Objective: To investigate the clinical effectiveness and safety of ONO-1101, a new ultrashort-acting (half-life 3-4 min), cardioselective beta-adrenoceptor blocker in attenuating the cardiovascular responses to endotracheal intubation in a dose-finding open study.
Methods: Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of succinylcholine, and saline or ONO-1101 0.1, 0.25 or 0.5 mg.kg-1, in 53 patients. Heart rate and blood pressure were continuously recorded beginning prior to administration until 5 min after administration of the drug, and the rate-pressure product was calculated.
Results: ONO-1101 was found to significantly blunt the increase in heart rate throughout the study. Administration of ONO-1101 0.25 or 0.5 mg.kg-1 decreased the incidence of tachycardia. However, these doses were not sufficient to suppress the increase in systolic blood pressure, although the maximal value in the ONO-1101 0.5 mg.kg-1 group was reduced. Rate-pressure product increased significantly after intubation in all groups, but the increase was suppressed in the ONO-1101 0.25 and 0.5 mg.kg-1 groups as compared with the saline group. Bradycardia was not observed in any patient, although hypotension might be caused by administration of ONO-1101 0.5 mg.kg-1.
Conclusion: ONO-1101, especially at a dose of 0.25 mg.kg-1, due to its beta-adrenoceptor blockade and ultrashort action, was shown to be effective and well tolerated by patients in this study, when used to attenuate the cardiovascular responses to laryngoscopy and endotracheal intubation.