title: The addition of epinephrine to tetracaine injected intrathecally sustains an increase in glutamate concentrations in the cerebrospinal fluid and worsens neuronal injury.
abstract: We have reported that large concentrations of intrathecal tetracaine increase glutamate concentrations in the cerebrospinal fluid (CSF) and cause neuronal injury in the spinal cord. In this study, we investigated whether the addition of epinephrine to tetracaine modulates these events. New Zealand white rabbits were assigned into five groups (six rabbits in each group) and intrathecally received 0.3 mL of epinephrine 0.1 mg/mL in NaCl solution (control), 1% tetracaine dissolved in saline (1%T), 1% tetracaine with epinephrine (1%TE), 2% tetracaine (2%T), or 2% tetracaine with epinephrine (2%TE). Glutamate concentrations in the lumbar CSF were monitored by microdialysis. Neurologic and histopathologic assessments were performed 1 wk after the administration. Glutamate concentrations significantly increased in all four groups that received tetracaine, whereas no change was observed in the Control group. The addition of epinephrine to tetracaine sustained large concentrations of glutamate. Sensory and motor dysfunction was observed in the 1%TE, 2%T, and 2%TE groups, and the dysfunction tended to be progressively exacerbated in this order. Characteristic histologic changes in animals with sensory and motor dysfunction were vacuolation in the dorsal funiculus and chromatolytic damage of motor neurons. The vacuolation of the dorsal funiculus in the 1%TE group was significantly worse than in the 1%T group. These results suggest that the addition of epinephrine to tetracaine may increase its neurotoxicity, which may possibly be related to a sustained increase of glutamate concentrations in the CSF.
  
  
  CONCLUSIONS
  Sustained increase of glutamate concentrations produced by the addition of epinephrine to intrathecal tetracaine can cause neuronal injury.
authors.affiliation: Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Oka
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Ohtake
authors.forename: T
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: K
authors.initials: K
authors.lastname: Nakakimura
authors.forename: T
authors.initials: T
authors.lastname: Sakabe
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D001784:Blood Gas Analysis; D004837:Epinephrine / Q000009:adverse effects*; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D006439:Hemodynamics / Q000187:drug effects; D007278:Injections, Spinal; D017551:Microdialysis; D009474:Neurons / Q000473:pathology*; D011817:Rabbits; D013119:Spinal Cord Injuries / Q000473:pathology*; D013748:Tetracaine / Q000009:adverse effects*; D014662:Vasoconstrictor Agents / Q000009:adverse effects*
chemical_list: D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D013748:Tetracaine; D018698:Glutamic Acid; D004837:Epinephrine