Sleep apnea

Sleep apnea

Obstructive sleep apnea
Classification and external resources
ICD-10 G47.3
ICD-9 327.23, 780.57
MedlinePlus 000811 003997
eMedicine ped/2114
MeSH D012891

Sleep apnea (or sleep apnoea in British English; /æpˈniːə/) is a sleep disorder characterized by pauses in breathing or instances of shallow or infrequent breathing during sleep. Each pause in breathing, called an apnea, can last for several seconds to several minutes, and may occur, by definition, at least 5 times in an hour.[1] Similarly, each abnormally shallow breathing event is called a hypopnea. Sleep apnea is classified as a dyssomnia, meaning abnormal behavior or psychological events occur during sleep.[2] When breathing is paused, carbon dioxide builds up in the bloodstream. Chemoreceptors in the blood stream note the high carbon dioxide levels. The brain is signaled to wake the person sleeping and breathe in air. Breathing normally will restore oxygen levels and the person will fall asleep again.[3] Sleep apnea is often diagnosed with an overnight sleep test called a polysomnogram, or "sleep study".

There are three forms of sleep apnea: central (CSA), obstructive (OSA), and complex or mixed sleep apnea (i.e., a combination of central and obstructive) constituting 0.4%, 84%, and 15% of cases, respectively.[4] In CSA, breathing is interrupted by a lack of respiratory effort; in OSA, breathing is interrupted by a physical block to airflow despite respiratory effort, and snoring is common. According to the National Institutes of Health, 12 million Americans have OSA. There are more cases of sleep apnea still because people either do not report the condition or do not know they have sleep apnea.[5]

Regardless of type, an individual with sleep apnea is rarely aware of having difficulty breathing, even upon awakening.[6] Sleep apnea is recognized as a problem by others witnessing the individual during episodes or is suspected because of its effects on the body (sequelae). Symptoms may be present for years (or even decades) without identification, during which time the sufferer may become conditioned to the daytime sleepiness and fatigue associated with significant levels of sleep disturbance. Sleep apnea affects not only adults but some children as well.[7]

People have issues with excessive daytime sleepiness (EDS) and impaired alertness.[7] In other words, common effects of sleep apnea include daytime fatigue, a slower reaction time, and vision problems.[7] OSA may increase risk for driving accidents and work-related accidents. If OSA is not treated, one has an increased risk of other health problems such as diabetes. Even death could occur from untreated OSA due to lack of oxygen to the body.[8] Moreover, patients are examined using "standard test batteries" in order to further identify parts of the brain that may be adversely affected by sleep apnea,[7] including those that govern:

Due to the disruption in daytime cognitive state, behavioral effects are also present. These include moodiness, belligerence, as well as a decrease in attentiveness and drive.[9] Another symptom of sleep apnea is waking up in sleep paralysis. In severe cases, the fear of sleep due to sleep paralysis can lead to insomnia. These effects become very hard to deal with, thus the development of depression may transpire.[10] There is also evidence that the risk of diabetes among those with moderate or severe sleep apnea is higher.[11] There is also increasing evidence that sleep apnea may also lead to liver function impairment, particularly fatty liver diseases (see steatosis).[9][12][13][14] Finally, because there are many factors that could lead to some of the effects previously listed, some patients are not aware that they suffer from sleep apnea and are either misdiagnosed, or just ignore the symptoms altogether.[7]

Risk factors

Sleep apnea can affect people regardless of gender, race, or age, including children. Risk factors include being male, overweight, obese, or over the age of 40; or having a large neck size (greater than 16–17 inches), enlarged tonsils, enlarged tongue, small jaw bone, gastroesophageal reflux, allergies, sinus problems, family history of sleep apnea, or deviated septum causing nasal obstruction.[15] Alcohol, sedatives and tranquilizers also promote sleep apnea by relaxing the throat. People who smoke have sleep apnea at three times the rate of people who have never smoked.[16] All the factors above may contribute to obstructive sleep apnea. Central sleep apnea is more influenced by being male, being older than 65 years, having heart disorders such as atrial fibrillation, and stroke or brain tumor. Brain tumors may hinder the brain's ability to regulate normal breathing.[16]

