Central and Complex Sleep Apnea: A Review of the Causes, Symptoms, and Treatments

By Admin

Central sleep apnea (CSA) may not be as common as obstructive sleep apnea (OSA), but it is also more difficult to diagnose, making its true prevalence unknown. Like OSA, CSA is more common among men over 40, and much more prevalent among those with heart conditions, strokes, or those who take central nervous system depressants. But unlike OSA, CSA tends to be less associated with weight and sleepiness, and more likely to develop from other conditions. And because there is a lot of crossover between OSA and CSA conditions, having OSA is a risk factor for developing CSA. Often, the central apneas occur as a “treatment emergent condition,” meaning that they develop after OSA is treated with CPAP. Just as a patient begins to overcome the symptoms of obstructive sleep apnea, central apneas occur irrespective of any blockage in the airway. This combination of two distinct types of sleep apnea is called complex or mixed sleep apnea, and it can be very difficult to treat. Unlike OSA, CSA is not caused by physical blockage in the airway. Central apneas occur when the autonomic nervous system fails to signal the body to breathe during sleep. These events can either lapse on their own after one or two minutes, or like OSA, can result in a partial or complete arousal, leading to fragmentation of sleep. This is why CSA is much more difficult to diagnose. Its symptoms can be very closely related to other conditions, and as a result, difficult to treat on their own. While media attention to OSA has grown rapidly in recent years, information on CSA is slightly less prominent. Below is a brief overview of the most common manifestations of the disorder, along with the best treatment options for each. Links are provided for further information and resources on CSA and mixed sleep apnea conditions.

Types of Central Sleep Apnea and Their Symptoms

According to the International Classification of Sleep Disorders-third edition (ICSD-3), central sleep apnea is a breathing disorder that causes your body to decrease or stop the effort of breathing during sleep, often associated with problems in the brain, heart, or nervous system. A diagnosis of central sleep apnea is made when central apneas and/or hypopneas constitute 50 percent or more of the respiratory events observed, with a total central apnea index (CAI) of 5 or more events per hour. Unlike obstructive sleep apnea, these apnea events are due to lapses in respiratory muscle activation, which stops breathing altogether. When we breathe, our brain sends signals to the muscles of our rib cage and diaphragm to make them contract, producing an inhalation response. But in CSA, there is a disconnect between the brain and body, and signals fail to send or activate correctly. While a few brief apneas of this kind is considered normal for a night of sleep, persistent lapses in breathing can cause the same health problems associated with obstructive sleep apnea; reducing blood oxygen levels, disrupting sleep, and contributing to comorbid conditions.

The symptoms of CSA can vary depending on the specific type or syndrome a person has, but the most common symptoms are similar to those of obstructive sleep apnea. The American College of Cardiology lists the following CSA symptoms as those commonly shared with OSA:

Pauses in breathing (apneas)
Non-restorative or insufficient sleep
Excessive daytime sleepiness (EDS)
Fatigue
Mood changes
Memory loss or difficulty concentrating
Headaches (particularly in the morning)
Dry mouth
Snoring (though more often in complex sleep apnea cases)
Other sleep problems (waking easily, etc.)

The primary symptom, the apneas themselves, are of course difficult to assess without a polysomnography sleep study overseen by a medical professional. Even when patients are aroused by apneas, they would have a difficult time distinguishing OSA events from those of CSA, apart from the slowed breathing that occurs in some types of CSA. In either case, there is a high risk of recurrent and/or persistent hypoxemia, which can potentially lead to cardiovascular problems. According to the American College of Cardiology list of CSA symptoms, some of the most common cardiovascular diseases associated with CSA include congestive heart failure, coronary artery disease, left and/or right ventricular dysfunction and a number of cardiac dysrhythmias, also known as arrhythmias or irregular heart beats.

How a CSA condition manifests, and what symptoms occur, will also depend on the type or subtype a patient develops. These types are generally classified as follows:

1. Primary Central Sleep Apnea — Sometimes called Idiopathic Central Sleep Apnea, this type is usually due to unknown causes.The symptoms of primary CSA are standard for sleep apnea of any type, though occurring without effort to breathe, as opposed to the choking or blocked breaths of OSA. This type is common among the middle-aged or elderly men, and there may be a tendency for inheritance. Some medical conditions, while not a direct cause, may increase the risk for primary CSA. For example, multi-system atrophy and Parkinson’s disease both show high rates of CSA.

2. Cheyne-Stokes Breathing (CSB) — A pattern of breathing, sometimes referred to as Cheyne-Stokes Respiration or Cheyne-Stokes Breathing Pattern, characterized by periods of slowed breathing that often lead to apnea events. This type of sleep apnea can be caused by heart failure, stroke, or possibly kidney failure. Like primary CSA, Cheyne-Stokes Breathing often occurs in men aged 60 and older. According to the Sleepeducation website, Cheyne-Stokes is seen in 25 to 40 percent of men with chronic congestive heart failure, and 10 percent of men who have a history of stroke. It is a rare condition for women.

