Interaction of Midazolam With Two Non-Depolarizing Neuromuscular Blocking Drugs in the Rat in Vivo Sciatic Nerve-Tibialis Anterior Muscle Preparation

Abstract

Studies of the possible interactions between the water-soluble benzodiazepine, midazolam, and two non-depolarizing neuromuscular blocking drugs, vecuronium and tubocurarine, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. Midazolam 0.5 and 5 mg kg-1 caused 17% and 34% depression of the twitch height, respectively, once a steady-state blockade of the twitch height had been induced by vecuronium. The potentiation of the tubocurarine steady state blockade by midazolam 5 mg kg-1 was quantitatively equal to that of vecuronium, but was slower in onset. The buffer solvent of midazolam 5 mg kg-1 did not change the steady-state blockade of vecuronium. Midazolam 5 mg kg-1 caused a shift to the left of the cumulative dose-response curves of vecuronium.

Midazolam does not potentiate the effect of vecuronium in patients

“…However, Driessen and co-workers observed that midazolam significantly prolonged the duration of vecuronium blockade in patients by 45% compared with diazepam, though insignificantly when compared with thiopentone (4). This indicates that the benzodiazepines may have differential effects on neuromuscular blockade in patients, as demonstrated in animal studies by the same workers (5,8). These investigators showed that midazolam enhances vecuronium-induced blockade of the tibialis anterior muscle in the rat.…”

“…These investigators showed that midazolam enhances vecuronium-induced blockade of the tibialis anterior muscle in the rat. Using 50% steadystate neuromuscular blockade, midazolam 0.5 and 5 mg kg-' caused additional 17% and 34% maximum depression of twitch height, respectively (5). There may be several explanations of the apparent discrepancy between findings in animals and in patients.…”

“…However, the new benzodiazepine, midazolam, appears to potentiate the erect of vecuronium. Driessen and co-workers demonstrated marked increase in vecuronium-induced block after midazolam in the rat (5). In patients, these investigators found that vecuronium had significantly longer duration of action after midazolam than after diazepam; however, compared with thiopentone-induction the increase in duration after midazolam was 25%, without reaching statistical significance (4).…”

The Effect of Midazolam Pre-Medication on Rocuronium-Induced Neuromuscular Blockade

“…3,4 Midazolam significantly enhanced a constant 50% neuromuscular block produced by infusion of vecuronium or pancuronium in cats. 3 By using an in vivo sciatic nerve-tibialis anterior muscle preparation of the rat, midazolam depressed the twitch height after a steady-state blockade produced by vecuronium or tubocurarine.…”

“…3 By using an in vivo sciatic nerve-tibialis anterior muscle preparation of the rat, midazolam depressed the twitch height after a steady-state blockade produced by vecuronium or tubocurarine. 4 In humans, the interaction between benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and nondepolarizing neuromuscular blocking agents (vecuronium and atracurium) has been investigated with the administration of these drugs during the induction of anaesthesia. 5,6 Driessen et al 5 reported that benzodiazepines did not cause significant potentiation of the neuromuscular blocking agents.…”