Author: Dr Robert C. Basner Columbia University 2008-06-10
Central Sleep Apnea: Non-obstructive sleep apnea
Central Sleep Apnea: Non-obstructive sleep apnea
The following is a discussion of non-obstructive, or
"central" sleep apnea. As with its companion piece, "obstructive sleep
apnea," its content is not intended to be a medical primer nor meant to
exhaustively cover all of the risks and complications possible with the
disorder and its diagnosis, treatment, and non-treatment. The author
stresses that this discussion does not substitute for the need to
personally discuss all aspects of the health effects, diagnosis, and
treatment of sleep apnea with a health care professional and, generally,
with an expert in sleep disorders medicine. It should also be noted
that the focus of this piece is on adult central sleep apnea; although
some aspects of central sleep apnea in children are discussed here, the
risks and benefits involved in the decision making process for testing
for and treating such a disorder in children are substantially different
than those for adults, as pediatric sleep apnea is often very different
in its manifestations and treatment requirements (see recommended
readings at the end of this piece).
"Sleep" apnea refers to the fact that the apneas occur during sleep, usually during the transition from the awake state to drowsiness and light sleep.
Normal persons tend to have transient central apneas during the transition from awake to sleep, due to normal sleep related changes in the brain’s control of breathing: that is, there is, less "drive" to breathe, and in specific, a sleep-related need for increased levels of carbon dioxide (CO2) to cause the central nervous system to signal the muscles of breathing to contract, and, in fact, breathe. It is normal for a person to have one or several of these events until sleep becomes more continuous. "Post-sigh" apneas are common during the sleep period when a person arouses; the person reflexively takes a large breath (sigh) or two, which abruptly decreases the carbon dioxide levels, followed by rapid transition back into sleep, with the onset of a central apnea due to the lack of enough carbon dioxide levels to drive the breathing effort. Just as with the first attempts to transition into sleep, this is a normal breathing response to cycling between sleep and awake states. While such "transitional" apneas are most likely associated with drowsiness and light sleep (non rapid-eye movement, or NREM), erratic breathing and intermittent central apneas are seen commonly in rapid-eye movement (REM) sleep. Therefore, a certain amount of central apneas may occur throughout a night of sleep that are considered normal responses; such cases are not associated with any underlying abnormality of the central nervous system or breathing apparatus, and are not known to cause any major harm to the person who displays such activity. Such "normal" apneas may be associated with the person coming to a full awakening with a feeling that she/he stopped breathing, possibly resulting in a feeling of fear, anxiety, or panic which may be associated with a racing heartbeat, and sweating.
However, if central apneas occur repetitively, generally in the range of five times per hour of sleep, an abnormal situation is considered to exist, and the person is considered to have "central sleep apnea." When a central apnea occurs in sleep, blood oxygen levels fall and carbon dioxide levels rise, and the frequent or repetitive occurrence of such apneas may have harmful effects on the heart, brain, and circulation. Further, with each resumption of breathing, there is typically an "arousal" from sleep, usually not within the awareness of the sufferer, but often obvious to an observer, who may see the person make an abrupt gasping sound with abrupt breathing movements of the chest and abdomen. These arousals are usually associated with a surge of adrenaline into the circulation, with speeding up of the heart and an increase in the blood pressure. Such apneas may occur in a repetitive or even cyclic fashion.
The frequency of apneas, however, is not the only criterion for deeming these events abnormal or significantly harmful; the length of events and degree of decrease in oxygen blood levels is also of importance in determining the potential harm and the treatment necesary, as is the clinical condition in which the apnea occurs.
In most cases, the central apneas that occur due to sleep are not seen when the person is alert and awake, although there are certain conditions of central sleep apnea associated with abnormal breathing patterns when awake. For example, see "Central sleep apnea due to Cheyne-Stokes breathing pattern" and "Central sleep apnea due to a medical condition (other than Cheyne-Stokes breathing)" below.
It is emphasized that any observed prolonged, or symptomatic, breathing pauses during sleep should be considered potentially harmful, particularly in persons with known heart problems such as heart failure, those with known cerebrovascular disease (such as having had a stroke), and should be reported to a health care provider, optimally one who is a sleep medicine specialist.
How is "central" sleep apnea
Obstructive
apneas are apneas in which, ultimately, the airflow into the lungs is
blocked by collapse of the soft airway passage between the nose, mouth,
and larynx. The sufferer will likely make a loud snoring noise at the
end of such an obstructive apnea as the airway re-opens. By definition, a
central apnea has no such blockage. While "central" and "obstructive"
apneas are very much related in terms of why and when they occur during
sleep and what may be done to treat them, ultimately the disorders are
also very different in many important ways. It should be noted,
however, that central and obstructive apneas may be difficult to
distinguish by the observer, as obstructive apneas often begin with very
shallow breathing, or in fact no breathing, followed by increasing
efforts to breathe without airflow occurring due to the collapsed air
passages in the nose, oral cavity, and throat. Central and obstructive
apneas may occur in the same person during sleep, and there may be
"mixed" apneas in which the apnea begins with no effort to breathe for
at least 10 seconds followed by obstructed breathing. Further, it is
known that some patients with obstructive sleep apnea will manifest
non-obstructive or central sleep apnea when treated with positive airway
pressure; this has recently been termed "complex sleep apnea."
Central sleep apnea is not a single medical disorder, but rather occurs in many settings, which sometimes reflects the medical or neurologic disorder it is seen with, and sometimes represents a disorder without clear underlying causes. All central sleep apnea disorders should be considered abnormal and potentially harmful to the person who has such a disorder. The typical central sleep apnea syndromes with notes regarding their recognition, importance, and possible treatments are detailed in the following section.
A discussion of each of the major types of central sleep apnea follows:
Diagnosed by polysomnography (PSG – a sleep study using both monitoring equipment and direct observation and described in detail below), this condition is defined as at least five central apneas per hour of sleep in association with symptoms of awakenings and inability
to stay asleep, sometimes with fear of sleeping because of awakening
with a sensation of not breathing, and/or excessive daytime sleepiness
due to sleep disruption in association with the apneas. It is not clear
that there are long term effects on the heart or vascular system from
this disorder, although patients diagnosed with primary central sleep
apnea may have concurrent atrial fibrillation (9). The cause of this
condition is unknown, but it is most often seen in middle aged and
elderly persons, and by definition is diagnosed in the absence of any
other major medical or sleep disorder.
The major task in diagnosing primary central sleep apnea is to be certain that a more serious disorder of breathing during sleep does not exist, including obstructive sleep apnea (see accompanying Google KNOL Obstructive Sleep Apnea), Cheyne-Stokes breathing (see below), or a breathing disorder while awake that may be exacerbated during sleep; this can include patients with chronic lung disease such as emphysema, or chest wall or neuromuscular disorders (see central sleep apnea due to a medical condition, below). It is also necessary to assess for other sleep fragmenting conditions which may predispose to arousal and sleep fragmentation, which in turn predisposes to central apneas as the person transitions back into sleep after arousal. Such fragmenting disorders may be intrinsic to sleep, such as periodic limb movement disorder, or extrinsic, such as chronic pain, sleep disruptive medications (for example, amphetamines, steroids, alcohol, nicotine, and certain blood pressure medications) or environmental light or noise. It is often difficult to define whether the central sleep apnea is causing the arousals, the arousals are causing the sleep apnea, or both, and this situation may be thought of as a "vicious cycle."
Treatment of primary central sleep apnea, once the condition is defined as such, may include avoidance of supine (lying on your back) sleep if this is shown to be a factor in the tendency to have the central apneas, avoidance of any medications and environmental conditions associated with poor sleep consolidation, and treatment of any medical or sleep disorders as noted which may predispose to sleep fragmentation and associated transitions between wake and sleep states. Consistent success with positive airway pressure (creating a flow of air that creates enough pressure during inhalation to keep the airway open) for this condition is not well documented. Other treatments, including respiratory stimulants (4, 14), oxygen, and carbon dioxide have been used in some patients, but there is not a large data base documenting consistent success for such treatment for primary central sleep apnea.
With each decrease or cessation of breathing effort, oxygen saturation of blood levels decrease, and at the end there is a speeding up of the heart rate along with an arousal of the central nervous system, thus disrupting sleep. The patient may be seen and heard to have a gasping breath at the end of the apnea, but not the explosive sound of snoring or opening of the upper airway typically seen with obstructive sleep apnea, although the two disorders often overlap in patients with heart failure.
Patients with chronic heart failure have a high risk of having this form of central sleep apnea ;
studies have found a prevalence range between 33%-40% of this type of
sleep-related breathing disorder in such patients. In patients admitted
to the hospital with an acute worsening of their chronic heart failure,
the prevalence of central sleep apnea with Cheyne-Stokes breathing
appears to be even higher (11). It should be noted that the prevalence
of obstructive sleep apnea is also high in chronic heart failure
patients, in the range of 12%-38% (7, 10, 13).
Such abnormal breathing in sleep in the setting of heart failure, while reflecting to some extent the severity of the heart failure, is associated with sleep-related decrease in oxygen levels in the blood, and increased adrenaline-like activity which can contribute to further deterioration in cardiac function if untreated. Untreated Cheyne-Stokes breathing in heart failure has been associated with increased risk of death compared with patients with heart failure without central sleep apnea with Cheyne-Stokes breathing (8). While optimizing treatment of the heart failure is an important and well-accepted strategy in patients with heart failure and central sleep apnea, it is not clear that even optimal medical management of the heart failure will improve the central sleep apnea (11) and therefore suggests that direct treatment of the breathing disorder is important.
In patients who have had a stroke, the likelihood of having a sleep-related breathing disorder including central sleep apnea with Cheyne-Stokes breathing in the first 72 hours following the stroke is high, with the latter occurring in more than 25% of such patients (12). It has been shown that the presence of a sleep related breathing disorder is associated with worse neurologic outcomes compared to acute stroke patients without demonstrated sleep related breathing disorder; such breathing disorders include obstructive as well as central apnea syndromes (6).
Treatment of central sleep apnea with Cheyne-Stokes breathing in the setting of heart failure may include many modalities. Positive airway pressure, usually delivered as a continuous pressure at the nose or mouth (thus, Continuous Positive Airway Pressure
or CPAP) is a major therapy for central sleep apnea with Cheyne-Stokes
breathing, and the one most studied up to now. CPAP is the usual
treatment for obstructive sleep apnea (see accompanying Ggoogle
Knol). CPAP is a safe and immediately applicable method of allowing the
sleep apnea sufferer to have a decreased frequency of central apneas,
direct improvement in heart function, decreased tendency to arousal,
with improved sleep quality. To use CPAP, the person wears a soft head
strap that holds a cushioned soft plastic mask snugly
in place around the nose, or in some cases the nose and mouth during
sleep. There are also "nasal pillows" which are soft tubes that fit into
the nostrils and thus avoid pressing onto the skin of the face and
bridge of the nose. The mask, (or nasal pillows), is
attached via plastic tubing to a small machine – an airflow generator –
that delivers a specific level of air pressure to the nose or nose and
mouth. Figure 1 (above) is an illustration of a patient wearing a nasal mask attached to a CPAP machine.
CPAP has been shown to decrease the frequency of central apneas in patients with stable chronic heart failure, but the largest prospective study of this treatment failed to show a benefit of this treatment in improving survival, or the need for heart transplant. There also was some concern that the treatment may have caused the risk of death to increase in some patients. A follow up analysis of these same data shows that, among the sub-set of patients who wore CPAP successfully and in whom the central apneas were decreased, there was an improvement in survival (2). Other methods of delivering positive pressure to improve the abnormal breathing in sleep are being studied in patients with central sleep apnea and heart failure, including methods which "adapt" to the patient’s waxing and waning breathing pattern using the same basic nasal or face mask and small ventilator machine.
Other treatments that may be tried under the supervision of experts in heart failure and sleep related breathing disorders are similar to those outlined above for primary sleep apnea, including oxygen, carbon dioxide, and respiratory stimulants. The long term effects of such treatments have not been well documented, and it should be remembered that in many cases one needs to be concerned with treating obstructive as well as central sleep apnea in patients with chronic heart failure, as noted above. Such treatment is optimally planned and given in a multidisciplinary manner, which includes experts in heart failure as well as experts in sleep related breathing disorders, particularly as some therapies may be effective in an individual patient, while some have the possibility of worsening the breathing in the same patient. For example, oxygen alone, while improving blood levels of oxygen during sleep in this patient population, may have the effect of prolonging apneas and/or raising carbon dioxide levels in the blood; positive airway pressure ventilation could cause a serious decrease in blood pressure in heart failure patients with a low blood volume and/or low blood pressure.
Treatment of central sleep apnea with Cheyne-Stokes breathing in the setting of stroke is less well-documented. Just as with heart failure, primary treatment is treatment of the stroke itself and its other complications and risk factors. While all of the treatments for primary central sleep apnea and Cheyne-Stokes breathing in heart failure may be considered for the sleep-related breathing disorder associated with stroke, these treatments have not been studied well enough in the acute setting to be sure of the correct treatment, and such treatment is best made in an individual patient with the multidisciplinary collaboration of an expert in sleep related breathing disorders and a stroke expert.
"physiologic"
response to breathing at high altitude, where the person has increased
drive to breathe because of the low oxygen tension in the atmosphere
available for the arterial blood. Persons with a greater responsiveness
to this low oxygen tension in the atmosphere as well as a greater
responsiveness to carbon dioxide levels in the blood which rise due to
decreased breathing in sleep have a greater tendency for this type of
sleep-related periodic breathing and central apnea (15). This
physiologic response of periodic breathing and central sleep apnea
occurs in contrast to other sleep-related periodic breathing with
central sleep apnea seen in persons with underlying abnormality of the
heart, lungs, or central nervous system.
Treatment for central sleep apnea associated with high altitude is primarily aimed at returning to a lower altitude; oxygen and respiratory stimulants may also be beneficial, but the use of such modalities in this setting should always be managed by an expert clinician, as such treatment has the potential to worsen breathing and the patient’s overall clinical condition.
Just as with Cheyne-Stokes breathing associated with heart failure, all of the sleep related breathing disorders in this category should be assessed by a sleep medicine expert in consultation with other expert clinicians, as each case requires its own diagnosis and treatment considerations regarding to what extent the central sleep apnea represents a health risk in and of itself that needs to be addressed while the underlying disorder is treated. Further, in all of these cases, the central apnea, or absent breathing, may occur on association with periods of very shallow breathing ("hypoventilation"); both the hypoventilation and the central apnea itself may lead to abnormal oxygen and carbon dioxide levels in the blood which may cause adverse effects on the overall health of the person as well as cause disrupted and non-restorative sleep.
A special case of central sleep apnea associated with medical or neurologic disorders is central alveolar hypoventilation syndrome .
This is a rare and usually congenital genetic disorder present at birth
but sometimes unrecognized immediately, which may be associated with
diminished severe hypoventilation, and sometimes outright central
apnea, all of which worsens with sleep. This disorder is life
threatening and requires immediate diagnosis and intervention with
assisted ventilation during sleep.
Central alveolar hypoventilation has also been seen as an acquired disorder in adults who develop a vascular, infectious, or inflammatory disorder of the brainstem, that portion of the brain which is primarily responsible for breathing. Again, such a situation is considered life threatening and requires consideration of assisted ventilation during sleep, usuallt via a tracheostomy. Such disorders, as with the other central apneas above, are optimally treated by a team of experts including a sleep expert, pulmonologist, and neurologist, and in the case of the congenital form of the disorder, a pediatricians with expertise in these fields.
