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Kelly Felmet works at the University of Pittsburgh Medical Center, Pittsburgh, Pa. Martha Petersen is an Assistant Professor at Duquesne University in Pittsburgh. The authors have indicated no relationships to disclose relating to the content of this article.

Obstructive sleep apnea (OSA) affects up to 5% of the population in Western countries, but as many as 80% of cases remain undiagnosed.^1,2 Prevalence increases with age, peaking at approximately 60 years.^1,3 Although 1 in 5 adults has mild OSA, only 1 in 15 has a moderate to severe case.¹

Obesity is a significant risk factor, partly because layers of fat adjacent to the pharynx narrow its lumen. A 10% increase in weight leads to a six-fold risk of developing OSA.¹ Thus, the incidence of OSA is expected to rise as the rate of obesity increases in the United States. Other risk factors for OSA include male sex and abnormalities of craniofacial morphology. Frequent alcohol use has also been considered a risk factor since it depresses the central respiratory drive and enhances muscle relaxation.^3,4

Patients with untreated OSA may present with conditions such as hypertension, coronary artery disease (including MI), diabetes, heart failure, stroke, and cognitive dysfunction. Although these conditions are commonly treated without a search for underlying pathology, OSA can be a major contributor. Previous research has focused on the cardiac effects of untreated OSA, such as hypertension, stroke, and arrhythmias.^5,6 However, a mechanism that causes cardiac dysfunction may also cause cognitive dysfunction resembling dementia. Failure to diagnose and treat OSA effectively may result in improper management of this dementia. With proper treatment, its progression may be halted—although the condition may not be completely reversed.

At present, no optimal treatment options are available for OSA. Continuous positive airway pressure (CPAP) therapy is the first-line treatment, but patient adherence is only 46% to 70% because of discomfort caused by the mask.^3,7

Physiology

OSA is defined as periods of apnea (cessation of breathing for longer than 10 seconds) or hypopnea (reduction but not complete cessation of airflow to less than 50% of normal) that occur throughout sleep. These are caused by partial or complete obstruction of the upper airway, usually the oropharynx, which inhibits inspiratory airflow ⁸ (see Figure 1).

Airway closure results from the relaxation during sleep of skeletal muscles—specifically, the pharyngeal dilator muscles and the genioglossus, which maintain the tongue in the anterior position when the person is supine. Too much muscle relaxation allows the tongue to slide posteriorly, partially or completely occluding the airway and causing the typical loud snoring and sudden choking and gasping for air. Other contributing anatomic anomalies include excessive soft palate tissue and enlarged tonsils, tongue base, or uvula.

Mechanism of action Cyclical oxygen desaturation occurs with each pause in breathing that stimulates arousal from sleep. In rapid eye movement (REM) sleep, muscle tone is most relaxed and apnea episodes are prolonged, with severe desaturations, often 60% to 70% lower than normal.⁹ Following each apneic or hypopneic event, a surge of sympathetic activity occurs, stimulating transient tachycardia and increasing BP.³ Over time, cardiac hypertrophy, arrhythmias, and cor pulmonale can result.¹⁰ Each interruption of their sleep pattern prevents patients from reaching the deep sleep stage. They wake feeling unrested and experience daytime somnolence.

OSA and motor vehicle accidents Patients with OSA perform poorly on driving-simulator tests^2,3,11,12 and have a 2% to 7% greater risk of a motor vehicle accident (MVA) caused by driver sleepiness, fatigue, and inattentiveness.² Up to 21% of patients who present to the emergency department (ED) following an MVA have undiagnosed OSA.² The true number may be even higher than reported, given that a significant number of crashes are attributed to comorbid conditions such as stroke and MI when OSA may have been a contributing cause. ED staff should be aware of the seriousness of OSA and screen MVA patients for this condition.

