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Epidemiology and pathogenesis of obesity hypoventilation syndrome

Amanda Piper, PhD
Brendon Yee, MBChB, PhD
Section Editor
M Safwan Badr, MD
Deputy Editor
Geraldine Finlay, MD


Obesity Hypoventilation Syndrome (OHS; "Pickwickian syndrome") is defined as the presence of awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg) in an obese individual (body mass index ≥30 kg/m2) which cannot be attributed to other conditions associated with alveolar hypoventilation (eg, neuromuscular disorders) [1-3].

The pathogenesis of OHS is reviewed here. Clinical manifestations, diagnosis, and treatment are discussed separately. (See "Clinical manifestations and diagnosis of obesity hypoventilation syndrome" and "Treatment and prognosis of the obesity hypoventilation syndrome" and "Noninvasive positive airway pressure therapy of the obesity hypoventilation syndrome".)


Prevalence estimates for OHS are inaccurate and vary significantly due to differences in disease definition, population studied, and methods of sample acquisition.

General population – Estimates based on rates of obesity and obstructive sleep apnea (OSA) in the community suggest 0.15 to 0.3 percent of the adult population in the United States are likely to have OHS [1].

Obese population – The prevalence of OHS increases as body mass index (BMI) rises [4,5]. In several retrospective studies among patients with OSA, the prevalence of OHS in those with a BMI of 30 to 35 kg/m2 is 8 to 12 percent, higher among those with a BMI ≥40 kg/m2 (18 to 31 percent) and those with a BMI ≥50 kg/m2 (50 percent) [1,5-9].

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Literature review current through: Sep 2017. | This topic last updated: Jul 06, 2017.
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  1. Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care 2010; 55:1347.
  2. Randerath W, Verbraecken J, Andreas S, et al. Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. Eur Respir J 2017; 49.
  3. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22:667.
  4. Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med 2004; 116:1.
  5. Macavei VM, Spurling KJ, Loft J, Makker HK. Diagnostic predictors of obesity-hypoventilation syndrome in patients suspected of having sleep disordered breathing. J Clin Sleep Med 2013; 9:879.
  6. Mokhlesi B, Tulaimat A, Faibussowitsch I, et al. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath 2007; 11:117.
  7. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest 2001; 120:369.
  8. Banerjee D, Yee BJ, Piper AJ, et al. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131:1678.
  9. Laaban JP, Chailleux E. Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy. Chest 2005; 127:710.
  10. Chau EH, Lam D, Wong J, et al. Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology 2012; 117:188.
  11. Sugerman HJ, Fairman RP, Baron PL, Kwentus JA. Gastric surgery for respiratory insufficiency of obesity. Chest 1986; 90:81.
  12. Domínguez-Cherit G, Gonzalez R, Borunda D, et al. Anesthesia for morbidly obese patients. World J Surg 1998; 22:969.
  13. Lecube A, Sampol G, Lloberes P, et al. Asymptomatic sleep-disordered breathing in premenopausal women awaiting bariatric surgery. Obes Surg 2010; 20:454.
  14. Marik PE, Desai H. Characteristics of patients with the "malignant obesity hypoventilation syndrome" admitted to an ICU. J Intensive Care Med 2013; 28:124.
  15. Povitz M, James MT, Pendharkar SR, et al. Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study. Ann Am Thorac Soc 2015; 12:921.
  16. Harada Y, Chihara Y, Azuma M, et al. Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels. Respirology 2014; 19:1233.
  17. Kawata N, Tatsumi K, Terada J, et al. Daytime hypercapnia in obstructive sleep apnea syndrome. Chest 2007; 132:1832.
  18. Akashiba T, Kawahara S, Kosaka N, et al. Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome. Chest 2002; 121:415.
  19. Akashiba T, Akahoshi T, Kawahara S, et al. Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study. Intern Med 2006; 45:1121.
  20. Kaw R, Hernandez AV, Walker E, et al. Determinants of hypercapnia in obese patients with obstructive sleep apnea: a systematic review and metaanalysis of cohort studies. Chest 2009; 136:787.
  21. Piper AJ. Obesity hypoventilation syndrome--the big and the breathless. Sleep Med Rev 2011; 15:79.
  22. Manuel AR, Hart N, Stradling JR. Is a raised bicarbonate, without hypercapnia, part of the physiologic spectrum of obesity-related hypoventilation? Chest 2015; 147:362.
  23. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948.
  24. Berger KI, Ayappa I, Chatr-Amontri B, et al. Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest 2001; 120:1231.
  25. Pérez de Llano LA, Golpe R, Ortiz Piquer M, et al. Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest 2005; 128:587.
  26. Rapoport DM, Garay SM, Epstein H, Goldring RM. Hypercapnia in the obstructive sleep apnea syndrome. A reevaluation of the "Pickwickian syndrome". Chest 1986; 89:627.
  27. Piper AJ, Wang D, Yee BJ, et al. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63:395.
  28. Ojeda Castillejo E, de Lucas Ramos P, Resano Barrios P, et al. Mortality in obesity-hypoventilation syndrome and prognostic risk factors. Arch Bronconeumol 2015; 51:304.
  29. Berger KI, Ayappa I, Sorkin IB, et al. Postevent ventilation as a function of CO(2) load during respiratory events in obstructive sleep apnea. J Appl Physiol (1985) 2002; 93:917.
  30. Ayappa I, Berger KI, Norman RG, et al. Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2002; 166:1112.
  31. Norman RG, Goldring RM, Clain JM, et al. Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model. J Appl Physiol (1985) 2006; 100:1733.
  32. Berger KI, Goldring RM, Rapoport DM. Obesity hypoventilation syndrome. Semin Respir Crit Care Med 2009; 30:253.
  33. Goldring RM, Turino GM, Heinemann HO. Respiratory-renal adjustments in chronic hypercapnia in man. Extracellular bicarbonate concentration and the regulation of ventilation. Am J Med 1971; 51:772.
  34. Berger KI, Ayappa I, Sorkin IB, et al. CO(2) homeostasis during periodic breathing in obstructive sleep apnea. J Appl Physiol (1985) 2000; 88:257.
  35. Hlavac MC, Catcheside PG, McDonald R, et al. Hypoxia impairs the arousal response to external resistive loading and airway occlusion during sleep. Sleep 2006; 29:624.
  36. Resta O, Foschino-Barbaro MP, Bonfitto P, et al. Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea. Respir Med 2000; 94:240.
  37. Javaheri S, Colangelo G, Lacey W, Gartside PS. Chronic hypercapnia in obstructive sleep apnea-hypopnea syndrome. Sleep 1994; 17:416.
  38. Lin CK, Lin CC. Work of breathing and respiratory drive in obesity. Respirology 2012; 17:402.
  39. Pankow W, Hijjeh N, Schüttler F, et al. Influence of noninvasive positive pressure ventilation on inspiratory muscle activity in obese subjects. Eur Respir J 1997; 10:2847.
  40. Rochester DF, Arora NS. Respiratory failure from obesity. In: Medical Complications of obesity, Mancini M, Lewis B, Contaldo F (Eds), Academic Press, London 1980. p.183.
  41. Lee MY, Lin CC, Shen SY, et al. Work of breathing in eucapnic and hypercapnic sleep apnea syndrome. Respiration 2009; 77:146.
  42. Sharp JT, Druz WS, Kondragunta VR. Diaphragmatic responses to body position changes in obese patients with obstructive sleep apnea. Am Rev Respir Dis 1986; 133:32.
  43. Monneret D, Borel JC, Pepin JL, et al. Pleiotropic role of IGF-I in obesity hypoventilation syndrome. Growth Horm IGF Res 2010; 20:127.
  44. Steier J, Jolley CJ, Seymour J, Roughton M, Polkey MI, Moxham J. Neural respiratory drive in obesity. Thorax. 2009 Aug;64(8):719-25.
  45. Lopata M, Onal E. Mass loading, sleep apnea, and the pathogenesis of obesity hypoventilation. Am Rev Respir Dis 1982; 126:640.
  46. Budweiser S, Jörres RA, Criée CP, et al. Prognostic value of mouth occlusion pressure in patients with chronic ventilatory failure. Respir Med 2007; 101:2343.
  47. Manuel AR, Hart N, Stradling JR. Correlates of obesity-related chronic ventilatory failure. BMJ Open Respir Res 2016; 3:e000110.
  48. Chouri-Pontarollo N, Borel JC, Tamisier R, et al. Impaired objective daytime vigilance in obesity-hypoventilation syndrome: impact of noninvasive ventilation. Chest 2007; 131:148.
  49. Zwillich CW, Sutton FD, Pierson DJ, et al. Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome. Am J Med 1975; 59:343.
  50. Jokic R, Zintel T, Sridhar G, et al. Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome. Thorax. 2000 Nov;55(11):940-5.
  51. Han F, Chen E, Wei H, et al. Treatment effects on carbon dioxide retention in patients with obstructive sleep apnea-hypopnea syndrome. Chest. 2001 June 1, 2001;119(6):1814-9.
  52. Kalra SP. Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions. Peptides 2008; 29:127.
  53. Tankersley CG, O'Donnell C, Daood MJ, et al. Leptin attenuates respiratory complications associated with the obese phenotype. J Appl Physiol (1985) 1998; 85:2261.
  54. O'Donnell CP, Schaub CD, Haines AS, et al. Leptin prevents respiratory depression in obesity. Am J Respir Crit Care Med. 1999 May;159:1477-84.
  55. Phipps PR, Starritt E, Caterson I, Grunstein RR. Association of serum leptin with hypoventilation in human obesity. Thorax 2002; 57:75.
  56. Campo A, Frühbeck G, Zulueta JJ, et al. Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients. Eur Respir J 2007; 30:223.
  57. Yee BJ, Cheung J, Phipps P, et al. Treatment of obesity hypoventilation syndrome and serum leptin. Respiration 2006; 73:209.
  58. Borel JC, Tamisier R, Gonzalez-Bermejo J, et al. Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized controlled trial. Chest 2012; 141:692.
  59. Redolfi S, Corda L, La Piana G, et al. Long-term non-invasive ventilation increases chemosensitivity and leptin in obesity-hypoventilation syndrome. Respir Med 2007; 101:1191.
  60. Javaheri S, Simbartl LA. Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it? Ann Am Thorac Soc 2014; 11:945.
  61. Rochester DF, Enson Y. Current concepts in the pathogenesis of the obesity-hypoventilation syndrome. Mechanical and circulatory factors. Am J Med 1974; 57:402.