Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory...

Area of Science:

• Respiratory Medicine
• Sleep Medicine
• Clinical Pharmacology

Background:

• Centrally acting agents have unpredictable effects in obstructive sleep apnoea (OSA) patients.
• Phenotyping individual OSA responses is crucial for identifying risks of respiratory depression and benefits from medications.

Purpose of the Study:

• To test the hypothesis that OSA patients with higher central chemosensitivity exhibit greater breathing instability after taking a sedative-hypnotic (temazepam).
• To explore the relationship between awake central chemosensitivity and polysomnographically measured sleep-disordered breathing following temazepam administration.

Main Methods:

• A double-blind, placebo-controlled, cross-over trial involving 20 men with mild-to-moderate OSA.
• Polysomnography (PSG) was used to measure the effects of temazepam (10 mg) versus placebo on sleep apnoea.
• Ventilatory chemoreflexes were assessed during wakefulness to measure central and peripheral chemosensitivity.

Main Results:

• Higher awake central chemosensitivity in OSA patients correlated significantly with increased oxygen desaturation (lower SpO₂ nadir and higher oxygen desaturation index) after temazepam compared to placebo.
• No significant correlation was found between central chemosensitivity and the change in apnoea-hypopnoea index (AHI).
• Peripheral chemosensitivity and ventilatory recruitment threshold did not correlate with changes in respiratory parameters.

Conclusions:

• Mild-to-moderate OSA patients with elevated awake central chemosensitivity experience greater respiratory impairment during sleep when administered temazepam.
• Daytime assessment of respiratory control may help predict the impact of sedative-hypnotic medications on breathing during sleep in OSA patients.