HHS Public Access: Obesity Hypoventilation Syndrome

HHS Public Access
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Curr Pulmonol Rep. Author manuscript; available in PMC 2016 March 01.
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Published in final edited form as:

Curr Pulmonol Rep. 2015 March 1; 4(1): 42–55. doi:10.1007/s13665-015-0108-6.
Obesity Hypoventilation Syndrome

Safal Shetty, MD and
Division Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine,
University of Arizona, 1501 N Campbell Ave., Rm 2342D, Tucson, AZ 85724, USA, Tel:
520-626-6109, Fax: 520-626-1876
Sairam Parthasarathy, MD
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Division Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Arizona
Respiratory Center, University of Arizona, 1501 N Campbell Ave., Rm 2342D, Tucson, AZ 85724,
USA, Tel: 520-626-6109, Fax: 520-626-1876
Safal Shetty: [email protected]; Sairam Parthasarathy: [email protected]
Abstract
Obesity hypoventilation syndrome is a respiratory consequence of morbid obesity that is
characterized by alveolar hypoventilation during sleep and wakefulness. The disorder involves a
complex interaction between impaired respiratory mechanics, ventilatory drive and sleep-
disordered breathing. Early diagnosis and treatment is important, because delay in treatment is
associated with significant mortality and morbidity. Available treatment options include non-
invasive positive airway pressure (PAP) therapies and weight loss. There is limited long-term data
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regarding the effectiveness of such therapies. This review outlines the current concepts of clinical
presentation, diagnostic and management strategies to help identify and treat patients with obesity-
hypoventilation syndromes.
Keywords
Obesity hypoventilation syndrome; Obstructive sleep apnea; Obesity; Noninvasive ventilation
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Correspondence to: Sairam Parthasarathy, [email protected].

Compliance with Ethics Guidelines
Conflict of Interest Statement
Dr. Parthasarathy reports grants from NIH/NHLBI, Patient Centered Outcomes Research Institute, US Department of Defense, grants
from NIH (National Cancer Institute) NCI, US Department of Army, Johrei Institute, personal fees from American Academy of Sleep
Medicine, Younes Sleep Technologies, Ltd., Niveus Medical Inc., and Philips-Respironics, Inc., outside the submitted work. Dr.
Parthasarathy also reports personal fees from American College of Chest Physicians, non-financial support from National Center for
Sleep Disorders Research of the NIH (NHLBI), USMLEWorld Inc., UpToDate Inc., and Philips-Respironics, Inc., outside the
submitted work. Dr. Parthasarathy also states has a patent UA 14-018 U.S.S.N. 61/884,654; PTAS 502570970 pending.
Dr. Shetty does not have any conflict of interest to declare.
Human and Animal Rights and Informed Consent
This article contains no studies with human or animal subjects performed by the author.
Shetty and Parthasarathy Page 2
Introduction
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Obesity is a global epidemic with increased prevalence over the last three decades. A recent
study on the prevalence of obesity in adults in the United States showed a prevalence of
35.5% among adult men and 35.8% among adult women [1]. Obesity hypoventilation
syndrome (OHS) is defined as a combination of Obesity (BMI>40 kg/m2), daytime
hypoventilation characterized by hypercapnia and hypoxemia (PaCO2 > 45 mm Hg and
PaO2 < 70 mm Hg at sea level) and sleep-disordered breathing (SDB) in the absence of an
alternative cause for hypoventilation like obstructive or restrictive lung disease, chest wall
disorders like kyphoscoliosis, neuromuscular disorders and congenital central
hypoventilation [2–4]. Approximately 90% of SDB in obesity hypoventilation syndrome is
Obstructive sleep apnea (OSA), with the remaining 10% of patients manifesting sleep-
related hypoventilation characterized by hypoxemia which is unrelated with obstructive
events of OSA – namely obstructive apneas or hypopneas [5, 6].
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Epidemiology
The precise prevalence of OHS in the general population is unclear, but is estimated to be
between 0.15% and 0.3%[7]. The prevalence of OHS in obese individuals was found to be
much higher at 19 to 31 % [8, 9]. A recent prospective and observational study with an
objective to determine the prevalence of OHS in hospitalized patients was conducted in
9,480 patients at a tertiary care hospital.[7] Patients with wake hypercapnia as demonstrated
by PaCO2 > or equal to 45 mmHg after arterial blood gas analysis were included. Three
hundred and thirty patients (3.4%) meeting the inclusion criteria were analyzed and 35.5%
of patients had chronic hypoventilation of which 24.6% (27 patients) was related to OHS
[7]. Other studies including a total of 1,326 patients, on evaluation of patients referred to
sleep centers with clinical symptoms of OSA found the prevalence of OHS to range from
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11–20%, with an overall prevalence rate of nearly 16% [5, 10–12]. Retrospective studies on
evaluation of 1,927 patients with a known diagnosis of OSA found the prevalence of OHS to
range from 9–14%, with an overall prevalence of 11% [13–15]. Therefore, the prevalence of
OHS can be said to be variable and dependent on the population that was studied, with the
prevalence rate to be least in population-based cohorts and the most in hospitalized patients.
The hospitalized patients are more likely to meet the hypercapnia criterion, which has led
some to suggest that the definition of OHS may need to be revisited. [16]
Pathophysiology
In healthy individuals, the arterial pH is maintained within a narrow range that is effected by
changes in alveolar ventilation in relation to the metabolic rate and renal acid-base status. In
patients with OHS, a complex interaction between abnormal respiratory mechanics, central
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respiratory drive, sleep-disordered breathing and Leptin resistance takes place and leads to
centrally (“respiratory controller”) facilitated alveolar hypoventilation. During sleep,
alveolar hypoventilation leads to nocturnal hypercapnia and hypoxia, which over time leads
to resetting of the chemostat of the respiratory controller and consequent daytime
hypercapnia and hypoxemia. The hypercapnia of OHS may be augmented by Leptin
resistance. Essentially, Leptin is a respiratory stimulant that augments respiratory controller
function and both leptin resistance associated with obesity and leptin deficiency can produce
defects in upper airway neuromechanical control.[17] However, the application of PAP over
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a short period of time can correct daytime hypercapnia [18].
Respiratory Mechanics
OHS patients have significant impairment of the respiratory system mechanics when
compared to equally obese eucapnic patients with or without sleep disordered breathing
[10]. In morbid obesity, central fat accumulation imposes a significant load on the
respiratory system, with overall effect of marked decrease in lung volumes, in lung and
chest wall compliance and increased airway resistance, in all contributing to a higher work
of breathing.[19] OHS patients show reductions in vital capacity (VC), total lung capacity
(TLC) and residual volume (RV) in comparison to eucapnic obese individuals at similar
levels of BMI [20, 21]. Individuals with OHS have greater degree of central obesity
reflected by larger neck circumferences and higher waist: hip ratios than those with eucapnic
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obesity or OSA, which explains the lower lung volumes seen in such individuals [10].
Tidal breathing at low resting lung volumes is partly responsible for significant reduction in
both chest wall and lung compliance [22–24] and the observed increase in airway
resistance[25]. When compared to subjects who are of normal weight, respiratory system
compliance has been shown to be about 20% less in eucapnic obese individuals and almost
60% less in patients with OHS[23, 26]. Small airway closure during exhalation can occur
while breathing at low lung volumes, thus creating expiratory flow limitation and intrinsic
positive and expiratory pressure (PEEPi) [27–29]. Such PEEPi, in turn, imposes an
additional threshold load on inspiratory muscles before any inspiratory flow is generated
thereby further increasing the work of breathing [27, 28, 30].
Patients with OHS have a significantly greater work of breathing when compared to
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individuals with normal weight or eucapnic obese patients with OSA while breathing
spontaneously on room air [27, 31]. Supine posture can further worsen the respiratory
system compliance [23] and functional residual capacity (FRC)[29], while increasing upper
airway inspiratory resistance to airflow [28]. Increased upper airway resistance is seen in
both the sitting and in the recumbent position in patients with OHS when compared to
eucapnic OSA patients who demonstrate resistance only in the supine position [32].
Hypoxemia is much more common in patients with OHS when compared to individuals with
eucapnic obesity [10]. Low ERV in morbidly obese individuals contributes to ventilation
perfusion mismatch, which is worsened in the supine posture. In order to optimize the
oxygen cost of breathing obese individuals adapt by breathing small tidal volumes and at
higher respiratory rates or “rapid shallow breathing” which is energy inefficient [19, 33–35].
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This pattern of breathing contributes to dead space ventilation and to hypoxia.

