Sleep apnea

Sleep apnea, sleep apnoea or sleep apnœa is a sleep disorder characterized by pauses in breathing during sleep. These episodes, called apneas (literally, "without breath"), each last long enough so one or more breaths are missed, and occur repeatedly throughout sleep. The standard definition of any apneic event includes a minimum 10 second interval between breaths, with either a neurological arousal (3-second or greater shift in EEG frequency, measured at C3, C4, O1, or O2), or a blood oxygen desaturation of 3-4 percent or greater, or both arousal and desaturation. Sleep apnea is diagnosed with an overnight sleep test called a polysomnogram.

Clinically significant levels of sleep apnea are defined as 5 or more events of any type per hour of sleep time (from the polysomnogram). There are three distinct forms of sleep apnea: Central, Obstructive and Complex (complex is a combination of central and obstructive) with 0.4%, 84% and 15% making up their respective percentages of cases.^[1] Breathing is interrupted by the lack of effort in central sleep apnea; in obstructive sleep apnea, breathing is interrupted by a physical block to airflow despite effort. In mixed sleep apnea, there is a transition from central to obstructive features during the events themselves.

Regardless of type, the individual with sleep apnea is rarely aware of having difficulty breathing, even upon awakening. 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, 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.

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Obstructive sleep apnea

Obstructive sleep apnea (OSA) is more frequent than central sleep apnea; it is a common condition in many parts of the world. If studied carefully in a sleep lab by polysomnography, approximately 1 in 5 American adults has at least mild OSA.^[2] Since the muscle tone of the body ordinarily relaxes during sleep, and since, at the level of the throat, the human airway is composed of walls of soft tissue, which can collapse, it is easy to understand why breathing can be obstructed during sleep. Although many individuals experience episodes of obstructive sleep apnea at some point in life, a much smaller percentage of people are afflicted with chronic severe obstructive sleep apnea.

Normal sleep/wakefulness in adults has distinct stages numbered 1 to 4, REM sleep, non-REM sleep NREM and consciousness. The deeper stages (3 to 4) of REM sleep are required for the physically restorative effects of sleep, and in pre-adolescents are the focus of release for human growth hormone. Stages 2 and REM, which combined are 70% of an average person's total sleep time, are more associated with mental recovery and maintenance. During REM sleep in particular, muscle tone of the throat and neck, as well as the vast majority of all skeletal muscles, is almost completely attenuated, allowing the tongue and soft palate/oropharynx to relax, and in the case of sleep apnea, to impede the flow of air to a degree ranging from light snoring to complete collapse. In the cases where airflow is reduced to a degree where blood oxygen levels fall, or the physical exertion to breathe is too great, neurological mechanisms trigger a sudden interruption of sleep, called a neurological arousal. These arousals may or may not result in complete awakening, but can have a significant negative effect on the restorative quality of sleep. In significant cases of obstructive sleep apnea, one consequence is sleep deprivation due to the repetitive disruption and recovery of sleep activity. This sleep interruption in stages 3 and 4 (also collectively called slow-wave sleep), can interfere with normal growth patterns, healing, and immune response, especially in children and young adults.

Many people experience elements of obstructive sleep apnea for only a short period of time. This can be the result of an upper respiratory infection that causes nasal congestion, along with swelling of the throat, or tonsillitis that temporarily produces very enlarged tonsils. The Epstein-Barr virus, for example, is known to be able to dramatically increase the size of lymphoid tissue during acute infection, and obstructive sleep apnea is fairly common in acute cases of severe infectious mononucleosis. Temporary spells of obstructive sleep apnea syndrome may also occur in individuals who are under the influence of a drug (such as alcohol) that may relax their body tone excessively and interfere with normal arousal from sleep mechanisms.

Laboratory findings

Polysomnography

  Results of polysomnography in obstructive sleep apnea show pauses in breathing. As in central apnea, pauses are followed by a relative decrease in blood oxygen and an increase in the blood carbon dioxide. Whereas in central sleep apnea the body's motions of breathing stop, in obstructive sleep apnea the chest not only continues to make the movements of inhalation, the movements typically become even more pronounced. Monitors for airflow at the nose and mouth show efforts to breathe are not only present, but that they are often exaggerated. The chest muscles and diaphragm contract and the entire body may thrash and struggle.

Obstructive sleep apnea is the most common category of sleep-disordered breathing. The prevalence of OSA among the adult population in western Europe and North America has not been confidently established, but in the mid-1990s was estimated to be 3-4% of women and 6-7% of men.

An "event" can be either an apnea, characterised by complete cessation of airflow for at least 10 seconds, or a hypopnea in which airflow decreases by 50 percent for 10 seconds or decreases by 30 percent if there is an associated decrease in the oxygen saturation or an arousal from sleep (American Academy of Sleep Medicine Task Force, 1999). To grade the severity of sleep apnea, the number of events per hour is reported as the apnea-hypopnea index (AHI). An AHI of less than 5 is considered normal. An AHI of 5-15 is mild; 15-30 is moderate and more than 30 events per hour characterizes severe sleep apnea.

Home oximetry

In patients who are at high likelihood of having OSA, a randomized controlled trial found that home oximetry may be adequate and easier to obtain than formal polysomnography.^[3] High probability patients were indentified by Epworth Sleepiness Scale (ESS) of 10 or greater and a Sleep Apnea Clinical Score (SACS) of 15 or greater.^[4]

Populations at risk

Individuals with decreased muscle tone, increased soft tissue around the airway, and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. Men, whose anatomy is typified by increased body mass in the torso and neck, are more typical sleep apnea sufferers, especially through middle age and older. Adult women suffer typically less frequently and to a lesser degree than men do, owing partially to physiology, but possibly to emerging links to levels of progesterone. Prevalence in post-menopausal women approaches that of men in the same age range.

Adults

In adults, the most typical individual with obstructive sleep apnea syndrome suffers from obesity, with particular heaviness at the face and neck. Obesity is not always present with OSA, in fact a significant number of adults with normal body mass indices (BMI) have decrease in muscle tone causing airway collapse and sleep apnea. The cause of the decreased tone is not presently understood. The hallmark symptom of obstructive sleep apnea syndrome in adults is excessive daytime sleepiness. Typically, an adult or adolescent with severe long-standing obstructive sleep apnea will fall asleep for very brief periods in the course of usual daytime activities if given any opportunity to sit or rest. This behavior may be quite dramatic, sometimes occurring during conversations with others at social gatherings.

Children

Although this so called "hypersomnolence" (excessive sleepiness) may also occur in children, it is not at all typical of young children with sleep apnea. Toddlers and young children with severe obstructive sleep apnea instead ordinarily behave as if "over-tired" or "hyperactive." Adults and children with very severe obstructive sleep apnea also differ in typical body habitus. Adults are generally heavy, with particularly short and heavy necks. Young children, on the other hand, are generally not only thin, but may have "failure to thrive," where growth is reduced. Poor growth occurs for two reasons: the work of breathing is high enough that calories are burned at high rates even at rest, and the nose and throat are so obstructed that eating is both tasteless and physically uncomfortable. Obstructive sleep apnea in children, unlike adults, is almost always caused by obstructive tonsils and adenoids and is usually cured with tonsillectomy and adenoidectomy.

This problem can also be caused by excessive weight. The symptoms are more like the symptoms adults feel: restlessness, exhaustion, and more.

Common signs and symptoms

(The signs and symptoms that follow apply to both adults and children suffering with sleep apnea)

Additional signs of obstructive sleep apnea include restless sleep, and loud snoring (with periods of silence followed by gasps). Other symptoms are non-specific: morning headaches, trouble concentrating, irritability, forgetfulness, mood or behavior changes, decreased sex drive, increased heart rate, anxiety, depression, weight gain, increased frequency of urination, nocturia (getting up during the night to urinate), esophageal reflux and heavy sweating at night.

The most serious consequence of obstructive sleep apnea is to the heart. In severe and prolonged cases, there are increases in pulmonary pressures that are transmitted to the right side of the heart. This can result in a severe form of congestive heart failure (cor pulmonale).

Health Risks

The sleep deprivation and lack of oxygen caused by sleep apnea increases health risks such as cardiovascular disease, high blood pressure, stroke, diabetes, weight gain and obesity.

Many studies indicate that it is the effect of the "fight or flight" response on the body that happens with each apneic event that increases these risks. The fight or flight response causes many hormonal changes in the body; those changes, coupled with the low oxygen saturation level of the blood, cause damage to the body over time.^[5][6][7][8]

Craniofacial syndromes

There are patterns of unusual facial features that occur in recognizable syndromes. Some of these craniofacial syndromes are genetic, others are from unknown causes. In many craniofacial syndromes, the features that are unusual involve the nose, mouth and jaw, or resting muscle tone, and put the individual at risk for obstructive sleep apnea syndrome.

Down Syndrome is one such syndrome. In this chromosomal abnormality, several features combine to make the presence of obstructive sleep apnea more likely. The specific features in Down Syndrome that predispose to obstructive sleep apnea include: relatively low muscle tone, narrow nasopharynx, and large tongue. Obesity and enlarged tonsils and adenoids, conditions that occur commonly in the western population, are much more likely to be obstructive in a person with these features than without them. Obstructive sleep apnea does occur even more frequently in people with Down Syndrome than in the general population. A little over 50% of all people with Down Syndrome suffer from obstructive sleep apnea (de Miguel-Díez, et al 2003), and some physicians advocate routine testing of this group (Shott, et al 2006).

In other craniofacial syndromes, the abnormal feature may actually improve the airway, but its correction may put the person at risk for obstructive sleep apnea after surgery, when it is modified. Cleft palate syndromes are such an example. During the newborn period, all humans are obligate nasal breathers. The palate is both the roof of the mouth and the floor of the nose. Having an open palate may make feeding difficult, but generally does not interfere with breathing, in fact - if the nose is very obstructed an open palate may relieve breathing. There are a number of clefting syndromes in which the open palate is not the only abnormal feature, additionally there is a narrow nasal passage - which may not be obvious. In such individuals, closure of the cleft palate- whether by surgery or by a temporary oral appliance, can cause the onset of obstruction.

Skeletal advancement in an effort to physically increase the pharyngeal airspace is often an option for craniofacial patients with upper airway obstruction and small lower jaws (mandibles). These syndromes include Treacher Collins Syndrome and Pierre Robin Sequence. Mandibular advancement surgery is often just one of the modifications needed to improve the airway, others may include reduction of the tongue, tonsillectomy or modified uvulopalatoplasty.

Pharyngeal flap surgery may cause obstructive sleep apnea

Obstructive sleep apnea is a serious complication that seems to be most frequently associated with pharyngeal flap surgery, compared to other procedures for treatment of velopharyngeal inadequacy (VPI).^[9] In OSA, recurrent interruptions of respiration during sleep are associated with temporary airway obstruction. Following pharyngeal flap surgery, depending on size and position, the flap itself may have an “obturator” or obstructive effect within the pharynx during sleep, blocking ports of airflow and hindering effective respiration.^[10][11] There have been documented instances of severe airway obstruction, and reports of post-operative OSA continue to increase as healthcare professionals (i.e. physicians, speech language pathologists) become more educated about this possible dangerous condition.^[12] Subsequently, in clinical practice, concerns of OSA have matched or exceeded interest in speech outcomes following pharyngeal flap surgery.

The surgical treatment for velopalatal insufficiency may cause obstructive sleep apnea syndrome. When velopalatal insufficiency is present, air leaks into the nasopharynx even when the soft palate should close off the nose. A simple test for this condition can be made by placing a tiny mirror at the nose, and asking the subject to say "P". This p sound, a plosive, is normally produced with the nasal airway closed off - all air comes out of the pursed lips, none from the nose. If it is impossible to say the sound without fogging a nasal mirror, there is an air leak - reasonable evidence of poor palatal closure. Speech is often unclear due to inability to pronounce certain sounds. One of the surgical treatments for velopalatal insufficiency involves tailoring the tissue from the back of the throat and using it to purposefully cause partial obstruction of the opening of the nasopharynx. This may actually cause obstructive sleep apnea syndrome in susceptible individuals, particularly in the days following surgery, when swelling occurs (see below: Special Situation: Anesthesia and Surgery).

Treatment

There are a variety of treatments for obstructive sleep apnea, depending on an individual’s medical history, the severity of the disorder and, most importantly, the specific cause of the obstruction.

In acute infectious mononucleosis, for example, although the airway may be severely obstructed in the first 2 weeks of the illness, the presence of lymphoid tissue (suddenly enlarged tonsils and adenoids) blocking the throat is usually only temporary. A course of anti-inflammatory steroids such as prednisone (or another kind of glucocorticoid drug) is often given to reduce this lymphoid tissue. Although the effects of the steroids are short term, in most affected individuals, the tonsillar and adenoidal enlargement are also short term, and will be reduced on its own by the time a brief course of steroids is completed. In unusual cases where the enlarged lymphoid tissue persists after resolution of the acute stage of the Epstein-Barr infection, or in which medical treatment with anti-inflammatory steroids does not adequately relieve breathing, tonsillectomy and adenoidectomy may be urgently required.

Obstructive sleep apnea in children is usually due to chronically enlarged tonsils and adenoids. Tonsillectomy and adenoidectomy is curative. The operation may be far from trivial, especially in the worst apnea cases, in which growth is retarded and abnormalities of the right heart may have developed. Even in these extreme cases, the surgery tends to cure not only the apnea and upper airway obstruction, but allows normal subsequent growth and development. Once the high end-expiratory pressures are relieved, the cardiovascular complications reverse themselves. The postoperative period in these children requires special precautions (see surgery and obstructive sleep apnea syndrome below).

The treatment for obstructive sleep apnea in adults with poor oropharyngeal airways secondary to heavy upper body type is varied. Unfortunately, in this most common type of obstructive sleep apnea, unlike some of the cases discussed above, reliable cures are not the rule.

Some treatments involve lifestyle changes, such as avoiding alcohol and medications that relax the central nervous system (for example, sedatives and muscle relaxants), losing weight, and quitting smoking. Some people are helped by special pillows or devices that keep them from sleeping on their backs, or oral appliances to keep the airway open during sleep. If these conservative methods are inadequate, doctors often recommend continuous positive airway pressure (CPAP), in which a face mask is attached to a tube and a machine that blows pressurized air into the mask and through the airway to keep it open. There are also surgical procedures that can be used to remove and tighten tissue and widen the airway, but the success rate is not high.^{[citation needed]} Some individuals may need a combination of therapies to successfully treat their sleep apnea.

Physical intervention

The most widely used current therapeutic intervention is positive airway pressure whereby a breathing machine pumps a controlled stream of air through a mask worn over the nose, mouth, or both. The additional pressure splints or holds open the relaxed muscles, just as air in a balloon inflates it. There are several variants:

• (CPAP), or continuous positive airway pressure, in which a controlled air compressor generates an airstream at a constant pressure. This pressure is prescribed by the patient's physician, based on an overnight test or titration. Newer CPAP models are available which slightly reduce pressure upon exhalation to increase patient comfort and compliance. CPAP is the most common treatment for obstructive sleep apnea.
• (VPAP), or variable positive airway pressure, also known as bilevel or BiPAP, uses an electronic circuit to monitor the patient's breathing, and provides two different pressures, a higher one during inhalation and a lower pressure during exhalation. This system is more expensive, and is sometimes used with patients who have other coexisting respiratory problems and/or who find breathing out against an increased pressure to be uncomfortable or disruptive to their sleep.
• (APAP), or automatic positive airway pressure, is the newest form of such treatment. An APAP machine incorporates pressure sensors and a computer which continuously monitors the patient's breathing performance. It adjusts pressure continuously, increasing it when the user is attempting to breathe but cannot, and decreasing it when the pressure is higher than necessary. Although FDA approved, these devices are still considered experimental by many, and are not covered by most insurance plans.

A second type of physical intervention, a Mandibular advancement splint (MAS), is sometimes prescribed for mild or moderate sleep apnea sufferers. The device is a mouthguard similar to those used in sports to protect the teeth. For apnea patients, it is designed to hold the lower jaw slightly down and forward relative to the natural, relaxed position. This position holds the tongue farther away from the back of the airway, and may be enough to relieve apnea or improve breathing for some patients. The FDA accepts only 16 oral appliances for the treatment of sleep apnea. A listing is available at its website.

Oral appliance therapy is less effective than CPAP, but is more 'user friendly'. Side-effects are common, but rarely is the patient aware of them.

Pharmaceuticals

There are no effective drug-based treatments for obstructive sleep apnea which have FDA approval, however a clinical trial of mirtazapine,^[13] has shown early promise at the University of Illinois at Chicago. This small, early study found a 50% decrease in occurrence of apnea episodes and 28% decrease in sleep disruptions in 100% of patients (twelve patients) taking them.^[14][15] Nonetheless, due to the risk of weight gain and sedation (two risk factors and consequences of sleep apnea) it is not recommended.^[16] An effort to improve the effects of mirtazapine by combining it with another existing medication was cancelled during Phase IIa trials in 2006.^[17] Dr. David Carley and Dr. Miodrag Radulovacki, the sleep researchers who were behind the initial clinical trial of mirtazapine are now working on a new treatment that consists of two other existing medications taken off-label together for treatment of sleep apnea.^[18]

Other serotonin effecting agents^[19] that have been explored as a treatment for apnea include prozac,^[20] tryptophan^[21] and protriptyline.^[22]

Oral administration of the methylxanthine theophylline (chemically similar to caffeine) can reduce the number of episodes of apnea, but can also produce side effects such as heart palpitations and insomnia. Theophylline is generally ineffective in adults with OSA, but is sometimes used to treat central sleep apnea (see below), and infants and children with apnea.

When other treatments do not completely treat the OSA, drugs are sometimes prescribed to treat a patient's daytime sleepiness or somnolence. These range from stimulants such as amphetamines to modern anti-narcoleptic medicines. The anti-narcoleptic medicine modafinil is seeing increased use in this role as of 2004.

In most cases, weight loss will reduce the number and severity of apnea episodes. In the morbidly obese, a major loss of weight (such as what occurs after bariatric surgery) can sometimes cure the condition.

Neurostimulation

Many researchers believe that OSA is at root a neurological condition, in which nerves that control the tongue and soft palate fail to sufficiently stimulate those muscles, leading to over-relaxation and airway blockage. A few experiments and trial studies have explored the use of pacemakers and similar devices, programmed to detect breathing effort and deliver gentle electrical stimulation to the muscles of the tongue.

This is not a common mode of treatment for OSA patients as of 2004, but it is an active field of research.

Surgical intervention

A number of different surgeries are available to improve the size or tone of a patient's airway. For decades, tracheostomy was the only effective treatment for sleep apnea. It is used today only in rare, intractable cases that have withstood other attempts at treatment. Modern operations employ one or more of several options, tailored to each patient's needs. Long term success rates are low, resulting in most doctors favoring CPAP.

• Nasal surgery, including turbinectomy (removal or reduction of a nasal turbinate), or straightening of the nasal septum, in patients with nasal obstruction or congestion which reduces airway pressure and complicates OSA.
• Tonsilectomy and/or adenoidectomy in an attempt to increase the size of the airway.
• Removal or reduction of parts of the soft palate and some or all of the uvula, such as uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP). Modern variants of this procedure sometimes use radiofrequency waves to heat and remove tissue.
• Reduction of the tongue base, either with laser excision or radiofrequency ablation.
• Genioglossus Advancement, in which a small portion of the lower jaw that attaches to the tongue is moved forward, to pull the tongue away from the back of the airway.
• Hyoid Suspension, in which the hyoid bone in the neck, another attachment point for tongue muscles, is pulled forward in front of the larynx.
• Maxillomandibular advancement (MMA). A more invasive surgery usually only tried in difficult cases where other surgeries have not relieved the patient's OSA, or where an abnormal facial structure is suspected as a root cause. In MMA, the patient's upper and lower jaw are detached from the skull, moved forward, and reattached with pins and/or plates.^[23]
• Pillar procedure, three small inserts are injected into the soft palate to offer support, potentially reducing snoring in mild to moderate sleep apnea.^[24]

The role of surgery in the treatment of sleep apnea has been questioned repeatedly as the long term success rate of the procedures has come into question. Surgery is generally only effective in obstructive sleep apnea where the obstruction can be effectively removed. The patient's age, weight and other factors may make them a bad candidate for surgery. Many sleep specialists still regard positive air pressure treatment as the gold standard. [5] [6] [7] [8] [9] [10] [11]

Special situation: surgery and anesthesia in patients with sleep apnea syndrome

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.

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.

Individuals with sleep apnea generally require more intensive monitoring after surgery for these reasons.

Alternative treatments

Breathing exercises, such as those used in Yoga, the Buteyko method, or didgeridoo playing can be effective.^[25] There are muscles which act to tension and open the airway during each inspiration. Exercises can, in some cases, restore sufficient function to these muscles to prevent or reduce apnea.

Gargling with salt water may shrink the tonsils due to osmosis, and can be used as an alternative treatment.^[26]

Position treatments

One of the best treatments is merely to sleep at a 30 degree angle^[27] or higher, as if in a recliner. Doing so helps prevent gravity from collapsing the airway. Lateral positions (sleeping on your side), as opposed to supine positions (sleeping on your back), are also recommended as a treatment for sleep apnea,^[28][29][30] largely because the effect of gravity is not as strong to collapse the airway in the lateral position. Nonetheless, sleeping at a 30 degree angle is a superior sleep position compared to either a supine or lateral position.^[31] A 30 degree position can be achieved by sleeping in a recliner, buying an adjustable bed, or buying a bed wedge to place under the mattress.

Central sleep 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 it 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 malfunctions and fails 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 (hypoxia) 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 terrible 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 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 due 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 brains' mandate for the body to breathe. Even in severe cases of central sleep apnea, the effects almost always result in pauses that make breathing irregular, rather than cause the total cessation of breathing.

• Normal Respiratory Drive: After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gasses with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. How do the changing blood levels of oxygen and carbon dioxide result in a breath? In any healthy animal, including humans, oxygen and carbon dioxide receptors in the blood stream (called chemoreceptors) send nerve impulses to the brain, which then signals reflex opening of the larynx (so that the opening between the vocal cords enlarges) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it. The body inhales.
• Physiologic effects of central apnea: During central apneas, the central respiratory drive is absent, and the brain does not respond to changing blood levels of the respiratory gases. No breath is taken despite the normal signals to inhale. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures. At worst, central sleep apnea may cause sudden death. Short of death, drops in blood oxygen may trigger seizures- even in the absence of epilepsy. In people with epilepsy, the hypoxia caused by apnea may trigger seizures that had previously been well controlled by medications. In other words, a seizure disorder may become unstable in the presence of sleep apnea. In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction).With longstanding recurrent episodes of apnea, over months and years, increases in carbon dioxide levels may change the pH of the blood enough to cause a metabolic acidosis.

Laboratory findings

Polysomnography of sleep apnea shows pauses in breathing that are followed by drops in blood oxygen and increases in blood carbon dioxide. In adults, a pause must last 10 seconds to be scored as an apnea. However in young children, who normally breathe at a much faster rate than adults, the pause may be many seconds shorter and still be considered apnea. The cessation of airflow in central sleep apnea has an association with no physical attempts to breathe. On polysomnograms, there is an absence of rib cage and abdominal movements while airflow ceases at the nose and lips. Obstructive sleep apnea show pauses in breathing for at least 10 seconds causing a decrease in blood oxygen and associates with physical attempts to breathe.

Hypopneas in adults are defined as a 50% reduction in air flow for more than 10 s, followed by a 4% desaturation, and/or arousal. The Apnea- Hypopnea Index (AHI) is expressed as the number of apneas and hypopneas per hour of sleep.

Clinical details

Any individual, no matter how healthy, who is given enough of a central respiratory depressant drug will develop apnea on a central basis. Generally, drugs that are central respiratory depressants also have sedative effects, and so the individual taking a toxic dose of such a drug is likely to be asleep, or at least in an altered state of consciousness, when breathing becomes irregular. Alcohol is such a central respiratory depressant in large doses, so are opiates, barbiturates, benzodiazepines, and many other tranquilizers. Some individuals have abnormalities that predispose them to central sleep apnea. The treatment for the condition depends on its specific cause.

Similarly, in any person who has some form of sleep apnea (including obstructive sleep apnea), breathing irregularities during sleep can be dangerously aggravated by taking one of these drugs. Quantities that are normally considered safe may cause the person with chronic sleep apnea to stop breathing altogether. Should these individuals have general anesthesia, for example, they require prolonged monitoring after initial recovery, as compared to a person with no history of sleep apnea, because apnea is likely to occur with even low levels of the drugs in their system.

Premature infants with immature brains and reflex systems are at high risk for central sleep apnea syndrome, even if these babies are otherwise healthy. Fortunately, those premature babies who have the syndrome will generally outgrow it as they mature, providing they receive careful enough monitoring and supportive care during infancy to survive. Because of the propensity toward apnea, medications that can cause respiratory drive depression are either not given to premature infants, or given under careful monitoring, with equipment for resuscitation immediately available. Such precautions are routinely taken for premature infants after general anesthesia. Caffeine has been found to help reduce apnea in preterm infants and to aid in care after general anesthesia.^[32]

Sudden infant death syndrome is sometimes theorized to be attributable to sleep apnea.

