title: A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits.
abstract: We have reported that increased glutamate concentrations in microdialysate of the cerebrospinal fluid (CSF) may be clue phenomena to elucidate mechanisms of neurotoxicity of intrathecal tetracaine. However, little is known about whether this is true for other local anesthetics. In this study, we compared the effects of local anesthetics on glutamate concentrations in CSF microdialysate and neurologic and histopathologic outcome. Rabbits were assigned into 5 groups (n = 6 in each) and intrathecally received 0.3 mL of NaCl solution (control), 2% tetracaine, 10% lidocaine, 2% bupivacaine, or 2% ropivacaine. Neurologic and histopathologic assessments were performed 1 wk after the administration. Intrathecal local anesthetics significantly increased glutamate concentrations with no significant differences among the four local anesthetics. The sensory and motor functions in the lidocaine group were significantly worse than in the other groups. Characteristic histopathologic changes were vacuolation in the dorsal funiculus and chromatolytic damage of motor neurons. The extent of vacuolation of the dorsal funiculus was in the order of lidocaine = tetracaine > bupivacaine > ropivacaine. Although the differences among the local anesthetics cannot be explained by glutamate concentrations, the results suggest that the margin of safety may be smallest with lidocaine.
  
  
  CONCLUSIONS
  Large concentrations of local anesthetics administered intrathecally increased glutamate concentrations in the cerebrospinal fluid. The margin of safety may be smallest with lidocaine.
authors.affiliation: Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yamashita
authors.forename: Mishiya
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Koji
authors.initials: K
authors.lastname: Kawai
authors.forename: Takefumi
authors.initials: T
authors.lastname: Sakabe
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000633:toxicity; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000633:toxicity; D017551:Microdialysis; D009068:Movement / Q000187:drug effects; D011817:Rabbits; D000077212:Ropivacaine; D012677:Sensation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013748:Tetracaine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D013748:Tetracaine; D018698:Glutamic Acid; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine