Obesity Hypoventilation Syndrome (OHS) (Pickwickian Syndrome)



  • Charles Dickens’ Character “Fat Joe” Appeared in The Pickwick Papers in 1836
    • Fat Joe was Known for Overeating and Falling Asleep at Any Time of the Day
  • Burwell First Coined the Term “Pickwickian Syndrome” to Describe Patients with What is Now Termed Obesity-Hypoventilation Syndrome (Am J Med, 1956) [MEDLINE]

Obesity (see Obesity, [[Obesity]])

  • Definition of Obesity (see Obesity, [[Obesity]])
    • Body Mass Index (BMI) is Expressed in kg/m2
    • BMI >28 kg/m2
    • BMI >40 kg/m2: severe obesity
  • Centers for Disease Control and Prevention (CDC) Statistics Related to Obesity (JAMA, 2014) [MEDLINE]
    • Approximately 34.9% of US Adults are Obese: accounts for 78.6 million people
    • Approximately 6.4% of US Adults are Severely Obese (BMI ≥40 kg/m2)
      • Prevalence of Severe Obesity in Non-Hispanic Black Adults: 12.2%


  • Approximately 0.15-0.3% of the Adult Population in the US Have OHS (Respir Care 2010) [MEDLINE]
    • The Prevalence of OHS Increases with Body Mass Index (BMI) (Chest, 2005) [MEDLINE]
      • BMI 30-35: prevalence of OHS is 8-12%
      • BMI ≥40: prevalence of OHS is 18-31%
      • BMI ≥50: prevalence of OHS is 50%


Factors Involved with the Pathogenesis of Obesity-Hypoventilation Syndrome

  • Impaired Control of Ventilation
    • Decreased Neural Drive Has Been Observed in OHS: in contrast, obese patients without OHS normally have increased neural drive, as compared to normal patients
    • Decreased Ventilatory Responsiveness to Hypoxemia/Hypercapnia are Decreased in OHS During Sleep
    • Leptin Resistance May Occur in OHS:
  • Increased Carbon Dioxide Production Due to Increased Body Surface Area (Ann Am Thorac Soc, 2014) [MEDLINE]
  • Altered Pulmonary Mechanics Due to Body Habitus
    • Restrictive Pulmonary Function Tests (PFT’s)
    • V/Q Mismatch with Decreased Lower Lung Zone Ventilation and Increased Lower Lung Zone Perfusion: ventilation abnormalities are due to decreased lung compliance, difficulty mobilizing the ribcage/diaphragm, and/or alveolar closure prior to the end of expiration
    • Modestly Decreased Respiratory Muscle Strength (Which is Worse in the Supine Position): this occurs despite increased inspiratory loads created by obesity
  • Sleep-Disordered Breathing
    • Approximately 90% of Patients with OHS Have Associated OSA, While 10% of Patients with OHS Have Sleep-Associated Hypoventilation Alone (without Airway Obstruction)
    • Inadequate Carbon Dioxide Clearance Occurs During Sleep: resulting in worsening of nocturnal hypercapnia (with resulting renal bicarbonate retention)
    • Nocturnal Hypoxemia Occurs During Sleep: the percentage of time spent with SaO2 <90% correlates with the development of daytime hypercapnia

Development of Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

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Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

  • Findings

Serum Chemistry

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

Thyroid Function Tests (TFT’s) (see Thyroid Function Tests, [[Thyroid Function Tests]])

  • Useful to Exclude Concomitant Hypothyroidism

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

  • Findings
    • Low Lung Volumes with Elevated Hemidiaphragms

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])

Restrictive Pattern

  • General Comments
    • Restriction is Common in Obese Patients: especially with BMI >50
    • Restriction Occurs Secondary to Simple Obesity Alone Only When the Weight/Height Ratio Exceeds 1.0
    • Note: Absence of a Restrictive Pattern on PFT’s Does Not Exclude the Diagnosis of OHS
  • Findings
    • FEV1: decreased (40% smaller than in simple obesity)
    • FEV1/FVC Ratio: normal (due to normal large airways)
    • VC: decreased (about 66% predicted)
    • TLC: decreased (about 80% predicted)
    • FRC: decreased (usually about 70-80% predicted)
    • Expiratory Reserve Volume (ERV): decreased
    • MVV: decreased (about 56% predicted)
    • DLCO: slightly decreased
    • MIP/MEP: decreased (MIP: about 60)
    • Lung Compliance: decreased (due to increased pulmonary blood volume/ increased closure of dependent airways)
    • Raw: increased (likely due to decreased lung volumes which occur in the setting of obesity) (Eur Respir J, 2005) [MEDLINE]

