Ellmauer S, Müller H, Dick W
Klinik für Anaesthesiologie und Intensivmedizin, Johannes Gutenberg-Universität Mainz.
Anaesthesist. 1988 Jul;37(7):432-9.
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.
在一项随机、前瞻性、双盲试验中，我们研究了苯二氮䓬拮抗剂RO 15 - 1788对57例接受普通外科手术患者的疗效和安全性。麻醉诱导和维持采用氟硝西泮 - 芬太尼 - 泮库溴铵联合用药。吸入性麻醉剂被排除在研究之外。在逆转任何残余的肌松效应后，我们通过静脉重复给药0.1 mg（= 1.0 ml）来滴定RO 15 - 1788或安慰剂，最大剂量为1.0 mg或直至出现明确的清醒反应。在注射试验药物前以及注射后5、10、15、30、60和120分钟，我们通过评分量表评估疗效（镇静、理解和协作能力、时间和空间定向）、顺行性遗忘的存在、副作用、血流动力学以及患者主观评估。RO 15 - 1788在给药后5、15、30和60分钟时，剂量为0.59±0.29 mg时显著改善了意识水平（P＜0.005），给药30分钟后时间和空间定向也显著改善（P＜0.005）。15、30和60分钟后顺行性遗忘明显减少（P＜0.005）。120分钟后出现的苯二氮䓬类药物反跳效应症状表明RO 15 - 1788的半衰期较短。我们未观察到任何血流动力学副作用。局部耐受性良好。RO 15 - 1788给药后以及安慰剂给药后均多次出现恶心（RO 15 - 1788组1例，安慰剂组2例）、呕吐（RO 15 - 1788组4例，安慰剂组6例）、欣快或烦躁不安（RO 15 - 1788组2例）、良性心律失常（RO 15 - 1788组1例）或兴奋状态（RO 15 - 1788组1例，安慰剂组肌肉震颤1例）等副作用。我们的结果表明RO 15 - 1788具有疗效和安全性。
