title: Neurotoxicity of intrathecally administered bupivacaine involves the posterior roots/posterior white matter and is milder than lidocaine in rats.
abstract: OBJECTIVE
  Clinical and laboratory studies suggest that lidocaine is more neurotoxic than bupivacaine. However, histological evidence of their comparative neurotoxicity is sparse. We thus pathologically and functionally compared the intrathecal neurotoxicity of these agents.
  
  
  METHODS
  Rats received 0.12 microL/g body weight lidocaine (0%, 2%, 10%, or 20%) or bupivacaine (0%, 0.5%, 2.5%, or 5%) in distilled water via an intrathecal catheter. The influence of high osmolarity was also examined using 5% bupivacaine in 20% glucose solution (5% BG) and a control 25% glucose solution. The L3 spinal cord, the posterior and anterior roots, and the cauda equina were examined by light and electron microscopy. Walking behavior and sensory threshold were investigated as neurofunctional tests.
  
  
  RESULTS
  The posterior root and posterior white matter showed axonal degeneration in rats treated with 10% and 20% lidocaine and 5% bupivacaine in distilled water (5% BDW) and in 5% BG, but not in rats treated with 2% lidocaine, 0.5% and 2.5% bupivacaine, distilled water, or 25% glucose solution. The histological damages were more severe in 20% lidocaine-treated rats than in 5% bupivacaine-treated rats. The damage of posterior white matter was observed only when the posterior root was severely injured. No significant difference of histological findings was observed between 5% BDW and 5% BG. Functional abnormalities were found only in rats treated with 20% lidocaine.
  
  
  CONCLUSIONS
  The neurotoxic lesions caused by bupivacaine and lidocaine were indistinguishable in the primary site and the extending pattern, such as axonal degeneration originating from the posterior roots and extending to the posterior white matter. The intrathecal neurotoxicity is greater in lidocaine than in bupivacaine.
authors.affiliation: Department of Anesthesiology, Kitasato University School of Medicine, 1-15-1 Kitasdato, Sagamihara, Kanagawa 228-8555, Japan. takenami@med.kitasato-u.ac.jp
authors.forename: Tamie
authors.initials: T
authors.lastname: Takenami
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Setsuko
authors.initials: S
authors.lastname: Murase
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hiruma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kawakami
authors.forename: Sumio
authors.initials: S
authors.lastname: Hoka
mesh_terms: D000762:Anesthesia Recovery Period; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D002420:Cauda Equina / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005950:Glucose Solution, Hypertonic / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration; D007278:Injections, Spinal / Q000379:methods; D008012:Lidocaine / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008859:Microscopy, Polarization / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012684:Sensory Thresholds / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D005950:Glucose Solution, Hypertonic; D008012:Lidocaine; D002045:Bupivacaine