Polysomnography (PSG) (see Polysomnography, [[Polysomnography]])

  • Required in Many Cases to Diagnose Associated Sleep-Disordered Breathing

Echocardiogram (see Echocardiogram, [[Echocardiogram]])

  • Findings
    • Pulmonary Hypertension (with/without Right Ventricular Enlargement)

Clinical Manifestations

General Comments

  • Working Definition (Respir Care, 2010) [MEDLINE]:
    • Obesity (with BMI >30 kg/m2) (see Obesity, [[Obesity]])
    • Chronic (Awake) Hypoventilation (with pCO2 ≥45 mm Hg at Sea Level) (see Chronic Hypoventilation, [[Chronic Hypoventilation]])
    • Absence of Alternative Etiology
      • Absence of Intrinsic Lung Disease: such as COPD, interstitial lung disease, etc
      • Absence of Neuromuscular Etiologies: such as myasthenia gravis, etc
      • Absence of Mechanical Etiologies: such as kyphoscoliosis, etc
      • Absence of Metabolic Etiologies: such as hypothyroidism, etc
    • Frequent Association with Sleep-Disordered Breathing

Cardiovascular Manifestations

  • Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
    • Right-Sided Congestive Heart Failure (Cor Pulmonale)
      • Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]]): may occur with/without congestive heart failure
    • Left-Sided Congestive Heart Failure
  • Hypertension (see Hypertension, [[Hypertension]])

Endocrine Manifestations

  • Metabolic Syndrome
  • Obesity (see Obesity, [[Obesity]])
    • Clinical: BMI >30 kg/m2

Gastrointestinal Manifestations

Neurologic Manifestations

Pulmonary Manifestations

  • Acute Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]])
    • Epidemiology
      • Females with OHS Tend to Present Later in the Disease Course More Frequently than Do Males with OHS (Respir Med, 2016) [MEDLINE]: they more frequently present with acute on chronic respiratory failure
  • Atelectasis (see Atelectasis, [[Atelectasis]])
    • Epidemiology: atelectasis is common in the setting of obesity with low lung volumes
    • Clinical
  • Chronic Hypoventilation (see Chronic Hypoventilation, [[Chronic Hypoventilation]])
    • Physiology
      • Decreased Central Respiratory Drive in Response to Carbon Dioxide
      • Mechanical Impedance to Breathing
    • Clinical
  • Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea, [[Obstructive Sleep Apnea]])
    • Epidemiology
      • Approximately 90% of Patients with OHS Have Associated OSA, While 10% of Patients with OHS Have Sleep-Associated Hypoventilation Alone (without Airway Obstruction)
    • Treatment
      • Treatment of Nocturnal Sleep-Disordered Breathing (with Positive-Pressure Ventilation, Tracheostomy) is Also Effective in the Treatment of OHS
  • Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])


Weight Loss (see Weight Loss, [[Weight Loss]])

  • Recommended
    • Improves VC, ERV, FRC, and MVV
    • Improves pCO2

Supplemental Oxygen (see Oxygen, [[Oxygen]])

  • Avoid Excessive Daytime Oxygen Therapy
    • While Oxygen Therapy May Improve Daytime Hypoxemia, it Can Acutely Worsen Hypoventilation (Via Worsening of the Dead Space Fraction)
      • Supplemental Oxygen Therapy (100%) in Stable OHS Has Been Demonstrated to Worsen Hypercapnia, Up to 10 mm Hg in Some Cases (Chest, 2011) [MEDLINE]\
    • Generally, Maintenance of SaO2 of 89-92% is Recommended to Avoid Hyperoxia in These Patients: these thresholds should be similarly applied in patients on noninvasive mechanical ventilation
  • Avoid Excessive Nocturnal Oxygen Therapy: while oxygen improves nocturnal hypoxemia, it can worsen nocturnal hypoventilation


