Reversal of flecainide-induced ventricular arrhythmia by hypertonic sodium bicarbonate in dogs

Flecainide occasionally produces incessant ventricular tachycardia that is difficult to treat. Reports of uncontrolled clinical studies have suggested a therapeutic role for hypertonic sodium bicarbonate (NaHCO₃). To test this observation, spontaneous and pacing-induced arrhythmia canine models were designed. In the spontaneous model, flecainide was infused at 0.5 mg/kg/min until ventricular tachycardia occurred spontaneously. In the pacing-induced model, flecainide was infused at 1.0 mg/kg/min load (0.5 mg/kg/min maintenance) stepwise until the QRS was widened 50%, 75%, and 100%, with programmed ventricular stimulation at each step until ventricular arrhythmia was induced. Dogs who developed spontaneous arrhythmia were treated blindly with three doses of either NaHCO₃ (3 mEq/kg/dose, with 1 minute between doses) or normal saline. Dogs who were induced in the second model were treated with the same three doses, 10 minutes apart, with programmed stimulation between each dose. Before unblinding in both protocols, dogs were classified as "responders" or "nonresponders" to therapy. In the spontaneous model, of 14 dogs with spontaneous ventricular tachycardia, all 7 dogs treated with NaHCO₃ showed response, compared with only 1 of 7 dogs treated with saline (P < .01). Ventricular QRS complexes/min were reduced by NaHCO₃ in that protocol. In the induced arrhythmia protocol, of 14 dogs with inducible arrhythmia, 6 of 7 responded to NaHCO₃, and 1 of 7 responded to placebo (P < .05). In both protocols, arterial pH and the serum sodium concentration were increased by NaHCO₃ but not by normal saline control treatment. QRS interval duration was shortened by NaHCO₃ therapy. Thus, prolongation of the QRS interval and ventricular arrhythmia can be produced in dogs by flecainide infusion and can be treated effectively by administration of hypertonic NaHCO₃. In view of the response to NaHCO₃, the mechanism of arrhythmia may be slowed intraventricular conduction caused by sodium channel inhibition. These data suggest that hypertonic NaHCO₃ may be useful in the treatment of ventricular arrhythmia due to flecainide overdose and, possibly, for proarrhythmia as well.