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The pharmacodynamics of mivacurium in the rabbit with carbon tetrachloride-induced liver disease

Published online by Cambridge University Press:  01 September 2007

M. A. Cheong ,
K. S. Kim  and
G. S. Lee
M. A. Cheong
Affiliation:
Hanyang University Hospital, Department of Anesthesiology, Seoul, Korea
K. S. Kim*
Affiliation:
Hanyang University Hospital, Department of Anesthesiology, Seoul, Korea
G. S. Lee
Affiliation:
Hanyang University Hospital, Department of Anesthesiology, Seoul, Korea
*
Correspondence to: Kyo Sang Kim, Department of Anesthesiology, Hanyang University Hospital, #17 Haengdang dong, Sungdong gu, Seoul 133-792, Korea. E-mail: kimks@hanyang.ac.kr; Tel: +82 2 2290 8680; Fax: +82 2 2299 0742
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Summary

Background and objective

Neuromuscular blocking effects according to the severity of liver dysfunction have not been evaluated. We assessed the neuromuscular effects of mivacurium in carbon tetrachloride (CCl4)-treated rabbits with toxic hepatitis in vivo.

Methods

We compared the dose–response relationships and the neuromuscular blocking effects of mivacurium in 66 rabbits randomly treated with 0.3 mL kg−1 of corn oil, 0.3 mL kg−1 of CCl4 or 0.6 mL kg−1 of CCl4 for 11 weeks, respectively. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured.

Results

Severe hepatitis was associated with a rightward shift of the mivacurium dose–response curves, but mild hepatitis had no effect. The calculated ED50 values for the control, mild and severe hepatitis were 17.1 ± 2.6, 18.2 ± 2.7 and 31.8 ± 3.2 μg kg−1, respectively. Rabbits with severe hepatitis had a significantly prolonged recovery time from neuromuscular blockade compared with other rabbits. Cholinesterase activity had a negative correlation with recovery indices of mivacurium even in severe hepatic injury. Severe hepatitis induced a prolongation of action duration of repeated doses, but maintained the constant intervals.

Conclusions

The dose–response and the time course of neuromuscular blockade of mivacurium differ in mild hepatitis compared with severe hepatitis, but required no adjustments of different doses for repeated injection after the desired depth of neuromuscular block, and had a negative correlation with the activity of plasma cholinesterase in both hepatic injuries.

Keywords

NEUROMUSCULAR BLOCKING AGENTS, mivacuriumLIVER DISEASES, toxic hepatitisTOXIC AGENTS, carbon tetrachlorideRABBITS
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue 9 , September 2007 , pp. 789 - 795
Copyright
Copyright © European Society of Anaesthesiology 2007

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