Crit Care Clin 24 (2008) 533549

Diagnosis and Management of Obesity

Hypoventilation Syndrome in the ICU
Won Y. Lee, MDa, Babak Mokhlesi, MD, MScb,*
a

Section of Pulmonary and Critical Care Medicine, The University of Chicago Pritzker
School of Medicine, 5841 South Maryland Avenue, Sleep Disorders Center W 4,
Chicago, IL 60637, USA
b
Section of Pulmonary and Critical Care Medicine, The University of Chicago Pritzker School
of Medicine, 5841 South Maryland Avenue, MC 0999/Room L11B, Chicago, IL 60637, USA

Historical perspective and denition

In 1955, Auchincloss and colleagues [1] described in detail the rst case of
a patient who had obesity hypoventilation syndrome (OHS). The following
year, Burwell and colleagues [2] compared patients who had OHS to an
obese, somnolent Charles Dickens character and popularized the description Pickwickian syndrome. The central features of OHS include obesity
(body mass index [BMI] R 30 kg/m2), chronic alveolar hypoventilation
leading to daytime hypercapnia (PaCO2 R 45 mm Hg), and sleep-disordered
breathing [3,4]. Essential to the diagnosis is exclusion of other causes of
alveolar hypoventilation, such as severe obstructive or restrictive pulmonary
disease, severe hypothyroidism, neuromuscular diseases, or other central
hypoventilation syndromes (Box 1).
Although obesity hypoventilation syndrome can exist autonomously, it is
frequently associated with obstructive sleep apnea (OSA), which is characterized by recurrent upper airway obstruction resulting in apneas, hypopneas, oxygen desaturation, and arousals from sleep. Approximately 90%
of patients who have OHS exhibit sleep-disordered breathing consisting of
obstructive apneas and hypopneas (apnea-hypopnea index [AHI] R 5),
whereas the remaining 10% of patients who have OHS have an AHI less
than 5 [46]. Because of this frequent association the term hypercapnic
OSA has been interchangeably used with OHS. In fact, most patients
who have OHS suer from severe OSA (AHI R 30) [4].

* Corresponding author.
E-mail address: bmokhles@medicine.bsd.uchicago.edu (B. Mokhlesi).
0749-0704/08/$ - see front matter 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.ccc.2008.02.003
criticalcare.theclinics.com

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LEE & MOKHLESI

Box 1. Common causes of hypercapnia other than obesity

hypoventilation syndrome
Chest wall restrictive disorders (eg, scoliosis)
Severe interstitial lung disease
Severe obstructive lung disease (FEV1 < 1 L or <35% predicted)
CNS structural defectsdtumor, cerebrovascular accidents,
brainstem or spinal cord lesions
Neuromuscular disorders
Severe hypothyroidism/myxedema
Severe electrolyte abnormalities (eg, hypophosphatemia and
hypocalcemia)
Idiopathic central alveolar hypoventilation
Metabolic alkalosis caused by high doses of loop diuretics

Morbidity and mortality

OHS is often unrecognized and treatment is frequently delayed, and can
cause secondary erythrocytosis, pulmonary hypertension, and cor pulmonale. The delay in recognizing and treating this condition increases health
care resource use and the likelihood of requiring hospitalization compared
with patients who have similar degrees of obesity [7]. The most common reasons for hospitalizations are dyspnea and acute-on-chronic hypercapnic respiratory failure. Once hospitalized, patients who have OHS are more likely
to require intensive care monitoring and invasive mechanical ventilation.
When compared to eucapnic morbidly obese hospitalized patients, OHS patients require more ICU admissions (40% versus 26%) and a large percentage also require long-term care on discharge (19% versus 2%) [8]. Although
many of these patients have had prior hospitalizations because of acuteon-chronic respiratory failure, the formal diagnosis of OHS is usually established late, in the fth or sixth decade of life, and after consultation by a
pulmonary and critical care specialist (Box 2) [5,8,9].
Compared to patients who have similar degrees of obesity, patients who
have OHS have a higher mortality. Earlier case series of hospitalized patients who had severe OHS reported a mortality rate approaching 50%, including cases of sudden unexpected deaths [10,11]. The reason for the
increased risk for mortality in these older series was attributed to progressive hypercapnia and obtundation or massive pulmonary embolism. In
two recent prospective studies, however, there were no in-hospital deaths
among a total of 64 consecutive patients who had OHS [8,12]. A retrospective study reported that 7 out of 15 patients who had OHS (46%) who refused long-term noninvasive positive airway pressure therapy died during
an average of 50-month follow-up period. In contrast, out of the 54 patients
who accepted and were adherent to long-term treatment with positive

