Dose Of Remimazolam Research Articles

Comparison of the anesthetic effects of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery

ObjectiveThe purpose of this study is to observe whether there is a difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery, so as to provide reference for clinical application.MethodsFifty patients, aged 18–65 years, ASA I-II, scheduled for hysteroscopy under total intravenous anesthesia were selected. The patients were randomly divided into two groups (n = 25): remimazolam tosilate group (group T) and remimazolam besylate group ( group R). The main observation index was the induction dose of remimazolam; secondary observation indicators were sleep time, anesthesia maintenance time, recovery time, induction maintenance dose of alfentanil, maintenance dose of remimazolam, and incidence of adverse events during anesthesia ( hypertension, hypotension, bradycardia, tachycardia).ResultsThere was no significant difference in anesthesia induction dose, recovery time, sleep time, anesthesia maintenance time, and incidence of adverse events during anesthesia ( body movement, cough, hypertension, hypotension, bradycardia, tachycardia) between the two groups (P > 0.05).ConclusionThere was no significant difference in the anesthetic effect of remimazolam tosilate and remimazolam besylate in daytime hysteroscopic surgery.Clinical trial RegistrationChinese Clinical Trial Registry, ChiCTR2400081688.

The dose of remimazolam combined with sufentanil for the induction of general anesthesia in obese patients undergoing bariatric surgery: an up-and-down sequential allocation trial.

Background and purpose: Remimazolam is a newly developed benzodiazepine drug with water-soluble, esterase degradation, and ultra-short-acting properties. The dose for general anesthesia induction in obese patients was not known. This study aimed to determine the optimal dose of remimazolam in combination with sufentanil for the induction of general anesthesia in obese patients. Methods: It was a prospective observational study. We recruited 46 patients scheduled for bariatric surgery from October 2022 to December 2023. One patient refused to provide informed consent, and six patients were receiving psychotropic medication. Thirty-nine patients were enrolled. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale was used to assess the patient's response. The dose of sufentanil was 0.5 µg/kg (lean body weight [LBW]). The initial dose of remimazolam was 0.3mg/kg (LBW). The dose of remimazolam was modified using the up-and-down allocation technique. Successful sedation (negative group) was characterized by achieving a MOAA/S score ≤ 1 within 3min of commencing remimazolam infusion. If negative, the next patient received a low-level dose at a ratio of 0.9. Failed sedation (positive group) was defined as a MOAA/S score of >1 within 3min of commencing remimazolam infusion. The patients in the positive group received propofol 0.5mg/kg as a remedial measure, and the next dose was increased to a higher level. The primary outcome was to determine the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam in combination with sufentanil 0.5 µg/kg for induction in obese patients. The secondary outcome was to determine the occurrence of adverse effects such as hypotension, hypertension, and intraoperative awareness. Results: The ED50 and ED95 values of remimazolam (LBW) combined with sufentanil (0.5 µg/kg) (LBW) were 0.115mg/kg (95% CI: 0.072-0.137) and 0.179mg/kg (95% CI: 0.150-0.434), respectively, and the time of loss of consciousness in the negative group was 120.13 ± 25.03s. The cardiovascular system was stable during the induction period. The incidence of post operative nausea and vomiting (PONV) was 38.5% in 39 patients. Respiratory depression, allergic reaction, intraoperative awareness, and delayed emergence were not observed in any patient. Conclusion: Remimazolam combined with sufentanil (0.5 µg/kg) (LBW) can be effectively used for general anesthesia induction in obese patients. The ED50 and ED95 values of remimazolam (LBW) were 0.115mg/kg and 0.179mg/kg, respectively. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200065602.

Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose-escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose-exposure-response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.

The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial

BackgroundThis study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences.MethodsUsing a modified Dixon’s up-and-down allocation approach, we sequentially enrolled male and female patients aged 19–60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer’s Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved.ResultsWe included 22 male and 22 female patients. Based on Dixon’s up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18–0.20) mg/kg in the male group and 0.29 (0.29–0.30) mg/kg in the female group.ConclusionsThere was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients.Trial registrationThis study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).

