de Boer H D, van Egmond J, van de Pol F, Bom A, Driessen J J, Booij L H D J
Department of Anaesthesiology, Radboud University Medical Centre Nijmegen The Netherlands.
Br J Anaesth. 2006 Nov;97(5):681-6. doi: 10.1093/bja/ael240. Epub 2006 Oct 3.
Reversal of neuromuscular block can be accomplished by chemical encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma-cyclodextrin derivative. The present study determined the time course of the reversal action of sugammadex on rocuronium-induced block in the anaesthetized Rhesus monkey using train-of-four stimulation.
A bolus injection of rocuronium 100 microg kg(-1) (about 1xED(90)) was given to determine the degree of neuromuscular block reached by this dose. After complete spontaneous recovery, a rapid bolus injection of sugammadex, 1 mg kg(-1), was given and at different time intervals (15, 30 or 60 min, in three different experiments) the effect of another rocuronium bolus injection of 100 microg kg(-1) was determined.
Injection of the first dose of rocuronium resulted in a mean neuromuscular block (depression of first twitch) of 93 (SEM=1.6)%. Fifteen minutes after injection of sugammadex the same rocuronium dose resulted in 17% (SEM=5.6) block. After 30 and 60 min these maximum blocks amounted to 49% (SEM=7.6) and 79% (SEM=4.2), respectively. The estimated half-life of sugammadex in Rhesus monkey is 30 (SEM=4.9) min.
The half-life of sugammadex (Org 25969), a new fast and efficient reversal agent for rocuronium-induced block, is relatively short in the Rhesus monkey, implying the possibility to perform neuromuscular block by rocuronium shortly after reversal of a prior block. In translation to the human situation differences in rocuronium sensitivity and kinetics should be taken into account.
通过化学包裹罗库溴铵的新型γ-环糊精衍生物舒更葡糖(Org 25969)可实现神经肌肉阻滞的逆转。本研究采用四个成串刺激法,测定了舒更葡糖对麻醉状态下恒河猴罗库溴铵诱导的神经肌肉阻滞的逆转作用时程。
静脉注射100 μg/kg(约1倍90%有效剂量)罗库溴铵,以确定该剂量所达到的神经肌肉阻滞程度。在自发完全恢复后,快速静脉注射1 mg/kg舒更葡糖,在不同时间间隔(在三个不同实验中分别为15、30或60分钟),测定再次静脉注射100 μg/kg罗库溴铵的效果。
注射首剂罗库溴铵后,平均神经肌肉阻滞(第一个肌颤搐抑制)为93%(标准误=1.6)。注射舒更葡糖15分钟后,相同剂量罗库溴铵导致的阻滞为17%(标准误=5.6)。30分钟和60分钟后,这些最大阻滞分别为49%(标准误=7.6)和79%(标准误=4.2)。舒更葡糖在恒河猴体内的估计半衰期为30分钟(标准误=4.9)。
舒更葡糖(Org 25969)作为罗库溴铵诱导阻滞的一种新型快速高效逆转剂,在恒河猴体内半衰期相对较短,这意味着在前次阻滞逆转后不久,有可能再次使用罗库溴铵进行神经肌肉阻滞。在应用于人体时,应考虑罗库溴铵敏感性和动力学方面的差异。