title: Intrathecally administered ropivacaine is less neurotoxic than procaine, bupivacaine, and levobupivacaine in a rat spinal model.
abstract: OBJECTIVE
  The aim of this study was to compare the neurotoxicity of intrathecal procaine, bupivacaine, levobupivacaine, and ropivacaine in an animal model.
  
  
  METHODS
  The study comprised two experiments. In the concentration experiment, rats (n = 78) were administered 0.12 μL·g(-1) body weight (BW) of 2% or 20% procaine, 0.5% or 5% bupivacaine, 0.5% or 5% levobupivacaine, or 0.5% or 5% ropivacaine. Based on the findings, the doses were increased by volume in the subsequent volume experiment using 0.12, 0.24, or 0.48 μL·g(-1) BW of 6% procaine, 6% levobupivacaine, or 6% ropivacaine (n = 79). Walking behaviour and sensory threshold were analyzed, and a histological examination of the spinal cord, posterior and anterior roots, and cauda equina was performed.
  
  
  RESULTS
  The concentration experiment showed abnormalities only in the 5% bupivacaine group, and these abnormal findings were in the posterior root (PR) and posterior column (PC). The volume experiment revealed that procaine 0.24 μL·g(-1) was neurotoxic, mainly affecting the PR. At 0.48 μL·g(-1), severe injury was observed in the PR and PC in all six procaine rats and four of six levobupivacaine rats, while milder injury was limited to the PR in one of six ropivacaine rats, which differed significantly from the former two groups (P = 0.006 and P = 0.014, respectively). Electron microscopy showed axonal degeneration.
  
  
  CONCLUSIONS
  All four local anesthetics seemed to cause identical neurotoxic lesions commencing in the PR and extending to the PC by axonal degeneration. Bupivacaine appeared to be the most neurotoxic of the four drugs, and the neurotoxicity at higher doses increased by volume with procaine > levobupivacaine > ropivacaine.
authors.affiliation: Department of Anesthesiology, Kitasato Clinical Research Center, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan. takenami@med.kitasato-u.ac.jp
authors.forename: Tamie
authors.initials: T
authors.lastname: Takenami
authors.forename: Guoqin
authors.initials: G
authors.lastname: Wang
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nara
authors.forename: Sayano
authors.initials: S
authors.lastname: Fukushima
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hiruma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kawakami
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000633:toxicity; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects*; D002045:Bupivacaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D000077554:Levobupivacaine; D008297:Male; D008854:Microscopy, Electron; D023421:Models, Animal; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D011343:Procaine / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D011343:Procaine; D000077212:Ropivacaine; D000077554:Levobupivacaine; D002045:Bupivacaine