Bupivacaine cardiovascular toxicity: comparison of treatment with bretylium and lidocaine.
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.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D001949:Bretylium Compounds / Q000627:therapeutic use*; D002045:Bupivacaine / Q000037:antagonists & inhibitors / Q000097:blood / Q000506:poisoning*; D004285:Dogs; D004562:Electrocardiography; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects*; D008012:Lidocaine / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology
D001949:Bretylium Compounds; D008012:Lidocaine; C045166:bretylium; D002045:Bupivacaine