–0.7 μg/kg/h to maintain a bispectral index (BIS) of 60–80. Anesthesia management Standard monitoring will include electrocardiogram (ECG), pulse oximetry, non-invasive blood pressure, and BIS. Sedation will be followed by an ultrasound-guided transverse abdominis plane (TAP) block using 0.25% ropivacaine. Postoperative care will be provided in the post-anesthesia care unit (PACU) or ward. Criteria for discontinuing or modifying allocated interventions {11b} Participants will be withdrawn if they experience severe adverse reactions or request to terminate participation. In cases of sedation failure or hemodynamic instability, adjustments to sedation protocols will be permitted. Strategies to improve adherence to interventions {11c} Not applicable. Interventions in this study will be completed during anesthesia and without the cooperation of patients. Relevant concomitant care permitted or prohibited during the trial {11d} Patients will receive standard perioperative care, including appropriate fluid management and monitoring. Additional sedatives or analgesics outside the protocol will be prohibited unless required for safety. Provisions for Post-Trial Care {30} Participants will receive routine follow-up for 24 hours postoperatively to monitor for adverse events. Any study-related adverse events will be managed free of charge. Outcomes {12} Primary outcome The primary outcome is the sedation success rate, defined as achieving a MOAA/S score of ≤1 within 10 minutes after drug administration. Secondary outcomes The secondary outcomes are categorized into efficacy and safety measures. For efficacy, the secondary outcomes include the following: (1) the time to sedation onset, defined as the time from drug administration to a MOAA/S score of ≤1 and BIS <80; (2) the incidence and frequency of intraoperative movements during surgical or nerve block procedures; (3) the duration of BIS values <60 or >80 during anesthesia maintenance. For safety, the secondary outcomes include the following: (1) the time to recovery, defined as the time from drug discontinuation to a MOAA/S score of 5; (2) hemodynamic stability, specifically the incidence of hypotension (sitting SBP ≤90 mmHg, or the mean arterial pressure [MAP] decrease exceeds 25% of the baseline) or bradycardia (HR<50 bpm); (3) respiratory stability, particularly when SpO 2 drops below 90%; (4) postoperative recovery outcomes, including the incidence of nausea, vomiting, and visual analog scale (VAS) on postoperative day 1 (POD1). Participant timeline {13} Participants will be screened within 2 days prior to surgery, randomized on the day of surgery, and followed up until 24 hours postoperatively. The schedule will include sedation assessment, intraoperative monitoring, and postoperative recovery evaluation, and is shown in Table 1 and Fig. 1. Table 1 The SPIRIT Figure of this trial. STUDY PERIOD Enrollment Allocation Intervention Post-intervention Time point Preoperative visit Allocation During induction until 20 minutes after induction POD1 ENROLLMENT: Eligibility screen Informed consent Demographic date Allocation × × × × INTERVENTIONS: Remimazolam Dexmedetomidine Adverse reaction Surgery and anesthesia date × × × × ASSESSMENTS: MOAA/S score BIS Intraoperative movements CVP/CO/SVR Nausea/vomiting HR/SBP/DBP/MBP/ SpO2 VAS × × × × × × × × × POD: postoperative day; MOAA/S score: Modified Observer's Assessment of Alertness/Sedation score; BIS: bispectral index; CVP: central venous pressure; CO: cardiac output; SVR: systematic vascular resistance; HR: hear rate; SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; VAS: Sample size {14} According to the literature[19, 20], the success rate of sedation with remimazolam at a dose of 0.3~0.4 mg/kg ranges from 94% to 100% (taken as 99%,). We assume that the success rate of sedation with dexmedetomidine is only 80% of that of remimazolam. A total sample of 80 participants (40 per group) was required to achieve 80% power and 5% significance level. A 10% dropout rate will be accounted for, resulting in a target enrollment of 88 participants. Recruitment {15} All patients aged more than 18 with diagnosed ESRD undergoing peritoneal dialysis catheter placement or removal will be screened by the investigator daily. Verbal and written information regarding the trial will be provided if they meet all inclusion criteria and no exclusion criteria. The recruitment of patients is on-going. Since we are high-volume centers, we will be able to identify eligible patients and recruit required sample size. Assignment of interventions: allocation Sequence generation {16a} Randomization will be performed using block randomization with block sizes of 2 or 4. Concealment mechanism {16b} Allocation will be concealed using opaque, sealed envelopes. Implementation {16c} Randomization will be performed by a statistician independent of the clinical team. Assignment of interventions: blinding Who will be blinded {17a} Participants, surgical teams, outcome assessors, and data analysts will be blinded to group allocation. The randomization list will be securely maintained by a designated unblinding officer in West China Hospital, who is not involved in the trial's clinical or assessment procedures. Procedure for unblinding if needed {17b} Unblinding will be permitted only in emergencies where knowledge of the allocated intervention is essential for the clinical management or safety of the participant. In such cases, the attending physician must contact the principal investigator (PI) or the designated unblinding officer, who will verify the necessity of unblinding and perform the procedure following a predefined protocol. The unblinding process will be documented in detail, including the reason for unblinding, the individuals involved, and the date and time of the event. The participant will remain in the study unless the unblinding reveals information that necessitates their withdrawal for safety reasons. Data collection and management Plans for assessments and collection of outcomes {18a} All collected data will be entered into a standardized case report form (CRF). Data collection will encompass baseline characteristics, intraoperative sedation levels, hemodynamic and respiratory parameters, and postoperative recovery metrics. Specifically, intraoperative data including sedation depth (measured by BIS), MOAA/S scores, blood pressure, heart rate, pulse oxygen saturation (SpO 2 ), and analgesic use will be documented. Postoperatively, the incidence of nausea and vomiting, as well as pain scores (assessed by VAS), will be recorded on postoperative day 1 (POD1). Plans to promote participant retention and complete follow-up {18b} During the preoperative visit, patients will be fully informed about the intraoperative procedure and postoperative follow-up. And the study investigators who are in charge of follow-up will visit patients within POD1. Data management {19} Data will be recorded in CRF and entered into a secure database. Regular monitoring by principal investigators (PL) will ensure data accuracy. All study members will receive protocol and device training (if necessary) before participating in the study to ensure protocol adherence. Data will be stored for at least 3 years after trial termination and publication of the final report. Confidentiality {27} Participant data will be de-identified and stored securely. Access will be limited to authorized personnel. Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} Not applicable. There exist no biological specimens to be collected in this study Statistical methods Statistical methods for primary and secondary outcomes {20a} Analyses will be performed using IBM SPSS 27 (version 27.0, IBM Corp., New York, NY, USA) software. For continuous variables and descriptive values, means, standard deviations (SDs) will be reported. For the variables with a normal distribution, statistical comparisons between the groups will be made by using a t-test. If the variables have a non-normal distribution or ordinal level, statistical comparison between groups will be made using the Mann-Whitney U test. Measures with a discrete distribution will be expressed as percentages and analyzed by the chi-squared test or Fisher’s exact test as appropriate. For the categorical variables, frequency and corresponding percentage will be given and analyzed using chi-square or Fisher's exact tests. All tests will be conducted with 95% confidence intervals (CIs). A P value of less than 0.05 will be considered statistically significant. Interim analyses {21b} No interim analyses are planned. Methods for additional analyses {20b} Subgroup analyses will be conducted based on age, gender, and baseline characteristics. Methods to handle missing data {20c} Methods in analysis to handle protocol non‑adherence and any statistical methods to handle missing data {20c} All outcomes will undergo an intent-to-treat (ITT) and per-protocol (PP) analyses based on the initial anesthesia allocation. Sensitivity