Central sleep apnea (CSA) is a sleep-related breathing disorder distinguished by recurrent episodes of apnea alternating with periods of normal respiration. Unlike obstructive sleep apnea, which involves physical airway blockage, CSA originates from the brain’s failure to send proper signals to breathing muscles. Automotive technicians experiencing symptoms such as abrupt awakenings with breathlessness, persistent insomnia, excessive daytime sleepiness, difficulty concentrating, or mood disturbances may be affected by CSA. This article provides an in-depth review of the pathophysiology, diagnostic criteria, and available treatments for central sleep apnea, emphasizing accurate diagnosis based on established criteria.
Understanding Central Sleep Apnea
Central sleep apnea (CSA) is characterized by a temporary disruption or cessation of the respiratory drive from the brainstem’s pontomedullary region. It’s a form of sleep-disordered breathing (SDB) where ventilation is briefly absent during sleep. CSA typically manifests in a cyclical pattern: periods of apnea or hypopnea alternate with periods of hyperpnea. While the primary issue in central events is the lack of respiratory effort, studies indicate that the upper airway can narrow or even collapse during these episodes, particularly at the retropalatal level during hypocapnic central apnea and hypopnea.
Although less prevalent than obstructive sleep apnea (OSA), CSA can frequently coexist with OSA. Patients may present with features of both conditions. The International Classification of Sleep Disorders – Third Edition (ICSD-3) categorizes CSA syndromes based on polysomnographic and clinical characteristics into:
- Primary Central Sleep Apnea
- Central Sleep Apnea with Cheyne-Stokes Breathing (CSB)
- Central Sleep Apnea due to a Medical Disorder without CSB
- Central Sleep Apnea due to Periodic High-Altitude Breathing
- Central Sleep Apnea due to a Medication or Substance
- Treatment-Emergent Central Sleep Apnea
Both hypoventilation and hyperventilation can lead to central apneas through distinct pathophysiological mechanisms. The level of alveolar ventilation is often used to classify CSA. For instance, heart failure patients often exhibit hypocapnia while awake and are more prone to hyperventilation-related CSA. Conversely, hypoventilation-related CSA is more common in conditions like neuromuscular diseases (e.g., amyotrophic lateral sclerosis, brainstem stroke), medication overuse (especially opioids), cervical spinal cord injury, and structural issues affecting lung mechanics (e.g., kyphoscoliosis).
Etiology of Central Sleep Apnea
Various underlying medical conditions can predispose individuals to central breathing instability during sleep, leading to CSA. Conditions such as atrial fibrillation (AF), heart failure (HF) with both preserved and reduced ejection fraction (EF), ischemic stroke, spinal cord injury, renal failure, and chronic opioid use are known to increase the risk of central apnea by causing transient reductions in ventilatory output. CSA is particularly prevalent in cardiovascular conditions and is recognized as an independent risk factor for adverse health outcomes. In some cases, the cause of CSA remains unidentified, classified as idiopathic or primary CSA.
Epidemiology of Central Sleep Apnea
Research indicates that the prevalence of central apnea increases with age. A study by Bixler et al. revealed a higher central apnea index in older adults compared to middle-aged individuals (12.1% vs. 1.8%). The incidence of CSA is notably higher in the elderly population, especially those over 65 years old. A cross-sectional study reported a 2.7% prevalence of CSA in men aged 65 and older, using a modified ICSD-3 classification.
This age-related increase may be attributed to heightened chemosensitivity in older adults, making them more susceptible to central apnea, particularly during non-rapid eye movement (NREM) sleep. Compared to men, women are generally less susceptible to CSA and typically require a greater degree of hypocapnia to develop central apnea.
Pathophysiology of Central Sleep Apnea
The pathophysiology of CSA is complex and varies depending on associated comorbidities. A key mechanism in the development of central apnea is hypoventilation or hyperventilation leading to hypocapnia, which falls below an apneic threshold. Reduced ventilatory drive during NREM sleep can trigger central apnea and hypopnea, even in healthy individuals. Central chemoreceptors and upper airway mechanics are significant factors in this process. Furthermore, ventilatory control can contribute to central apnea in susceptible populations, such as those with neuromuscular disorders or chest wall deformities.