Anesthesia management for percutaneous mitral valve repair in a patient with mitochondrial cardiomyopathy and low cardiac function: a case report

BackgroundMitochondrial cardiomyopathy occurs when impaired mitochondrial energy production leads to myocardial dysfunction. Anesthetic management in such cases is challenging due to risks of circulatory depression associated with anesthesia and mitochondrial dysfunction induced by anesthetics. Although there are reports of anesthetic management for patients with mitochondrial diseases, there are few reports specifically addressing cardiac anesthesia for patients with mitochondrial cardiomyopathy. We present a case where percutaneous mitral valve repair with MitraClip™ was successfully performed under remimazolam anesthesia in a patient with mitochondrial cardiomyopathy who developed functional mitral valve regurgitation due to low cardiac function and cardiomegaly.Case presentationA 57-year-old woman was diagnosed with chronic cardiac failure, with a 10-year history of dilated cardiomyopathy. She was diagnosed with mitochondrial cardiomyopathy 8 years ago. Over the past 2 years, her cardiac failure worsened, and mitral valve regurgitation gradually developed. Surgical intervention was considered but deemed too risky due to her low cardiac function, with an ejection fraction of 26%. Therefore, percutaneous MitraClip™ implantation was selected. After securing radial artery and central venous catheterization under sedation with dexmedetomidine, anesthesia was induced with a low dose of remimazolam 4 mg/kg/h. Anesthesia was maintained with remimazolam 0.35–1.0 mg/kg/h and remifentanil 0.1 μg/kg/min. Noradrenaline and dobutamine were administered intraoperatively, and the procedure was completed successfully without circulatory collapse. The patient recovered smoothly from anesthesia and experienced no complications. She was discharged on the eighth day after surgery.ConclusionAnesthesia management with remimazolam appears to be a safe and effective for MitraClip™ implantation in patients with mitochondrial cardiomyopathy.

Potential role of remimazolam in alleviating bone cancer pain in mice via modulation of translocator protein in spinal astrocytes

Bone cancer pain (BCP) is a complex clinical challenge, with current treatments often falling short of providing adequate relief. Remimazolam, a benzodiazepine receptor agonist recognized for its anxiolytic effects, has emerged as a potential agent in managing BCP. This study explores the analgesic properties of remimazolam and its interaction with the translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, in spinal astrocytes. In the context of BCP, previous research has indicated that TSPO expression in spinal astrocytes may serve a protective regulatory function in neuropathic pain models. Building on this, the BCP mice received various doses of remimazolam on the 15th day post-inoculation, and pain behavior was assessed over time. The results showed that BCP induced an upregulation of TSPO and astrocyte activation in the spinal dorsal horn, alongside increased extracellular signal-regulated kinase (ERK) signaling and inflammatory cytokine expression. Remimazolam administration resulted in a dose-dependent reduction of pain behaviors, which corresponded with a decrease in both ERK pathway activation and inflammatory factor expression. This suggests that remimazolam's analgesic effects are mediated through its action as a TSPO agonist, leading to the attenuation of neuroinflammation and pain signaling pathways. Importantly, the analgesic effects of remimazolam were reversed by the TSPO antagonist PK11195, underscoring the pivotal role of TSPO in the drug's mechanism of action. This reversal also reinstated the heightened levels of ERK activity and inflammatory mediators, further confirming the involvement of TSPO in the modulation of these pain-related processes. These findings open new avenues for the therapeutic management of bone cancer pain, positioning remimazolam as a promising candidate for further investigation and development.

Determination of the effective dose of remimazolam combined with sufentanil for inhibiting body movement during surgical abortion: An up-and-down sequential allocation trial.

Remimazolam, a recently developed anesthetic characterized by its rapid and ultra-short-acting properties, exhibits pharmacological attributes that make it potentially suitable for painless surgical abortion procedures. The objective of this study was to determine the effective dose of remimazolam when administered in combination with sufentanil, with the intention of inhibiting body movement during surgical abortion. Additionally, a secondary objective was to assess the recovery profile from general anesthesia. The study enrolled a total of 25 healthy women aged 20 to 40, with a body mass index between 18 and 28 kg/m2, in their first trimester of pregnancy (up to 12 weeks), and American Society of Anesthesiologists status I and II. Anesthesia induction was initiated by administering sufentanil at a dose of 0.1 μg/kg. The modified Dixon up-and-down method was employed to determine the induction dose of remimazolam for each patient. The 50% and 95% effective dose of remimazolam for inhibitory effects of body movement was estimated using centered isotonic regression to be 0.145 mg/kg (95% CI: 0.115, 0.207), and 0.242 mg/kg (95% CI: 0.232, 0.620), respectively. Five out of 25 (20%) experienced hiccups, with 1 patient having persistent hiccups until the end of the surgery. The mean time to first eye-opening was 51.4 ± 20.5 seconds, and the time to obey verbal command was 54.5 ± 20.6 seconds. Upon arrival at the postanesthesia care unit, 95.7% of the patients achieved a Modified Aldrete score ≥ 9. The 50% and 95% effective dose of remimazolam for inhibiting body movement during surgical abortion when used in combination with 0.1 μg/kg of sufentanil were 0.145 mg/kg and 0.242 mg/kg, respectively.

Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing colonoscopy: A phase III, investigator-initiated trial.

We conducted an investigator-initiated clinical trial in which remimazolam was used to achieve sedation in patients undergoing colonoscopy. This multicenter, double-blind, placebo-controlled, phase III investigator-initiated trial included patients who underwent colonoscopy under sedation achieved with remimazolam (initial dose: 3 mg; additional doses: 1 mg) or normal saline (placebo). The primary endpoint was the sedation success rate during colonoscopy, defined as successful sedation (modified observer's alertness/sedation [MOAA/S] score ≤4 prior to colonoscopy), the successful completion of the colonoscopy, and no more than five additional doses of remimazolam per 15 min during the procedure. The sedation success rate was 95.0% (38/40 patients) in the remimazolam group and 0.0% (0/11 patients) in the placebo group (p&lt;0.01). The time from the end of the procedure to awakening was 0.0 (interquartile range: 0.0-0.0) min in both groups. The time from the end of the procedure to ambulation was 5.0 min (interquartile range: 0.0-10.0 min) in the remimazolam group and 0.0 min (interquartile range: 0.0-0.0 min) in the placebo group (p=0.02). No serious adverse events occurred. The use of remimazolam to achieve sedation in Japanese patients undergoing colonoscopy was more effective than the use of a placebo. This study was registered in the Japan Registry of Clinical Trials (registration number: jRCT2031200360).

Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Efficacy and safety of remimazolam versus propofol for intraoperative sedation during regional anesthesia: A phase II, multicenter, randomized, active-controlled, single-blind clinical trial.