The tendency to central sleep apnea with opioids may be exacerbated when such substances are taken in combination with other respiratory suppressant medication, including substances such as benzodiazepines and alcohol. The short and long term health effects of central sleep apnea associated with such medications in this setting is not well studied. The benefits and risks of using such medications, and the potentially increased risks of combining such medications, including the potential for a fatal cessation of breathing during sleep, should always be considered by an expert in the field of sleep medicine in consultation with the provider of the medication.
refers
to abnormal breathing pauses in infants, generally of 20 seconds or
greater. The central apneas tend to occur in rapid-eye movement (REM)
sleep. If the infant has been born prematurely, such sleep apnea is
referred to as apnea of prematurity (1). The disorder by definition
results in one or more of the following: decreases in oxygen levels in
the blood, abnormal slowing of the heart rate, white or blue skin
changes in the infant, and the perceived need for resuscitation. Such
central sleep apnea is thought to be associated with a problem of the
central nervous system breathing control due to immaturity of the
system, or to some other medical, neurologic, or metabolic disturbance.
While premature birth is most commonly associated with this disorder;
other associations have included gastroesophageal reflux, viral
respiratory infections, other known respiratory problems, and
medications. Immediate intervention with ventilation or medications may
be necessary, as well as treatment of any associated illnesses, and
removal of exacerbating medications. Any suspected breathing disorder
associated with sleep in an infant or child, particularly in pre-term
infants, should be immediately evaluated by pediatrician and in
particular a person who specializes in pediatric sleep related breathing
disorders. It should be noted that this situation can resemble that of
the infant with central alveolar hypoventilation, discussed above.
The International Classification of Sleep Disorders of The American Academy of Sleep Medicine states that "although a small percentage of sudden infant death syndrome (SIDS) victims experience apnea symptoms prior to death, primary apnea in the newborn or infant has not been established as an independent risk factor for SIDS."
It has also been noted that few full term infants have apnea which causes the need for intervention, although a small percentage may have an apnea of 30 seconds or more during sleep in the first six months of life (1).
For all of the central sleep apneas discussed above, the diagnosis usually begins with observation of the patient by an observer at home, or by routine monitoring at the bedside in hospitalized patients. The presence of central sleep apnea can and should be anticipated by persons at risk as well as clinicians who are treating patients with the medical or neurologic disorders described above.
The next step after direct observation, or in the setting of a high clinical suspicion of sleep apnea, should be referral to a sleep expert, who will in most cases recommend specific testing including a polysomnogram (PSG) to attempt to define the diagnosis as well as the required treatment, if any. The PSG is a recording of multiple parameters during sleep, usually as all night monitoring (ideally obtaining 6 to 7 hours of sleep) in a sleep center as an outpatient procedure. The test is not dangerous and usually does not involve any "invasive" monitoring such as intravenous lines or blood testing. As noted in the companion Google Knol piece, "Obstructive Sleep Apnea," a typical PSG includes the following:
While patients may be concerned that they may not be able to sleep in such a setting, or that such sleep would be not representative of their sleep at home, a sleep expert will in fact be able to accurately determine whether and to what extent sleep apnea is present with such a test in the vast majority of cases, as well as in most cases what treatment is necessary or best. In particular, the level and type of positive airway pressure or other necessary breathing support can be determined on such a test once the diagnosis is established. Through this sophisticated testing set up the sleep expert will be able to determine the following:
Such monitoring can be achieved at the bedside with a portable monitoring system in patients who are too ill to be moved to the sleep laboratory, such as patients with acute heart failure or stroke, or in infants suspected of having central apnea. Diagnosis and treatment of all of these disorders must be tailored to the individual patient, and ideally involves a multidisciplinary approach which involves the patient and her/his family and caregivers, experts in the medical or neurologic disorder present (for example, a heart failure specialist in patients with chronic heart failure and central sleep apnea with Cheyne-Stokes breathing), and a specialist in sleep medicine. In most cases treatment of central sleep apnea, if indicated, is possible, and in many cases proper treatment predisposing conditions may substantially alleviate, or in fact eliminate, such apnea. Treatment may need to be chronic in many cases, and should not be discontinued by the patient without consultation with the treating clinician.
A review of congenital central alveolar hypoventilation is the following:
Chen ML, Keens TG. Congenital central hypoventilation syndrome: not just another rare disorder. Paediatr Respir Rev. 2004 Sep;5(3):182-189.
An excellent and comprehensive review of central sleep apnea is:
Bradley, TD, Phillipson, EA. Central sleep apnea. Clin Chest Med 1992; 13:493.
A major review of Cheyne-Stokes breathing and other breathing disorders in sleep associated with stroke is: Bassetti CL, Milanova M, Gugger M. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke 2006;37:967-972.
A comprehensive series of discussions of central sleep apnea syndrome may be found in the online version of the medical journal UpToDate (www.uptodate.com). Note that access to this journal requires a subscription.
The web sites of the following major organizations involved with sleep apnea should be consulted for further information regarding sleep apnea and resources for patients who may have such disorders:
The National Sleep Foundation (www.sleepfoundation.org)
The American Academy of Sleep Medicine (www.aasmnet.org)
The American Thoracic Society (www.thoracic.org)
The National Heart, Lung, and Blood Institute of the National Institutes of Health (www.nhlbi.nih.gov)
The American Apnea Association (www.sleepapnea.org)
References:
What is "central" sleep apnea?
"Apnea" means that there is no airflow in or out of the lungs for 10 seconds or longer. An apnea is non-obstructive, or "central" if there is no effort to breathe during this time; that is, the muscles which are necessary for breathing, primarily the diaphragm, do not move for that period, resulting in apnea. An observer would recognize this as the sufferer making no movements of the chest or abdomen to inspire or expire throughout the time of the apnea."Sleep" apnea refers to the fact that the apneas occur during sleep, usually during the transition from the awake state to drowsiness and light sleep.
Normal persons tend to have transient central apneas during the transition from awake to sleep, due to normal sleep related changes in the brain’s control of breathing: that is, there is, less "drive" to breathe, and in specific, a sleep-related need for increased levels of carbon dioxide (CO2) to cause the central nervous system to signal the muscles of breathing to contract, and, in fact, breathe. It is normal for a person to have one or several of these events until sleep becomes more continuous. "Post-sigh" apneas are common during the sleep period when a person arouses; the person reflexively takes a large breath (sigh) or two, which abruptly decreases the carbon dioxide levels, followed by rapid transition back into sleep, with the onset of a central apnea due to the lack of enough carbon dioxide levels to drive the breathing effort. Just as with the first attempts to transition into sleep, this is a normal breathing response to cycling between sleep and awake states. While such "transitional" apneas are most likely associated with drowsiness and light sleep (non rapid-eye movement, or NREM), erratic breathing and intermittent central apneas are seen commonly in rapid-eye movement (REM) sleep. Therefore, a certain amount of central apneas may occur throughout a night of sleep that are considered normal responses; such cases are not associated with any underlying abnormality of the central nervous system or breathing apparatus, and are not known to cause any major harm to the person who displays such activity. Such "normal" apneas may be associated with the person coming to a full awakening with a feeling that she/he stopped breathing, possibly resulting in a feeling of fear, anxiety, or panic which may be associated with a racing heartbeat, and sweating.
However, if central apneas occur repetitively, generally in the range of five times per hour of sleep, an abnormal situation is considered to exist, and the person is considered to have "central sleep apnea." When a central apnea occurs in sleep, blood oxygen levels fall and carbon dioxide levels rise, and the frequent or repetitive occurrence of such apneas may have harmful effects on the heart, brain, and circulation. Further, with each resumption of breathing, there is typically an "arousal" from sleep, usually not within the awareness of the sufferer, but often obvious to an observer, who may see the person make an abrupt gasping sound with abrupt breathing movements of the chest and abdomen. These arousals are usually associated with a surge of adrenaline into the circulation, with speeding up of the heart and an increase in the blood pressure. Such apneas may occur in a repetitive or even cyclic fashion.
The frequency of apneas, however, is not the only criterion for deeming these events abnormal or significantly harmful; the length of events and degree of decrease in oxygen blood levels is also of importance in determining the potential harm and the treatment necesary, as is the clinical condition in which the apnea occurs.
In most cases, the central apneas that occur due to sleep are not seen when the person is alert and awake, although there are certain conditions of central sleep apnea associated with abnormal breathing patterns when awake. For example, see "Central sleep apnea due to Cheyne-Stokes breathing pattern" and "Central sleep apnea due to a medical condition (other than Cheyne-Stokes breathing)" below.
It is emphasized that any observed prolonged, or symptomatic, breathing pauses during sleep should be considered potentially harmful, particularly in persons with known heart problems such as heart failure, those with known cerebrovascular disease (such as having had a stroke), and should be reported to a health care provider, optimally one who is a sleep medicine specialist.
How is "central" sleep apnea different from "obstructive" sleep apnea?
Obstructive
apneas are apneas in which, ultimately, the airflow into the lungs is
blocked by collapse of the soft airway passage between the nose, mouth,
and larynx. The sufferer will likely make a loud snoring noise at the
end of such an obstructive apnea as the airway re-opens. By definition, a
central apnea has no such blockage. While "central" and "obstructive"
apneas are very much related in terms of why and when they occur during
sleep and what may be done to treat them, ultimately the disorders are
also very different in many important ways. It should be noted,
however, that central and obstructive apneas may be difficult to
distinguish by the observer, as obstructive apneas often begin with very
shallow breathing, or in fact no breathing, followed by increasing
efforts to breathe without airflow occurring due to the collapsed air
passages in the nose, oral cavity, and throat. Central and obstructive
apneas may occur in the same person during sleep, and there may be
"mixed" apneas in which the apnea begins with no effort to breathe for
at least 10 seconds followed by obstructed breathing. Further, it is
known that some patients with obstructive sleep apnea will manifest
non-obstructive or central sleep apnea when treated with positive airway
pressure; this has recently been termed "complex sleep apnea." Central sleep apnea is not a single medical disorder, but rather occurs in many settings, which sometimes reflects the medical or neurologic disorder it is seen with, and sometimes represents a disorder without clear underlying causes. All central sleep apnea disorders should be considered abnormal and potentially harmful to the person who has such a disorder. The typical central sleep apnea syndromes with notes regarding their recognition, importance, and possible treatments are detailed in the following section.
