Efficacy and Safety of Remimazolam Besylate versus Dexmedetomidine for Sedation in Non-Intubated Older Patients with Agitated Delirium After Orthopedic Surgery: A Randomized Controlled Trial

Abstract

The purpose of the present study was to investigate the efficacy and safety of remimazolam besylate compared with dexmedetomidine for the relief of agitated delirium in non-intubated older patients after orthopedic surgery. Patients and methods: Seventy-five patients were randomly divided into two groups. Patients assigned to the remimazolam group received a loading dose of 0.075 mg/kg remimazolam besylate over 1 minute, followed by a continuous infusion of 0.1 to 0.3 mg/kg/h. Subjects randomized to the dexmedetomidine group received a loading infusion of 0.5 μg/kg dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.2 to 0.7 μg/kg/h. Meanwhile, RASS score-guided dose titration was followed. To assess the efficacy of the study drugs in terms of time to resolution of agitation, time to first achievement of target sedation, percentage of time within the target sedation range, and time to delirium resolution. Safety of the sedatives was evaluated by adverse events during hospitalization. Results: Time to resolution of agitation did not differ between the two groups. The time to first achievement of target sedation was 19.0 (9.5 to 31.0) minutes for remimazolam besylate vs 43.5 (15.0 to 142.5) minutes for dexmedetomidine (P < 0.001). Percentage of time within the target sedation range was 77.8% for remimazolam besylate-treated patients and 67.4% for dexmedetomidine-treated patients (P = 0.001). Patients in the remimazolam group had longer time to delirium resolution (29.5 [21.3 to 32.5] hours) than those in the dexmedetomidine group (22.8 [18.9 to 28.5] hours) (P = 0.042). Patients sedated with remimazolam besylate had more oversedation (P = 0.036) but less hypotension (P = 0.007). Conclusion: Compared with dexmedetomidine, remimazolam besylate was equally effective in relieving agitation, and resulted in earlier achievement of sedation goal and more controllable sedation. Remimazolam may be an ideal agent for obtaining rapid tranquillisation.

The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial

“…There are several similarities in terms of pharmacological and pharmacokinetic characterization between remimazolam and midazolam commonly given as intraoperative or preoperative agents for anxiety control as well as preventive therapy for ED in children (Urits et al, 2020). Other interesting findings have shown remimazolam besylate, compared with dexmedetomidine, was equally effective in relieving agitation in older patients aged ≥70 years following orthopedic surgery (Deng et al, 2022) and remimazolam provided a non-inferiority quality of recovery (QoR) on postoperative day 1 to propofol for general anesthesia in female patients aged 20-65 years undergoing thyroid surgery (Choi et al, 2022). The assessment of QoR on day 1 postoperatively depends on the QoR-15 questionnaire, which is a global measure of recovery after surgery.…”

Remimazolam and serious adverse events

“…Adverse events of remimazolam 845 34 UK Endoscopy Sedation 100 0% Cao 35 China Endoscopy Sedation 74 4% Hypotension Cao 36 China Endoscopy Sedation 19 0% Chae 128 Korea All kinds Anaesthesia 120 0% Chen 37 China Clinical study Sedation 87 0% Chen 38 China Endoscopy Sedation 189 13% Hypotension Chen 39 China Bronchoscopy Sedation 73 12% Hypotension Chen 40 China Endoscopy Sedation 196 24% Hypotension Chen 41 China Clinical study Sedation 83 0% Choi 42 Korea ENT Anaesthesia 70 26% Hypotension Choi 43 Korea LMA insertion Anaesthesia 40 0% Dai 44 China All kinds Anaesthesia 141 23% Hypotension Deng 45 China Orthopaedic Sedation 37 4 Hypotension Doi 46 Japan All kinds Anaesthesia 300 24% Hypotension, delayed emergence Doi 47 Japan All kinds Anaesthesia 67 31% Hypotension, delayed emergence Gao 48 China Bronchoscopy Sedation 60 27% Hypotension Guan 49 China Curettage Sedation 70 6% Hypotension Guo 50 China Oral surgery Sedation 20 5% Hypotension Guo 51 China Endoscopy Sedation 39 15% Hypotension Hari 52 Japan Laparoscopy Anaesthesia 30 0% Hu 53 China Endoscopy Sedation 173 32% Hypotension Ichijima 54 Japan Endoscopy Sedation 20 0% Jia 55 China Bronchoscopy Sedation 50 0% Jiang 56 China Urologic Anaesthesia 75 6% Hypotension Kaneko 57 Japan Cardiac Anaesthesia 40 0% Kleiman 58 Germany Clinical study Sedation 20 0% Lee 59 Korea Urologic Anaesthesia 45 0% Lee 60 Korea Laparoscopy Anaesthesia 64 3% Re-sedation Li 61 China Nerve Block Sedation 60 0% Liu 62 China Endoscopy Sedation 50 0% Liu 63 China Cardiac Anaesthesia 30 17% Hypotension Liu 64 China Endoscopy Sedation 115 13% Hypotension Lu 65 China Endoscopy Sedation 53 0% Lu 66 China Endoscopy Sedation 200 ...…”

Comparison of Remimazolam Versus Dexmedetomidine on the Quality of Recovery in Functional Endoscopic Sinus Surgery ： A Randomized Clinical Trial

“…In the group D,a loading dose of 1.0 µg/kg dexmedetomidine was infused over 10 min before anesthesia induction, followed by maintenance infusion at 0.5µg/kg per hour until the end of surgery. As described by Deng et al [14], in the group R, a loading dose of 0.075 mg/kg for remimazolam was infused over 1 min before anesthesia induction, followed by a maintenance infusion at 0.1 mg/kg per hour until the end of surgery, and the infusion was stopped when severe arrhythmia (supraventricular or ventricular)and hypotension (MAP less than 60 mmHg) occurred.And patients in the group C were given the same amount of placebo equal to dexmedetomidine.Anesthesia was induced with propofol (3.0 mg/kg), sufentanil (0.5 µg/kg), and cisatracurium (1.5 mg/kg). After endotracheal intubation (ID:7.5 mm or 7.0 mm), anesthesia was maintained with propofol and remifentanil at the effect-site, followed by target-controlled infusion (TCIs) of propofol and remifentanil using TCI pump.…”