Central sleep apnea: Pathogenesis
- M Safwan Badr, MD
M Safwan Badr, MD
- Section Editor — Sleep Related Breathing Disorders
- Professor and Chief, Pulmonary Critical Care and Sleep Medicine
- Wayne State University School of Medicine
Central apneas are periods of absent airflow due to lack of respiratory effort. They occur when inhibitory input to the respiratory center of the brain exceeds excitatory input, which may occur during sleep because sleep abolishes wakefulness-related excitatory input. Recurrent central apneas are the hallmark feature of central sleep apnea (CSA).
In this topic review, the pathogenesis of central sleep apnea is discussed. The definition of a central apnea is provided separately. The etiologies, clinical presentation, diagnosis, treatment, and outcome of CSA are also discussed separately. (See "Polysomnography in the evaluation of sleep-disordered breathing in adults" and "Central sleep apnea: Risk factors, clinical presentation, and diagnosis" and "Central sleep apnea: Treatment".)
CENTRAL APNEA DUE TO HYPERVENTILATION
Respiration during non-rapid eye movement (NREM) sleep is critically dependent on chemical influences, especially arterial carbon dioxide tension (PaCO2). Central apnea results if arterial PaCO2 is lowered below a highly sensitive "apneic threshold" (waveform 1) .
Central apnea is best conceptualized as the outcome to a sequence of events:
●First, any of a variety of stimuli induce hyperpnea. As an example, hypoxia (eg, due to secretions or decreased lung volumes) is a common trigger of hyperpnea during sleep [2-5].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Bradley TD, Phillipson EA. Central sleep apnea. Clin Chest Med 1992; 13:493.
- Trinder J, Whitworth F, Kay A, Wilkin P. Respiratory instability during sleep onset. J Appl Physiol (1985) 1992; 73:2462.
- Badr MS, Skatrud JB, Dempsey JA. Determinants of poststimulus potentiation in humans during NREM sleep. J Appl Physiol (1985) 1992; 73:1958.
- Badr MS, Morgan BJ, Finn L, et al. Ventilatory response to induced auditory arousals during NREM sleep. Sleep 1997; 20:707.
- Berssenbrugge A, Dempsey J, Iber C, et al. Mechanisms of hypoxia-induced periodic breathing during sleep in humans. J Physiol 1983; 343:507.
- Leevers AM, Simon PM, Dempsey JA. Apnea after normocapnic mechanical ventilation during NREM sleep. J Appl Physiol (1985) 1994; 77:2079.
- Khoo MC, Kronauer RE, Strohl KP, Slutsky AS. Factors inducing periodic breathing in humans: a general model. J Appl Physiol Respir Environ Exerc Physiol 1982; 53:644.
- Khoo MC. Determinants of ventilatory instability and variability. Respir Physiol 2000; 122:167.
- Chapman KR, Bruce EN, Gothe B, Cherniack NS. Possible mechanisms of periodic breathing during sleep. J Appl Physiol (1985) 1988; 64:1000.
- Cherniack NS, Longobardo GS. Mathematical models of periodic breathing and their usefulness in understanding cardiovascular and respiratory disorders. Exp Physiol 2006; 91:295.
- Tawadrous FD, Eldridge FL. Posthyperventilation breathing patterns after active hyperventilation in man. J Appl Physiol 1974; 37:353.
- Eldridge FL, Gill-Kumar P. Central neural respiratory drive and afterdischarge. Respir Physiol 1980; 40:49.
- Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol Respir Environ Exerc Physiol 1983; 55:813.
- Zhou XS, Shahabuddin S, Zahn BR, et al. Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep. J Appl Physiol (1985) 2000; 89:192.
- Badr MS, Kawak A. Post-hyperventilation hypopnea in humans during NREM sleep. Respir Physiol 1996; 103:137.
- Chow CM, Xi L, Smith CA, et al. A volume-dependent apneic threshold during NREM sleep in the dog. J Appl Physiol (1985) 1994; 76:2315.
- Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol (1985) 1995; 78:1806.
- Olson LG, Strohl KP. Airway secretions influence upper airway patency in the rabbit. Am Rev Respir Dis 1988; 137:1379.
- Harms CA, Zeng YJ, Smith CA, et al. Negative pressure-induced deformation of the upper airway causes central apnea in awake and sleeping dogs. J Appl Physiol (1985) 1996; 80:1528.
- Sahlin C, Svanborg E, Stenlund H, Franklin KA. Cheyne-Stokes respiration and supine dependency. Eur Respir J 2005; 25:829.
- Oksenberg A, Arons E, Snir D, et al. Cheyne-Stokes respiration during sleep: a possible effect of body position. Med Sci Monit 2002; 8:CS61.
- Szollosi I, Roebuck T, Thompson B, Naughton MT. Lateral sleeping position reduces severity of central sleep apnea / Cheyne-Stokes respiration. Sleep 2006; 29:1045.
- Issa FG, Sullivan CE. Reversal of central sleep apnea using nasal CPAP. Chest 1986; 90:165.
- Mezon BL, West P, Israels J, Kryger M. Sleep breathing abnormalities in kyphoscoliosis. Am Rev Respir Dis 1980; 122:617.
- Barlow PB, Bartlett D Jr, Hauri P, et al. Idiopathic hypoventilation syndrome: importance of preventing nocturnal hypoxemia and hypercapnia. Am Rev Respir Dis 1980; 121:141.
- Gothi D, Joshi JM. Late onset hypoventilation syndrome: is there a spectrum of idiopathic hypoventilation syndromes? Indian J Chest Dis Allied Sci 2005; 47:293.
- Grant JL, Arnold W Jr. Idiopathic hypoventilation. JAMA 1965; 194:119.
- Wolkove N, Altose MD, Kelsen SG, Cherniack NS. Respiratory control abnormalities in alveolar hypoventilation. Am Rev Respir Dis 1980; 122:163.
- Pack AI, Cola MF, Goldszmidt A, et al. Correlation between oscillations in ventilation and frequency content of the electroencephalogram. J Appl Physiol (1985) 1992; 72:985.
- Dunai J, Wilkinson M, Trinder J. Interaction of chemical and state effects on ventilation during sleep onset. J Appl Physiol (1985) 1996; 81:2235.
- Dunai J, Kleiman J, Trinder J. Ventilatory instability during sleep onset in individuals with high peripheral chemosensitivity. J Appl Physiol (1985) 1999; 87:661.
- Orem J. Neuronal mechanisms of respiration in REM sleep. Sleep 1980; 3:251.
- Orem J, Lovering AT, Dunin-Barkowski W, Vidruk EH. Tonic activity in the respiratory system in wakefulness, NREM and REM sleep. Sleep 2002; 25:488.