Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2020.04.008
Brazilian Journal of Anesthesiology
Scientific Article

Influence of different local anesthetics on atracurium neuromuscular blockade on rats

Influência de diferentes anestésicos locais no bloqueio neuromuscular produzido pelo atracúrio em ratos

João Paulo Soares da Silva Trizotti, Angélica de Fátima de Assunção Braga, Vanessa Henriques Carvalho, Franklin Sarmento da Silva Braga

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Abstract

Introduction
The association between Local Anesthetics (LAs) and Neuromuscular Blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs.

Objective
The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium.

Methods
Male Wistar rats, weighing from 250 g to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 μg.mL−1 (Group I); racemic bupivacaine 5 μg.mL−1 (Group II); atracurium 20 μg.mL−1 (Group III); atracurium 20 μg.mL−1 in a preparation previously exposed to lidocaine 20 μg.mL−1 and racemic bupivacaine 5 μg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane Potentials (MP) and Miniature Endplate Potentials (MEPPs).

Results
Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive.

Conclusions
Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Keywords

Local anesthetics;  Lidocaine;  Racemic bupivacaine;  Nondepolarizing neuromuscular blocking drugs;  Atracurium;  Animals Rats

Resumo

Introdução
A associação de Anestésicos Locais (AL) com Bloqueadores Neuromusculares (BNM) na prática clínica e a possibilidade de interação entre esses fármacos têm sido investigadas.

Objetivo
O objetivo do estudo foi avaliar, em modelo experimental, o efeito da lidocaína e da bupivacaína racêmica na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido pelo atracúrio.

Método
Ratos machos da linhagem Wistar, peso entre 250 e 300 g. A preparação foi realizada de acordo com a técnica proposta por Bulbring. Grupos (n = 5) de acordo com o fármaco em estudo: lidocaína 20 μg.mL−1 (Grupo I); bupivacaína racêmica 5 μg.mL−1 (Grupo II); atracúrio 20 μg.mL−1 (Grupo III); atracúrio 20 μg.mL−1 em preparação previamente exposta a lidocaína 20 μg.mL−1 e bupivacaína racêmica 5 μg.mL−1, Grupos IV e V, respectivamente. Foram avaliadas: 1) A amplitude das respostas do hemidiafragma à estimulação indireta antes e 60 minutos após a adição dos fármacos; 2) Os Potenciais de Membrana (PM) e os Potenciais de Placa Terminal em Miniatura (PPTM).

Resultados
Os AL, isoladamente, não alteraram a amplitude das respostas musculares. Com o uso prévio dos AL, o bloqueio neuromuscular (%) do atracúrio foi 86,66 ± 12,48 e 100, respectivamente, com diferença significante (p = 0,003) em relação ao produzido pelo atracúrio isoladamente (55,7 ± 11,22). Não alteraram o PM. A lidocaína inicialmente aumentou a frequência dos PPTM, seguido de bloqueio; com a bupivacaína, o bloqueio foi progressivo.

Conclusões
A lidocaína e a bupivacaína racêmica apresentaram efeito pré-sináptico expresso por alterações nos PPTM, podendo justificar a potencialização do bloqueio neuromuscular produzido pelo atracúrio.

Palavras-chave

Anestésicos locais Lidocaína;  Bupivacaína racêmica;  Bloqueadores neuromusculares não despolarizantes;  Atracúrio;  Animais;  Ratos

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