Effects of Edrophonium and/or Pseudocholinesterase for the Reversal of Mivacurium-Induced Paralysis in vitro

Abstract

Background: Mivacurium is a nondepolarizing neuromuscular blocking agent hydrolyzed by pseudocholinesterase. Anticholinesterase used in the reversal of mivacurium-induced muscle relaxation may also inhibit plasma pseudocholinesterase, and delay hydrolysis of mivacurium. In this study, the effects of edrophonium and/or bovine pseudocholinesterase (BpChE) in the reversal of mivacurium were investigated with the rat phrenic nerve-diaphragm preparation. Methods: Fifty Sprague-Dawley rats (150 - 200 g) were randomly allocated into 10 groups based on the dosage of edrophonium and BpChE. Each animal was anesthetized with thiopental sodium (40 mg/kg J.P.). The phrenic nerve-diaphragm was dissected and mounted in a bath containing an oxygenated Krebs' solution at 32. The phrenic nerve was stimulated at supramaximal intensity and the single twitch responses and train of four (TOF) ratio were measured. After stabilization of the twitch responses, mivacurium (1 /ml) was administered incrementally to obtain more than 95% twitch inhibition. Reversal of the mivacurium-induced block by edrophonium (0.01, 0.1, 1, or 10 ,/ml) and/or BpChE (0.1 u, or 1.0 u/ml) were tested. A single twitch height more than 75% of the baseline value was considered an adequate reversal. Results: Mivacurium-induced paralysis was recovered more effectively by BpChE 1.0 u/ml than the other groups. Edrophonium improved a single twitch in a dose dependent manner. Conclusions: Mivacurium-induced paralysis can be more effectively reversed by BpChE than edrophonium. Inhibition of pseudocholinesterase was not observed by increasing the dose of edrophonium.