Central sleep apnea (CSA) is a sleep breathing disorder caused by the failure of the central nervous system to properly transmit respiratory signals. It is manifested as repeated pauses or weakening of breathing during sleep without upper airway obstruction.
Unlike obstructive sleep apnea (OSA), the core problem of CSA lies in dysfunction of the brainstem respiratory control center or related diseases that interfere with respiratory regulation mechanisms. OSA patients may also experience episodes of significant central apnea, and patients who initially experience central apnea may develop obstructive or mixed apnea as respiratory movements resume.
Treatment plans for central sleep apnea must be tailored to the patient’s specific cause, severity, and the presence of other medical conditions. Primary treatments include controlling the underlying condition, using noninvasive respiratory support, medications, and lifestyle adjustments. Some patients may also require oxygen therapy or modularization to enhance efficacy.
Pathology Of Central Apnea
CSA is usually divided into hypercapnic or non-hypercapnic central apnea based on the level of alveolar ventilation.
Highly Carbonated CSA
Hypercapnic central apnea is not usually an independent disease, but a common manifestation of certain underlying diseases. Its root cause is the damage to the nervous system or respiratory muscles that control breathing, resulting in hypoventilation in patients even when awake.
Common underlying diseases include:
Neurological diseases:Â such as congenital central hypoventilation syndrome (CCHS), Arnold-Chiari malformation, and amyotrophic lateral sclerosis;
Neuromuscular diseases: such as various muscular dystrophies and post-polio syndrome;
Thoracic structural abnormalities: such as severe kyphoscoliosis;
Metabolic diseases: such as obesity hypoventilation syndrome (OHS).
From a physiological perspective, the causes of hypercapnic CSA can be divided into two categories: one is abnormality in the brain’s respiratory center commands (abnormal output of the central generator), and the other is impaired transmission of commands to the respiratory muscles (impaired respiratory initiation output).
Congenital central hypoventilation syndrome (CCHS) is a typical example of the former, which is usually caused by genetic factors rather than structural problems. Patients experience severe alveolar hypoventilation during sleep, resulting in significant hypercapnia and hypoxemia, often accompanied by complications such as polycythemia and pulmonary hypertension.
The characteristic breathing pattern of CCHS is a near-normal frequency but a significantly reduced breathing depth (tidal volume). Interestingly, unlike obstructive sleep apnea (OSA), CCHS patients experience more stable breathing during rapid eye movement (REM) sleep, likely due to a unique respiratory stimulation mechanism during REM sleep.
Also, patients experience decreased sensitivity to elevated carbon dioxide and decreased oxygen levels. While the condition is typically diagnosed in the neonatal period, milder cases have also been reported in adults in recent years.
Obesity hypoventilation syndrome (OHS) is another common form of hypercapnic CSA. It refers to unexplained hypercapnia in obese patients (BMI>30) while awake.
Hypoventilation worsens during non-rapid eye movement (NREM) and even REM sleep, leading to more pronounced carbon dioxide retention and decreased blood oxygen levels.
The clinical symptoms of patients with OHS are similar to those of obstructive sleep apnea (OSA), including excessive daytime sleepiness and morning headaches.
Because both are associated with obesity, the pathological mechanisms of OHS and OSA often overlap, leading to the coexistence of both in many patients.
Non-carbonated CSA
Non-hypercapnic central sleep apnea (CSA) is the most common type of CSA, characterized by a cyclical pattern of apnea and hyperpnea. Its etiology is diverse, ranging from incipient central apnea to the effects of high altitude, to conditions such as chronic heart failure and acromegaly, as well as idiopathic cases of unknown etiology.
The key physiological characteristic of this type of pulmonary embolism is an exaggerated response of the respiratory center to chemical signals in the body, such as carbon dioxide. This is the opposite of the weakened response in hypercapnic CSA.
Therefore, its essence is not a lack of respiratory drive, but rather a loss of stability in the respiratory control system, resulting in periodic fluctuations between “increases” and “pauses.”
Chemoreceptors are key to regulating ventilation. However, their sensitivity varies from person to person; excessive or insufficient sensitivity can disrupt respiratory stability.
Those with excessive sensitivity overreact to even the slightest changes in carbon dioxide levels, triggering hyperventilation. This, in turn, causes a sudden drop in carbon dioxide levels, leading to insufficient respiratory drive or even apnea.
Heart failure patients, due to delayed blood circulation, exacerbate this instability. Conversely, insufficient sensitivity can prevent the body from initiating adequate respiratory compensation even when blood gas levels are severely abnormal, similarly detrimental to physiological homeostasis.
