PHARMACODYNAMIC EFFECTS OF 3 DOSES OF ORG-9426 USED FOR ENDOTRACHEAL INTUBATION IN HUMANS

Study Objective: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. Design: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. Setting: Inpatients requiring surgery at Georgetown University Medical Center. Patients: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III,scheduled for general surgery. Interventions: After Georgetown University Institutional Review Board approval and patient consent, patients were premedicated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of-four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED95 of ORG 9426 (570 mug/kg, 710 mug/kg, or 850 mug/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T1). Measurements and Main Results: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T1 (T1 90% block), maximal T1 depression (onset time), intubating conditions, clinical duration (time for return of T1 to 25 % of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T1 90% block was achieved rapidly (75 +/- 25 seconds to 78 +/- 18 seconds, means +/- SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 +/- 18 minutes at 570 mug/kg to 42 +/-10 minutes at 850 mug/kg. Spontaneous twitch recovery from 10 % to 25 % was similar in all dosage groups (5 +/- 1 minutes to 6 +/- 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. Conclusion: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.