Comparative Efficacy and Safety of Ciprofol vs. Propofol for Non-operating Room Sedation and Anesthesia: A Systematic Review and Meta-Analysis

Comparative Efficacy and Safety of Ciprofol vs. Propofol for Non-operating Room Sedation and Anesthesia: A Systematic Review and Meta-Analysis | 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 Systematic Review Comparative Efficacy and Safety of Ciprofol vs. Propofol for Non-operating Room Sedation and Anesthesia: A Systematic Review and Meta-Analysis Lei Xie, Yazhi Xi, Xin Wang, Xinyao He, Qing-he Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5682557/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Propofol is a widely used intravenous anesthetic for procedural sedation in non-operating room settings, but its use is often accompanied by adverse events such as injection pain, respiratory depression, and hypotension. Ciprofol, a novel intravenous anesthetic, has gained attention as a potential alternative due to its favorable safety profile and comparable sedative efficacy. This systematic review and meta-analysis aimed to compare the efficacy, safety, and satisfaction outcomes of ciprofol and propofol in adults undergoing non-operating room procedures. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) comparing ciprofol and propofol. Data from eligible studies were extracted and analyzed using RevMan 5.3 and Stata 17. Risk ratio (RR) with 95% confidence interval (CI) were calculated for binary outcomes, and standard mean difference (SMD) with 95% CI were used for continuous outcomes. Heterogeneity was assessed using the I²statistic, with fixed-effects or random-effects models applied as appropriate. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity and ensure robustness. Results: Seven RCTs involving 1,458 participants were included. Ciprofol demonstrated comparable sedation success rates to propofol. Subgroup analyses indicated that combining ciprofol with short-acting opioids significantly improved sedation outcomes (RR 1.07, 95% CI 1.03–1.12; P < 0.01). Ciprofol was associated with significantly lower risks of injection pain (RR 0.13, 95% CI 0.06–0.28; P < 0.01), respiratory depression (RR 0.55, 95% CI 0.33–0.77; P < 0.01), and hypotension (RR 0.81, 95% CI 0.69–0.95; P < 0.01). No significant differences were observed between the two agents in induction time or time to full recovery. Conclusion: Ciprofol is a safe and effective alternative to propofol for non-operating room procedural sedation. Its superior safety profile, particularly in reducing injection pain, respiratory depression, and hypotension, makes it a promising option, especially when combined with short-acting opioids. Propofol Ciprofol Procedural sedation Non-operating room Safety Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction The widespread adoption of minimally invasive techniques and the increasing emphasis on painless medical care have led to a growing demand for sedation and anesthesia in non-operating room settings ( 1 ). Endoscopic procedures—such as gastroscopy, colonoscopy, bronchoscopy, cystoscopy, and hysteroscopy—as well as minor outpatient interventions, often require sedation or anesthesia to enhance patient comfort and facilitate the smooth execution of these procedures ( 2 ). Propofol, a widely used short-acting hypnotic agent, has become a cornerstone for sedation outside the operating room due to its rapid onset of action (within approximately 30 seconds) and efficient systemic distribution ( 3 ). However, despite its favorable safety profile, the administration of propofol is associated with potential risks, including hypotension and respiratory depression ( 4 , 5 ). These concerns have prompted ongoing research into safer and more effective alternatives that can further optimize sedation outcomes while ensuring patient safety and comfort in outpatient settings ( 6 ). Ciprofol, a novel sedative developed and patented in China, represents a promising alternative. This innovative short-acting benzodiazepine sedative demonstrates rapid metabolism, a lower risk of respiratory depression, stable sedative effects, and minimal adverse reactions, making it an appealing choice for sedation and anesthesia in non-operating room settings ( 7 – 10 ). To comprehensively evaluate the sedative efficacy, safety profile, and patient satisfaction associated with ciprofol, we conducted a systematic review and meta-analysis comparing its performance to that of propofol in non-operating room sedation and anesthesia. Methods Protocol and registration This systematic review and meta-analysis was conducted in strict compliance with the Cochrane Handbook for Systematic Reviews of Interventions. The study design and reporting adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor and transparency. The research protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42024603722. Systematic Literature Search We performed a comprehensive and unrestricted search of four major databases—PubMed, Embase, Cochrane Library, and Web of Science—from their inception to September 23, 2024. The search strategy was developed based on the “PICOS” framework. Specifically, Participants (P) were identified using terms such as “endoscopy,” “bronchoscopy,” “gastrointestinal endoscopy,” “hysteroscopy,”“gastroscopy,”“colonoscopy,”“cystoscopy,”and“proctoscopy.” For the Intervention (I), search terms included “propofol,” “disoprofol,” “ciprofol,” and “HSK3486.” A detailed search strategy is available in Supplementary S1 . A systematic search was also conducted for references corresponding to the eligible studies. Selection Criteria The inclusion criteria required randomized controlled trials (RCTs) comparing ciprofol and propofol for sedation in adult patients undergoing procedural sedation and anesthesia outside the operating room. Studies were eligible if they reported at least one relevant outcome measure. Only peer-reviewed RCTs published in English with complete original texts were included. Exclusion criteria encompassed studies with control groups receiving rescue doses of propofol, those involving standard indications for endotracheal intubation, as well as editorials, letters to the editor, literature reviews, meta-analyses, conference abstracts, duplicate publications, and studies that either lacked relevant outcome measures or full-text accessibility. Additionally, literature unable to provide valid data for comprehensive analysis was excluded. Outcome Measures The primary outcome measure was the success rate of sedation, which was defined as the absence of a need to switch to alternative sedatives or administer rescue sedation during endoscopic procedures. Secondary outcome measures included several time-related variables: induction time, defined as the interval from sedative administration to the loss of consciousness; time to full alertness, defined as the duration from cessation of sedative administration to the patient achieving a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score of 5; and anesthesia discharge time, defined as the time from discontinuation of sedative infusion to the patient meeting discharge criteria. Adverse events assessed in this study included injection pain, respiratory depression, hypotension, bradycardia, tachycardia, and other sedation-related complications. Respiratory depression was defined as ventilation rates < 8 breaths per minute, oxygen saturation < 95%, or both during sedation and recovery. Hypotension was defined as systolic blood pressure (SBP) of 80–90 mmHg, a ≥ 20% reduction in SBP, mean arterial pressure (MAP) < 60–65 mmHg, or a ≥ 20% reduction in MAP during sedation and recovery. Bradycardia was defined as a heart rate < 50 beats per minute, with minor variations in thresholds across studies (e.g., 100 beats per minute from sedation to recovery. Other adverse events included nausea, vomiting, dizziness, drowsiness, and patient-reported discomfort. In addition to safety and efficacy, both patient and physician satisfaction with the procedure were evaluated as secondary outcomes. Definitions for each outcome measure were standardized based on the most used criteria reported in the included studies. These definitions were finalized following data extraction to ensure consistency and reliability in the meta-analysis. Research Selection and Data Extraction After removing duplicates, two independent reviewers (He and Xi) screened the titles and abstracts using EndNote X9, followed by a full-text review of potentially eligible studies. Any disagreements during the screening process were resolved by a third reviewer (Wang), who made the final decision. Data extraction was performed systematically from the included studies. The following information was collected: general study details (title, authors, publication year, and study location), study design, participant characteristics (age, gender, body mass index [BMI], and American Society of Anesthesiologists [ASA] status), sample size, and surgical characteristics (type of procedure). Additionally, we recorded details regarding the usage and dosage of ciprofol, propofol, and short-acting opioids, sedation success rates, time-related variables (induction time, time to full recovery, and time to discharge post-anesthesia), and adverse events (injection pain, respiratory depression, hypotension, bradycardia, tachycardia, nausea, vomiting, dizziness, and somnolence). Patient and physician satisfaction scores were also extracted for further analysis. When research data lacks mean and standard deviation, we utilize the approach suggested by Wan et al. ( 11 ) and Luo et al. ( 12 ) to estimate the values using the median and range. Evaluation of Quality and Risk The quality assessment of RCTs meeting the inclusion criteria was performed using the Cochrane Collaboration’s tool for assessing the risk of bias ( 13 ). Two independent reviewers (Xi and Zhou) evaluated the risk of bias for each selected outcome variable, examining the following domains: allocation concealment, randomization methods, blinding of investigators and participants, blinding of outcome assessors, selective outcome reporting, completeness of data, and other potential sources of bias. The results of the assessment were classified into three categories: low risk of bias, unclear risk of bias, and high risk of bias. Any discrepancies in assessments were resolved through discussion or consultation with a third reviewer when necessary. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to evaluate the degree of confidence. The evaluation categorized the level of certainty as high, moderate, low, or very low, in accordance with the criteria. Statistical analysis The meta-analysis was conducted using RevMan 5.3 and Stata 17 (Stata Corporation, Texas, USA). Effect measures were selected based on the data type. For binary outcomes, the risk ratio (RR) with 95% confidence interval (CI) was employed to quantify the relative likelihood of events between groups. For continuous outcomes, the standard mean difference (SMD) with 95% CI was used to assess differences in mean values between groups. A P -value < 0.05 was considered statistically significant. Heterogeneity among studies was assessed using the I² statistic and P -value from Cochran’s Q test. An I²value 0.10 were interpreted as low heterogeneity, allowing the use of a fixed-effects model. Conversely, significant heterogeneity (I²≥50% or P ≤ 0.10) prompted the use of a random-effects model, and meta-regression was employed to explore potential sources of variability. Sensitivity analyses, performed by sequential exclusion of individual studies, were conducted to ensure the stability and robustness of the findings. All sensitivity analyses were carried out using Stata 17. To address potential clinical and methodological heterogeneity, subgroup analyses were conducted for the primary outcome based on the use of short-acting opioids during procedures, provided at least two studies were available in each subgroup. This approach helped isolate the influence of procedural differences on sedation outcomes. Due to the limited number of included studies, publication bias was not formally assessed using funnel plots or Egger’s test, as such analyses may lack power in small meta-analyses. Results Study selection During the literature search process, a total of 145 relevant articles were initially identified. After the removal of duplicate records, 87 articles remained. By screening the titles and abstracts, irrelevant studies were excluded, resulting in 11 full-text articles for further review. Following a comprehensive assessment of these 11 articles, seven were ultimately included ( 14 – 20 ). (Fig. 1 ) Baseline characteristics and study assessment A total of 1,458 patients were included in seven trials ( 14 – 20 ), with 728 (49.9%) receiving ciprofol and the remaining 730 (50.1%) receiving propofol. Regarding the use of short-acting opioids during sedation, two studies ( 18 , 20 ) utilized sufentanyl (507 patients, 34.8%), one study ( 19 ) used alfentanil (185 patients, 12.7%), and four studies ( 14 – 17 ) did not administer short-acting opioids (766 patients, 52.5%). Detailed descriptions of the baseline characteristics of the included studies are provided in Table 1 . Figure 2 provides an overview of the risk of bias assessment for each included trial. Table 1 Baseline characteristics of included studies. GY, gastroscopy;CY, colonoscopy༛FB, fiberoptic bronchoscope Study Design Sample size, n Age(yr), mean Male, n (%) BMI (kg/m 2 ), mean ASA 1/2, n (%) Procedure Opioid Gao and colleagues 2024 ( 15 ) Single-centre RCT 164 53.30 66(40.2%) 23.55 164(100%) GY No Chen and colleagues 2022 ( 14 ) Single-centre RCT 96 43.21 39(40.6%) 24.32 96(100%) GY, CY, or both No Zhang and colleagues 2024 ( 19 ) Single-centre RCT 185 52.81 104(56.2%) 23.35 185(100%) GY, CY, or both Alfentanil Li and colleagues 2022 ( 16 ) Single-centre RCT 289 43.95 118(40.8%) 23.30 289(100%) GY, CY, or both No Luo and colleagues 2022 ( 18 ) Multicentre RCT 267 46.75 135(50.6%) 23.06 263(98.5%) FB Sufentanil Zhou and colleagues 2024 ( 20 ) Single-centre RCT 240 48.37 118(49.2%) NA 240(100%) GY, CY, or both Sufentanil Li and colleagues 2024 ( 17 ) Single-centre RCT 217 46.85 97(44.7%) 23.31 217(100%) CY No Primary outcome The sedation success rate was reported across seven studies ( 14 – 20 ). Analysis demonstrated a significant increase in the sedation success rate when comparing the use of ciprofol to propofol (n = 1,458; RR 1.03; 95% CI 1.01–1.05; P < 0.01; I²=90%; moderate-quality evidence; Fig. 3 ; Table 2 ). Sensitivity analysis revealed that no individual study significantly influenced the effect estimate or heterogeneity. Subgroup analysis based on the use of short-acting opioids suggested that this variable may contribute to the observed heterogeneity. Moreover, the use of ciprofol alone showed sedation success rates comparable to propofol, with additional studies suggesting that combining ciprofol with short-acting opioids may effectively enhance induction success rates. Table 2 Pooled Analysis Results of Primary and Secondary Outcomes. CI: Confidence Interval; SMD: Standard Mean Difference; C: Ciprofol Group; P: Propofol Group; RR: risk ratio Outcome Included studies, n Sample size, n (C/P) Effect estimate (95% CI) P -value I 2 (%) Quality of Evidence Sedation success 7 728/730 RR1.03 (1.01–1.05) < 0.01 90% ⨁⨁⨁◯ MODERATE Induction time 7 728/730 SMD − 0.04 (-0.09 to 0.10) 0.12 95% ⨁⨁⨁◯ MODERATE time to full recovery 6 608/608 SMD0.05(-0.30 to 0.40) 0.79 89% ⨁⨁⨁◯ MODERATE time to discharge post-anesthesia 6 608/608 SMD − 0.01 (-0.36 to 0.33) 0.94 89% ⨁⨁⨁◯ MODERATE Respiratory depression 4 427/428 RR 0.50 (0.33–0.77) 0.51 0% ⨁⨁⨁⨁ HIGH injection pain 6 608/610 RR 0.13 (0.06–0.28) < 0.01 73% ⨁⨁⨁◯ MODERATE Hypotension 6 681/681 RR 0.81 (0.69–0.95) < 0.01 0% ⨁⨁⨁⨁ HIGH Bradycardia 5 561/561 RR 0.93 (0.62–1.39) 0.72 0% ⨁⨁⨁⨁ HIGH nausea and vomiting 4 417/416 RR 0.81 (0.47–1.38) 0.44 0% ⨁⨁⨁⨁ HIGH dizziness 5 561/560 RR 0.82 (0.68–1.00) 0.05 0% ⨁⨁⨁⨁ HIGH tachycardia 2 175/171 RR 0.43 (0.06–2.85) 0.38 0% ⨁⨁⨁⨁ HIGH somnolence 3 336/335 RR 0.75 (0.57–0.98) 0.03 0% ⨁⨁⨁⨁ HIGH Patient satisfaction 5 537/536 SMD 0.02 (-0.19 to 0.24) 0.82 69% ⨁⨁⨁◯ MODERATE Physician Satisfaction 4 417/416 SMD 0.22 (-0.23 to 0.67) 0.33 90% ⨁⨁⨁◯ MODERATE Time-related outcomes A total of seven studies ( 14 – 20 ) were included in the analysis of induction time, revealing no statistically significant difference between the propofol and ciprofol groups (n = 1,458; SMD = -0.04; 95% CI -0.09 to 0.10; P = 0.12; I² = 95%; moderate-quality evidence; Fig. 4 a; Table 2 ). This finding suggests that the two groups exhibited comparable speeds during anesthesia induction. Additionally, six studies ( 14 – 19 ) were analyzed for time to full recovery from anesthesia, showing no significant difference between the propofol and ciprofol groups (n = 1,216; SMD = 0.05; 95% CI -0.30 to 0.40; P = 0.79; I² = 89%; moderate-quality evidence; Fig. 4 b; Table 2 ), indicating similar rates of anesthesia recovery between the two groups. Sensitivity analysis revealed that excluding the study by Chen et al . ( 14 ) did not eliminate heterogeneity but did show a statistically significant difference time to full recovery from anesthesia between the propofol and ciprofol groups (n = 1,120; SMD = 0.25; 95% CI 0.05 to 0.45; P = 0.02; I² = 65%), indicating a faster emergence time with propofol. Six studies ( 14 – 19 ) reported time to discharge post-anesthesia, demonstrating no statistically significant difference between the propofol and ciprofol groups (n = 1,216; SMD = -0.01; 95% CI -0.36 to 0.33; P = 0.94; I² = 89%; moderate-quality evidence; Fig. 4 c; Table 2 ), suggesting comparable recovery rates in anesthesia emergence between the two groups. Safety-related outcomes In four studies ( 15 – 17 , 19 ), respiratory depression was assessed, with findings indicating a significant reduction in the risk of respiratory depression when using ciprofol compared to propofol (n = 855; RR 0.55; 95% CI 0.33–0.77; P < 0.01; I² = 0%; high-quality evidence; Fig. 5 a; Table 2 ). These findings suggest a clear advantage of ciprofol in reducing the risk of respiratory depression. The incidence of injection pain was reported in six studies ( 14 – 19 ), with the use of ciprofol for sedation significantly reducing the risk of injection pain compared to propofol (n = 1,218; RR 0.13; 95% CI 0.06–0.28; P < 0.01; I² = 73%; moderate-quality evidence; Fig. 5 b; Table 2 ). These results indicate a significant advantage of ciprofol in reducing the incidence of injection pain. Hypotension incidence was assessed in six studies ( 15 – 20 ), with analysis revealing a significant reduction in the risk of hypotension when using ciprofol compared to propofol (n = 1,362; RR 0.81; 95% CI 0.69–0.95; P < 0.01; I² = 0%; high-quality evidence; Fig. 5 c; Table 2 ). Sensitivity testing indicated that no individual study exerted undue influence on the effect estimate or heterogeneity. These findings suggest the superiority of ciprofol in reducing the occurrence of hypotension. Bradycardia incidence was reported in five studies ( 15 – 19 ), with no statistically significant difference in the risk of bradycardia between the two sedatives (n = 1,122; RR 0.93; 95% CI 0.62–1.39; P = 0.72; I² = 0%; high-quality evidence; Fig. 