First dose‐ranging study of remimazolam in Japanese patients undergoing gastrointestinal endoscopy: Phase II investigator‐initiated clinical trial

Abstract

Objectives: Remimazolam, an ultra-short-acting benzodiazepine, has been used for procedural sedation in the United States. We conducted an investigator-initiated clinical trial to determine the appropriate dose of remimazolam required for sedation during gastrointestinal endoscopy in Japanese subjects. Methods:In this single-center, open-label, uncontrolled, phase II trial, a three-stage cohort investigated the appropriate initial and additional doses of remimazolam required for gastrointestinal endoscopy. This study was designed with advice from the Pharmaceuticals and Medical Devices Agency. The initial and additional doses were 2 mg and 1 mg/dose, 3 mg and 1 mg/dose, and 5 mg and 2 mg/dose in cohorts 1, 2, and 3, respectively. Each cohort included 10 cases of upper gastrointestinal endoscopy and colonoscopy. The primary end-point was the success rate of sedation during gastrointestinal endoscopy.Results: Sedation was successful in all gastrointestinal endoscopies in cohorts 1 and 2. In cohort 1, sedation was achieved in five (25.0%) and 10 (50.0%) participants with the initial dose and total dose (initial dose + additional dose ≤ the initial dose of the next cohort), respectively, before endoscopy. In cohort 2, sedation was achieved in 11 (55.0%) and 18 (90.0%) participants with the initial dose and total dose, respectively, before endoscopy. No patient in either cohort lost consciousness or required flumazenil or manual ventilation. Conclusion:Initial and additional doses of 3 mg and 1 mg/dose of remimazolam, respectively, were shown to be effective and safe for sedation during gastrointestinal endoscopy in Japanese patients.

Effects of Remimazolam Combined with Esketamine Anesthesia on Circulatory and Respiratory Function during Painless Gastroenteroscopy

“…Remimazolam is a benzodiazepine, which has the characteristics of rapid onset of action, rapid postoperative drug recovery, and lighter inhibition of circulatory and respiratory functions than other anesthetic drugs and can reduce neuronal excitability by acting on GABA receptors, causing a reduction in the body activity and sedation, but it can cause postoperative complications such as neurological and memory dysfunction in patients, without analgesic effect. erefore, it is often used in combination with other analgesic anesthetic drugs [8,9]. A total of 38 of the 106 study subjects in this study experienced adverse reactions during the progress of the examination, accounting for 35.85% (38/106) of the total study subjects, of which a total of 4 study subjects experienced hypotension during the progress of the examination, accounting for 3.77% (4/106) of the 106 study subjects; 7.55% of the study subjects experienced bradycardia (8/106); a total of 4 patients (3.77% (4/106) of the total study subjects) with decreased oxygen saturation; 8.49% (9/106) with respiratory depression; and 12.26% (13/106) with local pain at the injection site.…”

“…Remimazolam is a benzodiazepine, which has the characteristics of rapid onset of action, rapid postoperative drug recovery, and lighter inhibition of circulatory and respiratory functions than other anesthetic drugs and can reduce neuronal excitability by acting on GABA receptors, causing a reduction in the body activity and sedation, but it can cause postoperative complications such as neurological and memory dysfunction in patients, without analgesic effect. Therefore, it is often used in combination with other analgesic anesthetic drugs [ 8 , 9 ].…”

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 ...…”

What is the best sedation method for high‐risk patients such as those with cirrhosis?

“…Remimazolam combines better safety with rapid recovery and early restoration of cognitive function. Recent reports also show its usefulness in the field of gastrointestinal endoscopy 3 …”

“…Recent reports also show its usefulness in the field of gastrointestinal endoscopy. 3 Propofol is another fast-acting drug with a short recovery and ambulation time. However, it has a narrow sedation threshold and causes hypotension, bradycardia, and hypoxemia, requiring continuous monitoring with an anesthesiologist during endoscopy.…”