[Efficacy and safety of the benzodiazepine antagonist RO 15-1788].
In a randomized, prospective, double-blind trial we investigated the efficacy and safety of the benzodiazepine antagonist RO 15-1788 in 57 patients undergoing general surgery. Anesthesia was induced and maintained by a combination of Flunitrazepam-Fentanyl-Pancuronium. Inhalation anesthetics were excluded from the study. After reversal of any residual relaxant effect we titrated RO 15-1788 or placebo by repeated i.v. administration of 0.1 mg (= 1.0 ml) up to a maximum dosage of 1.0 mg or to a definite arousal reaction. Before as well as 5, 10, 15, 30, 60, and 120 min after injection of the trial substance we evaluated efficacy (sedation, comprehension and collaboration, orientation in time and space), presence of anterograde amnesia, side-effects, hemodynamics, and subjective patient assessment by a point scale. RO 15-1788 significantly improved the level of consciousness (P less than 0.005) at a dosage of 0.59 +/- 0.29 mg at 5, 15, 30, and 60 min after administration as well as orientation in time and space (P less than 0.005) after 30 min. There was significantly less anterograde amnesia (P less than 0.005) after 15, 30, and 60 min. Symptoms of a benzodiazepine rebound effect after 120 min indicate a short half-life time of RO 15-1788. We did not observe any hemodynamic side effects. Local tolerance was good. Side effects in terms of nausea (1 case), vomiting (4), euphoria or dysphoria (2), benign cardiac arrhythmias (1) or a state of excitation (1) occurred several times after RO 15-1788 as well as after placebo (nausea 2, vomiting 6, muscular tremor 1). Our results indicate the efficacy and safety of RO 15-1788.
D000328:Adult; D000762:Anesthesia Recovery Period; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000009:adverse effects / Q000494:pharmacology*; D005445:Flunitrazepam / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D011897:Random Allocation
D001569:Benzodiazepines; D005442:Flumazenil; D005445:Flunitrazepam
Effektivität und Sicherheit des Benzodiazepin-Antagonisten RO 15-1788.