5 d; Table 2 ). Postoperative nausea, vomiting, or both were reported in four studies ( 15 , 17 , 18 , 19 ), with no statistically significant difference in the risk between the two sedatives (n = 833; RR 0.81; 95% CI 0.47–1.38; P = 0.44; I² = 0%; high-quality evidence; Fig. 5 e; Table 2 ). Postoperative dizziness was reported in five studies ( 15 – 19 ), with no statistically significant difference in the risk between the two sedatives (n = 1,121; RR 0.82; 95% CI 0.68–1.00; P = 0.05; I² = 0%; high-quality evidence; Fig. 5 f; Table 2 ). Postoperative tachycardia was reported in two studies ( 15 , 19 ), with no statistically significant difference in the risk between the two sedatives (n = 349; RR 0.43; 95% CI 0.06–2.85; P = 0.38; I² = 0% ; high-quality evidence; Fig. 5 g; Table 2 ). Postoperative somnolence was reported in three studies ( 15 , 18 , 20 ), with analysis revealing a significant reduction in the risk of postoperative somnolence with the use of ciprofol compared to propofol (n = 671; RR 0.75; 95% CI 0.57–0.98; P = 0.03; I² = 0%; high-quality evidence; Fig. 5 h; Table 2 ). Sensitivity analyses across all outcome measures indicated that no single study had an undue influence on the effect estimates or observed heterogeneity. Satisfaction-related outcomes The included studies evaluated patient and physician satisfaction with the procedure using a rating scale from 0 to 10, with higher scores indicating greater satisfaction. Five studies ( 15 , 17 – 20 ) reported patient satisfaction, showing no significant difference between groups (n = 1,073; SMD 0.02; 95% CI -0.19 to 0.24; P = 0.82; I² = 69%; moderate-quality evidence; Fig. 6 a; Table 2 ). Sensitivity analysis indicated that the removal of the study by Li et al . ( 17 ) significantly reduced heterogeneity (SMD 0.12; 95% CI -0.02 to 0.26; P = 0.09; I² = 5%). Four studies ( 15 , 17 – 19 ), involving 1,704 patients, were included in the analysis of physician satisfaction. Analysis showed no significant difference between groups (n = 833; SMD 0.22; 95% CI -0.23 to 0.67; P = 0.33; I² = 90%; moderate-quality evidence; Fig. 6 b; Table 2 ). Sensitivity analysis indicated a significant decrease in heterogeneity when the study by Zhang et al . ( 19 ) was excluded (SMD − 0.02; 95% CI -0.17 to 0.13; P = 0.80; I² = 0%). Discussion In this systematic review and meta-analysis, data from over 1,400 patients across seven studies were analyzed to compare the sedative efficacy, safety, and satisfaction outcomes of ciprofol and propofol in procedures performed outside the operating room. The principal findings from the pooled analysis are as follows: ( 1 ) ciprofol enhances sedation success rates, particularly when used in conjunction with short-acting opioids, demonstrating a marked effect in this setting. However, when administered alone, ciprofol does not show a statistically significant difference in sedation success rates compared to propofol. ( 2 ) ciprofol and propofol exhibit comparable induction times, full awakening times, and anesthesia discharge times. ( 3 ) ciprofol is associated with a lower risk of respiratory depression and injection pain and may also reduce the incidence of hypotension. ( 4 ) Both ciprofol and propofol yield comparable satisfaction levels among physicians and patients. In the field of anesthesiology, providing safe and effective sedation and anesthesia for patients, particularly in outpatient settings, remains a key area of ongoing interest. Recently, ciprofol has gained significant attention as a novel intravenous anesthetic. Studies indicate that ciprofol not only offers rapid onset, fast metabolism, and minimal accumulation but also exhibits reduced cardiovascular depressive effects, potentially giving it an advantage in clinical practice ( 21 , 22 ). The research findings indicate that there is no significant difference in the success rates of anesthesia induction between the two groups using ciprofol individually, reflecting an overall comparable effectiveness of ciprofol and propofol in anesthesia induction. However, ciprofol can achieve similar anesthetic effects to propofol at lower doses, approximately one-fifth to one-sixth of the dose of propofol, demonstrating a higher therapeutic index ( 23 , 24 ). Moreover, when used in combination with short-acting opioids, ciprofol significantly enhances the success rate of sedation. This suggests that opioids can synergistically enhance the sedative effects of ciprofol ( 25 , 26 ). The study also revealed no significant difference in induction time between the ciprofol group and the propofol group. However, the existing literature shows some inconsistency in the results regarding induction time. Research by Yang et al . ( 27 ) implies a shorter induction time for ciprofol compared to propofol in the operating room, although other studies suggest a relatively shorter induction time for propofol ( 28 ). The study posits that clinical heterogeneity may primarily stem from variations in drug dosage and types of adjuvant medications. Additionally, factors such as the type of surgery, procedural techniques, rate of anesthetic drug administration, and individual patient differences may also impact the consistency of outcomes. In conclusion, the findings of this study provide reliable data support and analytical references for future related research. In terms of safety, particularly when comparing the clinical efficacy of ciprofol to propofol with similar levels of patient and physician satisfaction—propofol is associated with dose-dependent cardiorespiratory depression. In contrast, ciprofol, due to its high lipid solubility, can achieve effective sedation at lower doses. Unlike conventional emulsions, ciprofol employs a formulation containing medium-chain triglycerides, resulting in a significant reduction in free molecule concentrations. This reduction not only diminishes post-injection pain but also has a less pronounced direct impact on the cardiovascular system ( 29 , 30 ). Moreover, ciprofol follows a relatively gentle metabolic pathway, primarily undergoing metabolism through glucose catalysis, oxidation, and sulfation to produce harmless glucuronide conjugates that are subsequently excreted by the kidneys ( 31 ). This metabolic characteristic reduces the risk of drug accumulation in the body, thereby lowering the likelihood of cardiorespiratory depression. Additionally, ciprofol exhibits highly specific activity toward GABA receptors, particularly the α1β2γ2 subtype, with minimal inhibitory effects on cytochrome P 450 enzymes, further mitigating its influence on heart rate, blood pressure, and the respiratory system ( 31 , 32 ). The data from this meta-analysis indicate that, in low-risk patients with an ASA risk classification of 3 or below, ciprofol significantly reduces critical respiratory and circulatory adverse events and injection site pain compared to propofol. While ciprofol demonstrates superior performance in certain aspects, it also has drawbacks and limitations. Primarily, ciprofol may not be suitable for maintaining general anesthesia, as its indications are restricted to short-term or single-dose use. Therefore, in complex or prolonged surgeries, it is typically necessary to combine ciprofol with other anesthetic agents to ensure sustained efficacy ( 8 ). Furthermore, as a novel anesthetic, the safety profile and potential risks of ciprofol in long-term administration remain inadequately elucidated, particularly in scenarios of repetitive or prolonged use, where safety data are still lacking. This study has several limitations. Firstly, all studies included in the analysis were conducted exclusively in China, raising questions about the generalizability of the findings to non-Asian populations. Secondly, during the data extraction process, outcome measures were defined based on prevailing definitions in the literature, potentially introducing subjective bias. Moreover, notable heterogeneity was observed in certain outcome measures across the studies. While sensitivity analysis helped identify some sources of heterogeneity, the leave-one-out method indicated that the overall results were not influenced by any individual study. Lastly, the limited number of large-scale studies highlights the need for further high-quality prospective research to validate the clinical utility of ciprofol. Conclusion In conclusion, the assessment and meta-analysis of this system suggest that outside the operating room, ciprofol demonstrates similar clinical effectiveness to propofol for sedation and anesthesia. Furthermore, when paired with short-acting opioids, ciprofol can augment sedation outcomes while upholding a superior safety profile in comparison to propofol. Additionally, there is no notable variance in patient and physician contentment with the anesthetic outcomes between the two agents. Declarations Acknowledgements Not applicable. Author Contributions LX, YX, and XW developed the original concept of this systematic review. LX, YX and XH contributed to the screening of eligible studies, data extraction, and data synthesis. LX, YX, XH, and XW drafted the first version of the manuscript. LX and QZ prepared tables and figures. All authors have edited and contributed for intellectual content. All authors read and approved the final manuscript and take public responsibility for it. Funding The author(s) declared that no financial support was received for the research, authorship, and/or publication of this article. Data availability statement All data related to the present systematic review are available from the original study corresponding author on reasonable request. Ethics approval and consent to participate Not applicable. 