This study aimed to evaluate the efficacy and safety of remimazolam for intraoperative sedation during regional anesthesia. It was a phase II-multicenter, randomized, single-blind, parallel-group, active-controlled clinical trial (No. ChiCTR2100054956). From May 6, 2021 to July 4, 2021, patients were randomly enrolled from 17 hospitals in China. A total of 105 patients aged 18-65 years who underwent selective surgery under regional anesthesia were included. Patients received different sedatives with different dosages: 0.1 mg/kg remimazolam (HR), 0.05 mg/kg remimazolam (LR), or 1.0 mg/kg propofol (P) group, followed by a maintenance infusion. Main outcome measures included the efficacy of sedation measured by Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) levels (1-4, 1-3, 2-3, 3, and 2-4) during the sedation procedure (the duration percentage) and incidence of adverse reactions. It showed that the duration percentage of MOAA/S levels 1-4 was 100.0 [8.1]% (median [interquartile range]), 89.9 [20.2]%, 100.0 [7.7]% in the HR, LR, and P groups, respectively. The percentage of patients in the HR, LR, and P groups who achieved MOAA/S levels 1-4 within 3 min after administration was 85.7%, 58.8%, and 82.9%, respectively. However, the time to recovery from anesthesia after withdrawal of sedatives (7.9 ± 5.7 min), incidence of anterograde amnesia (75%), and adverse effects were not statistically significant among the three groups. These findings suggest that a loading dose of remimazolam 0.1 mg/kg followed by a maintenance infusion of 0-3 mg/kg/h provides adequate sedation for patients under regional anesthesia without increasing adverse reactions.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP

BackgroundCompared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP).MethodsA dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded.ResultsA total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287–0.320). ED95 was 0.315 (95% CI = 0.312–0.323) and ED99 was 0.323 (95% CI = 0.323–0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients.ConclusionsA loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope.Trial registrationThe study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Remimazolam for anesthesia and sedation in cardiac surgery and for cardiac patients undergoing non-cardiac surgery: a systematic-narrative hybrid review.

Remimazolam, an ultra-short-acting benzodiazepine recognized and approved as an anesthetic and sedative in multiple countries, offers a distinctive pharmacokinetic profile, boasting advantages such as rapid onset, short action duration, and rapid recovery. These attributes may contribute to enhanced hemodynamic stability and a diminished risk of respiratory depression compared to other sedatives. We conducted the first comprehensive systematically structured narrative review to evaluate the role and potential application of remimazolam in cardiac surgery. Twenty-one studies published from 2021 to 2023 delved into remimazolam's application in open cardiac surgery, cardiac catheterization or electrophysiology laboratories, and high-risk cardiovascular patients undergoing non-cardiac surgery. Overall, remimazolam usage was apparently linked to potentially superior hemodynamic stability compared to other hypnotic drugs. However, findings regarding the reduction in postoperative delirium incidence with remimazolam and the doses of remimazolam for anesthesia induction and maintenance were inconsistent across the studies. Though remimazolam has demonstrated potential safety, efficacy, and ease-of-use for both anesthesia induction and maintenance in cardiac surgery patients and high-risk cardiovascular patients undergoing non-cardiac surgery, further research is imperative to delve into specific patient subgroups (e.g., the elderly or emergent procedures) so as to ascertain optimal dose ranges to suit diverse clinical scenarios.

Relationship between age and remimazolam dose required for inducing loss of consciousness in older surgical patients.

Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction. Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min. The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC. This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.

Effective bolus dose of remimazolam for i-gel® insertion in nonparalyzed patients: a dose-finding study

PurposeRemimazolam is a recently developed ultra-short-acting benzodiazepine used for anesthesia induction and maintenance. Nevertheless, the effective bolus dose of remimazolam for i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK) insertion without the use of neuromuscular blocking agents (NMBAs) has not been well established.MethodsThis study included 25 adult patients scheduled for surgery under general anesthesia who were eligible for i-gel use. Anesthesia was induced with predetermined bolus doses of remimazolam, starting at 0.3 mg·kg−1 for the first patient, without the use of NMBAs. All patients concurrently received remifentanil using target-controlled infusion (TCI) at a fixed effect-site concentration (Ce) of 3.0 ng·mL−1. Insertion of the i-gel was attempted 90 sec after remimazolam administration, and insertion conditions were assessed. Subsequent doses of remimazolam were decreased or increased by 0.05 mg·kg−1, depending on the success or failure of i-gel insertion.ResultsThe mean (standard deviation) 50% effective dose (ED50) of a remimazolam bolus for successful i-gel insertion as determined by the modified Dixon’s up-and-down method was 0.100 (0.027) mg·kg−1. The ED50 and ED95 estimated by isotonic regression were 0.111 (83% confidence interval [CI], 0.096 to 0.131) mg·kg−1 and 0.182 (95% CI, 0.144 to 0.195) mg·kg−1, respectively. None of the patients required treatment for hypotension or bradycardia during anesthesia induction.ConclusionBased on the ED95 of remimazolam bolus dose determined in our study, we recommend using 0.182 mg·kg−1 of remimazolam in combination with remifentanil TCI at a Ce of 3.0 ng·mL−1 for successful i-gel insertion without NMBAs in adult patients. This regimen seems effective with a low risk of hemodynamic instability during anesthesia induction.Study registrationClinicalTrials.gov (NCT05298228); first submitted 6 March 2022.

