Remimazolam 20mg powder for solution for injection vials

Background Remimazolam is a novel sedative drug approved for procedural sedation and general anesthesia. Clinical trials have already explored its use in elderly patients for general anesthesia. For elderly patients with declining physical and physiological function, anesthesia safety is crucial. Most current clinical studies compare the safety of remimazolam and propofol, though the results are inconsistent. Therefore, we conducted a meta-analysis to compare the safety of remimazolam and propofol in general anesthesia for elderly patients. Methods We systematically searched the PubMed, Cochrane Library, Embase, and Web of Science databases for all published randomized controlled trials comparing remimazolam and propofol for general anesthesia in elderly patients. We synthesized data from eligible studies using relative risk or mean difference, and analyzed differences in hemodynamic stability and adverse effects between the two drugs. Data extraction and quality assessment were performed independently by two researchers. Results Eight randomized controlled trials involving 571 participants were included. Compared to propofol, remimazolam was associated with a lower incidence of hypotension (RR = 0.51, 95% CI: [0.33, 0.81], I 2 = 18%, p = 0.3 > 0.1) and bradycardia (RR = 0.56, 95% CI: [0.31, 1.02], Z = 1.88, p = 0.06 < 0.05). The mean arterial pressure after induction was higher in the remimazolam group (WMD = 3.95, 95% CI: [3.197, 9.498], Z = 3.95, p < 0.00001). The remimazolam group had a higher heart rate (HR) after induction compared to the propofol group (WMD = 7.89, 95% CI: [−2.39, 18.17], Z = 1.5, p = 0.13 > 0.05), but this result was not statistically significant. Among other secondary outcomes, the remimazolam group had lower incidences of injection site pain, nausea and vomiting, and hypoxemia compared to the propofol group, and also had a shorter extubation time. Conclusion In this meta-analysis, compared to propofol, remimazolam reduced the incidence of hypotension, bradycardia, and injection site pain during general anesthesia in elderly patients. The mean arterial pressure (MAP) and heart rate (HR) were more stable after induction. Remimazolam may be a safer sedative for elderly patients. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024516950 , CRD42024516950.

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BACKGROUND: Elderly patients comprise an increasing proportion of patients undergoing surgery, and they require special attention due to age-related physiological changes. Propofol is the traditional agent for anaesthesia, and recently, remimazolam, a novel ultra-short-acting benzodiazepine, has emerged as an alternative to propofol in general anaesthesia. OBJECTIVES: We aim to compare remimazolam vs . propofol for general anaesthesia in elderly patients regarding hypotension, induction characteristics, haemodynamics and recovery outcomes. DESIGN: Meta-analysis with sensitivity and trial sequential analyses (TSA) to assess inconsistencies. Risk ratios and mean differences with 95% confidence intervals (95% CIs) were computed using a random effects model. Subgroups and meta-regression according to anaesthesia methods were also performed. DATA SOURCES: We systematically searched MEDLINE, Embase and Cochrane for randomised controlled trials (RCTs) up to January 1, 2024. ELIGIBILITY CRITERIA: Patients at least 60 years old, comparing remimazolam vs . propofol for general anaesthesia. RESULTS: Eleven RCTs (947 patients) were included. Compared with propofol, remimazolam was associated with lower postinduction and intra-operative hypotension (RR 0.41, 95% CI 0.27 to 0.62, P < 0.001) and incidence of bradycardia (risk ratio 0.58, 95% CI 0.34 to 0.98, P = 0.04), with a higher heart rate ( P = 0.01). The incidence of injection pain was lower ( P < 0.001), but remimazolam was associated with a longer time to loss of consciousness ( P < 0.001) and a higher bispectral index at loss of consciousness ( P = 0.04). No differences were found for mean arterial pressure, emergence time, extubation time and incidence of emergence agitation. The TSA was consistent and achieved the required information size for hypotension. CONCLUSIONS: Remimazolam significantly reduced the risk of hypotension, bradycardia and injection pain, despite an increase in the time to loss of consciousness. Remimazolam appears to be an effective and well tolerated alternative to propofol in elderly patients undergoing general anaesthesia.