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Comparison of ciprofol-alfentanil and propofol-alfentanil sedation during bidirectional endoscopy: A prospective, double-blind, randomised, controlled trial. Dig Liver Dis. 2024 Apr;56(4):663–71. Zhou R, Fu L, Liu S, et al. Influences of Propofol, Ciprofol and Remimazolam on Dreaming During Anesthesia for Gastrointestinal Endoscopy: A Randomized Double-Blind Parallel-Design Trial. Drug Des Devel Ther. 2024 May;29:18:1907–15. Wen J, Liu C, Ding X, et al. Efficacy and safety of ciprofol (HSK3486) for procedural sedation and anesthesia induction in surgical patients: A systematic review and meta-analysis. Heliyon. 2023;9(12):e22634. Teng Y, Ou MC, Wang X, et al. Pharmacokinetic and pharmacodynamic properties of ciprofol emulsion in Chinese subjects: a single center, open-label, single-arm dose-escalation phase 1 study. Am J Transl Res. 2021;13(12):13791–802. Li X, Yang D, Li Q, et al. Safety, Pharmacokinetics, and Pharmacodynamics of a Single Bolus of the γ-aminobutyric Acid (GABA) Receptor Potentiator HSK3486 in Healthy Chinese Elderly and Non-elderly. Front Pharmacol. 2021;12:735700. Gao SH, Tang QQ, Wang CM, et al. The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled trial. J Clin Anesth. 2024;95:111474. Wang S, Li Y, Chen F, et al. Comparison of the ED50 of Ciprofol Combined With or Without Fentanyl for Laryngeal Mask Airway Insertion in Children: A Prospective, Randomized, Open-Label, Dose-Response Trial. Drug Des Devel Ther. 2024;18:4471–80. Catalani V, Botha M, Corkery JM, et al. Designer Benzodiazepines' Activity on Opioid Receptors: A Docking Study. Curr Pharm Des. 2022;28(32):2639–52. Yang Y, Lang Z, Wang X, et al. Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review. BMC Anesthesiol. 2024;24(1):218. Wang X, Wang X, Liu J, et al. Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study. Eur Rev Med Pharmacol Sci. 2022;26(5):1607–17. Yang Y, Xia Z, Xu C, et al. Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis. Front Pharmacol. 2022;13:1037151. Teng Y, Ou M, Wang X, et al. Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials. Eur J Pharm Sci. 2021;164:105904. Bian Y, Zhang H, Ma S, et al. Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects. Br J Clin Pharma col. 2021 Jan;87(1):93–105. Liao J, Li M, Huang C, et al. Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic. Front Pharmacol. 2022;13:830791. Additional Declarations No competing interests reported. Supplementary Files SupplementaryS1.docx Supplementary material Supplementary S1 SupplementaryFigureS1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5682557","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":396236492,"identity":"606fe331-d458-40be-9f80-057b5655e7ab","order_by":0,"name":"Lei Xie","email":"","orcid":"","institution":"Affiliated Hospital of Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Xie","suffix":""},{"id":396236493,"identity":"ef24b6d4-3a5d-4ce0-beca-9c67574b0ff6","order_by":1,"name":"Yazhi Xi","email":"","orcid":"","institution":"Affiliated Hospital of Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Yazhi","middleName":"","lastName":"Xi","suffix":""},{"id":396236494,"identity":"6aeb79c6-fa19-4d42-b1f1-b0d8c0941278","order_by":2,"name":"Xin Wang","email":"","orcid":"","institution":"the First Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Wang","suffix":""},{"id":396236495,"identity":"7cad6af7-3431-4ddb-8c7c-b868cf3a1423","order_by":3,"name":"Xinyao He","email":"","orcid":"","institution":"Affiliated Hospital of Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Xinyao","middleName":"","lastName":"He","suffix":""},{"id":396236496,"identity":"6cc1481f-569c-4e67-9c87-49c0ae708849","order_by":4,"name":"Qing-he Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYFACHoYDCRU2PPwMDAkgLmMDEVoYD3w4kyYn2UCCFuaDM9sOGxscgHAJa5Fvzz1wmLctLXHz+QPPpHkYbGQ3HGB+9gCfFsaedwmHec7ZJG47cCDZmIchzXjDATZzA3xamCVyDA7zlKUlbjvYkPiYh+Fw4oYDPGwS+LSwgbWwHU7c3MwAtI7hP2EtPEAtB2eAvM/GALLlAGEtEjxvDMCBLHGGIdlwjkGy8czDbGZ4tci35xh/AEdl/5k0iTcVdrJ9x5uf4dUCjXOwG4EsUFAx41ePrIX9AEG1o2AUjIJRMDIBALEQTWDn9aoKAAAAAElFTkSuQmCC","orcid":"","institution":"The Affiliated Hospital of Jiaxing University","correspondingAuthor":true,"prefix":"","firstName":"Qing-he","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2024-12-20 09:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5682557/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5682557/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72740865,"identity":"3071a386-4403-4cce-9945-ba82e0f35708","added_by":"auto","created_at":"2025-01-01 09:37:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":131480,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of selection according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/6ca9eb6beceac7d11f7842d1.png"},{"id":72740178,"identity":"ad8a374d-74f8-48cd-b14b-c63da0966d22","added_by":"auto","created_at":"2025-01-01 09:29:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":263185,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias graph and risk of bias summary. (a) the risk of bias graph: review each risk of bias item presented as percentages across all included studies. (b) the risk of bias summary.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/f1f1a6b7fd8eae48c2b47743.png"},{"id":72740180,"identity":"e39306ee-82df-4163-b0b0-c3343dba720c","added_by":"auto","created_at":"2025-01-01 09:29:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":207023,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of Induction Success Rates\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/4734c4d8c09965446309585b.png"},{"id":72740870,"identity":"dfad17b0-ad3a-4c13-8f6b-e27bc207c7c1","added_by":"auto","created_at":"2025-01-01 09:37:40","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":273171,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of time-related outcomes, including: (a) induction time, (b) time to full recovery from anesthesia, and (c) time to discharge post-anesthesia.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/53a91ef9c0c3ce3577b7e1e9.png"},{"id":72740193,"identity":"59690ad1-2b15-4fdc-8b35-010daf248a91","added_by":"auto","created_at":"2025-01-01 09:29:40","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":446041,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of safety-related outcomes in the ciprofol and propofol groups, comparing the incidence rates of (a) respiratory depression, (b) injection pain, (c) hypotension, (d) bradycardia, (e) nausea and vomiting, (f) dizziness, (g) tachycardia, and (h) somnolence.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/1ff97a9030d14e929bf8c203.png"},{"id":72740869,"identity":"b6066e03-5b9c-44fb-82ea-912575dc216b","added_by":"auto","created_at":"2025-01-01 09:37:40","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":200394,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of Satisfaction Outcomes: (a) Patient Satisfaction, (b) Physician Satisfaction.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/ad5fc02dde00bead65482ddd.png"},{"id":106848445,"identity":"52f1ee1e-9521-4a5f-b657-7b0b377bdc40","added_by":"auto","created_at":"2026-04-14 05:41:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2466938,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/933e96c9-ccfc-41bc-b70f-a85c28e21506.pdf"},{"id":72740176,"identity":"d48d317d-a2a1-4c90-a02e-fdbd4cb9cb0a","added_by":"auto","created_at":"2025-01-01 09:29:40","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary S1\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"SupplementaryS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/824370240f29382effb35a07.docx"},{"id":72740866,"identity":"6f650929-beb2-4488-9a35-1cab0bc9000a","added_by":"auto","created_at":"2025-01-01 09:37:40","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1556754,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5682557/v1/d5917a8c0177043011f7b397.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Efficacy and Safety of Ciprofol vs. Propofol for Non-operating Room Sedation and Anesthesia: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe widespread adoption of minimally invasive techniques and the increasing emphasis on painless medical care have led to a growing demand for sedation and anesthesia in non-operating room settings (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Endoscopic procedures\u0026mdash;such as gastroscopy, colonoscopy, bronchoscopy, cystoscopy, and hysteroscopy\u0026mdash;as well as minor outpatient interventions, often require sedation or anesthesia to enhance patient comfort and facilitate the smooth execution of these procedures (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePropofol, a widely used short-acting hypnotic agent, has become a cornerstone for sedation outside the operating room due to its rapid onset of action (within approximately 30 seconds) and efficient systemic distribution (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, despite its favorable safety profile, the administration of propofol is associated with potential risks, including hypotension and respiratory depression (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). These concerns have prompted ongoing research into safer and more effective alternatives that can further optimize sedation outcomes while ensuring patient safety and comfort in outpatient settings (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Ciprofol, a novel sedative developed and patented in China, represents a promising alternative. This innovative short-acting benzodiazepine sedative demonstrates rapid metabolism, a lower risk of respiratory depression, stable sedative effects, and minimal adverse reactions, making it an appealing choice for sedation and anesthesia in non-operating room settings (\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo comprehensively evaluate the sedative efficacy, safety profile, and patient satisfaction associated with ciprofol, we conducted a systematic review and meta-analysis comparing its performance to that of propofol in non-operating room sedation and anesthesia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol and registration\u003c/h2\u003e \u003cp\u003eThis systematic review and meta-analysis was conducted in strict compliance with the \u003cem\u003eCochrane Handbook for Systematic Reviews of Interventions.