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Box 2. Adverse events associated with undiagnosed

and untreated obesity hypoventilation syndrome
Increased health care costs
Increased need for ICU monitoring
Higher requirement for invasive mechanical ventilation during
hospitalization
Increased need for long-term care on discharge
Worse quality of life
Higher risk for pulmonary hypertension
Increased risk for death
airway pressure therapy, only 3 (6%) died [6]. Similarly, a prospective study
of 47 OHS patients (of which only 13% received long-term treatment of hypoventilation) were followed after hospital discharge for 18 months. The
mortality of patients who had OHS was 23% versus 9% in patients who
had a similar degree of obesity but did not have hypoventilation (adjusted
hazards ratio 4.0) and most deaths occurred in the rst 3 months after hospital discharge [8]. Other long-term studies have reported mortality rates of
less than 10% during a 2-year follow-up in patients who have OHS who are
adherent to noninvasive positive pressure ventilation (NPPV) [7,13,14].
Surprisingly, the degree of daytime hypoxia before the initiation of NPPV
therapy seems to be a better predictor of long-term mortality than the degree
of hypercapnia [14].
Pathophysiology
The mechanism by which morbid obesity leads to hypoventilation is complex and not fully understood. Proposed mechanisms include abnormal respiratory system mechanics because of obesity, impaired central responses
to hypercapnia and hypoxia, sleep-disordered breathing, and neurohormonal abnormalities, such as leptin resistance (Box 3) [4,15].
Obesity imposes a signicant mechanical load leading to a reduction in total respiratory system compliance, increased lung resistance, and a relative
state of respiratory muscle weakness all leading to increased work of breathing [1619]. However, obesity does not appear to be the only determinant of
hypoventilation because less than a third of morbidly obese patients develop
chronic hypercapnia [20,21]. Other determinants of hypoventilation include
a blunted central responsiveness to hypercapnia and hypoxia, a state of leptin
resistance (a satiety protein that increases ventilation), and sleep-disordered
breathing. The role of sleep-disordered breathing in the pathogenesis of hypoventilation has been well established by the resolution of hypercapnia in most
patients who have OHS with either positive airway pressure therapy or tracheostomy without any concomitant change in body mass [6,2228].

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LEE & MOKHLESI

Box 3. Mechanisms implicated in obesity hypoventilation

syndrome
Decreased chest wall and lung compliance secondary to excess
adipose tissue
Increased upper airway and total respiratory system resistance
Respiratory muscle weakness
Impaired central driveddecreased ventilatory response to
hypercapnia and hypoxia
Increased work of breathing
Coexistent obstructive sleep apnea
Neurohormonal abnormalitiesdleptin resistance
Epidemiology
Because of the global obesity epidemic and the high prevalence of OSA in
the general population, critical care physicians are likely to encounter patients who have acute-on-chronic respiratory failure attributable to OHS
in their clinical practice. The prevalence of OHS amongst patients who
have OSA has been estimated between 10% and 20% and is higher in the
subgroup of patients who have extreme obesity (Fig. 1) [20,21]. The prevalence of OHS is even higher (31%) in obese patients admitted to inpatient
general medicine services [8].

