Central sleep apnea

Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation.^[1][2] CSA is usually due to an instability in the body's feedback mechanisms that control respiration.^[3] Central sleep apnea can also be an indicator of Arnold–Chiari malformation.^[4]

Description

Individuals without sleep apnea are while sleeping "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:^[5] After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the blood stream (called chemoreceptors) send nerve impulses to the brain, which then signals for reflexive opening of the larynx (enlarging the opening between the vocal cords) 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.^[6] In the absence of centrap apnea, any sudden drop in oxygen or excess of carbon dioxide, even if small, strongly stimulates the brain's respiratory centers to breathe; the respiratory drive is so strong that even conscious efforts to hold one's breath do not overcome it.

In pure central sleep apnea, the brain's respiratory control centers, located in the region of the human brain known as the pre-Botzinger complex,^[7] are imbalanced during sleep and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. The neurological feedback mechanism that monitors blood levels of carbon dioxide and in turn stimulates respiration fails to react quickly enough to maintain an even respiratory rate, allowing the entire respiratory system to cycle between apnea and hyperpnea, even for a brief time following an awakening during a breathing pause. The sleeper stops breathing for up to two minutes and then starts again.^[8] There is no effort made to breathe during the pause in breathing: there are no chest movements and no muscular struggling, although when awakening occurs in the middle of a pause, the inability to immediately operate the breathing muscles often results in cognitive struggle accompanied by a feeling of panic exacerbated by the feeling associated with excessive blood CO₂ levels. Even in severe cases of central sleep apnea, however, the effects almost always result in pauses that make breathing irregular rather than cause the total cessation of breathing over the medium term. After the episode of apnea, breathing may be faster and/or more intense (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases, absorb more oxygen, and, when voluntary, enable a return to normal instinctive breathing patterns by restoring oxygen to the breathing muscles themselves.

Differential diagnosis versus obstructive sleep apnea

Although central and obstructive sleep apnea have some signs and symptoms in common, others are present in one but absent in another, enabling differential diagnosis as between the two types:

Signs and symptoms of sleep apnea generally

• Signs:

• Observed breathing pauses during sleep
• High carbon-dioxide saturation of blood, especially just before awakenings during which a sufferer experiences urgent need to breathe (see "Symptoms" below)
• Low oxygen saturation of blood
• Heart rate increase (response to both hypercapnia and hypoxia), unless there also exist problems with the heart muscle itself or the autonomic nervous system severe enough to make this compensatory increase impossible

• Symptoms:

• High frequency of urgent need to breathe upon awakening (symptom created by hypercapnia), especially among subset of awakenings occurring at times other than normal for an individual's sleep schedule and circadian rhythms

Signs and symptoms of central sleep apnea

• Signs:

• Lack of abdominal and thoracic movement for 10 seconds or longer during sleep and coincident with breathing pauses

• Symptoms:

• Inability, either complete or without excessive effort, to voluntarily operate diaphragm and other thoracic muscles upon awakening

• The combination of this symptom with a high frequency of urgent need to breathe upon awakening is especially specific in that the co-presence of the latter symptom differentiates central sleep apnea's presentation from that of sleep paralysis generally.

Signs and symptoms of and conditions associated with obstructive sleep apnea^[9]

• Signs:

• Observably ineffective respiratory movements (observable lack of air flow despite observable muscle movements indicating efforts to breathe)
• Snoring (high-sensitivity but low-specificity)
• Observably dry mouth or throat (high-sensitivity but low-specificity)

• Symptoms:

• Sleepiness, fatigue, or tiredness, often rising to the level of excessive daytime sleepiness
• Frequent feelings of choking (airway and/or lung compression), as distinguished from mere feeling of suffocation nonspecific with respect to presence/absence of pressure, upon awakening

• Associated conditions:

• Large neck circumference (>16" for females, > 17" for males) (frequent causal factor and possible indirect symptom; see "Obesity" below)
• Obesity (frequent causal factor and possible, albeit low-specificity, sign both direct and indirect): Obesity frequently involves accumulation of fat below the chin and around the neck, depressing the trachea when one is in the supine position, and central obesity can, depending on an individual's fat distribution, lead to increased direct pressure on the thoracic cavity and/or compressive anterior (headward) displacement of the abdominal organs, in the second case reducing space for and increasing difficulty of the motion of the diaphragm. Poor breathing during sleep a] reduces oxygen available for metabolism and may therefore depress basal metabolic rate during sleep, increasing the difference between supply of food energy and demand for it during that time and thereby promoting weight gain, and b] reduces sleep quality and recovery per time unit of sleep, resulting in sleepiness and/or fatigue that may prompt sufferers to eat more in an attempt to increase short-term energy levels.
• Correlation with cardiac disorders:

• Atrial fibrillation (AF): A study in the medical journal Sleep found that the prevalence of atrial fibrillation among patients with idiopathic central sleep apnea was significantly higher than the prevalence among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and 3.3%, respectively). The study was based on 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF include a causal relationship in one direction or the other between the two conditions or a common cause involving an abnormality of central cardiorespiratory regulation.^[10]
• Adults suffering from congestive heart failure are at risk for a form of central apnea called Cheyne-Stokes respiration, which manifests itself both during sleep and during waking hours. Cheyne-Stokes respiration is characterized by periodic breathing featuring recurrent episodes of apnea alternating with episodes of rapid breathing. There is good evidence that replacement of the failing heart (heart transplant) cures central apnea in these patients. Temporary measures (e.g., those taken pending the availability of an organ donor) include the administration of drugs whose effects include respiratory stimulation, although these drugs are not universally effective in reducing the severity of Cheyne-Stokes apneas.

Special case: Congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS), often referred to by its older name "Ondine's curse," is a rare and very severe inborn form of abnormal interruption and reduction in breathing during sleep. This condition involves a specific homeobox gene, PHOX2B, which guides maturation of the autonomic nervous system; certain loss-of-function mutations interfere with the brain's development of the ability to effectively control breathing. There may be a recognizable pattern of facial features among individuals affected with this syndrome.^[11]

Once almost uniformly fatal, CCHS is now treatable. 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.

Persons with the syndrome who survive to adulthood are strongly instructed to avoid certain condition-aggravating factors, such as alcohol use, which can easily prove lethal.^[12]

Diagnostic standards and procedures

A diagnosis of sleep apnea requires examination by a physician. The examination will require a study of an individual in a sleep lab. There, the patient will be monitored while at rest, and the periods when breathing ceases will be measured with respect to length and frequency.^[13] During polysomnography, a person with sleep apnea shows breathing interruptions followed by drops/reductions in blood oxygen and increases in blood carbon dioxide level.

• 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, shorter pauses may still be considered apneas.
• Hypopneas in adults are defined as a 30% reduction in air flow for more than ten seconds, followed by oxygen-saturation declines of at least 3% and/or EEG arousal. The Apnea-Hypopnea Index (AHI) is expressed as the number of apneas or hypopneas per hour of sleep.^[14]

As noted above, in central sleep apnea, the cessation of airflow is associated with the absence of physical attempts to breathe; specifically, polysomnograms reveal correlation between absence of rib cage and abdominal movements and cessation of airflow at the nose and lips. By contrast, in obstructive sleep apnea, pauses are not correlated with the absence of attempts to breathe and may even be correlated with more effortful breathing in an instinctive attempt to overcome the pressure on the sufferer's airway. If the majority of a sleep-apnea sufferer's apneas/hypopneas are central, his/her condition is classified as central; likewise, if the majority are obstructive, his/her condition is classified as obstructive.

Secondary effects

The conditions of hypoxia and hypercapnia, whether caused by apnea or not, trigger additional effects on the body. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures, how short is the interval between failures to breathe, and the presence or absence of independent conditions whose effects amplify those of an apneic episode.

• Brain cells need constant oxygen to live, and if the level of blood oxygen remains low enough for long enough, brain damage and even death will occur. These effects, however, are rarely a result of central sleep apnea, which is a chronic condition whose effects are usually much milder.
• Drops in blood oxygen levels that are severe but not severe enough to trigger brain-cell or overall death may trigger seizures even in the absence of epilepsy.
• In severe cases of sleep apnea, the more translucent areas of the body will show a bluish or dusky cast from cyanosis, the change in hue ("turning blue") produced by the deoxygenation of blood in vessels near the skin.
• Compounding effects of independent conditions:

• In persons with epilepsy, the hypoxia caused by apnea may be powerful enough to trigger seizures even in the presence of medication that otherwise controls those seizures well.
• In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction).
• Longstanding and recurrent episodes of apnea may, over months and years, have the cumulative effect of increasing blood carbon-dioxide levels to the point that enough carbon dioxide dissolves in the blood to form carbonic acid in overall proportions sufficient to cause respiratory acidosis.
• In persons who have either or both forms of sleep apnea, breathing irregularities during sleep can be dangerously aggravated by taking respiration-depressing drugs, especially sedative drugs that operate by depressing the central nervous system generally; respiratory depressants include opiates, barbiturates, benzodiazepines, and, in large quantities, alcohol, the last three of which are broad-spectrum CNS depressants. Quantities that are normally considered safe may cause the person with chronic sleep apnea to stop breathing altogether. Should these individuals have general anaesthesia, for example, they require prolonged monitoring after initial recovery, as compared against a person with no history of sleep apnea, because apnea is likely to occur with even low levels of the drugs in their system.
• Sudden infant death syndrome is sometimes theorized to be attributable to sleep apnea; the recommendation, prevalent since the mid-1980s, of placing infants on their backs rather than their stomachs for sleep represents an attempt to prevent those instances of breathing cessation that are attributable to compressive obstruction.
• Premature infants with immature brains and reflex systems are at high risk for central sleep apnea syndrome, even if these babies are otherwise healthy. Premature babies who have the syndrome will generally outgrow it as they mature, provided that they receive careful enough monitoring and supportive care during infancy to survive. Because of premature infants' propensity toward central apnea, medications that can cause respiratory drive depression are either not given to them or administered to them only under careful monitoring, with equipment for resuscitation immediately available. Such precautions are routinely taken for premature infants after general anesthesia; administration of caffeine has been found not only to aid in maintenance of respiratory function after general anaesthesia but to reduce apnea for preterm infants regardless of context.^[15]

Treatment

After a patient receives a diagnosis, the diagnosing physician can provide different options for treatment.

• Mechanical regulation of airflow and/or airway pressure:

• For individuals with obstructive sleep apnea, one of the more common treatments is CPAP (continuous positive airway pressure). During CPAP treatment, the patient wears a mask that fits over the nose and sometimes the mouth and is connected to a device that compresses normal room air and blows it into the airway at a constant pressure. This pressure must be at a constant level high enough to prevent the airway from collapsing but low enough to permit exhalation of deoxygenated air and avoid damage to lung structures such as the alveoli.
• Treatment for central sleep apnea differs in that the device is set not at one constant optimal pressure but rather at two different settings, one for inhalation (IPAP) and for exhalation (EPAP), maintaining normal breathing rhythm by inflating the patient's lungs at regular intervals whose specifics, such as the breathing rate and the duration of a single breath, can be programmed. Devices tailored to this purpose are known as BiPAP ("bilevel positive airway pressure") devices.
• Both CPAP and BiPAP devices can be connected to a humidifier to humidify and heat the inhaled air, thus reducing unpleasant symptoms such as a sore throat or blocked nose that can result from inhaling cold, dry air.

• An experimental pacemaker for the diaphragm has recently shown promising results in overcoming central sleep apnea.^[16]

See also

• Sleep apnea
• Obstructive sleep apnea

References

Additional references

• Macey PM, Macey KE, Woo MA, Keens TG, Harper RM (April 2005). "Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome". Pediatric Research 57 (4): 500–9. doi:10.1203/01.PDR.0000155757.98389.53. PMID 15718375. 
• Bradley TD, Floras JS (April 2003). "Sleep apnea and heart failure: Part II: central sleep apnea". Circulation 107 (13): 1822–6. doi:10.1161/01.CIR.0000061758.05044.64. PMID 12682029. 
• Mansfield DR, Solin P, Roebuck T, Bergin P, Kaye DM, Naughton MT (November 2003). "The effect of successful heart transplant treatment of heart failure on central sleep apnea". Chest 124 (5): 1675–81. doi:10.1378/chest.124.5.1675. PMID 14605034. 
• Javaheri S (January 2006). "Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study". American Journal of Respiratory and Critical Care Medicine 173 (2): 234–7. doi:10.1164/rccm.200507-1035OC. PMID 16239622.