Role of Arousals in the Pathogenesis of Obstructive Sleep Apnea

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Abstract
Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced by dial-down of continuous positive airway pressure. Obstructions and hypopneas occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of dial-downs), the temporal relation between arousal and opening was inconsistent between and within patients. Frequency of opening without or before arousal increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p < 10(-6)). Time of opening was unaffected by whether arousal occurred before or after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already excessive when opening occurred without or before arousal (180 +/- 148% of initial flow decline) and was considerably higher when arousal occurred (267 +/- 154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater if arousal occurred (p < 0.01). It is concluded that arousals are incidental events that occur when thresholds for arousal and for arousal-independent opening are close. They are not needed to initiate opening or to obtain adequate flow and they likely increase the severity of the disorder by promoting greater ventilatory instability.