Evaluation of Bretylium Tosylate for the Treatment of Premature Ventricular Contractions

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Abstract
In a controlled setting bretylium tosylate was evaluated for efficacy, toxicity, onset, and duration of action in eight patients with frequent premature ventricular contractions (PVC). Four patients received a single im dose of bretylium, 4 mg/kg, with before and after control days; the other four patients received bretylium, 2 and 4 mg/kg, on different days with before and between control days. PVC were quantified from stored continuous ECG tape recordings by an automated arrhythmia-detection system. Five patients had 50% or more reduction of PVC frequency with bretylium 4 mg/kg, and one with 2 mg/kg. Bretylium 4 mg/kg but not 2 mg/kg reduced mean PVC frequency by half beginning at the sixth hour and continuing for 12 hours. Hypotension began within 1 hour. Maximum fall in mean supine blood pressure was 17/6 mm Hg with 2 mg/kg, and 25/12 mm Hg with 4 mg/kg. Plasma bretylium concentration was maximum at about 1 hour with a mean elimination half-life of 10 hours. A controlled quantitative method for evaluation of antiarrhythmic drugs in man demonstrated that bretylium can be effective in suppressing PVC frequency. The dissociation between hypotensive and antiarrhythmic effects of bretylium suggested that its antiarrhythmic effect was independent of adrenergic neuronal blockade.