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Background: Remimazolam is a new medication with sedative and hypnotic effects. It has been demonstrated non-inferior to propofol in general anesthesia with regard to efficacy and safety. However, whether general anesthesia with remimazolam is better than propofol in terms of patients’ recovery quality remains unknown. Patients and Methods: Patients enrolled in this study were randomized to remimazolam or propofol group. In remimazolam group, general anesthesia was induced with remimazolam and sufentanil and maintained with remimazolam and remifentanil. In propofol group, general anesthesia was induced with propofol and sufentanil and maintained with propofol and remifentanil. Neuromuscular blocking agent cisatracurium was also injected during anesthesia. Sedation level was monitored by bispectral index (BIS). Our primary outcome was the quality of patients’ postoperative recovery, using the Quality of Recovery-15 (QoR-15) scale. Secondary outcomes included SpO 2 , HR, MBP and frequency of application of vasoactive drugs during anesthesia, as well as incidences of adverse events in the post anesthesia care unit (PACU). Results: The global scores of QoR-15 scale were lower in remimazolam group at postoperative day 1 and day 3 compared to propofol group, but differences between the two groups only had clinical significance at postoperative day 1. Among the five dimensions of QoR-15 scale, scores for physical comfort and emotional state were lower in remimazolam group than propofol group. MBP and HR were higher in remimazolam group than propofol group after anesthesia induction. SpO 2 was similar in the two groups. The frequency of application of vasoactive drugs during anesthesia was higher in propofol group than remimazolam group. There was no statistical difference in the incidences of adverse events between the two groups. Conclusion: General anesthesia with remimazolam can provide more stable hemodynamics but also cause temporary reduction in the quality of recovery in patients undergoing urologic surgery, compared to propofol. Keywords: remimazolam, propofol, quality of recovery, urologic surgery

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INTRODUCTION: The association between remimazolam and emergence agitation (EA) remains unclear. This meta-analysis aimed to compare the relative risk of developing EA when using remimazolam vs. propofol in induction and maintenance of general anesthesia. METHOD: We searched PubMed, clinicaltrials.gov, Web of Science, Cochrane Library, and Embase databases to identify studies meeting the inclusion criteria. The primary outcome was the incidence of EA. Secondary outcomes included the incidence of postoperative delirium (POD) within 7 days after surgery, emergence time, extubation time, length of post-anesthesia care unit (PACU) stay, and adverse events. RESULTS: A total of 19 randomized controlled trials with 3031 patients were included in the meta-analysis. There was no statistically significant difference in the incidence of EA (RR = 0.82; 95 % confidence interval [CI], 0.41-1.65; p = 0.585) between remimazolam and propofol. Likewise, there were no significant intergroup differences in POD incidence, extubation time, emergence time, or length of PACU stay. Remimazolam exhibited superior hemodynamic stability, with a significantly reduced incidence of postinduction hypotension and intraoperative hypotension compared with propofol, while maintaining comparable safety profiles in terms of postoperative nausea and vomiting (PONV), intraoperative awareness, and hypoxemia. Subgroup analysis revealed that without routine postoperative antagonist administration, remimazolam was associated with prolonged extubation and length of PACU stay relative to propofol. In contrast, following antagonizing with flumazenil, the extubation and emergence times of the remimazolam group were shorter than those of the propofol group, while comparable PACU discharge time was maintained. CONCLUSION: The use of remimazolam for the induction and maintenance of general anesthesia does not lead to a higher occurrence of EA in adult patients undergoing surgery, relative to propofol. However, in patients with ASA III-IV, remimazolam may be linked to a greater risk of POD than propofol.

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BACKGROUND: To compare the POD rates in patients undergoing non-cardiac surgery who received remimazolam perioperatively versus placebo or other sedatives. METHODS: We systematically searched four major databases (Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed) for relevant randomized controlled trials (RCTs) up to July 11, 2024. Literature quality evaluation was used the bias risk table in Review Manager 5.4. The primary outcome of interest was POD, and secondary outcomes were the hypotension risk, bradycardia and, nausea and vomiting. RESULTS: Across 11 trials involving 1985 participants, we recorded 309 cases of POD during follow-up. In trials where the control group received saline, remimazolam decrease the risk of POD significantly by 70% (RR 0.30, 95% CI [0.19, 0.46]; p < 0.00001). Statistical analysis did not show significant difference in the risk of POD between the remimazolam group and the groups receiving either dexmedetomidine (RR 1.23 [0.64, 2.37]; p = 0.53) or propofol (RR 0.83 [0.60, 1.16]; p = 0.28). Regarding adverse events, remimazolam significantly reduces the morbidity of hypotension compared to dexmedetomidine (RR 0.25 [0.10, 0.65]; p = 0.004) and propofol (RR 0.45 [0.33, 0.60]; p < 0.00001). In addition, there were no significant differences in the incidence of bradycardia (RR 0.85; 95% CI [0.34-2.12], p = 0.72) and nausea and vomiting (RR 1.06; 95% CI [0.74-1.51], p = 0.77) between remimazolam and the control group. CONCLUSIONS: During the perioperative period, using remimazolam can lower POD risk after surgery for patients who had non-cardiac surgery, but remimazolam does not work better than dexmedetomidine or propofol. Compared with the dexmedetomidine and propofol, remimazolam also has apparent advantages in preventing intraoperative hypotension.

