PROLONGED INTERCOSTAL NERVE BLOCKADE IN SHEEP USING CONTROLLED-RELEASE OF BUPIVACAINE AND DEXAMETHASONE FROM POLYMER MICROSPHERES

Background: Previous work from the authors' group characterized a prol onged percutaneous blockade of the sciatic nerve in rats using bupivac aine-dexamethasone microspheres. The goals of the current study are to examine the (1) efficacy of bupivacaine microspheres with and without dexamethasone for intercostal blockade in sheep; (2) scaling of dose and duration with a 100-fold increase in body size from rats to sheep; (3) local toxicity and adverse systemic reactions to bupivacaine micr ospheres with and without dexamethasone. Methods: Intercostal blocks w ere performed percutaneously in sedated sheep. Sensory blockade was me asured at repeated time points by absent flinch response to skin pinch . Plasma bupivacaine concentrations were measured using high performan ce liquid chromatography. Chest wall specimens were examined by light microscopy. Results: The duration of intercostal blockade increased wi th bupivacaine dose for animals receiving from 8 to 80 mg/kg of micros pheres with and without dexamethasone. At each dose, microspheres cont aining dexamethasone had a longer duration of block than microspheres without dexamethasone. From 8 to 80 mg/kg, the mean duration of block with bupivacaine-dexamethasone microspheres increased from 4 to 13 day s. Plasma concentrations of bupivacaine remained 10-fold below the con vulsive EC50 concentration for sheep. Chest wall histology showed a si gnificant granulomatous reaction around bupivacaine microspheres but n ot around bupivacaine-dexamethasone microspheres. Conclusions: A singl e administration of bupivacaine-dexamethasone microspheres produces an effective chest wall analgesia of several days' duration. This may pr ove useful clinically for thoracic surgery or trauma.