Motor and blood pressure effects of epidural sustained-release bupivacaine from polymer microspheres: a dose-response study in rabbits.
The incorporation of local anesthetics into injectable polymer microspheres can be useful in providing prolonged regional effects. This randomized study was designed to compare the effects of bupivacaine and bupivacaine-loaded microspheres on the time course of motor block in rabbits injected epidurally. Bupivacaine-loaded microspheres and drug-free microspheres 1-10 microns in size were devised from poly-d,l-lactic acid by using a solvent evaporation/extraction method. The effects of bupivacaine and of similar amounts of bupivacaine-loaded microspheres were studied in 26 rabbits as follows: 0.9% sodium chloride, followed by drug-free microspheres, then 1.25 mg of bupivacaine and 1.25 mg of bupivacaine-loaded microspheres (Group I; n = 8); 2.5 mg of bupivacaine, then 2.5 mg of bupivacaine-loaded microspheres (Group II; n = 8); and 5 mg of bupivacaine and 5 mg of bupivacaine-loaded microspheres (Group III; n = 10). Motor block was evaluated blindly by observation of walking disturbances, using a scale from 0 (free movements) to 3 (total limb paralysis). A period of 3 days elapsed between each injection. No limitation on movements was observed after 0.9% sodium chloride and drug-free microsphere injection. With 5 mg, both bupivacaine solutions provided complete motor block which was significantly more prolonged (+244% +/- 129%, mean +/- SD) with bupivacaine-loaded microspheres than bupivacaine. With 2.5 and 1.25 mg, block intensity was less marked, and block duration was shorter after administration of bupivacaine-loaded microspheres than after bupivacaine. We concluded that blocks resulting from bupivacaine-loaded microspheres are highly influenced by the amount of drug initially released by the polymer.
Malinovsky
J M
JM
Département d'Anesthésie-Réanimation Chirurgicale, Hôtel-Dieu, Nantes, France.
Bernard
J M
JM
Le Corre
P
P
Dumand
J B
JB
Lepage
J Y
JY
Le Verge
R
R
Souron
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002045:Bupivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D007268:Injections, Epidural; D008863:Microspheres; D009043:Motor Activity / Q000187:drug effects*; D011108:Polymers; D011817:Rabbits
D003692:Delayed-Action Preparations; D011108:Polymers; D002045:Bupivacaine