Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study.
BACKGROUND
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% ropivacaine (doses from 0.4-4.0 mg; groups R0.2 to R2.0), 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 RINT); or a continuous intrathecal infusion of 0.2% ropivacaine at the rate of 1.8 ml/h over 45 min (2.7 mg; group RCONT). 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 RCONT and RINT. Seven days after the last intrathecal injection spinal cord and nerves were sampled for histopathologic study.


RESULTS
In groups R0.2 and RINT, the lowest dose of ropivacaine induced a clinically visible spinal block in only 50% of rabbits, but SEPs recorded in group RINT were decreased by 70% in the lumbar dermatome. Complete motor block was observed with doses greater than 1.5 mg of ropivacaine (group RCONT and R0.75 to R2.0). 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.


CONCLUSIONS
Ropivacaine induced dose-dependent spinal anesthesia, and did not induce any neurotoxicologic lesion in this experimental animal model.
Malinovsky
Jean-Marc
JM
Service d'Anesthésie-Réanimation, Chirurgicale, Hôtel-Dieu, Nantes Cedex, France. jeanmarc.malinovsky@chu-nantes.fr
Charles
Florence
F
Baudrimont
Marielle
M
Péréon
Yann
Y
Le Corre
Pascal
P
Pinaud
Michel
M
Benhamou
Dan
D
D000577:Amides / Q000494:pharmacology / Q000633:toxicity*; D000779:Anesthetics, Local / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007278:Injections, Spinal; D008012:Lidocaine / Q000494:pharmacology / Q000633:toxicity; D019148:Neuromuscular Blockade / Q000379:methods; D011817:Rabbits; D000077212:Ropivacaine; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology*
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D008012:Lidocaine