What every physician needs to know:

Obesity hypoventilation syndrome (OHS) is an acquired disorder characterized by the development of awake hypoventilation (paCO2>45mmHg) in individuals with a BMI above 30 kg/m2. Although obesity is a major criterion defining this syndrome, only some obese patients develop it. Before making the diagnosis, it is essential to rule out other possible disorders that might lead to hypoventilation, such as severe obstructive or restrictive lung diseases and neuromuscular diseases, among others.


Although OHS can vary in severity, no current classification exists. One way to classify OHS patients, albeit roughly, is by the presence or absence of co-existing sleep-disordered breathing. About 90 percent of patients with OHS have concurrent obstructive sleep apnea, while about 10 percent of OHS patients have no evidence of obstructive sleep apnea on polysomnogram.

Are you sure your patient has obesity-hypoventilation syndrome? What should you expect to find?

OHS is defined as the presence of awake hypercapnia (PaCO2>45mmHg) in an obese individual (BMI>30kg/m2) in the absence of concomitant pulmonary or neuromuscular disease that could otherwise explain the hypercapnia.

The clinical presentation of OHS is not specific to the disease and is frequently similar to that of patients with sleep-disordered breathing, namely, loud snoring, nocturnal choking, witnessed apneas, excessive daytime sleepiness, and morning headaches. However, because patients with OHS have lower daytime oxygen levels, they are more likely to report moderate to severe dyspnea. They are also more likely to present with peripheral edema, signs of cor pulmonale, or pulmonary hypertension.

Arterial blood gases, which are required for the diagnosis of OHS, are not routinely performed in a clinic or sleep laboratory setting. Therefore, cases of OHS can easily be missed unless one maintains a high index of suspicion. Other, more common clinical clues that can lead to a suspicion for OHS in an obese individual include an elevated serum bicarbonate level (>27mEq/L) and a resting awake oxygen saturation below 94 percent (suggesting a PaO2 below 70mmHg). If either of these clues is present, the diagnosis should be confirmed by obtaining arterial blood gases.

Beware: there are other diseases that can mimic obesity-hypoventilation syndrome:

Hypercapnia can be due to several disorders., so it is therefore necessary to look for and rule out any other possible causes for hypercapnia in obese patients before making a diagnosis of OHS. These other causes include severe obstructive or restrictive lung diseases, neuromuscular diseases, chest wall deformities like significant kyphoscoliosis, and severe hypothyroidism.

How and/or why did the patient develop obesity-hypoventilation syndrome?

The clinical features of patients with OHS published in the literature include the following:

  • Male to female ratio 3:2

  • Mean age: 52 years (range 42-61)

  • Mean BMI: 44 kg/m2(range 35-56)

  • Mean PaCO2: 56mmHg (range 47-61)

The pathophysiology that leads to the development of hypoventilation in the morbidly obese is complex, but several factors are thought to contribute to the pathogenesis, including abnormal respiratory mechanics that are due to obesity, impaired ventilatory drive, and upper airway obstruction secondary to sleep-disordered breathing.

Abnormal respiratory mechanics that are due to obesity

The excessive mechanical load on the respiratory system that is present in obesity significantly alters respiratory mechanics by reducing the lung volumes at which breathing occurs, leading to a decreased overall compliance of the respiratory system, as well as an increased airway resistance because of the airway closure that occurs at lower lung volumes. These effects are more prominent in patients with OHS than in eucapneic obese individuals.

The overall result is increased work in breathing, which has been shown to be present in the sitting and supine position in OHS patients, while it is present only in the supine position in equally obese eucapneic patients. There are two possible explanations for this discrepancy: the metabolic abnormalities of acidosis and hypoxemia lead to a state of relative respiratory muscle weakness, and higher proportions of central fat distribution that characterize patients with OHS result in a greater mechanical load on the chest.

Impaired ventilatory drive

Individuals who are morbidly obese normally have an increased respiratory drive that allows them to maintain eucapnia in the face of abnormal respiratory mechanics and increased work in breathing. In contrast, patients with OHS do not exhibit this augmented drive, so they have acquired a diminished ventilatory response to hypercapnia and hypoxia. This blunted central drive has been linked to leptin, a satiety hormone that has been shown to increase ventilatory drive in animal models.