Clinical presentation
OHS is slightly more prevalent in men and most patients are diagnosed in
their fth or sixth decade of life. The vast majority of patients have the classic symptoms of OSA, including loud snoring, nocturnal choking episodes
with witnessed apneas, excessive daytime sleepiness, and morning headaches. In contrast to eucapnic OSA, patients who have stable OHS frequently complain of dyspnea and may have signs of cor pulmonale. With
acute-on-chronic hypercapnic respiratory failure, patients who have OHS
can develop worsening dyspnea and obtundation in severe cases.
When evaluating a patient with hypercapnia, a thorough investigation
should be performed. A complete neurologic examination can diagnose
neuromuscular diseases, primary central nervous system structural defects,
or spinal cord injury. Medication and substance use should be carefully reviewed, searching for sedative, narcotic, or ethanol use that may lead to central nervous system depression, and a toxicology screen should be
considered. Other conditions that are frequently associated with hypercapnia should also be excluded (see Box 1).
Physical examination ndings can include a plethoric obese patient who
has an enlarged neck circumference, crowded oropharynx, and a prominent

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537

Percent of patients with OHS

40

30

20

10

0
30-34

35-39

>40

Body Mass Index Categories (kg/m2)

Fig. 1. Prevalence of OHS in patients who have OSA by categories of BMI in two studies performed in France [20] and the United States [21]. Squares, United States (n 359, mean BMI
43 kg/m2); circles, France (n 1141, mean BMI 34 kg/m2). The higher prevalence of extreme
obesity in the United States is associated with a higher prevalence of OHS. Sleep Breath
2007;11:122; with permission.)

pulmonic valve closure (loud P2) on cardiac auscultation. The patient may
be somnolent because of acute-on-chronic hypercapnia. A careful inspection
of the breathing pattern may reveal paradoxical breathing suggestive of diaphragmatic dysfunction or impending respiratory failure. Patients who
have OHS are typically rapid shallow breathers during steady state and tachypnea may become even more signicant during an exacerbation [19].
Several laboratory ndings are supportive of OHS, yet the denitive
test for alveolar hypoventilation is an arterial blood gas performed on
room air. Elevated serum bicarbonate level attributable to metabolic compensation of respiratory acidosis is common in patients who have OHS
and points toward the chronic nature of hypercapnia [21]. Assessment
of the pH helps direct the clinicians decision on admission to the general
medical oor, noninvasive or step-down respiratory care unit, or ICU. In
general, those who have a pH less than 7.30 should be monitored in an
ICU setting, whereas those who have a pH greater than 7.30 and do
not have signicant obtundation can be managed in a noninvasive respiratory care unit or step-down unit with close supervision. Other laboratory testing should evaluate for secondary erythrocytosis, severe
hypothyroidism, and drug intoxication. In patients who have cor pulmonale and pulmonary hypertension, chest imaging reveals enlargement of
the cardiac silhouette and prominent pulmonary vascular distribution. In
these patients, an electrocardiogram frequently reveals evidence of right
ventricular hypertrophy and right atrial enlargement, which can be conrmed by echocardiography.

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Once the patient has recovered from the acute exacerbation, a complete
pulmonary function test (PFT) should be performed to exclude other potential causes of hypercapnia (see Box 1). Common PFT ndings in patients
with OHS include a mild to moderate restrictive defect and reduction in expiratory reserve volume attributable to body habitus, accompanied by a normal FEV1/FVC ratio. Patients who have OHS may also have mild reductions
in maximum expiratory and inspiratory pressures related to the combination
of abnormal respiratory mechanics and weak respiratory muscles [19].

