Double-Blind Study of the Reversal of Midazolam-Supplemented General Anaesthesia With Ro 15–1788 †

Abstract

The actions and side effects of the benzodiazepine antagonist Ro 15-1788 were evaluated in a randomized double-blind clinical study in which midazolam was used as an anaesthetic agent. Sixty women who underwent laparoscopy were treated with Ro 15-1788 or with placebo after the surgical procedure. Ro 15-1788 reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, co-operative, oriented and had good recall of events after awakening. The effects were statistically better than placebo for up to 30 min after administration. Arterial pressure and heart rate remained stable and there were no significant side effects. The availability of Ro 15-1788 allows effective reversal of midazolam when this is used during general anaesthesia.

Flumazenil reduces the duration of thiopentone but not of propofol anaesthesia in humans

“…J-3 Alon et al found a reduction in sedation and improvement in orientation and comprehension in women that received the specific antagonist after midazolam anaesthesia. 4 Similar results have been reported by other investigators. Nilsson et al reported that flumazenil administration improved performance after general anaesthesia induced with midazolam and alfentanyl but resedation occurred.…”

The use of flumazenil in prevention of Diazepam dependence in the rat

“…So far the clinical use of flumazenil has been restricted to the reversal of benzodiazepine overdose (O'Sullivan and Wade, 1987) and the reversal of benzodiazepine-induced anaesthesia (Alon et al, 1987). It may also be of clinical value in the prevention of benzodiazepine dependence, although in this case its use may carry the risk of the precipitation of seizures.…”

Rapid determination of the benzodiazepine antagonist flumazenil, Ro 15‐1788, by high performance liquid chromatography

“…The imidazobenzodiazepine Flumazenil or Ro 15-1788 (l), is a benzodiazepine antagonist (Hunkeler et al,1 1981; Mohler and Richards, 1981;Jensen et al, 1987), used following general anaesthesia or sedation induced by benzodiazepines (Alon et al, 1987;Geller et al, 1986;Darragh et al, 1981) and i n benzodiazepine overdosage or intoxication (Amrein et al, 1987). A few methods for t h e quantification o f this c o m p o u n d in biological fluids have been described, involving gas/liquid chromatography ( G L C ) with nitrogen/phosphorus detection (Abernethy et al, 1983) and high performance liquid chromatography ( H P L C ) (Timm and Zell, 1983).…”