In human obesity, a state of leptin resistance is frequently present, and leptin levels are usually elevated. Leptin levels have been found to be a better predictor of hypercapnia than the degree of adiposity, and higher leptin levels have been linked to a decreased ventilatory response to hypercapnia, suggesting that the degree of leptin resistance affects the level to which the respiratory drive is blunted and leads to hypoventilation.

Upper airway obstruction secondary to sleep disordered breathing

The fact that about 90 percent of OHS patients have evidence of obstructive sleep apnea on polysomnogram and that relief of upper airway obstruction with CPAP often leads to the resolution of daytime hypercapnia speaks to a role for sleep-disordered breathing in the development of OHS. One model that links nocturnal obstructive events with daytime hypercapnia proposes that recurrent nocturnal rises in CO2 during apneic events could eventually lead to elevation in the serum bicarbonate level if the interval between these events is not sufficient to eliminate the accumulated CO2. This elevation in serum bicarbonate blunts the respiratory responsiveness to CO2 and leads to daytime hypoventilation.

Which individuals are at greatest risk of developing obesity-hypoventilation syndrome?

Body mass index is one of the major risk factors for development of OHS. The proportion of patients with obstructive sleep apnea who have concomittant OHS rises with increasing BMI such that less than 10 percent of those with a BMI of 30 to 34 and more than 25 percent of those with a BMI above 40 have the syndrome. However, less than a third of obese people in general develop OHS. Other risk factors include central obesity (Resta 2000, Borel 2009) and the proportion of sleep time spent with oxygen saturations less than 90 percent.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

To make the diagnosis of OHS, arterial blood gases should be obtained on room air while the patient is awake in order to establish hypercapnia with a PaCO2 greater than 45mmHg. Once the presence of hypercapnia in an obese individual is established, other tests should be run to rule out other causes for the disturbance. Since severe hypothyroidism can lead to hypoventilation, a serum thryroid-stimulating hormone should be obtained to rule hypothyroidism out if the clinical suspicion is present.

What imaging studies will be helpful in making or excluding the diagnosis of obesity-hypoventilation syndrome?

Chest imaging, starting with a PA and lateral chest roentgenogram, is used to rule out evidence of pulmonary disorders and chest wall deformities, such as severe restriction, severe emphysema, and significant kyphoscoliosis, that could result in hypoventilation.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of obesity-hypoventilation syndrome?

Pulmonary function tests (PFTs) are used to rule out severe restrictive or obstructive pulmonary disorders. In OHS, PFTs can be normal, but they often show a mild to moderate restrictive defect that is due to body habitus. The total lung capacity is usually slightly reduced, and the vital capacity and the expiratory reserve volume are markedly reduced. The diffusing capacity for carbon monoxide is usually normal unless there is another disease process at play.

What diagnostic procedures will be helpful in making or excluding the diagnosis of obesity-hypoventilation syndrome?

Overnight polysomnogram: About 90 percent of patients with obesity hypoventilation exhibit evidence of obstructive sleep apnea. The mean apnea hypopnea index of OHS patients in the literature is 66 events per hour (range 20-100), and the mean proportion of sleep time spent below a 90 percent oxygen saturation is 50 percent (range 46-56%). Monitoring of CO2 levels is not necessary for the diagnosis of OHS, but if such monitoring is used, elevated levels will be seen both at baseline and throughout the sleep period, with marked exaggeration during REM sleep. The presence of elevated CO
2 levels during sleep and not during wakefulness does not meet the diagnostic criteria for OHS but represents sleep-related hypoventilation, which some experts have suggested could be a precursor of OHS if the only identifiable cause is obesity.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of obesity-hypoventilation syndrome?

Not applicable.

If you decide the patient has obesity-hypoventilation syndrome, how should the patient be managed?

Treatment options for OHS include positive pressure ventilation, tracheostomy, and weight loss. Pharmacological therapy has also been investigated but is not well established.

Positive pressure ventilation

When OHS is associated with significant sleep-disordered breathing, reversal of the nighttime disorder with continuous positive airway pressure (CPAP) can eliminate daytime hypercapnia. Reversal can also be achieved when OHS is associated with significant prolonged periods of flow limitation without overt OSA. In these two instances, the relief of upper airway obstruction with CPAP can break the cycle that leads to CO2 retention.