The central sleep apneas may be classified into the following types according to the current American Academy of Sleep Medicine International classification of sleep disorders (1):
- Primary central sleep apnea
- Central sleep apnea due to Cheyne-Stokes breathing pattern
- Central sleep apnea due to high altitude periodic breathing
- Central sleep apnea due to a medical condition (other than Cheyne Stokes breathing)
- Central sleep apnea due to a drug or substance
- Primary sleep apnea of infancy
A discussion of each of the major types of central sleep apnea follows:
Primary central sleep apnea
Diagnosed by polysomnography (PSG – a sleep study using both monitoring equipment and direct observation and described in detail below), this condition is defined as at least five central apneas per hour of sleep in association with symptoms of awakening
The major task in diagnosing primary central sleep apnea is to be certain that a more serious disorder of breathing during sleep does not exist, including obstructive sleep apnea (see accompanying Google KNOL Obstructive Sleep Apnea), Cheyne-Stokes breathing (see below), or a breathing disorder while awake that may be exacerbated during sleep; this can include patients with chronic lung disease such as emphysema, or chest wall or neuromuscular disorders (see central sleep apnea due to a medical condition, below). It is also necessary to assess for other sleep fragmenting conditions which may predispose to arousal and sleep fragmentation, which in turn predisposes to central apneas as the person transitions back into sleep after arousal. Such fragmenting disorders may be intrinsic to sleep, such as periodic limb movement disorder, or extrinsic, such as chronic pain, sleep disruptive medications (for example, amphetamines, steroids, alcohol, nicotine, and certain blood pressure medications) or environmental light or noise. It is often difficult to define whether the central sleep apnea is causing the arousals, the arousals are causing the sleep apnea, or both, and this situation may be thought of as a "vicious cycle."
Treatment of primary central sleep apnea, once the condition is defined as such, may include avoidance of supine (lying on your back) sleep if this is shown to be a factor in the tendency to have the central apneas, avoidance of any medications and environmental conditions associated with poor sleep consolidation, and treatment of any medical or sleep disorders as noted which may predispose to sleep fragmentation and associated transitions between wake and sleep states. Consistent success with positive airway pressure (creating a flow of air that creates enough pressure during inhalation to keep the airway open) for this condition is not well documented. Other treatments, including respiratory stimulants (4, 14), oxygen, and carbon dioxide have been used in some patients, but there is not a large data base documenting consistent success for such treatment for primary central sleep apnea.
Central sleep apnea associated with Cheyne-Stokes breathing
Central sleep apnea associated with Cheyne-Stokes breathing was first described in a patient with heart failure and stroke in 1818, and named primarily after the describing physician (3). This form of central sleep apnea is defined as cyclic waxing and waning of breathing effort in sleep, in association with a heart failure, stroke, or renal failure, typically in a very regular pattern which resembles a diamond shape. At the point where the breathing becomes very shallow it will often cease completely for 10 or more seconds; this is the central apnea of Cheyne-Stokes breathing.With each decrease or cessation of breathing effort, oxygen saturation of blood levels decrease, and at the end there is a speeding up of the heart rate along with an arousal of the central nervous system, thus disrupting sleep. The patient may be seen and heard to have a gasping breath at the end of the apnea, but not the explosive sound of snoring or opening of the upper airway typically seen with obstructive sleep apnea, although the two disorders often overlap in patients with heart failure.
Such abnormal breathing in sleep in the setting of heart failure, while reflecting to some extent the severity of the heart failure, is associated with sleep-related decrease in oxygen levels in the blood, and increased adrenaline-like activity which can contribute to further deterioration in cardiac function if untreated. Untreated Cheyne-Stokes breathing in heart failure has been associated with increased risk of death compared with patients with heart failure without central sleep apnea with Cheyne-Stokes breathing (8). While optimizing treatment of the heart failure is an important and well-accepted strategy in patients with heart failure and central sleep apnea, it is not clear that even optimal medical management of the heart failure will improve the central sleep apnea (11) and therefore suggests that direct treatment of the breathing disorder is important.
In patients who have had a stroke, the likelihood of having a sleep-related breathing disorder including central sleep apnea with Cheyne-Stokes breathing in the first 72 hours following the stroke is high, with the latter occurring in more than 25% of such patients (12). It has been shown that the presence of a sleep related breathing disorder is associated with worse neurologic outcomes compared to acute stroke patients without demonstrated sleep related breathing disorder; such breathing disorders include obstructive as well as central apnea syndromes (6).
CPAP has been shown to decrease the frequency of central apneas in patients with stable chronic heart failure, but the largest prospective study of this treatment failed to show a benefit of this treatment in improving survival, or the need for heart transplant. There also was some concern that the treatment may have caused the risk of death to increase in some patients. A follow up analysis of these same data shows that, among the sub-set of patients who wore CPAP successfully and in whom the central apneas were decreased, there was an improvement in survival (2). Other methods of delivering positive pressure to improve the abnormal breathing in sleep are being studied in patients with central sleep apnea and heart failure, including methods which "adapt" to the patient’s waxing and waning breathing pattern using the same basic nasal or face mask and small ventilator machine.
Other treatments that may be tried under the supervision of experts in heart failure and sleep related breathing disorders are similar to those outlined above for primary sleep apnea, including oxygen, carbon dioxide, and respiratory stimulants. The long term effects of such treatments have not been well documented, and it should be remembered that in many cases one needs to be concerned with treating obstructive as well as central sleep apnea in patients with chronic heart failure, as noted above. Such treatment is optimally planned and given in a multidisciplinary manner, which includes experts in heart failure as well as experts in sleep related breathing disorders, particularly as some therapies may be effective in an individual patient, while some have the possibility of worsening the breathing in the same patient. For example, oxygen alone, while improving blood levels of oxygen during sleep in this patient population, may have the effect of prolonging apneas and/or raising carbon dioxide levels in the blood; positive airway pressure ventilation could cause a serious decrease in blood pressure in heart failure patients with a low blood volume and/or low blood pressure.
Treatment of central sleep apnea with Cheyne-Stokes breathing in the setting of stroke is less well-documented. Just as with heart failure, primary treatment is treatment of the stroke itself and its other complications and risk factors. While all of the treatments for primary central sleep apnea and Cheyne-Stokes breathing in heart failure may be considered for the sleep-related breathing disorder associated with stroke, these treatments have not been studied well enough in the acute setting to be sure of the correct treatment, and such treatment is best made in an individual patient with the multidisciplinary collaboration of an expert in sleep related breathing disorders and a stroke expert.
Central sleep apnea due to high altitude periodic breathing
This form of central sleep apnea is very similar to that seen in Cheyne-Stokes breathing discussed above; that is, cycles of decreasing and increasing breathing ("periodic" breathing), with absence of breathing (apnea) as the breathing wanes. As with the other breathing disorders of this discussion, there is no evidence of the upper airway collapsing, which is the hallmark of obstructive sleep apnea (see the separate discussion), and the central apneas occur at least five times per hour of sleep. This abnormal breathing in sleep occurs by definition in persons who have ascended to altitudes generally 4,000 meters and higher – and is more likely to occur the more quickly the climber has ascended to the altitude. The central apneas are associated with repetitive arousals from sleep thus fragmenting sleep, as well as causing decreased oxygen level in the bloods. This breathing pattern is considered a normal,Treatment for central sleep apnea associated with high altitude is primarily aimed at returning to a lower altitude; oxygen and respiratory stimulants may also be beneficial, but the use of such modalities in this setting should always be managed by an expert clinician, as such treatment has the potential to worsen breathing and the patient’s overall clinical condition.
Central sleep apnea due to a medical condition (other than Cheyne-Stokes breathing)
There are numerous medical conditions which predispose an individual to having central apneas during sleep, without showing the clear pattern of Cheyne-Stokes breathing discussed above in association with heart failure and stroke. Among these are neurologic disorders and/or muscular weaknesses or deformities of the chest wall or spine. This includes patients with disorders such as muscular dystrophy and amyotrophic lateral sclerosis, kyphoscoliosis, and post-polio disorders. It also includes patients with stroke who may have central apneas in sleep without Cheyne-Stokes breathing. Infectious and inflammatory disorders of the central nervous system, including encephalitis, may also be associated with central sleep apnea, as may breathing disorders associated with fibrosis of the lungs or chronic obstructive pulmonary disease (COPD). Hypothyroidism (low thyroid conditions) has also been associated with central sleep apnea.Just as with Cheyne-Stokes breathing associated with heart failure, all of the sleep related breathing disorders in this category should be assessed by a sleep medicine expert in consultation with other expert clinicians, as each case requires its own diagnosis and treatment considerations regarding to what extent the central sleep apnea represents a health risk in and of itself that needs to be addressed while the underlying disorder is treated. Further, in all of these cases, the central apnea, or absent breathing, may occur on association with periods of very shallow breathing ("hypoventilation"); both the hypoventilation and the central apnea itself may lead to abnormal oxygen and carbon dioxide levels in the blood which may cause adverse effects on the overall health of the person as well as cause disrupted and non-restorative sleep.
A special case of central sleep apnea associated with medical or neurologic disorders is central alveolar hypoventilation syndrome
Central alveolar hypoventilation has also been seen as an acquired disorder in adults who develop a vascular, infectious, or inflammatory disorder of the brainstem, that portion of the brain which is primarily responsible for breathing. Again, such a situation is considered life threatening and requires consideration of assisted ventilation during sleep, usuallt via a tracheostomy. Such disorders, as with the other central apneas above, are optimally treated by a team of experts including a sleep expert, pulmonologist, and neurologist, and in the case of the congenital form of the disorder, a pediatricians with expertise in these fields.
Central sleep apnea due to a drug or substance
This form of central sleep apnea occurs in patients who use chronic opioid medications, particularly methadone and oxycodone (5). The abnormal breathing in sleep, which may include hypoventilation as well as central sleep apnea, is usually seen after several months of use of the substance, although the effects of an overdose can occur more acutely. Such substances depress breathing by direct effect on the brainstem, that portion of the brain which controls breathing, which when added to the depressive effects of sleep on breathing may result in the central apneas. These events of apnea and/or very shallow breathing (hypoventilation) occur, by definition, at least five times per hour of sleep.The tendency to central sleep apnea with opioids may be exacerbated when such substances are taken in combination with other respiratory suppressant medication, including substances such as benzodiazepines and alcohol. The short and long term health effects of central sleep apnea associated with such medications in this setting is not well studied. The benefits and risks of using such medications, and the potentially increased risks of combining such medications, including the potential for a fatal cessation of breathing during sleep, should always be considered by an expert in the field of sleep medicine in consultation with the provider of the medication.
Primary sleep apnea of infancy
This diagnosisThe International Classification of Sleep Disorders of The American Academy of Sleep Medicine states that "although a small percentage of sudden infant death syndrome (SIDS) victims experience apnea symptoms prior to death, primary apnea in the newborn or infant has not been established as an independent risk factor for SIDS."
It has also been noted that few full term infants have apnea which causes the need for intervention, although a small percentage may have an apnea of 30 seconds or more during sleep in the first six months of life (1).
