Clemens R M Barends1, Mendy K Driesens2, Michel M R F Struys3, Anita Visser4, Anthony R Absalom2. 1. Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: c.r.m.barends@umcg.nl. 2. Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 3. Department of Anaesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium. 4. Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Abstract
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).
RCT Entities:
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).
Authors: Remco Vellinga; Beatrijs I Valk; Anthony R Absalom; Michel M R F Struys; Clemens R M Barends Journal: J Clin Med Date: 2022-06-17 Impact factor: 4.964