Since about 90 percent of OHS patients have evidence of concomitant OSA, CPAP is usually the initial approach to treatment. If, despite elimination of respiratory events, oxygen saturations during the initial titration night remain at less than 90 percent or CO2 levels remain elevated to more than 10mm Hg compared to the awake baseline, a switch to bilevel positive pressure ventilation (BPAP) is justified. It has been reported that about 20-50 percent of OHS patients must switch to bilevel-positive airway pressure ventilation.

However, a small study of 36 patients with OHS randomized to receive CPAP or BPAP showed no difference in compliance to therapy, no difference in awake CO2 levels, and no improvement in daytime sleepiness after three months. These results occurred even though some patients treated with CPAP continued to have oxygen saturations of 80-88 percent during the titration study. Less than half of these patients continued to have oxygen desaturations after three months of therapy, suggesting that CPAP may be effective, despite the lack of complete response initially.

The study excluded patients with more severe hypoventilation–that is, those with significant desaturations (<80% for more than ten minutes) on a level of CPAP that eliminated obstructive events, those with a rise in PaCO2 of more than 10 mmgHg during REM sleep, and those with an increase in PaCO2 of more than 10 mm Hg in the morning compared to the afternoon. Larger studies need to be done to improve available guidance in the choice of initial therapy in OHS patients.

In OHS patients with no evidence of upper airway obstruction on polysomnogram, initial titration with BPAP is appropriate, where the titration targets normalization of ventilation by using oxygen saturation levels as a surrogate marker.

A subset of patients with OHS requires supplemental oxygen along with positive airway pressure (PAP) treatment because of continued oxygen desaturation despite maximal PAP support. However, nocturnal oxygen alone is not adequate for treatment of OHS since it will not improve–and may even exacerbate–hypercapnia.


Tracheostomy is reserved for patients with OHS who are unable to tolerate positive airway pressure and who are developing life threatening complications, such as acute respiratory failure or cor pulmonale. By relieving upper airway obstruction, tracheostomy may result in improvement of the daytime hypercapnia. However, hypoventilation persists in some cases.

Weight loss

Weight loss is the best long-term treatment for patients with OHS. It results in improvement in lung function and in sleep-disordered breathing and ultimately in improvement in daytime hypoventilation. Weight loss can be achieved through dietary management, but bariatric surgery remains the most effective way to produce and maintain substantial weight loss. Patients with OHS are at increased risk of post-operative complications, particularly respiratory failure, so they should be treated perioperatively with positive airway pressure (CPAP or BPAP). Treatment with PAP should be continued until sufficient weight loss has occurred to improve respiratory mechanics and allow the withdrawal of PAP.


A number of pharmacological agents known to have respiratory stimulant properties have been studied in OHS. Small studies have reported positive results for acetazolamide, progesterone, and almitrine. However, no large-scale, randomized, controlled trials have been conducted, so use of these agents cannot be recommended at this time. One promising agent that has a role in pathogenesis of OHS is leptin. Animal studies in leptin-deficient mice showed that leptin replacement reversed OHS. However, in humans, leptin resistance, rather than deficiency, is present. Recent data on overcoming leptin resistance is promising for the future use of leptin to treat OHS in humans.

Bilevel titration in OHS

When using BPAP, the expiratory positive airway pressure (EPAP) is titrated up to eliminate apneas, and the inspiratory positive airway pressure (IPAP) is increased above EPAP to eliminate both hypopneas and respiratory-related arousals and to improve ventilation. Patients with OHS usually require a pressure support (the difference between IPAP and EPAP) of at least 6 to 7 cm of water to normalize their ventilation. During the titration, low oxygen saturation in the absence of respiratory events is frequently considered a surrogate marker for hypoventilation since most sleep laboratories do not measure CO2values. If CO2is being measured, then a CO2level of equal or less than the awake value should be targeted.

OHS in the ICU

A subset of patients with OHS will present with life-threatening conditions, such as acute decompensated respiratory failure and/or cor pulmonale. These patients should be hospitalized and monitored in a respiratory care unit, a step-down unit, or an intensive care unit to allow close observation and early detection of respiratory compromise that would require invasive mechanical ventilation. Treatment with non-invasive positive pressure ventilation should be started.

Figure 1 summarizes the management of OHS in patients who present with acute respiratory failure. (Reproduced with permission from Lee WY, Mokhlesi B. Crit Care Clin. 2008 Jul;24(3):533-49.)