Cognitive impairment

Untreated OSA has been strongly implicated in contributing to cardiovascular morbidity by increasing the risk of atherosclerosis, ischemia, and stroke⁵ (see Table 1). The proposed mechanism is increased levels of oxidative stress that contribute to excess free radical production,¹³ soluble adhesion molecules,^14,15 and decreased levels of nitric oxide (NO), a potent vasodilator.¹⁶ Repeated transient hypopnea/apnea and reoxygenation events resulting from untreated OSA also affect cerebral oxygenation and blood flow velocity.¹⁷ This produces a condition similar to myocardial hypoxia, resulting in increased production of free radicals and adhesion molecules and decreased levels of NO.¹⁸

Free radicals are highly reactive substances capable of doing extensive damage to healthy tissue if not properly contained within the mitochondria.¹⁸ NO suppression triggers vasoconstriction, elevated BP, and decreased oxygen supply to local brain tissue.¹⁶ It has been hypothesized that severe oxygen desaturation and decreased blood flow velocity to brain tissue may cause an infarct, similar to a cardiac infarct, resulting in death of brain tissue with permanent neuropsychological dysfunction.¹⁷ After several years of untreated OSA, the impact may become clinically evident as dementia. This destructive process is thought to represent vascular dementia rather than the degenerative dementia commonly seen in Alzheimer’s disease and Parkinson’s disease.^19,20 Patients currently classified as having dementia may not be treated properly if underlying OSA is not considered or treated. Effective CPAP therapy in patients with OSA can increase the NO concentration and rapidly decrease free radical and adhesion molecule release.^13,15 Thus, further cognitive damage may be prevented with adequate treatment.

Executive dysfunction

The cognitive dysfunction evident in patients with OSA has been proposed to be an executive dysfunction (see Table 2).^21-23 It resembles vascular dementia, during which ischemic lesions interrupt the prefrontal-subcortical circuits.¹⁹ In both OSA and vascular dementia, patients cannot correctly use core language skills, visual/perceptual abilities, and remote memory capacity.

It has been proposed that sleep disruption and blood gas abnormalities inhibit sleep-associated restorative processes, causing chemical and structural CNS cellular injury in prefrontal brain cortex regions.²¹ The recognizable pattern of executive dysfunction in OSA patients is detailed in Table 3.^21,24

The executive dysfunction found in untreated OSA is permanent.^25-27 Cognitive function was evaluated in patients after brief (15 days) and long-term (4 months) treatment with CPAP therapy.²⁵ Improvements in daytime somnolence and certain cognitive deficits were initially evident, but executive function and visual-constructive tests were not restored to normal levels, even with long-term therapy.²⁵ These cognitive deficits may be related to irreversible structural damage from chronic hypoxia in the frontal lobes.²⁵ It is important to continue to devote research to define the specific cognitive deficits associated with OSA to distinguish them from comorbid conditions.²⁸

Near-infrared spectroscopy (NIRS) is a noninvasive continuous means of monitoring changes in cerebral oxygenation and flow velocity in patients with OSA.¹⁷ NIRS has been used to show that cerebral blood flow is reduced in patients with OSA, with longer episodes of apnea and hypopnea in REM sleep causing greater fluctuations in cerebral blood flow and more severe desaturations.¹⁷

Diagnosis

The signs and symptoms associated with OSA are shared with other medical conditions (see Table 4). Patients (or their partners) complain of loud snoring and excessive daytime sleepiness, the two hallmark features of OSA. Other symptoms include restless sleep, choking during sleep, and morning headaches. A large number of patients with OSA will remain asymptomatic but will eventually develop long-term side effects. It is important to rule out other causes of daytime sleepiness and to recognize common signs found in patients with OSA, including obesity, a thick neck, tonsillomegaly, acromegaly, and craniofacial anomalies.⁴

The diagnosis of OSA is confirmed by an overnight sleep study using polysomnography (PSG), a noninvasive modality that detects the pattern of repetitive oxygen desaturation associated with heart rate variability that is specific for OSA. A complete PSG study requires a minimum of 2 to 4 hours of continuous sleep and monitors three variables: assessment of sleep stages, respiration, and limb movements. A diagnosis of mild, moderate, or severe OSA is based on one of three classification criteria: an apnea index (the apnea index is the number of episodes of apnea per hour of sleep—more than 5, more than 15, or more than 30); an apnea/hypopnea index (the number of episodes of apnea and hypopnea per hour); or a respiratory disturbance index (5-15, 16-30, or more than 30 disturbances).³

