The Duration of Immobilization Causes the Changing Pharmacodynamics of Mivacurium and Rocuronium in Rabbits

Abstract

In the clinical setting, in patients with a cast, it is not known whether the monitoring of the neuromuscular paralysis induced by either mivacurium or rocuronium in the contralateral limb is the correct interpretation. We compared the dose-response relationships and the neuromuscular blocking effects of mivacurium and rocuronium in 56 anesthetized rabbits immobilized in a plaster cast for 2, 4, and 6 wk. Train-of-four stimuli were simultaneously applied every 10 s to both common peroneal nerves, and the force of contraction of both tibialis anterior muscles was measured. Immobilization was associated with a rightward shift of the mivacurium and rocuronium dose-response curves after the duration of the immobilized limb, whereas no shift occurred in the contralateral limb. The 50% effective dose values for 0, 2, 4, and 6 wk of immobilization in the immobilized limb of mivacurium were 15.1 +/- 1.4, 18.2 +/- 1.5, 21.5 +/- 1.9, and 27.8 +/- 2.5 microg/kg, respectively, and they were unchanged in the contralateral limb. The calculated 50% effective dose values for the correspondence of rocuronium were 48.1 +/- 4.1, 56.2 +/- 4.2, 64.8 +/- 4.9, and 75.1 +/- 5.5 microg/kg, respectively, and they were unchanged in the contralateral limb. The rabbits receiving mivacurium and rocuronium had a significantly accelerated recovery from neuromuscular blockade compared with the placebo group in the immobilized limb after the immobilized duration, whereas there were no differences in the contralateral limb. The results of the present study showed that immobilization disuse atrophy produced by casting led to the development of resistance to both mivacurium and rocuronium; however, no resistance was shown in the contralateral limb. The peripheral nerve stimulator could be applied on the nonimmobilized limb, which might be associated with a normal recording if either mivacurium or rocuronium was used as neuromuscular relaxants.

Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits

“…This could explain why, after an optimal dose of sugammadex, the recovery of the TOF ratio to 0.9 precedes the recovery of T1, and why the TOF ratio may be fully recovered when this is not yet the case for T1 [25]. When antagonizing with classical reversal agents (anticholinesterase drugs) or natural recovery, the time course of recovery from NMBA varies from the case with sugammadex; first, there is the full return of T1 and then recovery of the TOF ratio to 90% [1026]. In this study, TOF [90] appeared at a time similar to T1 [75], and T1 [95] appeared later than TOF [90].…”

Influence of acute normovolemic hemodilution on the potency and time course of action of rocuronium in rabbits

“…Dose-response curves were evaluated using analysis of covariance (ANCOVA); when inhibition of the twitch reached 50% and 95%, the effective doses (ED50 and ED95, respectively) were calculated in the dose response curve. All intravenous administrations of muscle relaxants were performed within 5 s. Each dose of rocuronium was withheld until the muscle twitch had recovered from the preceding dose, and had remained at baseline value for at least twice the duration of block of the preceding dose [13]. After the experiment ended, a lethal dose of potassium chloride was administered for euthanasia of all rabbits.…”