L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats

Background The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg.kg(-1) iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. Methods In the first of two experiments, L-carnitine 100 mg.kg(-1) iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated SpragueDawley rats following which an infusion of bupivacaine 2.0 mg.kg(-1) .min -1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg.kg(-1) iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL.kg(-1), L-carnitine 100 mg.kg(-1), 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. Results In the first study, L-carnitine 100 mg.kg(-1) increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). Conclusion These findings suggest that acute administration of L-carnitine 100 mg.kg(-1) decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.