TOXICITY OF BUPIVACAINE ENCAPSULATED INTO LIPOSOMES AND INJECTED INTRAVENOUSLY - COMPARISON WITH PLAIN SOLUTIONS

The acute central nervous system and cardiac toxicities of 0.25% bupiv acaine, without adrenalin, encapsulated in multilamellar liposomes wer e compared with 0.25% plain solutions 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.k g-1) which produced seizure, ventricular tachycardia, and asystole wer e determined. The doses of bupivacaine inducing seizure and ventricula r tachycardia were significantly higher for liposomal bupivacaine than for the two plain solutions. A statistical comparison of the cumulati ve lethal doses of bupivacaine 0.25% with adrenalin and of liposomal b upivacaine led to a P = 0.06. Adrenalin did not modify the systemic to xicity of the local anesthetic. This study showed a reduction of nervo us and cardiac toxicity of bupivacaine encapsulated in multilamellar l iposomes when infused intravascularly.