Central sleep apnea (CSA) is a sleep-related breathing disorder distinguished by repeated episodes of stopped or reduced breathing, known as apneas and hypopneas, alternating with periods of normal respiration. Unlike obstructive sleep apnea, CSA originates from the brain’s failure to send proper signals to the muscles that control breathing. Individuals with CSA might experience abrupt awakenings accompanied by breathlessness, persistent insomnia, and overwhelming daytime sleepiness, alongside challenges in concentration and shifts in mood. This condition can be triggered by underlying health issues such as heart failure, stroke, or even high altitude. This article delves into the mechanisms behind central sleep apnea, its diagnosis, and the range of therapeutic approaches available, emphasizing the crucial role of a multidisciplinary healthcare team in effective management.
Decoding Central Sleep Apnea: An Overview
Central sleep apnea (CSA) is characterized by a temporary reduction or cessation of signals from the respiratory rhythm generator in the brainstem. CSA is a form of sleep-disordered breathing (SDB) resulting from brief lapses in ventilatory drive during sleep. It manifests cyclically during sleep, with periods of apnea or hypopnea alternating with hyperpnea. Despite the absence of breathing effort during central events, studies indicate that the upper airway can narrow or nearly collapse. Research using induced hypocapnic central apnea has consistently shown upper airway narrowing at the retropalatal level, as seen in video studies of induced central hypopnea. [1]
While CSA is less common than obstructive sleep apnea (OSA), both conditions can coexist, with patients exhibiting symptoms of both. The International Classification of Sleep Disorders – Third Edition (ICSD-3) [2] categorizes CSA syndromes based on distinct clinical and polysomnographic features:
- Primary CSA
- CSA with Cheyne-Stokes Breathing (CSB)
- CSA due to a medical disorder without CSB
- CSA due to periodic high-altitude breathing
- CSA due to medication or substance use
- Treatment-emergent CSA
Both hypoventilation and hyperventilation can lead to central apneas through different pathophysiological pathways. Alveolar ventilation levels often serve as a basis for classifying CSA. Patients with heart failure, often hypocapnic when awake, are prone to hyperventilation-related CSA. Conversely, hypoventilation-related CSA is common in neuromuscular diseases (like amyotrophic lateral sclerosis), medication overuse that depresses the central nervous system (opioids), cervical spinal cord injury, and structural issues affecting lung function (kyphoscoliosis). [3][4]
Unveiling the Causes of Central Sleep Apnea
Various medical conditions can create central breathing instability during sleep, leading to CSA. Conditions like atrial fibrillation (AF), heart failure (HF) with both preserved or reduced ejection fraction (EF), ischemic stroke, spinal cord injury, renal failure, and chronic opioid use increase susceptibility to central apnea by causing temporary reductions in ventilatory output. CSA is particularly prevalent in cardiovascular conditions and is independently linked to adverse health outcomes. In some cases, no clear cause is identified, and this is termed idiopathic or primary CSA. [5]
How Common is Central Sleep Apnea? Understanding the Epidemiology
Research by Bixler et al. indicated a higher central apnea index in older adults compared to middle-aged individuals (12.1% vs. 1.8%). [6] The prevalence of CSA increases with age, being more common in those over 65. A cross-sectional study using a modified ICSD-3 classification reported a 2.7% prevalence of CSA in men aged 65 and older. [7]
This age-related increase may be due to heightened chemoreceptor responsiveness in older individuals, making them more susceptible to central apnea, especially during non-rapid eye movement (NREM) sleep. [8] Compared to men, women are less prone and typically require a greater degree of hypocapnia to develop central apnea. [9]
Pathophysiology of CSA: Delving into the Mechanisms
The underlying mechanisms of CSA vary depending on associated health conditions. Hypoventilation or hyperventilation, resulting in hypocapnia below an apneic threshold, are key factors driving central apnea. Reduced ventilatory drive during NREM sleep can induce central apnea and hypopnea, even in healthy individuals. Complex mechanisms involve central chemoreceptors and upper airway mechanics. [10][11] Ventilatory control issues can contribute to central apnea in susceptible individuals, particularly those with neuromuscular disorders (like spinal cord injury) or chest wall abnormalities (like kyphoscoliosis).
