Clinical Manifestations and Diagnosis of Obesity Hypoventilation Syndrome - UpToDate

Clinical manifestations and diagnosis of obesity hypoventilation syndrome - UpToDate 02/01/21 18.
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Clinical manifestations and diagnosis of obesity

hypoventilation syndrome
Authors: Amanda Piper, PhD, Brendon Yee, MBChB, PhD
Section Editor: M Safwan Badr, MD
Deputy Editor: Geraldine Finlay, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2020. | This topic last updated: Aug 22, 2019.
INTRODUCTION
Obesity Hypoventilation Syndrome (OHS) is defined as the presence of awake alveolar

hypoventilation in an obese individual which cannot be attributed to other conditions
associated with alveolar hypoventilation [1-3]. OHS is associated with increased
cardiovascular morbidity and mortality. Consequently, early detection and treatment are
crucial to minimize these adverse effects.
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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Clinical manifestations and diagnosis of obesity hypoventilation syndrome - UpToDate 02/01/21 18.11
Risk factors in obese patients are poorly defined but may include [4-6]:
● Significant increase in waist:hip ratio (ie, central obesity)

● Reduced lung function due to obesity
● Reduced inspiratory muscle strength
● Severe obstructive sleep apnea (OSA; eg, apnea hypopnea index >50 events per hour)
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
chronic stable symptoms or chronic hypercapnic respiratory failure, about one-third

of patients present with acute-on-chronic respiratory failure prompting hospital
admission [14,16-20]. There is some evidence to suggest that women may present
later than men and are more likely to present with acute-on-chronic respiratory failure
[18,21]. Such patients are often misdiagnosed as having chronic obstructive
pulmonary disease (COPD) or asthma, despite an absence of obstruction on
pulmonary function testing [22]. Daytime hypoxemia and significant and sustained
reductions in overnight oximetry (eg, peripheral saturation <80 percent) are features
that are uncommon in OSA or obesity alone [23]. (See "Pulse oximetry" and "Home
sleep apnea testing for obstructive sleep apnea in adults", section on 'Pulse
oximetry'.)
● Right heart failure from pulmonary hypertension (dyspnea on exertion, elevated

jugular venous pressure, hepatomegaly, and pedal edema) and less commonly, facial
plethora from polycythemia.
Laboratory tests — OHS may be associated with the following findings:
● 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].
● Hypercapnia (arterial pressure of carbon dioxide [PaCO2] >45 mmHg) – Consistent

with the phenomenon of hypoventilation, all patients with OHS have hypercapnia on
arterial blood gas analysis when awake and on room air. Although most patients with
OHS present with chronic elevations in the PaCO2, about one-third have acute-on-
chronic respiratory failure [16,19,20]. A raised bicarbonate (>27 mmol/L) or base

excess (>3 mmol/L) in the absence of another cause for a metabolic alkalosis in an
obese individual with a PaCO2 <45 mmHg may be an early indicator of OHS,
warranting closer investigation [26,27]. (See "Arterial blood gases" and "Venous blood
gases and other alternatives to arterial blood gases".)
● Hypoxemia (PaO2 <70 mmHg) – Hypoxemia is usually present. The calculated

alveolar-arterial (A-a) oxygen gradient is classically normal, although a mild widening
is not unusual related to ventilation-perfusion mismatching or coexistent
parenchymal or vascular lung disease [28,29]. Severe nocturnal desaturation is also
common (eg, peripheral saturation <80 percent).
● Polycythemia — Polycythemia due to recurrent hypoventilation- or OSA-associated

hypoxemia is uncommon but may be present as a late manifestation.
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.
Evidence of right ventricle enlargement from pulmonary hypertension that complicates

advanced OHS may be seen on electrocardiography (EKG) and echocardiography [32,33].
DIAGNOSTIC APPROACH
The diagnostic approach focuses on establishing awake (often daytime) hypoventilation in

an obese patient in the absence of other causes of alveolar hypoventilation.
Polysomnography with continuous nocturnal carbon dioxide monitoring is the gold
standard for the evaluation of patients suspected of having obesity hypoventilation
syndrome (OHS). Testing should be performed to characterize the type of underlying sleep
disordered breathing (ie, OHS with or without coexisting obstructive sleep apnea [OSA]).
(See 'Identify coexistent sleep disordered breathing' below.)
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
individuals or in patients who have OSA alone [1,4,6,14-16,23,24,34].
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.)
Indicators of chronic alveolar hypoventilation — In patients in whom OHS is suspected,

the presence of chronic hypoventilation is usually inferred when a chronic respiratory
acidosis (hypercapnic respiratory acidosis) on arterial blood gas analysis (ABG) is
demonstrated together with compensatory metabolic alkalosis (ie, elevated bicarbonate).
● 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:
• Bicarbonate level >27 mEq/L – An elevated bicarbonate level greater than 27

mEq/L, significantly increases the likelihood of OHS and an ABG should be done
to investigate for the presence of chronic hypercapnic acidosis (partial pressure of
arterial carbon dioxide [PaCO2] >45 mmHg). ABGs can also identify hypoxemia.
Should chronic respiratory acidosis with compensatory metabolic alkalosis be
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.
Exclude other causes of hypercapnia and alveolar hypoventilation — For those in

whom a chronic respiratory acidosis 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. Disorders that commonly co-exist with
obesity that may contribute to hypercapnia include chronic obstructive pulmonary disease
(COPD), restrictive lung disease (eg, neuromuscular weakness, severe interstitial lung
disease, chest wall disease), hypothyroidism, electrolyte disturbances, and chronic
sedative use [1,11]. Testing should be individualized but generally includes:
● Serum chemistries and electrolytes – Electrolyte disturbances that may exacerbate

hypercapnia include hypophosphatemia, hypomagnesemia, and rarely,
hypermagnesemia, hypokalemia, or hypercalcemia. If found, these should be
corrected and the ABG repeated. (See "Hypomagnesemia: Clinical manifestations of
magnesium depletion" and "Hypophosphatemia: Clinical manifestations of phosphate
depletion".)
● 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
count may be consistent with neuropathy from eosinophilic myalgia. (See

"Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and
diagnosis", section on 'Neurologic disease' and "Diagnostic approach to the patient
with polycythemia", section on 'Causes of absolute polycythemia'.)
● Thyroid function tests – Hypothyroidism may contribute to the chronic ventilatory

failure of OHS by decreasing chemo-responsiveness, causing OSA (due to
macroglossia and/or upper airway dilator muscle dysfunction), or causing either a
myopathy or neuropathy that affects the respiratory muscles [39-42]. (See "Laboratory
assessment of thyroid function" and "Hypomagnesemia: Clinical manifestations of
magnesium depletion" and "Hypophosphatemia: Clinical manifestations of phosphate
depletion".)
● Pulmonary function tests – Pulmonary function tests (PFTs) including spirometry,

lung volumes, diffusing capacity, and inspiratory and expiratory pressures may
facilitate the identification and severity of a potential underlying lung disease and
should be performed in the chronic stable state. (See "Overview of pulmonary
function testing in adults" and "Tests of respiratory muscle strength".)
● Imaging – A chest radiograph should be performed to exclude parenchymal lung

disease, chest wall disease, asymmetrical elevation of a hemidiaphragm (ie,
diaphragm paralysis), and cardiomegaly.
● Other – Rarely, a toxicology screen (eg, concomitant benzodiazepine or narcotic use)

or creatine phosphokinase (eg, contributing myositis) are obtained.
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")
IDENTIFY COEXISTENT SLEEP DISORDERED BREATHING
Ideally, in-laboratory polysomnography (PSG) is performed in all patients suspected as

having OHS, in whom a diagnosis of obstructive sleep apnea (OSA) or other sleep
disordered breathing (SDB) does not already exist. However, many factors including third
party payor issues, degree of obesity, and likelihood of OSA or sleep-hypoventilation
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:
● Obesity (body mass index [BMI] >30 kg/m2)

● Awake alveolar hypoventilation as indicated by a partial arterial pressure of carbon
dioxide >45 mmHg
● Alternative causes hypercapnia and hypoventilation have been excluded (see 'Exclude
other causes of hypercapnia and alveolar hypoventilation' above)
Although the majority also have sleep-disordered breathing (nocturnal obstructive and
nonobstructive events), it is the awake (ie, typically daytime) hypoventilation that is critical
for diagnosis.
The absence of an alternative cause of hypercapnic hypoventilation is an important

requirement for the diagnosis of OHS. In clinical practice, patients frequently have
additional diseases that cause acute and/or chronic hypercapnia. However, assessing the
contributions of additional etiologies may be tricky and a matter of clinical judgement. If a
potential contributing etiology is mild or considered unlikely to cause hypercapnia, then it
is appropriate to diagnose OHS. In contrast, if a coexisting disease is severe and
considered likely contributing to hypercapnia, OHS cannot be diagnosed with certainty.
(See 'Exclude other causes of hypercapnia and alveolar hypoventilation' above and
'Differential diagnosis' below.)
Because symptoms are nonspecific, the diagnosis of OHS is frequently delayed. It is

commonly misdiagnosed as asthma or chronic obstructive pulmonary disease [22] and
some patients are not diagnosed until hospitalization for acute-on-chronic respiratory
failure occurs. (See 'Symptoms and signs' above.)
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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of parenchymal abnormalities and restriction on pulmonary function tests. (See

"Approach to the adult with interstitial lung disease: Clinical evaluation" and
"Approach to the adult with interstitial lung disease: Diagnostic testing".)
● Neuromuscular (NM) disorders – NM disorders may be identified by history (eg, weak

cough), weakness on examination, and restrictive deficit and muscle weakness on
lung function testing. Chest imaging may reveal an elevated hemidiaphragm to
suggest diaphragmatic paralysis. (See "Respiratory muscle weakness due to
neuromuscular disease: Clinical manifestations and evaluation".)
● Chest wall disorders – Such disorders (eg, kyphoscoliosis) may be obvious on clinical
examination or on imaging. (See "Chest wall diseases and restrictive physiology".)
● Hypothyroidism – Hypothyroidism is typically evident on laboratory testing. (See

"Clinical manifestations of hypothyroidism" and "Diagnosis of and screening for
hypothyroidism in nonpregnant adults".)
● 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:
● Mild to moderate pulmonary hypertension (PH) – Up to two-thirds of patients with

OHS have PH. Thus, at diagnosis we typically perform an electrocardiogram and
echocardiogram in this population to evaluate for PH, the details of which are
discussed separately. (See "Pulmonary hypertension due to lung disease and/or
hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and
diagnostic evaluation in adults".)
● Cardiovascular and metabolic comorbidities – Conditions such as hypertension,

congestive heart failure, and insulin resistance are all more common in patients with
OHS than in patients with eucapnic obesity, and may be present three or more years
prior to the diagnosis of OHS [4,48-50]. Thus, at the time of diagnosis we typically
perform fasting bloods assessing plasma glucose, triglycerides, and cholesterol to
ensure comorbid conditions have been identified and are being appropriately
managed. A cross sectional study of stable OHS patients found cardiovascular
morbidity risk was significantly higher in those with the predominantly sleep
hypoventilation OHS phenotype despite these individuals exhibiting less severe
nocturnal and awake gas exchange compared with those who had OHS and
significant OSA [51].
The natural history and prognosis of OHS is discussed separately. (See "Treatment and
prognosis of the obesity hypoventilation syndrome".)
SUMMARY AND RECOMMENDATIONS
● Obesity hypoventilation syndrome (OHS) is defined as the presence of awake alveolar

hypoventilation (partial arterial pressure of carbon dioxide [PaCO2] >45 mmHg) in an
obese individual (body mass index [BMI] >30 kg/m2), which cannot be attributed to
other conditions associated with hypoventilation. (See 'Introduction' above and
'Diagnosis' above.)
● 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
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.)
● OHS is a diagnosis of exclusion (obesity and awake alveolar hypoventilation which

cannot be attributed to other conditions associated with hypoventilation). Once
diagnosed, all patients with OHS should be assessed for common complications,
including pulmonary hypertension and cardiovascular disorders ( table 2). (See
'Diagnosis' above and 'Differential diagnosis' above and 'Assess complications' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Paul Suratt, MD, who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
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. The American Academy of Sleep Medicine: International classification of sleep

disorders: 3rd Ed., Darien, IL. The American Academy of Sleep Medicine, 2014.
4. Basoglu OK, Tasbakan MS. Comparison of clinical characteristics in patients with

