Pharmacodynamic Dose-Response and Safety Study of Cisatracurium (51W89) in Adult Surgical Patients During N2 O-O2-Opioid Anesthesia

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.