The Effect of Phenytoin on Rocuronium-Induced Neuromuscular Block in the Rat Phrenic Nerve-Hemidiaphragm Preparation

Abstract

Anticonvulsant therapy alters the action of nondepolarizing muscle relaxants. We determined the effects of acute and chronic administration of phenytoin on rocuronium-induced neuromuscular block using the rat phrenic nerve-hemidiaphragm preparation. Rats were divided into 3 groups: a saline control group (n = 10), an acute phenytoin-treated group (n = 30), and a chronic phenytoin-pretreated group (n = 30). Phrenic nerve-hemidiaphragm was dissected, mounted in a bath containing oxygenated Krebs solution, and the nerve was stimulated at supramaximal intensity. Single twitch responses were recorded by physiogram. In the acute phenytoin-treated group, acute effects of phenytoin were determined based on the phenytoin concentration of 1, 10, or 100 microg/mL in the bath. The chronic effects of phenytoin were determined using phrenic nerve-diaphragms from rats pretreated with phenytoin (50 mg/kg/d) for 1, 7, or 28 days. In rats with phenytoin 100 microg/mL in the bath, all concentrations of rocuronium produced twitch depression significantly different from those of other groups (P < 0.05), and the concentration-response curve shifted to the left. In rats with phenytoin 10 microg/mL in the bath, the effective concentrations for 50%, 90%, and 95% twitch depression values were significantly different from those of the control group (P < 0.05). In chronically (28 days) phenytoin-pretreated rats, the concentration-response curve significantly shifted to the right (P < 0.05). These findings show that acute administration of phenytoin augmented the neuromuscular blocking effects of rocuronium, whereas chronic phenytoin treatment causes resistance to the neuromuscular blocking effects of rocuronium in target organs.