THERAPY AND PREVENTION PHLARMACOLOGY A comparison of the electrophysiologic effects of intravenous and oral amiodarone

In 12 patients (nine with Wolff-Parkinson-White syndrome and three with ventricular tachycardia) the electrophysiologic effects of intravenous (5 mg/kg body weight in 1 min) and oral (total dose 9800 to 11,200 mg) amiodarone were studied with programmed stimulation of the heart. Intravenous and oral amiodarone had a similar (p < .05) effect of lengthening on the effective refractory period of the atrioventricular node. Only intravenous amiodarone prolonged (p < .05) the AH interval. Oral amiodarone was more effective than intravenous amiodarone in lengthening the anterograde effective refractory period of the accessory atrioventricular pathway. Only oral amiodarone prolonged the effective refractory period of atrium and ventricle and the HV interval, all significantly (p < .05). Intravenous amiodarone slowed (p < .05) the rate of circus-movement tachycardia in patients with Wolff-Parkinson-White syndrome, and further slowing was observed after oral amiodarone. Termination of tachycardia by intravenous amiodarone predicted prevention of reinitiation of tachycardia during oral amiodarone. These data indicate that intravenous and oral amiodarone do not have the same electrophysiologic effects. It is not clear whether cumulative effects, active metabolites, or both are responsible for these differences. Circulation 69, No. 1, 120-124, 1984. IT HAS BEEN established that amiodarone administered orally is a very powerful drug for the treatment of arrhythmias occurring at the supraventricular and ventricular level.1`8 Although its mechanism of action at the cellular level is not quite clear, the electrophysiologic effects of oral amiodarone have been well studied.2', 915 A major problem in using oral amiodarone is the necessity of giving the drug for several days to weeks before it can reach its maximal effect. This limits its use in patients in whom an immediate antiarrhythmic effect is required. The introduction of intravenous amiodarone'6 was therefore received with great interest. In this article we report on the comparison between the electrophysiologic effects of intravenous and oral amiodarone. During programmed stimulation of the heart, we studied the effects of intravenous amiodarone in 12 patients. In the same patients the same stimuFrom the Department of Cardiology, University of Limburg, Annadal Hospital, Maastricht, The Netherlands. Address for correspondence: Dr. Hein J. J. Wellens, Department of Cardiology, University of Limburg, Annadal Hospital, Maastricht, The Netherlands. Received August 15, 1983; revision accepted September 29, 1983. 120 lation program was repeated 5 to 6 weeks after administration of oral amiodarone. Materials and methods Twelve patients were studied, and their clinical data are given in table 1. After informed consent was obtained, a study of programmed stimulation was performed. Our methods of stimulation and recording and our definitions of the different electrophysiologic parameters have been reported previously.'7 The following measurements were made: (1) heart rate during sinus rhythm, (2) the effective refractory period of the right atrium, (3) the effective refractory period of the right ventricle, (4) the effective refractory period of the atrioventricular (AV) node, (5) the refractory period of the accessory AV pathway (in the nine patients with Wolff-Parkinson-White syndrome), (6) the AH and HV interval, and (7) the site of origin, mechanism, and pathway of tachycardia. The effect of intravenous and oral amiodarone was studied as follows: amiodarone was given intravenously in 1 min with a dosage of 5 mg/kg body weight. Thereafter, the electrophysiologic parameters were measured immediately, 10, 20, and 30 min after administration of the drug. Each set of measurements lasted approximately 5 min. The patient was then placed on oral amiodarone (loading dose of 600 mg/day for 1 week and maintenance dose of 200 mg/day) and was restudied 5 to 6 weeks later. At that time the total dose of amiodarone given varied individually from 9800 to 11,200 mg. During the stimulation study, similar pacing cycle lengths and premature beat intervals were used before and after the intravenous and oral administration of amiodarone. Statistical significance of the results were analyzed with Student's t test. Apart from the cycle length during sinus rhythm, CIRCULATION by gest on A ril 8, 2017 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-PHARMACOLOGY