Enhanced chemosensitivity to arterial carbon dioxide levels during sleep increases loop gain, causing ventilatory instability and CSA, especially in heart failure patients. Opioids and other CNS depressants can suppress the brainstem’s respiratory rhythm generator. Therefore, CSA can result from either reduced central ventilatory motor output or high loop gain. Regardless of the initial cause, once a cycle of apnea begins, it tends to perpetuate, leading to repeated episodes of hypoxia, irregular breathing, and ultimately, upper airway narrowing.
History and Physical Examination in CSA Diagnosis
Patients with CSA often present with complaints similar to those with other forms of sleep apnea, primarily related to disrupted sleep. Common symptoms include poor sleep quality, nocturnal awakenings, sleep fragmentation, excessive daytime sleepiness (EDS), morning headaches, fatigue, and impaired concentration. Notably, snoring is not always a prominent symptom in CSA. While OSA and CSA are distinct conditions, they can coexist, resulting in mixed presentations. While a higher body mass index is linked to increased OSA risk, CSA patients are typically less obese.
In hypercapnic central apnea, symptoms related to the underlying disease process may be more pronounced. Interestingly, patients with heart failure may not always recognize or report daytime sleepiness despite objective evidence, possibly due to increased daytime sympathetic activity counteracting sleepiness.
A recent study indicated an inverse relationship between subjective daytime sleepiness and mortality risk in heart failure patients with sleep apnea. Therefore, in elderly heart failure patients, fatigue complaints, even without typical EDS, should prompt consideration of sleep apnea diagnosis.
Central Sleep Apnea Diagnosis Criteria and Evaluation
Early detection of CSA based solely on self-reported sleep disruption symptoms can be challenging. Nocturnal polysomnography (PSG) is the gold standard diagnostic test for evaluating central apnea. The American Academy of Sleep Medicine (AASM) in ICSD-3 has established specific Central Sleep Apnea Diagnosis Criteria, which vary based on the CSA type. Generally, diagnosis requires PSG evidence of recurrent central apneas and exclusion of other potential diagnoses. A central apnea is defined as a cessation of airflow for at least 10 seconds during sleep without respiratory effort.
Diagnostic Criteria for Primary Central Sleep Apnea
Primary CSA diagnosis is confirmed if PSG reveals ≥5 central apneas and/or central hypopneas per hour of sleep, with central events constituting >50% of all respiratory events in the apnea-hypopnea index (AHI). Cheyne-Stokes breathing must be absent. Additionally, at least one sleep-disruption related complaint (sleepiness, insomnia, awakening with shortness of breath, snoring, or witnessed apneas) must be present.
Diagnostic Criteria for Central Sleep Apnea with Cheyne-Stokes Breathing (CSB)
CSA with CSB is diagnosed when primary CSA criteria are met, along with three or more consecutive central apneas or hypopneas separated by a crescendo-decrescendo respiratory pattern with a cycle length ≥40 seconds.
Diagnostic Criteria for Treatment-Emergent Central Sleep Apnea
Treatment-emergent central apnea is diagnosed in patients initially diagnosed with OSA (AHI ≥ 5 obstructive respiratory events per hour of sleep) who show resolution of obstructive apnea but develop or maintain CSA during positive airway pressure (PAP) titration. This CSA must not be explained by other diseases or substances.
Figure 1: Polygraph illustrating central and obstructive apnea events. Central apnea is characterized by a cessation of airflow with absent respiratory effort, while obstructive apnea shows airflow cessation despite continued effort.
Treatment and Management of Central Sleep Apnea
The primary goals in CSA management are to stabilize sleep by reducing abnormal respiratory events and to optimize treatment for comorbid conditions. Positive airway pressure (PAP) therapy, including continuous PAP (CPAP), Bi-level PAP (BPAP), and adaptive servo-ventilation (ASV), remains a standard treatment. Other options include supplemental oxygen, carbon dioxide administration, and pharmacological agents. Studies indicate CPAP and BPAP are effective for CSA management in heart failure and opioid-induced CSA.
Given the heterogeneity of CSA, individualized treatment strategies are necessary. Treatment modalities can include mechanical pressure devices, oxygen therapy, nerve stimulation, and pharmacological interventions.
