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

Abstract

Background and objectives: The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still underinvestigated; 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 g mL −1 ); pancuronium (2 g mL −1 ); ropivacaine + pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2 g mL −1 and 20 g 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.Effect of ropivacaine-pancuronium on neuromuscular transmission 137 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. Efeito da associação ropivacaina-pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4-aminopiridina na reversão do bloqueio: estudo experimentalResumo 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 g mL −1 ); pancurônio (2 g mL −1 ); ropivacaína + pancurônio. A neostigmina e a 4-aminopiridina foram usadas nas concentrações de 2 g mL −1 e 20 g 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 rop...

Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats

“…Presynaptic and postsynaptic events have been described [1][2][3][4]9,10 . To identify the probable mechanism of interaction and potentiation of the block produced by pancuronium, in a preparation previously exposed to levobupivacaine, electrophysiological studies were conducted.…”

“…To explain the interaction between local anesthetics and neuromuscular blocking agents, several mechanisms have been described, including a presynaptic action by inhibition of acetylcholine release, a postsynaptic action due to stabilization of the postjunctional membrane, and interference with the phenomenon of excitation-contraction coupling of the muscle fiber [1][2][3][4] . Although only high concentrations of local anesthetics can produce neuromuscular blockade, the interaction between these drugs and nondepolarizing neuromuscular blocking agents in particular is relevant in clinical practice, when both groups of drugs are used simultaneously and careful patient monitoring is required.…”

“…Pancuronium is a longacting aminosteroid, nondepolarizing neuromuscular blocking agent, used in prolonged surgeries and in intensive care units 1 .…”

Influence of different local anesthetics on atracurium neuromuscular blockade on rats☆

“…For calculating the sample size we used the results of a previous experimental study 15 in which the degree of neuromuscular blockade produced by pancuronium (93.8%) was significantly higher in rats previously exposed to ropivacaine, compared to those unexposed to AL (54.9%), or a difference of 38.9%. Thus, to calculate the sample size, we used the degree of motor blockade as the variable.…”