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舒更葡糖钠,一种用于麻醉恒河猴中罗库溴铵诱导的神经肌肉阻滞的新型逆转剂。

Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

作者信息

de Boer H D, van Egmond J, van de Pol F, Bom A, Booij L H D J

机构信息

Department of Anaesthesiology, Radboud University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands.

出版信息

Br J Anaesth. 2006 Apr;96(4):473-9. doi: 10.1093/bja/ael013. Epub 2006 Feb 7.

Abstract

BACKGROUND

Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced by rocuronium or the non-steroidal neuromuscular blocking drugs, mivacurium or atracurium, in the anaesthetized Rhesus monkey.

METHODS

After a bolus injection of rocuronium, mivacurium or atracurium, a continuous infusion of these drugs was started to maintain the first twitch contraction of the train-of-four at approximately 10% of its baseline value. After a steady state block of at least 10 min the infusion was stopped and the preparation was allowed to recover spontaneously. This process was repeated, but at the time the infusion was stopped, either sugammadex 0.5 or 1.0 mg kg(-1) was given in the rocuronium-induced blockade and sugammadex 1.0 mg kg(-1) was given in the mivacurium- and atracurium-induced blockade.

RESULTS

Sugammadex caused a rapid and complete reversal of rocuronium-induced neuromuscular block. The recovery time to train of four ratio=0.9 after spontaneous recovery was 14.4 min (sd=3.4 min; n=14). This was reduced significantly (P<0.001) to 3.7 min (sd=3.3 min; n=4) with sugammadex 0.5 mg kg(-1) and to 1.9 min (sd=1.0 min; n=4) with sugammadex 1.0 mg kg(-1). Signs of residual blockade or re-curarization were not observed. Reversal of mivacurium- or atracurium-induced neuromuscular block (n=2 in each experiment) by sugammadex (1.0 mg kg(-1)) was not effective. In all experiments, injection of sugammadex had no effects on blood pressure or heart rate.

CONCLUSIONS

Sugammadex is effective in reversing rocuronium, but not mivacurium- or atracurium-induced neuromuscular block.

摘要

背景

环糊精与罗库溴铵的甾体分子结合是逆转神经肌肉阻滞的一个新概念。本研究评估了合成的γ-环糊精衍生物舒更葡糖Org 25969在麻醉的恒河猴中逆转由罗库溴铵或非甾体类神经肌肉阻滞药物米库氯铵或阿曲库铵诱导的约90%的持续神经肌肉阻滞的能力。

方法

在单次注射罗库溴铵、米库氯铵或阿曲库铵后,开始持续输注这些药物,以将四个成串刺激的第一个颤搐收缩维持在其基线值的约10%。在至少10分钟的稳定状态阻滞之后,停止输注,并使标本自行恢复。重复该过程,但在停止输注时,在罗库溴铵诱导的阻滞中给予舒更葡糖0.5或1.0 mg·kg⁻¹,在米库氯铵和阿曲库铵诱导的阻滞中给予舒更葡糖1.0 mg·kg⁻¹。

结果

舒更葡糖能迅速、完全地逆转罗库溴铵诱导的神经肌肉阻滞。自发恢复后四个成串刺激比值=0.9的恢复时间为14.4分钟(标准差=3.4分钟;n = 14)。使用舒更葡糖0.5 mg·kg⁻¹时,该时间显著缩短(P<0.001)至3.7分钟(标准差=3.3分钟;n = 4),使用舒更葡糖1.0 mg·kg⁻¹时缩短至1.9分钟(标准差=1.0分钟;n = 4)。未观察到残余阻滞或再次肌松的迹象。舒更葡糖(1.0 mg·kg⁻¹)对米库氯铵或阿曲库铵诱导的神经肌肉阻滞的逆转无效(每个实验n = 2)。在所有实验中,注射舒更葡糖对血压或心率均无影响。

结论

舒更葡糖能有效逆转罗库溴铵诱导的神经肌肉阻滞,但不能逆转米库氯铵或阿曲库铵诱导的神经肌肉阻滞。

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