Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea

Abstract

Our purpose was to determine whether exposure to mild intermittent hypoxia leads to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events. Ten male participants were treated with twelve 2-min episodes of hypoxia ([Formula: see text] ≈50 mmHg) separated by 2-min intervals of normoxia in the presence of [Formula: see text] that was sustained 3 mmHg above baseline. During recovery from the last episode, the positive airway pressure was reduced in a stepwise fashion until flow limitation was evident. The participants also completed a sham protocol under normocapnic conditions, which mimicked the time frame of the intermittent hypoxia protocol. After exposure to intermittent hypoxia, the therapeutic pressure was significantly reduced (i.e., 5 cmHO) without evidence of flow limitation (103.4 ± 6.3% of baseline, = 0.5) or increases in upper airway resistance (95.6 ± 15.0% of baseline, = 0.6). In contrast, a similar decrease in pressure was accompanied by flow limitation (77.0 ± 1.8% of baseline, = 0.001) and an increase in upper airway resistance (167.2 ± 17.5% of baseline, = 0.01) after the sham protocol. Consistent with the initiation of long-term facilitation of upper airway muscle activity, exposure to intermittent hypoxia reduced the therapeutic pressure required to eliminate apneic events that could improve treatment compliance. This possibility, coupled with the potentially beneficial effects of intermittent hypoxia on comorbidities linked to sleep apnea, suggests that mild intermittent hypoxia may have a multipronged therapeutic effect on sleep apnea. Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent with previous results, which have shown that long-term facilitation of upper muscle activity can be initiated following exposure to intermittent hypoxia in humans.

Moderate and severe hypoxia elicit divergent effects on cardiovascular function and physiological rhythms

“…; El‐Chami et al . ), although the corresponding effects in health are unknown. To determine pathophysological mechanisms, it is important to first establish the effect of variable hypoxic gradations in health.…”

“…By contrast, individuals living in high-altitude, moderately hypoxic environments do not show elevations in blood pressure (Ruiz & Peñaloza, 1977;Bruno et al 2014); however, the latter findings could be the result of long-term genetic adaptations (Hochachka et al 1996;Moore, 2001;Lorenzo et al 2014). Interestingly, exposure to mild, intermittent hypoxia can be cardioprotective (Navarrete-Opazo & Mitchell, 2014;Mateika et al 2015;El-Chami et al 2017), although the corresponding effects in health are unknown. To determine pathophysological mechanisms, it is important to first establish the effect of variable hypoxic gradations in health.…”

Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea

“…More specifically, reductions in therapeutic pressure (El‐Chami et al . , Mateika & Komnenov, ) combined with increases in the arousal threshold could lead to improved treatment compliance and outcome measures (Mateika & Komnenov, ). This effect, combined with the direct beneficial effects of mild forms of intermittent hypoxia that extend beyond motor function to autonomic, cardiovascular, metabolic and neurocognitive function (Mateika et al .…”

“…), and improved upper airway mechanics when individuals are treated with continuous positive airway pressure (El‐Chami et al . ). This dichotomy probably exists because long‐term facilitation and the coincident improvement of upper airway patency is dependent on the maintenance of carbon dioxide levels (Harris et al .…”

“…These outcomes are evident even though exposure to mild intermittent hypoxia leads to sustained increases in upper airway muscle activity (i.e. long-term facilitation) (Harris et al 2006;Chowdhuri et al 2008), and improved upper airway mechanics when individuals are treated with continuous positive airway pressure (El-Chami et al 2017). This dichotomy probably exists because long-term facilitation and the coincident improvement of upper airway patency is dependent on the maintenance of carbon dioxide levels (Harris et al 2006).…”