Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-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.
Lepage
J Y
JY
Department of Anesthesiology, Hôtel-Dieu, Centre Hospitalier et Universitaire de Nantes, France.
Malinovsky
J M
JM
Malinge
M
M
Lechevalier
T
T
Dupuch
C
C
Cozian
A
A
Pinaud
M
M
Souron
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D001279:Atracurium / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D008297:Male; D008874:Midazolam / Q000008:administration & dosage; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage*; D009388:Neostigmine / Q000008:administration & dosage; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D009609:Nitrous Oxide / Q000008:administration & dosage*; D010100:Oxygen / Q000008:administration & dosage*; D012449:Safety; D013514:Surgical Procedures, Operative; D013874:Thiopental / Q000008:administration & dosage
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D009292:Narcotic Antagonists; D009294:Narcotics; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D009388:Neostigmine; D013874:Thiopental; D009609:Nitrous Oxide; C101584:cisatracurium; D008874:Midazolam; D010100:Oxygen