Antagonism of benzodiazepine-fentanyl anaesthesia with flumazenil

The specific benzodiazepine antagonist flumazenil (Ro 15-1788) (Ro) was given in a double-blind study to 40 adult orthopaedic patients in order to determine if it shortens the immediate recovery time after benzodiazepine-fentanyl anaesthesia. On the evening before operation the patients were premedicated orally with 1-2 mg of flunitrazepam and 30 min before the induction of anaesthesia with 7.5 mg midazolam. Induction of anaesthesia was carried out with flunitrazepam 0.03-0.04 mg.kg-1 and fentanyl 0.1 mg IV. Anaesthesia was maintained with fentanyl (5.9 microgram.kg-1.h-1) and nitrous oxide. After the reversal of muscle relaxation, 20 patients received a placebo and 20 patients Ro, as boluses up to 10 ml, until the effect of awakening was noticed. The dose of Ro (0.1 mg.ml-1) required was 6.8 +/- 2.9 micrograms.kg-1 and that of placebo 10 +/- 0 ml. Patients given Ro woke up faster than patients given placebo. Ro patients were more alert than patients given placebo until 120 min after the injection or the test drug. After this patients in both groups behaved similarly. Eight patients given Ro and one given placebo showed some mild adverse reaction for 5-60 min after the administration of Ro or placebo (e.g., nausea, shivering). This study indicates that flumazenil speeds up awakening after benzodiazepine-fentanyl anaesthesia.