Pathogenesis of sleep disordered breathing in the setting of opioid use: A multiple mediation analysis using physiology.

STUDY OBJECTIVES: Opioid medications are commonly used and are known to impact both breathing and sleep, and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing pathogenesis are not established. METHODS: Patients who underwent clinically-indicated polysomnography confirming sleep-disordered breathing (SDB) (AHI≥5/hr) were included. Each patient using opioids was matched by sex, age, and BMI to three control individuals not using opioids. Physiology known to influence SDB pathogenesis were determined from validated polysomnography-based signal analysis. PSG and physiology paramters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics. RESULTS: 178 individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs 1.7 events/hr; p=0.001) and worsened hypoxemia (5 vs 3% sleep with SpO2<88%; p=0.013), with similar overall AHI. Use of opioids was associated with higher loop gain, a lower respiratory rate and higher respiratory rate variability. Higher loop gain and increased respiratory rate variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia. CONCLUSIONS: Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate deleterious respiratory consequences of chronic opioid use.

Beyond CPAP: modifying upper airway output for the treatment of OSA.

Obstructive Sleep Apnea (OSA) is exceedingly common but often under-treated. Continuous positive airway pressure (CPAP) has long been considered the gold standard of OSA therapy. Limitations to CPAP therapy include adherence and availability. The 2021 global CPAP shortage highlighted the need to tailor patient treatments beyond CPAP alone. Common CPAP alternative approaches include positional therapy, mandibular advancement devices, and upper airway surgery. Upper airway training consists of a variety of therapies, including exercise regimens, external neuromuscular electrical stimulation, and woodwind instruments. More invasive approaches include hypoglossal nerve stimulation devices. This review will focus on the approaches for modifying upper airway muscle behavior as a therapeutic modality in OSA.