analysis will be performed to handle protocol violation and deviation cases using the per-protocol principle. The missing value will be filled up by last-observation-carried-forward (LOCF) method. No multiple imputation will be used for missing data. Plans to give access to the full protocol, participant-level data, and statistical code {31c} The datasets analyzed during the current study and statistical code are available from the corresponding author on reasonable request, as is the full protocol. Oversight and monitoring Composition of the coordinating center and trial steering committee {5d} The coordinating team consists of anesthesiologists and statisticians overseeing trial implementation and data integrity. The study team has a conference online weekly to discuss the problems in the conduct of the trial. There is no trial steering committee or stakeholder and public involvement group. Composition of the data monitoring committee, its role, and reporting structure {21a} Not applicable. There is no data monitoring committee in this study. Instead, the principal investigator will check the appropriateness of the data and conduction of the trial every 2 weeks. Adverse event reporting and harms {22} Adverse events related to this study protocol primarily include severe hypotension and sedation failure. In the event of hypotension, vasoactive drugs will be administered during anesthesia induction when the systolic blood pressure (SBP) drops below 90 mmHg or exhibits a 30% reduction from baseline. If sedation fails, rescue sedative medications, such as propofol, midazolam, or etomidate, will be used to complete anesthesia induction. Additionally, dexmedetomidine, an alpha-2 adrenergic agonist, may be employed as a sedative adjunct due to its properties of providing sedation without significant respiratory depression, which can be beneficial in managing sedation failures. Its potential side effects, such as bradycardia and hypotension, will be monitored closely. All adverse events will be treated immediately and reported to the institutional review board. Participants will also be followed up until adverse events are fully resolved or therapy is terminated. Frequency and plans for auditing trial conduct {23} The department of research office and the ethics committee of West China Hospital will audit the study annually. And the principal investigator will check the appropriateness of the data and conduction of the trial every 2 weeks. Plans for communicating important protocol amendments to relevant parties (e.g., trail participants, ethical committees) {25} Any protocol amendments will be written into a formal substantial amendment reviewed by the institutional review board of the West China Hospital before application. Dissemination plans {31a} All patients will provide written informed consent before the start of any protocol-specified procedures or assessments. The results of the study will be presented at relevant conferences and submitted to international peer-reviewed journals and conferences. Discussion ESRD patients undergoing procedural sedation are faced with unique challenges due to altered drug metabolism, susceptibility to hemodynamic instability, and increased perioperative risks. Despite the growing use of remimazolam and dexmedetomidine in clinical practice, evidence comparing their effects on sedation efficacy and safety in this high-risk population is lacking. This trial protocol is designed to address this gap by rigorously comparing these two agents in patients undergoing peritoneal dialysis catheter placement or removal. The primary focus of this RCT is to evaluate sedation success rates, onset and recovery times, and hemodynamic stability, which are crucial factors in optimizing perioperative outcomes for ESRD patients. Previous studies[9, 21, 22] have highlighted the advantages of remimazolam, including its rapid onset and offset, favorable hemodynamic profile, and metabolism by tissue esterases into inactive metabolites, making it an ideal agent for patients with renal dysfunction. In contrast, dexmedetomidine is well-regarded for its stable respiratory profile and sedative-analgesic properties but has limitations such as delayed onset, prolonged recovery, and risks of bradycardia and hypotension[23, 24]. The study has been developed in strict accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines[25] to ensure methodological rigor and transparency. The design of this trial incorporates rigorous methodology to ensure high-quality data. Randomization and blinding will minimize bias, while the use of standardized sedation protocols ensures consistency across groups. Primary outcomes, such as sedation success rate and time to achieve sedation, will provide clear measures of efficacy, while secondary outcomes, including hemodynamic stability and adverse event rates, will comprehensively evaluate safety. Additionally, the follow-up period will allow for the assessment of immediate postoperative outcomes, providing holistic understanding of each agent's effects. All efforts are made to ensure that the findings will be relevant and applicable to clinical practice. The results of this trial are expected to contribute high-quality evidence to guide the choice of sedation agents in ESRD patients. We hypothesize that remimazolam will demonstrate superior performance in terms of faster onset and recovery, higher sedation success rates, and comparable or reduced adverse event rates compared to dexmedetomidine. This may help improve perioperative management and patient satisfaction. In conclusion, this trial protocol is designed to generate robust and reliable evidence on the comparative efficacy and safety of remimazolam and dexmedetomidine for procedural sedation in ESRD patients. By adhering to CONSORT guidelines, we ensure the reliability and reproducibility of our findings. Future multicenter studies with larger sample sizes may validate and expand upon these results, further advancing the standard of care in this challenging patient population. Strengths and limitations Despite its strengths, this study has certain limitations. As a single-center trial, the findings may not fully capture variations in patient populations or practice patterns across different institutions. While the sample size is powered to detect differences in primary outcomes, rare adverse events may not be adequately evaluated. Additionally, the exclusion of patients with severe cardiovascular instability or psychiatric disorders limits the generalizability of the results to these subgroups. Trial status The current protocol is version 2.0 and was issued on 6 July 2023. At the time of manuscript submission, the study is in the phase of recruitment. Recruitment has been begun in March 2024 and is expected to be completed by June 2025. Abbreviations ASA: American Society of Anesthesiologists; BIS: Bispectral Index; CIs: Confidence intervals; CRF: Case Report Form; DBP: Diastolic Blood Pressure; ECG: Electrocardiogram; eGFR: Estimated Glomerular Filtration Rate; ESRD: End-Stage Renal Disease; HR: Heart Rate; ITT: Intent-to-Treat; MAP: Mean Arterial Pressure; MOAA/S: Modified Observer's Assessment of Alertness/Sedation; NYHA: New York Heart Association; PACU: Post-Anesthesia Care Unit; PI: Principal Investigator; POD1: Postoperative Day 1; PP: Per-Protocol; RCT: Randomized Controlled Trial; SBP: Systolic Blood Pressure; SD: Standard Deviation; SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials; SpO 2 : pulse oxygen saturation; TAP: Transversus Abdominis Plane; VAS: Visual Analog Scale; Declarations Acknowledgements We thank the patients and staff at the Department of Nephrology for their assistance throughout this study. Author’s contributions {31b} Peng Liang planned the study. Zhao Xu performed the statistical design of the study. All authors contributed to the design and development of the trial. Jie Gao and Hong Yu drafted the manuscript. Yongqing Xu and Yuwei Wu critically revised the manuscript. All authors read and approved the final manuscript. Funding {4} None. Availability of data and material {29} Any data required to support the protocol can be supplied on request. Ethical Approval and Consent to participate {24} The study protocol has been approved by the Ethics Committee of West China Hospital of Sichuan University [Ethic Committee No. 2023(1083)] and registered at chictr.org.cn (ID: ChiCTR2300075278) on August 31, 2023. All patients will provide written informed consent before the start of any protocol-specified procedures or assessments. The patients can withdraw from the trial at any time. The results of the study will be presented at relevant conferences and submitted to international peer-reviewed journals. 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Gastrointest Endosc. 2015;83:984–92. doi: 10.1016/j.gie.2015.08.062 Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, et al. A Phase IIa, Randomized, Double-Blind Study of Remimazolam (CNS 7056) Versus Midazolam for Sedation in Upper Gastrointestinal Endoscopy. Anesthesia Analg. 