bubble_chart Overview

To maintain the metabolic demands of vital organs, uninterrupted gas exchange is required during sleep to intake O₂, expel CO₂, and maintain internal homeostasis. If the airflow through the oropharynx and nasopharynx ceases for more than ten seconds during sleep, it is referred to as sleep apnea. Frequent episodes of sleep apnea can lead to CO₂ retention and hypoxemia, further causing complications such as elevated systemic and pulmonary circulation pressure and cardiac arrhythmias.

bubble_chart Pathogenesis

Breathing and Sleep:

Sleep can be divided into rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep, with the latter further categorized into light sleep (Stages I and II) and deep sleep (Stages III and IV).

(1) REM Sleep: Metabolism and brain activity increase. Except for the eye muscles and diaphragm, skeletal muscle tone—including the intercostal muscles, inspiratory muscles, and abnormal rising of qi tract muscles—is significantly suppressed. Heart rate and blood pressure become irregular, and ventilatory responses to hypoxia and high CO₂ stimulation are markedly weakened. Sleep arousal responses are also notably delayed. REM sleep typically lasts 20–30 minutes and recurs every 90–120 minutes.

(2) NREM Sleep: Metabolism and brain activity decrease, and diffuse slow waves can be observed on the electroencephalogram (EEG). Heart rate tends to be slow and regular, ventilation slightly decreases, and PaCO₂ may rise by 0.27–0.4 kPa (2–3 mmHg). Inhalation of low-oxygen or high-CO₂ gases can trigger sleep arousal responses. NREM sleep usually lasts 70–100 minutes, and in normal sleep, NREM precedes REM, alternating cyclically. Each night, REM sleep accounts for about 20–25% of total sleep time, while NREM accounts for 75–80%.

(3) The Effect of Sleep on Abnormal Rising of Qi Tract and Thoracic Muscles: Normal breathing requires highly coordinated contraction of respiratory muscles. The abnormal rising of qi tract muscles maintains a certain baseline tone to keep the airway open. Before each diaphragmatic contraction, neural discharge causes the abnormal rising of qi tract muscles to contract. The genioglossus muscle contracts to pull the tongue forward, stabilizing the pharyngeal wall and further keeping the abnormal rising of qi tract open while resisting the collapsing effect of negative pharyngeal pressure during inspiration. Subsequently, the intercostal muscles contract to stabilize the chest wall, and the diaphragm contracts to generate negative intrathoracic pressure, completing inspiration. During normal NREM sleep, the baseline tone of abnormal rising of qi tract muscles decreases, the airway diameter narrows, and airway resistance increases. However, the phasic discharge of abnormal rising of qi tract muscles and the rhythmic contraction of intercostal muscles remain intact. During REM sleep, the baseline tone of abnormal rising of qi tract muscles, intercostal muscles, and most skeletal muscles is further suppressed. Reduced pharyngeal muscle tone can cause the abnormal rising of qi tract to collapse during inspiration. Decreased baseline tone of the genioglossus muscle may lead to backward displacement of the tongue root and airway narrowing. Reduced intercostal muscle tone can result in chest wall instability during inspiration, causing paradoxical chest-abdominal movement. During REM sleep, the inspiratory phasic discharge of abnormal rising of qi tract and intercostal muscles may also be suppressed. When negative intrathoracic pressure increases after diaphragmatic contraction, it exacerbates the tendency for abnormal rising of qi tract collapse and chest wall instability.

Additionally, during REM sleep, sleep arousal and responses to external stimuli are largely suppressed, making ineffective or obstructive ventilation more likely to occur.

bubble_chart Clinical Manifestations

① Morning headache, daytime drowsiness and fatigue, accompanied by recurrent severe snoring and unstable sleep. ② Obesity, with significant hypoxemia and arrhythmia during sleep. ③ Diaphragmatic or thoracic impairment related to kyphoscoliosis or muscle atrophy. ④ Chronic obstructive pulmonary disease with sleep apnea. ⑤ Pulmonary diseases with severely impaired ventilation/perfusion ratio and diffusion, such as pulmonary fibrosis, cystic fibrosis, fibrotic pulmonary subcutaneous nodules. ⑥ Diseases affecting the respiratory center. ⑦ Obesity hypoventilation syndrome. ⑧ Chronic mountain sickness, with recurrent hypoxemia during sleep. ⑨ Long-term use of potent diuretics leading to metabolic alkalosis and suppressed ventilation.