Congenital Central Hypoventilation Syndrome: This rare, inborn condition involves a specific gene, PHOX2B. This homeobox gene guides maturation of the autonomic nervous system, and loss-of-function mutations lead to the failure of the brain to effectively control breathing during sleep in patients with the syndrome. There may be a pattern of recognizable facial features among individuals affected with this syndrome.^[2]

Once almost uniformly fatal, congenital hypoventilation ("abnormally low ventilation") syndrome is now treatable. The children who have it must have tracheotomies and access to mechanical ventilation on respirators while sleeping, but most do not need to use a respirator while awake. The use of a diaphragmatic pacemaker may offer an alternative for some patients. When pacemakers have enabled some children to sleep without the use of a mechanical respirator, reported cases still required the tracheotomy to remain in place, because the vocal cords did not move apart with inhalation. This form of central sleep apnea has been called Ondine's curse. Now that some children with the syndrome have grown up, there is particular need for their avoidance of adolescent behaviors, such as alcohol use, which can easily be lethal.^[33]

Adults suffering from congestive heart failure are at risk for a form of central sleep apnea called Cheyne-Stokes respiration. This is periodic breathing with recurrent episodes of apnea alternating with episodes of rapid breathing. In those who have it, Cheyne-Stokes respirations occur while both awake and asleep. There is good evidence that replacement of the failed heart (heart transplant) cures central apnea in these patients. The use of some medications that are respiratory stimulants decrease the severity of apnea in some patients.

Section references

1) Macey PM. Macey KE. Woo MA. Keens TG. Harper RM. Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome.[see comment]. [Journal Article] Pediatric Research. 57(4):500-9, 2005 Apr. 2) Bradley TD. Floras JS. Sleep apnea and heart failure: Part II: central sleep apnea. [Review] [55 refs] [Journal Article. Review] Circulation. 107(13):1822-6, 2003 April 8. 3) Mansfield DR. Solin P. Roebuck T. Bergin P. Kaye DM. Naughton MT. The effect of successful heart transplant treatment of heart failure on central sleep apnea.[see comment]. [Journal Article] Chest. 124(5):1675-81, 2003 Nov. 4)Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. [Clinical Trial. Journal Article. Randomized Controlled Trial] American Journal of Respiratory & Critical Care Medicine. 173(2):234-7, 2006 Jan 15.

Mixed apnea and complex sleep apnea

Some people with sleep apnea have a combination of both types. When obstructive sleep apnea syndrome is severe and longstanding, episodes of central apnea sometimes develop. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown, but is most commonly related to acid-base and CO₂ feedback malfunctions stemming from heart failure. There is a constellation of diseases and symptoms relating to body mass, cardiovascular, respiratory, and occasionally, neurological dysfunction that have a synergistic effect in sleep-disordered breathing. The presence of central sleep apnea without an obstructive component is a common result of chronic opiate use (or abuse), due to the characteristic respiratory depression caused by large doses of narcotics.

Complex sleep apnea has recently been described by researchers as a novel presentation of sleep apnea. Patients with complex sleep apnea exhibit OSA, but upon application of positive airway pressure, the patient exhibits persistent central sleep apnea. This central apnea is most commonly noted while on CPAP therapy, after the obstructive component has been eliminated. This has long been seen in sleep laboratories, and has historically been managed either by CPAP or BiLevel therapy. Adaptive servo-ventilation modes of therapy have been introduced to attempt to manage this complex sleep apnea. Studies have demonstrated marginally superior performance of the adaptive servo ventilators in treating Cheyne-Stokes breathing, however, no longitudinal studies have yet been published, nor have any results been generated which suggest any differential outcomes versus standard CPAP therapy. At the AARC 2006 in Las Vegas, NV, researchers reported successful treatment of hundreds of patients on Adapt SV therapy, however these results have not been reported in peer reviewed publications as of July, 2007.

An important finding by Dernaika, et al., (Chest 2007, 132) suggests that transient central apnea produced during CPAP titration (the so called "complex sleep apnea") is "... transient and self-limited." The central apneas may in fact be secondary to sleep fragmentation during the titration process. As of July 2007, there has been no alternate convincing evidence produced that these central sleep apnea events associated with CPAP therapy for obstructive sleep apnea are of any significant pathophysiologic import.

Treatment

One method of treating central sleep apnea is with a special kind of positive airway pressure machine providing additional pressure during inhalation, including a Spontaneous / Time (ST) feature. This machine will automatically deliver pressure to the patient if it fails to detect a certain minimum number of breaths per minute.

For unknown reasons, possibly due to changes in pulmonary oxygen stores,^[34] sleeping in the lateral position has also been found to be helpful for central sleep apnea (CSA).

Medications like Acetazolamide^[35][36] lower blood pH and encourage respiration. Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.^[37][38][39]

History

The first reports of what is now called obstructive sleep apnea, in the medical literature date only from 1965, when it was independently described by French and German investigators. However, 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 Dicken's novel, The Pickwick Papers, is an accurate clinical picture of adult 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. Tracheostomy was the recommended treatment and, though it could be life-saving, post-operative complications in the stoma were frequent in these very obese and short-necked individuals.

