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Neurotoxicity of Intrathecally Administered Bupivacaine Involves the Posterior Roots/Posterior White Matter and Is Milder Than Lidocaine in Rats
  1. Tamie Takenami, M.D.,
  2. Saburo Yagishita, M.D.,
  3. Setsuko Murase,
  4. Hiromi Hiruma, M.D.,
  5. Tadashi Kawakami, M.D. and
  6. Sumio Hoka, M.D.
  1. From the Department of Anesthesiology, Kitasato University School of Medicine, Kanagawa, Japan (T.T.,S.H.)
  2. Department of Pathology, Kanagawa Rehabilitation Center, Kanagawa, Japan (S.Y.)
  3. Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan (S.M.)
  4. Department of Physiology, Kitasato University School of Medicine, Kanagawa, Japan (H.H.,T.K.).
  1. Reprint requests: Tamie Takenami, M.D., Department of Anesthesiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. E-mail: takenami{at}


Background and Objectives 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 μL/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.

  • Local anesthetics
  • Neurotoxicity
  • Histopathology
  • Sensory impairment
  • Axonal degeneration

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  • This study was supported by a grant from the Japanese Society for Promotion of Science (JSPS), Grant-in-Aid for Scientific Research (C)(2) (KAKENHI No13671611. to T.T.).

    Presented in part at the annual meeting of the American Society of Anesthesiology, New Orleans, LA, October 13-17, 2001.