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Clinical Trial
Journal Article
Randomized Controlled Trial
Dose-response relationships for edrophonium and neostigmine antagonism of rocuronium bromide (ORG 9426)-induced neuromuscular blockade.
Anesthesiology 1993 October
BACKGROUND: Rocuronium bromide (ORG 9426) is a new nondepolarizing muscle 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 rocuronium 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 applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (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 function in another eight subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery in patients who were not given antagonists.
RESULTS: The dose-response curves for neostigmine- and edrophonium-assisted antagonism of rocuronium bromide neuromuscular blockade for the single twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% and 80% recovery (ED50 and ED80, respectively) of the first twitch after 10 min were 0.017 (0.001) and 0.033 (0.001) mg/kg (mean (standard error of estimate for the mean)), respectively. Corresponding ED50 and ED80 values for edrophonium were 0.161 (0.001) and 0.690 (0.001) mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.5 (0.56) and 21 (0.67) for first twitch ED50 and ED80 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 for 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) than first twitch (potency ratio of 6.7 and 9.5 at 5 and 10 min, respectively) during antagonism of rocuronium bromide-induced blockade. Edrophonium was found to be less effective than neostigmine at reversing rocuronium bromide-induced TOF fade.
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 applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (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 function in another eight subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery in patients who were not given antagonists.
RESULTS: The dose-response curves for neostigmine- and edrophonium-assisted antagonism of rocuronium bromide neuromuscular blockade for the single twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% and 80% recovery (ED50 and ED80, respectively) of the first twitch after 10 min were 0.017 (0.001) and 0.033 (0.001) mg/kg (mean (standard error of estimate for the mean)), respectively. Corresponding ED50 and ED80 values for edrophonium were 0.161 (0.001) and 0.690 (0.001) mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.5 (0.56) and 21 (0.67) for first twitch ED50 and ED80 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 for 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) than first twitch (potency ratio of 6.7 and 9.5 at 5 and 10 min, respectively) during antagonism of rocuronium bromide-induced blockade. Edrophonium was found to be less effective than neostigmine at reversing rocuronium bromide-induced TOF fade.
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