ORG 9487 neuromuscular block at the adductor pollicis and the laryngeal adductor muscles in humans.
BACKGROUND
ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis.


METHODS
In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group).


RESULTS
Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P < 0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle.


CONCLUSIONS
ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.
Debaene
B
B
Department of Anesthesia, Institut Gustave Roussy, Villejuif, France.
Lieutaud
T
T
Billard
V
V
Meistelman
C
C
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007275:Injections, Intravenous; D007821:Laryngeal Muscles / Q000187:drug effects / Q000294:innervation*; D008875:Middle Aged; D009407:Nerve Block; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics; D013997:Time Factors; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; C082938:rapacuronium