title: Intrathecal lidocaine neurotoxicity: combination with bupivacaine and ropivacaine and effect of nerve growth factor.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Guangyi
authors: G
authors: Zhao
authors: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Xudong
authors: X
authors: Ding
authors: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors: Yao
authors: Y
authors: Guo
authors: Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: zhaobaisong819@163.com.
authors: Weimin
authors: W
authors: Chen
mesh_terms: D000577:Amides / Q000009:adverse effects; D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002045:Bupivacaine / Q000009:adverse effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D007278:Injections, Spinal; D008012:Lidocaine / Q000009:adverse effects; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D004338:Drug Combinations; D018696:Neuroprotective Agents; D000077212:Ropivacaine; D020932:Nerve Growth Factor; D008012:Lidocaine; D053148:Caspase 3; D002045:Bupivacaine
keywords: Bupivacaine; Caspase; Lidocaine; Local anesthetics; Nerve growth factor; Neurotoxicity; Ropivacaine