The management of obstructive sleep apnea was revolutionized with the introduction of continuous positive airway pressure (CPAP), first described in 1981 by Colin Sullivan and associates in Sydney, Australia. 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.

Symptoms, signs and sequelae

This section summarizes the clinical picture and consequences of obstructive sleep apnea syndrome.

As already mentioned, snoring is almost a uniform finding in an individual with this syndrome, but many people snore without having apnea. Snoring is the turbulent sound of air moving through the back of the mouth, nose and throat. 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 if snoring stops. If it does, along with breath, while the persons' chest and body tries to breathe - that is literally a description of an event in obstructive sleep apnea syndrome. When breathing starts again, there is typically a deep gasp, and then the resumption of snoring.

Sometimes, elevated arterial pressure (commonly called high blood pressure) is a sequela of obstructive sleep apnea syndrome.^[40] 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.^[41] Stroke is associated with obstructive sleep apnea.^[42] Sleep apnea sufferers also have a 30% higher risk of heart attack or death than those unaffected.^[43]

References

General references

• Maninder Kalra; Ranajit Chakraborty (March 2007). "Genetic susceptibility to obstructive sleep apnea in the obese child". Sleep Medicine 8 (2): 169-175. PMID 17275401.
• American Academy of Sleep Medicine Task Force (1999). "Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research.". Sleep 22 (5): 667-89. PMID 10450601.
• Bell, R. B. (2001). "Skeletal advancement for the treatment of obstructive sleep apnea in children". Cleft Palate-Craniofacial Journal 38 (2): 147-54.
• Caples S, Gami A, Somers V (2005). "Obstructive sleep apnea.". Ann Intern Med 142 (3): 187-97. PMID 15684207.
• Cohen, M. M. J.; Kreiborg, S. (1992). "Upper and lower airway compromise in the Apert syndrome". American Journal of Medical Genetics 44: 90-93.
• de Miguel-Díez J, Villa-Asensi J, Alvarez-Sala J (2003). "Prevalence of sleep-disordered breathing in children with Down syndrome: polygraphic findings in 108 children." (PDF). Sleep 26 (8): 1006-9. PMID 14746382.
• Mathur R, Douglas N (1994). "Relation between sudden infant death syndrome and adult sleep apnoea/hypopnoea syndrome.". Lancet 344 (8925): 819-20. PMID 7916096.
• Mortimore I, Douglas N (1997). "Palatal muscle EMG response to negative pressure in awake sleep apneic and control subjects.". Am J Respir Crit Care Med 156 (3 Pt 1): 867-73. PMID 9310006.
• Perkins, J. A.; Sie, K. C. Y., Milczuk, H., & Richardson, M. A. (1997). "Airway management in children with craniofacial anomalies". Cleft Palate-Craniofacial Journal 34 (2): 135-40.
• Sculerati N.; Gottlieb MD. Zimbler MS. Chibbaro PD. McCarthy JG. (1998 December). "Airway management in children with major craniofacial anomalies.". Laryngoscope 108 (12): 1806-12.
• Shepard, J. W.; Thawley, S. E. (1990). "Localization of upper airway collapse during sleep in patients with obstructive sleep apnea". American Review of Respiratory Disorders 141: 1350-55.
• Sher, A. (1990). Obstructive sleep apnea syndrome: a complex disorder of the upper airway. Otolaryngologic Clinics of North America, 24, 600.
• Shott S, Amin R, Chini B, Heubi C, Hotze S, Akers R (2006). "Obstructive sleep apnea: Should all children with Down syndrome be tested?". Arch Otolaryngol Head Neck Surg 132 (4): 432-6. PMID 16618913.
• Shouldice RB, O'Brien LM, O'Brien C, de Chazal P, Gozal D, Heneghan C (2004). "Detection of obstructive sleep apnea in pediatric subjects using surface lead electrocardiogram features". Sleep 27 (4): 784-92. PMID 15283015.
• Slovis B. & Brigham K. (2001). "Disordered Breathing", in ed Andreoli T. E.: Cecil Essentials of Medicine. Philadelphia: W.B. Saunders, pp210-211. 
• Strollo P, Rogers R (1996). "Obstructive sleep apnea.". N Engl J Med 334 (2): 99-104. PMID 8531966.
• Sullivan C, Issa F, Berthon-Jones M, Eves L (1981). "Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares.". Lancet 1 (8225): 862-5. PMID 6112294.