Increased chemosensitivity to arterial carbon dioxide levels during sleep, especially in heart failure patients, leads to ventilatory instability and CSA due to increased loop gain. [12] Opioids and other CNS depressants can suppress the brainstem’s respiratory rhythm generator. Thus, CSA development can stem from reduced central ventilatory motor output or high loop gain. Regardless of the cause, once a cycle begins, it perpetuates, leading to repeated hypoxia and irregular breathing, ultimately causing upper airway narrowing. [1]
Recognizing CSA: History and Physical Examination
Patients with CSA often present with sleep disruption complaints similar to other forms of sleep apnea. They commonly report poor sleep quality, nighttime awakenings, fragmented sleep, excessive daytime sleepiness (EDS), morning headaches, fatigue, and difficulty concentrating. However, snoring might not be a prominent symptom in CSA. While OSA and CSA are distinct, they can coexist, leading to mixed symptoms. While a higher body mass index is linked to OSA risk, CSA patients are typically less obese.
In hypercapnic central apnea, symptoms related to the underlying condition are also relevant. Interestingly, heart failure patients may not recognize or report daytime sleepiness despite objective evidence. [13][14] Increased daytime sympathetic activity might explain this lack of perceived sleep disruption, enhancing alertness and counteracting sleepiness. [15]
A study highlighted an inverse correlation between subjective daytime sleepiness and mortality risk. [16] Therefore, sleep apnea should be suspected in elderly heart failure patients with fatigue complaints, even without typical EDS.
CSA Diagnosis: Evaluation and Testing
Early detection of CSA based solely on self-reported sleep disruption symptoms can be challenging. Nocturnal polysomnography (PSG) is the gold standard for Csa Diagnosis. The American Academy of Sleep Medicine (AASM) in ICSD-3 [2] published diagnostic criteria for CSA, varying by CSA type. [17] Generally, CSA diagnosis requires evidence of recurrent central apneas on PSG and ruling out alternative diagnoses. Central apnea is defined as airflow cessation during sleep for at least 10 seconds without breathing effort (figure 1). [18]
- Primary CSA Diagnosis: PSG showing ≥5 central apneas and/or central hypopneas per hour of sleep, with central events comprising >50% of total respiratory events in the apnea-hypopnea index, and no Cheyne-Stokes breathing. [18] At least one sleep disruption complaint (sleepiness, insomnia, waking with shortness of breath, snoring, or witnessed apneas) must be present for CSA diagnosis.
- CSA with CSB Diagnosis: Requires primary CSA criteria plus three or more consecutive central apneas or hypopneas with a crescendo–decrescendo respiratory pattern cycle length ≥40 seconds for CSA diagnosis.
- Treatment-Emergent Central Apnea Diagnosis: Requires a prior OSA diagnosis (apnea-hypopnea index ≥ 5 obstructive events per hour) followed by obstructive apnea resolution and CSA emergence or persistence (not due to other conditions or substances) during positive airway pressure (PAP) titration study for CSA diagnosis.
Managing Central Sleep Apnea: Treatment Options
The main goals in CSA management are to stabilize sleep by reducing abnormal respiratory events and optimizing treatment for coexisting conditions. Positive airway pressure (PAP), including continuous PAP (CPAP), bi-level PAP therapy (BPAP), and adaptive servo-ventilation (ASV), is a standard treatment for both central and obstructive apnea. Other treatments include supplemental oxygen, carbon dioxide, and medications. Studies indicate CPAP and BPAP are effective for CSA management in heart failure and opioid use. [19]
Due to the variability of CSA, individualized therapies are necessary rather than a uniform approach. Treatment options include mechanical pressure devices, oxygen, nerve stimulators, and pharmacological therapies. [20]
Mechanical Devices
Nocturnal oxygen therapy has been shown to decrease apneic episodes in CHF patients, improve NYHA functional class, quality of life, and ejection fraction over 12 weeks. [28] These benefits were sustained over 52 weeks in a similar study, confirming improved quality of life. [29]
Unilateral phrenic nerve stimulators are another treatment for central sleep apnea, associated with reduced disease severity and improved quality of life. It has also shown significant improvements in arousal index, quality of life, and reduced daytime sleepiness, independent of heart failure status. [30] Peripheral nerve stimulation helps restore normal breathing mechanics.
