In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide - oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 ± 0.12 min in group 1 and in 1.2 ± 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 ± 3.2 (15-73) min in group 1 and 39.3 ± 2.4 (19-57) min in group 2. Clinical duration of the first repeat dose of 0.1, 0.15, or 0.2 mg/kg ORG9426, administered whenever the twitch tension elicited by the first train-of-four impulse recovered to 25% of control were 11.0 ± 1.0 (4-16), 18.3 ± 1.6 (7-50), and 28.1 ± 6.3 (7-69) min, respectively. The recovery index was 16.7 ± 1.2 (4-64) min. In 89 patients residual neuromuscular block at the end of anesthesia could be antagonized with 0.5 mg/kg edrophonium + 0.015 mg/kg atropine in 2 to 5 min. No circulatory or other side effects attributable to ORG9426 and no signs or symptoms of recurrent paralysis were observed in the postanesthetic recovery room. The onset time of ORG9426 was shorter than those of other nondepolarizing muscle relaxants previously studied in identically anesthetized patients. ''Priming'' did not shorten the onset time of 2 x ED95 ORG9426. Because of its rapid onset of action, of the currently available nondepolarizing muscle relaxants, ORG9426 may prove useful for facilitating rapid sequence intubation.
- Neuromuscular relaxants, ORG9426: pharmacodynamics
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine