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Literature review current through: Dec 2020. | This topic last updated: Aug 22, 2019.
INTRODUCTION
The clinical manifestations, diagnosis, and complications of OHS are reviewed here, while
the pathogenesis and treatment are discussed separately. (See "Epidemiology and
pathogenesis of obesity hypoventilation syndrome" and "Treatment and prognosis of the
obesity hypoventilation syndrome" and "Noninvasive positive airway pressure therapy for
the obesity hypoventilation syndrome".)
RISK FACTORS
The major risk factor for OHS is obesity (body mass index [BMI] >30 kg/m2), in particular,
severe obesity (BMI >50 kg/m2), where prevalence may be as high as 50 percent. However,
not all patients with obesity develop OHS.
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Risk factors in obese patients are poorly defined but may include [4-6]:
Unlike OSA, male gender is not a risk factor for OHS [7-9]. However, women may present
somewhat differently.
Patients with OHS usually present in the fifth and sixth decades of life.
CLINICAL MANIFESTATIONS
The clinical manifestations of OHS are nonspecific and reflect the manifestations of
obesity, coexistent obstructive sleep apnea (OSA is present in 90 percent of OHS) or of
OHS-related complications (eg, pulmonary hypertension).
Symptoms and signs — Patients with OHS are obese (body mass index [BMI] >30 kg/m2),
hypersomnolent individuals. Ninety percent have at least some coexisting OSA (apnea-
hypopnea index [AHI] >5 events per hour), with severe disease (AHI >30 events per hour)
seen in 70 percent of patients [10]. Symptoms and physical findings of OSA include
daytime hypersomnolence, loud snoring, choking during sleep, resuscitative snorting,
fatigue, impaired concentration and memory, a small oropharynx, and a thick neck [1,11].
The 10 percent of individuals with OHS who have coexistent sleep hypoventilation without
significant OSA present similarly to those with the OHS-OSA phenotype, except witnessed
apneas during sleep are less common [11]. They are also more likely to be older females
[12,13]. The manifestations of OSA and nocturnal hypoventilation are provided in detail
separately. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults"
and "Central sleep apnea: Risk factors, clinical presentation, and diagnosis", section on
'Clinical findings'.)
Many patients with OHS present late in the course of their disease and have
manifestations of endstage disease including [1,6,14-16]:
● Severe hypoxemic hypercapnic respiratory failure - While many patients present with
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● Elevated serum bicarbonate (>27 mEq/L) – Almost all patients with OHS have an
elevated serum bicarbonate (venous and/or arterial), which is usually a clue that the
patient is chronically hypercapnic. However, it is nonspecific since other etiologies can
raise the bicarbonate level (eg, dehydration, medications) and it is not 100 percent
sensitive since other conditions (eg, lactic acidosis, chronic hyperventilation) may
lower the bicarbonate level.
This cut-off is based upon limited data. One observational study reported that a
venous serum bicarbonate of >27 mEq/L had a 92 percent sensitivity for identifying
awake hypercapnia in obese individuals, although specificity was significantly lower
(50 percent) [24]. A bicarbonate level <27 mEq/L had 97 percent negative predictive
value for excluding the diagnosis in this study. Another study reported a sensitivity of
85 percent and specificity of 89 percent in patients with levels >27 mEq/L when
capillary blood gas samples were used [25].
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Pulmonary function tests — Although findings of restriction are more commonly seen in
obese patients with OHS than in eucapnic obese patients, they are nonspecific, and
normal pulmonary function tests (PFTs) do not exclude the diagnosis. In general, PFTs are
more useful for ruling out underlying causes of hypoventilation. (See 'Exclude other
causes of hypercapnia and alveolar hypoventilation' below.)
In OHS a restrictive pattern on PFTs due to obesity is common, particularly in those with a
higher BMI (eg, BMI >50 kg/m2); both forced vital capacity (FVC) and forced expiratory
volume in one second (FEV1) are reduced, while the FEV1/FVC ratio is preserved [30,31].
More commonly, a reduction in functional residual capacity and expiratory reserve volume
is seen [31]. FVC values were found in one study to be lower in patients with OHS than
OSA but the threshold was ill-defined [4]. (See "Overview of pulmonary function testing in
adults".)
Severe restriction is uncommon with obesity and may indicate another restrictive lung
disorder.
Imaging and cardiac studies — In OHS, typical findings on chest radiograph include
elevation of both hemidiaphragms due to the obese abdomen and the heart may be
enlarged due to right ventricular hypertrophy.
