TY - JOUR
T1 - Randomized Trial on the Effects of High-Dose Zopiclone on OSA Severity, Upper Airway Physiology, and Alertness
AU - Carter, Sophie G.
AU - Carberry, Jayne C.
AU - Grunstein, Ronald R.
AU - Eckert, Danny J.
PY - 2020/7
Y1 - 2020/7
N2 - Background: Studies indicate that standard doses of hypnotics reduce or do not change the apnea-hypopnea index (AHI) or pharyngeal muscle activity. A 1-month trial of nightly zopiclone (7.5 mg) modestly reduced the AHI vs baseline without changing other sleep parameters or next-day sleepiness. Research Question: This study aimed to determine the effects of high-dose zopiclone (15 mg) on AHI, arousal threshold, genioglossus muscle responsiveness, and next-day alertness in selected people with OSA (low to moderate arousal thresholds without major overnight hypoxemia). We hypothesized that high-dose zopiclone would yield greater increases in arousal threshold and therefore larger reductions in AHI but may come at the expense of increased hypoxemia and next-day impairment. Study Design and Methods: Twenty-eight participants (AHI = 29 ± 20 events/h) suspected to have low to moderate arousal thresholds were studied during two in-laboratory polysomnographies, separated by 1 week, with an epiglottic pressure catheter and genioglossus intramuscular electrodes. Participants received 15 mg of zopiclone or placebo at each visit according to a double-blind, randomized, crossover design. Each morning, subjective sleepiness and alertness via a driving simulator task were assessed. Results: The AHI did not change from placebo to zopiclone (−1.5 events/h; 95% CI, −6.6 to 3.5 events/h; P = .54). Arousal threshold, genioglossus muscle responsiveness, and most other sleep parameters and measures of next-day sleepiness and alertness also did not change with zopiclone. Interpretation: A single night of treatment with high-dose zopiclone does not systematically reduce the AHI or increase the arousal threshold in selected people with OSA. The mechanisms for these unexpected findings require further investigation. Trial Registry: Australian New Zealand Clinical Trials Registry; No.: ACTRN12617000988358; URL: https://www.anzctr.org.au
AB - Background: Studies indicate that standard doses of hypnotics reduce or do not change the apnea-hypopnea index (AHI) or pharyngeal muscle activity. A 1-month trial of nightly zopiclone (7.5 mg) modestly reduced the AHI vs baseline without changing other sleep parameters or next-day sleepiness. Research Question: This study aimed to determine the effects of high-dose zopiclone (15 mg) on AHI, arousal threshold, genioglossus muscle responsiveness, and next-day alertness in selected people with OSA (low to moderate arousal thresholds without major overnight hypoxemia). We hypothesized that high-dose zopiclone would yield greater increases in arousal threshold and therefore larger reductions in AHI but may come at the expense of increased hypoxemia and next-day impairment. Study Design and Methods: Twenty-eight participants (AHI = 29 ± 20 events/h) suspected to have low to moderate arousal thresholds were studied during two in-laboratory polysomnographies, separated by 1 week, with an epiglottic pressure catheter and genioglossus intramuscular electrodes. Participants received 15 mg of zopiclone or placebo at each visit according to a double-blind, randomized, crossover design. Each morning, subjective sleepiness and alertness via a driving simulator task were assessed. Results: The AHI did not change from placebo to zopiclone (−1.5 events/h; 95% CI, −6.6 to 3.5 events/h; P = .54). Arousal threshold, genioglossus muscle responsiveness, and most other sleep parameters and measures of next-day sleepiness and alertness also did not change with zopiclone. Interpretation: A single night of treatment with high-dose zopiclone does not systematically reduce the AHI or increase the arousal threshold in selected people with OSA. The mechanisms for these unexpected findings require further investigation. Trial Registry: Australian New Zealand Clinical Trials Registry; No.: ACTRN12617000988358; URL: https://www.anzctr.org.au
KW - genioglossus muscle responsiveness
KW - hypnotics
KW - respiratory arousal threshold
KW - sleep disordered breathing
KW - upper airway physiology
UR - http://www.scopus.com/inward/record.url?scp=85086735144&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2020.02.057
DO - 10.1016/j.chest.2020.02.057
M3 - Article
C2 - 32197956
AN - SCOPUS:85086735144
SN - 0012-3692
VL - 158
SP - 374
EP - 385
JO - Chest
JF - Chest
IS - 1
ER -