Intrathecal Ropivacaine in Rabbits: Pharmacodynamic and Neurotoxicologic Study
Jean-Marc Malinovsky, Florence Charles, Marielle Baudrimont, Yann Péréon, Pascal Le Corre, Michel Pinaud, Dan Benhamou
Ropivacaine is available for spinal or intrathecal use in humans, although data on neurotoxicity after spinal injection are not yet available. The authors experimentally determined the relationship between doses of intrathecal ropivacaine and spinal effects and local neurotoxic effects. Methods: Eighty rabbits equipped with an intrathecal lumbar catheter were studied. Sixty were randomly assigned to receive 0.2 ml of intrathecal solutions as a sole injection of: 0.2%, 0.75%, 1.0%, and 2.0%
... acaine (doses from 0.4 -4.0 mg; groups R 0.2 to R 2.0 ), 5.0% lidocaine (10 mg; group L), or 0.9% NaCl as control (group C). Twenty other rabbits received either repeated injections of 0.2 ml of 0.2% ropivacaine every 2 days during 2 weeks (total dose of 2.8 mg; group R INT ); or a continuous intrathecal infusion of 0.2% ropivacaine at the rate of 1.8 ml/h over 45 min (2.7 mg; group R CONT ). Injection rate was 30 s in all groups except RCONT. Time to onset, duration and extent of motor block, and variations of mean arterial blood pressure were recorded in all groups. Somatosensory evoked potentials were also recorded in group R CONT and R INT . Seven days after the last intrathecal injection spinal cord and nerves were sampled for histopathologic study. Results: In groups R 0.2 and R INT , the lowest dose of ropivacaine induced a clinically visible spinal block in only 50% of rabbits, but SEPs recorded in group R INT were decreased by 70% in the lumbar dermatome. Complete motor block was observed with doses greater than 1.5 mg of ropivacaine (group R CONT and R 0.75 to R 2.0 ). Onset time was shorter and duration of block increased as doses of ropivacaine increased. Significant hypotension was observed only with 4.0 mg of ropivacaine (concentration of 2.0%). Complete paralysis and hypotension were observed with 5.0% lidocaine. No neurologic clinical lesion was observed in rabbits receiving saline or ropivacaine within the 7 days after the last intrathecal injection, and histopathologic study revealed no sign of neurotoxicity in these groups. In contrast, intrathecal lidocaine induced clinical and histopathologic changes. Conclusion: Ropivacaine induced dose-dependent spinal anesthesia, and did not induce any neurotoxicologic lesion in this experimental animal model.