Figure 1.

Management of patients with obesity hypoventilation syndrome requiring hospitalization because of acute or chronic hypercapnic respiratory failure. (Reproduced with permission from Lee WY, Mokhlesi B. Crit Care Clin. 2008 Jul;24(3):533-49.)

What is the prognosis for patients managed in the recommended ways?

There is limited data on long-term outcomes in patients with OHS who are untreated. A study from 2004 followed forty-seven patients with OHS after hospitalization and found a mortality rate of 23 percent at eighteen months compared to 9 percent with obesity not complicated by hypoventilation. Other studies also found that OHS patients had higher rates of use of health-care resources and, compared to normal obese controls, had a higher rate of morbidity, including congestive heart failure, angina pectoris, and cor pulmonale.

More recent studies following patients on non-invasive positive pressure ventilation (NIPPV) have found a mortality rate of 12.7 percent with a mean follow-up of 41.3 months, and 18.5 percent over a 4.1-year follow-up period. These results were better than historical rates for untreated OHS patients. The compliance with long-term NIPPV was elevated at 80 percent to 94.5 percent at about three years, indicating that NIPPV was overall well tolerated. In one study, female gender was associated with decreased compliance with NIPPV. Indicators of poor survival included hypoxemia, an elevated pH, and elevated inflammatory markers.

In summary, it appears that treatment with NIPPV is well tolerated and that it leads to improved long-term survival when compared to historical controls.

What other considerations exist for patients with obesity-hypoventilation syndrome?

Not applicable

What’s the evidence?

Auchincloss, JH, Cook, E, Renzetti, AD. “Clinical and physiological aspects of a case of obesity, polycythemia and alveolar hypoventilation”. J Clin Invest. vol. 34. 1955. pp. 1537-45. (First description of the obesity hypoventilation syndrome.)

Bickelmann, AG, Burwell, CS, Robin, ED, Whaley, RD. “Extreme obesity associated with alveolar hypoventilation; a Pickwickian syndrome”. Am J Med. vol. 21. 1956. pp. 811-8. (Early description of OHS with coining of the term "Pickwickian syndrome." )

Mokhlesi, B, Kryger, MH, Grunstein, RR. “Assessment and management of patients with obesity hypoventilation syndrome”. Proc Am Thorac Soc. vol. 5. 2008. pp. 218-25. (Excellent review paper on OHS.)

Piper, AJ, Grunstein, RR. “Obesity hypoventilation syndrome: mechanisms and management”. Am J Respir Crit Care Med. vol. 183. 2011. pp. 292-8. (An excellent review and the most recent review paper on OHS.)

Mokhlesi, B, Tulaimat, A, Faibussowitsch, I, Wang, Y, Evans, AT. “Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea”. Sleep Breath. vol. 11. 2007. pp. 117-24. (Observational study describing the prevalence and clinical characteristics of OHS in a population of patients referred to a sleep center.)

Kessler, R, Chaouat, A, Schinkewitch, P. “The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases”. Chest. vol. 120. 2001. pp. 369-76. (Prospective study describing clinical characteristics of thirty-four patients with OHS.)

Akashiba, T, Akahoshi, T, Kawahara, S. “Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study”. Intern Med (Tokyo, Japan). vol. 45. 2006. pp. 1121-5. (Observational study of clinical characteristics of 611 patients with OHS in Japan.)

Behazin, N, Jones, SB, Cohen, RI, Loring, SH. “Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity”. J Appl Physiol. vol. 108. 2010. pp. 212-8. (Case control study of fifty-one OHS patients and ten controls. Looks at the respiratory system mechanics in obesity and shows low respiratory system compliance in OHS patients compared to controls, resulting from breathing at abnormally low lung volumes.)

Pelosi, P, Croci, M, Ravagnan, I, Vicardi, P, Gattinoni, L. “Total respiratory system, lung, and chest wall mechanics in sedated-paralyzed postoperative morbidly obese patients”. Chest. vol. 109. 1996. pp. 144-51. (Case control study of ten OHS patients and ten controls. Looks at respiratory mechanics under sedation and paralysis and shows marked derangements in chest wall and pulmonary mechanics, as well as reduction in lung volumes in patients vs. controls.)

