GLUCOCORTICOIDS PROLONG RAT SCIATIC-NERVE BLOCKADE IN-VIVO FROM BUPIVACAINE MICROSPHERES

Background: previous work showed that incorporation of dexamethasone ( 0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivaca ine microspheres alone. The determinants of dexamethasone's block-prol onging effect were examined and reported here. Methods: Polylactic-co- glycolic acid polymer microspheres (65/35) with 75 weight/weight perce ntage bupivacaine were prepared. Microspheres were injected adjacent t o the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a susp ension of bupivacaine microspheres. Results: Dexamethasone alone in su spension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspendi ng solution of microspheres prolonged block by up to five times. Gluco corticoids prolonged block in proportion to glucocorticoid/antiinflamm atory potency. The corticosteroid antagonist cortexolone inhibited dex amethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophi l depletion. Microspheres were extracted from rats at time points rang ing from 7 h to 7 days, and residual microsphere dry weight and bupiva caine content were similar in groups of rats injected with either bupi vacaine microspheres or bupivacaine microspheres containing dexamethas one, respectively. Conclusions: Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinet ics of bupivacaine release in vivo.