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DIAGNOSTIC APPROACH
For patients who present with acute-on-chronic hypercapnic respiratory failure suspected
to be due to OHS, immediate treatment with positive pressure therapy is appropriate to
stabilize their clinical condition [16,18,20]. Once the patient has improved and is stable, a
diagnostic evaluation can be initiated. The treatment of OHS is discussed separately. (See
"Treatment and prognosis of the obesity hypoventilation syndrome" and "Noninvasive
positive airway pressure therapy for the obesity hypoventilation syndrome".)
Suspecting obesity hypoventilation — A strong clinical suspicion for OHS is critical for
the diagnosis. We typically initiate evaluation in obese patients (body mass index [BMI]
>30 kg/m2) with suspected or known OSA (or sleep disordered breathing), particularly
those with severe OSA (eg, apnea hypopnea index >60 events per hour, since the
prevalence is high in this population).
We also initiate evaluation in obese individuals with or without OSA who have the
following clinical features:
● Unexplained awake room air peripheral saturation (SpO2) ≤94 percent or an overnight
nadir saturation <80 percent
● Unexplained dyspnea on exertion
● Symptoms and signs of pulmonary hypertension and/or right-sided heart failure (eg,
elevated jugular venous pressure, hepatomegaly, and pedal edema)
● Facial plethora, which may indicate polycythemia
● A raised bicarbonate on venous blood sampling
Many of these features are more common in patients with OHS than in eucapnic obese
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Hypoventilation first becomes apparent during sleep in patients with obesity [2]. In one
study, the prevalence of obesity-related sleep hypoventilation (ORSH) had a prevalence of
19 percent amongst 94 obese patients (BMI >40kg.m-2). These individuals experienced a
rise in carbon dioxide (CO2) during sleep with a normal or raised bicarbonate during
wakefulness while PaCO2 remained <45 mmHg [2]. Predictors of ORSH were awake
oxygen saturation ≤93 percent, and a partial arterial pressure of carbon dioxide of ≥45
mmHg in the supine position [35]. These findings have led some experts to suggest that
ORSH is a precursor to OHS. However, further studies are needed to confirm the evolution
of ORSH to OHS.
Further details regarding the clinical manifestations of OHS are discussed above. (See
'Clinical manifestations' above.)
● ABG – Whether an ABG should be obtained in all patients suspected of having OHS
has been the subject of debate. We and others suggest that when the suspicion for
OHS is strong, an ABG should be measured. ABGs should be performed while the
patient is awake, sitting upright, and breathing room air (so that A-a oxygen gradient
can be calculated). Where ABGs are difficult to obtain, venous blood sampling can be
used as a surrogate for pH, PaCO2, and bicarbonate [36,37]. (See "Arterial blood
gases" and "Venous blood gases and other alternatives to arterial blood gases".)
● Serum bicarbonate – For those in whom the suspicion is low to moderate (eg, <20
percent), obtaining serum bicarbonate is typically sufficient. Based upon the results
we suggest the following:
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identified, then OHS is likely, and if not identified then OHS is unlikely.
Interpretation of acid-base disturbances and distinguishing acute, acute-on-
chronic, and chronic hypercapnia ( figure 1 and figure 2 and figure 3) are
discussed separately (See "The evaluation, diagnosis, and treatment of the adult
patient with acute hypercapnic respiratory failure", section on 'Arterial blood gas
analysis' and "Simple and mixed acid-base disorders", section on 'Respiratory
acid-base disorders'.)
• Bicarbonate level is ≤27 mEq/L – If the bicarbonate level is ≤27 mEq/L, OHS is
unlikely, particularly when the suspicion for OHS is low to moderate. An ABG is
not absolutely necessary in this population. However, the approach in this
population should be individualized. An ABG may be considered in obese patients
with borderline elevations in bicarbonate, reduced oxygenation parameters, and
suspected complex acid-base disturbance (eg, acute-on-chronic hypercapnia,
triple acid-base disturbance), as well as in those in whom an ABG would facilitate
excluding an alternate diagnosis.
