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 microsp heres can be useful in providing prolonged regional effects. This rand omized study was designed to compare the effects of bupivacaine and bu pivacaine-loaded microspheres on the time course of motor block in rab bits injected epidurally. Bupivacaine-loaded microspheres and drug-fre e microspheres 1-10 mu m in size were devised from poly-d,l-lactic aci d by using a solvent evaporation/extraction method. The effects of bup ivacaine and of similar amounts of bupivacaine-loaded microspheres wer e 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 bup ivacaine-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 wal king disturbances, using a scale from 0 (free movements) to 3 (total l imb paralysis). A period of 3 days elapsed between each injection. No limitation on movements was observed after 0.9% sodium chloride and dr ug-free microsphere injection. With 5 mg, both bupivacaine solutions p rovided 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, an d block duration was shorter after administration of bupivacaine-loade d microspheres than after bupivacaine. We concluded that blocks result ing from bupivacaine-loaded microspheres are highly influenced by the amount of drug initially released by the polymer.