Symptoms Of Central Apnea
The clinical manifestations of central sleep apnea (CSA) vary depending on whether carbon dioxide retention (hypercapnia) is present.
Hypercapnic CSA is characterized by apnea or hypopnea during sleep. The underlying problem is a significant decrease in expiratory movement, leading to alveolar hypoventilation.
In addition to typical symptoms such as poor sleep at night and daytime sleepiness, patients also exhibit signs of underlying chronic hypoventilation, such as morning headaches, cor pulmonale, and lower limb edema.
Symptoms of non-hypercapnic CSA are more diverse. Some patients experience symptoms similar to those of obstructive sleep apnea, such as snoring and daytime sleepiness.
Others may primarily experience insomnia and light sleep with frequent awakenings. This may be due to frequent alternations between wakefulness and light sleep during the night.
It should be noted that the current understanding of the clinical manifestations of CSA is mostly based on summaries of small sample case reports.
Diagnosis Of Central Apnea
Central apnea is a more complex respiratory problem, and its diagnostic criteria involve many aspects.
(1) Polysomnography (PSG)
In polysomnography (PSG), a crucial diagnostic tool, the identification of central sleep apnea events is crucial. Generally speaking, a central sleep apnea event is defined as a cessation of airflow from the mouth and nose for at least 10 seconds, accompanied by a cessation of chest and abdominal respiratory movements.
This standard is based on extensive clinical research and practical experience. Researchers analyzed monitoring data from numerous patients with sleep-disordered breathing and found that the simultaneous cessation of oral and nasal airflow and chest and abdominal breathing movements for 10 seconds or longer significantly impacts a patient’s respiratory function and sleep quality. This is the time limit for determining an event.
(2) Central Apnea-Hypopnea Index (CAH)
The Central Apnea-Hypopnea Index (CAH) is an important indicator for diagnosing central sleep apnea. It is generally believed that if the average number of central apnea and central hypopnea events per hour of sleep exceeds 5, there is a high suspicion of central apnea.
Central hypoventilation (CAH) refers to a decrease in oral and nasal airflow exceeding 30% below baseline during sleep, accompanied by a decrease in arterial oxygen saturation exceeding 4%, or sleep arousals.
The diagnostic threshold of 5 episodes per hour is based on extensive clinical research and epidemiological data. Studies have found that when CAH reaches this level, patients typically experience clinical symptoms such as daytime sleepiness, memory loss, and difficulty concentrating, which can significantly impact their quality of life and physical well-being.
(3) Symptom
The patient’s clinical symptoms are crucial for diagnosis. Typical manifestations include: recurring breathing interruptions during sleep, sometimes noticeable to those nearby; or sudden awakening due to dyspnea, often accompanied by wheezing.
Many patients also experience night sweats, light sleep, and frequent tossing and turning. These common symptoms provide the clinical basis for doctors to make a diagnosis.
At the same time, other diseases that may cause similar symptoms also need to be ruled out. For example, obstructive sleep apnea hypopnea syndrome should be ruled out.
Obstructive sleep apnea is mainly caused by upper airway obstruction. Although there is apnea, chest and abdominal respiratory movements still exist when the oral and nasal airflow stops. This is significantly different from central apnea, in which oral and nasal airflow and chest and abdominal respiratory movements stop at the same time.
In addition, secondary respiratory abnormalities caused by some neurological diseases, cardiovascular diseases, etc. need to be ruled out. Only after these interfering factors are ruled out can central apnea be diagnosed more accurately according to the above standards.
Treatment Of Central Sleep Apnea
Treatment for CSA is highly individualized and must be tailored based on the type (hypercapnic or non-hypercapnic), specific etiology, and whether or not there is concurrent obstructive sleep apnea (OSA). Due to the lack of large-scale research data, clinical decision-making relies heavily on a comprehensive physician assessment.
The cornerstone of treatment is precise intervention for the underlying cause. For example, reducing opioid use may improve drug-induced CSA, weight loss can help treat OHS, and optimizing cardiac function can improve CSA associated with heart failure.
Currently, positive pressure ventilation, medications, and oxygen therapy are the mainstays of treatment.
(1) Treatment Of Primary Disease
If CSA is caused by heart failure, optimal heart failure treatment (such as diuretics and vasodilators) is necessary. Improved cardiac function can reduce respiratory disturbances.
Combined neurological disorders (such as brainstem lesions) require targeted interventions (such as rehabilitation or surgery) in conjunction with a neurology specialist.
Discontinuing precipitating medications (such as opioid sedatives) may significantly improve symptoms.
(2) Lifestyle And Behavioral Interventions
Weight loss: Obesity may worsen respiratory disturbances. Weight control is recommended for those with a BMI ≥ 25.