[33]Individuals with OHS are exposed to prolonged periods of daytime and nocturnal
hypoxia and are consequently at higher risk for pulmonary hypertension [36], congestive
heart failure and cor pulmonale [37, 38].
Respiratory muscle function is impaired and worse in the supine position in OHS when
compared to eucapnic morbidly obese individuals [39–41]. Several theories have been
postulated to explain this observation. Diaphragmatic impairment by mechanical
overstretching by abdominal fat [41], chronic hypoxia and hypercapnic state [42], low
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insulin growth factor (IGF-I) levels, reduced ventilatory drive are all potential mechanisms
[43].
Central Respiratory drive

Eucapnic obese individuals have a higher rate of oxygen consumption and CO2 production
at baseline. This is generally compensated by increased respiratory drive to increase minute
ventilation and maintain alveolar ventilation [28, 44]. However, individuals with OHS fail to
compensate their respiratory drive in response to the added load created by excess weight,
thus permitting a gradual increase in PCO2 [32, 45, 46]. Central ventilatory responsiveness
to both hypoxia and hypercapnia are attenuated in OHS compared to non-obese and
eucapnic obese patients with or without OSA [47, 48]. The decreased ventilatory response is
attributed secondary to the blunted neural response to hypercapnia [46, 47], which in turn
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has been shown to improve within days or weeks after initiating PAP therapy, in the absence
of significant change in weight [49–52].
Sleep disordered breathing

OHS is strongly associated with sleep disordered breathing (90%), most commonly OSA
[53] and about 10% of the time of the time being primarily sleep-related hypoventilation
[54]. Wake hypercapnia is seen only in minority of patients with severe OSA. Meta-analysis
of 15 studies, found that patients with hypercapnia had higher BMI and AHI and lower lung
volumes consistent with restrictive lung physiology and more significant hypoxia on
overnight pulse oximetry when compared to eucapnic obese patients with OSA[8].
Leptin resistance and OHS

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Leptin is a protein synthesized by adipose tissue. Leptin acts on the central respiratory center
to stimulate ventilation and Leptin levels are noted to be increased in obese individuals with
higher serum leptin levels in patients with OSA and OHS when compared to those without
such sleep-disordered breathing [55–58]. Increased levels of Leptin in human obesity may
compensate for the increased load on the respiratory system by maintaining adequate
ventilation [59]. But, this stimulatory effect of Leptin is reduced in some individuals hence
predisposing them to hypoventilation and consequent hypercapnia [56].
Campo and colleagues found that in obese patients, higher concentrations of serum leptin
are associated with a reduced respiratory drive and a reduced hypercapnic response [60].
Hypercapnic OSA patients have significantly lower hypercapnic ventilatory response when
compared to eucapnic OSA patients with similar leptin levels [56]. Consequently, in humans
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with OHS, Leptin resistance is thought to contribute to the pathophysiology in a manner

similar to that described in a leptin-deficient mouse model manifested by reduction in lung
volumes, compliance, abnormal respiratory muscle function, and defects in upper airway
neuromechanical control[17] [61, 62].
Clinical features and diagnosis

OHS is a diagnosis of exclusion that requires evaluation for other potential causes of
hypoventilation and hypercapnia such as obstructive or restrictive lung diseases,
neuromuscular disease, severe restrictive chest wall disorders, metabolic causes like
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hypothyroidism and congenital hypoventilation syndromes [2–4]. Patients with OHS are
diagnosed either with a presentation of acute on chronic respiratory failure to the hospital or
on routine outpatient evaluation by a pulmonologist or sleep physician [6]. Diagnosis is
usually in the fifth or sixth decade of life and is frequently delayed. The delay translating
into higher use of health care resources when compared to that of obese eucapnic patients
[37]. Patients with OHS are frequently misdiagnosed during hospitalization and treated as
Chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) or as a
combination of both [7]. Nowbar et al have previously reported that a majority of
hospitalized patients identified as having OHS were subsequently discharged without home-
based PAP therapy [9].
Basaglu et al performed a case-control study aimed at comparing the clinical characteristics

