Intrathecal lidocaine neurotoxicity: combination with bupivacaine and ropivacaine and effect of nerve growth factor

Life Sci. 2014 Sep 1;112(1-2):10-21. doi: 10.1016/j.lfs.2014.07.003. Epub 2014 Jul 23.

Abstract

Aims: The study aims to investigate the neurotoxicity induced by combined use of intrathecal lidocaine with bupivacaine and ropivacaine, and to examine the effect of nerve growth factor (NGF) on lidocaine-induced neurotoxicity.

Main methods: All rats received intrathecal infusion of anesthetics and NGF. To study the neurotoxicity of combined use of lidocaine with bupivacaine and ropivacaine, rats received saline, 5% lidocaine, 1.065% bupivacaine, 1.5% ropivacaine, 5% lidocaine+bupivacaine, or 5% lidocaine+1.5% ropivacaine. To study the neurotoxicity of different proportions of lidocaine and bupivacaine, mixtures were made by mixing 10% lidocaine and 2.5% bupivacaine in ratios of 1:3, 1:2, 1:1, 2:1 and 3:1 by volume. To study the effect of NGF on lidocaine-induced neurotoxicity, rats received saline or 10 μg NGF for 1, 2, 5 and 8 days.

Key findings: The neurotoxicity of lidocaine was significantly increased when combined with ropivacaine. A mixture of lidocaine and bupivacaine in a ratio of ≤1:1 did not significantly increase lidocaine-induced neurotoxicity. NGF significantly reduced lidocaine-induced neurobehavioral and morphological damage in the spinal cord. This was accompanied by downregulation of caspase 3 expression.

Significance: Ropivacaine is not safe when intrathecally administered with lidocaine at the concentrations used in this study. Bupivacaine may be safely used with lidocaine at a ratio of 1:1. NGF can reduce lidocaine-induced neurotoxicity, possibly via inhibition of caspase 3-mediated apoptosis.

Keywords: Bupivacaine; Caspase; Lidocaine; Local anesthetics; Nerve growth factor; Neurotoxicity; Ropivacaine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / adverse effects
  • Anesthetics, Local / adverse effects*
  • Animals
  • Apoptosis / drug effects
  • Bupivacaine / adverse effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Down-Regulation
  • Drug Combinations
  • Injections, Spinal
  • Lidocaine / adverse effects
  • Male
  • Nerve Growth Factor / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Ropivacaine
  • Spinal Cord / drug effects*
  • Spinal Cord / physiopathology

Substances

  • Amides
  • Anesthetics, Local
  • Drug Combinations
  • Neuroprotective Agents
  • Ropivacaine
  • Nerve Growth Factor
  • Lidocaine
  • Caspase 3
  • Bupivacaine