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- Tomohisa Niiya, Michiaki Yamakage, Masanori Yamauchi, and Eichi Narimatsu.
- Department of Traumatology and Critical Care Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. enarimat@sapmed.ac.jp
- Am J Emerg Med. 2012 Jul 1;30(6):901-7.
ObjectiveThe composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium.MethodsIsometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant.ResultsRocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6).DiscussionParaoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition.Copyright © 2012 Elsevier Inc. All rights reserved.
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