2015;120:771–80. doi: 10.1213/ane.0000000000000548 Yoshida A, Kurata S, Kida K, Tsubokawa T. Anesthetic management for the sleep-awake-sleep technique of awake craniotomy using a novel benzodiazepine remimazolam and its antagonist flumazenil. JA Clin Rep. 2021;7. doi: 10.1186/s40981-021-00417-z Chen Q, Qin B, Zhang M, Zhou Y, Shi X, Xie Y. The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial. DDDT. 2024;Volume 18:967–78. doi: 10.2147/dddt.s446222 Xu H, Wang L, Zhu W, Ren C, Liu G, Liu Y. Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmedetomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial. DDDT. 2024;Volume 18:2317–27. doi: 10.2147/dddt.s460949 Zhou L, Zou J, Li X, Zuo X, Gu M, Sun K, et al. Efficacy and safety of remimazolam versus dexmedetomidine for patients undergoing flexible fiberoptic bronchoscopy: A randomized, clinical trial. J Clin Anesth. 2024;99:111677–111677. doi: 10.1016/j.jclinane.2024.111677 Chen X, Xin D, Xu G, Zhao J, Lv Q. The Efficacy and Safety of Remimazolam Tosilate Versus Dexmedetomidine in Outpatients Undergoing Flexible Bronchoscopy: A Prospective, Randomized, Blind, Non-Inferiority Trial. Front Pharmacol. 2022;13. doi: 10.3389/fphar.2022.902065 Hong S-W, Park J-Y, Rhee K-Y, Kim S-H. Comparison emergence of sedation, using dexmedetomidine and remimazolam, in spinal anaesthesia - double blinded randomized controlled trial. Int J Med Sci. 2024;21:1552–8. doi: 10.7150/ijms.95736 DAI G, PEI L, DUAN F, LIAO M, ZHANG Y, ZHU M, et al. Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia. Minerva Anestesiol. 2021;87. doi: 10.23736/s0375-9393.21.15517-8 Siemens K, Parmar K, Harris J, Hunt BJ, Tibby SM. Fibrinolytic activity in infants undergoing cardiac surgery on cardiopulmonary bypass with routine tranexamic acid. Eur J Anaesthesiol. 2025. doi: 10.1097/eja.0000000000002124 Chen L, Qin W, Wu J, Zhao G, Jiang X, Li M, et al. Effect of Remimazolam on Induction and Maintenance of General Anesthesia in Kidney Transplant Patients. IJGM. 2024;Volume 17:2455–63. doi: 10.2147/ijgm.s464530 Dai Q-C, Zhao J-L, Miao X-Y, Wang R, Hui Z. Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock. Eur Rev Med Pharmacol Sci. 2024;28:2483–92. doi: 10.26355/eurrev_202403_35755 Kim H, Kim Y, Bae J, Yoo S, Lim Y-J, Kim J-T. Comparison of remimazolam and dexmedetomidine for intraoperative sedation in patients undergoing lower extremity surgery under spinal anesthesia: a randomized clinical trial. Reg Anesth Pain Med. 2023;49:110–6. doi: 10.1136/rapm-2023-104415 Lee S. Dexmedetomidine: present and future directions. Korean J Anesthesiol. 2019;72:323–30. doi: 10.4097/kja.19259 Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials. International Journal of Surgery. 2010;340 mar23 1:c869–c869. doi: 10.1136/bmj.c869 Supplementary Files Additionalfile1SPIRITchecklistrevised.docx Additional file 1: The SPIRIT 2013 checklist of this trial. Additionalfile2modelconsentform.docx Additional file 2: The model consent form. Cite Share Download PDF Status: Published Journal Publication published 16 Apr, 2026 Read the published version in Trials → Version 1 posted Editorial decision: Major revision 29 Mar, 2025 Reviewers agreed at journal 18 Mar, 2025 Reviewers invited by journal 18 Mar, 2025 Editor invited by journal 04 Mar, 2025 Editor assigned by journal 18 Feb, 2025 First submitted to journal 17 Feb, 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. 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. 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-6037634\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":430423208,\"identity\":\"4e55ac7e-568b-403e-99d9-945eff50db12\",\"order_by\":0,\"name\":\"Jie Gao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"West China Hospital of Sichuan University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jie\",\"middleName\":\"\",\"lastName\":\"Gao\",\"suffix\":\"\"},{\"id\":430423209,\"identity\":\"b7258d9f-3768-48f5-9744-b8c6a0a9c1df\",\"order_by\":1,\"name\":\"Hong 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chart.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6037634/v1/58490daba99759b60f71d04a.png\"},{\"id\":107350889,\"identity\":\"835650b9-612c-4924-b704-a94e5d9617e5\",\"added_by\":\"auto\",\"created_at\":\"2026-04-20 16:06:24\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1116379,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6037634/v1/f4bce90e-07c0-4be8-8dd9-f446d1364e0e.pdf\"},{\"id\":79339441,\"identity\":\"5b4bd22d-c100-4fdd-8cb6-e3b4c133e9b9\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 08:24:33\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":45035,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAdditional file 1: The SPIRIT 2013 checklist of this trial.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Additionalfile1SPIRITchecklistrevised.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6037634/v1/40a1a6030bca77e69a3b11b5.docx\"},{\"id\":79339434,\"identity\":\"671c8013-1eb1-4fe3-a91e-71b49f4f0e6e\",\"added_by\":\"auto\",\"created_at\":\"2025-03-27 08:24:33\",\"extension\":\"docx\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":27004,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAdditional file 2: The model consent form.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Additionalfile2modelconsentform.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6037634/v1/88549905a721147e8de93c5c.docx\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial\",\"fulltext\":[{\"header\":\"Administrative information\",\"content\":\"\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eTitle {1}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eEfficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eTrial registration {2a and 2b}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eChinese Clinical Trial Registry ID: ChiCTR2300075278, August 16, 2021\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eProtocol version {3}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003e6 July 2023, version 2.0\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eFunding {4}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eNone.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eAuthor details {5a}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eJie Gao, MD.\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. gaojiedr@163.com.\\u003c/p\\u003e\\n \\u003cp\\u003eHong Yu, MD.\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. happyjia1990@foxmail.com.\\u003c/p\\u003e\\n \\u003cp\\u003eZhao Xu, MD.\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. davidxuzhao@gmail.com.\\u003c/p\\u003e\\n \\u003cp\\u003eYongqing Xu, MD.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. 1305923280@qq.com.\\u003c/p\\u003e\\n \\u003cp\\u003eYuwei Wu, MD.\\u0026nbsp;\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. wywberyl@qq.com\\u003c/p\\u003e\\n \\u003cp\\u003ePeng Liang, MD.\\u003c/p\\u003e\\n \\u003cp\\u003eDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041. Day Surgery Center, General Practice Medical Center，West China Hospital, Sichuan University, Chengdu 610041, China. liangpeng_world@foxmail.com\\u003cu\\u003e.\\u0026nbsp;\\u003c/u\\u003eCorresponding author.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eName and contact information for the trial sponsor {5b}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eThe trial sponsor is the West China Hospital of Sichuan University, Chengdu, China. Postal address: No.37 Guoxue Alley, Chengdu 610041, Sichuan, China. Tel: +862885423592, Fax: 86-28-85423593.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 132px;\\\"\\u003e\\n \\u003cp\\u003eRole of sponsor {5c}\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 421px;\\\"\\u003e\\n \\u003cp\\u003eThe trial sponsor has a regulatory role and will play a part in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\"},{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground and rationale {6a}\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDialysis is a key treatment for patients with end-stage renal disease (ESRD), who often requires procedures such as arteriovenous fistula (AVF) creations or placement and removal of peritoneal dialysis catheters[1]. To alleviate the discomfort and anxiety of patient, and facilitate a smooth procedure, regional anesthesia combined with sedation is often used. However, for patients with ESRD, the selection of sedatives needs to be cautious, as impaired renal function may cause altered pharmacokinetics, prolonged drug half-life, and difficulty in the clearance of drugs or their metabolites[2]. These increase the risk of anesthetic overdose and postoperative complications. Therefore, it\\u0026rsquo;s important to develop a strategy that strikes a balance between efficacy, safety, and renal function.