\u003c/em\u003e The study design and reporting adhered to the \u003cem\u003ePreferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/em\u003e (PRISMA) guidelines to ensure methodological rigor and transparency. The research protocol was prospectively registered in the \u003cem\u003eInternational Prospective Register of Systematic Reviews\u003c/em\u003e (PROSPERO) under the registration number CRD42024603722.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSystematic Literature Search\u003c/h3\u003e\n\u003cp\u003eWe performed a comprehensive and unrestricted search of four major databases\u0026mdash;PubMed, Embase, Cochrane Library, and Web of Science\u0026mdash;from their inception to September 23, 2024. The search strategy was developed based on the \u0026ldquo;PICOS\u0026rdquo; framework. Specifically, Participants (P) were identified using terms such as \u0026ldquo;endoscopy,\u0026rdquo; \u0026ldquo;bronchoscopy,\u0026rdquo; \u0026ldquo;gastrointestinal endoscopy,\u0026rdquo; \u0026ldquo;hysteroscopy,\u0026rdquo;\u0026ldquo;gastroscopy,\u0026rdquo;\u0026ldquo;colonoscopy,\u0026rdquo;\u0026ldquo;cystoscopy,\u0026rdquo;and\u0026ldquo;proctoscopy.\u0026rdquo; For the Intervention (I), search terms included \u0026ldquo;propofol,\u0026rdquo; \u0026ldquo;disoprofol,\u0026rdquo; \u0026ldquo;ciprofol,\u0026rdquo; and \u0026ldquo;HSK3486.\u0026rdquo; A detailed search strategy is available in \u003cb\u003eSupplementary S1\u003c/b\u003e. A systematic search was also conducted for references corresponding to the eligible studies.\u003c/p\u003e\n\u003ch3\u003eSelection Criteria\u003c/h3\u003e\n\u003cp\u003eThe inclusion criteria required randomized controlled trials (RCTs) comparing ciprofol and propofol for sedation in adult patients undergoing procedural sedation and anesthesia outside the operating room. Studies were eligible if they reported at least one relevant outcome measure. Only peer-reviewed RCTs published in English with complete original texts were included.\u003c/p\u003e \u003cp\u003eExclusion criteria encompassed studies with control groups receiving rescue doses of propofol, those involving standard indications for endotracheal intubation, as well as editorials, letters to the editor, literature reviews, meta-analyses, conference abstracts, duplicate publications, and studies that either lacked relevant outcome measures or full-text accessibility. Additionally, literature unable to provide valid data for comprehensive analysis was excluded.\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cp\u003eThe primary outcome measure was the success rate of sedation, which was defined as the absence of a need to switch to alternative sedatives or administer rescue sedation during endoscopic procedures. Secondary outcome measures included several time-related variables: induction time, defined as the interval from sedative administration to the loss of consciousness; time to full alertness, defined as the duration from cessation of sedative administration to the patient achieving a Modified Observer\u0026rsquo;s Assessment of Alertness/Sedation (MOAA/S) score of 5; and anesthesia discharge time, defined as the time from discontinuation of sedative infusion to the patient meeting discharge criteria.\u003c/p\u003e \u003cp\u003eAdverse events assessed in this study included injection pain, respiratory depression, hypotension, bradycardia, tachycardia, and other sedation-related complications. Respiratory depression was defined as ventilation rates\u0026thinsp;\u0026lt;\u0026thinsp;8 breaths per minute, oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;95%, or both during sedation and recovery. Hypotension was defined as systolic blood pressure (SBP) of 80\u0026ndash;90 mmHg, a\u0026thinsp;\u0026ge;\u0026thinsp;20% reduction in SBP, mean arterial pressure (MAP)\u0026thinsp;\u0026lt;\u0026thinsp;60\u0026ndash;65 mmHg, or a\u0026thinsp;\u0026ge;\u0026thinsp;20% reduction in MAP during sedation and recovery. Bradycardia was defined as a heart rate\u0026thinsp;\u0026lt;\u0026thinsp;50 beats per minute, with minor variations in thresholds across studies (e.g., \u0026lt; 40\u0026ndash;60 beats per minute). Tachycardia was defined as a heart rate\u0026thinsp;\u0026gt;\u0026thinsp;100 beats per minute from sedation to recovery. Other adverse events included nausea, vomiting, dizziness, drowsiness, and patient-reported discomfort.\u003c/p\u003e \u003cp\u003eIn addition to safety and efficacy, both patient and physician satisfaction with the procedure were evaluated as secondary outcomes. Definitions for each outcome measure were standardized based on the most used criteria reported in the included studies. These definitions were finalized following data extraction to ensure consistency and reliability in the meta-analysis.\u003c/p\u003e\n\u003ch3\u003eResearch Selection and Data Extraction\u003c/h3\u003e\n\u003cp\u003eAfter removing duplicates, two independent reviewers (He and Xi) screened the titles and abstracts using EndNote X9, followed by a full-text review of potentially eligible studies. Any disagreements during the screening process were resolved by a third reviewer (Wang), who made the final decision.\u003c/p\u003e \u003cp\u003eData extraction was performed systematically from the included studies. The following information was collected: general study details (title, authors, publication year, and study location), study design, participant characteristics (age, gender, body mass index [BMI], and American Society of Anesthesiologists [ASA] status), sample size, and surgical characteristics (type of procedure). Additionally, we recorded details regarding the usage and dosage of ciprofol, propofol, and short-acting opioids, sedation success rates, time-related variables (induction time, time to full recovery, and time to discharge post-anesthesia), and adverse events (injection pain, respiratory depression, hypotension, bradycardia, tachycardia, nausea, vomiting, dizziness, and somnolence). Patient and physician satisfaction scores were also extracted for further analysis.\u003c/p\u003e \u003cp\u003eWhen research data lacks mean and standard deviation, we utilize the approach suggested by Wan et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) and Luo et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) to estimate the values using the median and range.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of Quality and Risk\u003c/h2\u003e \u003cp\u003eThe quality assessment of RCTs meeting the inclusion criteria was performed using the Cochrane Collaboration\u0026rsquo;s tool for assessing the risk of bias (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Two independent reviewers (Xi and Zhou) evaluated the risk of bias for each selected outcome variable, examining the following domains: allocation concealment, randomization methods, blinding of investigators and participants, blinding of outcome assessors, selective outcome reporting, completeness of data, and other potential sources of bias. The results of the assessment were classified into three categories: low risk of bias, unclear risk of bias, and high risk of bias. Any discrepancies in assessments were resolved through discussion or consultation with a third reviewer when necessary. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to evaluate the degree of confidence. The evaluation categorized the level of certainty as high, moderate, low, or very low, in accordance with the criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe meta-analysis was conducted using RevMan 5.3 and Stata 17 (Stata Corporation, Texas, USA). Effect measures were selected based on the data type. For binary outcomes, the risk ratio (RR) with 95% confidence interval (CI) was employed to quantify the relative likelihood of events between groups. For continuous outcomes, the standard mean difference (SMD) with 95% CI was used to assess differences in mean values between groups. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eHeterogeneity among studies was assessed using the I\u0026sup2; statistic and \u003cem\u003eP\u003c/em\u003e-value from Cochran\u0026rsquo;s \u003cem\u003eQ\u003c/em\u003e test. An I\u0026sup2;value\u0026thinsp;\u0026lt;\u0026thinsp;50% and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.10 were interpreted as low heterogeneity, allowing the use of a fixed-effects model. Conversely, significant heterogeneity (I\u0026sup2;\u0026ge;50% or \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.10) prompted the use of a random-effects model, and meta-regression was employed to explore potential sources of variability. Sensitivity analyses, performed by sequential exclusion of individual studies, were conducted to ensure the stability and robustness of the findings. All sensitivity analyses were carried out using Stata 17.