Bupivacaine Cardiovascular Toxicity

Using anesthetized dogs, this study compared treatment with lidocaine or bretylium for bupivacaine-induced cardiovascular toxicity. Pentobarbital-anesthetized and -ventilated dogs (n = 10) were given a bolus dose of bupivacaine, 4 mg/kg, and a constant infusion of 0.2 mg X kg-1 X min-1 to produce steady-state serum levels of 7.1 +/- 1.8 microgram/ml of bupivacaine. Using burst ventricular pacing, the ventricular tachycardia threshold was determined, along with hemodynamic and electrophysiologic parameters. The animals were then treated with bretylium, 20 mg/kg (n = 5), or lidocaine, 2 mg/kg, followed by a continuous infusion of lidocaine, 0.1 mg X kg-1 X min-1 (n = 5). Bupivacaine-induced alterations in cardiac output, stroke volume, heart rate, and systemic vascular resistance were corrected by bretylium but not lidocaine. Bupivacaine caused a significant lowering of the ventricular tachycardia threshold, which was consistently raised by bretylium, while lidocaine was either ineffective or caused a further lowering of the threshold. Bupivacaine caused a significant increase in the Q-TU interval and resulted in an undulating polymorphic ventricular tachycardia, similar to that seen in Torsades de Pointes.