\\u003c/p\\u003e\\n\\u003cp\\u003eDexmedetomidine, an \\u0026alpha;-2 adrenergic agonist, is widely used as it provides sedation without respiratory depression. It has been shown to reduce perioperative renal injury in cardiac surgery patients in several randomized controlled trials (RCTs)[3\\u0026ndash;5]. Midazolam also has analgesic effects, thereby reducing the use of analgesics. Dexmedetomidine is metabolized in the liver into inactive metabolites, and its renal clearance is unaffected by renal impairment[6]. However, its long onset time prevents it from achieving satisfactory sedation quickly. And increased dosage can result in adverse effects like bradycardia, hypotension, and delayed recovery, which potentially exacerbate complications in critically ill patients, including those with ESRD[7, 8].\\u003c/p\\u003e\\n\\u003cp\\u003eRemimazolam, a novel benzodiazepine derivative, offers a possible alternative to dexmedetomidine due to its unique pharmacokinetics. Remimazolam bypasses the renal pathway and is metabolized to inactive metabolites by tissue esterases, so its plasma clearance is comparable in patients with renal insufficiency and healthy individuals[9]. It has a rapid onset (1\\u0026ndash;3 minutes) and fast metabolism (terminal half-life of 0.75 hours), enabling more predictable and faster awakening[10]. Due to its short-acting properties, it is a promising sedative for procedures that require sedation but not deep anesthesia, such as local anesthesia in patients with ESRD. Phase II trials have demonstrated sufficient sedation depth for endoscopic procedures, with a faster awakening than midazolam[11, 12]. Studies suggest that its unique pharmacokinetics allow its use in patients with hepatic or renal impairment without dosage adjustments[9].\\u0026nbsp;Additionally, remimazolam\\u0026apos;s sedative effects can be rapidly reversed by flumazenil, further enhancing its safety profile[13].\\u003c/p\\u003e\\n\\u003cp\\u003eRemimazolam may have certain advantages in safety and efficacy under specific clinical circumstances. For example, in patients undergoing flexible bronchoscopy, remimazolam demonstrated non-inferiority to dexmedetomidine with better time metrics, enhanced hemodynamic stability, fewer procedure interruptions and reduced need for rescue medications[14\\u0026ndash;17]. In patients undergoing spinal anesthesia for orthopedic surgery, remimazolam similarly demonstrated faster induction and onset of sedation, without significant differences in hemodynamics and hypoventilation[18]. Considering its faster onset and offset, remimazolam may be particularly advantageous in reducing sedation time and minimizing recovery delays, critical for patients requiring kidney protection.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eObjectives {7}\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn summary, remimazolam may be a potentially superior sedative to dexmedetomidine for ESRD patients. However, no studies have specifically compared the efficacy and safety of these two drugs in sedating ESRD patients. This study aims to provide evidence to guide anesthesiologists in making safer and more effective sedation choices for ESRD patients, especially those requiring peritoneal dialysis. By directly comparing remimazolam and dexmedetomidine, this study seeks to fill gaps in the current literature and offer valuable insights for optimizing sedation protocols in one of the most challenging patient populations in anesthesiology.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial design {8}\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis is a single-center, randomized, parallel-controlled clinical trial conducted to compare the efficacy and safety of remimazolam versus dexmedetomidine for sedation in patients with ESRD.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eStudy Setting {9}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study is being conducted at West China Hospital of Sichuan University. Ethical approval has been obtained from the hospital\\u0026rsquo;s Ethics Committee. All participants will provide written informed consent prior to enrollment. The study adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Additional file 1).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEligibility Criteria {10}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eInclusion criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients meeting all of the following criteria will be included in this trial:\\u003c/p\\u003e\\n\\u003cp\\u003e(1) Adults aged \\u0026ge;18 years.\\u003c/p\\u003e\\n\\u003cp\\u003e(2) American Society of Anesthesiologists (ASA) classification III or IV.\\u003c/p\\u003e\\n\\u003cp\\u003e(3) Diagnosed with ESRD (eGFR 25\\u0026ndash;60 ml/min/1.73 m\\u0026sup2;) requiring peritoneal dialysis catheter placement or removal.\\u003c/p\\u003e\\n\\u003cp\\u003e(4) Signed informed consent.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eExclusion criteria\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients meeting one or more criteria listed below will be excluded from this trial:\\u003c/p\\u003e\\n\\u003cp\\u003e(1) Severe arrhythmias, including resting heart rate \\u0026le;50 bpm, conduction block (e.g., second- or third-degree atrioventricular block), frequent ventricular ectopy, or prolonged QTc (male \\u0026ge;450 ms, female \\u0026ge;470 ms)\\u003c/p\\u003e\\n\\u003cp\\u003e(2) Cardiovascular instability, including acute heart failure, unstable angina, or myocardial infarction within the last 6 months\\u003c/p\\u003e\\n\\u003cp\\u003e(3) Current heart failure (NYHA class III and IV) or severe valvular heart disease\\u003c/p\\u003e\\n\\u003cp\\u003e(4) Uncontrolled hypertension [Sitting systolic blood pressure (SBP) \\u0026ge;160 mmHg and/or sitting diastolic blood pressure (DBP) \\u0026ge;100 mmHg] or severe hypotension (Sitting SBP \\u0026le;90 mmHg).\\u003c/p\\u003e\\n\\u003cp\\u003e(5) Known contraindications to benzodiazepines or dexmedetomidine.\\u003c/p\\u003e\\n\\u003cp\\u003e(6) Pregnant or lactating women.\\u003c/p\\u003e\\n\\u003cp\\u003e(7) Psychiatric disorders requiring long-term psychotropic medications, or cognitive impairment.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eWho will take informed consent? {26a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTrained study investigators will explain the purpose, methods, risks, and benefits of the study to potential participants during preoperative visits. Written informed consent will be obtained from participants or their legal representatives before any study-related procedures.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eAdditional Consent Provisions for Collection and Use of Participant Data and Biological Specimens {26b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study does not involve the collection or storage of biological specimens for future research. Data collected will be used solely for the purposes of this study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eInterventions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eExplanation for the choice of comparators {6b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eRemimazolam is a novel benzodiazepine with rapid onset and offset and minimal respiratory or hemodynamic effects. It is being compared to dexmedetomidine, a commonly used sedative in patients with renal dysfunction, due to its potential renal protective effects and stable sedation.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eIntervention description {11a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStudy Drug Administration\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBoth patients in the two groups will be administered with an intravenous injection of sufentanil at a dose of 0.1 \\u0026micro;g/kg for pre-sedation. Subsequently, participants in the remimazolam group will receive a bolus dose of remimazolam at 0.15\\u0026ndash;0.2 mg/kg over 3 minutes. Additional doses of 0.1 mg/kg will be administered as needed to achieve a Modified Observer\\u0026apos;s Assessment of Alertness/Sedation (MOAA/S) score of \\u0026le;1. Continuous intravenous infusion of remimazolam at a rate of 0.1\\u0026ndash;0.3 mg/kg/h will be maintained to achieve a bispectral index (BIS) of 60\\u0026ndash;80. Participants in the dexmedetomidine group\\u0026nbsp;will then receive a loading dose of dexmedetomidine at 0.5 \\u0026mu;g/kg over 10 minutes, followed by a maintenance infusion of dexmedetomidine at a rate of 0.2\\u0026ndash;0.7 \\u0026mu;g/kg/h to maintain a bispectral index (BIS) of 60\\u0026ndash;80.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAnesthesia management\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eStandard monitoring will include electrocardiogram (ECG), pulse oximetry, non-invasive blood pressure, and BIS. Sedation will be followed by an ultrasound-guided transverse abdominis plane (TAP) block using 0.25% ropivacaine.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003ePostoperative care will be provided in the post-anesthesia care unit (PACU) or ward.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eCriteria for discontinuing or modifying allocated interventions {11b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants will be withdrawn if they experience severe adverse reactions or request to terminate participation. In cases of sedation failure or hemodynamic instability, adjustments to sedation protocols will be permitted.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eStrategies to improve adherence to interventions {11c}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable. Interventions in this study will be completed during anesthesia and without the cooperation of patients.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eRelevant concomitant care permitted or prohibited during the trial {11d}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatients will receive standard perioperative care, including appropriate fluid management and monitoring. Additional sedatives or analgesics outside the protocol will be prohibited unless required for safety.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eProvisions for Post-Trial Care {30}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants will receive routine follow-up for 24 hours postoperatively to monitor for adverse events. Any study-related adverse events will be managed free of charge.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eOutcomes {12}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePrimary outcome\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe primary outcome is the sedation success rate, defined as achieving a MOAA/S score of \\u0026le;1 within 10 minutes after drug administration.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eSecondary outcomes\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe secondary outcomes are categorized into efficacy and safety measures.\\u003c/p\\u003e\\n\\u003cp\\u003eFor efficacy, the secondary outcomes include\\u0026nbsp;the following: (1) the time to sedation onset, defined as the time from drug administration to a MOAA/S score of \\u0026le;1 and BIS \\u0026lt;80; (2) the incidence and frequency of intraoperative movements during surgical or nerve block procedures; (3) the duration of BIS values \\u0026lt;60 or \\u0026gt;80 during anesthesia maintenance.\\u003c/p\\u003e\\n\\u003cp\\u003eFor safety, the secondary outcomes include\\u0026nbsp;the following: (1) the time to recovery, defined as the time from drug discontinuation to a MOAA/S score of 5; (2) hemodynamic stability, specifically the incidence of hypotension (sitting SBP \\u0026le;90 mmHg, or the mean arterial pressure\\u0026nbsp;[MAP] decrease exceeds 25% of the baseline) or bradycardia (HR\\u0026lt;50 bpm); (3) respiratory stability, particularly when SpO\\u003csub\\u003e2\\u003c/sub\\u003e drops below 90%; (4) postoperative recovery outcomes, including the incidence of nausea, vomiting, and visual analog scale (VAS) on postoperative day 1 (POD1).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eParticipant timeline {13}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants will be screened within 2 days prior to surgery, randomized on the day of surgery, and followed up until 24 hours postoperatively. The schedule will include sedation assessment, intraoperative monitoring, and postoperative recovery evaluation, and is shown in Table 1 and Fig. 1.\\u003c/p\\u003e\\n\\u003cp\\u003eTable 1 The SPIRIT Figure of this trial.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cdiv align=\\\"center\\\"\\u003e\\n \\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"99%\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd colspan=\\\"4\\\" valign=\\\"top\\\" style=\\\"width: 77px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eSTUDY PERIOD\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eEnrollment\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eAllocation\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eIntervention\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ePost-intervention\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003eTime point\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003ePreoperative visit\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003eAllocation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003eDuring induction until 20 minutes after induction\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003ePOD1\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"5\\\" valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eENROLLMENT:\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eEligibility screen\\u003c/p\\u003e\\n \\u003cp\\u003eInformed consent\\u003c/p\\u003e\\n \\u003cp\\u003eDemographic date\\u003c/p\\u003e\\n \\u003cp\\u003eAllocation\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"5\\\" valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eINTERVENTIONS:\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eRemimazolam\\u003c/p\\u003e\\n \\u003cp\\u003eDexmedetomidine\\u003c/p\\u003e\\n \\u003cp\\u003eAdverse reaction\\u003c/p\\u003e\\n \\u003cp\\u003eSurgery and anesthesia date\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd rowspan=\\\"8\\\" valign=\\\"top\\\" style=\\\"width: 22px;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eASSESSMENTS:\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003cp\\u003eMOAA/S score\\u003c/p\\u003e\\n \\u003cp\\u003eBIS\\u003c/p\\u003e\\n \\u003cp\\u003eIntraoperative movements\\u003c/p\\u003e\\n \\u003cp\\u003eCVP/CO/SVR\\u003c/p\\u003e\\n \\u003cp\\u003eNausea/vomiting\\u003c/p\\u003e\\n \\u003cp\\u003eHR/SBP/DBP/MBP/ SpO2\\u003c/p\\u003e\\n \\u003cp\\u003eVAS\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 14px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 9px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 37px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 15px;\\\"\\u003e\\n \\u003cp\\u003e\\u0026times;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n \\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cp\\u003ePOD: postoperative day; MOAA/S score: Modified Observer\\u0026apos;s Assessment of Alertness/Sedation score; BIS: bispectral index; CVP: central venous pressure; CO: cardiac output; SVR: systematic vascular resistance; HR: hear rate; SBP: systolic blood pressure; DBP: diastolic blood pressure; MBP: mean blood pressure; VAS:\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSample size {14}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAccording to the literature[19, 20], the success rate of sedation with remimazolam at a dose of 0.3~0.4 mg/kg ranges from 94% to 100% (taken as 99%,). We assume that the success rate of sedation with dexmedetomidine is only 80% of that of remimazolam. A total sample of 80 participants (40 per group) was required to achieve 80% power and 5% significance level. A 10% dropout rate will be accounted for, resulting in a target enrollment of 88 participants.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eRecruitment {15}\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll patients aged more than 18 with diagnosed ESRD\\u0026nbsp;undergoing\\u0026nbsp;peritoneal dialysis catheter placement or removal will be screened by the investigator daily. Verbal and written information regarding the trial will be provided if they meet all inclusion criteria and no exclusion criteria. The recruitment of patients is on-going. Since we are high-volume centers, we will be able to identify eligible patients and recruit required sample size.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssignment of interventions: allocation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eSequence generation {16a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eRandomization will be performed using block randomization with block sizes of 2 or 4.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConcealment mechanism {16b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAllocation will be concealed using opaque, sealed envelopes.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eImplementation {16c}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eRandomization will be performed by a statistician independent of the clinical team.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssignment of interventions: blinding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eWho will be blinded {17a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipants, surgical teams, outcome assessors, and data analysts will be blinded to group allocation. The randomization list will be securely maintained by a designated unblinding officer in West China Hospital, who is not involved in the trial\\u0026apos;s clinical or assessment procedures.