title: The potency (ED50) and cardiovascular effects of rapacuronium (Org 9487) during narcotic-nitrous oxide-propofol anesthesia in neonates, infants, and children.
abstract: We studied the neuromuscular blocking effects of rapacuronium (Org 9487) (dose-response curve, onset, and 50% effective dose [ED50] value), and changes in heart rate and blood pressure, as well as evidence of histamine release in neonates, infants, and children in an open-label, randomized, two-center study. Fifteen neonates, 30 infants, and 30 children were studied. Anesthesia was induced and maintained with propofol, nitrous oxide:oxygen (60:40), and fentanyl. Mechanomyographic monitoring of neuromuscular function was performed at the thumb. The potency (ED50) for neonates, infants, and children were 0.32 (95% confidence interval [CI] 0.15-0.61), 0.28 (95% CI 0.11-0.61), and 0.39 (95% CI 0.17-0.85) mg/kg, respectively. Neonates who received 0.3, 0.6, or 0.9 mg/kg Org 9487 developed a maximum T1 twitch depression of 34 +/-28%, 98 +/- 3%, and 99 +/- 2%, respectively. Time-to-peak effect (onset time) for 0.9 mg/kg Org 9487 was 57 +/- 20 s. Maximum percent T1 twitch depression (+/-SD) in infants who received 0.3, 0.6, or 0.9 mg/kg rapacuronium was 41 +/- 34%, 96 +/- 7%, and 100 +/- 1%, respectively. Time-to-peak effect for 0.9 mg/kg Org 9487 was 62 +/- 29 s. In children 0.3, 0.6, and 0.9 mg/kg rapacuronium resulted in an average percent T1 twitch suppression of 29 +/- 23, 83 +/- 11, and 90 +/- 16, respectively. Time-to-peak effect of 0.9 mg/kg Org 9487 was 96 +/- 33 s, respectively. There was no evidence of histamine release or significant changes in heart rate or blood pressure in either group at any dose. Rapacuronium is a low-potency nondepolarizing muscle relaxant with a fast onset of relaxation and minimal cardiovascular effects. Its potency (ED50) is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg). T1 suppression (90% +/- 16) is less and time to peak effect (96 +/- 33 s) is greater (0.9 mg/kg rapacuronium) in children, compared with the combined group of infants and neonates.
  
  
  CONCLUSIONS
  This study assesses the potency of rapacuronium (Org 9487) in pediatric patients. The potency of rapacuronium is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg).
authors.affiliation: Department of Anesthesiology, Children's National Medical Center, Washington, DC 20010, USA. rkaplan@cnmc.org
authors.forename: R F
authors.initials: RF
authors.lastname: Kaplan
authors.forename: J E
authors.initials: JE
authors.lastname: Fletcher
authors.forename: R S
authors.initials: RS
authors.lastname: Hannallah
authors.forename: D T
authors.initials: DT
authors.lastname: Bui
authors.forename: J S
authors.initials: JS
authors.lastname: Slaven
authors.forename: E J
authors.initials: EJ
authors.lastname: Darrow
authors.forename: K T
authors.initials: KT
authors.lastname: Tsai
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001794:Blood Pressure / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019148:Neuromuscular Blockade; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage*; D009609:Nitrous Oxide; D015742:Propofol; D011446:Prospective Studies; D014673:Vecuronium Bromide / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; C082938:rapacuronium; D009609:Nitrous Oxide; D015742:Propofol