Types of sleep-disordered breathing:

(1) Obstructive Sleep Apnea Syndrome (OSAS) OSAS is the predominant disorder among adult sleep-disordered breathing conditions. The diagnosis is based on the absence of airflow in the upper respiratory tract for more than 10 seconds despite the presence of thoracoabdominal respiratory movements. This occurs more than 5 times per hour or over 30 times during 6 hours of sleep per night.

OSAS is primarily seen in obese individuals and may coexist with hypothyroidism, acromegaly, or congenital and acquired abnormalities such as enlarged tonsils, adenoid hypertrophy, or micrognathia that cause narrowing of the abnormal rising of qi passage. Most adult OSAS cases show no significant anatomical changes, and the pathophysiology is not fully understood. However, it is generally believed to be related to reduced basal muscle tone in the intermediate qi passage during sleep, loss of abnormal rising of qi muscle discharge, or discoordination between discharge and diaphragmatic contraction. Anatomical abnormalities in the abnormal rising of qi passage that cause significant narrowing or increased compliance can also lead to collapse of the abnormal rising of qi passage during inspiration, resulting in OSAS.

Sleep arousal responses triggered by apnea can occur in all sleep phases but are typically observed during NREM stage II light sleep. This is because arousal responses frequently occur before reaching deep sleep, resulting in a lack of deep sleep (stages III and IV) and a relatively prolonged REM sleep phase. The duration of sleep following apnea is very brief, lasting only 10–30 seconds. Breathing may be normal upon arousal, or snoring may occur due to partial obstruction in the abnormal rising of qi passage.

During apnea, despite the absence of airflow in the abnormal rising of qi passage, thoracoabdominal respiratory movements persist, with large fluctuations in intrathoracic negative pressure, which can reach as high as 7.8 kPa (80 cmH₂O). Due to the collapse of the abnormal rising of qi passage, little or no external air enters the alveoli for moving qi exchange, leading to severe hypoxemia and CO₂ retention, progressive bradycardia, and transient tachycardia at the end of apnea. Occasionally, sinus block, atrioventricular dissociation, junctional or ventricular escape beats, and atrial or ventricular ectopic rhythms may occur due to hypoxemia-induced acidosis and myocardial ischemia. Severe OSAS patients may experience daytime drowsiness, persistent hypercapnia while awake, or even pulmonary stirred pulse hypertension and right heart failure.

(2) Central Sleep Apnea Syndrome (CSAS) CSAS is defined as the absence of airflow in the abnormal rising of qi passage for more than 10 seconds without thoracoabdominal respiratory movements. CSAS is less common and may coexist with OSAS. It can occur in any sleep phase but is most pronounced during NREM sleep. CSAS may occur alone or coexist with central nervous system diseases such as brainstem trauma, tumors, infarction, or infections. Cases have also been reported in association with neuromuscular disorders like poliomyelitis and myotonic dystrophy. While ventilation may remain adequate while awake, respiratory center dysregulation during sleep leads to central (or obstructive) apnea.

(3) Sleep-related breathing disorders in patients with chronic obstructive pulmonary disease Patients with chronic obstructive pulmonary disease may experience significant deterioration in breathing and gas exchange during sleep, primarily characterized by severe stirred pulse oxygen desaturation and transient specific breathing abnormalities such as apnea and hypopnea. These manifestations are most pronounced during REM sleep, though the underlying mechanisms remain unclear and may be related to abnormal respiratory activity associated with this sleep phase. Additionally, these patients exhibit blunted chemoreceptor responses even when awake, which can further worsen during sleep, leading to reduced ventilatory responses.

(4) Apnea-like Phenomena There are two types of apnea-like phenomena that can be confused with sleep apnea syndrome: ① Epilepsy Grade I epilepsy without tonic-clonic seizures may also present with apnea. If it occurs during sleep or in a postictal sleep-like state, it can be mistaken for sleep apnea, but an electroencephalogram (EEG) can help differentiate the two. ② Cheyne-Stokes Respiration This can be observed in patients with reduced cardiac output or prolonged circulation time, as well as in various neurological disorders affecting the respiratory center and in some elderly individuals. It is difficult to distinguish from central sleep apnea, and the two may coexist. However, Cheyne-Stokes respiration exhibits gradual changes in breathing amplitude, starting small, increasing, then decreasing until apnea occurs, with relatively short apnea durations. Central sleep apnea tends to occur suddenly and is often accompanied by arousal responses, with longer apnea durations, potentially lasting up to 60 seconds. Additionally, Cheyne-Stokes respiration can persist into wakefulness, whereas central sleep apnea does not occur during wakefulness and often worsens during REM sleep.