Diagnosis

The diagnosis of sleep apnea is based on the conjoint evaluation of clinical symptoms (e.g. excessive daytime sleepiness and fatigue) and of the results of a formal sleep study (polysomnography, or reduced channels home based test). The latter aims at establishing an "objective" diagnosis indicator linked to the quantity of apneic events per hour of sleep (Apnea Hypopnea Index(AHI), or Respiratory Disturbance Index (RDI)), associated to a formal threshold, above which a patient is considered as suffering from sleep apnea, and the severity of their sleep apnea can then be quantified. Mild OSA (Obstructive Sleep Apneas) ranges from 5 to 14.9 events per hour of sleep, moderate OSA falls in the range of 15–29.9 events per hour of sleep, and severe OSA would be a patient having over 30 events per hour of sleep.

Nevertheless, due to the number and variability in the actual symptoms and nature of apneic events (e.g., hypopnea vs apnea, central vs obstructive), the variability of patients' physiologies, and the intrinsic imperfections of the experimental setups and methods, this field is opened to debate.[17] Within this context, the definition of an apneic event depends on several factors (e.g. patient's age) and account for this variability through a multi-criteria decision rule described in several, sometimes conflicting, guidelines.[18][19] One example of a commonly adopted definition of an apnea (for an adult) includes a minimum 10 second interval between breaths, with either a neurological arousal (a 3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2) or a blood oxygen desaturation of 3–4% or greater, or both arousal and desaturation.

Oximetry

Oximetry, which may be performed overnight in a patient's home, is an easier alternative to formal sleep study (polysomnography). In one study, normal overnight oximetry was very sensitive and so if normal, sleep apnea was unlikely.[20] In addition, home oximetry may be equally effective in guiding prescription for automatically self-adjusting continuous positive airway pressure.[21]

Classification

Obstructive sleep apnea

Screenshot of a PSG system showing an obstructive apnea.

Obstructive sleep apnea (OSA) is the most common category of sleep-disordered breathing. The muscle tone of the body ordinarily relaxes during sleep, and at the level of the throat the human airway is composed of collapsible walls of soft tissue which can obstruct breathing during sleep. Mild occasional sleep apnea, such as many people experience during an upper respiratory infection, may not be important, but chronic severe obstructive sleep apnea requires treatment to prevent low blood oxygen (hypoxemia), sleep deprivation, and other complications.

Individuals with low muscle tone and soft tissue around the airway (e.g., because of obesity) and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. The elderly are more likely to have OSA than young people. Men are more likely to suffer sleep apnea than women and children are, though it is not uncommon in the last two population groups.[22]

The risk of OSA rises with increasing body weight, active smoking and age. In addition, patients with diabetes or "borderline" diabetes have up to three times the risk of having OSA.

Common symptoms include loud snoring, restless sleep, and sleepiness during the daytime. Diagnostic tests include home oximetry or polysomnography in a sleep clinic.

Some treatments involve lifestyle changes, such as avoiding alcohol or muscle relaxants, losing weight, and quitting smoking. Many people benefit from sleeping at a 30-degree elevation of the upper body[23] or higher, as if in a recliner. Doing so helps prevent the gravitational collapse of the airway. Lateral positions (sleeping on a side), as opposed to supine positions (sleeping on the back), are also recommended as a treatment for sleep apnea,[24][25][26] largely because the gravitational component is smaller in the lateral position. Some people benefit from various kinds of oral appliances such as the Mandibular advancement splint to keep the airway open during sleep. Continuous positive airway pressure (CPAP) is the most effective treatment for severe obstructive sleep apnea but oral appliances are considered a first line approach equal to CPAP for mild to moderate sleep apnea according to the AASM parameters of care.[27] There are also surgical procedures to remove and tighten tissue and widen the airway.

Snoring is a common finding in people with this syndrome. Snoring is the turbulent sound of air moving through the back of the mouth, nose, and throat. Although not everyone who snores is experiencing difficulty breathing, snoring in combination with other conditions such as overweight and obesity has been found to be highly predictive of OSA risk.[28] The loudness of the snoring is not indicative of the severity of obstruction, however. If the upper airways are tremendously obstructed, there may not be enough air movement to make much sound. Even the loudest snoring does not mean that an individual has sleep apnea syndrome. The sign that is most suggestive of sleep apneas occurs when snoring stops.

