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七氟醚会增加儿童使用罗库溴铵后对强直刺激后单爆发刺激(TOF)的神经肌肉反应衰减。一项药代动力学/药效学分析。

Sevoflurane increases fade of neuromuscular response to TOF stimulation following rocuronium administration in children. A PK/PD analysis.

作者信息

Woloszczuk-Gebicka Bogumila, Wyska Elzbieta, Grabowski Tomasz

机构信息

Department of Pediatric Anesthesiology and Intensive Therapy, Medical University of Warsaw, Warsaw, Poland.

出版信息

Paediatr Anaesth. 2007 Jul;17(7):637-46. doi: 10.1111/j.1460-9592.2006.02181.x.

DOI:10.1111/j.1460-9592.2006.02181.x
PMID:17564645
Abstract

BACKGROUND

Sevoflurane enhances neuromuscular block produced by rocuronium, affecting not only single twitch response but also the response to high-frequency stimulation, increasing tetanic [or train-of-four (TOF)] fade.

METHODS

We compared the degree of fade during spontaneous recovery from rocuronium-induced neuromuscular block in 24 children (3-11 years old, ASA groups I and II), anesthetized with nitrous oxide-sevoflurane (one MAC, endtidal concentration) or nitrous oxide-fentanyl. Neuromuscular transmission was monitored electromyographically (EMG), stimulating the ulnar nerve at the wrist with TOF, 2 Hz for 2 s, repeated at 20-s intervals and recording EMG potential from adductor pollicis brevis. Depression of the fourth twitch, T4, was used as a measure of fade. Following an intubating dose of rocuronium, 0.6 mgxkg(-1), continuous infusion of rocuronium was given to maintain stable 90-99% T1 depression. Plasma concentration of rocuronium was determined with high performance liquid chromatography with electrochemical detection (HPLC-EC) method at the moment of discontinuation of rocuronium infusion and 10, 20, 30, 40, 50, 60, and 75 min afterwards. A two compartment model was used for pharmacokinetic (PK) calculations. PK parameters were fixed and pharmacodynamic data were fitted to effect compartment model proposed by Sheiner.

RESULTS

Sevoflurane reduced rocuronium concentration in effect compartment producing 50% inhibition of both T1 and T4 response and significantly delayed not only T1, but also T4 recovery.

CONCLUSIONS

Potentiating effect of sevoflurane on rocuronium-induced neuromuscular block influences not only postsynaptic, but also the presynaptic part of the neuromuscular junction, enhancing fade of neuromuscular response to high-frequency stimulation. The intensity of this latter effect is clinically relevant.

摘要

背景

七氟烷可增强罗库溴铵产生的神经肌肉阻滞作用,不仅影响单刺激反应,还影响对高频刺激的反应,增加强直刺激(或四个成串刺激)衰减。

方法

我们比较了24名3至11岁、美国麻醉医师协会分级为I级和II级的儿童,在接受氧化亚氮-七氟烷(一个最低肺泡有效浓度,呼气末浓度)或氧化亚氮-芬太尼麻醉后,罗库溴铵诱导的神经肌肉阻滞自发恢复过程中的衰减程度。通过肌电图(EMG)监测神经肌肉传递,在腕部刺激尺神经,采用四个成串刺激,频率为2Hz,持续2秒,每隔20秒重复一次,并记录拇短收肌的肌电图电位。将第四个肌颤搐的抑制程度(T4)作为衰减的指标。给予插管剂量的罗库溴铵(0.6mg/kg-1)后,持续输注罗库溴铵以维持T1抑制稳定在90%至99%。在停止输注罗库溴铵时以及之后10、20、30、40、50、60和75分钟时,采用高效液相色谱-电化学检测(HPLC-EC)法测定罗库溴铵的血浆浓度。采用二室模型进行药代动力学(PK)计算。PK参数固定,药效学数据拟合至Sheiner提出的效应室模型。

结果

七氟烷降低了效应室中罗库溴铵的浓度,对T1和T4反应产生50%的抑制作用,不仅显著延迟了T1恢复,还延迟了T4恢复。

结论

七氟烷对罗库溴铵诱导的神经肌肉阻滞的增强作用不仅影响突触后,还影响神经肌肉接头的突触前部分,增强了神经肌肉对高频刺激反应的衰减。后一种效应的强度具有临床相关性。

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