obesity hypoventilation syndrome and obese obstructive sleep apnea syndrome: a
case-control study. Clin Respir J 2014; 8:167.
5. Piper AJ, Grunstein RR. Obesity hypoventilation syndrome: mechanisms and

management. Am J Respir Crit Care Med 2011; 183:292.
6. Mokhlesi B, Kryger MH, Grunstein RR. Assessment and management of patients with
obesity hypoventilation syndrome. Proc Am Thorac Soc 2008; 5:218.
7. Castro-Añón O, Pérez de Llano LA, De la Fuente Sánchez S, et al. Obesity-

hypoventilation syndrome: increased risk of death over sleep apnea syndrome. PLoS
One 2015; 10:e0117808.
8. 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.
9. BaHammam AS. Prevalence, clinical characteristics, and predictors of obesity

hypoventilation syndrome in a large sample of Saudi patients with obstructive sleep
apnea. Saudi Med J 2015; 36:181.
10. Masa JF, Corral J, Alonso ML, et al. Efficacy of Different Treatment Alternatives for
Obesity Hypoventilation Syndrome. Pickwick Study. Am J Respir Crit Care Med 2015;
192:86.
11. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005; 118:948.
12. Masa JF, Corral J, Caballero C, et al. Non-invasive ventilation in obesity

hypoventilation syndrome without severe obstructive sleep apnoea. Thorax 2016;
71:899.
13. BaHammam AS, Pandi-Perumal SR, Piper A, et al. Gender differences in patients with
obesity hypoventilation syndrome. J Sleep Res 2016; 25:445.
14. Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in
hospitalized patients: prevalence, effects, and outcome. Am J Med 2004; 116:1.
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. 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.
17. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome

revisited: a prospective study of 34 consecutive cases. Chest 2001; 120:369.
18. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute

hypercapnic respiratory failure caused by obesity hypoventilation syndrome and
chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186:1279.
19. Borel JC, Burel B, Tamisier R, et al. Comorbidities and mortality in hypercapnic obese
under domiciliary noninvasive ventilation. PLoS One 2013; 8:e52006.
20. Priou P, Hamel JF, Person C, et al. Long-term outcome of noninvasive positive
pressure ventilation for obesity hypoventilation syndrome. Chest 2010; 138:84.
21. Palm A, Midgren B, Janson C, Lindberg E. Gender differences in patients starting

long-term home mechanical ventilation due to obesity hypoventilation syndrome.
Respir Med 2016; 110:73.
22. Marik PE, Desai H. Characteristics of patients with the "malignant obesity
hypoventilation syndrome" admitted to an ICU. J Intensive Care Med 2013; 28:124.
23. Bingol Z, Pıhtılı A, Cagatay P, et al. Clinical predictors of obesity hypoventilation

syndrome in obese subjects with obstructive sleep apnea. Respir Care 2015; 60:666.
24. 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.
25. 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.
26. 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.
27. Hart N, Mandal S, Manuel A, et al. Obesity hypoventilation syndrome: does the
current definition need revisiting? Thorax 2014; 69:83.
28. Littleton SW. Impact of obesity on respiratory function. Respirology 2012; 17:43.
29. Andersen J, Rasmussen JP, Eriksen J. Pulmonary function in obese patients scheduled
for jejuno-ileostomy. Acta Anaesthesiol Scand 1977; 21:346.
30. Heinemann F, Budweiser S, Dobroschke J, Pfeifer M. Non-invasive positive pressure

ventilation improves lung volumes in the obesity hypoventilation syndrome. Respir
Med 2007; 101:1229.
31. Piper AJ. Obesity hypoventilation syndrome--the big and the breathless. Sleep Med
Rev 2011; 15:79.
32. Castro-Añón O, Golpe R, Pérez-de-Llano LA, et al. Haemodynamic effects of non-

invasive ventilation in patients with obesity-hypoventilation syndrome. Respirology
2012; 17:1269.
33. Kauppert CA, Dvorak I, Kollert F, et al. Pulmonary hypertension in obesity-

hypoventilation syndrome. Respir Med 2013; 107:2061.
34. Mandal S, Suh ES, Boleat E, et al. A cohort study to identify simple clinical tests for
chronic respiratory failure in obese patients with sleep-disordered breathing. BMJ
Open Respir Res 2014; 1:e000022.
35. Sivam S, Yee B, Wong K, et al. Obesity Hypoventilation Syndrome: Early Detection of
Nocturnal-Only Hypercapnia in an Obese Population. J Clin Sleep Med 2018; 14:1477.
36. Mokhlesi B, Masa JF, Brozek JL, et al. Evaluation and Management of Obesity
Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice
Guideline. Am J Respir Crit Care Med 2019; 200:e6.
37. Hollier CA, Maxwell LJ, Harmer AR, et al. Validity of arterialised-venous P CO2, pH and
bicarbonate in obesity hypoventilation syndrome. Respir Physiol Neurobiol 2013;

