Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers

Knudsen, Kai; Suurküla, Madis; Blomberg, S; Sjövall, Jan; Edvardsson, Nils

doi:10.1093/bja/78.5.507

Cited by 925 publications

(641 citation statements)

References 24 publications

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“…The clinical advantages of epidural anaesthesia are well established [1][2][3]. Recent developments to enhance safety of the epidural procedure have been in the fields of needle design, pharmacology and correct positioning of the epidural needle [8,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Clinical results with a new acoustic device to identify the epidural space

Lechner¹,

Wijk²,

Maas

2002

Anaesthesia

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SummaryFifty patients scheduled for surgery under lumbar epidural anaesthesia were included in a study to evaluate the possibility of localising the epidural space solely by means of an acoustic signal. With an experimental set-up, the pressure generated during the epidural puncture procedure was translated into a corresponding acoustic signal. One anaesthetist held the epidural needle with both hands and detected the epidural space by means of this acoustic signal. At the same time, a second anaesthetist applied the loss of resistance technique and functioned as control. In all patients the epidural space was located with the acoustic signal. This was confirmed by conventional loss of resistance in 49 (98%) of the patients; in one patient (2%) it was not. We conclude that it is possible to locate the epidural space using an acoustic signal alone.

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Section: Discussionmentioning

confidence: 99%

Clinical results with a new acoustic device to identify the epidural space

Lechner¹,

Wijk²,

Maas

2002

Anaesthesia

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“…[4][5][6][7][8]18 The toxicity of racemic bupivacaine was only 1.5-2 times greater than that of the S-forms, levobupivacaine and ropivacaine. 4,18 However, the present study showed that intrathecally administered bupivacaine was at least 4.8 times as neurotoxic as the S-form drugs (5% bupivacaine 0.12 lLÁg -1 vs 6% ropivacaine 0.48 lLÁg -1 ).…”

Section: Discussionmentioning

confidence: 98%

“…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%

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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confidence: 97%

“…Notably, the intra-arterial concentration of unbound bupivacaine for inducing CNS toxicity is approximately 50 % of unbound ropivacaine, both of which are three-and four-fold higher, respectively, than the intravenous concentration [1]. Cumulative case reports and animal experiments have also shown that the systemic toxicity of levobupivacaine and ropivacaine is less than bupivacaine [3,4].…”

mentioning

confidence: 99%

Pharmacokinetics and systemic toxicity of local anesthetics in children

Oda

2016

J Anesth

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toxicity is 2-3 µg/ml of total (protein bound and unbound) and 0.1-0.2 µg/ml of unbound bupivacaine, levobupivacaine and ropivacaine [1,2]. Notably, the intra-arterial concentration of unbound bupivacaine for inducing CNS toxicity is approximately 50 % of unbound ropivacaine, both of which are three-and four-fold higher, respectively, than the intravenous concentration [1]. Cumulative case reports and animal experiments have also shown that the systemic toxicity of levobupivacaine and ropivacaine is less than bupivacaine [3,4]. Infants are prone to develop CNS toxicity by bupivacaine at total and unbound concentrations lower than these values [5]. Although the threshold plasma concentration for cardiac toxicity is higher than for CNS, symptoms such as dysrhythmia and QRS widening due to decreased intraventricular conduction by long-acting local anesthetics may appear prior to any neurological manifestations in infants [6]. As neonates and infants have a higher heart rate than adults, the intensity of the block is also higher (use-dependent block) and they are more prone to the toxic effects of bupivacaine, levobupivacaine and ropivacaine than adults. Hypoxia, acidosis, hypothermia and electrolyte disorders increase cardiac toxicity [3]. Protein binding and dispositionAmide local anesthetics are predominantly bound to plasma alpha 1 -acid glycoprotein (AAG), and to a minor extent to albumin. The plasma concentration of AAG at birth is approximately 20-50 % of that in adults. During the first 6-9 months of life, it progressively increases to reach adult levels by the end of the first year [7] (Fig. 1a). Although the levels of albumin in neonates are also lower than in adults, its affinity to local anesthetics is approximately 5,000-10,000 times lower than AAG, suggesting that albumin

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Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers

Cited by 925 publications

References 24 publications

Clinical results with a new acoustic device to identify the epidural space

Clinical results with a new acoustic device to identify the epidural space

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

Pharmacokinetics and systemic toxicity of local anesthetics in children

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