● Complete blood count – Chronic hypoxemia from underlying lung disease may be
associated with polycythemia, which may be a useful tool to monitor response to
therapy [30,38]. Although rare, an elevated eosinophil fraction on a complete blood
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Further details regarding the evaluation of acute hypercapnia ( table 1) are discussed
separately (see "The evaluation, diagnosis, and treatment of the adult patient with acute
hypercapnic respiratory failure")
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determine what sleep test is chosen. Factors favoring in-laboratory PSG include morbid
obesity (body mass index [BMI] >40 kg/m2), high likelihood of sleep-related
hypoventilation (as CO2 monitoring is available only with in-center testing), heart failure,
and significant daytime or nocturnal hypoxemia. Home sleep apnea testing (HSAT) is not
ideal for rule out OHS as HSAT is best suited for uncomplicated, high probability
obstructive sleep apnea cases. It should be noted that HSAT does not detect sleep-related
hypoventilation, thus necessitating PSG with continuous nocturnal carbon dioxide
monitoring. HSAT may be suitable in those with non-morbid obesity (BMI 30 to 40 kg/m2)
in whom the likelihood of OSA is high or those in whom the issue of cost expressly
prohibits PSG evaluation. Although PSG or HSAT is not required to diagnose OHS, sleep
testing distinguishes the 90 percent of patients with OHS who have coexistent OSA from
the 10 percent of patients who have sleep-related hypoventilation alone [11,43].
Determining the type of SDB is important since it has implications for the type of therapy
administered. Further details regarding diagnostic testing are provided separately. (See
"Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on
'Diagnostic tests' and "Home sleep apnea testing for obstructive sleep apnea in adults"
and "Central sleep apnea: Risk factors, clinical presentation, and diagnosis".)
Although, the apnea hypopnea index [AHI] is likely to be higher in OHS patients than
those with eucapnic OSA, it doesn’t distinguish these groups [24,44]. However, patients
with OHS tend to have severe OSA (eg, AHI >50/hour) [24,44,45] and usually have more
profound oxygen desaturation during sleep than patients with OSA alone, spending a
significantly larger part of sleep time with saturations <90 percent [44,46,47]. (See
"Polysomnography in the evaluation of sleep-disordered breathing in adults".)
DIAGNOSIS
OHS is a diagnosis of exclusion that can be made when the following criteria are met:
Although the majority also have sleep-disordered breathing (nocturnal obstructive and
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nonobstructive events), it is the awake (ie, typically daytime) hypoventilation that is critical
for diagnosis.
DIFFERENTIAL DIAGNOSIS
The main competing diagnosis for the symptoms of OHS is obstructive sleep apnea (OSA).
Apart from the presence of chronic respiratory acidosis with compensatory metabolic
alkalosis, both disorders are often clinically indistinguishable from one another. (See
"Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on
'Clinical features'.)
Common etiologies for respiratory hypercapnia and alveolar hypoventilation are typically
distinguished by history, examination, pulmonary function testing, imaging, and
laboratory findings:
● Chronic obstructive pulmonary disease (COPD) – COPD may be identified in those with
a smoking history, obstruction on pulmonary function tests, and imaging findings of
emphysema. (See "Chronic obstructive pulmonary disease: Definition, clinical
manifestations, diagnosis, and staging".)
● Interstitial lung diseases (ILD) – ILD may be identified in those with imaging findings
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● Chest wall disorders – Such disorders (eg, kyphoscoliosis) may be obvious on clinical
examination or on imaging. (See "Chest wall diseases and restrictive physiology".)
● Chronic sedative use - Use of sedatives may be found on history or toxicology testing.
(See "General approach to drug poisoning in adults".)
ASSESS COMPLICATIONS
All patients with obesity hypoventilation syndrome (OHS) should be assessed for common
complications, many of which are shared with obesity alone ( table 2) [48]. These are
discussed in detail separately. (See "Overweight and obesity in adults: Health
consequences" and "Treatment and prognosis of the obesity hypoventilation syndrome",
section on 'Treatment of comorbid conditions'.)
Specifically, patients with OHS should be assessed for the following common
complications:
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The natural history and prognosis of OHS is discussed separately. (See "Treatment and
prognosis of the obesity hypoventilation syndrome".)
● The clinical manifestations of OHS are nonspecific and are more reflective of the
manifestations of obesity, coexistent obstructive sleep apnea (OSA; eg,
hypersomnolence, snoring, witnessed apneas), or OHS-related complications (eg,
pulmonary hypertension). Sleep-related desaturation and daytime hypoxemia are
common. (See 'Clinical manifestations' above.)