Diagnosis of Central Sleep Apnea
For all of the central sleep apneas discussed above, the diagnosis usually begins with observation of the patient by an observer at home, or by routine monitoring at the bedside in hospitalized patients. The presence of central sleep apnea can and should be anticipated by persons at risk as well as clinicians who are treating patients with the medical or neurologic disorders described above.
The next step after direct observation, or in the setting of a high clinical suspicion of sleep apnea, should be referral to a sleep expert, who will in most cases recommend specific testing including a polysomnogram (PSG) to attempt to define the diagnosis as well as the required treatment, if any. The PSG is a recording of multiple parameters during sleep, usually as all night monitoring (ideally obtaining 6 to 7 hours of sleep) in a sleep center as an outpatient procedure. The test is not dangerous and usually does not involve any "invasive" monitoring such as intravenous lines or blood testing. As noted in the companion Google Knol piece, "Obstructive Sleep Apnea," a typical PSG includes the following:
- Electrodes on the scalp and forehead attached with a special paste, to determine brain wave activity and the stages of sleep
- Electrodes with paste on the skin at the side of the eyes to determine eye movements of REM sleep
- Electrodes with paste on the skin under the chin to determine muscle activity of breathing and sleep
- Soft sensors in front of the nose and mouth to measure the degree of airflow into the body, and carbon dioxide levels in the airway
- Soft belts around the rib cage and abdomen to measure breathing efforts
- Electrodes with paste on the chest (electrocardiogram) to measure heart rhythm
- A soft probe on the finger to monitor continuous oxygen saturation levels
- A soft probe on the throat to measure snoring activity
- Audiovisual recording with a camera and sound system
While patients may be concerned that they may not be able to sleep in such a setting, or that such sleep would be not representative of their sleep at home, a sleep expert will in fact be able to accurately determine whether and to what extent sleep apnea is present with such a test in the vast majority of cases, as well as in most cases what treatment is necessary or best. In particular, the level and type of positive airway pressure or other necessary breathing support can be determined on such a test once the diagnosis is established. Through this sophisticated testing set up the sleep expert will be able to determine the following:
- The frequency of central apneas per hour of sleep
- The degree to which such apneas represent normal, or physiologic, responses to sleep-wake transitions or REM sleep
- The length of the apneas
- The degree to which the oxygen saturation levels of the blood decrease, including the lowest level and the time the oxygen saturation is below 90%, a usual cut-off for physiologically significant decrease in blood oxygen levels
- The degree to which carbon dioxide levels in the body increase
- The stages of sleep in which the apnea was improved or worsened
- The positions of sleep (supine, prone, side) in which the apnea was improved or worsened
- The degree to which sleep is disrupted by the breathing disorder
- The degree to which disorders of arousal such a periodic limb movements contribute to the tendency to cause arousal from sleep and promote sleep-wake transitioning and therefore central apnea with sleep
- The degree to which other disorders of breathing (such as obstructive sleep apnea, periodic waxing and waning of breathing, and periods of decreased but not absent airflow), occur in association with the central apneas
Such monitoring can be achieved at the bedside with a portable monitoring system in patients who are too ill to be moved to the sleep laboratory, such as patients with acute heart failure or stroke, or in infants suspected of having central apnea. Diagnosis and treatment of all of these disorders must be tailored to the individual patient, and ideally involves a multidisciplinary approach which involves the patient and her/his family and caregivers, experts in the medical or neurologic disorder present (for example, a heart failure specialist in patients with chronic heart failure and central sleep apnea with Cheyne-Stokes breathing), and a specialist in sleep medicine. In most cases treatment of central sleep apnea, if indicated, is possible, and in many cases proper treatment predisposing conditions may substantially alleviate, or in fact eliminate, such apnea. Treatment may need to be chronic in many cases, and should not be discontinued by the patient without consultation with the treating clinician.
Recommended readings and sources:
The reader who wants to learn more about sleep apnea in infants and children is referred to: Loughlin G, Carroll J, Marcus C (eds). Sleep and Breathing in Children, Vol 147. New York: Marcel Dekker Inc. 2000.A review of congenital central alveolar hypoventilation is the following:
Chen ML, Keens TG. Congenital central hypoventilation syndrome: not just another rare disorder. Paediatr Respir Rev. 2004 Sep;5(3):182-189.
An excellent and comprehensive review of central sleep apnea is:
Bradley, TD, Phillipson, EA. Central sleep apnea. Clin Chest Med 1992; 13:493.
A major review of Cheyne-Stokes breathing and other breathing disorders in sleep associated with stroke is: Bassetti CL, Milanova M, Gugger M. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke 2006;37:967-972.
A comprehensive series of discussions of central sleep apnea syndrome may be found in the online version of the medical journal UpToDate (www.uptodate.com). Note that access to this journal requires a subscription.
The web sites of the following major organizations involved with sleep apnea should be consulted for further information regarding sleep apnea and resources for patients who may have such disorders:
The National Sleep Foundation (www.sleepfoundation.org)
The American Academy of Sleep Medicine (www.aasmnet.org)
The American Thoracic Society (www.thoracic.org)
The National Heart, Lung, and Blood Institute of the National Institutes of Health (www.nhlbi.nih.gov)
The American Apnea Association (www.sleepapnea.org)
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- White DP, Gleeson K, Pickett CK, Rannels AM, Cymerman A, Weil JV. Altitude acclimatization: influence of periodic breathing and chemoresponsiveness during sleep. J Appl Physiol 1987;63:401-412.
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