Comparison of efficacy and safety of equivalent doses of remimazolam versus propofol for gastroscopy anesthesia in elderly patients

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160–0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007–1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn.

The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial

PurposePrevious reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages.MethodsIncluded in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon ‘up-and-down’ design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated.ResultsThe ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221–0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183–0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231–0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200–0.254 mg/kg) in the NSD group.ConclusionsIn the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group.

ED50 of remimazolam combined with different doses butorphanol for first trimester artificial abortion.

Remimazolam (RMZ) is a novel intravenous sedative drug of ultra-short benzodiazepine. The optimal dose of RMZ plus butorphanol for sedation during first trimester artificial abortion is unknown. Therefore, the present study aimed to evaluate the median effective dose (ED50) of RMZ combined with different doses of butorphanol on the sedative effect for first-trimester artificial abortion. Sixty-one female patients were randomly assigned to Group B10 (31 patients) and Group B15 (30 patients). RMZ was administered 5 min after IV butorphanol at doses of 10 μg/kg (Group B10) and 15 μg/kg (Group B15). Cervical dilatation at the time of using a cervical dilating rod, if the patient has body movement and affects the gynecologist's operation, we define it as "Ineffective." Therefore, the dose of RMZ was increased in the next patient. Otherwise, it was defined as "Effective," and the dose of RMZ was reduced in the next patient. According to the pre-experiment, the first dose of RMZ in the first patient was 0.35 mg/kg, and the adjacent geometric dose ratio was 0.9. The centered isotonic regression was performed to determine the ED50 of RMZ. The total RMZ dose administered, recovery time, and anesthesia-related adverse events were all recorded. The ED50 (90% CI) of RMZ was 0.263 (0.215-0.310) mg/kg in Group B10, and 0.224 (0.191-0.261) mg/kg in Group B15, respectively. The recovery time in Group B10 was significantly shorter than in Group B15 (9.8 ± 2.3 vs. 12.5 ± 3.6 min, p ≤ 0.001). There was no significant difference in the incidence rate of all anesthesia-related adverse events between the two groups (p > 0.05). The ED50 of RMZ combined with a 10 μg/kg or 15 μg/kg dose of butorphanol was 0.263 and 0.224 mg/kg during painless first trimester artificial abortion. However, RMZ combined with a 10 μg/kg dose of butorphanol seems to have a shorter recovery time. https://www.chictr.org.cn/bin/project/edit?pid=166623.

The Impact of Fentanyl on the Effective Dose of Remimazolam-Induced Sedation in Elderly Female Patients: An Up-and-Down Sequential Allocation Trial.

This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia. Sixty female patients aged 65-80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 μg/kg), while Group R received remimazolam alone. Dosing adjustments (±2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845-5.859) and 8.184 mg (95% CI, 6.636-13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533-8.068) and 11.298 mg (95% CI, 9.101-19.617), respectively. This study provides compelling evidence that the administration of 1 μg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 μg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.

