In 1955, J. Howland Achincloss1 and colleagues first described in a patient the features of what is now known as obesity-related hypoventilation syndrome. Their patient was severely obese and had chronic daytime hypercapnia and hypoxemia, polycythemia, excessive sleepiness, and right-sided heart failure. The presence of hypercapnia and hypoxemia—evidence of hypoventilation—was perplexing since the patient had no lung disease or other factors that could explain it. Many obese people similarly have persistent hypoventilation that appears not to be secondary to other factors other than obesity, hence obesity-related hypoventilation (OHS). Why OHS occurs is unclear. Some theories look at the role of restricted lung mechanics due to excessive fatty tissue surrounding the lungs or an impaired central nervous system response to hypercapnia. In recent years, scientists have investigated the role that sleep-disordered breathing may play in the pathogenesis of OHS.

Obesity affects nearly 34% of Americans and morbid obesity affects nearly 6% of Americans.2 About 31% of people with a BMI of 35 kg/m2 or greater have OHS.3 The characteristic findings of a person with OHS are 1) a BMI of 30 kg/m2 or greater and 2) an increase in the arterial partial pressure of carbon dioxide (Paco2) that is greater than 45 mm Hg during wake and that is not secondary to a lung disease or other known causes of hypoventilation.4 Many people with OHS also have polycythemia. The pathophysiology of these symptoms may be as follows.

Chronic hypercapnia and hypoxemia may result from the impact of excess fatty tissue on lung mechanics5,6 or may result from an inherent or acquired blunted response to carbon dioxide.3,7 Excessive fat tissue around the ribs, diaphragm, and abdomen reduces chest wall compliance and the respiratory muscles become fatigued more easily. As a result, the person takes short, fast breaths that bring insufficient amounts of air to the alveoli where gas exchange occurs in the lungs. Elevated levels of CO2 consequently remain in the blood since it is not effectively cleared out of the lungs. Genetic factors (or other inherent factors) and respiratory diseases that can impair ventilation may allow blood levels of CO2 to increase. As the blood levels of CO2 increase, the blood becomes more acidic, which triggers the release of bicarbonate into the blood. If the CO2 level remains chronically high, the bicarbonate level also remains elevated and causes the brain’s respiratory center to become less sensitive to an excessive carbon dioxide level. Because of this insensitivity, a greater-than-normal level of hypercapnia and hypoxemia is needed to trigger the ventilatory response. This therefore results in chronic hypoventilation.

Polycythemia may result from chronic hypoxia. Chronically low levels of oxygen trigger the increased release of erythropoietin, a hormone that stimulates the production of red blood cells. This then results in the presence of excess red blood cells.

Pulmonary hypertension and right-sided heart failure may both result from chronic hypoxia. Hypoxia induces vasoconstriction, which increases the pressure in the pulmonary arteries. The pulmonary arteries carry unoxygenated blood from the right ventricle to the lungs for oxygenation. However, when these arteries are constricted, the right ventricle has to work harder to push the blood toward the lungs. If pulmonary hypertension continues for an extended period of time, the muscle tissue of the right ventricle becomes thick and stiff. This ultimately impairs the ability of the right side of the heart to pump blood effectively.3 Pulmonary hypertension and right-sided heart failure can be fatal if left untreated.


Scientists estimate that 90% of people with OHS who have sleep-disordered breathing have obstructive sleep apnea3; the remaining 10% of people with OHS do not meet the criteria for sleep-disordered breathing, but nevertheless have a CO2 level that is more elevated (by at least 10 mm Hg) than the daytime level.

The prevalence of OSA in people with OHS increases with increasing BMI. An estimated 8% to 10% of OHS patients with a BMI of 30–34 kg/m2 have OSA, and 18% to 25% of OHS patients with a BMI greater than 40 kg/m2 have OSA.4

In OSA, the upper airway muscles relax excessively during sleep allowing the tonsils, adenoids, and other structures supported by the muscles to be drawn into the upper airway with inspirations. As a result, the airflow through the upper airway becomes partially or totally blocked, causing the oxygen saturation (Sao2) in the blood to fall. Once the Sao2 falls to a certain point, the neurons of the respiratory center in the brain become stimulated and trigger an arousal. The upper airway muscle tone is restored with the arousal, which opens up the airway, thereby restoring airflow and allowing a person to quickly take some deep breaths. This restores the Sao2 level to normal and the person resumes sleep. However, once asleep, this process can recur. A person who has five or more obstructive apnea episodes per hour during sleep is considered to have OSA. In addition to arousals during sleep, other consequences of OSA are intermittent episodes of hypoxia and hypercapnia, and excessive daytime sleepiness (resulting from insufficient sleep due to apnea-induced arousals). These factors may play the following roles in the development of OHS.

