Amide local anesthetic alterations of effective refractory period temporal dispersion: relationship to ventricular arrhythmias.
The hemodynamic and electrophysiologic effects of bupivacaine, etidocaine, mepivacaine, and lidocaine were investigated in 32 pentobarbital-anesthetized adult mongrel dogs. Following equipotent dosing, all four agents produced similar hemodynamic effects: decrease in stroke volume and cardiac output, heart rate slowing, increase in systemic vascular resistance, and increases in pulmonary arterial pressure (PAP) and pulmonary capillary wedge pressure (PCWP). The effects of the various agents on the ECG were different. Compared with the control period, mepivacaine and lidocaine produced slight increases and etidocaine and bupivacaine much greater increases in: the area under the curve of the T-wave; lengthening of the QTU interval; and enhancement of the "slow wave" or U-wave following the T-wave. The effects of the various agents on effective refractory period (ERP) temporal dispersion were dramatically different. The ERP temporal dispersion increased to 48.3 +/- 36.0 ms following mepivacaine, 37.4 +/- 10.1 ms following lidocaine, 97.1 +/- 36.2 ms following bupivacaine, and 92.5 +/- 30.5 ms following etidocaine. Six of seven bupivacaine, six of seven etidocaine, two of eight mepivacaine, and none of eight lidocaine animals sustained a polymorphic, undulating ventricular tachycardia similar to Torsades de Pointes following burst ventricular pacing. The results of this study suggest that bupivacaine, etidocaine, and occasionally mepivacaine can result in a Torsades de Pointes-like syndrome following intravenous administration. The magnitude of ERP temporal dispersion differences between the various agents appears to explain their differential arrhythmogenicity.
D000577:Amides / Q000494:pharmacology / Q000633:toxicity; D000779:Anesthetics, Local / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002045:Bupivacaine / Q000494:pharmacology / Q000633:toxicity; D004285:Dogs; D004562:Electrocardiography; D005041:Etidocaine / Q000494:pharmacology / Q000633:toxicity; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology / Q000633:toxicity; D008619:Mepivacaine / Q000494:pharmacology / Q000633:toxicity
D000577:Amides; D000779:Anesthetics, Local; D008012:Lidocaine; D008619:Mepivacaine; D005041:Etidocaine; D002045:Bupivacaine