Mechanical Devices for CSA Treatment
Nocturnal oxygen therapy has shown effectiveness in reducing apneic episodes and improving quality of life in CHF patients with CSA. Studies have demonstrated improvements in NYHA functional class and ejection fraction after 12 weeks and sustained quality of life improvements over 52 weeks.
Unilateral phrenic nerve stimulators represent another treatment option, associated with decreased disease severity, improved quality of life, arousal index, and reduced daytime sleepiness, independent of heart failure status. Peripheral nerve stimulation works by restoring normal breathing mechanics.
Pharmacological Treatments for CSA
Several pharmacological agents are under investigation for CSA treatment, although no medications are currently FDA-approved specifically for CSA. Hypnotics like triazolam and zolpidem may reduce wakefulness and sleep instability, potentially increasing total sleep time and decreasing central apnea index and arousals.
Respiratory stimulants, such as acetazolamide (a carbonic anhydrase inhibitor), induce mild metabolic acidosis, increasing respiratory drive and reducing central apnea frequency. Other medications like buspirone and mirtazapine have shown promise in reducing susceptibility to hypocapnic central apnea in spinal cord injury patients. Theophylline, an adenosine receptor antagonist, may benefit CSA in heart failure patients by stimulating ventilation via medullary adenosine receptor inhibition. Recent research suggests selective adenosine A1 receptor blockade may alleviate CSA in cervical spinal cord injury models.
Differential Diagnosis of Central Sleep Apnea
When diagnosing central sleep apnea, it is crucial to rule out other conditions that can cause excessive daytime sleepiness and sleep disruption. These include:
- Obstructive sleep apnea
- Periodic limb movements of sleep
- Narcolepsy
- Obstructive and restrictive lung diseases
- Neuromuscular diseases
- Shift work sleep disorder and irregular sleep-wake rhythm disorder
Prognosis of Central Sleep Apnea
Patients with heart failure and CSA, particularly with Cheyne-Stokes breathing, generally have a poorer prognosis, emphasizing the importance of optimizing heart failure therapy.
Adaptive servo-ventilation (ASV), while initially considered promising, has been linked to increased all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction without significant symptom or quality of life improvement. Increased mortality has been reported in this patient group using ASV.
Complications of Untreated Central Sleep Apnea
Untreated sleep apnea syndrome, including CSA, increases the risk of various systemic complications such as systemic and pulmonary hypertension, arrhythmias (including atrial fibrillation), excessive daytime sleepiness, mood disorders, chronic respiratory failure, narcolepsy, and hypercapnic respiratory failure.
Deterrence and Patient Education for CSA
Patient and family education about the physiology and mechanisms of sleep apnea is vital. In CSA, disrupted breathing control and rhythm lead to transient cessations of airflow and reduced breathing. CSA can significantly impact long-term health and quality of life, manifesting as restless sleep, low energy, concentration and memory issues, and unrefreshing sleep.
Polysomnography remains the gold standard for diagnosis, measuring breathing effort, airflow, vital signs, and blood oxygen levels during sleep stages. Treatment involves identifying and addressing underlying causes and precipitating factors. Referral to a sleep specialist is essential for proper evaluation and management.
Enhancing Healthcare Team Outcomes in CSA Management
Effective management of central sleep apnea necessitates a multidisciplinary approach. Cardiologists are crucial in optimizing heart failure treatment in relevant cases. Respiratory therapists and nurses play a vital role in educating patients on non-invasive ventilation techniques and equipment. Pharmacists contribute by evaluating and identifying medications that may exacerbate CSA. A collaborative, multidisciplinary team ensures comprehensive care for patients with central sleep apnea.
Review Questions
This section would ideally contain multiple-choice questions related to central sleep apnea diagnosis criteria and management, similar to the original article, but is omitted here for brevity as per instructions.
Figure 2: Video demonstrating upper airway collapse at the retropalatal level during an episode of central apnea, highlighting the physiological mechanisms involved.
References
[List of references as provided in the original article]
Disclosure: Abdul Rana declares no relevant financial relationships with ineligible companies.
Disclosure: Abdulghani Sankari declares no relevant financial relationships with ineligible companies.