Resta, O, Foschino-Barbaro, MP, Bonfitto, P. “Prevalence and mechanisms of diurnal hypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea”. Respir Med. vol. 94. 2000. pp. 240-6. (Study of 285 patients referred to a sleep center. Shows that the development of hypercapnia in morbidly obese patients was correlated with a restrictive pattern on pulmonary function tests and with the degree of obstructive sleep apnea.)

Perez de Llano, LA, Golpe, R, Ortiz Piquer, M. “Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome”. Chest. vol. 128. 2005. pp. 587-94. (Descriptive study on retrospectively collected data on fifty-four patients with OHS treated with NIPPV and followed over a mean period of fifty months. Shows an improvement of gas exchange and clinical status with treatment.)

Piper, AJ, Wang, D, Yee, BJ, Barnes, DJ, Grunstein, RR. “Randomised trial of CPAP vs. bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation”. Thorax. vol. 63. 2008. pp. 395-401. (Randomized, controlled study of thirty-six patients with OHS without severe hypoxemia who received CPAP vs. bilevel PAP treatment for OHS. Shows overall equivalence of treatment in terms of compliance and improvement of daytime hypercapnia.)

Berry, RB, Chediak, A, Brown, LK. “Best clinical practices for the sleep center adjustment of noninvasive positive pressure ventilation (NPPV) in stable chronic alveolar hypoventilation syndromes”. J Clin Sleep Med. vol. 6. 2010. pp. 491-509. (The American Academy of Sleep Medicine expert panel's recommendations for treatment of OHS with non-invasive positive pressure ventilation provide a good review of the current evidence.)

Lee, WY, Mokhlesi, B. “Diagnosis and management of obesity hypoventilation syndrome in the ICU”. Crit Care Clin. vol. 24. 2008. pp. 533-49, vii. (Review of OHS management in the ICU.)

Sugerman, HJ, Fairman, RP, Baron, PL, Kwentus, JA. “Gastric surgery for respiratory insufficiency of obesity”. Chest. vol. 90. 1986. pp. 81-6. (Observational study describing the improvements in pulmonary function after bariatric surgery.)

Thomas, PS, Cowen, ER, Hulands, G, Milledge, JS. “Respiratory function in the morbidly obese before and after weight loss”. Thorax. vol. 44. 1989. pp. 382-6. (Prospective study of twenty-nine patients that shows respiratory changes before and after surgery.)

Nowbar, S, Burkart, KM, Gonzales, R. “Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome”. Am J Med. vol. 116. 2004. pp. 1-7. (Prospective study that follows forty-seven patients over eighteen months who had obesity hypoventilation and were hospitalized. The study found a higher rate of intensive care utilization and need for mechanical ventilation during hospitalization, as well as a higher rate of discharge to a long-term facility. At eighteen months follow-up, there was 23 percent mortality among patients with obesity hypoventilation vs. 9 percent mortality among those with obesity alone.)

Berg, G, Delaive, K, Manfreda, J, Walld, R, Kryger, MH. “The use of health-care resources in obesity-hypoventilation syndrome”. Chest. vol. 120. 2001. pp. 377-83. (Retrospective observational cohort study describing a higher rate of health care utilization in twenty patients with obesity hypoventilation prior to their diagnosis and treatment. The study found a reduction in days hospitalized once the diagnosis of OHS was made and treatment was instituted.)

Budweiser, S, Riedl, SG, Jorres, RA, Heinemann, F, Pfeifer, M. “Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation”. J Intern Med. vol. 261(Apr). 2007. pp. 375-83. (A retrospective descriptive analysis of 126 patients with OHS on non-invasive positive pressure ventilation (NIPPV) followed for a mean of 41.3 months. The study found good tolerance of and adherence to NIPPV, improvement in gas exchange and lung function, and improved survival (one-, two-, and five-year survival of 97.1%, 92.0%, and 70.2%, respectively), compared to historical (largely untreated) controls.)

Priou, P, Hamel, JF, Person, C. “Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome”. Chest. vol. 138. 2010. pp. 84-90. (Retrospective analysis of 130 patients with OHS who were started on NIPPV in either an outpatient or an inpatient setting. The study found an 80 percent adherence to NIPPV at three years and improved survival with treatment (one-, two-, three-, and five-year survival probabilities of 97.5%, 93.0%, 88.3%, and 77.3%, respectively), compared to historical controls.)

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