Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study

Angélica de Fátima Braga; Vanessa Henriques Carvalho; Franklin Sarmento Braga; Gloria Maria Braga Potério; Filipe Nadir Caparica Santos

doi:10.1016/j.bjane.2013.10.022

Scientific Article

Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study

Efeito da associação ropivacaina-pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4-aminopiridina na reversão do bloqueio: estudo experimental

Angélica de Fátima Braga; Vanessa Henriques Carvalho; Franklin Sarmento Braga; Gloria Maria Braga Potério; Filipe Nadir Caparica Santos

http://dx.doi.org/10.1016/j.bjane.2013.10.022 Braz J Anesthesiol, vol.65, n2, p.136-140, 2015

PDF

Downloads: 0

Abstract

BACKGROUND AND OBJECTIVES: The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. METHODS: Rats were divided into groups (n = 5) according to the study drug: ropivacaine (5 µg mL-1); pancuronium (2 µg mL-1); ropivacaine + pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2 µg mL-1 and 20 µg mL-1, respectively. The effects of ropivacaine on membrane potential and miniature endplate potential, the amplitude of diaphragm responses before and 60 min after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine), and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. RESULTS: Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature endplate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. CONCLUSIONS: Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine.

Keywords

Local anesthetics, ropivacaine, Neuromuscular blockers, Nondepolarising, pancuronium, Animals, rats

Resumo

JUSTIFICATIVA E OBJETIVOS: Os efeitos dos anestésicos locais na junção neuromuscular e sua influência no bloqueio produzido por bloqueadores neuromusculares não-despolarizantes é ainda alvo de pouca investigação, no entanto esta interação tem sido descrita em trabalhos experimentais e em humanos. O objetivo deste estudo foi avaliar in vitro, a interação da ropivacaína com o pancurônio, a influência na transmissão e bloqueio neuromuscular e a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio. MÉTODO: Ratos foram distribuídos em grupos (n = 5) de acordo com o fármaco estudado: ropivacaína (5 µg mL-1); pancurônio (2 µg mL-1); ropivacaína + pancurônio. A neostigmina e a 4-aminopiridina foram usadas nas concentrações de 2 µg mL-1 e 20 µg.mL-1, respectivamente. Avaliou-se: 1) efeitos da ropivacaína sobre o potencial de membrana e potenciais de placa terminal em miniatura; 2) a amplitude das respostas do diafragma antes e 60 minutos após a adição da ropivacaína; o grau de bloqueio neuromuscular com o pancurônio e com a associação pancurônio - ropivacaína; 3) a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio neuromuscular. RESULTADOS: A ropivacaína não alterou a amplitude das respostas musculares, os potenciais de membrana, mas diminuiu a frequência e a amplitude dos potenciais de placa terminal em miniatura. O bloqueio produzido pelo pancurônio foi potencializado pela ropivacaína, e parcial e totalmente revertido pela neostigmina e 4-aminopiridina, respectivamente. CONCLUSÕES: A ropivacaína potencializou o bloqueio neuromuscular produzido pelo pancurônio. O antagonismo completo com a 4-aminopiridina sugere ação pré-sináptica da ropivacaína.

Palavras-chave

Anestésicos Locais, Ropivacaina, Bloqueadores neuromusculares, Não despolarizantes, Pancurônio, Animais, Ratos

References

Toft P, Kirkegaard Nielsen H, Severinsen I. Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade. Acta Anaesthesiol Scand.. 1990;34:649-52.

Taivainen T, Meretoja OA, Rosenberg PH. The effect of epidural bupivacaine on vecuronium-induced neuromuscular blockade in children. Acta Anesthesiol Scand.. 1994;38:453-6.

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;99:721-5.

Sahin SH, Colak A, Sezer A. Effect of epidural levobupivacaine on recovery from vecuronium-induced neuromuscular block in patients undergoing lower abdominal surgery. Anaesth Intensive Care.. 2011;39:607-10.

Loyola YC, Braga Ade F, Potério GM. Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation. Rev Bras Anestesiol.. 2006;56:147-56.

Braga AF, Carvalho VH, Braga FS. Influence of local anesthetics on the neuromuscular blockade produced by rocuronium: effects of lidocaine and 50% enantiomeric excess bupivacaine on the neuromuscular junction. Rev Bras Anestesiol.. 2009;59:725-34.

Carvalho VH, Braga AF, Braga FS. The influence of lidocaine and racemic bupivacaine on neuromuscular blockade produced by rocuronium. A study in rat phrenic nerve-diaphragm preparation. Acta Cir Bras.. 2009;24:211-5.

Covino BG. Pharmacology of local anaesthetic agents. Br J Anaesth.. 1986;58:701-16.

McLure HA, Rubin AP. Review of local anaesthetic agents. Minerva Anestesiol.. 2005;71:59-74.

Stoelting RK, Hillier SC. Neuromuscular blocking drugs. Pharmacology & phisiology in anesthetic practice. 2006:p. 208-50.

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

Cardoso LSM, Martins CR, Tardelli MA. Efeitos da lidocaína por via venosa sobre a farmacodinâmica do rocurônio. Rev Bras Anestesiol.. 2005;55:371-80.

Matsuo S, Rao DB, Chaudry I. Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. Anesth Analg.. 1978;57:580-7.

Barash PG, Cullen BF, Stoelting RK. Anesthetic agents, adjuvants, and drug interaction. Clinical anesthesia. 2009:514-5.

Carpenter RL, Mulroy MF. Edrophonium antagonize combined lidocaine-pacuronium and verapamil-pancuronium neuromuscular blockade in cats. Anesthesiology.. 1986;65:506-10.

Neher E, Steinbach JH. Local anesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol.. 1990;277:153-76.

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

Suzuki T, Nagai H, Katsumata N. Investigation of fading responses induced by non-depolarising muscle relaxants in the evoked EMG of the gastrocnemius muscle of the cat. Acta Anaesthesiol Scand.. 1999;43:658-62.

Usubiaga JE, Wikinski JA, Morales RL. Interaction of intravenously administered procaine, lidocaine and succinylcholine in anesthetized subjects. Anesth Analg.. 1967;46:39-45.

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;174:277-82.

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.

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;44:303-9.

Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study

Efeito da associação ropivacaina-pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4-aminopiridina na reversão do bloqueio: estudo experimental

Angélica de Fátima Braga; Vanessa Henriques Carvalho; Franklin Sarmento Braga; Gloria Maria Braga Potério; Filipe Nadir Caparica Santos

Abstract

Keywords

Resumo

Palavras-chave

References

Links

Share

Braz J Anesthesiol