Abstract
Abstract Background: Rocuronium is an alternative to succinylcholine for rapid tracheal intubation after major thermal injury and other forms of critical illness that cause denervation changes in skeletal muscle. Rocuronium may decrease the potencies of non-depolarizing muscle relaxants. Objectives: Examine whether potency of rocuronium changed during the first month after denervation, and investigate the effects of skeletal muscle denervation on potency of rocuronium. Methods: The denervation mouse model was developed to create denervated individual cells from the flexor digitorum brevis of the hindfoot. The skeletal muscle cells were examined at day 0 in the innervated control and days 1, 4, 7, 14, 21, and 28 in the denervation group. Nicotinic acetylcholine receptors in the cells were activated with 30 M acetylcholine, alone or in combination with various concentrations of rocuronium. Currents were recorded with a whole-cell patch-clamp technique. Results: Rocuronium reversibly inhibited acetylcholine-activated currents in a dose-dependent fashion at different times after denervation. The inhibition concentration for the half-maximal responses of rocuronium increased 1.2- (p >0.05), 1.8-, 2.8-, 2.3-, 2.1-, and 1.9-fold (p <0.01) at day 1, 4, 7, 14, 21, and 28 after denervation, respectively, compared to that at day 0 after denervation. Conclusion: Rocuronium dose required to achieve satisfactory clinical effects changed at different durations after skeletal muscle denervation.
Highlights
Rocuronium is an alternative to succinylcholine for rapid tracheal intubation after major thermal injury and other forms of critical illness that cause denervation changes in skeletal muscle
We examined the effects of denervation on potency of rocuronium by applying ACh to innervated skeletal muscle
Determination of the changed potencies of rocuronium at nicotinic acetylcholine receptors (nAChRs) in the short-term after denervation of skeletal muscle is most important because the amount of membrane nAChRs and the proportion of -AChR after denervation change with time, which may lead to increased dosing requirements of rocuronium to complete rapid tracheal intubation
Summary
Rocuronium is an alternative to succinylcholine for rapid tracheal intubation after major thermal injury and other forms of critical illness that cause denervation changes in skeletal muscle. Objectives: Examine whether potency of rocuronium changed during the first month after denervation, and investigate the effects of skeletal muscle denervation on potency of rocuronium. The skeletal muscle cells were examined at day 0 in the innervated control and days 1, 4, 7, 14, 21, and 28 in the denervation group. Nicotinic acetylcholine receptors in the cells were activated with 30 M acetylcholine, alone or in combination with various concentrations of rocuronium. Results: Rocuronium reversibly inhibited acetylcholine-activated currents in a dose-dependent fashion at different times after denervation. The inhibition concentration for the half-maximal responses of rocuronium increased 1.2- (p >0.05), 1.8-, 2.8-, 2.3-, 2.1-, and 1.9-fold (p
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