Borkett Keith M, Riff Dennis S, Schwartz Howard I, Winkle Peter J, Pambianco Daniel J, Lees James P, Wilhelm-Ogunbiyi Karin
From the *PAION UK Ltd., Cambridge, United Kingdom; †Advanced Clinical Research Institute, Anaheim, California; ‡Miami Research Institute, Miami, Florida; §Charlottesville Medical Research, Charlottesville, Virginia; and ∥PAION Deutschland GmbH, Aachen, Germany.
Anesth Analg. 2015 Apr;120(4):771-80. doi: 10.1213/ANE.0000000000000548.
This exploratory study was the first study of remimazolam in patients to assess the safety and efficacy of different single doses for procedural sedation.
Patients scheduled to undergo a diagnostic upper gastrointestinal endoscopy were randomized to receive 1 of 3 doses of remimazolam or midazolam (25 per group) in a double-blind manner. After a single dose of study drug to achieve sedation, patients underwent gastroscopy. We assessed the success of the procedure, sedation levels, recovery from sedation, and safety.
A single dose of remimazolam resulted in a successful procedure in 32%, 56%, and 64% of patients in the low (0.10), middle (0.15), and high (0.20 mg/kg) dose groups compared with 44% of patients in the midazolam (0.075 mg/kg) dose group. The onset of sedation was 1.5 to 2.5 minutes in the remimazolam dose groups compared with 5 minutes for midazolam. Because this was a single administration study, sedation could be maintained for as long as necessary to complete the procedure, using rescue midazolam or propofol. Recovery from sedation was rapid for all treatment groups but was influenced by the choice of rescue medication. There were no obvious differences in the safety profiles of remimazolam and midazolam.
This exploratory dose-finding study showed that a single administration of remimazolam (0.10-0.20 mg/kg) was capable of inducing rapid sedation with a quick recovery profile in patients undergoing a diagnostic upper gastrointestinal endoscopy. The safety profile was favorable and appeared to be similar to that of midazolam, warranting further development of this short-acting compound.
本探索性研究是首次在患者中对瑞米唑仑进行的研究，旨在评估不同单剂量用于程序镇静的安全性和有效性。
计划接受诊断性上消化道内镜检查的患者以双盲方式随机接受3种剂量的瑞米唑仑或咪达唑仑中的1种（每组25例）。在给予单剂量研究药物以达到镇静效果后，患者接受胃镜检查。我们评估了操作的成功率、镇静水平、镇静恢复情况和安全性。
低剂量（0.10mg/kg）、中剂量（0.15mg/kg）和高剂量（0.20mg/kg）瑞米唑仑组分别有32%、56%和64%的患者操作成功，而咪达唑仑（0.075mg/kg）剂量组为44%。瑞米唑仑剂量组的镇静起效时间为1.5至2.5分钟，而咪达唑仑为5分钟。由于这是一项单次给药研究，可使用抢救性咪达唑仑或丙泊酚将镇静维持至完成操作所需的任意时长。所有治疗组的镇静恢复都很快，但受抢救药物选择的影响。瑞米唑仑和咪达唑仑的安全性方面无明显差异。
这项探索性剂量探索研究表明，单次给予瑞米唑仑（0.10 - 0.20mg/kg）能够在接受诊断性上消化道内镜检查的患者中诱导快速镇静且恢复迅速。其安全性良好，且似乎与咪达唑仑相似，值得对这种短效化合物进行进一步研发。
