Toxicity of Bupivacaine Encapsulated into Liposomes and Injected Intravenously

The acute central nervous system and cardiac toxicities of 0.25% bupivacaine, without adrenalin, encapsulated in multilamellar liposomes were compared with 0.25% plain with and without adrenalin after intravenous infusion at a rate of 0.15 mg·kg−1·min−1 with an increase of 0.035 mg·kg−1·min−1 every 10 min. Three groups of six anesthetized, unventilated rabbits were studied, The doses of bupivacaine (in mg·kg−1) which produced seizureular tachycardia, and asystole were determined. The doses of bupivacaine inducing seizure and ventricular tachycardia were significantly higher for liposomal bupivacaine than for the two plain solutions. A statistical comparison of the cumulative lethal doses of bupivacaine 0.25% with adrenalin and of liposomal bupivacaine led to a p = 0.06. Adrenalin did not modify the systemic toxicity of the local anesthetic. This study showed a reduction of nervous and cardiac toxicity of bupivacaine encapsulated in multilamellar liposomes when infused intravascularly.