Pralidoxime inhibits paraoxon-induced depression of rocuronium- neuromuscular block in a time-dependent fashion

Objective: The 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. Methods: Isometric 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. Results: Rocuronium 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). Discussion: Paraoxon 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.