Ventricular arrhythmias with or without programmed electrical stimulation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine

It is unclear whether the mechanism of death from local anesthetic (LA) int oxication is primarily a consequence of cardiac arrhythmias or myocardial c ontractile depression, and whether LAs might differ in this susceptibility to these two mechanisms. By using programmable electrical stimulation (PES) protocols in anesthetized, ventilated dogs, we compared the arrhythmogenic potential of bupivacaine (BUP), ropivacaine (ROP), levobupivacaine (LBUP), and lidocaine (LIDO). Open-chest dogs were randomized to receive escalatin g incremental infusions of the four local anesthetics until cardiovascular collapse. We assumed a concentration relationship of 4:1 for LIDO/BUP, LBUP , and ROP. The effective refractory period did not change significantly unt il the dose increment corresponding to target concentrations of 8 and 32 mu g/mL for BUP, LBUP, ROP, and LIDO, respectively. Thirty percent to 50% incr eases in effective refractory period occurred in surviving dogs at this dos e. The incidence of spontaneous or PES-induced ventricular tachycardia and ventricular fibrillation did not differ among groups. Compared with LIDO, t he incidence of PES-induced extrasystoles was more frequent for BUP- and LB UP-treated dogs (P < 0.05). ROP-treated dogs did not differ from LIDO-treat ed dogs with respect to PES-induced extrasystoles. At the dose increment pr eceding cardiovascular collapse, all LAs produced significant increases in heart rate and reductions in blood pressure compared with their respective baseline values. The incidence of programmable electrical stimulation-induc ed ventricular tachycardia and fibrillation with BUP does not differ from t he incidence that occurs with the single S(-) enantiomers LBUP and ROP, pro viding further evidence against stereoselective arrhythmogenesis as a prima ry component of local anesthetic-induced cardiotoxicity.