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 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats.

METHODS

In the first of two experiments, L-carnitine 100 mg·kg iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg·min 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 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg, L-carnitine 100 mg·kg, 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 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 decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.