3. CSA Caused By a Medical Condition Other Than Cheyne-Stokes — This type of CSA is caused by other medical conditions besides Cheyne-Stokes Breathing, often due to heart and kidney problems. It may also be caused by problems in the area of the brain where breathing is controlled. While this type of CSA is rarer than other forms, unfortunately, it is also a particularly dangerous condition. According to Medline Plus, CSA can be more problematic when it is a byproduct of another disease. In addition to heart disease and stroke, neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis can cause central sleep apneas due to weakness in the respiratory muscles.

4. High-Altitude Periodic Breathing (HAPB) — This type of CSA is caused by sleeping at high altitudes, usually higher than about 10,000 feet. The breathing pattern that results can be similar to that of Cheyne-Stokes Breathing in their oscillations, but tend to be faster and more strained, eventually lapsing into apnea. This form of sleep apnea can occur in anyone, regardless of health history or related conditions. According to Sleepeducation.org, men are more susceptible because they tend to be more responsive to changes in the oxygen and carbon dioxide levels. Generally, the higher the elevation, the more likely breathing will slow.for anyone. The good news is that a lower elevation will almost always return breathing patterns to normal. In some cases, climbers or those visiting high altitudes will bring along a PAP device to treat HAPB symptoms.

5. CSA Due to a Drug or Substance — CSA due to medications or other substances are usually caused by substances in the opioid or synthetic opiate categories, sometimes collectively called narcotics . When these substances are taken, especially in high doses or for longer periods, there is a chance that breathing may slow or stop completely, sometimes following a rhythmic pattern similar to Cheynes-Stokes Breathing. Other times, breathing can become irregular throughout the night. While tolerance will take effect when using these substances for longer periods, it is generally observed that high dosages of long-acting drug types (Oxycodone, Percocet, etc.) will induce this form of CSA, although the precise amount will vary depending on individual physiology. While this type of sleep apnea can be treated by reducing or weaning from higher dosages of the drug, it is often difficult to detect. Any of the symptoms listed above may be a sign of the condition and should merit further inquiry by a medical professional.

In addition to these five categories, CSA syndromes can also be broadly classified into two main groups according to CO2 levels in the body. These groups are called hypercapnic and non-hypercapnic. Hypercapnia occurs when the lungs are unable to clear carbon dioxide properly, leading to forms of respiratory acidosis. While the number of disparities exist within these groups, the CO2 levels can tell you a lot about the condition and its effect on gas exchange during the night.

Hypercapnic CSA

Hypercapnia is caused by impaired ventilatory output (hypoventilation), which heightens levels of carbon dioxide in the body. This will often carry over into wakefulness. When CSA continues without arousal, hypercapnia can worsen throughout the night. Sometimes hypercapnic CSA is further categorized according to the nature of the dysfunction, for example, those who stop making an effort to breathe (“won’t breathe”) vs. those whose breathing signals fail to induce the proper breathing patterns (“can’t breathe”). These forms are commonly caused by other diseases, brain damage, or other related disorders. One form of very specific hypercapnic CSA is central hypoventilation syndrome (CHS). Once called Ondine’s curse due to its mythological history as a curse of lost breath, this rare condition creates central sleep apneas when hyperventilation occurs during sleep, often resulting in severe hypercapnia and hypoxemia. CHS can either be congenital (CCHS) at birth or acquired (ACHS), but both conditions can be fatal if left untreated. CHS is one of several diseases believed to cause the phenomenon of sudden infant death syndrome (SIDS).

The respiratory effects of narcotic medications are considered hypercapnic as well, as long-term use leads to an increased propensity for CSA, which can even be a cause of death. Along with the high risk for abuse and possibility of overdose or adverse reactions, development of CSA is yet another reason to safely regulate narcotic medications, especially when prescribed to patients already experiencing sleep disorders.

Non-hypercapnic CSA

CSA without impaired ventilatory output includes, primarily, Cheyne-Stokes Breathing and Idiopathic cases. Non-hypercapnic cases tend to involve more hyperventilation from changes in breathing. Since Cheyne-Stokes Breathing results in a waxing and waning pattern of breathing, it is less likely to result in heightened levels of carbon dioxide in the blood. But this does not mean that respiration is stable in CSB cases. For the most part, the cycle time between moments of unstable ventilation is much longer than other forms of CSA, but the instability exists throughout the night and includes apnea and hypopnea events.

