Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942009000600008
Brazilian Journal of Anesthesiology
Scientific Article

Influência de anestésicos locais sobre o bloqueio neuromuscular produzido pelo rocurônio: ação da lidocaína e da mistura enantiomérica em excesso de 50% de bupivacaína na junção neuromuscular

Influence of local anesthetics on the neuromuscular blockade produced by rocuronium: effects of lidocaine and 50% enantiomeric excess bupivacaine on the neuromuscular junction

Angélica de Fátima de Assunção Braga; Vanessa Henriques Carvalho; Franklin Sarmento da Silva Braga; Léa Rodrigues-Simioni; Yolanda Christina S Loyola; Glória Braga Potério

Downloads: 0
Views: 1104

Resumo

JUSTIFICATIVA E OBJETIVOS: Os efeitos dos anestésicos locais (AL) na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido por bloqueadores neuromusculares competitivos são ainda alvo de pouca investigação. O objetivo do estudo foi avaliar in vitro os efeitos da lidocaína e da mistura enantiomérica em excesso de 50% de bupivacaína (S75-R25) no bloqueio neuromuscular produzido pelo rocurônio. MÉTODOS: Ratos foram distribuídos em cinco grupos (n = 5) de acordo com o fármaco estudado: lidocaína, bupivacaína (S75-R25), rocurônio, isoladamente (grupos I, II e III); rocurônio em preparações previamente expostas aos AL (grupos IV e V). As concentrações utilizadas foram: 20 µg.mL-1, 5 µg.mL-1 e 4 µg.mL¹ para lidocaína, bupivacaína (S75-R25) e rocurônio, respectivamente. Avaliaram-se: 1) a força de contração muscular do diafragma à estimulação elétrica indireta, antes e 60 minutos após a adição dos AL e do rocurônio isoladamente, e a associação AL-rocurônio; 2) os efeitos dos AL sobre o potencial de membrana (PM) e potenciais de placa terminal em miniatura (PPTM). Em preparação biventer cérvicis de pintainho, foi avaliado o efeito do AL na resposta contraturante à acetilcolina. RESULTADOS: A lidocaína e a bupivacaína (S75-R25) isoladamente não alteraram as respostas musculares e os valores do PM. Nas preparações expostas aos AL, o bloqueio pelo rocurônio foi significativamente maior em relação ao produzido pelo rocurônio isoladamente. Em preparação biventer cervicis de pintainho, a lidocaína e a bupivacaína (S75-R25) diminuíram a resposta de contração à acetilcolina. A lidocaína aumentou a frequência dos PPTM, seguido de bloqueio; a bupivacaína (S75-R25) produziu diminuição seguida de bloqueio. CONCLUSÕES: Os anestésicos locais potencializaram o bloqueio neuromuscular causado pelo rocurônio. Os resultados mostraram ação pré-sináptica e póssináptica.

Palavras-chave

ANESTÉSICOS, Local, ANESTÉSICOS, Local, ANIMAIS, BLOQUEADORES NEUROMUSCULARES, Não despolarizantes

Abstract

BACKGROUND AND OBJECTIVES: The effects of local anesthetics (LA) on neuromuscular transmission and their influence on the neuromuscular blockade produced by competitive neuromuscular blockers have not been fully investigated. The objective of this study was to evaluate, in vitro, the effects of lidocaine and 50% enantiomeric excess bupivacaine (S75-R25) on the neuromuscular blockade produced by rocuronium. METHODS: The rats were divided in five groups (n = 5) according to the drug used: isolated lidocaine, bupivacaine (S75-R25), or rocuronium (groups I, II, and II); and rocuronium in preparations previously exposed to LAs (groups IV and V). The concentrations used were as follows: 20 µg.mL-1, 5 µg.mL-1, and 4 µg.mL-1 of lidocaine, bupivacaine (S75-R25), and rocuronium, respectively. The following parameters were evaluated: 1) the strength of muscular contraction of the diaphragm to indirect electrical stimulations, before and 60 minutes after the isolated addition of the LAs and rocuronium, and the association AL-rocuronium; and 2) the effects of LAs on membrane potential (MP) and miniature end-plate potentials (MEPP). The effect of LAs on muscle contraction in response to acetylcholine was evaluated in chick biventer cervicis preparations. RESULTS: Isolated lidocaine and bupivacaine (S75-R25) did not change the muscular response and the levels of MPs. In preparations exposed to LAs, rocuroniuminduced blockade was significantly greater than that produced by rocuronium alone. In chick biventer cervicis preparations, lidocaine and bupivacaine (S75R25) decreased contraction in response to acetylcholine. Lidocaine increased the frequency of MEPPs, which was followed by the blockade; bupivacaine (S75R25) caused a reduction in MEPPs followed by blockade. CONCLUSIONS: Local anesthetics caused a potentiation of the neuromuscular blockade produced by rocuronium. The results showed pre- and post-synaptic effects.

Keywords

ANESTHETICS, Local, ANESTHETICS, Local, ANIMALS, NEUROMUSCULAR BLOCKERS, Non-depolarizing

References

Toft P, Kirkegaard Nielsen H, Severinsen I. Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade. Acta Anaesthesiol Scand. 1990;34:649-652.

Taivainen T, Meretoja OA, Rosenberg PH. The effect of epidural bupivacaine on vecuronium-induced neuromuscular blockade in children. Acta Anaesthesiol Scand. 1994;38:453-456.

