A Dose-ranging Study of Rapacuronium in Pediatric Patients

Background: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. Methods: Sixty-five infants (< 1 yr), 51 younger children (1–6 yr), and 49 older children (7–12 yr) were studied. Anesthesia was induced with thiopental–nitrous oxide–oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide–oxygen and alfentanil (12.5–50 &mgr;g/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. Results: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0–2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. Conclusions: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

[1]  A. Turkistani,et al.  Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children. , 1997, British journal of anaesthesia.

[2]  T. Taivainen,et al.  Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children. , 1997, British journal of anaesthesia.

[3]  R. Matteo,et al.  Dose-Ranging Study in Younger Adult and Elderly Patients of ORG 9487, a New, Rapid-Onset, Short-Duration Muscle Relaxant , 1997, Anesthesia and analgesia.

[4]  G. Meakin,et al.  A comparison of acceleromyography and mechanomyography for determination of the dose–response curve of rocuronium in children , 1997, Anaesthesia.

[5]  L. Skovgaard,et al.  Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents , 1996, Acta anaesthesiologica Scandinavica.

[6]  E. Martin,et al.  Dose-response, time-course of action and recovery of rocuronium bromide in children during halothane anaesthesia. , 1995, European journal of anaesthesiology. Supplement.

[7]  R. Mirakhur,et al.  The TOF‐Guard neuromuscular transmission monitor , 1995, Anaesthesia.

[8]  T. Taivainen,et al.  Dose-response and time-course of effect of rocuronium bromide in paediatric patients. , 1995, European journal of anaesthesiology. Supplement.

[9]  J. Proost,et al.  Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent. , 1994, British journal of anaesthesia.

[10]  F. McGowan,et al.  Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide‐halothane anaesthesia , 1994 .

[11]  N. Harper,et al.  Monitoring neuromuscular block by acceleromyography: comparison of the Mini-Accelograph with the Myograph 2000. , 1994, British journal of anaesthesia.

[12]  J. Wierda,et al.  Preliminary investigations of the clinical pharmacology of three short-acting non-depolarizing neuromuscular blocking agents, Org 9453, Org 9489 and Org 9487 , 1994, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[13]  R. Morton,et al.  Low quantal content of the endplate potential reduces safety factor for neuromuscular transmission in the diaphragm of the newborn rat. , 1994, British journal of anaesthesia.

[14]  Ronald D. Miller,et al.  Comparison of Rocuronium, Succinylcholine, and Vecuronium for Rapid‐sequence Induction of Anesthesia in Adult Patients , 1993, Anesthesiology.

[15]  K.,et al.  Time Course of Action and Endotracheal Intubating Conditions of Org 9487, a New Short‐Acting Steroidal Muscle Relaxant; A Comparison with Succinylcholine , 1993, Anesthesia and analgesia.

[16]  D. R. Cook,et al.  Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia. , 1992, Anesthesiology.

[17]  R. Morton,et al.  Age-dependent variation in response to tubocurarine in the isolated rat diaphragm. , 1992, British journal of anaesthesia.

[18]  O. Meretoja Is vecuronium a long-acting neuromuscular blocking agent in neonates and infants? , 1989, British journal of anaesthesia.

[19]  G. Meakin,et al.  Comparison of atracurium-induced neuromuscular blockade in neonates, infants and children. , 1988, British journal of anaesthesia.

[20]  P. Neuvonen,et al.  Age‐Dependence of the Dose‐Response Curve of Vecuronium in Pediatric Patients during Balanced Anesthesia , 1988, Anesthesia and analgesia.

[21]  J. Viby Mogensen,et al.  Measurement of acceleration: a new method of monitoring neuromuscular function , 1988, Acta anaesthesiologica Scandinavica.

[22]  Ronald D. Miller,et al.  Vecuronium kinetics and dynamics in anesthetized infants and children , 1985, Clinical pharmacology and therapeutics.

[23]  R. Sorva,et al.  A Novel Format for a Growth Chart , 1984, Acta paediatrica Scandinavica.

[24]  R. Miller,et al.  Neuromuscular Effects of Vecuronium (ORG NC45) in Infants and Children during N2O, Halothane Anesthesia , 1983, Anesthesiology.

[25]  G. Graham Congenital Diseases of the Heart , 1976 .