BACKGROUND The aim of this double-blind, placebo-controlled, single-ascending-dose study was to determine the safety and tolerability of intranasal dexmedetomidine in the elderly. METHODS We randomly assigned 48 surgical patients ≥65 yr of age to receive single intranasal doses of dexmedetomidine or placebo (5:1 ratio) in four sequential dose cohorts: 0.5, 1.0, 1.5, and 2.0 μg kg-1. Each dose cohort comprised two groups of six subjects: a group of subjects using β-blockers and a group not taking β-blockers. Vital signs and sedation depth (Modified Observer's Assessment of Alertness and Sedation [MOAA/S] and bispectral index) were measured for 2 h after administration. Blood samples were taken to determine dexmedetomidine plasma concentrations. RESULTS One subject (1.0 μg kg-1) had acute hypotension requiring ephedrine. Systolic arterial BP decreased >30% in 15 of 40 subjects (37.5%) receiving dexmedetomidine, lasting longer than 5 min in 11 subjects (27.5%). The MAP decreased >30% (>5 min) in 10%, 20%, 50%, and 30% of subjects receiving dexmedetomidine 0.5, 1.0, 1.5, and 2.0 μg kg-1, respectively, irrespective of β-blocker use. HR decreased 10-26%. MOAA/S score ≤3 occurred in 18 (45%) subjects; eight (20%) subjects receiving dexmedetomidine showed no signs of sedation. Tmax was 70 min. Cmax was between 0.15 ng ml-1 (0.5 μg kg-1) and 0.46 ng ml-1 (2.0 μg kg-1). CONCLUSIONS Intranasal dexmedetomidine in elderly subjects had a sedative effect, but caused a high incidence of profound and sustained hypotension irrespective of β-blocker use. The technique is unsuitable for routine clinical use. CLINICAL TRIAL REGISTRATION NTR5513 (The Netherlands Trial Registry 5513).

中文翻译：

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有或没有β受体阻滞剂的老年受试者的鼻内右美托咪定：一项随机双盲单升剂量队列研究。

背景技术这项双盲，安慰剂对照，单剂量研究的目的是确定老年人鼻内右美托咪定的安全性和耐受性。方法我们随机分配48位≥65岁的外科手术患者，分别以0.5、1.0、1.5和2.0μgkg-1的四个剂量依次接受鼻内右美托咪定或安慰剂（比例为5：1）。每个剂量组包括两组，每组六个受试者：一组使用β受体阻滞剂的受试者和一组不使用β受体阻滞剂的受试者。给药后2小时测量生命体征和镇静深度（改良的观察者对机敏性和镇静的评估[MOAA / S]和双光谱指数）。采集血样以确定右美托咪定血浆浓度。结果1名受试者（1.0μgkg-1）患有需要使用麻黄碱的急性低血压。40名接受右美托咪定的受试者中有15名的收缩期动脉血压下降> 30％，而11名受试者（27.5％）的持续时间超过5分钟。MAP分别在接受右美托咪定0.5、1.0、1.5和2.0μgkg-1的受试者中有10％，20％，50％和30％的受试者的MAP降低了> 30％（> 5分钟），而与β-受体阻滞剂的使用无关。人力资源下降10-26％。18名（45％）受试者发生MOAA / S分数≤3；接受右美托咪定的八名（20％）受试者无镇静迹象。Tmax为70分钟。Cmax在0.15 ng ml-1（0.5μgkg-1）和0.46 ng ml-1（2.0μgkg-1）之间。结论老年患者的鼻内右美托咪定具有镇静作用，但无论使用β受体阻滞剂如何，都会引起深刻而持续的低血压。该技术不适合常规临床使用。