Prolongation of Spinal Anesthesia with Bupivacaine-Loaded (DL-Lactide) Microspheres

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Abstract
There is considerable interest in developing a sustained-release local anesthetic formulation to provide long-lasting anesthesia and to decrease systemic toxicity. Bupivacaine (B), 10 mg, loaded in two different types of polylactide microspheres (PLA1 and PLA2) was evaluated after spinal injection and compared with plain bupivacaine (pB), 2 mg. Experiments were performed in six New Zealand rabbits. Duration of motor block was significantly prolonged for PLA1 compared to pB (177.5 +/- 79.5 min vs 44.6 +/- 18.0 min; P < 0.05), as well as for the recovery time (545.0 +/- 299.6 min vs 44.2 +/- 21.5 min; P < 0.05). The duration and recovery were not prolonged for PLA2. Systemic release of B after intrathecal injection was measured from blood samples by using high-performance liquid chromatography. There was no significant difference in maximum B plasma concentration between pB and PLA1 (326 +/- 81 mg/mL vs 321 +/- 57 ng/mL). The time taken to reach the maximum plasma concentration (6.6 +/- 2.6 min vs 41.7 +/- 20.4 min; P < 0.05) was significantly different. This study demonstrated that the use of bupivacaine-loaded (DL-lactide) microspheres can prolong spinal motor block.