Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: estudo em preparação nervo frênico-diafragma de rato

Yolanda Christina S. Loyola; Angélica de Fátima de Assunção Braga; Glória Maria Braga Potério; Silmara Rodrigues de Sousa; Samanta Cristina Antoniassi Fernandes; Franklin S. da Silva Braga

doi:10.1590/S0034-70942006000200006

Scientific Article

Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: estudo em preparação nervo frênico-diafragma de rato

Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation

Yolanda Christina S. Loyola; Angélica de Fátima de Assunção Braga; Glória Maria Braga Potério; Silmara Rodrigues de Sousa; Samanta Cristina Antoniassi Fernandes; Franklin S. da Silva Braga

http://dx.doi.org/10.1590/S0034-70942006000200006 Braz J Anesthesiol, vol.56, n2, p.147-156, 2006

PDF

Downloads: 0

Resumo

JUSTIFICATIVA E OBJETIVOS: O mecanismo de ação dos anestésicos locais (AL) na junção neuromuscular motivou a realização de vários estudos. Em baixas doses eles não interferem na transmissão neuromuscular, mas em altas doses podem comprometer a transmissão neuromuscular e potencializar os efeitos de bloqueadores neuromusculares. O objetivo do estudo foi avaliar, em diafragma de rato, a interação da lidocaína com o rocurônio através da influência no grau de bloqueio neuromuscular. MÉTODO: Foram utilizados ratos, com peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica descrita por Bulbring. Formaram-se grupos (n = 5) de acordo com a droga em estudo: lidocaína - 20 µg.mL-1 (Grupo I); rocurônio - 4 µg.mL-1 (Grupo II) e rocurônio - 4 µg.mL-1 com lidocaína - 20 µg.mL-1 (Grupo III). Foram avaliadas: 1) a amplitude das respostas do músculo diafragma à estimulação indireta, antes e 60 minutos após a adição da lidocaína e do bloqueador neuromuscular; 2) os potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM); 3) a eficácia da neostigmina e 4-aminopiridina na reversão do bloqueio neuromuscular. RESULTADOS: A lidocaína isoladamente não alterou a amplitude das respostas musculares. Com o uso prévio de lidocaína o bloqueio neuromuscular do rocurônio foi de 82,8% ± 1,91%, com diferença significativa (p = 0,0079) em relação ao grupo com rocurônio isolado (57,8% ± 1,9%). O bloqueio foi parcial e totalmente revertido pela neostigmina e 4-aminopiridina, respectivamente. A lidocaína não alterou o potencial de membrana e ocasionou aumento inicial na freqüência dos PPTM, seguido de bloqueio. CONCLUSÕES: A lidocaína potencializou o bloqueio neuromuscular produzido pelo rocurônio. As alterações do PPTM identificam ação pré-sináptica. O antagonismo completo da 4-aminopiridina sugere componente pré-sináptico, idéia que é suportada pelo antagonismo parcial pela neostigmina.

Palavras-chave

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

Abstract

BACKGROUND AND OBJECTIVES: The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS: Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II), and rocuronium - 4 µg.mL-1 with lidocaine - 20 µg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS: When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% ± 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% ± 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS: Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.

Keywords

ANESTHETICS, Local, ANIMALS, NEUROMUSCULAR BLOCKERS, Nondepolarizing

References

Donati F. Onset of action of relaxants. Can J Anesth. 1988;35:S52-S58.

Telivuo L, Katz RL. The effects of modern intravenous local analgesics on respiration during partial neuromuscular block in man. Anesthesia. 1970;25:30-35.

Hamaya Y, Dohi S. Differences in cardiovascular response to air-way stimulation at different sites and blockade of the response by lidocaine. Anesthesiology. 2000;93:95-103.

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

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

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

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

Engbaek J, Viby-Mogensen J. Can rocuronium replace succinylcholine in a rapid-sequence induction of anesthesia?. Acta Anesthesiol Scand. 1999;43:1-3.

Andrews JI, Kumar N, van den Brom RH. A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anesthesia along with propofol. Acta Anesthesiol Scand. 1999;43:4-8.

Matsuo S, Rao DB, Chaudry I. Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. Anesth Analg. 1978;57:580-587.

Usubiaga JE, Wikinski JA, Morales RL. Interaction of intravenously administered procaine, lidocaine and succinylcholine in anesthetized subjects. Anesth Analg. 1967;46.

Straughan DW. The action of procaine at the neuromuscular junction. J Pharm Pharmacol. 1971;41:94-104.

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

Neher E, Steinbach JH. Local anesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol. 1978;277:153-176.

Pederneiras SG. Interação de drogas com relaxantes musculares. Rev Bras Anestesiol. 1988;38:63-73.

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

Ellis CH, Wnuck AL, De Beer EJ. Modifying actions of procaine on the myoneural blocking actions of succinylcholine, decamethonium and d-tubocurarine in dogs and cats. Am J Physiol. 1953;174:277-282.

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

Harrah MD, Way WL, Katzung BG. The interaction of d-tubocurarine with antiarrhythmic drugs. Anesthesiology. 1970;33:406-410.

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.

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

Cohen JB, Boyd ND, Shera NS. Interactions of Anesthetics with Nicotinic Postsynaptic Membranes Isolated from Torpedo Electric Tissue. Molecular Mechanisms of Anesthesia. Progress in Anesthesiology. 1980:165-174.

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

Yeh JZ, Oxford GS, Wu CH. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976;16:77-81.

Ulbricht W, Wagner HH. Block of potassium channels of the nodal membrane by 4-aminopyridine and its partial removal on depolarization. Pflugers Arch. 1976;367:77-87.

Brazil OV, Fontana MD, Pavani NJ. Effect of 4-aminopyridine on the postsynaptic action of polymyxin B. Eur J Pharmacol. 1989;159:47-51.

Vital Brazil O, Fontana MD, Pavani NJ. Effect of 4-aminopyridine on end-plate receptor desensitization caused by carbachol. Eur J Pharmacol. 1982;86:199-205.

Harvey AL, Marshall IG. The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle. Naunyn Schmiedebergs Arch Pharmacol. 1977;299:53-60.

Harvey AL, Marshall IG. The actions of three diaminopyridines on the chick biventer cervicis muscle. Eur J Pharmacol. 1977;44:303-309.

Bowman WC, Harvey AL, Marshall IG. The actions of aminopyridines on avian muscle. Naunyn Schmiedebergs Arch Pharmacol. 1977;297:99-103.

Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: estudo em preparação nervo frênico-diafragma de rato

Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation

Yolanda Christina S. Loyola; Angélica de Fátima de Assunção Braga; Glória Maria Braga Potério; Silmara Rodrigues de Sousa; Samanta Cristina Antoniassi Fernandes; Franklin S. da Silva Braga

Resumo

Palavras-chave

Abstract

Keywords

References

Links

Share

Braz J Anesthesiol