of patients with OSA and OHS and factors that predict the occurrence of hypercapnia in
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patients with OSA. In 2,188 consecutive patients admitted to the sleep laboratory for
evaluation for sleep-disordered breathing by polysomnography over a 6-year period clinical
characteristics of 59 patients with OHS and 295 patients with OSAS were compared. The
cases and controls were matched for BMI. Daytime hypersomnia was measured by a
Turkish version of Epworth sleepiness scale (score > 10). Pulmonary function tests, Chest
X-rays, arterial blood gas and overnight in-lab polysomnogram was performed in all
individuals. Individuals with OHS were found to be have a greater proportion of individuals
with hypersomnia (90% versus 69%) and manifest lower FVC and FEV1 measured by
pulmonary function testing than controls. Arterial blood gas analysis showed lower PaO2
(72 ± 13 versus 81 ± 13 mmHg) and higher PCO2 (49 ± 5 versus 35 ± 4 mmHg) and serum
bicarbonate (32 ± 4 versus 25 ± 3.5 meq/dL) in the OHS than in the control group.
Overnight polysomnography revealed greater degree of nocturnal oxygen desaturation and
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amount of time spent with oxygen saturation < 90% in the OHS than in the control group
[63]. Multivariate analysis showed hypercapnia to be associated independently with serum
bicarbonate and oxygen saturation. A serum bicarbonate > or equal to 27 Meq/L and oxygen
saturation < or equal to 95% had a high sensitivity and specificity to identify patients with
OHS [63].
In a recent prospective observational study to determine the predictors of OHS in

hospitalized patients at a tertiary care hospital, arterial blood gas on 9,480 patients with
hypercapnia were evaluated over a one year period. Three hundred and thirty patients met
the inclusion criteria for hypoventilation based on arterial blood gas PCO2 > or equal to 45
mmHg, normal PH and elevated serum bicarbonate. Chronic hypoventilation was found in
36% (n=118) patients. Twenty-seven patients were identified as having OHS. Patients in the
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OHS group were found to have a higher BMI (43 ± 9 versus 26 ± 5 kg/m2), lower PaO2 and
oxygen saturation. Than those without OHS No significant difference was found between
the PCO2 and serum bicarbonate between the two groups. OHS was misdiagnosed as either
COPD or CHF in twenty patients. Only five cases (17%) had been diagnosed correctly as
OHS. The ratio of PCO2/BMI had the highest diagnostic accuracy for identifying OHS as
measured by area under ROC curve analysis (AUC: 0.90, 95% CI: 0.84–0.98, P < 0.001)
with the sensitivity and the specificity of PaCO2/BMI ratio for diagnosing OHS at <1.5
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being 97% and 69% [7].
In a retrospective study, Macavei et al determined the prevalence of OHS and predictors of

OHS in patients with OSA. In 525 consecutive patients referred to the sleep medicine clinic
Prevalence of OSA among obese patients was 79.9% (275/344 patients) and OHS
prevalence among OSAHS patients was 22.1% (61/275 patients) in those undergoing
polygraphy. Patients with OHS had lower lung volumes, lower mean oxygen saturations,
and greater time spent below 90% oxygen saturation and higher oxygen desaturation index
when compared to OSA patients. A calculated bicarbonate threshold of 27 mmol/L was
most effective in detecting obesity hypoventilation syndrome with 85.7% sensitivity and
89.5% specificity [47]. Mokhlesi and colleagues in an observational study demonstrated
similar findings and identified three independent variables to predict OHS; AHI, lowest
oxygen saturation during sleep and serum bicarbonate. They found that the serum
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bicarbonate less than 27 had a negative predictive value of 97% to exclude hypercapnia
during wakefulness [5]. Moreover, Manuel et al hypothesized that isolated elevation of
serum bicarbonate or base excess in the absence of a wakefulness hypercapnia may be a
marker for a subset of patients may develop OHS patients subsequently [64].
OHS if untreated at hospital discharge is associated with a mortality of 23% at 18 months

and this reduces to 3% in adequately treated patients of OHS. Untreated OHS patients are
also likely to require invasive mechanical ventilation and hence prolonged hospital stay [9].
Early diagnosis of patients with OHS is important with careful emphasis and recognition of
factors predictive of OHS. Although the gold standard for diagnosis for OHS remains an
arterial blood gas and exclusion of other causes of hypercapnia in the correct setting, less
non-invasive testing like measurement of serum bicarbonate may help in the early
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recognition of patients with OHS. But, it is still unclear as to how the coexistence of
metabolic alkalosis due to loop diuretics in patients with CHF may affect the predictive
power of this test.
Treatment
The treatment for OHS is directed at the underlying pathophysiological factors contributing
to hypoventilation. It may be broadly divided into PAP therapy, weight loss induced by
medical or surgical means and pharmacotherapy.
Positive airway pressure (PAP) therapy

PAP therapy has a significant favorable impact on health-related quality of life, health care
costs and mortality [65]. PAP therapy has been shown to improve daytime blood gases and
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quality of sleep [65–68]. PAP therapy is usually in the form of continuous positive airway
pressure (CPAP) therapy or non-invasive positive pressure ventilation (NIPPV) using a bi-
level PAP or other advanced PAP modalities.
Since majority of patients with OHS have OSA, CPAP therapy is recommended initially to
improve nocturnal gas exchange by preventing obstructive apneas and hypopneas and
reducing the work of breathing related to small airway closure and expiratory flow limitation
[28, 31]. PAP therapy improves FRC and the abrogates the effects of PEEPi [28] which in
turn decreases the cost of breathing by reducing swings in intrathoracic pressures needed to
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maintain breathing. Additionally, PAP therapy opens up the smaller airways and thereby
decreases ventilation perfusion mismatch and consequently improves oxygenation.
Following initiation of therapy over a period of few months, improvement in other
physiological parameters such as gas exchange during wakefulness[69, 70] and ventilatory
response to hypoxia and hypercapnia [49, 51, 52] and also improvement in symptoms[71]
and health-related quality of life[70, 71] has been reported following use of CPAP in OHS.
Most studies that demonstrated the efficacy of CPAP therapy in OHS patients have been
small and retrospective in nature.
Banerjee et al conducted a prospective study whereby they compared 23 patients with

(moderate to severe) OSA with an equal number of subjects with OHS and OSA of similar
severity and then measured the effect of one night of CPAP therapy on sleep architecture
[72]. CPAP therapy failed to correct the oxygen desaturation in 43% of subjects with OHS
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and OSA who continued to spend > 20% of total sleep time with oxygen saturation less than
90% [72]. In a recent prospective study, Salord and colleagues followed newly diagnosed
patients with OHS and OSA (n=29) for a period of three months to evaluate the effect the
long-term effect of CPAP therapy on oxygen saturation and daytime PaCO2 and to explore
factors that might predict the failure of CPAP. The effect of CPAP therapy on the pro-
inflammatory markers adipokine and C-reactive protein (CRP); which are thought be raised
in response to chronic inflammation due to hypoxia was also assessed. Treatment failure
after 3 months was defined by a daytime PaCO2 > 45 mm Hg and/or SpO2 < 90% for > 30%
of the night. All patient underwent overnight polysomnography or respiratory polygraphy.
Patients with an AHI > 15/hour had a CPAP titration. Patient with a mean nighttime oxygen
saturation <85% were switched over to bi-level PAP therapy. An early morning arterial
blood gas and another repeated after 4 hours of awakening were obtained. After three
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months of CPAP treatment there was a significant decrease in nighttime oxygen

desaturation, daytime PaCO2, early morning PaCO2, and improvement in early morning
PaO2. At the end of the study, seven patients met the criteria for treatment failure: six with
persistent daytime PaCO2 > 45 mmHg and one with persistent nocturnal hypoxemia.
Significant improvement is sleep architecture was also seen with more slow wave and REM
sleep and subjective improvement in daytime sleepiness. No significant changes were seen
with respect to the levels of the inflammatory markers at the end of the study. Seven patients
met the criteria for treatment failure. Patients with CPAP failure had lower mean nocturnal
oxygen saturations following CPAP titration, lower daytime PaO2 and higher PaCO2 at one
month following initiation of CPAP therapy when compared to patients with a favorable
response. The study showed a favorable effect of CPAP therapy on nighttime oxygenation
and daytime PaCO2. The study also emphasized the importance of early monitoring of
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daytime PaCO2 in the first month after initiating CPAP therapy and low overnight oxygen
saturation on the night of CPAP titration as a tool to detect patients are more likely to fail
long term treatment [73].
Bi-level PAP
CPAP is recommended as first line treatment in stable OHS patients with mild-to-moderate
hypercapnia OSA. Close attention to early identification of patients with OHS who will
benefit from long-term treatment with CPAP therapy and early treatment failure is important
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[73]. NIPPV (with bilevel PAP or advanced modalities) when used long-term in patients
with OHS who have failed CPAP therapy has been shown to effectively improve
hypoventilation and daytime symptoms.[50, 74–76]
Bi-level PAP therapy is beneficial in preventing obstructive events, improving expiratory

flow limitation and also improves tidal volume by providing inspiratory pressure support.
Bilevel therapy when used long term has been shown to improve blood gases, quality of life
and ventilator responsiveness to CO2 [50, 70, 77–81]. Bi-level PAP therapy unloads
inspiratory muscles and has been shown to reduce diaphragmatic effort by nearly 40% [34].
Piper et al performed a randomized controlled trial in patients with OHS whereby they
compared the efficacy of CPAP versus bi-level PAP therapy to compare their efficacy in
treating daytime hypercapnia, health-related quality of life, cognitive function while also
comparing adherence to such treatment. Thirty-six patients were enrolled and underwent
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baseline sleep study, spirometry and arterial blood gas analysis and PAP titration study.
Patients with significant desaturation (oxygen saturation remaining below 80% continuously
for > 10 min) in the absence of obstructive events, acute rise in transcutaneous carbon
dioxide retention of 10 mmHg of greater during REM sleep or increase in afternoon to
morning PaCO2 of 10 mmHg or greater in those patients with an awake PaCO2 greater than
55 mmHg during an initial CPAP trial were excluded from participation. Patients were
randomized to receive Bilevel PAP or CPAP therapy over three months. Repeat
measurements performed at baseline, including a repeat sleep study while the patient was
receiving the PAP therapy. No significant difference was seen in daytime PaCO2, weight
loss, adherence to therapy or daytime sleepiness. The bi-level PAP therapy group reported
better subjective sleep quality and performed better on a psychomotor vigilance task than the
CPAP group [70].
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In observational studies, NIPPV has been shown to have a favorable effect on metabolic and
cardiovascular parameters. A recent randomized control trial aimed to compare the effects of
NIPPV to lifestyle counseling in patients with mild OHS [82]. In this study, Borel et al
noted that NIPPV improved daytime arterial blood gas measurements and ventilation during
sleep when compared with the lifestyle counseling group. All patients underwent an
overnight polysomnogram, measurement of biomarkers for inflammation, spirometry and
measurement of arterial wall stiffness. Thirty-five newly diagnosed OHS patients were
randomized to either the treatment arm to receive NIPPV (Bi-level) for a duration of one
month or be part of the control group with lifestyle modification. Participants undergoing
lifestyle modification were educated on health risks associated with obesity, and advised to
reduce fat intake and change eating behavior and increase physical activity. At one month
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follow up, baseline measurements were repeated. Significant improvements in nocturnal

hypoxemia and daytime PaCO2 which consequentially improved sleep architecture in the
NIPPV group where noted when compared to that in the control group. There was no
difference between the cardiovascular, metabolic and inflammatory parameters or in
daytime sleepiness between the two study arms [82].
Bi-Level ventilators provide 3 different modes: (1) Spontaneous mode, in which each
pressurization by the ventilator is triggered and cycled by the patient; (2) Spontaneous/timed
(S/T) mode, in which, if the patient fails to initiate a pressurization within a time frame
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based on a back-up respiratory rate, the device will deliver a machine-triggered cycle for a
defined inspiratory time; (3) Timed mode, in which the device delivers pressurizations at a
preset respiratory rate, during a preset inspiratory time, without taking into account the
patient’s inspiratory efforts [83]. Although OHS remains one of the most common
indications for NIPPV [74], there remains a paucity of evidenced-based guidelines on the
choice of equipment, modes of ventilation and ventilator settings. American Academy of
Sleep Medicine (AASM) guidelines for the adjustment of NIPPV in chronic alveolar
hypoventilation syndromes that were derived mostly from expert consensus recommended
the spontaneous mode as the default setting, unless patients manifests a significant number
of central apneas or a low spontaneous respiratory rate and are unable to trigger the
ventilator [84]. In the latter case a back-up respiratory rate was recommended.
Contal et al performed a randomized controlled trial that aimed to determine the impact of
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changes in back-up respiratory rate with respect to efficacy of ventilation and quality of
sleep in stable patients with chronic hypercapnic respiratory failure under long-term
treatment with a bi-level NIPPV device [85]. In this study, ten patients with OHS were
identified and underwent three consecutive polysomnograms which were performed in a
random order with different backup respiratory rate settings. The different settings were no
back-up respiratory rate (spontaneous mode), low back-up respiratory rate (S/T mode with 2
breaths below the average nocturnal respiratory rate) and high back-up respiratory rate (S/T
mode with respiratory rate set at the 95th percentile of nocturnal respiratory rate). During the
spontaneous mode, participants had significantly increased apnea-hypopnea index
(consisting mainly of central and mixed apneas), and higher oxygen desaturation index when
compared to patients on S/T mode. No significant difference in sleep architecture or quality
of sleep was observed between the spontaneous and S/T modes. The quality of sleep was
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slightly better with lower perceived arousals in the low back-up respiratory rate when
compared to the high back-up respiratory rate mode. The findings of this study were limited
by the small sample size [85].
In summary, a recommendation can be made that bi-level PAP should be strongly

considered in patients who fail a CPAP trial, in OHS patients without OSA and in severe
hypercapnic OHS where CPAP has not proven to be effective. However, larger and
adequately powered randomized controlled trials are needed to document the long effect of
NIPPV on patient-outcomes in this population. Additionally, the effects of such therapy on
metabolic, cardiovascular and inflammatory parameters needs closer study. In a recent
study, Chironos and colleagues demonstrated that in adults with obesity and OSA, CPAP
combined with a weight-loss intervention did not reduce CRP levels more than either
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intervention alone[86]. However, they did not target patients with OHS and OSA,
nevertheless, and therefore the effect of combinatorial therapies that include PAP and
weight-loss intervention needs to be performed in patients with OHS.
Volume assured pressure assistance

Newer PAP modalities like averaged volume-assured pressure support (AVAPS) combine
the benefits of targeting minute ventilation and tidal volumes while delivering the comfort
and advantages of pressure support ventilation making them ideal for patients with
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hypoventilation[79, 87]. This modality was initially used in critically ill patients receiving
mechanical ventilation. Subsequently, the application of AVAPS has been extended to use
in sleep disordered breathing and hypoventilation syndromes [65, 88].
AVAPS modality is designed to detect tidal volume (or minute ventilation) over a variable
(1–5 minute) period of time. The device detects decrease in tidal volume below a certain
threshold with an increase in IPAP (or pressure support) in order to restore the tidal volume
approximately to the preset tidal volume [65]. The inspiratory pressure is aimed at ensuring
a tidal volume, calculated based on the ideal body weight (usually 8 mL/Kg ideal body
weight or at 110% of the patients tidal volume)[87]. These devices combine the technology
of auto-PAP therapy to help determine optimal EPAP pressures.
Storre et al in a randomized crossover trial aimed to investigate the physiologic and clinical
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benefits of AVAPS versus bilevel-PAP with a backup respiratory rate mode of ventilation
alone in patients with OHS. Ten patients with stable OHS who had failed CPAP therapy
were randomized to receive one of the two modes of ventilation and then followed up over
six weeks of home ventilation. No significant difference was seen in terms of the quality of
sleep, health-related quality of life parameters, or daytime gas exchange between the two
groups. The beneficial physiological effect of addition of AVAPS to bilevel PAP with
backup rate was seen as a significant decrease in nighttime end tidal CO2 [79].
In a different study, Ambrogio et al performed a randomized controlled trial aimed at

comparing sleep efficiency between AVAPS and bilevel PAP therapy with the majority of
the patients carrying a diagnosis of OHS and found no significant differences between sleep
architecture, sleep quality or quantity between the two groups [87]. AVAPS was comparable
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to bilevel PAP therapy with regard to sleep, but statistically greater minute ventilation was
observed during AVAPS than bilevel PAP therapy, but this difference is of unclear clinical
significance. Potentially, AVAPS modality may prevent alveolar hypoventilation and
improve oxygenation by assuring the fixed tidal volume [87].
Murphy et al in a recent large single blind, randomized control trial on patients with OHS
aimed to evaluate the effect of AVAPS on daytime hypercapnia, physical activity and
health-related quality of life when compared to individuals on fixed-level pressure support
ventilation [89]. In 50 morbidly obese participants (BMI 50±7 kg/m2) who were randomized
to receive AVAPS and bilevel PAP therapy for 3 months, there was no difference in sleep
architecture or efficiency, PaCO2, gas exchange, lung volumes, daytime somnolence or
health-related quality of life measures. Also, there was no change in overnight oximetry,
transcutaneous CO2, or the need for supplemental oxygen.
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Kelly et al performed a crossover randomized controlled trial to evaluate physiological

outcomes and adherence on individuals with hypoventilation randomized to receive
Intelligent Volume assured pressure support (iVAPS, with automated selection of ventilator
settings) and standard bilevel PAP therapy [67]. Eighteen participants (eight patients with
OHS) underwent polysomnography and transcutaneous CO2 monitoring at baseline and one
month after each treatment period. No significant difference was noted between the
treatment arms with respect to lung volumes, respiratory muscle strength, sleep efficiency
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and architecture, overnight pulse-oximetry and transcutaneous CO2. The adherence was
slightly better in the iVAPS mode with greater average daily use of by one hour and better
subjective measure of ventilator comfort than the fixed pressure support mode, probably
because of the lower median pressure support with the iVAPS mode needed to achieve the
comparable respiratory outcomes [67].
In summary, (a) AVAPS possibly may demonstrate better treatment adherence secondary to
better patient-ventilator synchrony and lower median pressure support; (b) No significant
improvements were noticed for AVAPS modality when compared to bilevel PAP therapy
with regards to patient-outcomes (such as daytime hypercapnia, nocturnal gas exchange,
sleep architecture and efficiency and health-related quality of life measures); and (c) We
need to undertake larger, adequately powered randomized controlled trials in to better
understand the role of such treatment modalities.
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NIV in AHRF in OHS

Patients with OHS often present with symptoms of acute hypercapnic respiratory failure
(AHRF) with a need for hospitalization and noninvasive ventilation. The role of non-
invasive ventilation during an episode of AHRF in COPD patients is well documented.
Previous studies on similar effects in patients with OHS have been retrospective and limited
by small sample size. Carrillo et al conducted a study aimed at assessing the efficacy of
NIPPV in OHS patients during an episode of AHRF with the hypothesis that they would
respond similarly to patients with COPD with a similar presentation [66]. Consecutive
patients (n=716) who were admitted to the ICU with AHRF were identified as either OHS or
COPD. Patients with arterial pH less than 7.35 and PaCO2 > 45 mmHg were identified as
being in AHRF. NIPPV (bi-level PAP ventilation) was initiated in any patient with
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symptoms of respiratory distress with moderate to severe dyspnea and with accompanying
use of accessory muscles of respiration, respiratory acidosis and respiratory rate > or equal
to 25. Patients who received NIV were followed over a period of 1 year after discharge to as
assess hospital readmissions and survival. Patients with OHS had lower rates of late NIPPV
failure (defined as a new episode of AHRF with respiratory acidosis at least 48 hours after
initial stabilization), better outcomes seen as lower rates of readmission to the ICU and
lower ICU and hospital mortality, and lower PaCO2 on hospital discharge when compared to
patients with COPD. The results of the study suggest that patients with OHS in AHRF
respond more favorably to NIPPV with improved outcomes, gas exchange and mortality
than patients with COPD [66].
Oxygen therapy in OHS

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In a recent double-blind randomized crossover study, Hollier et al investigated the effect of

moderate concentrations of supplemental oxygen and on changes in PaCO2, pH and
respiratory variables over a period of time in patients with stable untreated OHS and
compared this to healthy controls [90]. Arterialized-venous PCO2 (PavCO2), pH, minute
ventilation and dead space fraction were measured at baseline, then every 5 min over a 20
min of exposure to They both 28% and 50% FiO2. At FiO2 of 28%, PavCO2 increased by
0.3 ± 0.2 kPa and was accompanied by an increase in dead space fraction of 1 ± 5% (p =
0.012) without any significant change in minute ventilation. At FiO2 of 0.50 PavCO2
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increased by 0.5 ± 0.4 kPa, induced acidaemia and increased dead space fraction by 3 ± 3%
with a reduction of minute ventilation of 1.2 ± 2.1 L/min [90]. In summary, hyperoxia
induced by increments in FiO2 initially caused minimal changes in pH or minute ventilation,
but further increments in FiO2 caused hypoventilation and acidaemia. The effect on
ventilation was more pronounced in obese patients with hypercapnia receiving 100% FiO2,
with marked decrease in minute ventilation and increase in PavCO2 [91, 92]. These findings
suggest that a greater degree of respiratory depression occurs with higher oxygen
concentrations. The mechanisms by which hyperoxia induces hypoventilation in OHS
remain unclear. Inter-individual variability of response, in the study suggests OHS patients
with higher baseline PCO2 and serum bicarbonate are more likely to develop worsening
hypercapnia to hyperoxia [90]. But, the precise factors that underlie such inter-individual
differences and the role of concomitant NIPPV remain less clear [92]. Clinicians should be
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aware and monitor for PaCO2 retention in states of acute-on-chronic hypercapnic respiratory
failure related to OHS.
Long term effects, mortality and prognosis of PAP therapy

Limited data is available on the long-term effects of NIPPV for OHS. In a prospective
observational study, Heinemann et al studied the long term effect of home nocturnal
ventilation with NIPPV on lung function and gas exchange on patients with OHS [93]. In 35
patients they performed physiological measurements prior to initiation of NIPPV and
repeated them at 12 and 24 months after NIPPV therapy. Significant improvements in
pulmonary function tests (total lung capacity, vital capacity, residual capacity and expiratory
reserve volume) were seen at 12 months. There was no further change in such measurements
at 24 months. Blood gas analysis showed significant decrease in wake daytime PaCO2 and
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base excess with improved hypoxemia at 12 and 24 months. No significant difference in

alveolar-arterial gradient was seen. Significant improvement in polycythemia was seen at 12
months and mortality at 24 months was 9% [93].
Priou et al performed a retrospective study to compare long term outcomes and treatment
adherence in consecutive patients discharged home with NIPPV for OHS. Patients were
initiated with NIPPV under stable conditions following an episode of acute hypercapnic
respiratory failure. In 92 of the 130 patients with OHS, NIPPV was initiated in a stable
condition and in 38 following ICU management of an acute episode of acute hypercapnic
respiratory failure with a follow-up period of 10 years. At 6 months, there was significant
improvement in of PaO2, PaCO2, bicarbonate, and pH. No significant difference in the
arterial blood gas results were noticed between the acute and stable groups. On Kaplan-
Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and
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77.3%, respectively with no significant difference noted between the two groups. Analysis
of possible prognostic factors like heart disease, baseline PCO2 > 50 mmHg, baseline serum
bicarbonate >30 meq/dL and hypoxia showed that supplemental oxygen was the only
independent predictor of mortality [77].
Budweiser et al performed a retrospective analysis on patients with OHS on NIPPV to

assess the long-term survival and predictors of mortality [94]. A total of 126 patients with a
diagnosis of OHS were assessed at 3–6 months following hospital discharge. In these
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patients who were receiving NIPPV at home, they found significant improvement in arterial
blood gases and lung volumes. Additionally, they found significant decrease in hematocrit
and CRP levels. During the mean observation time of 41.3 months, the all-cause mortality
was 12.7%. After 1, 2 and 3 years, the survival was 97%, 92% and 70%. Analysis of factors
predictive of mortality showed that baseline PaO2 < 50, pH > 7.44, white blood cell count of
> 7,800/mm3 were independent predictors of mortality. After initiation of NIPPV, a
reduction in both nocturnal PaCO2 by > 23% and hemoglobin level compared to baseline
were associated with better prognosis [94].
Hypoxia has been shown to be an independent predictor of mortality in OHS[77, 94].

Pulmonary arterial vasoconstriction secondary to hypoxia may cause pulmonary arterial
hypertension but there appears to be significant inter-individual differences in such a
response [95–97]. In a study by Held et al, a cohort of 18 patients were identified to have
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with pulmonary hypertension and hypoventilation [68]. The goal of the study was to
characterize the association of pulmonary arterial hypertension due to hypoventilation and
exercise capacity (with preserved cardiac index), and the effect of noninvasive ventilation on
hemodynamics and functional capacity. Functional capacity was characterized by a 6 min
walk test and pulmonary hypertension was confirmed by either right heart catheterization or
echocardiography. All 18 patients were treated with NIPPV and were followed up 3 months
after initiation of the ventilation therapy to assess for changes from baseline hemodynamics
and functional capacity. Significant improvement in both mean and systolic pulmonary
arterial pressure, pulmonary vascular resistance, six minute walk distance (in meters),
increase in maximum work rate, right ventricular systolic function, lung volumes and gas
exchange. These findings demonstrate the favorable effect of NIPPV on hemodynamics and
functional capacity in these patients [68]. Similar findings were documented in another
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study by Castro et al who demonstrated the hemodynamic effects of NIPPV in patients with
OHS that was measured by echocardiography and six-minute walk test [98]. After 6 months
of NIPPV therapy, significant decrease in pulmonary arterial pressure and improvement in
six-minute walk distance was seen [98].
Withdrawal from positive airway pressure therapy has been shown to be associated with
worsening nocturnal gas exchange in patients with chronic respiratory insufficiency related
to restrictive thoracic disorders [99]. The recovery of chemoreceptor secondary to improved
gas exchange following NIPPV constitutes a very important factor in producing both clinical
and functional improvements in patients with OHS [75]. De Miguel Díez et al performed an
open-label prospective design study of the effect of withdrawal of NIPPV on 12 patients
with OHS who had been on NIPPV for at least one year [100]. The hypothesis was that
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improved gas exchange at the end of one year of NIPPV with normalization of central
controller response to the chemical stimuli. After a 3-month follow-up of these patients,
there was no change in body weight, lung function, daytime or nighttime arterial blood gases
or nighttime oxygen saturation. The study was limited by the small sample size and short
follow up. A follow up within 3 months might be too short to predict the appearance of
respiratory insufficiency later [100]. In summary, based on the above findings of long-term
effects of NIPPV in OHS patients, NIPPV can be noted to improve lung function as
evidenced by significant improvement in lung volumes, better gas exchange and is
associated with reduced mortality. Moreover, NIPPV improves pulmonary hemodynamics