Various pharmacological agents have been investigated for CSA treatment. However, these remain investigational, with no approved pharmacological treatment for CSA currently available. Hypnotics like triazolam and zolpidem can reduce wakefulness and unstable sleep. [31] These may increase total sleep, decrease central apnea index, and reduce brief arousals. [31]
Respiratory stimulants such as acetazolamide, a carbonic anhydrase inhibitor, induce mild metabolic acidosis, increasing respiratory drive and reducing central apnea frequency. [32] Other medications like Buspirone [33] and Mirtazapine have also been studied. [33][34] Both reduced susceptibility to hypocapnic central apnea in spinal cord injury patients. Theophylline, a non-selective adenosine receptor antagonist, has been used for central sleep apnea in heart failure patients, potentially due to inhibiting medullary adenosine receptors, increasing ventilatory stimulation. [35] Recent studies suggest selective adenosine A1 receptor blockade may alleviate cervical spinal cord injury-induced CSA. [36]
Differential Diagnosis: Conditions to Rule Out
Several conditions must be considered and excluded in the CSA diagnosis process due to overlapping symptoms like excessive daytime sleepiness and sleep disruption. These include:
- Obstructive sleep apnea
- Periodic limb movements of sleep
- Narcolepsy
- Obstructive and restrictive lung diseases
- Neuromuscular disease
- Shift work sleep disorder and irregular sleep-wake rhythm disorder
Prognosis and Outcomes
Heart failure patients with CSA and CSB tend to have poorer prognoses, and treatment focuses on optimizing heart failure management. [37]
Adaptive servo-ventilation (ASV), delivering servo-controlled inspiratory pressure support, has been studied. A 2015 study showed that in heart failure patients with reduced EF, ASV was linked to increased all-cause and cardiovascular mortality without significant benefits in symptoms or quality of life. [38] Increased mortality has been reported in heart failure patients with reduced EF using adaptive servo-ventilation. [39]
Potential Complications of Untreated CSA
Patients with sleep apnea syndrome face increased risks of systemic complications, including systemic hypertension, pulmonary hypertension, arrhythmias like atrial fibrillation, sleep disturbances with excessive daytime sleepiness, mood disorders, chronic respiratory failure, narcolepsy, and hypercapnic respiratory failure. [40]
Deterrence and Patient Education for CSA
Educating patients and families about the physiology and mechanisms of sleep apnea is essential. In CSA, normal airflow through the respiratory tract is disrupted by temporary cessations and reductions in breathing due to changes in breathing control and rhythm. Central sleep apnea can significantly impact long-term health and quality of life. Symptoms can include restless sleep, low energy, concentration issues, memory problems, and waking up feeling unrefreshed.
The gold standard for CSA diagnosis is polysomnography, a sleep study measuring breathing effort and airflow, vital signs, and blood oxygen levels during sleep stages. Treatment involves identifying and addressing underlying causes and contributing factors. Evaluation by a sleep physician is ideally recommended for these patients.
The Healthcare Team’s Role in Managing CSA
For patients with central sleep apnea, a multidisciplinary approach is critical for comprehensive care. This often includes a cardiologist for heart failure patients to optimize treatment. Respiratory therapists and nurses play vital roles in educating patients on using non-invasive ventilation machines and masks, a cornerstone of CSA management. Pharmacists are crucial in identifying medications that may worsen the condition. Overall, a multidisciplinary team approach is essential for effectively managing patients with central sleep apnea and ensuring accurate CSA diagnosis and treatment.
Review Questions
Figure
Video demonstrating upper airway collapse at the retropalatal level during central apnea. Contributed by Dr. Abdulghani Sankari, MD.
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Disclosures: Abdul Rana declares no relevant financial relationships with ineligible companies.
Disclosures: Abdulghani Sankari declares no relevant financial relationships with ineligible companies.
