Arousal from sleep: implications for obstructive sleep apnea pathogenesis and treatment

Historically, brief awakenings from sleep (cortical arousals) have been assumed to be vitally important in restoring airflow and blood-gas disturbances at the end of obstructive sleep apnea (OSA) breathing events. Indeed, in patients with blunted chemical drive (e.g., obesity hypoventilation syndrome) and in instances when other defensive mechanisms fail, cortical arousal likely serves an important protective role. However, recent insight into the pathogenesis of OSA indicates that a substantial proportion of respiratory events do not terminate with a cortical arousal from sleep. In many cases, cortical arousals may actually perpetuate blood-gas disturbances, breathing instability, and subsequent upper airway closure during sleep. This brief review summarizes the current understanding of the mechanisms mediating respiratory-induced cortical arousal, the physiological factors that influence the propensity for cortical arousal, and the potential dual roles that cortical arousal may play in OSA pathogenesis. Finally, the extent to which existing sedative agents decrease the propensity for cortical arousal and their potential to be therapeutically beneficial for certain OSA patients are highlighted.