阿曲库铵用于逆转中效罗库溴铵诱导的神经肌肉阻滞。

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

机构信息

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.

出版信息

Br J Clin Pharmacol. 2022 Aug;88(8):3760-3770. doi: 10.1111/bcp.15320. Epub 2022 Apr 2.

DOI:10.1111/bcp.15320

PMID:35304924

Abstract

AIMS

The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients.

METHODS

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.

RESULTS

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%.

CONCLUSION

Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

摘要

目的

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。

方法

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。

结果

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%。