Determining the 90% Effective Dose of Remimazolam Inhibiting Responses to Upper Gastrointestinal Endoscopy Insertion in Adults: A Double-Blind Study Utilizing a Biased Coin Up-and-Down Sequential Method

Background. Remimazolam, a benzodiazepine sedative with clinical advantages, is used for anesthesia during GI endoscopy. However, the accurate clinical dosage remains understudied. This study aims to investigate the 90% effective dose (ED90) of remimazolam in inhibiting responses to upper GI endoscopy insertion and evaluate its efficacy and safety for upper GI endoscopic diagnosis and treatment. Methods. A total of 54 adult patients undergoing upper GI endoscopy under procedural sedation were included, and they were anesthetized with an intravenous bolus of remimazolam. The first patient was given a dose of 0.3 mg/kg of remimazolam and was next randomized according to a biased coin design (BCD) method, and each patient received a dose of remimazolam depending on the response of the previous patient. A positive reaction was defined as no choking cough, nausea and vomiting, and/or motor response during placement of the upper GI endoscope into pharyngeal cavity or within 3 minutes after placement; otherwise, it was a negative reaction. If positive, randomize the next patient’s dose of remimazolam to be unchanged or decrease by 0.05 mg/kg. If negative, increase the next patient’s dose of remimazolam by 0.05 mg/kg. According to the study protocol, at least 45 patients with positive reactions were needed to suspend the trial while monitoring anesthesia-related adverse events. Results. The ED90 of remimazolam for upper gastrointestinal endoscopy insertion was 0.556 mg/kg (95% CI: 0.399–0.578). All patients maintained stable circulation and no serious adverse events were observed during sedation. Patient satisfaction was 4.89 ± 0.69 points, anesthesiologist satisfaction was 4.57 ± 0.96 points, and endoscopist satisfaction was 4.67 ± 0.87 points (full score 5 points, minimum 1 point). Conclusion. The use of remimazolam for upper gastrointestinal endoscopy was safe and effective, with a single intravenous bolus at an ED90 dose of 0.556 mg/kg inhibiting responses to the procedure.

ED95 of remimazolam in nasal administration for attenuating preoperative anxiety in children.

Preoperative anxiety often prevails in children at higher levels than adults, which is a common impediment for surgeons and anesthesiologists. It is of great necessity to explore an appropriate medication to improve this situation. Remimazolam, a type of benzodiazepine drug, has been indicated for the induction and maintenance of procedural sedation in adults since 2020. To date, rare studies were reported to investigate the effect of remimazolam on children. In this study, we investigated the safety and efficacy of intranasal drops of remimazolam and tried to determine the 95% effective dose (ED95) of remimazolam in single intranasal administration in attenuating preoperative anxiety in children. In this study, 114 children were enrolled who underwent laparoscopic high-level inguinal hernia ligation between January 2021 and December 2022 and were divided into an early childhood children group and a pre-school children group. The biased coin design (BCD) was used to determine the target doses. A positive response was defined as the effective relief of preoperative anxiety (modified Yale Preoperative Anxiety Scale, mYPAS < 30). The initial nasal dose of remimazolam was 0.5 mg·kg-1 in the two groups. An increment or decrement of 0.1 mg·kg-1 was applied depending on the sedative responses. Isotonic regression and bootstrapping methods were used to calculate the ED95 and 95% confidence intervals (CIs), respectively. A total of 80 children completed the study, including 40 in the early childhood group and 40 in the pre-school children group. As statistical analysis indicated, the ED95 of a single intranasal infusion of remimazolam for the relief of preoperative anxiety is 1.57 mg·kg-1 (95% CI: 1.45-1.59 mg·kg-1) in early childhood children and 1.09 mg·kg-1 (95% CI: 0.99-1.11 mg·kg-1) in pre-school children, and the CIs did not overlap each other. Remimazolam is an effective medication to relieve preoperative anxiety in children. Moreover, the ED95 of single nasal administration of remimazolam for effective relief of preoperative anxiety was 1.57 and 1.09 mg·kg-1 in early childhood children and pre-school children, respectively.