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and functional capacity in patients with comorbid pulmonary hypertension.
Adherence to therapy
Long-term adherence was better in patients with OHS when compared to patients with OSA
alone. In mild OSA the discontinuation rate is expected to be between 12% to 25% [101,
102]. Priou et al in their study found the discontinuation rate of 20% at 3 years and with
average nightly use of > 7 hours with female sex being the only significant predictive factor
for NIPPV discontinuation [77]. Budweiser et al, observed similar adherence to NIPPV in
OHS patients of 82% and an average nightly use of 6.5 hours after a mean follow-up of 41
months [94]. Mokhlesi et al performed a retrospective study that studied the effect of PAP
therapy on hypercapnia and hypoxia in patients with OSA and daytime hypercpania. In
patients with OSA (AHI > 10/hr) and hypercapnia (stable daytime PaCO2 > 45 mmHg) on
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PAP therapy, 45% of patients had PAP adherence more than 4.5 hrs/day and the average
drop in PaCO2 was 7.7 ± 5 mmHg, compared to 2.4±4 mm Hg (in patients with less than 4.5
hours per day) and average increase in PaO2 was 9.2±11 mmHg compared to 1.8±9 mmHg
in patients whose adherence was < 4.5 hrs/day. A nonlinear relationship between hours of
PAP therapy use and improvement in PCO2 was demonstrated with a plateau in
improvement after 7 hours of PAP therapy [103]. The adherence of NPPV is high in patients
with OHS, likely because these patients may be perceiving the most health benefits when
being adherent to PAP therapy.
Non-PAP treatment modalities in OHS

NIPPV has been shown to be beneficial in patients with OHS by improving diurnal
hypoventilation, quality of sleep, improve gas exchange and symptoms associated with
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hypercapnia and mortality. The benefits are somewhat limited by poor adherence and
intolerance in some patients. It has been shown to have a limited impact on weight loss and
may not reduce the co-morbidities associated with obesity [104]. Non-PAP treatment
options include exercise and rehabilitation, weight reduction, tracheostomy respiratory
stimulants and oxygen therapy.
Weight loss has been shown to improve lung function, respiratory muscle strength, and
respiratory drive and sleep disordered breathing. Several studies have documented the
impact of weight loss by showing significant improvements in pulmonary function testing
[105–108] and improvement in gas exchange [40, 105, 109]. Substantial weight loss is
needed for such benefits to be realized, which are seldom achieved with medical and
conservative approaches alone. Dixon et al performed a randomized controlled trial aimed at
determining the effectiveness of conventional (medical) weight loss therapy in comparison
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to surgically induced weight loss in the management of OSA [110]. The BMI ranged from
35 to 55 Kg/m2 with moderate to severe OSA (AHI > 20/hr) prior to bariatric surgery and
OHS on PPV were excluded from the study. Patients on the conventional weight loss
therapy arm had access to diet, physical activity and behavioral programs. The patients on
the surgical therapy arm underwent lap-band procedure. Both groups underwent a
polysomnogram at baseline and at the end of 2 years of follow up. The surgical group
achieved a significantly greater mean weight loss of 27.8 kg compared to 5.1 kg in the
medical group. Both groups had a significant reduction in total AHI between baseline and
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two years, with the reduction being more pronounced in the surgical (post lap-band) group
with a reduction in AHI of 25 events/hour when compared to a reduction of 14 events/hour
in the medical group. The health-related quality of life outcomes were not statistically
different between the groups although the surgical group had greater improvement in scores
at two years when compared to baseline [110].
In a meta-analysis of RCTs aimed at comparing the effectiveness of bariatric surgery versus

non-surgical treatment for obesity, 11 RCTs with 796 participants and mean BMI of 30–52
kg/m2 were analyzed. Patients allocated to bariatric surgery lost more weight mean
difference−26 kg (95% confidence interval −31 to −21 kg) and were found to have greater
improvement in health-related quality of life when compared to individuals who received
non-surgical weight loss therapy [111].
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Patients with BMI> 40 kg/m2 who have failed conservative management for weight loss or
with BMI >35 kg/m2 who have obesity-related co-morbidities are candidates for bariatric
surgery. Various surgical approaches exist but the Roux-en-Y gastric bypass procedure is
considered the gold-standard for weight loss with the best long-term weight loss results
[112]. Weight loss secondary to bariatric surgery has been shown to have a favorable
outcome in terms of observed improvement of severity of sleep-disordered breathing,
daytime and nighttime gas exchange, improved lung volumes and improved respiratory
muscle strength [108, 113, 114]. In a recent study Lumachi et al evaluated the impact of
weight loss and daytime oxygenation following bariatric surgery on 11 patients with an
average BMI 52 Kg/m2 and with baseline hypoxia. At three, six and twelve months after
surgery, the estimated weight loss was 19%, 26%, and 39%, respectively. At one-year the
daytime SpO2, lung function tests, demonstrated significant improvement compared to
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baseline [115]. Sustained weight loss post-bariatric surgery has been shown to improve sleep
apnea and OHS and can obviate the need for PAP therapy.
De Cesare et al evaluated the long and short term results of malabsorptive surgery in 102
morbidly obese patients. They showed that at before surgery 16 patients were identified as
having OHS and 22 with OSA. Maximum weight loss occurred between 12–24 months post
operatively at which time none of the patients fulfilled criteria for OHS and only 2 of the
patients continued to need CPAP therapy for symptoms of OSA [116]. Similar findings were
documented by Marti-valeri et al, wherein 30 morbidly obese patients on non-invasive
ventilation by either CPAP or Bi-level PAP therapy (OHS (n=9) and OSA (n=14 patients))
were followed for one year after bariatric surgery. Most patient were able to be withdrawn
from NIPPV [117]. In summary, the weight loss from medical management of obesity may
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not be sufficient when compared to surgical treatment. Benefits of bariatric surgery extend
to improvements in BMI, AHI, alveolar ventilation and lack of need for NIPPV in most
patients. More importantly, surgical weight loss provides additional metabolic effects such
as better control of diabetes and hypertension and an overall reduction in mortality and
morbidity [118]. Randomized controlled trials that examine the longer-term effects of
surgery in comparison with conventional treatment on weight loss, comorbidities and health-
related quality of life are not available so far, so it is unclear if the benefits are maintained
over time.
Tracheostomy
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Tracheostomy can reduce obstructive events associated with sleep-disordered breathing by

