Motor nerve blockade potency and toxicity of non‐racemic bupivacaine in rats

Trachez, Margarete M.; Zapata‐Sudo, Gisele; Moreira, O. R.; Chedid, Nubia G.; Russo, Vincenzo; Russo, Elisa Maria de Sousa; Sudo, Roberto T.

doi:10.1111/j.1399-6576.2004.00536.x

Cited by 16 publications

(17 citation statements)

References 19 publications

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“…The present study confirmed the myocardial contractile dysfunction caused by potent LA 2,8,13,14 . Developed tension and maximum rate of tension development were both decreased more intensely with 100 mM racemic bupivacaine in relation to other LA in this study (Figures 2 and 4).…”

Section: Discussionsupporting

confidence: 76%

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Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

et al. 2015

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Brazil. Conception, design, intellectual and scientific content of the study; critical revision; final approval. ABSTRACT PURPOSE:To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS:Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication.Data were analyzed as relative changes of variation. RESULTS:Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS:Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine.Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine.Key words: Anesthetics, Local. Cardiotoxicity. Papillary Muscles. Rats. Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

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Section: Discussionsupporting

confidence: 76%

“…Adding 25% of the R isomer to S(-)bupivacaine (S75/R25) promoted stronger muscle relaxation and motor nerve blockade than bupivacaine isomers alone 13 . However, the effects of non-racemic bupivacaine (S75/R25) on myocardial contractile function remain understudied.…”

Section: Introductionmentioning

confidence: 99%

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

et al. 2015

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“…The difference was due to R (+) enantiomer of bupivacaine exerting a synergistic effect on binding characteristics of S (-) enantiomer of bupivacaine to the motor nerves and in their absence binding is less and effect terminates earlier. (20) Locatelli et al (10) because of the delayed surgical duration (31 ± 23 minutes) had a statistically significant differentiation between the groups. Modified Bromage score 0 at wakeup with Bupivacaine vs. Levobupivacaine was 28% vs. 67%, (p= 0.01).…”

Section: Discussionmentioning

confidence: 94%

A Comparative Study of Levobupivacaine and Rac-Bupivacaine for Caudal Analgesia in Paediatric Subumbilical Surgeries

Sundararajan¹,

Vanamai²

2018

jemds

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BACKGROUND Safety margin of various local anaesthetics have been analysed in the context of toxicity. Many studies have shown that Levobupivacaine has a higher safety profile, but there have been very few studies demonstrating an overwhelming benefit of Levobupivacaine over racemic Bupivacaine for paediatric regional anaesthesia. MATERIALS AND METHODSA randomised, double-blinded study was aimed to determine the presence of clinically significant differences in the analgesic efficacy and motor blockade of Levobupivacaine and Bupivacaine for caudal block under propofol based anaesthesia in children. After obtaining Ethical Committee approval and informed written parental consent, sixty children 2 -12 years of either sex belonging to ASA PS I -II, undergoing elective subumbilical surgeries were equally randomised and received 1 mL/kg, 0.25% of either Levobupivacaine (Group L) or Bupivacaine (Group B) caudally. Intraoperatively, onset of analgesia and haemodynamic variability were noted. Caudal block was assessed using FLACC pain score (0-10), time for first rescue analgesia and motor blockade with Modified Bromage score (0 -3). Statistical analysis was done with SPSS version 16.0. The independent 't' test, chi-square or Fisher's exact test were used to analyse the variables. Significance was defined as 'p' value was < 0.05. RESULTSOnset of analgesia was 21.68 ± 1.28 minutes in Group B and 26.12 ± 1.48 minutes in Group L, showing statistical significance (p value= 0.01). BP (systolic and diastolic) was significantly lower in Group B at 25, 30, 45 and 60 minutes. FLACC pain score at recovery was < 3 in both groups. Time for first rescue analgesia was 313.20 ± 63.10 minutes in Group B and 345.60 ± 73.55 minutes in Group L (p value > 0.05). Motor blockade at 120 minutes showed that complete recovery (score 0) was 36% higher in Group L than Group B (p value-0.02).