Therapeutic options
In an ICU setting there are several therapeutic modalities that can improve ventilation and oxygenation in patients who have OHS who are experiencing an acute-on-chronic hypercapnic respiratory failure: NPPV,
endotracheal intubation with invasive mechanical ventilation, and tracheostomy with or without mechanical ventilation. Although most of these
patients need supplemental oxygen therapy in addition to positive airway
pressure therapy, supplemental oxygen alone is inadequate and does not
improve ventilation [29]. Continuous positive airway pressure (CPAP), although eective in many patients who have stable OHS [22,30,31], should
not be used in cases of acute-on-chronic hypercapnic respiratory failure
due to its inability to improve alveolar ventilation when compared to NPPV.
Pharmacologic interventions, such as acetazolamide or medroxyprogesterone, can improve ventilation in some patients when used in conjunction
with positive airway pressure therapy but are ineective when used as monotherapy, particularly in cases of acute-on-chronic hypercapnic respiratory
failure [4]. Phlebotomy has not been systematically studied in patients
who have OHS who develop secondary erythrocytosis. Secondary erythrocytosis is a physiologic response to tissue hypoxia to enhance oxygen carrying capacity. Hyperviscosity impairs oxygen delivery, however, and can
counteract the benecial eects of erythrocytosis. In adult patients who
have congenital cyanotic heart disease, phlebotomy has been recommended
if the hematocrit is greater than 65% only if symptoms of hyperviscosity are
present [32]. It is dicult to extrapolate this recommendation to patients
who have OHS, however, because many symptoms of hyperviscosity are
similar to the symptoms of OHS. Reversing hypoventilation and hypoxemia
with positive airway pressure therapy eventually improves secondary erythrocytosis and phlebotomy is rarely needed in patients who have OHS [33].

Noninvasive positive pressure ventilation

Contrary to eucapnic OSA, eective treatment strategies for OHS must
relieve upper airway obstruction and increase alveolar ventilation. The

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539

therapy of choice for the acutely decompensated patient who has OHS with
hypercapnic respiratory failure is NPPV. NPPV can be applied with volumelimited, or more commonly, pressure-limited devices (eg, bilevel positive airway pressure [bilevel PAP] or pressure support ventilation). Although these
two modes of NPPV have not been compared in patients who have acuteon-chronic hypercapnic respiratory failure attributable to OHS, both modes
seem to be equally eective in patients who have acute exacerbation of
chronic obstructive pulmonary disease (COPD) and in patients who have
chronic respiratory failure because of restrictive chest wall disorders [34
37]. Pressure-limited NPPV is easier to tolerate; however, volume-limited
NPPV provides a more stable tidal volume and can generate higher peak
pressures if the patient has higher airway resistance [38,39]. Positive pressure
should be administered during sleep and wakefulness during the acute hospital setting. Bilevel PAP provides inspiratory positive airway pressure
(IPAP) and expiratory positive airway pressure (EPAP), each of which is
set independently. EPAP maintains upper airway patency while the delta between the IPAP and the EPAP represents pressure support ventilation. Increasing the delta therefore leads to larger tidal volumes and increased
ventilation. Given that most patients who have OHS have concomitant severe OSA, the EPAP typically needs to be set at a higher level compared
with patients requiring NPPV because of neuromuscular disease or acute exacerbation of COPD [4]. The decision on pressure- or volume-limited ventilation should be based on local expertise and sta familiarity, and should be
tailored to the individual patient [38].
The use of NPPV in patients experiencing acute-on-chronic hypercapnic
respiratory failure associated with OHS is attractive because it improves ventilation and oxygenation, may avoid invasive mechanical ventilation, and is
readily available. The physiologic benets of NPPV include decreasing the
work of breathing by unloading the respiratory muscles, improving central
chemosensitivity after few days of use, and opening the atelectatic lung regions
[22,24,40]. NPPV, when applied correctly, can acutely improve hypersomnolence, dyspnea, and obstructive apneas/hypopneas [6,40,41]. Moreover,
NPPV has a modest benecial eect on right ventricular function [42].
Long-term therapy in patients who are adherent with NPPV can lead to further improvements in gas exchange and increases survival compared with
less adherent patients. Patients who have OHS who used positive airway pressure therapy for more than 4.5 hours per day experienced larger improvement
in PaCO2 and PaO2 compared with less adherent patients (DPaCO2 7.7 versus
2.4 mm Hg, P!.001; DPaO2 9.2 versus 1.8 mm Hg, P!.001) [22]. Recent large
observational studies have reported increased mortality and cardiovascular
morbidity in patients who had severe OSA who were not adherent with positive airway pressure therapy [43,44]. Although these reports did not exclusively include patients who had OHS, most patients who have OHS do have
severe OSA. The survival benets of NPPV are sustained at least up to 2 years
in patients who have OHS who are adherent with therapy [13,14].

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Approach to initiating and monitoring noninvasive positive pressure

ventilation in obesity hypoventilation syndrome
Just as important as recognizing when to initiate NPPV is the recognition
of clinical contraindications that make NPPV unsafe. Clinical criteria
should therefore be established for selecting patients who should be admitted to the ICU and those who should be observed in a step-down respiratory
care unit. More importantly, decisions on where NPPV should be initiated
(emergency room, ICU, or step-down respiratory care unit) should depend
on sta experience and available local resources [45,46]. An appropriately
responsive patient who is hemodynamically stable without life-threatening
arrhythmias can be managed with NPPV in a step-down respiratory care
unit under close nursing and respiratory care supervision [47]. Those individuals who have a pH less than 7.30, altered mentation, or are intolerant
of NPPV should be directly admitted to the ICU and may require invasive
mechanical ventilation (Boxes 4 and 5).
The importance of careful observation of the acutely hypercapnic obese
patient using NPPV cannot be overemphasized because potential catastrophes, such as massive aspiration, unnoticed progressive respiratory failure,
and even death, can result if inadequately supervised. Our experience is similar to prior studies that NPPV is as labor intensive as endotracheal intubation and invasive mechanical ventilation [48]. A multidisciplinary approach
involving skilled nurses, respiratory therapists, and intensivists is therefore
crucial to successful titration of NPPV [46]. In addition, institutions that
have successfully implemented NPPV programs for patients who have
acute-on-chronic hypercapnic respiratory failure have established a centralized monitoring unit with a favorable nurse-to-patient ratio to ensure early
recognition of NPPV failure requiring invasive mechanical ventilation.
Several clinical parameters should be monitored frequently during the
rst hours of initiating NPPV, such as blood pressure, heart rate, mental status, evidence of respiratory distress, oxygen saturation, and arterial blood
gases [47,49]. Successful alveolar ventilation leads to tidal volumes of 8 to
10 mL/kg and decreases the respiratory rate to fewer than 25 breaths per

Box 4. Indications for ICU monitoring in patients

who have obesity hypoventilation syndrome
Significant acute acidemia (pH < 7.30)
Hemodynamic instability or unstable cardiac rhythm
Altered mental status
Multiple organ failuredelevated acute physiology and chronic
health evaluation (APACHE II) or sequential organ failure
assessment (SOFA) score
Intolerance to noninvasive positive pressure ventilation

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541

Box 5. Contraindications to noninvasive positive pressure

ventilation
Hemodynamic instability or unstable cardiac arrhythmia
Inability to protect airway or adequately clear secretions
Active upper gastrointestinal bleeding
Significant abdominal distension
Cerebrovascular accident or intracranial hemorrhage
Interface contraindications
Facial/cranial/eye trauma or recent facial surgery
Persistent epistaxis
Unable to appropriately fit mask
Uncooperative or agitated patient
minute. Arterial blood gases should be followed closely over the rst 2 hours
with special attention to pH and PaCO2 trends. Box 6 provides early clinical
markers that indicate NPPV failure and should alert the clinician of impending respiratory failure. The rate of NPPV failure in patients who have
COPD (not OHS) experiencing an acute hypercapnic respiratory failure
has been reported between 5% and 40% [49]. The best predictor of early
NPPV failure (within the rst 1 to 3 hours) was the lack of improvement
in pH and PaCO2 after 1 hour of NPPV [50]. A more recent prospective study
reported an NPPV failure rate of 36% among 33 consecutive morbidly
obese patients developing acute respiratory failure from multiple causes.
In this study, a higher BMI was predictive of NPPV failure (46.9 kg/m2 in
successful NPPV versus 62.5 kg/m2 in NPPV failure) [51]. Ortega Gonzalez
and colleagues [12] did not report any cases of NPPV failure in 17 consecutive patients admitted to an ICU with an acute-on-chronic hypercapnic respiratory failure.
Approximately 50% of morbidly obese patients who have acute respiratory failure who require emergent endotracheal intubation have a dicult
intubation dened as requiring more than three attempts by experienced clinicians [51,52]. These patients are also at increased risk for peri-intubation
complications, including cardiorespiratory arrest. The clinician planning to
intubate these patients should be cognizant of the limited neck mobility and
the diculty with visualizing the vocal cords because of the crowded oropharynx [52]. Furthermore, obese patients are at risk for severe oxygen desaturation that can occur precipitously because of a lower functional
residual capacity and atelectasis that is exacerbated in the supine position
[19,53]. For these reasons, the most experienced clinician should attempt
to intubate a decompensated patient who has OHS who has failed a trial
of NPPV. Finally, in the dicult airway the clinician may consider placing
a temporary laryngeal mask device or perform intubation with the assistance of a exible beroptic bronchoscope.

