A randomized controlled crossover trial of acute intermittent and continuous hypoxia exposure in mild-moderate obstructive sleep apnea: A feasibility study

Abstract

In a prospective, randomized, controlled crossover study, we explored the effects of acute intermittent hypoxia and acute continuous hypoxia on patients with mild-moderate obstructive sleep apnea. Over three single-night sessions, subjects were alternately exposed to normoxia, acute continuous hypoxia and acute intermittent hypoxia before sleep. The apnea-hypopnea index and oxygen desaturation index were used to diagnose obstructive sleep apnea and evaluate efficacy. A responder was defined as a participant with a ≥ 50% reduction in apnea-hypopnea index between normoxia and hypoxia exposure. Sixteen participants with mild-moderate obstructive sleep apnea completed the study. Compared with normoxia, the mean apnea-hypopnea index decreased by 8.9 events per hr (95% confidence interval, 4.2-13.6, p = 0.001) with acute intermittent hypoxia and by 4.1 events per hr (95% confidence interval, 0.5-8.8, p = 0.082) with acute continuous hypoxia, equating to a mean decrease in apnea-hypopnea index of 4.8 events per hr (95% confidence interval, 0.1-9.5, p = 0.046) with acute intermittent hypoxia compared with acute continuous hypoxia. Compared with normoxia, the mean oxygen desaturation index decreased by 9.8 events per hr (95% confidence interval, 4.4-15.1, p = 0.001) with acute intermittent hypoxia but did not significantly decrease with acute continuous hypoxia; the mean oxygen desaturation index decreased by 7.2 events per hr (95% confidence interval, 1.8-12.6, p = 0.010) with acute intermittent hypoxia compared with acute continuous hypoxia. Of the 16 participants, 11 responded to acute intermittent hypoxia and four responded to acute continuous hypoxia (p = 0.032), of whom eight of 11 cases and all four cases had oxygen desaturation indexes <5 events per hr, respectively (p = 0.273). All participants tolerated acute intermittent hypoxia and there were no obvious adverse events during acute intermittent hypoxia exposure. In conclusion, acute intermittent hypoxia exposure improved apnea-hypopnea index and oxygen desaturation index in patients with mild-moderate obstructive sleep apnea, suggesting that further prospective validation of intermittent hypoxia exposure in patients with obstructive sleep apnea is needed to establish its clinical feasibility as a therapeutic modality.

Keywords: acute intermittent hypoxia exposure; cardiopulmonary function; continuous hypoxia exposure; neuroplasticity; obstructive sleep apnea.