Toxicity of bupivacaine encapsulated into liposomes and injected intravenously: comparison with plain solutions

The acute central nervous system and cardiac toxicities of 0.25% bupivacaine, without adrenalin, encapsulated in multilamellar liposomes were compared with 0.25% plain solutions with and without adrenalin after intravenous infusion at a rate of 0.15 mg.kg-1 x min-1 with an increase of 0.036 mg.kg-1 x min-1 every 10 min. Three groups of six anesthetized, unventilated rabbits were studied. The doses of bupivacaine (in mg.kg-1) which produced seizure, ventricular 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.