Avoid supine sleeping: Some patients may experience fewer respiratory events while sleeping on their side.
Quit smoking and limit alcohol consumption: Alcohol and nicotine may suppress central respiratory function.
(3) Positive Pressure Therapy
Nasal continuous positive airway pressure (CPAP) is a common treatment for obstructive sleep apnea and may also be effective for some types of central sleep apnea.
This approach is particularly useful in two situations: first, patients with both central and obstructive sleep apnea (i.e., mixed sleep apnea);
Second, patients with isolated CSA whose central apnea worsens in the supine position and is accompanied by upper airway narrowing or collapse. CPAP may also be effective.
The mechanism of action is that CPAP maintains upper airway patency during sleep, thereby preventing the narrowing or complete obstruction of the throat that occurs during central apnea.
By stabilizing the upper airway, CPAP helps alleviate the hyperventilation and unstable respiratory rhythm caused by apnea, thereby breaking the vicious cycle of repeated apnea.
Nasal CPAP therapy may benefit patients with heart failure and central sleep apnea (CSA), both through upper airway support through air pressure and indirectly through improvements in respiratory muscle and cardiac function.
Recent studies have shown that this therapy improves left ventricular ejection fraction and significantly reduces the combined risk of death and heart transplantation by 81%. This effect was not seen in heart failure patients without CSA, highlighting the potential value of CPAP for this specific population.
Noninvasive positive pressure ventilation (NIPPV) is an important respiratory support therapy. It is primarily used to treat central apnea and nocturnal respiratory failure associated with elevated carbon dioxide levels.
This therapy currently utilizes a bi-level pressure mode. Studies have shown that it is also effective for another type of central apnea not associated with elevated carbon dioxide levels.
The principle is that when a patient experiences respiratory arrest, NIPPV can help maintain basic ventilation, thereby preventing overbreathing due to body compensation and preventing the respiratory rhythm from falling into an unstable cycle of “apnea-hyperbreathing-apnea again”.
The clinical application of noninvasive positive pressure ventilation (NIPPV) in the treatment of CSA has certain limitations. The primary issue is the lack of strong evidence.
Currently, its benefit has only been demonstrated for ventilatory failure associated with amyotrophic lateral sclerosis, while its efficacy for other types of CSA remains unclear.
Secondly, there is a lack of recognized standards at the operational level. Both the assessment of disease severity and the setting of treatment pressure mainly rely on subjective indicators during the wakeful period and the improvement of ventilation during sleep. Its scientific nature and superiority still need to be verified.
The effectiveness of biphasic positive airway pressure (BPAP) for treating CSA requires careful evaluation.
On the one hand, it carries the risk of hyperventilation; on the other hand, in certain patients, such as those with OHS, proper settings can significantly improve breathing and reduce carbon dioxide.
Although current evidence is limited, it suggests potential value in alleviating symptoms and enhancing cardiac function.
(4) Drug Therapy
Currently, drug treatments for central sleep apnea (CSA) have limited efficacy, with only two drugs showing some benefit in small studies: acetazolamide and theophylline.
Acetazolamide: This diuretic affects the body’s acid-base balance, causing a mild metabolic acidosis that lowers the CO2 threshold that triggers apnea. A 250-mg dose at bedtime may be effective, but its long-term effects are unknown.
Theophylline: It stimulates the respiratory center and enhances myocardial contractility. Evidence suggests it can improve CSA in patients with heart failure and Cheyne-Stokes respiratory failure without disrupting sleep or causing arrhythmias.
Overall limitations: As the existing evidence is based on small studies rather than large-scale clinical trials, respiratory stimulants cannot currently be used as a routine treatment for CSA, and their effectiveness and safety still need further exploration.
(5) Supplemental Oxygen
For non-hypercapnic central sleep apnea (CSA), supplemental oxygen may be beneficial. Its principle is to improve the body’s hypoxic state directly, thereby avoiding hyperventilation caused by hypoxia and helping to stabilize respiratory rhythm.
However, uncertainty remains regarding the application of this therapy. First, there is a lack of large-scale, long-term studies to clarify which patients are best suited for oxygen therapy and its long-term effects.
Second, there are concerns that oxygen therapy may adversely affect cardiac function, making its use in patients with heart failure and CSA particularly cautious.
However, recent studies have begun to show that oxygen therapy may be beneficial to cardiovascular function. Therefore, its exact efficacy and safety still need to be confirmed by larger-scale clinical trials.
Conclusion
The best treatment for CSA depends on the underlying cause, the severity of the condition, and the person’s personal preferences. A healthcare professional can help determine the most appropriate treatment plan.