Idiopathic cases can be similar to Cheyne-Stokes Breathing in that both exhibit patterns of breathing that disrupt normal respiration and lead periodically to apnea events. But idiopathic cases differ from those of CSB in that they do not display the waxing and waning pattern of CSB and can lead to both hypercapnic and non-hypercapnic results depending on the specifics of each case.

Complex Sleep Apnea Conditions

When both types of sleep apnea are present, or when central apneas are treatment emergent, doctors will often use more than one treatment option to address the condition. Complex sleep apnea, involving both OSA and CSA, does not always emerge when initiating CPAP, but it is a common form of the disorder. In either case, doctors will conduct further tests to determine the specifics of the condition. In some cases, according to research published in journal Patient Preference and Adherence, treatment-emergent central sleep apnea (TECSA) is transient in nature and will dissipate with continued use of CPAP or other forms of PAP therapy. Of course, this is not always the case. Complex sleep apnea was named for its complexities, and both diagnosis and treatment can be challenging.

Currently, the ICSD-3 includes complex sleep apnea and TECSA as separate disorders. While both of these disorders involve the combination of obstructive and central apneas, TECSA is recognized by distinct patterns related specifically to the treatment of OSA. The ICSD-3 defines TECSA as the emergence or persistence of central apnea events during PAP treatment (CSA defined as noted with a CAI of ≥5/h and majority of events being central in origin). However, it should also be noted that CSA has been reported during other non-CPAP treatments for OSA, including surgery and the use of oral appliances. This tells us that TECSA is not unique to CPAP, and that complex sleep apnea is not yet completely understood. Thus, identifying the mechanisms of TECSA and other forms of complex sleep apnea is of paramount importance.

Treatment of Central and Complex Sleep Apnea

Treatment for CSA can vary as much as the disorder itself, depending on the patient’s condition, preferences, and overall health and history, but some of the more common treatments involve the use of PAP therapy with other supplemental sleep aids such as medication, bedtime regimens, or other lifestyle changes. One of the most common treatments for both central and complex sleep apnea is adapto-servo ventilation, or ASV. ASV is a form of non-invasive ventilatory support that is similar to CPAP but more advanced in its capabilities. Rather than pumping air at a singular pressure setting, or switching between separate inspiratory and expiratory pressures like BiPAP, ASV continuously monitors and adjusts pressures to match and improve patient breathing patterns. According to the National Institutes of Health (NIH), a sleep medicine specialist would be best to review the various treatment options for a central sleep apnea patient. Often with CSA, treating an underlying condition will take precedence, as the condition may be causing or exacerbating the CSA symptoms. NIH reports show that ASV is best for complex or mixed sleep apnea conditions, but not recommended for patients with certain chronic conditions, for example, chronic hypoventilation (shallow breathing), chronic obstructive lung disease (COPD), chronic heart failure, or some types of restrictive lung or neuromuscular diseases. In fact, PAP device manufacturer ResMed released a warning regarding the use of ASV for patients with heart failure, which can damage the heart further in weakened conditions. This, once again, highlights the difficulties involved in the diagnosis and treatment of central sleep apnea conditions. The most effective treatment for one patient may be harmful to another. This is why every patient should seek professional guidance not only for diagnosis and prescribed treatments, but also for ongoing therapy support and referrals to medical specialists whenever necessary.

Other supplemental treatments such as oxygen therapy have shown to be effective in lowering the apnea-hypopnea index (AHI). This is often prescribed in addition to CPAP or ASV, acting as an additional support therapy for proper breathing pressures and steady rhythms throughout the night. Medications such as acetazolamide (Diamox), theophylline (Theo-24, Theochron), and Zolpidem have been used to stimulate breathing in patients with CSA. These medications can be used to prevent CSA in high altitudes when traveling. Most sleep apnea surgeries are aimed specifically at OSA, but some are more suited for central origins. One example is transvenous phrenic nerve stimulation, which uses an implanted device to stimulate the nerve that runs from the brain to the diaphragm. The device acts as a pacemaker to help with breathing and can be very effective with patients who are unable to use ASV due to heart failure. These novel treatments, while showing promise, will often be prescribed as alternatives when the gold standard of PAP therapy is not effective in treating the disorder. Often, CPAP with the addition of Expiratory Pressure Relief (EPR), heated humidification, and other comfort features will be the starting point for CSA treatment, with follow-up assessments used to determine the effectiveness of the treatment.

The key to treating central sleep apnea is addressing all related health conditions with a close eye to detail. The type of treatment for CSA depends on the type and/or subtype of the disorder, as well as any related comorbidities. In any case, the first step will always be a visit to your primary physician. From there, you can be referred to a sleep clinic or specialist to develop a tailored treatment plan for your specific needs. While CSA may be difficult in some cases to identify and treat properly, the medical community is gaining new insights into the disorder through research and improved technologies. As healthcare continues to advance in this area, patients continue to experience the benefits.