Intranasal dexmedetomidine in elderly subjects with or without beta blockade: a randomised double-blind single-ascending-dose cohort study

Clemens R. M. Barends*, Mendy K. Driesens, Michel M. R. F. Struys, Anita Visser, Anthony R. Absalom

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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).

Original languageEnglish
Pages (from-to)411-419
Number of pages9
JournalBritish Journal of Anaesthesia
Volume124
Issue number4
Early online date3-Feb-2020
DOIs
Publication statusPublished - Apr-2020

Keywords

  • beta-blockade
  • complication
  • dexmedetomidine
  • elderly
  • hypotension
  • intranasal
  • safety
  • sedation
  • INTRAOPERATIVE HYPOTENSION
  • POSTOPERATIVE DELIRIUM
  • PHARMACODYNAMICS
  • PHARMACOKINETICS
  • ANESTHESIA
  • SEDATION
  • MIDAZOLAM

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