Determination of the Hemodynamics and Histamine Release of Rocuronium (Org 9426) when Administered in Increased Doses Under N2O/O2-sufentanil Anesthesia

The cardiovascular effects, histamine release potential, and pharmacodynamics of rocuronium were determined in adult patients randomized to receive rapid (5 s) intravenous (i.v.) bolus doses of 600, 900, or 1200 micrograms/kg (2.0, 3.0, and 4.0 times the ED95) with maintenance doses of 150 micrograms/kg. There were no statistically significant hemodynamic effects (heart rate, blood pressure, mean arterial pressure [MAP] or electrocardiogram [ECG]) after administration of rocuronium. There were no increases in plasma histamine levels at 1, 3, and 5 min after the rapid i.v. bolus of rocuronium as determined by a new radioimmunoassay (RIA) with a sensitivity for histamine quantification of 0.05 ng/mL. Endotracheal intubation was successfully performed 6 min after rocuronium administration (and after plasma samples were obtained). The mean +/- SD clinical durations of 600-, 900-, and 1200-micrograms/kg intubating doses of rocuronium under N2O/O2-sufentanil anesthesia were 45 +/- 20 min, 66 +/- 16 min, and 85 +/- 22 min, respectively. We conclude that rocuronium can be administered safely over a wide range of doses (2-4 x ED95), with minimum hemodynamic effects or histamine release.