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eProcedure for unblinding if needed {17b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eUnblinding will be permitted only in emergencies where knowledge of the allocated intervention is essential for the clinical management or safety of the participant. In such cases, the attending physician must contact the principal investigator (PI) or the designated unblinding officer, who will verify the necessity of unblinding and perform the procedure following a predefined protocol. The unblinding process will be documented in detail, including the reason for unblinding, the individuals involved, and the date and time of the event. The participant will remain in the study unless the unblinding reveals information that necessitates their withdrawal for safety reasons.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData collection and management\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePlans for assessments and collection of outcomes {18a}\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll collected data will be entered into a standardized case report form (CRF). Data collection will encompass baseline characteristics, intraoperative sedation levels, hemodynamic and respiratory parameters, and postoperative recovery metrics. Specifically, intraoperative data including sedation depth (measured by BIS), MOAA/S scores, blood pressure, heart rate, pulse oxygen saturation (SpO\\u003csub\\u003e2\\u003c/sub\\u003e), and analgesic use will be documented. Postoperatively, the incidence of nausea and vomiting, as well as pain scores (assessed by VAS), will be recorded on postoperative day 1 (POD1).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePlans to promote participant retention and complete follow-up {18b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDuring the preoperative visit, patients will be fully informed about the intraoperative procedure and postoperative follow-up. And the study investigators who are in charge of follow-up will visit patients within POD1.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eData management {19}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eData will be recorded in CRF and entered into a secure database. Regular monitoring by principal investigators (PL) will ensure data accuracy. All study members will receive protocol and device training (if necessary) before participating in the study to ensure protocol adherence. Data will be stored for at least 3 years after trial termination and publication of the final report.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConfidentiality {27}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eParticipant data will be de-identified and stored securely. Access will be limited to authorized personnel.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePlans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable. There exist no biological specimens to be collected in this study\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStatistical methods\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eStatistical methods for primary and secondary outcomes {20a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAnalyses will be performed using IBM SPSS 27 (version 27.0, IBM Corp., New York, NY, USA) software. For continuous variables and descriptive values, means, standard deviations (SDs) will be reported. For the variables with a normal distribution, statistical comparisons between the groups will be made by using a t-test. If the variables have a non-normal distribution or ordinal level, statistical comparison between groups will be made using the Mann-Whitney U test. Measures with a discrete distribution will be expressed as percentages and analyzed by the chi-squared test or Fisher\\u0026rsquo;s exact test as appropriate. For the categorical variables, frequency and corresponding percentage will be given and analyzed using chi-square or Fisher\\u0026apos;s exact tests. All tests will be conducted with 95% confidence intervals (CIs). A P value of less than 0.05 will be considered statistically significant.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eInterim analyses {21b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNo interim analyses are planned.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eMethods for additional analyses {20b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eSubgroup analyses will be conducted based on age, gender, and baseline characteristics.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eMethods to handle missing data {20c}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eMethods in analysis to handle protocol non‑adherence and any statistical methods to handle missing data {20c}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll outcomes will undergo an intent-to-treat (ITT) and per-protocol (PP) analyses based on the initial anesthesia allocation. Sensitivity analysis will be performed to handle protocol violation and deviation cases using the per-protocol principle. The missing value will be filled up by last-observation-carried-forward\\u0026nbsp;(LOCF)\\u0026nbsp;method. No multiple imputation will be used for missing data.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePlans to give access to the full protocol, participant-level data, and statistical code {31c}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets analyzed during the current study and statistical code are available from the corresponding author on reasonable request, as is the full protocol.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eOversight and monitoring\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eComposition of the coordinating center and trial steering committee {5d}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe coordinating team consists of anesthesiologists and statisticians overseeing trial implementation and data integrity. The study team has a conference online weekly to discuss the problems in the conduct of the trial. There is no trial steering committee or stakeholder and public involvement group.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eComposition of the data monitoring committee, its role, and reporting structure {21a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable. There is no data monitoring committee in this study. Instead, the principal investigator will check the appropriateness of the data and conduction of the trial every 2 weeks.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eAdverse event reporting and harms {22}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAdverse events related to this study protocol primarily include severe hypotension and sedation failure. In the event of hypotension, vasoactive drugs will be administered during anesthesia induction when the systolic blood pressure (SBP) drops below 90 mmHg or exhibits a 30% reduction from baseline. If sedation fails, rescue sedative medications, such as propofol, midazolam, or etomidate, will be used to complete anesthesia induction.\\u003c/p\\u003e\\n\\u003cp\\u003eAdditionally, dexmedetomidine, an alpha-2 adrenergic agonist, may be employed as a sedative adjunct due to its properties of providing sedation without significant respiratory depression, which can be beneficial in managing sedation failures. Its potential side effects, such as bradycardia and hypotension, will be monitored closely. All adverse events will be treated immediately and reported to the institutional review board. Participants will also be followed up until adverse events are fully resolved or therapy is terminated.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eFrequency and plans for auditing trial conduct {23}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe department of research office and the ethics committee of West China Hospital will audit the study annually. And the principal investigator will check the appropriateness of the data and conduction of the trial every 2 weeks.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003ePlans for communicating important protocol amendments to relevant parties (e.g., trail participants, ethical committees) {25}\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAny protocol amendments will be written into a formal substantial amendment reviewed by the institutional review board of the West China Hospital before\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eapplication.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eDissemination plans {31a}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll patients will provide written informed consent before the start of any protocol-specified procedures or assessments. The results of the study will be presented at relevant conferences and submitted to international peer-reviewed journals and conferences.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eESRD patients undergoing procedural sedation are faced with unique challenges due to altered drug metabolism, susceptibility to hemodynamic instability, and increased perioperative risks. Despite the growing use of remimazolam and dexmedetomidine in clinical practice, evidence comparing their effects on sedation efficacy and safety in this high-risk population is lacking. This trial protocol is designed to address this gap by rigorously comparing these two agents in patients undergoing peritoneal dialysis catheter placement or removal.