Levänen J, Mäkelä M L, Scheinin H
Department of Anesthesiology, Central Military Hospital, Helsinki, Finland.
Anesthesiology. 1995 May;82(5):1117-25. doi: 10.1097/00000542-199505000-00005.
Dexmedetomidine is a new potent and highly selective alpha 2-adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulatory effects and attenuating the adverse central nervous system effects of ketamine.
A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micrograms/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according to clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.
Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra- and postoperative bradycardia.
These results suggest that premedication with 2.5 micrograms/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.
右美托咪定是一种新型强效且高度选择性的α2肾上腺素能受体激动剂,具有镇静催眠和麻醉辅助特性。因其具有交感神经抑制活性,可能在平衡氯胺酮的心脏兴奋作用及减轻其对中枢神经系统的不良影响方面发挥作用。
采用双盲、随机、平行对照研究设计,纳入40例美国麻醉医师协会(ASA)身体状况为1级、计划在氯胺酮麻醉下行择期浅表手术的志愿者。在麻醉诱导前45分钟,20例肌肉注射右美托咪定(2.5微克/千克),另20例肌肉注射咪达唑仑(0.07毫克/千克)。静脉注射2毫克/千克氯胺酮诱导麻醉,并用维库溴铵实现肌肉松弛。气管插管后,根据临床和心血管标准,用氧化亚氮/氧气(2:1)及额外静脉注射1毫克/千克氯胺酮维持麻醉。分别通过增加晶体液静脉输注速率和静脉注射阿托品治疗低血压和心动过缓。比较两组的镇静和抗焦虑特性、术中和术后药物需求、精神运动和认知功能损害以及心血管效应。
肌肉注射后,右美托咪定和咪达唑仑的镇静和抗焦虑效果相当,但右美托咪定引起的术前精神运动损害和顺行性遗忘明显少于咪达唑仑。与咪达唑仑相比,右美托咪定减少了术中氯胺酮的用量,在减轻氯胺酮引起的中枢神经系统不良反应方面更有效。总体而言,右美托咪定在减轻插管时的血流动力学反应和氯胺酮的心脏兴奋作用方面也优于咪达唑仑,但增加了术中和术后心动过缓的发生率。
这些结果表明,术前使用2.5微克/千克右美托咪定可有效减轻氯胺酮的心脏兴奋作用和麻醉后谵妄效应。然而,鉴于其有导致心动过缓的倾向,应考虑常规使用抗胆碱能药物。