Intranasal dexmedetomidine in elderly subjects with or without beta blockade: a randomised double-blind single-ascending-dose cohort studyBarends, C. R. M., Driesens, M. K., Struys, M. M. R. F., Visser, A. & Absalom, A. R., Apr-2020, In : British Journal of Anaesthesia. 124, 4, p. 411-419 9 p.
Research output: Contribution to journal › Article › Academic › peer-review
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).
|Number of pages||9|
|Journal||British Journal of Anaesthesia|
|Early online date||3-Feb-2020|
|Publication status||Published - Apr-2020|
- beta-blockade, complication, dexmedetomidine, elderly, hypotension, intranasal, safety, sedation, INTRAOPERATIVE HYPOTENSION, POSTOPERATIVE DELIRIUM, PHARMACODYNAMICS, PHARMACOKINETICS, ANESTHESIA, SEDATION, MIDAZOLAM