Central Sleep Apnea: a Brief Review

Abstract

Purpose of Review

The purpose of this review is to discuss the pathogenesis, clinical manifestations, diagnosis, and treatment, including areas of controversy and uncertainty.

Recent Findings

Central apnea may be due to hypoventilation or to hypocapnia following hyperventilation. The occurrence of central apnea initiates a cascade of events that perpetuates breathing instability, recurrent central apnea, and upper airway narrowing. In fact, breathing instability and upper airway narrowing are key elements of central and obstructive apnea. Clinically, central apnea is noted in association with obstructive sleep apnea, heart failure, atrial fibrillation, cerebrovascular accident tetraplegia, and chronic opioid use. Management strategies for central apnea aim to eliminate abnormal respiratory events, stabilize sleep, and alleviate the underlying clinical condition. Positive pressure therapy (PAP) remains a standard therapy for central as well as obstructive apnea. Other treatment options include adaptive servo-ventilation (ASV), supplemental oxygen, phrenic nerve stimulation, and pharmacologic therapy. However, ASV is contraindicated in patients with central sleep apnea who had heart failure with reduced ejection fraction, owing to increased mortality in this population.

Summary

There are several therapeutic options for central apnea. Randomized controlled studies are needed to ascertain the long-term effectiveness of individual, or combination, treatment modalities in different types of central apnea.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.

    Javaheri S, Dempsey JA. Central sleep apnea. Compr Physiol. 2013;3(1):141–63.

    CAS  PubMed  Google Scholar 

  2. 2.

    Chowdhuri S, Badr MS. Central sleep apnoea. Indian J Med Res. 2010;131:150–64.

    PubMed  Google Scholar 

  3. 3.

    Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(3):813–22.

    CAS  PubMed  Google Scholar 

  4. 4.

    Zhou XS, Shahabuddin S, Zahn BR, Babcock MA, Badr MS. Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep. J Appl Physiol (1985). 2000;89(1):192–9.

    CAS  Article  Google Scholar 

  5. 5.

    Badr MS, Kawak A. Post-hyperventilation hypopnea in humans during NREM sleep. Respir Physiol. 1996;103(2):137–45.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Chow CM, Xi L, Smith CA, Saupe KW, Dempsey JA. A volume-dependent apneic threshold during NREM sleep in the dog. J Appl Physiol (1985). 1994;76(6):2315–25.

    CAS  Article  Google Scholar 

  7. 7.

    Badr MS, Skatrud JB, Dempsey JA. Determinants of poststimulus potentiation in humans during NREM sleep. J Appl Physiol (1985). 1992;73(5):1958–71.

    CAS  Article  Google Scholar 

  8. 8.

    Badr MS, Morgan BJ, Finn L, Toiber FS, Crabtree DC, Puleo DS, et al. Ventilatory response to induced auditory arousals during NREM sleep. Sleep. 1997;20(9):707–14.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Cao M, Javaheri S. Effects of chronic opioid use on sleep and wake. Sleep Med Clin. 2018;13(2):271–81.

    PubMed  Article  Google Scholar 

  10. 10.

    McKay LC, Janczewski WA, Feldman JL. Sleep-disordered breathing after targeted ablation of preBotzinger complex neurons. Nat Neurosci. 2005;8(9):1142–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    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(3):644–59.

    CAS  PubMed  Google Scholar 

  12. 12.

    Wellman A, Malhotra A, Fogel RB, Edwards JK, Schory K, White DP. Respiratory system loop gain in normal men and women measured with proportional-assist ventilation. J Appl Physiol (1985). 2003;94(1):205–12.

    Article  Google Scholar 

  13. 13.

    Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med. 1999;341(13):949–54.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Leevers AM, Simon PM, Dempsey JA. Apnea after normocapnic mechanical ventilation during NREM sleep. J Appl Physiol (1985). 1994;77(5):2079–85.

    CAS  Article  Google Scholar 

  15. 15.

    Badr MS, Toiber F, Skatrud JB, Dempsey J. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl Physiol (1985). 1995;78(5):1806–15.

    CAS  Article  Google Scholar 

  16. 16.

    Olson LG, Strohl KP. Airway secretions influence upper airway patency in the rabbit. Am Rev Respir Dis. 1988;137(6):1379–81.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Morrell MJ, Arabi Y, Zahn BR, Meyer KC, Skatrud JB, Badr MS. Effect of surfactant on pharyngeal mechanics in sleeping humans: implications for sleep apnoea. Eur Respir J. 2002;20(2):451–7.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    American Academy of Sleep Medicine Task F. International Classification of Sleep Disorders. 3rd ed. Darien; 2014.

  19. 19.