Current diagnostic testing for OSA is time-consuming, expensive, distracting, and uncomfortable for the patient, who must try to sleep normally in the clinic setting. Promising alternative tools for routine mass screening in high-risk patients include nocturnal ECG Holter monitoring for measuring heart rate increment²⁹ and heart rate spectral analysis of nocturnal pulse oximetry,³⁰ both of which have equal or higher sensitivity and specificity and may be simpler and less expensive than PSG for diagnosing OSA.

Treatment

There are three main treatment options for OSA.^31,32 The treatment of choice is CPAP therapy and weight loss. The second-line therapy is surgery. A last resort in patients with severe, life-threatening OSA who do not respond to CPAP or surgery is a tracheotomy, which is 100% curative but rarely used. Alternative treatment options for patients with mild OSA include oral prosthetic devices (mandibular repositioning device, tongue retaining devices, and soft palate lifters), avoiding alcohol and other sedatives, and altering sleeping positions, such as elevating the head of the bed or lying on one’s side rather than supine.³³ There are no pharmacologic treatments for OSA.

CPAP therapy Although not curative, CPAP therapy is considered the best treatment option for moderate to severe OSA. The CPAP device provides airway pressure throughout respiration to prevent airway collapse.²³ During use, the patient places a mask over the mouth, which is held in place by headgear with tubing connected to an electrical unit that provides a constant flow of air into the mask. Patient adherence to this treatment is disappointing, in part because of the side effects, which include sleep disruption, dry mouth/nose, sore throat, nosebleeds, claustrophobia, and facial skin abrasions from mask straps.³³

When used correctly, CPAP therapy has been shown to decrease the production of adhesion molecules and free radicals and to increase circulating levels of NO, all of which may decrease the risk of atherosclerosis and ischemic stroke.^10,16 While it cannot reverse all cognitive impairment, CPAP therapy has been shown to benefit patients with cardiac complications. Residual executive dysfunction remains evident following 4 to 6 weeks of CPAP therapy,²⁶ implying that some degree of cognitive impairment is permanent. Even a 6-month delay in treating patients with severe OSA deprives them of significant improvement in quality of life.³⁴ If CPAP therapy were shown to protect against the onset of cognitive dysfunction and other comorbid conditions in patients with OSA, support would strengthen for a large-scale effort to diagnose and treat OSA as early as possible.⁴ Daytime somnolence has significant economic effects, and the comorbid conditions caused by OSA reduce job productivity and increase automobile accidents, depression, and relationship problems.

Surgery If a trial of CPAP therapy fails, the next step is to consider uvulopalatopharyngoplasty (UPPP). The most common surgical procedure for OSA, UPPP involves a tonsillectomy, reorientation of the anterior/posterior pillars, and excision of the uvula and posterior rim of the soft palate.³² UPPP is effective for patients with mild to moderate cases of OSA. It reduces symptoms in 90% of patients, decreases the number of apneic events in 60%, and achieves a cure in 50%.³²

The PA’s role

PAs should be aware of the signs and symptoms of OSA and be aggressive in treating it as early as possible. Once you suspect OSA, recommend PSG to accurately determine its severity. Explain the disease to the patient, and describe the long-term complications that can result from lack of treatment. If the patient is overweight, urge weight loss, which may help reduce the severity of the obstruction. Management of moderate to severe OSA includes CPAP therapy or possibly surgery if there is a definite structural abnormality. The patient must become an active participant in order to ensure long-term compliance, especially if CPAP therapy is used. Explain that treatment will not cure the condition and that permanent lifestyle changes are needed to prevent complications. Most importantly, PAs should follow patients closely, answering their questions, adjusting the treatment options, and helping them to manage complications to ensure long-term compliance.

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