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“…duration, 0.2 Hz frequency) by a pair of platinum electrodes connected to a stimulator (Astromed Grass Model S88). The nerve branch innervating the gastrocnemius muscle was selectively preserved and the tendon of this muscle exposed and tightly connected to a force transducer (Grass FT 03) for isometric tension recording (Astromed Grass, Model 7400) [14]. Muscle twitches were recorded prior to and after incremental bolus injection of azumolene or dantrolene sodium at total doses of 0.5, 1, 2.5, 5 and 7.5 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Effects of Azumolene on Normal and Malignant Hyperthermia‐Susceptible Skeletal Muscle

Sudo

Carmo

Trachez

et al. 2007

Basic Clin Pharma Tox

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Malignant hyperthermia is a pharmacogenetic disease of skeletal muscle in which a life-threatening, hypermetabolic syndrome is induced by exposure of susceptible patients to halogenated general anaesthetics and/or succinylcholine. Dantrolene sodium, the only drug effective for treatment of malignant hyperthermia, has low water solubility that makes its clinical use difficult. The aim of this study was to investigate the potency of azumolene, a 30-fold more water-soluble analogue, in comparison to the prototype dantrolene sodium, on mammalian and human skeletal muscles. The twitches of extensor digitorum longus and soleus muscles from mice were inhibited by azumolene with IC 50 of 2.8 ± 0.8 and 2.4 ± 0.6 μ M, respectively. The IC 50 of dantrolene sodium in these muscles was 1.6 ± 0.4 and 3.5 ± 1.2 μ M, respectively, with no difference in comparison to azumolene. Previous in vitro exposure of mouse soleus muscle to azumolene and dantrolene sodium (10 μ M) significantly inhibited 8 mM caffeine-induced contractures. Azumolene was just effective as dantrolene sodium in relaxing caffeine-induced contractures of mouse soleus muscle. Intravenous injection caused dose-dependent decreases in twitches of guinea pig gastrocnemius muscle with IC 50 of 1.2 ± 0.1 and 1.5 ± 0.2 mg/kg for azumolene and dantrolene sodium, respectively. Azumolene, 10 μ M, was effective in blocking and reversing caffeine-induced contracture of human malignant hyperthermia susceptible skeletal muscle in vitro . These studies provide evidence that azumolene is equipotent to dantrolene sodium in blocking pharmacologic-induced muscle contractures and that azumolene should be efficacious for treatment/prevention of malignant hyperthermia.Malignant hyperthermia is a pharmacogenetic disorder characterized by abnormal increase of Ca 2+ release from sarcoplasmic reticulum triggered by volatile halogenated anaesthetics and/or succinylcholine [1]. The cause for malignant hyperthermia and consequently the dysregulation of myoplasmic Ca 2+ is related to a mutation of the Ca 2+ release channel (RyR1) of sarcoplasmic reticulum [2,3]. RyR1 causal mutations have been found in over 50% of malignant hyperthermiasusceptible families [4]. Dantrolene, 1-<{[5-(4-nitrophenyl)-2-furfuryl]methylene}amino>-2,4-imidazoleidinedione, is the only drug effective for treatment and prevention of malignant hyperthermia and as a consequence of its clinical introduction, mortality decreased from 70% to 5 -10% [5]. Dantrolene is a skeletal muscle relaxant that modulates the activity of RyR1 promoting inhibition of Ca 2+ efflux from sarcoplasmic reticulum [6,7]. The treatment of a malignant hyperthermia episode consists of an initial intravenous injection of 2.5 mg/kg of dantrolene sodium [8]. Due to low water solubility (about 0.3 mg/ml) this amount of dantrolene sodium must be dissolved in about 500 ml of water in a 70-kg patient that represents risks from consuming time and for aggravating the cardiac failure usually present in an malignant hyperthermia crisis. A 30-fold mo...

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Motor nerve blockade potency and toxicity of non‐racemic bupivacaine in rats

Abstract: The potency of S(-) bupivacaine to block the motor activity in the sciatic nerve was enhanced when 25% of the S(-) isomer was replaced by the antipode R(+) bupivacaine. This effect was not associated with increased toxicity.

Cited by 16 publications

References 19 publications

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

A Comparative Study of Levobupivacaine and Rac-Bupivacaine for Caudal Analgesia in Paediatric Subumbilical Surgeries

Effects of Azumolene on Normal and Malignant Hyperthermia‐Susceptible Skeletal Muscle

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