Haywood PT, Divekar N, Karalliedde LD. Concurrent medication and the neuromuscular junction. Eur J Anaesthesiol. 1999;16:77-91.

Nonaka A, Sugawara T, Suzuki S. Pretreatment with lidocaine accelerates onset of vecuronium-induced neuromuscular blockade. Masui. 2002;51:880-883.

Munakata K, Suzuki T, Watanabe N. Influence of epidural lidocaine injection on vecuronium-induced neuromuscular blockade. Masui. 2004;53:1377-1380.

Cardoso LSM, Martins CR, Tardelli MA. Efeitos da lidocaína por via venosa sobre a farmacodinâmica do rocurônio. Rev Bras Anestesiol. 2005;55:371-380.

Loyola YCS, Braga AFA, Potério GMB. Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: Estudo em Preparação Nervo Frênico-Diafragma de Rato. Rev Bras Anestesiol. 2006;56:147-156.

Braga AFA, Munoz DC, Braga FS. Influence of stimulus frequency on blockade induced by pancuronium and rocuronium: study on rats phrenic nerve-diaphragm preparation. Acta Cir Bras. 2007;22:446-450.

Martins TD, Loyola YCS, Braga AFA. Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular. Rev Bras Anestesiol. 2007;57:74-82.

Suzuki T, Mizutani H, Ishikawa K. Epidurally administered mepivacaine delays recovery of train-of-four ratio from vecuronium-induced neuromuscular block. Br J Anaesth. 2007;99:721-725.

Braga AD, Barcelos CC, Braga FS. Phenobarbital influence on neuromuscular block produced by rocuronium in rats. Acta Cir Bras. 2008;23:343-347.

Yorukoglu D, Asik Y, Okten F. Rocuronium combined with i.v. lidocaine for rapid tracheal intubation. Acta Anaesthesiol Scand. 2003;47:583-587.

Bulbring E. Observation on the isolated phyrenic nerve-diaphragm preparation of the rat. Br J Pharmacol. 1946;1:38-61.

Ginsborg BL, Warriner J. The isolated chick biventer cervicis nerve-muscle preparation. Br J Pharmacol Chemother. 1960;15:410-411.

Ferez D, Machado RC. Disritmias Cardíacas e Antidisrítmicos. Tratado de Anestesiologia - SAESP. 2007:615-654.

Carpenter RL, Mulroy MF. Edrophonium antagonizes combined lidocaine-pacuronium and verapamil-pancuronium neuromuscular blockade in cats. Anesthesiology. 1986;65:506-510.

Fontana MD, Vital Brazil O. Mecanismo da potencialização causada pela quinidina e procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina. Ciênc Cult. 1973;25.

Hirst GD. On the neuromuscular paralysis produced by procaine. Br J Pharmacol. 1971;41:94-104.

Matthews EK, Quilliam JP. Effects of central depressant drugs upon acetylcholine release. Br J Pharmacol Chemother. 1964;22:415-440.

Usubiaga JE, Standaert F. The effects of local anesthetics on motor nerve terminals. J Pharmacol Exp Ther. 1968;159:353-361.

Sine SM, Taylor P. Local anesthetics and histrionicotoxin are allosteric inhibitors of the acetylcholine receptor. J Biol Chem. 1982;257:8106-8114.

Neher E, Steinback JH. Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol (London). 1978;277:153-176.

Ruff RL. The kinetics of local anesthetic blockade of end-plate channels. Biophys J. 1982;37:625-631.

Steinbach AB. Alteration of xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. J Gen Physiol. 1968;52:144-161.

Ragsdale DS, Avoli M. Sodium channels as molecular targets for antiepileptic drugs. Brain Res Rev. 1998;26:16-28.

Li HL, Galue A, Meadows L. A molecular basis for the different local anesthetic affinities of resting versus open and inactivated states of the sodium channel. Mol Pharmacol. 1999;55:134-141.

Mizogami M, Tsuchiya H, Harada J. Membrane effects of ropivacaine compared with those of bupivacaine and mepivacaine. Fundam Clin Pharmacol. 2002;16:325-330.

de Paula E, Schreier S. Molecular and physicochemical aspects of local anesthetic-membrane interaction. Braz J Med Biol Res. 1996;29:877-894.

Schreier S, Malheiros SVP, de Paula E. Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects. Biochim Biophys Acta. 2000;1508:210-234.

Fraceto LF, De Paula E. Interação de anestésicos locais com lipossomos determinada por espectroscopia de infravermelho. Rev Ciênc Farm Básica Apl. 2006;27:27-35.

Barrett JC, Harvey AL. Effects of the venom of the green mamba, Dendroaspis angusticeps on skeletal muscle and neuromuscular transmission. Br J Pharmacol. 1979;67:199-205.

Miranda FG, Marín JS, Aränó JA. Neurofisiologia de la union neuromuscular. Relajantes Musculares em Anestesia y Terapia Intensiva. 2000:61-70.

Ueta K, Sugimoto M, Suzuki T. In vitro antagonism of recombinant ligand-gated ion-channel receptors by stereospecific enantiomers of bupivacaine. Reg Anesth Pain Med. 2006;31:19-25.

Fatt P, Katz B. Spontaneous subthreshold activity at motor nerve endings. J Physiol. 1952;117:109-128.

5dd58d010e88256255c8fca7 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections