Edrophonium effectively antagonizes neuromuscular block at the laryngeal adductors induced by rapacuronium, rocuronium and cisatracurium, but not mivacurium.

PURPOSE: To examine the efficacy of antagonism of rapacuronium-, mivacurium-, rocuronium- and cisatracurium-induced neuromuscular block at the laryngeal adductors (LA). METHODS: One hundred four patients were randomly assigned to one of eight study groups. They either received rapacuronium 1.5 mg x kg(-1), mivacurium 0.25 mg x kg(-1), rocuronium 0.9 mg x kg(-1) or cisatracurium 0.15 mg x kg(-1). Patients in each treatment group either received edrophonium (0.5 mg x kg(-1)) at 10% recovery of the first twitch (T1) of train-of-four (TOF) at the LA or were allowed to recover spontaneously from neuromuscular block. The effect of antagonism on speed of recovery of neuromuscular function at the LA was evaluated. RESULTS: The time to recovery to a TOF ratio of 0.9 at the LA, when compared to the spontaneous recovery group, was significantly shortened by the administration of edrophonium in patients receiving rapacuronium [19.2 +/- 7.8 vs 26.2 +/- 4.9 (mean +/- SD) min], rocuronium (24.7 +/- 14.3 vs 44.4 +/- 13.0 min) and cisatracurium (24.2 +/- 5.7 vs 35.1 +/- 7.6 min). Edrophonium administration did not shorten complete recovery from mivacurium-induced block (15.7 +/- 8.0 vs 17.6 +/- 6.1 min). CONCLUSION: Recovery from rapacuronium-, rocuronium- or cisatracurium- induced neuromuscular block to a TOF ratio of 0.9 as measured at the LA was shortened by the administration of edrophonium, when compared to spontaneous recovery.

Clinical pharmacology of GW280430A in humans.

BACKGROUND: An ultrashort-acting nondepolarizing neuromuscular blocking agent that could be an alternative to succinylcholine has been the focus of a concerted effort in the field of muscle relaxants. GW280430A showed a promising pharmacodynamic profile in preclinical work and a wide margin of safety and so was selected for study in humans. METHODS: Thirty-one volunteers participated in this study, which determined the dose producing 95% block (ED95) and the safety and pharmacodynamics of increasing ED95 multiples. Anesthesia was induced and maintained with propofol, midazolam, and fentanyl. Neuromuscular transmission was measured at the adductor pollicis using ulnar nerve stimulation, and responses were recorded continuously by standard mechanomyographic monitoring. RESULTS: The ED95 for GW280430A is 0.19 mg/kg. The time to onset of 90% block ranged from 1.3 to 2.1 min, depending on the dose. Clinical durations ranged from 4.7 to 10.1 min and increased with increasing dose. Five to 95% and 25-75% recovery rates were approximately 7 and 3 min, respectively, and were independent of the dose administered. Transient cardiovascular side effects were observed at doses beginning at 3 x ED95 and above and were suggestive of histamine release. Most volunteers receiving 4 x ED95 exhibited plasma histamine concentrations indicative of significant histamine release. CONCLUSIONS: GW280430A has a rapid onset and ultrashort duration of action. The recovery rate is rapid, predictable, and independent of dose. Doses at least up to 2.5 x ED95 seem to be free of side effects and seem to be able to provide relaxation within 60-90 s.