Sepsis attenuates the intensity of the neuromuscular blocking effect of d-tubocurarine and the antagonistic actions of neostigmine and edrophonium accompanying depression of muscle contractility of the diaphragm.

Abstract

Prolonged effects of non-depolarizing muscle relaxants in septic patients have been reported, although the influence of sepsis on neuromuscular transmission has not yet been clarified satisfactorily. These studies were intended to elucidate the influence of sepsis on neuromuscular transmission and on the action of drugs being utilized for regulation of muscle tone (a neuromuscular blocker and anti-cholinesterase (anti-ChE) drugs). The effect of d-tubocurarine (dTc) on neuromuscular transmission and the antagonistic action of anti-ChE drugs (neostigmine and edrophonium) on dTc-induced twitch depression were estimated using sham control and septic rat nerve-hemidiaphragm preparations in vitro. Isometric twitch tension elicited by indirect (phrenic nerve) or direct (muscle) stimulation at 0.1 Hz was evaluated. Sepsis induced by panperitonitis attenuated the twitch tension elicited by indirect or direct stimulation (P < 0.01) without obvious morphological inflammatory damage to the diaphragm. dTc dose-dependently decreased twitch tension elicited by indirect stimulation (P < 0.01) less intensely in the septic group than in the sham group (P < 0.01). The antagonistic actions of the anti-ChE drugs on dTc (1 microM)-induced twitch depression were less intense in the septic group (P < 0.01 or 0.05). These results demonstrate that sepsis in the acute phase attenuates the effects of a neuromuscular blocker and anti-ChE drugs and depresses muscle contractility simultaneously.