Sleep-related breathing disorder comprises obstructive sleep apnea, central sleep apnea, and obesity hypoventila-tion syndrome. Obstructive sleep apnea is the most notable of these conditions because of its high prevalence and association with numerous medical conditions if untreated. Obstructive apnea is defined as cessation of airflow that lasts at least 10 seconds owing to impedance of respiratory effort as the result of airway obstruction. Hy-popnea is defined as reduction in airflow resulting in atleast a 4% decrease in oxygen saturation. Table American Academy of Sleep Medicine diagnostic criteria for obstructive sleep apnea outlines the diagnostic criteria for obstructive sleep apnea. Apnea and hypopnea both are considered clinically significant markers of disease and as a result are reported together as the apnea-hypopnea index. Since these criteria were published, sleep specialists have recognized that hypopnea with an oxygen desaturation greater than or equal to 4% must be quantified in addition to pure apnea.
TABLE American Academy of Sleep Medicine diagnostic criteria for obstructive sleep apnea
|Essential signs and symptoms|
|1. Excessive daytime sleepiness|
|2. Obstructed breathing during sleep|
|Essential polysomnographic findings|
|1. More than five episodes of apnea (>10 seconds) per hour of sleep with evidence of respiratory muscle effort and one of the following:
a. Apnea causing frequent arousals
b. Apnea causing oxygen desaturation ≥4%
Patients with obstructive sleep apnea are the largest subgroup of patients referred to sleep disorders centers. This disorder, which affects at least 2% of women and 4% of men ages 30-60 years, is strongly associated with obesity. Obstructive sleep apnea is more common without marked obesity in several racial groups, including Asians, in whom craniofacial anatomic features can produce a narrower nasopharyngeal airway. Advanced age, male sex, and postmenopausal state are all associated with a higher prevalence of this condition. In subpopulations of patients with hypertension, heart disease, and adult-onset diabetes mellitus, as many as 30%-40% of patients can have obstructive sleep apnea.
Most patients with obstructive sleep apnea snore. Family members may observe disruptive snoring intermixed with quiet periods and reduced respiration. Although essentially all patients with obstructive sleep apnea snore, the reverse is not the case. Snoring is an extremely common phenomenon in the community, affecting 25% of men and 15% of women. For this reason, screening for obstructive sleep apnea must rely on more than simply a history of snoring. Patients may have restless sleep at times, to the point they are believed to have a parasomnia such as REM sleep behavior disorder. Excessive sweating and morning headaches can be present. Patients may report choking or being awakened by their snoring. An increased rate of nocturia has been described, possibly because the patient is more aware of bladder fullness when awakened by the breathing disorder. Obstructive apnea can lead to respiratory arousals and oxygen desaturation, which can cause transient elevations in blood pressure initially at night. Hypertension is common, especially in patients with severe obstructive sleep apnea. Initially, blood pressure increases follow each obstructive event, but if apneic or hypopneic episodes are frequent, blood pressure can remain elevated throughout the night and day. Pulmonary hypertension also has been an associated finding, particularly with severe obstructive sleep apnea.
The hemodynamic alterations of obstructive sleep apnea include systemic hypertension, increased right and left ventricular afterload, and increased cardiac output. Earlier reports attributed the association between obstructive sleep apnea and cardiovascular disease to the common risk factors such as age, sex, and obesity. However, newer epidemiological data confirm an independent association between obstructive sleep apnea and these cardiovascular diseases. Possible mechanisms include a combination of intermittent hypoxia and hypercapnia, repeated arousals, sustained increase in sympathetic tone, increased platelet aggregation, reduced baroreflex sensitivity, and elevated plasma fibrinogen and homocysteine levels.
Patients with obstructive sleep apnea experience intermittent compromise of the upper airway. The most common site of obstruction is the pharynx, a hollow tube that collapses during swallowing and speech. The pharyngeal musculature serves to keep the upper airway open and opposes the subatmospheric pressure in the pharynx itself. The genioglossus muscles also pull forward to keep the upper airway clear of obstruction. This balance is further influenced by anatomic structures (adipose tissue, tongue size, mandibular length, soft palate, and tonsils) and neuromuscular mechanisms (activity of the pharyngeal muscles affected by sleep state, muscle relaxant, and hypnotic medications). The obstructed upper airway leads to cessation or reduction of airflow that results in the finding of an arousal on the EEG tracing. Some patients have marked respiratory arousals without actual apnea or partial apnea (hypopnea). Snoring or increased effort to ventilate due to narrowing but not full collapse of the airway is called upper airway resistance syndrome, a potentially distressing but subclinical form of obstructive sleep apnea that occurs more often in women than in men.
Results of polysomnography conducted in a sleep disorders center are the standard of reference for the diagnosis of breathing-related sleep disorder. Other screening techniques, such as overnight pulse oximetry and use of portable devices, have not been demonstrated to be cost-effective, reliable, or sufficiently sensitive. Many centers use “split-night” sleep studies, often in response to reimbursement issues. Under these circumstances, patients are observed for at least 2 hours while they are sleeping, ideally experiencing both NREM and REM sleep in both the supine and nonsupine positions. Once a diagnosis of breathing-related sleep disorder is established, the technologist introduces treatments such as nasal continuous positive airway pressure (CPAP). Nasal CPAP is applied through a nasal mask connected to a blower that can be adjusted so that pressurized air is delivered to the upper airway. Having positive pressure keep open the airway is particularly important during expiration, when the airway most commonly collapses in patients with obstructive sleep apnea. The nasal CPAP pressure setting can be carefully titrated in response to airway narrowing during the rest of the sleep study. In the morning, the patient can be asked about comfort and acceptance of this therapy. A split-night study is an opportunity for clinician and patient to compare the untreated versus the newly treated state. The procedure is controversial because of the limited time available for both the diagnostic study and the treatment trial. In most cases, a split-night study eliminates the need for a second night in the laboratory.
