Barends Clemens R M, Driesens Mendy K, Struys Michel M R F, Visser Anita, Absalom Anthony R
Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Br J Anaesth. 2020 Apr;124(4):411-419. doi: 10.1016/j.bja.2019.12.025. Epub 2020 Feb 3.
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.
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. 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.
One subject (1.0 μg kg) 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, 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. T was 70 min. C was between 0.15 ng ml (0.5 μg kg) and 0.46 ng ml (2.0 μg kg).
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.
NTR5513 (The Netherlands Trial Registry 5513).
这项双盲、安慰剂对照、单剂量递增研究的目的是确定老年患者鼻内给予右美托咪定的安全性和耐受性。
我们将48名年龄≥65岁的外科手术患者随机分配，按照5:1的比例在四个连续剂量组中接受单剂量鼻内右美托咪定或安慰剂：0.5、1.0、1.5和2.0μg/kg。每个剂量组包括两组，每组6名受试者：一组使用β受体阻滞剂的受试者和一组未服用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（改良警觉/镇静观察评分[MOAA/S]和脑电双频指数）。采集血样以测定右美托咪定的血浆浓度。
一名受试者（1.0μg/kg）出现急性低血压，需要麻黄碱治疗。在接受右美托咪定的40名受试者中，有15名（37.5%）收缩压下降>30%，其中11名受试者（27.5%）持续时间超过5分钟。接受0.5、1.0、1.5和2.0μg/kg右美托咪定的受试者中，分别有10%、20%、50%和30%的受试者平均动脉压下降>30%（>5分钟），与是否使用β受体阻滞剂无关。心率下降10 - 26%。MOAA/S评分≤3出现在18名（45%）受试者中；8名（20%）接受右美托咪定的受试者未表现出镇静迹象。达峰时间为70分钟。血药浓度在0.15 ng/ml（0.5μg/kg）至0.46 ng/ml（2.0μg/kg）之间。
老年受试者鼻内给予右美托咪定有镇静作用，但无论是否使用β受体阻滞剂，均会导致严重且持续低血压的高发生率。该技术不适用于常规临床应用。
NTR5513（荷兰试验注册5513）。
