Physiology of arousal in OSA and potential impacts for sedative treatment

Abstract

Treatment options for patients with obstructive sleep apnea (OSA) intolerant of continuous positive airway pressure (CPAP) are limited. Thus, new therapies are sought. Recently, there has been interest in using sedatives to delay arousal from sleep, allowing upper airway dilator muscle recruitment sufficient to re-open the airway while maintaining sleep. In this review the rationale for sedative use and prior sedative studies in OSA are presented, along with a description of six factors that may determine sedative treatment success. It is proposed that in order for a sedative to treat OSA the patient must have each of the following three traits: 1) a mild to moderately collapsible upper airway, 2) responsive and effective upper airway dilator muscles and 3) a low to moderate arousal threshold. In addition (4), proponents of sedative treatment generally believe that to be effective the sedative must increase the arousal threshold. Finally (5), sedatives may have additional utility in patients with large ventilatory responses to arousal and (6) the metric used to define sedative success needs to be considered. To date, few of these factors have been evaluated in sedative trials. Further, it is likely only a relatively small percentage of patients will have all of the required traits. If sedative treatment is successful in appropriate patients, easily measured surrogate markers for the factors that determine sedative success will be critical for implementation in the clinic. Finally, sedatives may have detrimental outcomes for some patients and prospective identification of such patients will be required.