DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF ROCURONIUM BROMIDE (ORG-9426)-INDUCED NEUROMUSCULAR BLOCKADE

Background. Rocuronium bromide (ORG 9426) is a new nondepolarizing mus cle relaxant with a rapid onset but an intermediate duration of action . The dose-response relationships for neostigmine and edrophonium were studied during antagonism of neuromuscular block induced by rocuroniu m bromide. Methods: Sixty-four ASA physical status 1 or 2 adults were given 0.6 mg/kg rocuronium bromide during thiopental-fentanyl-nitrous oxide-isoflurane anesthesia. Train-of-four (TOF) stimulation was appli ed to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of fi rst twitch height reached 10% of its initial control value, edrophoniu m (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0. 05 mg/kg) was administered by random allocation. Neuromuscular functio n in another eight subjects was allowed to recover spontaneously. Assi sted recovery was defined as actual recovery minus mean spontaneous re covery in patients who were not given antagonists. Results: The dose-r esponse curves for neostigmine- and edrophonium-assisted antagonism of rocuronium bromide neuromuscular blockade for the single twitch and T OF ratio were not parallel. The doses of neostigmine required to achie ve 50% and 80% recovery (ED50 and ED80, respectively) of the first twi tch after 10 min were 0.017 (0.001) and 0.033 (0.001) mg/kg (mean (sta ndard error of estimate for the mean)), respectively. Corresponding ED 50 and ED80 values for edrophonium were 0.161 (0.001) and 0.690 (0.001 ) mg/kg. respectively. These values corresponded to neostigmine:edroph onium potency ratios of 9.5 (0.56) and 21 (0.67) for first twitch ED50 and ED50 height, respectively. The calculated doses producing ED50 of the TOF ratio at 10 min were 0.017 (0.001) and 0.469 (0.001) mg/kg fo r neostigmine and edrophonium, respectively. These values corresponded to a potency ratio of 27.5 (1.66). Conclusions. Under the conditions described in this study, if reversal was attempted at 10% first twitch recovery, edrophonium was less capable than neostigmine of reversing fade (potency ratio of 19.2 and 27.5 at 5 and 10 min, respectively) th an first twitch (potency ratio of 6.7 and 9.5 at 5 and 10 min, respect ively) during antagonism of rocuronium bromide-induced blockade. Edrop honium was found to be less effective than neostigmine at reversing ro curonium bromide-induced TOF fade.