Central sleep apnea (CSA) is a heterogeneous group of conditions characterized by changes in ventilatory drive without airway obstruction (in contrast to obstructive sleep apnea). The diagnosis is based on symptoms (such as sleepiness and awakening short of breath) and polysomnography findings. Treatment varies by cause.
Central sleep apnea (CSA) is much less common than obstructive sleep apnea but is not rare. CSA is present in about 0.9% of people in the community (1). CSA is more common in older adults, males, and patients with cardiovascular disease such as heart failure. CSA also may occur in children (2).
General references
1. Donovan LM, Kapur VK: Prevalence and characteristics of central compared to obstructive sleep apnea: analyses from the sleep heart health study cohort. Sleep 39(7):1353–1359, 2016. doi: 10.5665/sleep.5962
2. McLaren AT, Bin-Hasan S, Narang I: Diagnosis, management and pathophysiology of central sleep apnea in children. Paediatr Respir Rev 30:49–57, 2019. doi:10.1016/j.prrv.2018.07.005
Pathophysiology of Central Sleep Apnea
Unlike with obstructive sleep apnea, in which airway obstruction restricts airflow, central sleep apnea (CSA) is caused by alterations in respiratory drive, which during sleep is highly dependent on carbon dioxide levels. Two mechanisms are distinguished:
Hypoventilation-related CSA: Decreased ventilatory drive causes transient decreases and/or pauses in respiration.
Hyperventilation-related CSA: Increased ventilatory drive during sleep leads to hypocapnia which causes a compensatory fall in ventilation that, if abnormally prolonged, leads to recurrent central apnea with arousals.
Hypoventilation-related CSA can result from either an anatomical or functional lesion of the respiratory centers that directly impairs ventilation, resulting in high carbon dioxide (CO2) levels (hypercapnia). Hypoventilation-related CSA can occur in patients with a central nervous system or neuromuscular disorder. Opioids and other medications are common causes of hypoventilation-related CSA.
Paradoxically, in hyperventilation-related CSA, periods of hyperventilation lead to subsequent apneas. Transient increases in ventilation for any reason may overshoot the target CO2 level, causing hypocapnia. The hypocapnia causes periods of subsequent hypoventilation and/or apnea, eventually resulting in hypercapnia and subsequent repeat of the cycle. Patients may alternate periodically between hyper- and hypoventilation, as in Cheyne-Stokes breathing, in which patients have brief periods of apnea followed by progressively faster and deeper breathing, which then becomes slower and shallower until they become apneic again and repeat the cycle.
Disturbed ventilation occurs primarily during sleep because during wakefulness there are additional external stimuli for respiration.
Etiology of Central Sleep Apnea
Causes of hypoventilation-related CSA with hypercapnia include hypothyroidism, neural lesions (eg, brain stem infarctions, encephalitis1).
Congenital central hypoventilation syndrome (Ondine curse) is a rare form of idiopathic CSA manifesting in neonates, in some cases associated with Hirschsprung disease. A mutation in the PHOX2 gene is responsible for 80 to 90% of cases (2). This mutation produces variable phenotypes, some of which may become recognizable later in life (3). Clinically evident cases are inherited in a dominant pattern. Sleep hypoventilation can be found in the parents.
An extremely rare condition that can cause CSA is a syndrome of Rapid-Onset obesity (marked weight gain in < 1 year) with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD); cause is multifactorial. Patients present in their second or third decade, often after a stress such as infection or surgery (4).
Hyperventilation-related CSA occurs at high altitude in healthy people as a consequence of hypobaric hypoxia. It also occurs in patients with heart failure and Cheyne-Stokes respiration and occasionally during treatment of obstructive apneas with positive airway pressure (PAP).
Etiology references
1. Javaheri S, Cao M: Chronic Opioid Use and Sleep Disorders. Sleep Med Clin 17(3):433–444, 2022. doi:10.1016/j.jsmc.2022.06.008
2. Genetic and Rare Diseases Information Center: Congenital central hypoventilation syndrome. National Institutes of Health, National Center for Advancing Translational Medicine, Genetic and Rare Diseases Information Center. Updated June 2024. Accessed July 2024. Congenital central hypoventilation syndrome - About the Disease - Genetic and Rare Diseases Information Center (nih.gov)
3. Antic NA, Malow BA, Lange N, et al: PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation in adulthood. Am J Respir Crit Care Med 174(8):923–927, 2006. doi:10.1164/rccm.200605-607CR
4. Chew HB, Ngu LH, Keng WT: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD): a case with additional features and review of the literature. BMJ Case Rep 2011:bcr0220102706, 2011. doi:10.1136/bcr.02.2010.2706
Symptoms and Signs of Central Sleep Apnea
Central sleep apnea may be asymptomatic, detected by caretakers or bed partners who notice long, quiet respiratory pauses and shallow breaths followed by hyperpnea, or restless sleep. Or it may be symptomatic with night time arousals from sleep (sleep maintenance insomnia) or excessive daytime sleepiness (sometimes called wake-time sleepiness), lethargy, or morning headache.
