Comparative Neurotoxicity of Stereoisomers and Racemic Bupivacaine Administered Intrathecally in the Rat

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The aim of this study was to compare the functional and morphologic effects of intrathecally administered R(+), S(-), and racemic bupivacaine using a rat model.Methods : With approval from our Committee on Animal Research, 83 male Sprague-Dawly rats were implanted with 32-gauge intrathecal catheters, and ramdomly divided into four groups to receive a single 2-hr intrathecal infusion (1μl/min) of 1 % R(+) bupivacaine (n = 22), 1 % S(-) bupivacaine (n = 24), 1 % racemic bupivacaine (n = 24), or normal saline (n = 13). Animals were assessed for persistant sensory impairment 4 and 7 days after infusion using the tail-flick test. Tail flick latencies at the proximal, mid, and distal portions of the tail were averaged and converted to % MPE = [(post-drug latency - baseline latency)/(cut-off - baseline latency)] x 100. Animals were sacrificed 7 days after infusion. The nerve roots were sectioned 12 mm caudal to the conus. Each nerve fascicle was assigned an injury score of 0-2 (0 = nomal and mild, 1 = moderate, 2 = sever). The injury score of each cross-section was calculated as the average of all fascicles present in the slide. These data were compared using the Kruskal-Wallis test and Mann-Whitney test.Results : When assessed 4 days after infusion, sensory dysfunction did not appeare in three bupivacaine-treated groups. However, histologic damage remained in three bupivacaine-treated groups ; especially injury by S(-) or racemic bupivacaine was significantly greater than by R(+) bupivacaine.Conclusions : R(+) bupivacaine administered intrathecally has a lower potential for producing neurotoxicity than does S(-) or racemic bupivacaine. We should observe the neurotoxic potential of intrathecally administered levobupivacaine.