Central sleep apnea
Encyclopedia
Central sleep apnea 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
. It is a collective term referring to two breathing disorders: Cheyne-Stokes respiration
and periodic breathing
. CSA is usually due to an instability in the body's feedback mechanisms that control 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. 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.
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 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 shows 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 ten seconds, followed by a 3% desaturation, and/or arousal. The Apnea-Hypopnea Index
(AHI) is expressed as the number of apneas and hypopneas per hour of sleep.
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
, barbiturate
s, benzodiazepines, and many other tranquilizer
s. 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.
Sudden infant death syndrome
is sometimes theorized to be attributable to sleep apnea.
Congenital Central Hypoventilation Syndrome (CCHS): This very severe condition of abnormally low breathing during sleep is rare and is an inborn condition that 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 recognizable pattern of facial features among individuals affected with this syndrome.
Once almost uniformly fatal, CCHS is now treatable. The children who have it must have tracheotomies
and access to mechanical ventilation on respirator
s 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
. People with the syndrome who survive to adulthood need to avoid certain risk factors, such as alcohol use, which can easily prove lethal.
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 stimulant
s decrease the severity of apnea in some patients.
There is an association between atrial fibrillation
(AF) and central sleep apnea. A study 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). There was a total of 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF are a causal relationship between the two conditions, or an abnormality of central cardiorespiratory regulation.
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
-related disorder in which the effort to breathe
Breathing
Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...
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
Oxygen saturation
Oxygen saturation or dissolved oxygen is a relative measure of the amount of oxygen that is dissolved or carried in a given medium. It can be measured with a dissolved oxygen probe such as an oxygen sensor or an optode in liquid media, usually water.It has particular significance in medicine and...
. It is a collective term referring to two breathing disorders: Cheyne-Stokes respiration
Cheyne-Stokes respiration
Cheyne-Stokes respiration is an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing called an apnea. The pattern repeats, with each cycle usually taking 30 seconds to 2...
and periodic breathing
Periodic breathing
Periodic breathing is an abnormal pattern of breathing characterized by oscillation of ventilation between hyperpnea and hypopnea with a crescendo-decrescendo pattern in the depth of respirations, to compensate for changing serum partial pressures of oxygen and carbon dioxide.Cheyne-Stokes...
. CSA is usually due to an instability in the body's feedback mechanisms that control respiration
Respiration (physiology)
'In physiology, respiration is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction...
.
Definition
In pure central sleep apneaSleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
the brain's respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
, 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
Hypercapnia
Hypercapnia or hypercapnea , also known as hypercarbia, is a condition where there is too much carbon dioxide in the blood...
). In turn, these conditions of hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
and hypercapnia
Hypercapnia
Hypercapnia or hypercapnea , also known as hypercarbia, is a condition where there is too much carbon dioxide in the blood...
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
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
, 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. 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 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 reflex opening of the larynxLarynxThe larynx , commonly called the voice box, is an organ in the neck of amphibians, reptiles and mammals involved in breathing, sound production, and protecting the trachea against food aspiration. It manipulates pitch and volume...
(so that the opening between the vocal cords enlarges) and movements of the rib cage muscles and diaphragm. These muscles expand the thoraxThoraxThe thorax is a division of an animal's body that lies between the head and the abdomen.-In tetrapods:...
(chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it. - 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 seizureSeizureAn epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, even in the absence of epilepsyEpilepsyEpilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
. 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 infarctionMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
). Longstanding recurrent episodes of apnea, over months and years, may cause an increase in carbon dioxide levels that can change the pH of the blood enough to cause a metabolic acidosisMetabolic acidosisIn medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
.
Diagnosis
| AHI | Rating |
|---|---|
| <5 | Normal |
| 5-15 | Mild |
| 15-30 | Moderate |
| >30 | Severe |
Polysomnography
Polysomnography
Polysomnography , also known as a sleep study, is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. The test result is called a polysomnogram, also abbreviated PSG...
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 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 shows 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 ten seconds, followed by a 3% desaturation, and/or arousal. The Apnea-Hypopnea Index
Apnea-hypopnea index
The apnea-hypopnea index is an index of sleep apnea severity that combines apneas and hypopneas. The apneas must last for at least 10 seconds and are associated with a decrease in blood oxygenation...
(AHI) is expressed as the number of apneas and hypopneas per hour of sleep.
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
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
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
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
is such a central respiratory depressant in large doses; so are opiates
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
, barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
s, benzodiazepines, and many other tranquilizer
Tranquilizer
A tranquilizer, or tranquilliser , is a drug that induces tranquility in an individual.The term "tranquilizer" is imprecise, and is usually qualified, or replaced with more precise terms:...
s. 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
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
has been found to help reduce apnea in preterm infants and to aid in care after general anesthesia.
Sudden infant death syndrome
Sudden infant death syndrome
Sudden infant death syndrome is marked by the sudden death of an infant that is unexpected by medical history, and remains unexplained after a thorough forensic autopsy and a detailed death scene investigation. An infant is at the highest risk for SIDS during sleep, which is why it is sometimes...
is sometimes theorized to be attributable to sleep apnea.
Congenital Central Hypoventilation Syndrome (CCHS): This very severe condition of abnormally low breathing during sleep is rare and is an inborn condition that involves a specific gene, PHOX2B
PHOX2B
Paired-like homeobox 2b , also known as neuroblastoma Phox , is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4....
. 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 recognizable pattern of facial features among individuals affected with this syndrome.
Once almost uniformly fatal, CCHS is now treatable. The children who have it must have tracheotomies
Tracheotomy
Among the oldest described surgical procedures, tracheotomy consists of making an incision on the anterior aspect of the neck and opening a direct airway through an incision in the trachea...
and access to mechanical ventilation on respirator
Respirator
A respirator is a device designed to protect the wearer from inhaling harmful dusts, fumes, vapors, or gases. Respirators come in a wide range of types and sizes used by the military, private industry, and the public...
s while sleeping, but most do not need to use a respirator while awake. The use of a diaphragmatic pacemaker
Diaphragmatic pacemaker
A diaphragmatic pacemaker, in medicine, is a surgically-implanted device used to help patients breathe following complications from spinal cord injuries. The device works through pacing of the diaphragm.-Mechanism:...
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
Ondine's curse
Ondine's Curse, also called congenital central hypoventilation syndrome or primary alveolar hypoventilation, is a respiratory disorder that is fatal if untreated...
. People with the syndrome who survive to adulthood need to avoid certain risk factors, such as alcohol use, which can easily prove lethal.
Association with heart disease
Adults suffering from congestive heart failureCongestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
are at risk for a form of central sleep apnea called Cheyne-Stokes respiration
Cheyne-Stokes respiration
Cheyne-Stokes respiration is an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing called an apnea. The pattern repeats, with each cycle usually taking 30 seconds to 2...
. 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 stimulant
Respiratory stimulant
A respiratory stimulant is a drug which acts to increase the action of the respiratory system.An example is doxapram....
s decrease the severity of apnea in some patients.
There is an association between atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
(AF) and central sleep apnea. A study 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). There was a total of 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF are a causal relationship between the two conditions, or an abnormality of central cardiorespiratory regulation.