Other indicators include (but are not limited to): hypersomnolence, obesity BMI >30, large neck circumference (16 in (410 mm) in women, 17 in (430 mm) in men), enlarged tonsils and large tongue volume, micrognathia, morning headaches, irritability/mood-swings/depression, learning and/or memory difficulties, and sexual dysfunction.

The term "sleep-disordered breathing" is commonly used in the U.S. to describe the full range of breathing problems during sleep in which not enough air reaches the lungs (hypopnea and apnea). Sleep-disordered breathing is associated with an increased risk of cardiovascular disease, stroke, high blood pressure, arrhythmias, diabetes, and sleep deprived driving accidents.[29][30][31][32] When high blood pressure is caused by OSA, it is distinctive in that, unlike most cases of high blood pressure (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping.[33] Stroke is associated with obstructive sleep apnea.[34]

It has been revealed that people with OSA show tissue loss in brain regions that help store memory, thus linking OSA with memory loss.[35] Using magnetic resonance imaging (MRI), the scientists discovered that sleep apnea patients' mammillary bodies were nearly 20 percent smaller, particularly on the left side. One of the key investigators hypothesized that repeated drops in oxygen lead to the brain injury.[36]

Central sleep apnea

Main article: Central sleep apnea
Screenshot of a PSG system showing a central apnea.

In pure central sleep apnea or Cheyne–Stokes respiration, the brain's respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide, and the neurological feedback mechanism that monitors them, do not react quickly enough to maintain an even respiratory rate, with the entire system cycling between apnea and hyperpnea, even during wakefulness. The sleeper stops breathing and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no struggling. After the episode of apnea, breathing may be faster (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases and absorb more oxygen.

While sleeping, a normal individual is "at rest" as far as cardiovascular workload is concerned. Breathing is regular in a healthy person during sleep, and oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant. The respiratory drive is so strong that even conscious efforts to hold one's breath do not overcome it. Any sudden drop in oxygen or excess of carbon dioxide (even if tiny) strongly stimulates the brain's respiratory centers to breathe.

In central sleep apnea, the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. If the pause in breathing is long enough, the percentage of oxygen in the circulation will drop to a lower than normal level (hypoxaemia) and the concentration of carbon dioxide will build to a higher than normal level (hypercapnia). In turn, these conditions of hypoxia and hypercapnia will trigger additional effects on the body. Brain cells need constant oxygen to live, and if the level of blood oxygen goes low enough for long enough, the consequences of brain damage and even death will occur. Fortunately, central sleep apnea is more often a chronic condition that causes much milder effects than sudden death. The exact effects of the condition will depend on how severe the apnea is and on the individual characteristics of the person having the apnea. Several examples are discussed below, and more about the nature of the condition is presented in the section on Clinical Details.

In any person, hypoxia and hypercapnia have certain common effects on the body. The heart rate will increase, unless there are such severe co-existing problems with the heart muscle itself or the autonomic nervous system that makes this compensatory increase impossible. The more translucent areas of the body will show a bluish or dusky cast from cyanosis, which is the change in hue that occurs owing to lack of oxygen in the blood ("turning blue"). Overdoses of drugs that are respiratory depressants (such as heroin, and other opiates) kill by damping the activity of the brain's respiratory control centers. In central sleep apnea, the effects of sleep alone can remove the brain's mandate for the body to breathe.

Mixed apnea and complex sleep apnea

Some people with sleep apnea have a combination of both types; its prevalence ranges from 0.56% to 18%. The condition is generally detected when obstructive sleep apnea is treated with CPAP and central sleep apnea emerges. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown but is most likely related to incorrect settings of the CPAP treatment and other medical conditions the person has.[37]

Management

Treatment often starts with behavioral therapy. Many patients are told to avoid alcohol, sleeping pills, and other sedatives, which can relax throat muscles, contributing to the collapse of the airway at night.[38] As sleep apnea is inherently worse in the supine position for many patients (positional sleep apnea), sleeping on one's side is often advised.

