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罗库溴铵在内收拇指肌和咬肌中的药代动力学和药效学

Rocuronium pharmacokinetics and pharmacodynamics in the adductor pollicis and masseter muscles.

作者信息

Vega E A, Ibacache M E, Anderson B J, Holford N H G, Nazar C E, Solari S, Allende F A, Cortínez L I

机构信息

Departamento de Anestesiología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, PO Box: 114-D, Santiago, Chile.

Department of Anaesthesiology, University of Auckland, Auckland, New Zealand.

出版信息

Acta Anaesthesiol Scand. 2016 Jul;60(6):734-46. doi: 10.1111/aas.12703. Epub 2016 Feb 22.

Abstract

BACKGROUND

The aim of this study was to characterize the dose-effect relationship of rocuronium at the adductor pollicis and masseter muscles.

METHODS

Ten, ASA I, adult patients, received a bolus dose of rocuronium 0.3 mg/kg during propofol based anesthesia. Train-of-four (TOF) was simultaneously monitored at the masseter and the adductor pollicis muscles until recovery. Rocuronium arterial serum concentrations were measured during 120 min. The first twitch of the TOF response was used to characterize the time-effect profile of both muscles using pharmacokinetic-pharmacodynamic analysis in NONMEM. A decrease in NONMEM objective function (∆OFV) of 3.84 points for an added parameter was considered significant at the 0.05 level.

RESULTS

Onset time at the masseter (mean ± SD, 1.5 ± 0.9 min) was faster than at the adductor pollicis (2.7 ± 1.4 min, P < 0.05). Recovery, measured as the time to TOF ratio = 0.9 was similar between muscles 29.9 ± 6.7 (adductor pollicis) vs. 29.3 ± 8.1 (masseter). (P = 0.77). The estimated pharmacodynamic parameters [mean (95% CI)] of the adductor pollicis muscle and the masseter muscle were; plasma effect-site equilibration half-time (teq) 3.25 (2.34, 3.69) min vs. 2.86 (1.83, 3.29) min, (∆OFV 383.665); Ce50 of 1.24 (1.13, 1.56) mg/l vs. 1.19 (1.00, 1.21) mg/l, (∆OFV 184.284); Hill coefficient of 3.97 (3.82, 5.62) vs. 4.68 (3.83, 5.71), (∆OFV 78.906).

CONCLUSIONS

We found that the masseter muscle has faster onset of blockade and similar recovery profile than adductor pollicis muscle. These findings were best, explained by a faster plasma effect-site equilibration of the masseter muscle to rocuronium.

摘要

背景

本研究旨在描述罗库溴铵在内收拇肌和咬肌的剂量-效应关系。

方法

10例美国麻醉医师协会(ASA)I级成年患者在丙泊酚麻醉期间接受0.3mg/kg的罗库溴铵单次静脉注射。在咬肌和内收拇肌同时监测四个成串刺激(TOF)直至恢复。在120分钟内测定罗库溴铵动脉血血清浓度。使用NONMEM中的药代动力学-药效学分析,将TOF反应的第一个肌颤搐用于描述两块肌肉的时效特征。对于增加的参数,NONMEM目标函数(∆OFV)降低3.84个点在0.05水平被认为具有显著性。

结果

咬肌的起效时间(平均值±标准差,1.5±0.9分钟)快于内收拇肌(2.7±1.4分钟,P<0.05)。以TOF比值=0.9时的时间衡量的恢复情况在两块肌肉之间相似,内收拇肌为29.9±6.7分钟,咬肌为29.3±8.1分钟(P=0.77)。内收拇肌和咬肌的估计药效学参数[平均值(95%可信区间)]为:血浆效应室平衡半衰期(teq),内收拇肌为3.25(2.34,3.69)分钟,咬肌为2.86(1.83,3.29)分钟(∆OFV 383.665);半数效应浓度(Ce50),内收拇肌为1.24(1.13,1.56)mg/l,咬肌为1.19(1.00,1.21)mg/l(∆OFV 184.284);希尔系数,内收拇肌为3.97(3.82,5.62),咬肌为4.68(3.83,5.71)(∆OFV 78.906)。

结论

我们发现咬肌的阻滞起效比内收拇肌快,恢复情况相似。这些发现最好的解释是咬肌对罗库溴铵的血浆效应室平衡更快。

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