Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

Abstract

Centrally active agents have a variable impact in patients with obstructive sleep apnoea (OSA) that is unexplained. How to phenotype the individual OSA response is clinically important, as it may help to identify who will be at risk of respiratory depression and who will benefit from a centrally active agent. Based on loop gain theory, we hypothesized that OSA patients with higher central chemosensitivity have higher breathing instability following the use of a hypnosedative, temazepam. In 20 men with OSA in a double-blind, placebo-controlled cross-over trial we tested the polysomnographically (PSG) measured effects of temazepam 10 mg versus placebo on sleep apnoea. Treatment nights were at least 1 week apart. Ventilatory chemoreflexes were also measured during wakefulness in each subject. The patients (mean ± standard deviation; 44 ± 12 years) had predominantly mild-to-moderate OSA [baseline apnoea-hypopnoea index (AHI) = 16.8 ± 14.1]. Patients' baseline awake central chemosensitivity correlated significantly with both the change of SpO₂ nadir between temazepam and placebo (r = -0.468, P = 0.038) and oxygen desaturation index (ODI; r = 0.485, P = 0.03), but not with the change of AHI (r = 0.18, P = 0.44). Peripheral chemosensitivity and ventilatory recruitment threshold were not correlated with the change of SpO₂ nadir, ODI or AHI (all P > 0.05). Mild-moderate OSA patients with higher awake central chemosensitivity had greater respiratory impairment during sleep with temazepam. Relatively simple daytime tests of respiratory control may provide a method of determining the effect of sedative-hypnotic medication on breathing during sleep in OSA patients.