Possibly owing to changes in pulmonary oxygen stores, sleeping on one's side (as opposed to on one's back) has been found to be helpful for central sleep apnea with Cheyne–Stokes respiration.[26]

Continuous positive airway pressure

Patient using a CPAP mask, covering only nose
CPAP machine with two models of full face masks

For moderate to severe sleep apnea, the most common treatment is the use of a continuous positive airway pressure (CPAP) or automatic positive airway pressure (APAP) device.[38][39] These splints the persons airway open during sleep by means of pressurized air. The person typically wears a plastic facial mask, which is connected by a flexible tube to a small bedside CPAP machine.[40] The CPAP machine generates the required air pressure to keep the person's airways open during sleep. While pure CPAP machines require one to input a desired pressure (usually determined in an overnight sleep study), an APAP machine will automatically titrate the air pressure as needed to minimize apneas and hypopneas. Advanced models may warm or humidify the air and monitor the patient's breathing to ensure proper treatment.

Retail cost for CPAP machines is between $300–$2,000. The extra CPAP supplies include the mask, tubes, and filters averaging between $300–$800 per year. CPAP machine costs may be higher if a humidifier is included. Humidifiers add comfort to using the device and some reported a decrease in side effects.[41]

Although CPAP therapy is extremely effective in reducing apneas and less expensive than other treatments, some patients find it extremely uncomfortable. Patients complain of feeling trapped, having chest discomfort, and skin or nose irritation. Other side effects a patient may experience are dry mouth, dry nose, nosebleeds, sore lips and gums.[42] Many patients refuse to continue the therapy or fail to use their CPAP machines on a nightly basis, especially in the long term.[43]

Surgery

Illustration of surgery on the mouth and throat.

Several surgical procedures (sleep surgery) are used to treat sleep apnea, although they are normally a second line of treatment for those who reject CPAP treatment or are not helped by it. Surgical treatment for obstructive sleep apnea needs to be individualized to address all anatomical areas of obstruction.

Nasal obstruction

Often, correction of the nasal passages needs to be performed in addition to correction of the oropharynx passage. Septoplasty and turbinate surgery may improve the nasal airway.

Pharyngeal obstruction

Tonsillectomy and uvulopalatopharyngoplasty (UPPP or UP3) are available to address pharyngeal obstruction.

Uvulopalatopharyngoplasty. A) pre-operative, B) original UPPP, C) modified UPPP, and D) minimal UPPP.

The Pillar Procedure is a minimally invasive treatment for snoring and obstructive sleep apnea. This procedure was FDA indicated in 2004. During this procedure, three to six or more Dacron (the material used in permanent sutures) strips are inserted into the soft palate, using a modified syringe and local anesthetic. While the procedure was initially approved for the insertion of three "pillars" into the soft palate, it was found that there was a significant dosage response to more pillars, with appropriate candidates. After this brief and virtually painless outpatient operation, which usually lasts no more than 30 minutes, the soft palate is more rigid and snoring and sleep apnea can be reduced. This procedure addresses one of the most common causes of snoring and sleep apnea — vibration or collapse of the soft palate (the soft part of the roof of the mouth). If there are other factors contributing to snoring or sleep apnea, such as the nasal airway or an enlarged tongue, it will likely need to be combined with other treatments to be more effective.

Hypopharyngeal or base of tongue obstruction

Base-of-tongue advancement by means of advancing the genial tubercle of the mandible, tongue suspension, or hyoid suspension (aka hyoid myotomy and suspension or hyoid advancement) may help with the lower pharynx.

Other surgery options may attempt to shrink or stiffen excess tissue in the mouth or throat; procedures done at either a doctor's office or a hospital. Small shots or other treatments, sometimes in a series, are used for shrinkage, while the insertion of a small piece of stiff plastic is used in the case of surgery whose goal is to stiffen tissues.[38]

Multi-level surgery

The Stanford Center for Excellence in Sleep Disorders Medicine achieved a 95% cure rate of sleep apnea patients by surgery.[44] Maxillomandibular advancement (MMA) is considered the most effective surgery for sleep apnea patients,[45] because it increases the posterior airway space (PAS).[46] The main benefit of the operation is that the oxygen saturation in the arterial blood increases.[46] In a study published in 2008, 93.3.% of surgery patients achieved an adequate quality of life based on the Functional Outcomes of Sleep Questionnaire (FOSQ).[46] Surgery led to a significant increase in general productivity, social outcome, activity level, vigilance, intimacy, and intercourse.[46] Overall risks of MMA surgery are low: The Stanford University Sleep Disorders Center found 4 failures in a series of 177 patients, or about one out of 44 patients.[47] However, health professionals are often unsure as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impeding surgery; or significant craniofacial abnormalities which hinder device use.[48] Maxillomandibular advancement surgery is often combined with genioglossus advancement, as both are skeletal surgeries for sleep apnea.