\u003c/p\u003e \u003cp\u003eTo address potential clinical and methodological heterogeneity, subgroup analyses were conducted for the primary outcome based on the use of short-acting opioids during procedures, provided at least two studies were available in each subgroup. This approach helped isolate the influence of procedural differences on sedation outcomes. Due to the limited number of included studies, publication bias was not formally assessed using funnel plots or Egger\u0026rsquo;s test, as such analyses may lack power in small meta-analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy selection\u003c/h2\u003e \u003cp\u003eDuring the literature search process, a total of 145 relevant articles were initially identified. After the removal of duplicate records, 87 articles remained. By screening the titles and abstracts, irrelevant studies were excluded, resulting in 11 full-text articles for further review. Following a comprehensive assessment of these 11 articles, seven were ultimately included (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics and study assessment\u003c/h2\u003e \u003cp\u003eA total of 1,458 patients were included in seven trials (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), with 728 (49.9%) receiving ciprofol and the remaining 730 (50.1%) receiving propofol. Regarding the use of short-acting opioids during sedation, two studies (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) utilized sufentanyl (507 patients, 34.8%), one study (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) used alfentanil (185 patients, 12.7%), and four studies (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) did not administer short-acting opioids (766 patients, 52.5%). Detailed descriptions of the baseline characteristics of the included studies are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides an overview of the risk of bias assessment for each included trial.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of included studies. GY, gastroscopy;CY, colonoscopy༛FB, fiberoptic bronchoscope\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDesign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSample size, n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAge(yr),\u003c/p\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMale,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e),\u003c/p\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eASA 1/2,\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eProcedure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eOpioid\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGao and colleagues 2024 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e66(40.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e164(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen and colleagues 2022 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e39(40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e96(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGY, CY,\u003c/p\u003e \u003cp\u003eor both\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZhang and colleagues 2024 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e104(56.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e185(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGY, CY,\u003c/p\u003e \u003cp\u003eor both\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAlfentanil\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi and colleagues 2022 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e118(40.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e289(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGY, CY,\u003c/p\u003e \u003cp\u003eor both\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLuo and colleagues 2022 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMulticentre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e135(50.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e263(98.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSufentanil\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZhou and colleagues 2024 (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e118(49.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e240(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGY, CY,\u003c/p\u003e \u003cp\u003eor both\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSufentanil\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi and colleagues 2024 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-centre RCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e97(44.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e217(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cp\u003eThe sedation success rate was reported across seven studies (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Analysis demonstrated a significant increase in the sedation success rate when comparing the use of ciprofol to propofol (n\u0026thinsp;=\u0026thinsp;1,458; RR 1.03; 95% CI 1.01\u0026ndash;1.05; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; I\u0026sup2;=90%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sensitivity analysis revealed that no individual study significantly influenced the effect estimate or heterogeneity. Subgroup analysis based on the use of short-acting opioids suggested that this variable may contribute to the observed heterogeneity. Moreover, the use of ciprofol alone showed sedation success rates comparable to propofol, with additional studies suggesting that combining ciprofol with short-acting opioids may effectively enhance induction success rates.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePooled Analysis Results of Primary and Secondary Outcomes. CI: Confidence Interval; SMD: Standard Mean Difference; C: Ciprofol Group; P: Propofol Group; RR: risk ratio\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncluded\u003c/p\u003e \u003cp\u003estudies, n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSample size,\u003c/p\u003e \u003cp\u003en (C/P)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEffect estimate (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eI\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQuality of Evidence\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSedation success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e728/730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR1.03 (1.01\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInduction time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e728/730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD \u0026minus;\u0026thinsp;0.04 (-0.09 to 0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etime to full recovery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e608/608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD0.05(-0.30 to 0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etime to discharge post-anesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e608/608\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD \u0026minus;\u0026thinsp;0.01 (-0.36 to 0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e427/428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.50 (0.33\u0026ndash;0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einjection pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e608/610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.13 (0.06\u0026ndash;0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e681/681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.81 (0.69\u0026ndash;0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradycardia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e561/561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.93 (0.62\u0026ndash;1.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e417/416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.81 (0.47\u0026ndash;1.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edizziness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e561/560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.82 (0.68\u0026ndash;1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etachycardia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175/171\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.43 (0.06\u0026ndash;2.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esomnolence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e336/335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRR 0.75 (0.57\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁⨁\u003c/p\u003e \u003cp\u003eHIGH\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient satisfaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e537/536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD 0.02 (-0.19 to 0.