SELF-ANTAGONISM: A POSSIBLE MECHANISM OF TACHYPHYLAXIS IN SUXAMETHONIUM-INDUCED NEUROMUSCULAR BLOCK IN MAN

Twelve adults receiving halothane-nitrous oxide anaesthesiafor elective surgery were investigated during suxamethonium-inducedneuromuscular block, using the train-of-four twitch for measurementof both the degree of block and the magnitude of fade (decreasein fourth-to-first ratio). The residual neuromuscular blockresulting from prolonged exposure to suxamethonium could beantagonized by bolus injections of suxamethonium itself, indoses which increased the block in Phase I. When self-antagonismwas demonstrated, larger doses were necessary to increase theresidual block, but only after overcoming the self-antagonizingeffect. A biphasic response, first antagonizing then increasingthe block, was observed following injection of a single bolusof suxamethonium. The self-antagonizing effect was more obviousin the fourth twitch of the train-of-four, resulting in a markeddecrease in train-of-four fade (increase in train-of-four ratio).It was concluded that self-antagonism may be an important causeof tachyphylaxis in suxamethonium-induced neuromuscular blockin man.