Interaction of Muscle Relaxants and Local Anesthetics at the Neuromuscular Junction

Abstract

The effects on neuromuscular (NM) function of combinations of relaxants (d-tubocurarine, pancuronium, and succinylcholine) and local anesthetics (cocaine, procaine, lidocaine, etidocaine, and a quaternized derivative of procaine, procaine methobromide) were investigated using the rat's phrenic nerve--hemidiaphragm preparation. Combinations of ineffective concentrations of NM blocking agents with ineffective concentrations of local anesthetics caused a greater than 90% NM block. Preliminary administration of ineffective concentrations of local anesthetics significantly ( p less than 0.001) decreased the ED50 of NM blocking agents. The administration of ineffective concentrations of NM blocking agents caused a similar decrease of the ED50 of local anesthetics. Concentrations of d-tubocurarine and pancuronium which alone produced partial NM block had additive effects. These findings suggest that the interaction of NM blocking agents and local anesthetics consists of true potentiation caused by the different sites of action of the two types of compounds at the NM junction. The degree of potentiation may be enough to cause clinically significant NM block in patients who at the same time receive high enough doses of both agents. In vitro the NM block caused by the combinations of local anesthetics and NM blocking agents can be reversed by 4-aminopyridine.

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

“…5---7,11,13,16---19 A concentração de ropivacaína empregada foi estabelecida em projeto piloto e determinada a partir de dados apresentados em estudos realizados em nosso meio, onde foram utilizados outros anestésicos locais amino--amidas com características semelhantes à ropivacaína. 6,7 Matsuo et al, 13 em preparação semelhante à utilizada neste estudo, avaliaram a associação de d-tubocurarina com diferentes anestésicos locais, e observaram que mesmo em concentrações ineficazes, os anestésicos locais potencializaram o bloqueador neuromuscular, evidenciado pela diminuição significativa da ED50. Em relação à influên-cia dos bloqueadores neuromusculares nos efeitos dos anestésicos locais, estes autores também descreveram que concentrações ineficazes de d-tubocurarina causaram similar diminuição da ED50 e aumento na potência dos anestésicos locais.…”

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

“…5---7,11,13,16---19 The ropivacaine concentration used was established in a pilot study and determined from data presented in studies carried out in Brazil, where other amino-amide local anesthetics with similar characteristics to ropivacaine were used. 6,7 Matsuo et al 13 evaluated, in preparation similar to that used in this study, the association of d-tubocurarine with different local anesthetics and found that, even in ineffective concentrations, local anesthetics potentiated neuromuscular blocker, as evidenced by significant decrease in the ED50. Regarding the influence of neuromuscular blockers on the effects local anesthetics, these authors also reported that ineffective concentrations of d-tubocurarine caused a similar decrease of ED50 and increase of local anesthetic potency.…”

Efecto de la asociación ropivacaína-pancuronio en la transmisión neuromuscular. Eficacia de la neostigmina y 4-aminopiridina en la reversión del bloqueo. Estudio experimental

“…Matsuo et al 13 , en una preparación similar a la utilizada en este estudio, calcularon la asociación de d-tubocurarina con diferentes anestésicos locales, y observaron que incluso en concentraciones ineficaces los anestésicos locales potenciaron el bloqueante neuromuscular, evidenciado por la disminución significativa de la ED50. Con relación a la influencia de los bloqueantes neuromusculares en los efectos de los anestésicos locales, esos autores también describieron que concentraciones ineficaces de d-tubocurarina causaron una disminución similar de la ED50 y el aumento en la potencia de los anestésicos locales.…”