    Dempsey JA, Smith CA, Przybylowski T, Chenuel B, Xie A, Nakayama H, et al. The ventilatory responsiveness to CO(2) below eupnoea as a determinant of ventilatory stability in sleep. J Physiol. 2004;560(Pt 1):1–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Wang D, Teichtahl H, Drummer O, Goodman C, Cherry G, Cunnington D, et al. Central sleep apnea in stable methadone maintenance treatment patients. Chest. 2005;128(3):1348–56.

    PubMed  Article  Google Scholar 

  21. 21.

    Douglas NJ, White DP, Weil JV, Pickett CK, Zwillich CW. Hypercapnic ventilatory response in sleeping adults. Am Rev Respir Dis. 1982;126(5):758–62.

    CAS  PubMed  Google Scholar 

  22. 22.

    Orem J. Medullary respiratory neuron activity: relationship to tonic and phasic REM sleep. J Appl Physiol Respir Environ Exerc Physiol. 1980;48(1):54–65.

    CAS  PubMed  Google Scholar 

  23. 23.

    Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep. 1991;14(6):486–95.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Phillips BA, Berry DT, Schmitt FA, Magan LK, Gerhardstein DC, Cook YR. Sleep-disordered breathing in the healthy elderly. Clinically significant? Chest. 1992;101(2):345–9.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age on sleep apnea in men: I. Prevalence and severity. Am J Respir Crit Care Med. 1998;157(1):144–8.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Pack AI, Cola MF, Goldszmidt A, Ogilvie MD, Gottschalk A. Correlation between oscillations in ventilation and frequency content of the electroencephalogram. J Appl Physiol (1985). 1992;72(3):985–92.

    CAS  Article  Google Scholar 

  27. 27.

    Chowdhuri S, Pranathiageswaran S, Loomis-King H, Salloum A, Badr MS, et al. J Appl Physiol (1985). 2018;124(1):83–90.

    CAS  Article  Google Scholar 

  28. 28.

    Kapur VK, Koepsell TD, de Maine J, Hert R, Sandblom RE, Psaty BM. Association of hypothyroidism and obstructive sleep apnea. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1379–83.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Leung RS, Huber MA, Rogge T, Maimon N, Chiu KL, Bradley TD. Association between atrial fibrillation and central sleep apnea. Sleep. 2005;28(12):1543–6.

    PubMed  Article  Google Scholar 

  30. 30.

    Issa FG, Sullivan CE. Reversal of central sleep apnea using nasal CPAP. Chest. 1986;90(2):165–71.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med. 2001;163(3 Pt 1):608–13.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Javaheri S, Parker TJ, Wexler L, Michaels SE, Stanberry E, Nishyama H, et al. Occult sleep-disordered breathing in stable congestive heart failure. Ann Intern Med. 1995;122(7):487–92.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med. 1999;160(4):1101–6.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Cereda CW, Petrini L, Azzola A, Ciccone A, Fischer U, Gallino A, et al. Sleep-disordered breathing in acute ischemic stroke and transient ischemic attack: effects on short- and long-term outcome and efficacy of treatment with continuous positive airways pressure--rationale and design of the SAS CARE study. Int J Stroke. 2012;7(7):597–603.

    PubMed  Article  Google Scholar 

  35. 35.

    Parra O, Arboix A, Bechich S, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med. 2000;161(2 Pt 1):375–80.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344(2):102–7.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Grunstein RR, Ho KY, Sullivan CE. Sleep apnea in acromegaly. Ann Intern Med. 1991;115(7):527–32.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Hernandez-Gordillo D, Ortega-Gomez Mdel R, Galicia-Polo L, et al. Sleep apnea in patients with acromegaly. Frequency, characterization and positive pressure titration. Open Respir Med J. 2012;6:28–33.

    PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    • Sankari A, Bascom AT, Chowdhuri S, Badr MS. Tetraplegia is a risk factor for central sleep apnea. J Appl Physiol (1985). 2014;116(3):345–53 This study identified tetraplegia as a distinct risk factor for central apnea, independent of opioid use.

    Article  Google Scholar 

  40. 40.

    Sankari A, Bascom A, Oomman S, Badr MS. Sleep disordered breathing in chronic spinal cord injury. J Clin Sleep Med. 2014;10(1):65–72.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Xie A, Wong B, Phillipson EA, Slutsky AS, Bradley TD. Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea. Am J Respir Crit Care Med. 1994;150(2):489–95.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Rupprecht S, Hoyer D, Hagemann G, Witte OW, Schwab M. Central sleep apnea indicates autonomic dysfunction in asymptomatic carotid stenosis: a potential marker of cerebrovascular and cardiovascular risk. Sleep. 2010;33(3):327–33.

