Role of common hypnotics on the phenotypic causes of obstructive sleep apnoea: paradoxical effects of zolpidem

Eur Respir J. 2017 Dec 28;50(6):1701344. doi: 10.1183/13993003.01344-2017. Print 2017 Dec.

Abstract

Hypnotics are contraindicated in obstructive sleep apnoea (OSA) because of concerns of pharyngeal muscle relaxation and delayed arousal worsening hypoxaemia. However, human data are lacking. This study aimed to determine the effects of three common hypnotics on the respiratory arousal threshold, genioglossus muscle responsiveness and upper airway collapsibility during sleep.21 individuals with and without OSA (18-65 years) completed 84 detailed sleep studies after receiving temazepam (10 mg), zolpidem (10 mg), zopiclone (7.5 mg) and placebo on four occasions in a randomised, double-blind, placebo-controlled, crossover trial (ACTRN12612001004853).The arousal threshold increased with zolpidem and zopiclone versus placebo (mean±sd -18.3±10 and -19.1±9 versus -14.6±7 cmH2O; p=0.02 and p<0.001) but not with temazepam (-16.8±9 cmH2O; p=0.17). Genioglossus muscle activity during stable non-REM sleep and responsiveness during airway narrowing was not different with temazepam and zopiclone versus placebo but, paradoxically, zolpidem increased median muscle responsiveness three-fold during airway narrowing (median -0.15 (interquartile range -1.01 to -0.04) versus -0.05 (-0.29 to -0.03)% maximum EMG per cmH2O epiglottic pressure; p=0.03). The upper airway critical closing pressure did not change with any of the hypnotics.These doses of common hypnotics have differential effects on the respiratory arousal threshold but do not reduce upper airway muscle activity or alter airway collapsibility during sleep. Rather, muscle activity increases during airway narrowing with zolpidem.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arousal / drug effects
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / adverse effects
  • Continuous Positive Airway Pressure
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects*
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Respiratory System / drug effects
  • Sleep / drug effects*
  • Sleep Apnea, Obstructive / chemically induced*
  • Sleep Apnea, Obstructive / therapy*
  • Temazepam / administration & dosage
  • Temazepam / adverse effects
  • Tongue / drug effects
  • Zolpidem / administration & dosage*
  • Zolpidem / adverse effects

Substances

  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • zopiclone
  • Zolpidem
  • Temazepam

Associated data

  • ANZCTR/ACTRN12612001004853