\\u003c/p\\u003e\\n\\u003cp\\u003eThe primary focus of this RCT is to evaluate sedation success rates, onset and recovery times, and hemodynamic stability, which are crucial factors in optimizing perioperative outcomes for ESRD patients. Previous studies[9, 21, 22]\\u0026nbsp;have highlighted the advantages of remimazolam, including its rapid onset and offset, favorable hemodynamic profile, and metabolism by tissue esterases into inactive metabolites, making it an ideal agent for patients with renal dysfunction. In contrast, dexmedetomidine is well-regarded for its stable respiratory profile and sedative-analgesic properties but has limitations such as \\u0026nbsp;delayed onset, prolonged recovery, and risks of bradycardia and hypotension[23, 24].\\u003c/p\\u003e\\n\\u003cp\\u003eThe study has been developed in strict accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines[25]\\u0026nbsp;to ensure methodological rigor and transparency. The design of this trial incorporates rigorous methodology to ensure high-quality data. Randomization and blinding will minimize bias, while the use of standardized sedation protocols ensures consistency across groups. Primary outcomes, such as sedation success rate and time to achieve sedation, will provide clear measures of efficacy, while secondary outcomes, including hemodynamic stability and adverse event rates, will comprehensively evaluate safety. Additionally, the follow-up period will allow for the assessment of immediate postoperative outcomes, providing holistic understanding of each agent\\u0026apos;s effects. All efforts are made to ensure that the findings will be relevant and applicable to clinical practice.\\u003c/p\\u003e\\n\\u003cp\\u003eThe results of this trial are expected to contribute high-quality evidence to guide the choice of sedation agents in ESRD patients. We hypothesize that remimazolam will demonstrate superior performance in terms of faster onset and recovery, higher sedation success rates, and comparable or reduced adverse event rates compared to dexmedetomidine. This may help improve perioperative management and patient satisfaction. In conclusion, this trial protocol is designed to generate robust and reliable evidence on the comparative efficacy and safety of remimazolam and dexmedetomidine for procedural sedation in ESRD patients. By adhering to CONSORT guidelines, we ensure the reliability and reproducibility of our findings. Future multicenter studies with larger sample sizes may validate and expand upon these results, further advancing the standard of care in this challenging patient population.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStrengths and limitations\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDespite its strengths, this study has certain limitations. As a single-center trial, the findings may not fully capture variations in patient populations or practice patterns across different institutions. While the sample size is powered to detect differences in primary outcomes, rare adverse events may not be adequately evaluated. Additionally, the exclusion of patients with severe cardiovascular instability or psychiatric disorders limits the generalizability of the results to these subgroups.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial status\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe current protocol is version 2.0 and was issued on 6 July 2023. At the time of manuscript submission, the study is in the phase of recruitment. Recruitment has been begun in March 2024 and is expected to be completed by June 2025.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eASA: American Society of Anesthesiologists; BIS: Bispectral Index; CIs: Confidence intervals; CRF: Case Report Form; DBP: Diastolic Blood Pressure; ECG: Electrocardiogram; eGFR: Estimated Glomerular Filtration Rate; ESRD: End-Stage Renal Disease; HR: Heart Rate; ITT: Intent-to-Treat; MAP: Mean Arterial Pressure; MOAA/S: Modified Observer\\u0026apos;s Assessment of Alertness/Sedation; NYHA: New York Heart Association; PACU: Post-Anesthesia Care Unit; PI: Principal Investigator; POD1: Postoperative Day 1; PP: Per-Protocol; RCT: Randomized Controlled Trial; SBP: Systolic Blood Pressure; SD: Standard Deviation; SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials; SpO\\u003csub\\u003e2\\u003c/sub\\u003e: pulse oxygen saturation; TAP: Transversus Abdominis Plane; VAS: Visual Analog Scale;\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eAcknowledgements\\u0026nbsp;\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eWe thank the patients and staff at the Department of Nephrology for their assistance throughout this study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eAuthor\\u0026rsquo;s contributions {31b}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePeng Liang planned the study.\\u0026nbsp;Zhao Xu\\u0026nbsp;performed the statistical design of the study. All authors contributed to the design and development of the trial. Jie Gao and Hong Yu drafted the manuscript.\\u0026nbsp;Yongqing Xu and\\u0026nbsp;Yuwei Wu critically revised the manuscript. All authors read and approved the final manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eFunding {4}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eAvailability of data and material {29}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAny data required to support the protocol can be supplied on request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eEthical Approval and Consent to participate {24}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study protocol has been approved by the Ethics Committee of West China Hospital of Sichuan University [Ethic Committee No. 2023(1083)] and registered at chictr.org.cn (ID: ChiCTR2300075278) on August 31, 2023. All patients will provide written informed consent before the start of any protocol-specified procedures or assessments. The patients can withdraw from the trial at any time. The results of the study will be presented at relevant conferences and submitted to international peer-reviewed journals.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eConsent for publication {32}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable - no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Informed consent materials are available from the corresponding author on request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cem\\u003eCompeting interests {28}\\u003c/em\\u003e\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eLok CE, Huber TS, Lee T, Shenoy S, Yevzlin AS, Abreo K, et al. KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update. Am J Kidney Dis. 2020;75:S1\\u0026ndash;164. doi: 10.1053/j.ajkd.2019.12.001\\u003c/li\\u003e\\n\\u003cli\\u003eVerbeeck RK, Musuamba FT. Pharmacokinetics and dosage adjustment in patients with renal dysfunction. Eur J Clin Pharmacol. 2009;65:757\\u0026ndash;73. doi: 10.1007/s00228-009-0678-8\\u003c/li\\u003e\\n\\u003cli\\u003eCho JS, Shim J-K, Soh S, Kim MK, Kwak Y-L. Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int. 2015;89:693\\u0026ndash;700. doi: 10.1038/ki.2015.306\\u003c/li\\u003e\\n\\u003cli\\u003eSoliman R, Hussien M. Comparison of the renoprotective effect of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery: A double-blind randomized study. Ann Card Anaesth. 2017;20:408\\u0026ndash;408. doi: 10.4103/aca.aca_57_17\\u003c/li\\u003e\\n\\u003cli\\u003eZhai M, Kang F, Han M, Huang X, Li J. The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass: A double-blind randomized controlled trial. J Clin Anesth. 2017;40:33\\u0026ndash;8. doi: 10.1016/j.jclinane.2017.03.053\\u003c/li\\u003e\\n\\u003cli\\u003eBarr J, Fraser GL, Puntillo K, Ely EW, G\\u0026eacute;linas C, Dasta JF, et al. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Crit Care Med. 2012;41:263\\u0026ndash;306. doi: 10.1097/ccm.0b013e3182783b72\\u003c/li\\u003e\\n\\u003cli\\u003eDesai N, Kirkham KR, Albrecht E. Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review. Anaesthesia. 2021;76:100\\u0026ndash;9. doi: 10.1111/anae.15245\\u003c/li\\u003e\\n\\u003cli\\u003eHall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, Amnestic, and Analgesic Properties of Small-Dose Dexmedetomidine Infusions. Anesthesia Analg. 2000;90:699\\u0026ndash;705. doi: 10.1097/00000539-200003000-00035\\u003c/li\\u003e\\n\\u003cli\\u003eSt\\u0026ouml;hr T, Colin PJ, Ossig J, Pesic M, Borkett K, Winkle P, et al. Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment. Br J Anaesth. 2021;127:415\\u0026ndash;23. doi: 10.1016/j.bja.2021.05.027\\u003c/li\\u003e\\n\\u003cli\\u003eAntonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A Placebo- and Midazolam-Controlled Phase I Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam (CNS 7056). Anesthesia Analg. 