188:165.
38. Budweiser S, Riedl SG, Jörres RA, et al. Mortality and prognostic factors in patients
with obesity-hypoventilation syndrome undergoing noninvasive ventilation. J Intern
Med 2007; 261:375.
39. Martinez FJ, Bermudez-Gomez M, Celli BR. Hypothyroidism. A reversible cause of

diaphragmatic dysfunction. Chest 1989; 96:1059.
40. Ladenson PW, Goldenheim PD, Ridgway EC. Prediction and reversal of blunted
ventilatory responsiveness in patients with hypothyroidism. Am J Med 1988; 84:877.
41. MASSUMI RA, WINNACKER JL. SEVERE DEPRESSION OF THE RESPIRATORY CENTER IN
MYXEDEMA. Am J Med 1964; 36:876.
42. Skatrud J, Iber C, Ewart R, et al. Disordered breathing during sleep in

hypothyroidism. Am Rev Respir Dis 1981; 124:325.
43. Kessler R, Chaouat A, Weitzenblum E, et al. Pulmonary hypertension in the

obstructive sleep apnoea syndrome: prevalence, causes and therapeutic
consequences. Eur Respir J 1996; 9:787.
44. 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.
45. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation

syndrome. Clin Chest Med 2009; 30:467.
46. Banerjee D, Yee BJ, Piper AJ, et al. Obesity hypoventilation syndrome: hypoxemia
during continuous positive airway pressure. Chest 2007; 131:1678.
47. 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.
48. Jennum P, Ibsen R, Kjellberg J. Morbidity prior to a diagnosis of sleep-disordered

breathing: a controlled national study. J Clin Sleep Med 2013; 9:103.
49. Berg G, Delaive K, Manfreda J, et al. The use of health-care resources in obesity-
hypoventilation syndrome. Chest 2001; 120:377.
50. Borel JC, Roux-Lombard P, Tamisier R, et al. Endothelial dysfunction and specific
inflammation in obesity hypoventilation syndrome. PLoS One 2009; 4:e6733.
51. Masa JF, Corral J, Romero A, et al. Protective Cardiovascular Effect of Sleep Apnea
Severity in Obesity Hypoventilation Syndrome. Chest 2016; 150:68.
Topic 7698 Version 29.0
GRAPHICS
Expected compensation ranges for simple acid-base disorders
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.
Graphic 79833 Version 9.0
Compensations to acute respiratory acidosis and alkalosis
Combined significance bands for plasma pH and concentrations of H+ and HCO3- in

acute respiratory acidosis and alkalosis in humans. In uncomplicated acute
respiratory acid-base disorders, values for the H+ and HCO3- concentrations will,
with an estimated 95 percent probability, fall within the band. Values lying outside
the band indicate the presence of a complicating metabolic acid-base disturbance.
Arbus GS, Herbert LA, Levesque PR, et al. N Engl J Med 1969; 280:117. By permission from the
New England Journal of Medicine.
Compensation to chronic respiratory acidosis
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.
Etiologies and mechanism of hypercapnia
Respiratory pathway affecting carbon dioxide elimination