● For those in whom OHS is strongly suspected (eg, morbidly obese patients with
suspected or known OSA), we suggest that an arterial blood gas (ABG) be obtained to
look for evidence of alveolar hypoventilation (ie, PaCO2 >45 mmHg). For those in
whom the suspicion is low to moderate (eg, <20 percent), obtaining serum
bicarbonate is typically sufficient; an elevated bicarbonate level >27 mEq/L, increases
the likelihood of OHS and should prompt an ABG, while a bicarbonate level ≤27 mEq/L
suggests that OHS is unlikely, and unless an alternate etiology or complex acid-base
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disturbance is suspected, an ABG is not usually indicated. For those in whom a chronic
respiratory acidosis (PaCO2 >45 mmHg) with compensatory metabolic alkalosis is
found, additional testing is necessary to exclude other diseases that can cause or
contribute to chronic alveolar hypoventilation or hypercapnia. (see 'Diagnostic
approach' above)
● For those with suspected OHS in whom a diagnosis of OSA does not already exist, in-
laboratory polysomnography should ideally be performed based upon the rationale
that 90 percent of patients with OHS have coexistent OSA of at least mild to moderate
severity while the remainder have sleep-related hypoventilation only. Home sleep
apnea testing may be a suitable alternative in those who do not have morbid obesity
(ie, BMI 30 to 40 kg/m2) in whom the likelihood of OSA is high or those in whom cost
is an issue. (See 'Identify coexistent sleep disordered breathing' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Paul Suratt, MD, who
contributed to an earlier version of this topic review.
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GRAPHICS
Reproduced with permission from: Harrington JT, Cohen JJ, Kassirer JP. Mixed acid-base disturbances. In: Acid/Base, Cohen
JJ, Kassirer JP (Eds), Little, Brown, Boston: 1982. Copyright © 1982 Lippincott Williams & Wilkins. www.lww.com.
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Arbus GS, Herbert LA, Levesque PR, et al. N Engl J Med 1969; 280:117. By permission from the
New England Journal of Medicine.
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95% significance bands for plasma pH and H + and HCO 3 – concentrations in chronic
hypercapnia. Because of the compensatory rise in the plasma HCO 3 –
concentration, there is much less change in H + concentration and pH than in acute
hypercapnia.
Schwartz WB, Brackett NC Jr, Cohen JJ. J Clin Invest 1965; 44:291. By copyright permission of the
American Society for Clinical Investigation.
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Respiratory muscles
↓
"Can't breathe"
Chest wall and pleura
↓
Upper airway
↓
Schematic figure representing the respiratory pathway, along which a variety of diseases can affect carbon dioxide
elimination and result in hypercapnia. Note that gas exchange abnormalities alone are relatively uncommon causes of
hypercapnia, but gas exchange problems in the setting of reduced mechanical capability of the ventilatory pump are
very common explanations for acute and chronic hypercapnia.
Mechanism Etiologies
Decreased central Sedative overdose (eg, narcotic or benzodiazepine, some anesthetics, tricyclic
respiratory drive antidepressants)
Encephalitis
Stroke
Central and obstructive sleep apnea
Obesity hypoventilation
Congenital central alveolar hypoventilation
Brainstem disease
Metabolic alkalosis
Hypothyroidism*
Hypothermia
Starvation
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Increased dead space (gas exchange abnormalities; pulmonary parenchymal causes or airway disorders)
Fever
Thyrotoxicosis
Increased catabolism (sepsis, steroids)
Overfeeding
Metabolic acidosis
Exercise
Multifactorial
Decreased mechanical ventilation can also cause hypercapnic respiratory acidosis (eg, permissive hypercapnia).
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Importantly, any factor that limits the mechanical function of the ventilatory pump (such as airway obstruction or
weak muscles), when combined with a gas exchange abnormality (increased physiological dead space), may lead to
hypercapnia. For further details regarding the mechanisms that underlie these pathologies, please refer to the
UpToDate topic on mechanisms, causes, and effects of hypercapnia.
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Cognitive deficit
Upper airway
Respiratory
Pulmonary hypertension
Hypercapnia/hypoxemia
Metabolic
Central obesity
Metabolic syndrome
Chronic inflammation
IGF-1 deficit
Cardiovascular
Endothelial dysfunction
General
Peripheral edema
Increased morbi-mortality
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Contributor Disclosures
Amanda Piper, PhD Consultant/Advisory Boards: Philips [COPD]. Speaker's Bureau: ResMed, Asia
Pacific; Philips, Asia Pacific [Noninvasive ventilation in OHS, COPD and other hypoventilation
syndromes]. Brendon Yee, MBChB, PhD Nothing to disclose M Safwan Badr, MD Nothing to
disclose Geraldine Finlay, MD Consultant/Advisory Boards: LAM Board of directors, LAM scientific
grant review committee for The LAM Foundation.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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