Diagnosis of Central Sleep Apnea
History and physical examination
Often polysomnography
Diagnosis of CSA is based on careful review of medical history, medication review, and clinical findings, and, when necessary, is confirmed by sleep testing at home with portable equipment or in a sleep laboratory using polysomnography (1, 2). However, testing may not be necessary if the cause is evident and reversible (eg, travel to high altitude, heart failure).
Arterial blood gases and bicarbonate levels during wakefulness are helpful in distinguishing hypercapnic from hypocapnic pathophysiology. To diagnose central nervous system causes of apnea with hypercapnia, brain or brain stem imaging may be indicated. If a Cheyne-Stokes pattern is observed, cardiac evaluation, including echocardiography, may also be warranted.
Diagnosis references
1. Baillieul S, Revol B, Jullian-Desayes I, Joyeux-Faure M, Tamisier R, Pépin JL: Diagnosis and management of central sleep apnea syndrome. Expert Rev Respir Med 13(6):545–557, 2019. doi:10.1080/17476348.2019.1604226
2. The American Association of Sleep Medicine: The AASM International Classification of Sleep Disorders – Third Edition, Text Revision (ICSD-3-TR). AASM Darien, IL. 2023.
Treatment of Central Sleep Apnea
Treatment of underlying disorders
Supportive care
Medications and devices
Primary treatment of symptomatic central sleep apnea is often optimal management of underlying disorders (eg, heart failure) and avoidance or reduction of opioids, alcohol, and other sedatives (1). Secondary treatment of patients with symptomatic CSA can be a trial of supplemental oxygen or respiratory stimulants. Other patients may use positive airway pressure or other devices, depending on the underlying disorder. Patients with minimal symptoms may not require specific therapy.
For patients who have CSA and Cheyne-Stokes breathing despite optimization of cardiac function, supplemental oxygen may decrease apneic and hypopneic episodes. Similarly, continuous positive airway pressure (CPAP) can sometimes be effective in treating heart failure and Cheyne-Stokes breathing by decreasing hypoxemia and reducing preload and afterload.
More advanced PAP ventilation strategies such as adaptive servoventilation (ASV) have also been used. These ventilation algorithms provide respiratory support or breaths during periods of apnea then diminish support when patients breathe on their own. The overall effect is to regularize minute ventilation. However, based on clinical trial results, ASV is contraindicated in patients with a reduced ejection fraction (2, 3).
metabolic acidosis and stimulates respiration, is effective for CSA caused by high altitude and is useful in some patients with heart failure.
Electrical pacing of the diaphragm, typically done by transvenous phrenic nerve stimulation, is an option, such as for children > 2 years with congenital central hypoventilation syndrome, or for adults with symptomatic recurrent CSA. Programmable phrenic nerve or diaphragm stimulation systems can produce a rhythmic breathing pattern that stabilizes tidal volume, airflow, and oxygenation, entrains breathing during sleep, and potentially alters disease progression (4).
Treatment references
1. Dempsey JA: Central sleep apnea: misunderstood and mistreated! F1000Res. 8:F1000 Faculty Rev-981, 2019. doi: 10.12688/f1000research.18358.1
2. Cowie MR, Woehrle H, Wegscheider K, et al: Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N Engl J Med 373(12):1095–1105, 2015. doi:10.1056/NEJMoa1506459
3. Bradley TD, Logan AG, Lorenzi Filho G, et al: Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial. Lancet Respir Med 12(2):153–166, 2024. doi:10.1016/S2213-2600(23)00374-0
4. Schwartz AR, Sgambati FP, James KJ, et al: Novel phrenic nerve stimulator treats Cheyne-Stokes respiration: polysomnographic insights. J Clin Sleep Med 16(5):817–820, 2020. doi: 10.5664/jcsm.8328
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American Thoracic Society: What is Central Sleep Apnea in Adults?: Brief central sleep apnea summary for patients
American Academy of Sleep Medicine: Detailed patient information explaining the importance of healthy sleep and treatment options for sleep disorders