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician Satisfaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e417/416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD 0.22 (-0.23 to 0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e \u003cp\u003eMODERATE\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eTime-related outcomes\u003c/h2\u003e \u003cp\u003eA total of seven studies (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) were included in the analysis of induction time, revealing no statistically significant difference between the propofol and ciprofol groups (n\u0026thinsp;=\u0026thinsp;1,458; SMD = -0.04; 95% CI -0.09 to 0.10; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.12; I\u0026sup2; = 95%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This finding suggests that the two groups exhibited comparable speeds during anesthesia induction. Additionally, six studies (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) were analyzed for time to full recovery from anesthesia, showing no significant difference between the propofol and ciprofol groups (n\u0026thinsp;=\u0026thinsp;1,216; SMD\u0026thinsp;=\u0026thinsp;0.05; 95% CI -0.30 to 0.40; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.79; I\u0026sup2; = 89%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), indicating similar rates of anesthesia recovery between the two groups. Sensitivity analysis revealed that excluding the study by Chen \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) did not eliminate heterogeneity but did show a statistically significant difference time to full recovery from anesthesia between the propofol and ciprofol groups (n\u0026thinsp;=\u0026thinsp;1,120; SMD\u0026thinsp;=\u0026thinsp;0.25; 95% CI 0.05 to 0.45; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02; I\u0026sup2; = 65%), indicating a faster emergence time with propofol. Six studies (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) reported time to discharge post-anesthesia, demonstrating no statistically significant difference between the propofol and ciprofol groups (n\u0026thinsp;=\u0026thinsp;1,216; SMD = -0.01; 95% CI -0.36 to 0.33; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.94; I\u0026sup2; = 89%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), suggesting comparable recovery rates in anesthesia emergence between the two groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSafety-related outcomes\u003c/h2\u003e \u003cp\u003eIn four studies (\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), respiratory depression was assessed, with findings indicating a significant reduction in the risk of respiratory depression when using ciprofol compared to propofol (n\u0026thinsp;=\u0026thinsp;855; RR 0.55; 95% CI 0.33\u0026ndash;0.77; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These findings suggest a clear advantage of ciprofol in reducing the risk of respiratory depression. The incidence of injection pain was reported in six studies (\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), with the use of ciprofol for sedation significantly reducing the risk of injection pain compared to propofol (n\u0026thinsp;=\u0026thinsp;1,218; RR 0.13; 95% CI 0.06\u0026ndash;0.28; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; I\u0026sup2; = 73%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These results indicate a significant advantage of ciprofol in reducing the incidence of injection pain. Hypotension incidence was assessed in six studies (\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), with analysis revealing a significant reduction in the risk of hypotension when using ciprofol compared to propofol (n\u0026thinsp;=\u0026thinsp;1,362; RR 0.81; 95% CI 0.69\u0026ndash;0.95; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ec; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sensitivity testing indicated that no individual study exerted undue influence on the effect estimate or heterogeneity. These findings suggest the superiority of ciprofol in reducing the occurrence of hypotension. Bradycardia incidence was reported in five studies (\u003cspan additionalcitationids=\"CR16 CR17 CR18\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), with no statistically significant difference in the risk of bradycardia between the two sedatives (n\u0026thinsp;=\u0026thinsp;1,122; RR 0.93; 95% CI 0.62\u0026ndash;1.39; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.72; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ed; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative nausea, vomiting, or both were reported in four studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), with no statistically significant difference in the risk between the two sedatives (n\u0026thinsp;=\u0026thinsp;833; RR 0.81; 95% CI 0.47\u0026ndash;1.38; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.44; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ee; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative dizziness was reported in five studies (\u003cspan additionalcitationids=\"CR16 CR17 CR18\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), with no statistically significant difference in the risk between the two sedatives (n\u0026thinsp;=\u0026thinsp;1,121; RR 0.82; 95% CI 0.68\u0026ndash;1.00; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ef; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative tachycardia was reported in two studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), with no statistically significant difference in the risk between the two sedatives (n\u0026thinsp;=\u0026thinsp;349; RR 0.43; 95% CI 0.06\u0026ndash;2.85; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.38; I\u0026sup2; = 0% ; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eg; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative somnolence was reported in three studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), with analysis revealing a significant reduction in the risk of postoperative somnolence with the use of ciprofol compared to propofol (n\u0026thinsp;=\u0026thinsp;671; RR 0.75; 95% CI 0.57\u0026ndash;0.98; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03; I\u0026sup2; = 0%; high-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eh; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sensitivity analyses across all outcome measures indicated that no single study had an undue influence on the effect estimates or observed heterogeneity.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eSatisfaction-related outcomes\u003c/h2\u003e \u003cp\u003eThe included studies evaluated patient and physician satisfaction with the procedure using a rating scale from 0 to 10, with higher scores indicating greater satisfaction. Five studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) reported patient satisfaction, showing no significant difference between groups (n\u0026thinsp;=\u0026thinsp;1,073; SMD 0.02; 95% CI -0.19 to 0.24; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.82; I\u0026sup2; = 69%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003ea; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sensitivity analysis indicated that the removal of the study by Li \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) significantly reduced heterogeneity (SMD 0.12; 95% CI -0.02 to 0.26; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09; I\u0026sup2; = 5%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFour studies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), involving 1,704 patients, were included in the analysis of physician satisfaction. Analysis showed no significant difference between groups (n\u0026thinsp;=\u0026thinsp;833; SMD 0.22; 95% CI -0.23 to 0.67; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.33; I\u0026sup2; = 90%; moderate-quality evidence; Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003eb; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sensitivity analysis indicated a significant decrease in heterogeneity when the study by Zhang \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) was excluded (SMD \u0026minus;\u0026thinsp;0.02; 95% CI -0.17 to 0.13; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.80; I\u0026sup2; = 0%).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review and meta-analysis, data from over 1,400 patients across seven studies were analyzed to compare the sedative efficacy, safety, and satisfaction outcomes of ciprofol and propofol in procedures performed outside the operating room. The principal findings from the pooled analysis are as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) ciprofol enhances sedation success rates, particularly when used in conjunction with short-acting opioids, demonstrating a marked effect in this setting. However, when administered alone, ciprofol does not show a statistically significant difference in sedation success rates compared to propofol. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) ciprofol and propofol exhibit comparable induction times, full awakening times, and anesthesia discharge times. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) ciprofol is associated with a lower risk of respiratory depression and injection pain and may also reduce the incidence of hypotension. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Both ciprofol and propofol yield comparable satisfaction levels among physicians and patients.\u003c/p\u003e \u003cp\u003eIn the field of anesthesiology, providing safe and effective sedation and anesthesia for patients, particularly in outpatient settings, remains a key area of ongoing interest. Recently, ciprofol has gained significant attention as a novel intravenous anesthetic. Studies indicate that ciprofol not only offers rapid onset, fast metabolism, and minimal accumulation but also exhibits reduced cardiovascular depressive effects, potentially giving it an advantage in clinical practice (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe research findings indicate that there is no significant difference in the success rates of anesthesia induction between the two groups using ciprofol individually, reflecting an overall comparable effectiveness of ciprofol and propofol in anesthesia induction. However, ciprofol can achieve similar anesthetic effects to propofol at lower doses, approximately one-fifth to one-sixth of the dose of propofol, demonstrating a higher therapeutic index (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Moreover, when used in combination with short-acting opioids, ciprofol significantly enhances the success rate of sedation. This suggests that opioids can synergistically enhance the sedative effects of ciprofol (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The study also revealed no significant difference in induction time between the ciprofol group and the propofol group. However, the existing literature shows some inconsistency in the results regarding induction time. Research by Yang \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) implies a shorter induction time for ciprofol compared to propofol in the operating room, although other studies suggest a relatively shorter induction time for propofol (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The study posits that clinical heterogeneity may primarily stem from variations in drug dosage and types of adjuvant medications. Additionally, factors such as the type of surgery, procedural techniques, rate of anesthetic drug administration, and individual patient differences may also impact the consistency of outcomes. In conclusion, the findings of this study provide reliable data support and analytical references for future related research.