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Javaheri S, Parker TJ, Liming JD, Corbett WS, Nishiyama H, Wexler L, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation. 1998;97(21):2154–9.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Javaheri S, Smith J, Chung E. The prevalence and natural history of complex sleep apnea. J Clin Sleep Med. 2009;5(3):205–11.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Farre R, Montserrat JM, Navajas D. Noninvasive monitoring of respiratory mechanics during sleep. Eur Respir J. 2004;24(6):1052–60.

  46. 46.

    Morrell MJ, Badr MS, Harms CA, Dempsey JA. The assessment of upper airway patency during apnea using cardiogenic oscillations in the airflow signal. Sleep. 1995;18(8):651–8.

  47. 47.

    • Aurora RN, Chowdhuri S, Ramar K, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012;35(1):17–40 Practice parameters by the American Academy of Sleep Medicine (AASM) providing evidence-based recommendations for the treatment of central apnea.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Arzt M, Floras JS, Logan AG, Kimoff RJ, Series F, Morrison D, et al. Suppression of central sleep apnea by continuous positive airway pressure and transplant-free survival in heart failure: a post hoc analysis of the Canadian continuous positive airway pressure for patients with central sleep apnea and heart failure trial (CANPAP). Circulation. 2007;115(25):3173–80.

    PubMed  Article  Google Scholar 

  49. 49.

    Hannan LM, Dominelli GS, Chen YW, Darlene Reid W, Road J. Systematic review of non-invasive positive pressure ventilation for chronic respiratory failure. Respir Med. 2014;108(2):229–43.

    PubMed  Article  Google Scholar 

  50. 50.

    Javaheri S, Brown LK, Randerath WJ. Positive airway pressure therapy with adaptive servoventilation: part 1: operational algorithms. Chest. 2014;146(2):514–23.

    PubMed  Article  Google Scholar 

  51. 51.

    Teschler H, Dohring J, Wang YM, Berthon-Jones M. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure. Am J Respir Crit Care Med. 2001;164(4):614–9.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    • Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N Engl J Med. 2015;373(12):1095–105 This study demonstrated the failure of adaptive servo-ventilation (ASV) as a treatment for central apnea in patients with heart failure and reduced ejection fraction. Instead, this therapy was associated with increased all-cause and cardiovascular mortality. Therefore, ASV is contraindicated in this setting.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    • Aurora RN, Bista SR, Casey KR, et al. Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline: "The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses". J Clin Sleep Med. 2016;12(5):757–61 Updated practice parameters by the American Academy of Sleep Medicine (AASM). Recent findings mandated a change in the recommendations indicating a standard-level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an option-level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS.

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Javaheri S, Brown LK, Randerath W, Khayat R. SERVE-HF: more questions than answers. Chest. 2016;149(4):900–4.

    PubMed  Article  Google Scholar 

  55. 55.

    De Backer WA, Verbraecken J, Willemen M, Wittesaele W, De Cock W, Van de Heyning P. Central apnea index decreases after prolonged treatment with acetazolamide. Am J Respir Crit Care Med. 1995;151:87–91.

  56. 56.

    Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006;173:234–7.

  57. 57.

    Javaheri S, Parker TJ, Wexler L, Liming JD, Lindower P, Roselle GA. Effect of theophylline on sleep-disordered breathing in heart failure. N Engl J Med 1996;335:562–7.

  58. 58.

    Javaheri S, Ahmed M, Parker TJ, Brown CR. Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure. Sleep. 1999;22(8):1101–6.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Becker HF, Polo O, McNamara SG, Berthon-Jones M, Sullivan CE. Effect of different levels of hyperoxia on breathing in healthy subjects. J Appl Physiol (1985). 1996;81(4):1683–90.

    CAS  Article  Google Scholar 

  60. 60.

    • Costanzo MR, Ponikowski P, Javaheri S, et al. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet. 2016;388(10048):974–82 This is a randomized clinical trial demonstrating the effectiveness of transvenous neurostimulation in reducing the severity of central sleep apnea, including improvements in sleep metrics, oxygenation, and quality of life.

    PubMed  Article  Google Scholar 

  61. 61.

    Javaheri S, Brown LK, Randerath WJ. Clinical applications of adaptive servoventilation devices: part 2. Chest. 2014;146(3):858–68.

    PubMed  Article  Google Scholar 

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Correspondence to M. Safwan Badr.

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Shahrokh Javaheri reports fees from Respicardia as a consultant.

M. Safwan Badr declares no conflict of interest.

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Badr, M.S., Javaheri, S. Central Sleep Apnea: a Brief Review. Curr Pulmonol Rep 8, 14–21 (2019). https://doi.org/10.1007/s13665-019-0221-z

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Keywords

  • Central apnea
  • Sleep
  • Opioid
  • Heart failure
  • Positive pressure therapy
  • CPAP
  • BPAP
  • Adaptive servo-ventilation