title: Motor and blood pressure effects of epidural sustained-release bupivacaine from polymer microspheres: a dose-response study in rabbits.
abstract: 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.
authors.affiliation: Département d'Anesthésie-Réanimation Chirurgicale, Hôtel-Dieu, Nantes, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Malinovsky
authors.forename: J M
authors.initials: JM
authors.lastname: Bernard
authors.forename: P
authors.initials: P
authors.lastname: Le Corre
authors.forename: J B
authors.initials: JB
authors.lastname: Dumand
authors.forename: J Y
authors.initials: JY
authors.lastname: Lepage
authors.forename: R
authors.initials: R
authors.lastname: Le Verge
authors.forename: R
authors.initials: R
authors.lastname: Souron
mesh_terms: 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
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D002045:Bupivacaine