Morphine alters respiratory control but not other key obstructive sleep apnoea phenotypes: a randomised trial

Abstract

Accidental opioid-related deaths are increasing. These often occur during sleep. Opioids such as morphine may worsen obstructive sleep apnoea (OSA). Thus, people with OSA may be at greater risk of harm from morphine. Possible mechanisms include respiratory depression and reductions in drive to the pharyngeal muscles to increase upper airway collapsibility. However, the effects of morphine on the 4-key phenotypic causes of OSA (upper airway collapsibility [Pcrit], pharyngeal muscle responsiveness, respiratory arousal threshold and ventilatory control [loop gain] during sleep) are unknown. Twenty one men with OSA (AHI range=7–67 events·h⁻¹) were studied on 2 nights (1-week wash-out) according to a double-blind, randomised, cross-over design (ACTRN12613000858796). Participants received 40 mg of MS-Contin on one visit and placebo on the other. Brief reductions in continuous positive airway pressure (CPAP) from the therapeutic level were delivered to induce airflow limitation during non-REM sleep to quantify the 4 phenotypic traits. CO₂ was also delivered via nasal mask on therapeutic CPAP to quantify hypercapnic ventilatory responses during non-REM sleep. Compared to placebo, 40 mg of morphine did not change Pcrit (−0.1±2.4 versus −0.4±2.2 cmH₂O, p=0.58), genioglossus muscle responsiveness (−2.2[−0.87 to −5.4] versus −1.2[−0.3 to −3.5]microV/cmH₂O, p=0.22), or arousal threshold (−16.7±6.8 versus −15.4±6.0 cmH₂O, p=0.41), but did reduce loop gain (−10.1±2.6 versus −4.4±2.1 dimensionless, p=0.04) and hypercapnic ventilatory responses (7.3±1.2 versus 6.1±1.5 L·min⁻¹, p=0.006). Concordant with recent clinical findings, 40 mg of MS-Contin does not systematically impair airway collapsibility, pharyngeal muscle responsiveness or the arousal threshold in moderately severe OSA patients. However, consistent with blunted chemosensitivity, ventilatory control is altered.