Department of Anesthaesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
National-Local Joint Engineering Research Center of Translational Medicine of Anesthaesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Br J Clin Pharmacol. 2022 Aug;88(8):3760-3770. doi: 10.1111/bcp.15320. Epub 2022 Apr 2.
The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients.
Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo.
The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%.
Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.
本研究旨在探讨在外科患者中使用阿曲库铵的有效性、安全性和药代动力学。
48 名年龄在 18-64 岁的患者被随机分为接受阿曲库铵（2、4、6 和 8mg/kg）或安慰剂，比例为 10:2，以逆转 0.6mg/kg 罗库溴铵诱导的神经肌肉阻滞。通过 TOF-Watch®SX 监测神经肌肉功能。当手术结束时 TOF 比恢复时，患者接受阿曲库铵或安慰剂的静脉注射。
TOF 比值恢复至 0.9 的恢复时间从安慰剂组的 39.3[29.5, 50.2]分钟显著缩短至 3.0[2.3, 3.9]分钟，P<0.0001；2.1[1.5, 3.0]分钟，P<0.0001；2.1[1.8, 3.3]分钟，P<0.0001；和 1.8[1.5, 2.2]分钟，P<0.0001，分别在 2、4、6 和 8mg/kg 阿曲库铵组。然后，阿曲库铵也缩短了 TOF 比值恢复至 0.8 和 0.7 的恢复时间。阿曲库铵耐受性良好，未观察到过敏反应、术后出血、再肌松、基本生命体征异常和 QT 间期延长。阿曲库铵在血浆中的药代动力学呈剂量依赖性增加。24 小时尿液中阿曲库铵的累积分数为 65-83%，使用阿曲库铵后罗库溴铵的累积分数从 15%增加到约 25-30%。
阿曲库铵对逆转罗库溴铵诱导的神经肌肉阻滞有效，在患者中安全且耐受良好。
