Sleepiness and residual sleepiness in adults with obstructive sleep apnea

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Abstract

Sleepiness is a common, but not necessary symptom of the obstructive sleep apnea syndrome (OSA) and is a frequent chief complaint of patients with OSA who seek medical attention. While sleepiness may seem simple in nature, the underlying mechanisms producing daytime sleepiness in OSA are complex and poorly characterized. Moreover, the meaningful assessment of pathological sleepiness is frequently far from straightforward. Effective treatment of OSA is generally expected to resolve or ameliorate daytime sleepiness. An unknown percentage of treated OSA patients, however, remain sleepy during waking hours. The assessment and treatment of residual sleepiness in treated OSA can range from simple to difficult, depending on the nature and causes of the continued sleepiness. Recently, however, data from clinical trials have been generated which provide direction in the evaluation and management of the OSA patient suffering residual daytime sleepiness.

Introduction

Individuals with commonly occurring cyclical or repetitive obstructive respiratory events during sleep generally suffer a condition known as obstructive sleep apnea (OSA) syndrome (Guilleminault et al., 1976, Bassiri and Guilleminault, 2000). OSA has been established to be a common (Young et al., 1993, Ohayon et al., 2000) medical condition with a potential for a negative impact on health (Nieto et al., 2000, Young et al., 1997a, Shahar et al., 2001, Mooe et al., 1996) as well as the common symptom of daytime sleepiness (Gastaut et al., 1966, Young et al., 1993). Appropriate OSA treatment commonly improves or eliminates sleepiness when present; however, some patients experience residual sleepiness despite treatment. In this review, certain features of sleepiness are explored in OSA in general and residual sleepiness in treated OSA specifically, with an emphasis on evaluation and treatment in these patients.

Section snippets

Sleepiness in OSA

To adequately address the topic of residual sleepiness, a brief discussion of sleepiness in OSA is essential. Often, OSA is associated with the complaint of “excessive daytime sleepiness”. Indeed, sleepiness occurs with enough frequency that most definitions of the syndrome have required the presence of subjective, but not necessarily objective, sleepiness (Young et al., 1993). Sleepiness, however, is not reported by all patients with OSA, even when the condition is moderate or severe (Barbe et

Assessment of sleepiness

As is indicated by the preceding discussion, the meaning and experience of sleepiness varies across individuals; hence, the evaluation of sleepiness is a task far from simple. Multiple instruments have been developed in an attempt to rate or quantify sleepiness in OSA. These tools have been designed to assess sleepiness from the patient's subjective perspective as well as objectively.

Soon after the multiple sleep latency test (MSLT) was developed to measure sleep propensity in sleep-deprived

Theoretical causes of sleepiness in OSA

Ultimately, a better understanding of the physiological processes leading to daytime sleepiness and/or other cognitive function changes in OSA would yield an improved evaluation and treatment approach to residual sleepiness in treated OSA. Unfortunately, many ideas about the causes of OSA-related sleepiness exist, but little is clear. A brief review of observations fueling these ideas follows.

Variability of sleepiness across patients

While a correlation between OSA severity, as measured by AHI, and sleepiness severity has been observed in many studies, this correlation is generally lower than might be expected (Chervin and Aldrich, 1998, Engleman et al., 2000). This incomplete correlation is due to the varied sleepiness response, both subjectively and objectively, manifested by OSA patients. Patients with identical AHI's can range from profoundly sleepy to not at all sleepy (Morisson et al., 2001, Barbe et al., 2001).

That

OSA treatment and sleepiness

Whatever the cause or variability of sleepiness, treatment of OSA generally improves this symptom and often subjectively resolves it (Jenkinson et al., 1999, McFadyen et al., 2001, Morisson et al., 2001). Of interest is that in one multi-center study of OSA wherein subjects reported no sleepiness (i.e. ESS<10) subjective and objective measures of sleepiness (ESS and MSLT) did not improve with continuous positive pressure treatment (CPAP) leading the authors to conclude that treatment is not

Residual sleepiness in treated OSA

While the usual expectation is that OSA-related sleepiness will improve with appropriate treatment, many patients continue to suffer despite what would appear to be adequate treatment of the primary obstructive process (Morisson et al., 2001). Residual sleepiness in otherwise well-treated OSA is not uncommon and is a frequent challenge to the treating physician; however, the prevalence is unknown. As suggested by the work of Chervin (2000), any estimate of the prevalence of reduced daytime

Possible causes of residual sleepiness

Some researchers have postulated that those suffering residual sleepiness following treatment may suffer transient or permanent CNS malfunction unrelated to acute OSA processes, but as a longer-term consequence of OSA (Salorio et al., 2002, Beebe and Gozal, 2002). Others have suggested that a large percentage of these patients are only partially treated and that clinically relevant airflow disturbance or resistance persists. Such patients are then likely to benefit from careful treatment

Evaluation and treatment of residual sleepiness

Very few studies exist which have been designed to evaluate and/or treat residual sleepiness in treated OSA; therefore, a discussion of rational approaches to management of residual sleepiness is, by default, somewhat speculative and relies heavily on clinical experience. In consideration of the possible causes of residual sleepiness, reviewed in the previous section, multiple issues must be addressed in exploring potential causes of residual sleepiness in treated OSA.

Sub-optimal treatment,

Symptomatic treatment of persistent residual sleepiness

Occasionally attempts to address all causal factors of residual sleepiness in treated OSA are inadequate. Only after optimal airway management has been obtained should symptomatic treatment of residual sleepiness with medications be considered. In these instances, clinical experience along with a handful of studies suggests that treatment with a wake-promoting agent such as modafinil may be beneficial when all appropriate evaluation and treatment measures, as outlined in the previous section or

Summary

Sleepiness or other symptoms of reduced daytime vigilance or energy, such as tiredness and fatigue, are common, but not ubiquitous in OSA. The pathophysiology of sleepiness in OSA remains unknown; however, OSA treatment frequently ameliorates or resolves sleepiness in addition to treating OSA. An unknown, but presumably sizeable number of sleepy patients may experience residual sleepiness despite treatment. Careful evaluation of the many possible causes of residual sleepiness, including

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