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LEE & MOKHLESI

Box 6. Clinical features suggestive of noninvasive positive

pressure ventilation failure and need for invasive
mechanical ventilation
Deterioration of mental status or psychomotor agitation
pH persistently less than 7.25 or lack of improvement in
hypercapnia after 1 to 2 hours of NPPV
Persistent and refractory hypoxemia
Lack of improvement in tachypnea and dyspnea
Hypotension or bradycardia
Increased use of accessory muscles with impending respiratory
failure
Increased risk for aspiration and inability to clear secretions
Poor tolerance of the interface

Setting up noninvasive positive pressure ventilation equipment: choice

of interface and ventilatory mode
The two most commonly used interfaces are the oronasal mask (full face
mask) or the nasal mask, and an appropriate tting interface ensures adequate gas exchange without signicant leakage. Oronasal masks are usually
recommended in acutely ill patients because they allow the delivery of higher
pressures with less leakage and permit mouth breathing [38]. Unfortunately
full-face interfaces can be uncomfortable and it is dicult for patients to
communicate or eat. Nasal masks can be more comfortable and better tolerated especially in the claustrophobic patient, but to achieve adequate pressure delivery, a closed mouth is required. One small study found that in
stable patients who had chronic hypercapnic respiratory failure, NPPV applied through an oronasal mask was slightly more eective in lowering the
PaCO2 because of an increase in the tidal volume compared with nasal masks
[54]. Patients experiencing an acute-on-chronic hypercapnic respiratory failure tend to perform a signicant amount of mouth breathing, therefore in
this setting an oronasal mask is advisable [38]. The interface can be later
switched to a nasal mask once the patient is more stable and if prolonged
NPPV is deemed necessary. The choice of interface should be highly individualized; to establish an eective NPPV protocol it is imperative to have
a wide variety of interfaces available. If a patient has been previously tted
with a mask as an outpatient, then that particular type of mask could be
used. The mask should be secured rmly with a head strap but excessive
tightening should be avoided because it can increase leakage.
Pressures should be titrated slowly to allow the patient to acclimate to the
device. Careful attention should be paid to nasal passage drying, nasal
bridge skin breakdown, or discomfort from an improperly tting mask.

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543

Heated humidity can prevent drying of the nasal passages and a hydrocolloid
dressing can be applied at the nasal bridge to prevent ulceration [38].
Pressure-limited NPPV can be delivered by conventional modern ventilators that provide biphasic positive airway pressure ventilation or by way of
bilevel PAP generators. Volume preset ventilators can be used for NPPV
also based on availability and local expertise. Given that pressure-limited
NPPV is easier to tolerate [39], bilevel PAP should be considered rst-line
therapy for noninvasive support in patients who have OHS experiencing
an acute-on-chronic hypercapnic respiratory failure. Pressure settings
should be tailored to each patient; however, a reasonable starting point includes an EPAP set at 5 cm H2O and the IPAP set at 10 cm H2O. A repetitive cyclical pattern of oxygen desaturationdmeasured by pulse oximetry
(SpO2)dis typically associated with obstructive apneas and hypopneas.
With real-time monitoring of the pulse oximetry tracing, the EPAP can be
gradually increased until the disappearance of repetitive dips in SpO2 and
resolution of clinically apparent apneas or snoring during sleep. The
IPAP can then be increased until there is an acceptable level of steady oxygenation (SpO2O92%) suggestive of an improvement in ventilation. In
studies that have reported signicant improvement in hypercapnia and hypoxia with bilevel PAP therapy, the IPAP was at least 8 to 10 cm H2O greater
than EPAP to achieve adequate ventilation [6,55]. Patients who have acuteon-chronic hypercapnic respiratory failure attributable to OHS typically require high IPAP (mean of 18 cm H2O; range 1230 cm H2O) and EPAP
(mean of 9 cm H2O; range 513 cm H2O) [6,12]. Despite delivering high positive airway pressure many of these patients remain hypoxic and require the
addition of supplemental oxygen to positive airway pressure therapy
(Fig. 2). Although the maximal amount of inspiratory pressure necessary
or tolerated in patients who have OHS with acute-on-chronic hypercapnic
respiratory failure has not been systematically studied, in general patients
have diculty tolerating IPAP greater than 20 cm H2O. Similarly, patients
who have COPD exacerbation or chest wall deformity had little to be gained
by increasing inspiratory pressures more than 25 cm H2O [56].
Initially NPPV should be continuous during nighttime and during the day.
Patients should be given breaks to allow eating or communication with family. Concurrent therapy for cor pulmonale should be initiated with diuretics
and supplemental oxygen. Some patients may not reach eucapniadreecting
chronic respiratory acidosisdtherefore following the pH may be the
best marker of acute clinical improvement. Patients should be expected to
improve within 1 to 3 hours of therapy, with most patients who have
OHS reaching near-normal pH within 12 to 24 hours. Acute-on-chronic hypercapnic respiratory failure in patients who have OHS resolves more rapidly compared with patients who have COPD and congestive heart failure
[12]. Once acidbase stability is achieved (a persistent pH greater than
7.35) then daytime NPPV can be discontinued, yet nighttime support
should be continued.

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LEE & MOKHLESI

OHS risk factors?

BMI 35 kg/m2
PaCO2 45 mm Hg
History suggestive of sleepdisordered breathing

Yes

Unstable medical status?

pH < 7.25
Altered mental status
Hemodynamic instability
Multi-organ failure

Yes

Transfer to ICU
Consider invasive
mechanical ventilation

No
Contraindications to NPPV?
Hemodynamic instability
Inability to protect airway
Unable to clear secretions
Psychomotor agitation
Stroke
Upper gastrointestinal bleeding
Abdominal distention
Unable to properly fit interface
Interface intolerance

Yes

No
Initiating and monitoring NPPV in a respiratory care unit or ICU
Closely monitor respiratory rate, heart rate, blood pressure, oxygen saturation, and
mental status
Reassess arterial blood gases in 1-2 hours
Favorable nurse or respiratory therapist to patient ratio
InterfaceStart with oronasal mask and if intolerant use nasal mask
Bi-level PAP titration
EPAP: Start at 5 cm H2O
Increase by 2 cm H2O to alleviate clinically obvious apneas,
snoring, and repetitive SpO2 desaturations
IPAP: Start at 10 cm H2O
Increase by 2 cm H2O to improve a steady SpO2 at 92
IPAP typically needs to be at least 8 to 10 cm H2O above EPAP to
achieve adequate ventilation in OHS
Add supplemental oxygen to bi-level PAP to keep SpO2 92

Goals achieved?
Decrease work of breathing (RR < 25 breaths/min)
Improvement in acidosis and hypercapnia within 1-2 h
Sustained improvement in hypoxia (SpO2 92 )

No

Yes
Continue NPPV
NPPV should be continuous during day and night
Breaks to allow eating or communication
Most OHS patients reach near normal pH within
12-24 h of NPPV

Fig. 2. Management of patients who have OHS requiring hospitalization because of acute-onchronic hypercapnic respiratory failure.

