Neurotoxicity of intrathecally administered tetracaine commences at the posterior roots near entry into the spinal cord

Takenami, Tamie; Yagishita, Saburo; Asato, Fumio; Hoka, Sumio

doi:10.1053/rapm.2000.6444

Cited by 18 publications

(20 citation statements)

References 29 publications

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“…In our previous study using the same protocol, we reported the induction of histological lesions by bupivacaine, mepivacaine, and prilocaine (each at eight times), 11 lidocaine (3.7 times), 9 and tetracaine (four times) 10 higher than their clinical respective concentrations. In the present study, the concentration experiment indicated that procaine, levobupivacaine, and ropivacaine did not induce lesions even when used at ten times the clinical concentrations, suggesting that these three agents are less toxic than the drugs tested previously.…”

Section: Discussionmentioning

confidence: 95%

“…bupivacaine for the central nervous and cardiovascular systems in animals 4,5 and humans. [6][7][8] In a series of studies, we determined the neurotoxicities of lidocaine, tetracaine, bupivacaine, mepivacaine, prilocaine, and procaine [9][10][11][12] in a rat spinal model. These studies showed that all these agents, with the exception of procaine, were neurotoxic, with lesions displaying common features irrespective of the anesthetic agent and affecting mainly axons of the dorsal root entry zone.…”

Section: Résumémentioning

confidence: 99%

“…These samples were then prepared for light and electron microscopy, as described in our previous studies. [9][10][11][12] Briefly, all specimens were embedded in epoxy resin. The spinal cord at L3 was divided into two parts.…”

Section: Tissue Preparationmentioning

confidence: 99%

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

Takenami

Wang

Nara

et al. 2012

Can J Anesth/J Can Anesth

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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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Section: Discussionmentioning

confidence: 95%

Section: Résumémentioning

confidence: 99%

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

Takenami

Wang

Nara

et al. 2012

Can J Anesth/J Can Anesth

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“…Em local próxi-mo à raiz posterior, imediatamente antes da sua entrada na substância branca medular, encontra-se uma zona desmielinizada, que contém neurônios desnudos. Estes neurônios são mais sensíveis à neurotoxicidade de drogas introduzidas no líquor 27 . Para concluir, pode-se dizer que grandes volumes de lidocaí-na a 2% determinaram alterações histológicas sobre o tecido nervoso da medula espinhal, mais intensas que aquelas determinadas pela ropivacaína a 1%.…”

Section: Resultsunclassified

“…In a site close to the posterior root, immediately before its insertion in the spinal cord white matter, there is a demyelinized region with nude neurons. These neurons are more sensitive to neurotoxicity of drugs introduced in the CSF 27 . In conclusion, large 2% lidocaine volumes determine more severe histological changes on spinal cord nervous tissue as compared to 1% ropivacaine.…”

mentioning

confidence: 99%

Efeitos da administração subaracnóidea de grandes volumes de lidocaína a 2% e ropivacaína a 1% sobre a medula espinhal e as meninges: estudo experimental em cães

Ganem¹,

Vianna²,

Marques³

et al. 2003

Rev. Bras. Anestesiol.

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A case of transient neurologic symptoms following epidural mepivacaine and spinal tetracaine

Takenami

Kondou

Kimotsuki

et al. 2002

Journal of Anesthesia

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injected. Cold sensation was lost from T10 to S3 on the left side and from T10 to L1 on the right side 15 min after epidural injection. Because the level of hypesthesia was considered insufficient for the curettage procedure, especially on the right side, 20 min after the epidural injection, spinal puncture was performed using a 25-gauge Sprotte needle after removal of the epidural catheter. Two milliliter of 0.5% tetracaine dissolved in 5% glucose solution was intrathecally injected at the L4-L5 interspace with the patient in the left lateral position. This resulted in the spreading of hypesthesia bilaterally from the T4 to the S5 level that was considered sufficient for the operation. Both anesthetic procedures were performed easily, without any bleeding, and no paresthesia occurred during insertion of the needle or catheter or during drug injection. The patient was subsequently placed in the lithotomy position for approximately 30 min. The curettage procedure was uneventful and lasted for 10 min. Vital signs were stable during curettage. Six hours after intrathecal injection, sensory and motor functions were completely recovered in both lower extremities.On the first postoperative day, the patient complained of numbness on the posterior side of the left lower extremity, and the numbness radiated to the ankle. The patient could not walk because of severe pain in the left leg that occurred when her feet touched the floor. At rest, she felt numbness rather than pain. On the second postoperative day, the numbness spread bilaterally to the lower back, buttocks, and thighs. She did not complain of bowel or bladder dysfunction. There was no significant hyperalgesia or sensory loss according to the cold and pinprick tests. Motor nerve function was intact in both extremities, and there was no impairment of deep tendon reflexes. There were no abnormalities on lumbar radiographic examination. The symptoms gradually disappeared 4 days after surgery, and the patient was discharged 5 days after surgery without any symptoms.

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Neurotoxicity of intrathecally administered tetracaine commences at the posterior roots near entry into the spinal cord

Abstract: Our results suggest that the initial target of intrathecal tetracaine neurotoxicity may be the posterior roots at their entry into the spinal cord, where the axons are devoid of myelin sheath and thus representing a sensitive area for neurotoxic change.

Cited by 18 publications

References 29 publications

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

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

Efeitos da administração subaracnóidea de grandes volumes de lidocaína a 2% e ropivacaína a 1% sobre a medula espinhal e as meninges: estudo experimental em cães

A case of transient neurologic symptoms following epidural mepivacaine and spinal tetracaine

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