2012;115:274\\u0026ndash;83. doi: 10.1213/ane.0b013e31823f0c28\\u003c/li\\u003e\\n\\u003cli\\u003ePambianco DJ, Borkett KM, Riff DS, Winkle PJ, Schwartz HI, Melson TI, et al. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2015;83:984\\u0026ndash;92. doi: 10.1016/j.gie.2015.08.062\\u003c/li\\u003e\\n\\u003cli\\u003eBorkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, et al. A Phase IIa, Randomized, Double-Blind Study of Remimazolam (CNS 7056) Versus Midazolam for Sedation in Upper Gastrointestinal Endoscopy. Anesthesia Analg. 2015;120:771\\u0026ndash;80. doi: 10.1213/ane.0000000000000548\\u003c/li\\u003e\\n\\u003cli\\u003eYoshida A, Kurata S, Kida K, Tsubokawa T. Anesthetic management for the sleep-awake-sleep technique of awake craniotomy using a novel benzodiazepine remimazolam and its antagonist flumazenil. JA Clin Rep. 2021;7. doi: 10.1186/s40981-021-00417-z \\u003c/li\\u003e\\n\\u003cli\\u003eChen Q, Qin B, Zhang M, Zhou Y, Shi X, Xie Y. The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial. DDDT. 2024;Volume 18:967\\u0026ndash;78. doi: 10.2147/dddt.s446222\\u003c/li\\u003e\\n\\u003cli\\u003eXu H, Wang L, Zhu W, Ren C, Liu G, Liu Y. Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmedetomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial. DDDT. 2024;Volume 18:2317\\u0026ndash;27. doi: 10.2147/dddt.s460949\\u003c/li\\u003e\\n\\u003cli\\u003eZhou L, Zou J, Li X, Zuo X, Gu M, Sun K, et al. Efficacy and safety of remimazolam versus dexmedetomidine for patients undergoing flexible fiberoptic bronchoscopy: A randomized, clinical trial. J Clin Anesth. 2024;99:111677\\u0026ndash;111677. doi: 10.1016/j.jclinane.2024.111677\\u003c/li\\u003e\\n\\u003cli\\u003eChen X, Xin D, Xu G, Zhao J, Lv Q. The Efficacy and Safety of Remimazolam Tosilate Versus Dexmedetomidine in Outpatients Undergoing Flexible Bronchoscopy: A Prospective, Randomized, Blind, Non-Inferiority Trial. Front Pharmacol. 2022;13. doi: 10.3389/fphar.2022.902065 \\u003c/li\\u003e\\n\\u003cli\\u003eHong S-W, Park J-Y, Rhee K-Y, Kim S-H. Comparison emergence of sedation, using dexmedetomidine and remimazolam, in spinal anaesthesia - double blinded randomized controlled trial. Int J Med Sci. 2024;21:1552\\u0026ndash;8. doi: 10.7150/ijms.95736\\u003c/li\\u003e\\n\\u003cli\\u003eDAI G, PEI L, DUAN F, LIAO M, ZHANG Y, ZHU M, et al. Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia. Minerva Anestesiol. 2021;87. doi: 10.23736/s0375-9393.21.15517-8 \\u003c/li\\u003e\\n\\u003cli\\u003eSiemens K, Parmar K, Harris J, Hunt BJ, Tibby SM. Fibrinolytic activity in infants undergoing cardiac surgery on cardiopulmonary bypass with routine tranexamic acid. Eur J Anaesthesiol. 2025. doi: 10.1097/eja.0000000000002124 \\u003c/li\\u003e\\n\\u003cli\\u003eChen L, Qin W, Wu J, Zhao G, Jiang X, Li M, et al. Effect of Remimazolam on Induction and Maintenance of General Anesthesia in Kidney Transplant Patients. IJGM. 2024;Volume 17:2455\\u0026ndash;63. doi: 10.2147/ijgm.s464530\\u003c/li\\u003e\\n\\u003cli\\u003eDai Q-C, Zhao J-L, Miao X-Y, Wang R, Hui Z. Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock. Eur Rev Med Pharmacol Sci. 2024;28:2483\\u0026ndash;92. doi: 10.26355/eurrev_202403_35755\\u003c/li\\u003e\\n\\u003cli\\u003eKim H, Kim Y, Bae J, Yoo S, Lim Y-J, Kim J-T. Comparison of remimazolam and dexmedetomidine for intraoperative sedation in patients undergoing lower extremity surgery under spinal anesthesia: a randomized clinical trial. Reg Anesth Pain Med. 2023;49:110\\u0026ndash;6. doi: 10.1136/rapm-2023-104415\\u003c/li\\u003e\\n\\u003cli\\u003eLee S. Dexmedetomidine: present and future directions. Korean J Anesthesiol. 2019;72:323\\u0026ndash;30. doi: 10.4097/kja.19259\\u003c/li\\u003e\\n\\u003cli\\u003eMoher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials. International Journal of Surgery. 2010;340 mar23 1:c869\\u0026ndash;c869. doi: 10.1136/bmj.c869\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"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\":true,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"trials\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"trls\",\"sideBox\":\"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)\",\"snPcode\":\"13063\",\"submissionUrl\":\"https://www.editorialmanager.com/trls\",\"title\":\"Trials\",\"twitterHandle\":\"MedicalEvidence\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Randomized controlled trial, Remimazolam, Dexmedetomidine, End-stage renal disease, Sedation, Anesthesia, Peritoneal dialysis\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6037634/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6037634/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e: Procedural sedation for patients with end-stage renal disease (ESRD) is challenging due to impaired renal function, which affects drug metabolism and increases the risk of adverse events. Remimazolam, a novel, ultrashort-acting intravenous sedative-hypnotic, offers rapid onset and clearance independent of renal function, making it a potential alternative to dexmedetomidine for sedation in this patient population. This study aims to compare the efficacy and safety of remimazolam and dexmedetomidine in ESRD patients undergoing procedural sedation. The primary hypothesis is that remimazolam will demonstrate superior sedation efficacy and a better safety profile, with reduced hemodynamic instability and faster recovery.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods\\u003c/strong\\u003e: This is a single-center, prospective, double-blind, randomized controlled trial (RCT). A total of 88 ESRD patients aged ≥18 years scheduled for peritoneal dialysis catheter placement or removal will be randomly assigned to receive either remimazolam or dexmedetomidine. The primary outcome is the sedation success rate, defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≤1 within 10 minutes of drug administration. Secondary outcomes include time to sedation, intraoperative movement, the duration of BIS values \\u0026lt;60 or \\u0026gt;80 during anesthesia maintenance, recovery time, incidence of adverse events (e.g., hypotension, bradycardia, hypoxemia), postoperative pain scores and incidence of postoperative nausea and vomiting.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDiscussion\\u003c/strong\\u003e: This is the first RCT to directly compare remimazolam and dexmedetomidine for sedation in ESRD patients undergoing procedural sedation. The results of this study will provide valuable insights into optimizing sedation strategies in this high-risk population, potentially improving clinical outcomes by minimizing complications associated with drug metabolism and recovery.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial registration: \\u003c/strong\\u003eChinese Clinical Trial Registry. \\u003cstrong\\u003echictr.org.cn \\u003c/strong\\u003eChiCTR2300075278. Registered on August 31, 2023. https://www.chictr.org.cn/showproj.html?proj=205061\\u003c/p\\u003e\",\"manuscriptTitle\":\"Efficacy and safety of remimazolam for sedation of patients with end-stage renal disease: a prospective, randomized controlled clinical trial\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-03-27 08:24:28\",\"doi\":\"10.21203/rs.3.rs-6037634/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Major revision\",\"date\":\"2025-03-29T06:59:22+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"\",\"date\":\"2025-03-18T10:29:41+00:00\",\"index\":0,\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-03-18T10:27:36+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"Trials\",\"date\":\"2025-03-04T11:14:18+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-02-18T12:01:30+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Trials\",\"date\":\"2025-02-18T02:23:57+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"trials\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"trls\",\"sideBox\":\"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)\",\"snPcode\":\"13063\",\"submissionUrl\":\"https://www.editorialmanager.com/trls\",\"title\":\"Trials\",\"twitterHandle\":\"MedicalEvidence\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"1f60714c-52f4-43aa-9697-44044ee56a5e\",\"owner\":[],\"postedDate\":\"March 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-04-20T16:03:49+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-6037634\",\"link\":\"https://doi.org/10.1186/s13063-026-09700-9\",\"journal\":{\"identity\":\"trials\",\"isVorOnly\":false,\"title\":\"Trials\"},\"publishedOn\":\"2026-04-16 15:58:37\",\"publishedOnDateReadable\":\"April 16th, 2026\"},\"versionCreatedAt\":\"2025-03-27 08:24:28\",\"video\":\"\",\"vorDoi\":\"10.1186/s13063-026-09700-9\",\"vorDoiUrl\":\"https://doi.org/10.1186/s13063-026-09700-9\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6037634\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6037634\",\"identity\":\"rs-6037634\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}