Central nervous system
"Won't breathe"
↓
Peripheral nervous system

↓
Respiratory muscles
↓
"Can't breathe"
Chest wall and pleura
↓
Upper airway
↓
Lungs Abnormal gas exchange: "Can't breathe enough"
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 and etiologies of hypercapnia
Mechanism Etiologies
Decreased minute ventilation (global hypoventilation; extra pulmonary causes)
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
Decreased Primary spinal cord/lower Thoracic cage disorders Metabolic disorders Δ

respiratory motor neuron/muscle Kyphoscoliosis Hypophosphatemia
neuromuscular or disorders Thoracoplasty Hypomagnesemia
thoracic cage Cervical spine injury Flail Chest Hypothyroidism
function or disease (eg,
Ankylosing Hyperthyroidism
trauma
spondylitis
syringomyelia) ¶ Toxins, poisoning, drugs
Pectus excavatum
Amyotrophic lateral Tetanus
Fibrothorax
sclerosis Dinoflagellate
Poliomyelitis poisoning
Guillain-Barré Shellfish poisoning

syndrome (red tide)
Phrenic nerve injury Ciguatera poisoning
Critical illness Botulism
polymyoneuropathy Organophosphates
Myasthenia gravis Succinylcholine and
Muscular dystrophy neuromuscular
Polymyositis blockade
Tetanus Procainamide
Transverse myelitis
(eg, multiple
sclerosis)
Tick paralysis
Acute intermittent
porphyria
Eaton Lambert
syndrome
Neuralgic
amyotrophy
Periodic paralysis
Glycogen storage and
mitochondrial
diseases
Respiratory muscle
fatigue
Increased dead space (gas exchange abnormalities; pulmonary parenchymal causes or airway disorders)
Anatomic Short shallow breathing
Physiologic Pulmonary embolism (usually severe)

Pulmonary vascular disease (usually severe)
Dynamic hyperinflation (eg, upper and lower airway disorders including chronic
obstructive pulmonary disease, severe asthma)
Endstage interstitial lung disease
Increased carbon dioxide production
Fever
Thyrotoxicosis
Increased catabolism (sepsis, steroids)
Overfeeding
Metabolic acidosis
Exercise
Multifactorial
Upper airway disorders ◊

Severe laryngeal or tracheal disorders
(stenosis/tumors/angioedema/tracheomalacia)
Vocal cord paralysis
Epiglottitis
Foreign body aspiration
Retropharyngeal disorders
Obstructive goiter
Decreased mechanical ventilation can also cause hypercapnic respiratory acidosis (eg, permissive hypercapnia).
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.
* Hyperthyroidism is also a rare cause of respiratory muscle weakness.

¶ Injury or disease process needs to be between cervical spine level 3 and 5 (C3 to 5) for clinically significant diaphragmatic
paresis/paralysis to occur.
Δ Hypermagnesemia, hypokalemia, and hypercalcemia can also cause respiratory muscle weakness and contribute to
hypercapnia.
◊ Upper airway disorders are rare causes of hypercapnia. They either diminish total ventilation or lead to dynamic
hyperinflation and reduced tidal volume, while simultaneously causing increased work of breathing and carbon dioxide
production.
Medical impairments associated with obesity hypoventilation syndrome
Central nervous system
Cognitive deficit
Decrease neuronal drive
Upper airway
Obstructive sleep apnea
Increased intubation risk
Respiratory
Restrictive lung function
Pulmonary hypertension
Hypercapnia/hypoxemia
Metabolic
Central obesity
Metabolic syndrome
Chronic inflammation
IGF-1 deficit
Cardiovascular
Endothelial dysfunction
Coronary artery disease
Chronic heart failure
General
Peripheral edema
Increased morbi-mortality
Decreased physical activity
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.
Conflict of interest policy

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Clinical manifestations and diagnosis of obesity hypoventilation syndrome - UpToDate 02/01/21 18.

Official reprint from UpToDate®

Clinical manifestations and diagnosis of obesity

Obesity Hypoventilation Syndrome (OHS) is defined as the presence of awake alveolar

● Significant increase in waist:hip ratio (ie, central obesity)

chronic stable symptoms or chronic hypercapnic respiratory failure, about one-third

● Right heart failure from pulmonary hypertension (dyspnea on exertion, elevated

Laboratory tests — OHS may be associated with the following findings:

● Hypercapnia (arterial pressure of carbon dioxide [PaCO2] >45 mmHg) – Consistent

chronic respiratory failure [16,19,20]. A raised bicarbonate (>27 mmol/L) or base

● Hypoxemia (PaO2 <70 mmHg) – Hypoxemia is usually present. The calculated

● Polycythemia — Polycythemia due to recurrent hypoventilation- or OSA-associated

Evidence of right ventricle enlargement from pulmonary hypertension that complicates

The diagnostic approach focuses on establishing awake (often daytime) hypoventilation in

individuals or in patients who have OSA alone [1,4,6,14-16,23,24,34].