The use of medications that may further exacerbate hypoventilation, especially sedative-hypnotic or narcotic agents, should be limited. In addition
patients who have OHS are at high risk for thromboembolic diseases [10,11];
therefore adequate deep vein thrombosis prophylaxis is essential. Finally,
elevating the head of the bed can decrease the risk for aspiration and may
decrease the pressure required to resolve obstructive apneas, hypopneas,
and hypoventilation [57,58].

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In follow-up, an outpatient polysomnogram with positive airway pressure titration should be performed after discharge from the hospital.
Many patients who have OHS who initially require bilevel PAP can be
switched to CPAP after the resolution of hypercapnia [6,59]. Furthermore,
with adequate adherence with positive airway pressure therapy long-term
supplemental oxygen can be discontinued in many patients [22].
Tracheostomy
Tracheostomy should be reserved for patients who have refractory OHS
who have failed other modes of ventilatory support, are intolerant of NPPV,
have severe cor pulmonale, or have a longstanding history of nonadherence
with outpatient NPPV therapy. Tracheostomy may also become necessary
in a subset of patients who cannot be successfully extubated and liberated
from invasive mechanical ventilation. Tracheostomy bypasses the crowded
upper airway and can substantially decrease apneas and hypopneas in patients who have uncomplicated OSA. In patients who have OHS tracheostomy can lead to improvement but not complete resolution of sleepdisordered breathing. Nevertheless, the improvement in the severity of
sleep-disordered breathing after tracheostomy can lead to the resolution
of hypercapnia [60]. The clinician should be aware of anatomic characteristics of obesity that make tracheostomy technically challenging. An inferiorly
located larynx creates the potential for postoperative vascular complications
because the tracheostomy tube is closer to the great vessels of the chest, and
thick layers of adipose tissue within the tracheostomy site may stimulate
increased production of granulation tissue leading to infection and bleeding
[61]. Tracheostomy should be performed by an experienced otolaryngologist
in carefully selected patients.
Discusssion
Because of the global obesity epidemic and the high prevalence of OSA in
the general population, critical care physicians are likely to encounter patients
who have acute-on-chronic hypercapnic respiratory failure attributable to
OHS in their clinical practice. We believe that early recognition of OHS leads
to eective treatment and likely results in a decrease in morbidity and mortality. In the ICU setting, implementation of NPPV has marked benecial eects
leading to improvement in alveolar ventilation, hypercapnia, and hypoxia,
and can avoid the need for endotracheal intubation and invasive mechanical
ventilation. It is essential for these patients to be discharged from the ICU
on adequate NPPV therapy. Ultimately, the improvements in outcomes are directly related to adherence with positive airway pressure therapy. Early outpatient follow-up is therefore imperative and should include repeat measurement
of arterial blood gases and objective assessment of adherence with therapy because patients frequently overestimate adherence.

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LEE & MOKHLESI

Summary
 OHS is characterized by obesity (BMI R 30 kg/m2), daytime hypercapnia (PaCO2 R 45 mm Hg), and sleep-disordered breathing in the absence
of other known causes of hypercapnia.
 Patients who have OHS have increased health care resources use and
require more frequent hospitalization because of dyspnea or acute-onchronic hypercapnic respiratory failure compared with patients who
have similar degrees of obesity.
 The pathophysiology of OHS is multifactorial and includes abnormal
respiratory system mechanics attributable to obesity, blunted central response to hypercapnia and hypoxia, sleep-disordered breathing, and
neurohormonal abnormalities, such as leptin resistance.
 NPPV with bilevel PAP is the treatment of choice in acute and chronic
hypercapnic respiratory failure in patients who have OHS.
 Management of acute-on-chronic hypercapnic respiratory failure can be
performed in a respiratory care unit with close nursing supervision,
a dedicated management plan, and careful recognition of progressive respiratory failure requiring invasive mechanical ventilation.
 Signicant weight loss, typically by weight reduction surgery, or longterm adherence with positive airway pressure therapy (CPAP or bilevel
PAP) are the therapeutic options that will ultimately improve the high
morbidity and mortality associated with OHS.

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