  • Avoid Creation of Pre-Renal Azotemia in the Setting of an Acute Illness
    • During Acute Illness, Worsening Hypoxemia and Hypercapnia Can Result in an Increase in Catecholamines, Resulting in Increased Renal Vascular Resistance: during this illness, diuretics may exacerbate the azotemia
      • For This Reason, Diuresis May Need to Be Withheld Until the Acute Hypoxemia/Hypercapnia Improve
  • Avoid Excessive Diuresis/Contraction Alkalosis During the Treatment of Peripheral Edema (see Metabolic Alkalosis, [[Metabolic Alkalosis]])
    • Excessive Alkalemia Blunts the Ventilatory Response, Worsening Hypercapnia
      • For This Reason, Periodic Acetazolamide (Diamox) Therapy May Be Useful to Avoid an Excessive Increase in Serum Bicarbonate Which Occurs in the Setting of Diuretic Use, Restoring the Reactivity of the Respiratory Drive to Carbon Dioxide (see Acetazolamide, [[Acetazolamide]]) (Respir Care, 2010) [MEDLINE] and (Respir Care, 2010) [MEDLINE]


  • Avoid (or Minimize) the Use of Any Agents Which Depress the Central Respiratory Drive

Treatment of Sleep-Disordered Breathing


  • Nocturnal Non-Invasive Positive Pressure Ventilation (NIPPV)

Clinical Efficacy

  • Retrospective Study of Nasal NIPPV in Morbidly Obese Patients (Mean BMI 44) with Obesity-Hypoventilation Syndrome (Chest, 2005) [MEDLINE]
    • Approximately 87% of the Studied Patients Had Sleep Apnea
    • Nasal NIPPV Improved Gas Exchange, Dyspnea, and Daytime Sleepiness

Ventilatory Stimulants

Treatment of Acute (on Chronic) Respiratory Failure

  • Careful Consideration of the Approach to Airway Management is Crucial in These Patients
    • Awake Fiberoptic Intubation with Concomitant Nasal BiPAP Ventilation is Usually the Preferred Approach: as sedation/paralysis (per standard rapid sequence intubation methods) may result in airway compromise with difficulty bag-mask ventilating (and intubating) the patient


  • Extreme obesity associated with alveolar hypoventilation: a Pickwickian syndrome. Am J Med 1956;21:811–818 [MEDLINE]
  • The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. 2001;120(2):369 [MEDLINE]
  • Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy. Chest. 2005;127(3):710 [MEDLINE]
  • The effects of body weight on airway calibre. Eur Respir J 2005;25:896–901 [MEDLINE]
  • Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. 2005 Aug;128(2):587-94 [MEDLINE]
  • Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007;11(2):117 [MEDLINE]
  • Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest. 2007;131(6):1678 [MEDLINE]
  • Assessment and management of patients with obesity hypoventilation syndrome.  Proc Am Thorac Soc.  2008;5:218–225 [MEDLINE]
  • Obesity hypoventilation syndrome: a state-of-the-art review. Respir Care 2010;55:1347–1362 [MEDLINE]
  • Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects. Respir Care 2010;55:1442–1448 [MEDLINE]
  • Obesity hypoventilation syndrome: bicarbonate concentration and acetazolamide. Respir Care 2010;55: 1504–1505 [MEDLINE]
  • The effect of supplemental oxygen on hypercapnia in subjects with obesity- associated hypoventilation: a randomized, crossover, clinical study. Chest 2011;139:1018–1024 [MEDLINE]
  • Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012 Dec;186(12):1279-85. Epub 2012 Oct 26 [MEDLINE]
  • Diagnostic predictors of obesity-hypoventilation syndrome in patients suspected of having sleep disordered breathing. J Clin Sleep Med. 2013 Sep;9(9):879-84 [MEDLINE]
  • Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014;311: 806–814 [MEDLINE]
  • Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it? Ann Am Thorac Soc. 2014 Jul;11(6):945-50 [MEDLINE]
  • Obesity hypoventilation syndrome: current theories of pathogenesis. Curr Opin Pulm Med.  2015;21:557–562 [MEDLINE]
  • Avoiding management errors in patients with obesity hypoventilation syndrome.  Ann Am Thorac Soc.  2016;13:109–114 [MEDLINE]
  • Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome. Respir Med. 2016 Jan;110:73-8. Epub 2015 Nov 26 [MEDLINE]