(5) Irregular Breathing During Normal Sleep In healthy individuals, breathing is typically regular during REM sleep. However, an unstable breathing period lasting several minutes may occur at sleep onset and disappear once stable sleep is achieved. The apneas observed during this period lack respiratory effort and may be mistaken for central sleep apnea syndrome (CSAS). Asymptomatic healthy individuals may also exhibit obstructive sleep apnea, but it usually occurs fewer than 20 times per night, with only grade I stirred pulse oxygen desaturation. If it occurs during REM sleep, due to weakened arousal responses, it can lead to significant stirred pulse oxygen desaturation.

bubble_chart Auxiliary Examination

Sleep Respiratory Monitoring:

Monitoring Methods Sleep respiratory monitoring involves observing the functions of the patient's central nervous, respiratory, and cardiovascular systems during sleep, as well as the outcomes of sleep-related breathing disorders, to provide a basis for diagnosis. Standard polysomnography should record the following variables throughout the night: electroencephalogram (EEG), electromyogram (EMG), electrocardiogram (ECG), ventilation, thoracoabdominal respiratory movements, and the results of respiratory disturbances. Direct monitoring of ventilation requires the use of a mouthpiece or mask to collect exhaled air, but patients often find this uncomfortable, and it may disrupt natural sleep. Indirect monitoring of ventilation includes both qualitative and semi-quantitative methods. Qualitative methods may involve using thermistors or rapid CO₂ analyzers to monitor respiratory gases through the nose and mouth. Semi-quantitative methods can employ magnetometers or respiratory inductive plethysmography. Thoracoabdominal respiratory movements can be monitored using diaphragmatic electromyography, transdiaphragmatic pressure measurement, or respiratory inductive plethysmography. Monitoring the outcomes of respiratory disturbances primarily involves direct or indirect measurement of arterial blood oxygen partial pressure, CO₂ partial pressure, and oxygen saturation.

bubble_chart Treatment Measures

(1) General Measures ① Weight Loss In obese individuals, abnormal deposition of fat around the airway leads to narrowing of the lumen and increased compliance, making the airway prone to collapse during inhalation. Additionally, this is often accompanied by reduced functional residual capacity and tidal volume, which can cause ventilation/perfusion mismatch and hypoxemia. Significant improvement is often achieved after weight loss, though some patients find it difficult to adhere to long-term weight management. ② Oxygen Therapy For patients with hypoxemia, low-concentration oxygen therapy may be considered to maintain PaO₂ at 8–10 kPa (60–75 mmHg). Besides improving apnea duration and oxygen saturation, this can also prevent complications such as bradycardia, pulmonary arterial hypertension, and cor pulmonale caused by sleep apnea. ③ Alcohol Abstinence and Avoidance of Sedatives Alcohol and sedatives can reduce the activity of muscles around the airway, including the genioglossus, thereby triggering sleep apnea. Therefore, avoiding alcohol and sedatives before bedtime can aid in the treatment of sleep apnea.

(2) Special Measures

(1) Treatment of OSAS ① Nasal Continuous Positive Airway Pressure (CPAP) CPAP helps maintain airway dilation and effectively prevents sleep apnea. ② Relief of Mechanical Airway Obstruction In cases of tonsillar or adenoid hypertrophy, surgical removal can yield favorable results. Uvulopalatopharyngoplasty (UPPP) is particularly effective for sleep apnea caused by nasopharyngeal obstruction. ③ Tracheostomy Tracheostomy bypasses airway collapse, but it is often poorly accepted by patients, and once performed, decannulation is difficult.

(2) Treatment of CSAS Respiratory stimulants such as theophylline, acetazolamide, and progesterone may be administered, though reported efficacy varies. In severe cases of CSAS where drug therapy is ineffective, tracheostomy and nocturnal mechanical ventilation may be considered.