Some research indicates that sleep deprivation can reduce one’s ventilatory response to hypercapnia. For example, researchers Cooper and Phillips found that healthy subjects had a 20% decrease in the hypercapnic ventilatory response when subjected to hypercapnia after a period of sleep deprivation.8 People with OSA tend to be chronically sleep-deprived because of the apnea-induced arousals that occur during sleep. This may set the stage for a blunted hypercapnic response and result in the increased blood levels of CO2 in people with OHS.

The repetitive nature of the apneic events may result in chronic hypercapnia. Each time a person arouses from an apneic event, the amount of air exhaled per minute increases momentarily. This would normally quickly decrease the CO2 level in the blood. However, elevated levels of CO2 can remain in the blood if the amount of increased ventilation after an OSA event is insufficient to restore the CO2 level to normal. The excess CO2 results in the release of bicarbonate into the blood. Since bicarbonate is removed more slowly from the blood, compared with CO2, the bicarbonate level may remain somewhat elevated before the person has the next apneic event. A chronically elevated bicarbonate then blunts the ventilatory response to CO2 so that the threshold for triggering the ventilatory response becomes increasingly higher. This ultimately results in the blood CO2 level remaining chronically high.

There are currently no drugs that effectively treat OHS.4 However, the following treatments have been beneficial for people with OHS.


Bariatric surgery is often a last resort in helping a person losing weight. The weight loss may effectively reduce episodes of OSA and improve ventilation (thereby improving OHS symptoms) once a person’s weight decreases sufficiently.


In people with OSA and OHS, positive airway pressure (PAP) treatment can allow uninterrupted respiration and ventilation during sleep, thereby preventing the impact that apnea-induced arousals and intermittent hypoxia and hypercapnia may be playing in OHS.


About one-half of people with OHS need supplemental oxygen while being treated with PAP therapy.3 (Supplemental oxygen alone is inadequate to improve hypoventilation.) The added oxygen, combined with positive pressure from PAP therapy, may enhance gas exchange in the alveoli, thereby improving ventilation. The need for nocturnal and daytime supplemental oxygen often decreases significantly as a person adheres to PAP therapy.


The creation of a surgical opening in the trachea is a treatment of last resort for people with OSA. A tracheostomy is performed at the area of the sternal notch. Since this area lies below the upper airway, a tracheostomy bypasses upper airway restriction, thereby maintaining airflow and effectively resolving OSA. This treatment may improve OHS by allowing uninterrupted respiration and ventilation.

The prevalence of OHS may actually be higher than the estimated 31%. Hypoventilation is determined through blood work, which is not routinely performed in an office setting. Most people diagnosed with OHS typically receive a diagnosis after a hospital stay or as a result of a physician’s trying to rule out other known factors for hypercapnia. For this reason, an obese person may have undiagnosed OHS for many years. OHS, if left untreated or improperly treated, can lead to pulmonary hypertension or right-sided heart failure, both of which are potentially fatal diseases. Therefore, it is important to diagnose and treat OHS, particularly if it is associated with sleep-disordered breathing.

Regina Patrick, RPSGT, is a contributing writer for Sleep Review. She can be reached at [email protected]


  1. Auchincloss JH, Cook E, Renzerri AD. Clinical and physiological aspects of a case of obesity, polycythemia and alveolar hypoventilation. J Clin Invest. 1955;34:1537–1545.
  2. National Institutes of Health (NIH). National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Weight-control Information Network (WIN). Statistics Related to Overweight and Obesity. Publication Number 04–4158. Bethesda, Md: WIN; 2010. Accessed May 18, 2010.
  3. Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. 2007;132:1322–1336.
  4. Powers MA. The obesity hypoventilation syndrome. Respir Care. 2008;53:1723–1730.
  5. Jubber AS. Respiratory complications of obesity. Int J Clin Pract. 2004;58:573–580.
  6. Poulain M, Doucet M, Major GC, et al. The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. Can Med Assoc J. 2006;174:1293–1299.
  7. Fayyaz J , Lessnau KD. Hypoventilation Syndromes. eMedicine Specialties. Accessed May 18, 2010.
  8. Cooper KR, Phillips BA. Effect of short-term sleep loss on breathing. J Appl Physiol. 1982;53:855–858.