Intrathecally administered ropivacaine is less neurotoxic than procaine, bupivacaine, and levobupivacaine in a rat spinal model

Abstract

Purpose 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 lLÁg -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 lLÁg -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 lLÁg -1 was neurotoxic, mainly affecting the PR. At 0.48 lLÁg -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. Conclusion All four local anesthetics seemed to cause identical neurotoxic lesions commencing in the PR and Author contributions Tamie Takenami designed and initiated this study, took part in all aspects of the experiments, collected data for statistical analysis, and wrote the manuscript. Guoqin Wang performed statistical tests, assisted with the statistical analysis, and proposed the method of statistical analysis to validate the injury score. Yoshihiro Nara assisted with catheterization, drug injection, and securing the catheters. He also performed evaluations for the ambulation and paw stimulation tests. Sayano Fukushima assisted with the assessment of the injury scores. Saburo Yagishita verified the pathological changes. Hiromi Hiruma and Tadashi Kawakami allowed use of their laboratory during the study and reviewed the manuscript. Hiromi Hiruma, Tadashi Kawakami, and Hirotsugu Okamoto offered their advice. 123Can J Anesth/J Can Anesth (2012) 59: 456-465 DOI 10.1007/s12630-012-9685-9 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. RésuméObjectif L'objectif de cette e´tude e´tait de comparer la neurotoxicite´intrathe´cale de la procaı¨ne, de la bupivacaı¨ne, de la le´vobupivacaı¨ne et de la ropivacaı¨ne dans un mode`le animal. Méthodes L'e´tude a comporte´deux expe´rimentations. Dans une expe´rience sur la concentration, des rats (n = 78) ont reçu 0,12 lLÁg -1 de poids corporel de procaı¨ne a`2 % ou 20 %, de bupivacaı¨ne a`0,5 % ou 5 %, de le´vobupivacaı¨ne a`0,5 % ou 5 % ou de...

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