Indicators of chronic alveolar hypoventilation — In patients in whom OHS is suspected,

• Bicarbonate level >27 mEq/L – An elevated bicarbonate level greater than 27

Exclude other causes of hypercapnia and alveolar hypoventilation — For those in

● Serum chemistries and electrolytes – Electrolyte disturbances that may exacerbate

count may be consistent with neuropathy from eosinophilic myalgia. (See

● Thyroid function tests – Hypothyroidism may contribute to the chronic ventilatory

● Pulmonary function tests – Pulmonary function tests (PFTs) including spirometry,

● Imaging – A chest radiograph should be performed to exclude parenchymal lung

● Other – Rarely, a toxicology screen (eg, concomitant benzodiazepine or narcotic use)

IDENTIFY COEXISTENT SLEEP DISORDERED BREATHING

Ideally, in-laboratory polysomnography (PSG) is performed in all patients suspected as

● Obesity (body mass index [BMI] >30 kg/m2)

The absence of an alternative cause of hypercapnic hypoventilation is an important

Because symptoms are nonspecific, the diagnosis of OHS is frequently delayed. It is

of parenchymal abnormalities and restriction on pulmonary function tests. (See

● Neuromuscular (NM) disorders – NM disorders may be identified by history (eg, weak

● Hypothyroidism – Hypothyroidism is typically evident on laboratory testing. (See

● Mild to moderate pulmonary hypertension (PH) – Up to two-thirds of patients with

● Cardiovascular and metabolic comorbidities – Conditions such as hypertension,

SUMMARY AND RECOMMENDATIONS

● Obesity hypoventilation syndrome (OHS) is defined as the presence of awake alveolar

● OHS is a diagnosis of exclusion (obesity and awake alveolar hypoventilation which

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2. Randerath W, Verbraecken J, Andreas S, et al. Definition, discrimination, diagnosis

3. The American Academy of Sleep Medicine: International classification of sleep

4. Basoglu OK, Tasbakan MS. Comparison of clinical characteristics in patients with

5. Piper AJ, Grunstein RR. Obesity hypoventilation syndrome: mechanisms and

7. Castro-Añón O, Pérez de Llano LA, De la Fuente Sánchez S, et al. Obesity-

8. Harada Y, Chihara Y, Azuma M, et al. Obesity hypoventilation syndrome in Japan and

9. BaHammam AS. Prevalence, clinical characteristics, and predictors of obesity

12. Masa JF, Corral J, Caballero C, et al. Non-invasive ventilation in obesity

14. Nowbar S, Burkart KM, Gonzales R, et al. Obesity-associated hypoventilation in

hospitalized patients: prevalence, effects, and outcome. Am J Med 2004; 116:1.

17. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome

18. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute

21. Palm A, Midgren B, Janson C, Lindberg E. Gender differences in patients starting

23. Bingol Z, Pıhtılı A, Cagatay P, et al. Clinical predictors of obesity hypoventilation

24. Mokhlesi B, Tulaimat A, Faibussowitsch I, et al. Obesity hypoventilation syndrome:

breathing. J Clin Sleep Med 2013; 9:879.

30. Heinemann F, Budweiser S, Dobroschke J, Pfeifer M. Non-invasive positive pressure

32. Castro-Añón O, Golpe R, Pérez-de-Llano LA, et al. Haemodynamic effects of non-

33. Kauppert CA, Dvorak I, Kollert F, et al. Pulmonary hypertension in obesity-

bicarbonate in obesity hypoventilation syndrome. Respir Physiol Neurobiol 2013;

39. Martinez FJ, Bermudez-Gomez M, Celli BR. Hypothyroidism. A reversible cause of

42. Skatrud J, Iber C, Ewart R, et al. Disordered breathing during sleep in

43. Kessler R, Chaouat A, Weitzenblum E, et al. Pulmonary hypertension in the

45. Littleton SW, Mokhlesi B. The pickwickian syndrome-obesity hypoventilation

47. Resta O, Foschino-Barbaro MP, Bonfitto P, et al. Prevalence and mechanisms of

48. Jennum P, Ibsen R, Kjellberg J. Morbidity prior to a diagnosis of sleep-disordered