Potential complications

Several inpatient and outpatient procedures use sedation. Many drugs and agents used during surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards. In an individual with either central, obstructive or mixed sleep apnea, these low doses may be enough to cause life-threatening irregularities in breathing or collapses in a patient's airways.[49] Use of analgesics and sedatives in these patients postoperatively should therefore be minimized or avoided.

Surgery on the mouth and throat, as well as dental surgery and procedures, can result in postoperative swelling of the lining of the mouth and other areas that affect the airway. Even when the surgical procedure is designed to improve the airway, such as tonsillectomy and adenoidectomy or tongue reduction, swelling may negate some of the effects in the immediate postoperative period. Once the swelling resolves and the palate becomes tightened by postoperative scarring, however, the full benefit of the surgery may be noticed.

A sleep apnea patient undergoing any medical treatment must make sure his or her doctor and anesthetist are informed about the sleep apnea. Alternative and emergency procedures may be necessary to maintain the airway of sleep apnea patients.[50]

Other

Neurostimulation

In 2014 the U.S. Food and Drug Administration granted pre-market approval for use of an upper airway stimulation system in people who cannot use a continuous positive airway pressure device. The system senses respiration and increases muscle tone at the back of the tongue by delivering a mild electrical pulse so that the tongue will not block the airway.[51]

Medications

There is limited evidence for medication but acetazolamide "may be considered" for the treatment of central sleep apnea; it also found that zolpidem and triazolam may be considered for the treatment of central sleep apnea, but "only if the patient does not have underlying risk factors for respiratory depression".[39] Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.[52][53][54]

Oral appliances

General dentists can fabricate an oral appliance. The oral appliance, called a mandibular advancement splint, is a custom-made mouthpiece that shifts the lower jaw forward and opens the bite slightly, which opens up the airway. Oral appliance therapy (OAT) is usually successful in patients with mild to moderate obstructive sleep apnea.[55]

Epidemiology

The Wisconsin Sleep Cohort Study estimated in 1993 that roughly one in every 15 Americans was affected by at least moderate sleep apnea.[56][57] It also estimated that in middle-age as many as nine percent of women and 24 percent of men were affected, undiagnosed and untreated.[56][57][58]

The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S. the average untreated sleep apnea patient's annual health care costs $1,336 more than an individual without sleep apnea. This may cause $3.4 billion/year in additional medical costs. Whether medical cost savings occur with treatment of sleep apnea remains to be determined.[59]

Prognosis

A 2012 study has shown that hypoxia (an inadequate supply of oxygen) that characterizes sleep apnea promotes angiogenesis which increase vascular and tumor growth, which in turn results in a 4.8 times higher incidence of cancer mortality.[60][61][62]

History

The clinical picture of this condition has long been recognized as a character trait, without an understanding of the disease process. The term "Pickwickian syndrome" that is sometimes used for the syndrome was coined by the famous early 20th century physician, William Osler, who must have been a reader of Charles Dickens. The description of Joe, "the fat boy" in Dickens's novel The Pickwick Papers, is an accurate clinical picture of an adult with obstructive sleep apnea syndrome.

The early reports of obstructive sleep apnea in the medical literature described individuals who were very severely affected, often presenting with severe hypoxemia, hypercapnia and congestive heart failure.

The management of obstructive sleep apnea was improved with the introduction of continuous positive airway pressure (CPAP), first described in 1981 by Colin Sullivan and associates in Sydney, Australia.[63] The first models were bulky and noisy, but the design was rapidly improved and by the late 1980s CPAP was widely adopted. The availability of an effective treatment stimulated an aggressive search for affected individuals and led to the establishment of hundreds of specialized clinics dedicated to the diagnosis and treatment of sleep disorders. Though many types of sleep problems are recognized, the vast majority of patients attending these centers have sleep-disordered breathing. Sleep apnea awareness day is April 18 in recognition of Colin Sullivan's.[64]

See also

References

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