The complications of obstructive sleep apnea lead to significant morbidity and mortality. Risk factors for obstructive sleep apnea (“Evaluating Sleep”) are male sex, older age, high body mass index, greater neck circumference, snoring, and observed pauses in breathing at night. Untreated obstructive sleep apnea has been associated with systemic hypertension, right-sided heart failure, and cerebrovascular accidents. The excessive daytime sleepiness that can result from untreated obstructive sleep apnea can put patients at risk of motor vehicle accidents, cognitive problems, and interpersonal difficulties. An association once was found between obstructive sleep apnea and gastroesophageal reflux; however, more recent work indicated that one condition does not appear to cause the other. Nevertheless, treatment with antireflux medication reduces arousals but not apneic episodes, and intervention for obstructive sleep apnea with nasal CPAP does reduce reflux.
Since the early 1980s, the treatment of obstructive sleep apnea has been revolutionized by the use of nasal CPAP. This treatment involves delivering pressurized air (typically 3-18 cm of water pressure) to sites of upper airway collapse (generally the oropharynx and less commonly the nasopharynx) and forcing the airway open. Apnea and snoring are eliminated, allowing the patient to sleep continuously without being aroused to breathe. Nasal CPAP is generally introduced when the patient is sleeping in the sleep laboratory, where staff can adjust the pressure appropriately and assist with mask fit. Newer technology entails the use of self-titrating devices that modify the pressure setting breath by breath without requiring technologist involvement. The extent to which these more sophisticated machines may replace nasal CPAP titrations conducted in a sleep laboratory is not clear.
Patients with severe obstructive sleep apnea often report marked improvement, within days, in their mood and energy. This improvement is positive reinforcement that leads to good compliance with nasal CPAP treatment. Patients with mild to moderate obstructive sleep apnea have more adherence problems, the compliance rate being estimated at 10%-50%. Even patients who use this device nightly typically use it for only several hours.
Patients with obstructive sleep apnea who consume alcohol close to bedtime pose a challenge, because alcohol has been observed to decrease the neuromuscular tone of the upper airway. These patients often need higher nasal CPAP settings to prevent apnea. In addition, if the sleep study is done when the patient has not been consuming alcohol often, the selected pressure settings are insufficient on nights when the patient has ingested alcohol. Certain medications, especially long-acting benzodiazepines, can exert a similar effect and can depress the reticular activating system to reduce the arousal threshold and prevent arousals that effectively interrupt prolonged episodes of apnea.
Another treatment of obstructive sleep apnea is bilevel positive airway pressure. This therapy represents a modification of CPAP whereby the positive pressure fluctuates depending on whether the airflow is inspiratory or expiratory. Bilevel pressure therapy is considerably more expensive than conventional CPAP and is reserved for patients who cannot tolerate CPAP because of discomfort or emergence of central apnea at necessary pressure settings. Supplemental oxygen alone is inadequate for obstructive sleep apnea because the oxygen cannot pass the obstruction to reach the lungs. Patients with both breathing-related sleep disorder and intrinsic lung disease who have persistent hypoxia despite CPAP can benefit from supplemental oxygen delivered through the nasal CPAP mask.
For patients who have apnea only in the supine position, effective treatment may include having them use a device such as a T-shirt with an attached cloth tube of tennis balls. This soft lump keeps patients from lying on their backs. Inflatable devices resembling backpacks can serve the same purpose. Few data are available regarding long-term adherence with these practical interventions. Some patients who refuse CPAP and have severe apnea during REM sleep have been offered a REM-suppressant medication such as a monoamine oxi-dase inhibitor. No published data are available regarding this practice. Abrupt discontinuation of the pharmacological agent should be avoided because of REM rebound, which can increase the risk of apnea.
Weight loss through diet and exercise is an important component of the treatment plan for any overweight patient with breathing-related sleep disorder. Motivated patients can succeed. Weight loss should be primary treatment only of patients with mild to moderate disease, particularly if they are not interested in other modalities. Gastric bypass surgery can be especially important for management of medically complicated obesity (“Surgery”). In general, a 10-pound weight loss can reduce the required CPAP pressure; however, many patients eventually seem to gain rather than lose weight with the result that CPAP pressure needs to be increased.
Patients with abnormalities of the soft tissue or skeletal structures surrounding the upper airway may consider surgery. Surgical procedures include laser-assisted uvulopalatopharyngoplasty, tonsillectomy, mandibular advancement, and tracheostomy. Patients must be carefully selected. They must have upper airway obstructions that are resectable, for example, large tonsils, and have no other comorbid conditions, such as an elevated body mass index that compromises upper airway patency at multiple points.
There have been promising results with oral appliances that pull the tongue or mandible forward. Hypnotic agents may be used to treat patients with obstructive sleep apnea, particularly if adherence to nasal CPAP is suboptimal because of discomfort causing insomnia. Medications such as zolpidem and zaleplon have been well tolerated. Benzodiazepines should be used cautiously in the care of patients with obstructive sleep apnea. These agents may prevent a patient from arousing during an episode of apnea and taking a compensatory breath. Some clinicians fear that if patients using benzodiazepines remove the nasal CPAP mask, they may experience longer apnea because they are not aroused when hypoxia develops. Furthermore, nightly use of benzodiazepines may decrease the amount of slow wave sleep and lead to physical dependence.
Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.