bypassing the upper airway [18, 119]. Tracheotomy used to be the only effective treatment
for obstructive sleep apnea until Sullivan et al successfully managed five patients with PAP
therapy [120]. Since then tracheostomy is seldom performed and is reported in a small
subset of patients receiving home mechanical ventilation. El Solh et al have previously
reported on postoperative complications of tracheostomy in critically ill morbidly obese
patients with BMI greater than or equal to 40. They found that morbid obesity was
independently associated with tracheostomy related complications secondary to tube
obstruction and malpositioning secondary to excess adipose tissue around the neck [121].
Tracheostomy is currently limited to management of OHS when other options for treatment
have failed. No recent publications evaluating long term home ventilation on tracheostomy
has been reported.
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Pharmacotherapy
Pharmacological agents that alter the ventilatory response to hypercapnia could be
considered as adjuncts or alternatives to NIPPV. Acetazolamide, a carbonic anhydrase
inhibitor, may stimulate ventilation by decreasing the serum bicarbonate and creating
metabolic acidosis.[122] Raurich et al, investigated the relationship between CO2 response,
BMI and plasma bicarbonate concentration, and the effect of acetazolamide on plasma
bicarbonate and CO2 response in 25 patients with OHS in the ICU recovering from acute
hypercapnic respiratory failure. Patients with the highest bicarbonate had the lowest CO2
response. Addition of acetazolamide decreased the serum bicarbonate and improved
ventilatory response to hypercapnia. This ventilatory response has been shown to be variable
[123–127] and and also not high enough to treat OHS [128]. In a recent Cochrane review of
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30 randomized controlled trials to determine the efficacy of 25 drugs involving 560

individuals with OSA, medications such as fluticasone, Donepezil, paroxetine and
combination of high dose ondansetron and fluoxetine showed improved from baseline AHI
and subjective sleepiness during the day. The studies were limited by the small sample size
and short duration. Insufficient evidence was found to recommend pharmacological
treatment in patients with OSA [129].
Exercise and Rehabilitation

Patients with OHS treated with NIPPV have been shown to improve their functional
capacity (as measured by 6 minute walk test) [68, 98]. It is thought that the improved
nocturnal ventilation and daytime symptoms might be contributing to increased physical
activity during the day [89]. Patients with OHS are likely to benefit from exercise and
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rehabilitation program, though the benefits and timing of initiation of rehabilitation need to
be confirmed with long term randomized control trials.
Conclusion
The prevalence of OHS is bound to increase with the obesity epidemic. OHS is frequently
under diagnosed and sometimes misdiagnosed. Left untreated and undiagnosed these
patients have a poor health-related quality of life, prolonged hospitalization and worsening
co-morbidities associated with the condition and high mortality. Emphasis to close attention
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to early diagnosis and institution of therapy is critical to reduce the significant mortality and
morbidity of untreated OHS. Recognition of clinical characteristics and predictive factors
during overnight polysomnogram and clinic visits may provide early diagnostic clue. A
multimodal and multi-disciplinary approach to management with weight loss, rehabilitation
programs in conjunction with NIPPV is likely to have a greater impact on cardiovascular,
metabolic and HRQoL outcomes [130].
Acknowledgments
Funding support from NIH/NHLBI (5R01HL095748), and PCORI contract (IHS-1306-2505) to SP. The funding
institutions did not have any role in the design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript
for publication.
Author Manuscript
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Figure 1.
Kaplan–Meier survival curves (log rank) from respiratory and cardiovascular causes of
death in the total group of patients. Panels are referring to daytime PaO2 (panel a; P =
0.004), and daytime pH (panel b; P = 0.0034) with supplemental oxygen as described above
and leucocytes (panel c; P = 0.0184). The cut-off values used are indicated within the plots.
Reproduced with permission from reference [94].
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Obesity Hypoventilation Syndrome

Correspondence to: Sairam Parthasarathy, [email protected].

a short period of time can correct daytime hypercapnia [18].

This pattern of breathing contributes to dead space ventilation and to hypoxia.

Central Respiratory drive

Sleep disordered breathing

Leptin resistance and OHS

with OHS, Leptin resistance is thought to contribute to the pathophysiology in a manner

Clinical features and diagnosis

Basaglu et al performed a case-control study aimed at comparing the clinical characteristics

In a recent prospective observational study to determine the predictors of OHS in

being 97% and 69% [7].

In a retrospective study, Macavei et al determined the prevalence of OHS and predictors of

OHS if untreated at hospital discharge is associated with a mortality of 23% at 18 months

Positive airway pressure (PAP) therapy

Banerjee et al conducted a prospective study whereby they compared 23 patients with

months of CPAP treatment there was a significant decrease in nighttime oxygen

Bi-level PAP therapy is beneficial in preventing obstructive events, improving expiratory

follow up, baseline measurements were repeated. Significant improvements in nocturnal

In summary, a recommendation can be made that bi-level PAP should be strongly

Volume assured pressure assistance

In a different study, Ambrogio et al performed a randomized controlled trial aimed at

Kelly et al performed a crossover randomized controlled trial to evaluate physiological

NIV in AHRF in OHS

Oxygen therapy in OHS

In a recent double-blind randomized crossover study, Hollier et al investigated the effect of

Long term effects, mortality and prognosis of PAP therapy

base excess with improved hypoxemia at 12 and 24 months. No significant difference in

Budweiser et al performed a retrospective analysis on patients with OHS on NIPPV to

Hypoxia has been shown to be an independent predictor of mortality in OHS[77, 94].

associated with reduced mortality. Moreover, NIPPV improves pulmonary hemodynamics

and functional capacity in patients with comorbid pulmonary hypertension.

Non-PAP treatment modalities in OHS

In a meta-analysis of RCTs aimed at comparing the effectiveness of bariatric surgery versus

Tracheostomy can reduce obstructive events associated with sleep-disordered breathing by

30 randomized controlled trials to determine the efficacy of 25 drugs involving 560

Exercise and Rehabilitation

··Of outstanding importance

132(4):1322–36. [PubMed: 17934118]

Chest. 2005; 127(3):710–5. [PubMed: 15764748]

obesity. J Appl Physiol (1985). 2010; 108(1):212–8. [PubMed: 19910329]

79(4):1199–205. [PubMed: 8567562]

consecutive cases. Chest. 2001; 120(2):369–76. [PubMed: 11502631]

obese patients. Surg Today. 2014; 44(8):1424–33. [PubMed: 24519396]

123. Wagenaar M, et al. Comparison of acetazolamide and medroxyprogesterone as respiratory

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