\u003c/p\u003e \u003cp\u003eIn terms of safety, particularly when comparing the clinical efficacy of ciprofol to propofol with similar levels of patient and physician satisfaction\u0026mdash;propofol is associated with dose-dependent cardiorespiratory depression. In contrast, ciprofol, due to its high lipid solubility, can achieve effective sedation at lower doses. Unlike conventional emulsions, ciprofol employs a formulation containing medium-chain triglycerides, resulting in a significant reduction in free molecule concentrations. This reduction not only diminishes post-injection pain but also has a less pronounced direct impact on the cardiovascular system (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Moreover, ciprofol follows a relatively gentle metabolic pathway, primarily undergoing metabolism through glucose catalysis, oxidation, and sulfation to produce harmless glucuronide conjugates that are subsequently excreted by the kidneys (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). This metabolic characteristic reduces the risk of drug accumulation in the body, thereby lowering the likelihood of cardiorespiratory depression. Additionally, ciprofol exhibits highly specific activity toward GABA receptors, particularly the α1β2γ2 subtype, with minimal inhibitory effects on cytochrome P\u003csub\u003e450\u003c/sub\u003e enzymes, further mitigating its influence on heart rate, blood pressure, and the respiratory system (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). The data from this meta-analysis indicate that, in low-risk patients with an ASA risk classification of 3 or below, ciprofol significantly reduces critical respiratory and circulatory adverse events and injection site pain compared to propofol.\u003c/p\u003e \u003cp\u003eWhile ciprofol demonstrates superior performance in certain aspects, it also has drawbacks and limitations. Primarily, ciprofol may not be suitable for maintaining general anesthesia, as its indications are restricted to short-term or single-dose use. Therefore, in complex or prolonged surgeries, it is typically necessary to combine ciprofol with other anesthetic agents to ensure sustained efficacy (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Furthermore, as a novel anesthetic, the safety profile and potential risks of ciprofol in long-term administration remain inadequately elucidated, particularly in scenarios of repetitive or prolonged use, where safety data are still lacking.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Firstly, all studies included in the analysis were conducted exclusively in China, raising questions about the generalizability of the findings to non-Asian populations. Secondly, during the data extraction process, outcome measures were defined based on prevailing definitions in the literature, potentially introducing subjective bias. Moreover, notable heterogeneity was observed in certain outcome measures across the studies. While sensitivity analysis helped identify some sources of heterogeneity, the leave-one-out method indicated that the overall results were not influenced by any individual study. Lastly, the limited number of large-scale studies highlights the need for further high-quality prospective research to validate the clinical utility of ciprofol.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the assessment and meta-analysis of this system suggest that outside the operating room, ciprofol demonstrates similar clinical effectiveness to propofol for sedation and anesthesia. Furthermore, when paired with short-acting opioids, ciprofol can augment sedation outcomes while upholding a superior safety profile in comparison to propofol. Additionally, there is no notable variance in patient and physician contentment with the anesthetic outcomes between the two agents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLX, YX, and XW developed the original concept of this systematic review. LX, YX and XH contributed to the screening of eligible studies, data extraction, and data synthesis. LX, YX, XH, and XW drafted the first version of the manuscript. LX and QZ prepared tables and figures. All authors have edited and contributed for intellectual content. All authors read and approved the final manuscript and take public responsibility for it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared that no financial support was received for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data related to the present systematic review are available from the original study corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMelloni C. 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Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study. Eur Rev Med Pharmacol Sci. 2022;26(5):1607\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Xia Z, Xu C, et al. Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis. Front Pharmacol. 2022;13:1037151.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeng Y, Ou M, Wang X, et al. Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials. Eur J Pharm Sci. 2021;164:105904.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBian Y, Zhang H, Ma S, et al. Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects. Br J Clin Pharma col. 2021 Jan;87(1):93\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiao J, Li M, Huang C, et al. Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic. Front Pharmacol. 2022;13:830791.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Propofol, Ciprofol, Procedural sedation, Non-operating room, Safety, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-5682557/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5682557/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePropofol is a widely used intravenous anesthetic for procedural sedation in non-operating room settings, but its use is often accompanied by adverse events such as injection pain, respiratory depression, and hypotension. Ciprofol, a novel intravenous anesthetic, has gained attention as a potential alternative due to its favorable safety profile and comparable sedative efficacy. This systematic review and meta-analysis aimed to compare the efficacy, safety, and satisfaction outcomes of ciprofol and propofol in adults undergoing non-operating room procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) comparing ciprofol and propofol. Data from eligible studies were extracted and analyzed using RevMan 5.3 and Stata 17. Risk ratio (RR) with 95% confidence interval (CI) were calculated for binary outcomes, and standard mean difference (SMD) with 95% CI were used for continuous outcomes. Heterogeneity was assessed using the I²statistic, with fixed-effects or random-effects models applied as appropriate. Sensitivity and subgroup analyses were performed to explore sources of heterogeneity and ensure robustness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Seven RCTs involving 1,458 participants were included. Ciprofol demonstrated comparable sedation success rates to propofol. Subgroup analyses indicated that combining ciprofol with short-acting opioids significantly improved sedation outcomes (RR 1.07, 95% CI 1.03–1.12; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01). Ciprofol was associated with significantly lower risks of injection pain (RR 0.13, 95% CI 0.06–0.28; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01), respiratory depression (RR 0.55, 95% CI 0.33–0.77; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01), and hypotension (RR 0.81, 95% CI 0.69–0.95; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01). No significant differences were observed between the two agents in induction time or time to full recovery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Ciprofol is a safe and effective alternative to propofol for non-operating room procedural sedation. Its superior safety profile, particularly in reducing injection pain, respiratory depression, and hypotension, makes it a promising option, especially when combined with short-acting opioids.\u003c/p\u003e","manuscriptTitle":"Comparative Efficacy and Safety of Ciprofol vs. Propofol for Non-operating Room Sedation and Anesthesia: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 09:29:35","doi":"10.21203/rs.3.rs-5682557/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6a3f26a6-21de-45f7-a3ec-689d60f44a43","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T05:41:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 09:29:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5682557","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5682557","identity":"rs-5682557","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}