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.
Boogaerts
J
J
Laboratory of Physiopathology, Free University of Brussels, Belgium.
Declercq
A
A
Lafont
N
N
Benameur
H
H
Akodad
E M
EM
Dupont
J C
JC
Legros
F J
FJ
D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004337:Drug Carriers; D006323:Heart Arrest / Q000139:chemically induced*; D007262:Infusions, Intravenous; D008081:Liposomes; D011817:Rabbits; D012640:Seizures / Q000139:chemically induced*; D017180:Tachycardia, Ventricular / Q000139:chemically induced*
D004337:Drug Carriers; D008081:Liposomes; D002045:Bupivacaine