老年患者右美托咪定滴鼻联用或不用β受体阻滞剂：随机双盲单一递增剂量队列研究
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Intranasal dexmedetomidine in elderly subjects with or without beta blockade: a randomised double-blind single-ascending-dose cohort study
背景与目的
本项双盲、安慰剂对照、单一递增剂量研究旨在明确老年人右美托咪定滴鼻的安全性和耐受性。
方 法
我们随机分配48名年龄≥65岁的外科患者，按0.5、1.0、1.5和2.0 μg kg-1四个顺序剂量，接受右美托咪定或安慰剂（5:1比率）单次滴鼻。每个剂量包括两组，每组6名受试者：一组使用β受体阻滞剂，另一组不使用β受体阻滞剂。给药后2h测量生命体征和镇静深度（改良的观察者对警觉性及镇静评估[MOAA/s]和双谱指数）。取血样测定右美托咪定血药浓度。
结 果
一名受试者（1.0μg kg-1）出现需要注射麻黄碱的急性低血压。40名接受右美托咪定滴鼻的受试者中，15名（37.5%）收缩压下降超过30%，11名受试者（27.5%）收缩压下降持续时间超过5min。按0.5、1.0、1.5和2.0μg kg-1顺序剂量接受右美托咪定滴鼻的受试者中，分别有10%、20%、50%和30%受试者MAP下降超过30%（>5 min），无论是否使用β受体阻滞剂。心率下降了10～26%。18名（45%）受试者MOAA/S评分≤3分；8名（20%）接受右美托咪定滴鼻的受试者没有出现镇静症状。Tmax为70min。Cmax介于0.15ng ml-1（0.5μg kg-1）与0.46ng ml-1（2.0μg kg-1）之间。
结 论
老年患者右美托咪定滴鼻可产生镇静作用，但无论是否使用β受体阻滞剂，都会导致高发的严重持续低血压。该技术不适合常规临床应用。
原始文献摘要
Barends CRM, Driesens MK, Struys MMRF, et al. Intranasal dexmedetomidine in elderly subjects with or without beta blockade: a randomised double-blind single-ascending-dose cohort study.[J].Br J Anaesth 2020 Feb 03.
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 b-blockers and a group not taking b-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 b-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 b-blocker use. The technique is unsuitable for routine clinical use.
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贵州医科大学高鸿教授课题组
翻译：冯玉蓉 编辑：冯玉蓉 审校：王贵龙