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Remimazolam, a short-acting benzodiazepine, may be used for induction and maintenance of total intravenous anaesthesia, but its role in the management of patients with multiple comorbidities remains unclear. In this phase 3 randomised controlled trial, we compared the anaesthetic efficacy and the incidence of postinduction hypotension during total intravenous anaesthesia with remimazolam vs. propofol. A total of 365 patients (ASA physical status 3 or 4) scheduled for elective surgery were assigned randomly to receive total intravenous anaesthesia with remimazolam (n = 270) or propofol (n = 95). Primary outcome was anaesthetic effect, quantified as the percentage of time with Narcotrend® Index values ≤ 60, during surgery (skin incision to last skin suture), with a non-inferiority margin of -10%. Secondary outcome was the incidence of postinduction hypotensive events. Mean (SD) percentage of time with Narcotrend Index values ≤ 60 during surgery across all patients receiving remimazolam (93% (20.7)) was non-inferior to propofol (99% (4.2)), mean difference (97.5%CI) -6.28% (-8.89-infinite); p = 0.003. Mean (SD) number of postinduction hypotension events was 62 (38.1) and 71 (41.1) for patients allocated to the remimazolam and propofol groups, respectively; p = 0.015. Noradrenaline administration events (requirement for a bolus and/or infusion) were also lower in patients allocated to remimazolam compared with propofol (14 (13.5) vs. 20 (14.6), respectively; p < 0.001). In conclusion, in patients who were ASA physical status 3 or 4, the anaesthetic effect of remimazolam was non-inferior to propofol.

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OBJECTIVES: Sedation for endoscopic retrograde cholangiopancreatography (ERCP) is challenging owing to patient comorbidities and procedural complexity. Remimazolam, a novel benzodiazepine, has potential safety benefits. We aimed to systematically compare the efficacy and safety of remimazolam and propofol for ERCP sedation through a meta-analysis and trial sequential analysis (TSA). METHODS: We searched Ovid-MEDLINE, Ovid-Embase, Cochrane Central, and Google Scholar for randomized controlled trials (RCTs) that compared efficacy and safety of remimazolam and propofol in ERCP sedation. Sensitivity analysis and TSA were also performed. RESULTS: Five RCTs (965 participants) were included. In these trials, remimazolam significantly reduced hypoxia (risk ratio [RR], 0.522; 95% confidence interval [CI] 0.348-0.783; Grading of Recommendations, Assessment, Development, and Evaluation [GRADE], high), hypotension (RR, 0.507; 95% CI 0.396-0.649; GRADE, high), and bradycardia (RR, 0.475; 95% CI 0.308-0.732; GRADE, high). However, it increased tachycardia (RR, 3.363; 95% CI, 1.466-7.714; GRADE, moderate) and body movement (RR, 2.744; 95% CI, 1.216-6.193; GRADE, moderate). Delirium and agitation (RR, 0.586; 95% CI, 0.157-2.179; GRADE, moderate) and completion rate (RR, 1.009; 95% CI, 0.97-1.042; GRADE, moderate) were comparable. Recovery quality was higher in remimazolam group (mean difference, 1.541; 95% CI, 0.057-3.024; GRADE, low). Other outcomes, including induction and recovery times, were similar. CONCLUSION: Remimazolam demonstrated superior safety profile than propofol for ERCP sedation, significantly reducing hypoxia, hypotension, and bradycardia with high certainty evidence and TSA confirmation. Despite the higher incidence of tachycardia and body movement associated with remimazolam, the completion rate and risk of delirium or agitation were similar for both sedatives.

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Background and Objectives: This meta-analysis compares the safety and efficacy of remimazolam and dexmedetomidine for sedation during regional anesthesia, focusing on respiratory and hemodynamic outcomes. Materials and Methods: A systematic search of CENTRAL, Embase, PubMed, Scopus, and Web of Science up to November 2024 identified randomized controlled trials (RCTs) comparing remimazolam with dexmedetomidine. Outcomes included respiratory depression (primary outcome), bradycardia, hypotension, hypertension, respiratory and heart rates, mean arterial pressure, sedation onset time, emergence time, and postoperative nausea and vomiting (PONV). Effect sizes were calculated as relative risks (RRs) or mean differences (MDs) using random-effects models. Results: Five RCTs involving 439 participants were included. Remimazolam did not significantly increase respiratory depression risk compared to dexmedetomidine (RR: 1.36, 95% CI [0.39, 4.71], p = 0.6305, I2 = 44%). Bradycardia incidence was lower with remimazolam (RR: 0.15, 95% CI [0.06, 0.39], p = 0.0001, I2 = 0%). Remimazolam showed faster sedation onset (MD: −6.04 min, 95% CI [−6.99, −5.09], p = 0.0000, I2 = 68%). Both drugs demonstrated similar occurrences of hypotension and hypertension, respiratory rates, mean arterial pressures, emergence times, and incidences of PONV. Conclusions: Remimazolam offers comparable safety and efficacy to dexmedetomidine, with advantages such as lower bradycardia risk and faster sedation onset. These findings support remimazolam as a viable sedative option during regional anesthesia, although further large-scale studies are warranted to confirm these results and optimize sedation practices.

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