eMedicine Specialties > Pulmonology > Sleep-Related Disorders

Hypoventilation Syndromes: Differential Diagnoses & Workup

Author: Jazeela Fayyaz, DO, Senior Fellow, Department of Pulmonology, Lenox Hill Hospital
Coauthor(s): Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Contributor Information and Disclosures

Updated: Sep 18, 2009

Differential Diagnoses

ALA Dehydratase Deficiency Porphyria
Obesity
Botulism
Opioid Abuse
Chronic Bronchitis
Respiratory Acidosis
Chronic Obstructive Pulmonary Disease
Sedative, Hypnotic, Anxiolytic Use Disorders
Diaphragm Disorders
Diaphragmatic Paralysis
Emphysema

Other Problems to Be Considered

The differential diagnosis for hypoventilation syndromes is broad, and all the potential diagnoses listed in Causes and the above listed differentials should be considered. A thorough history, physical examination, and laboratory evaluation should be helpful in limiting the differential diagnosis.

Workup

Laboratory Studies

  • Serum chemistries
    • The most common finding in chronic hypoventilation after chemistry analysis is the presence of a compensatory increase in the serum bicarbonate (HCO3) concentration secondary to respiratory acidosis. 
    • Patients also occasionally may have hypercalcemia and hyperkalemia
  • CBC count
    • Many patients with chronic hypoventilation also are hypoxemic.
    • These patients also may have secondary polycythemia, and a CBC count may reveal an elevated hematocrit level.
  • Thyroid function studies
    • Hypothyroidism is a potential cause of obesity. Obesity can contribute to hypoventilation and obstructive sleep apnea (OSA).
    • Thyroid function should be evaluated in all patients with alveolar hypoventilation who are suspected of having central etiology or OSA.

Imaging Studies

  • Chest radiography
    • Perform a chest radiograph to rule out pulmonary disease as a cause of hypoventilation.
    • Findings on chest radiographs that may help determine the etiology of hypoventilation syndromes include hyperinflation of lung volumes, diaphragm flattening, and elevation of the diaphragms. Hyperinflation of lung volumes and diaphragm flattening occur secondary to severe obstructive airway disease. Elevation of the hemidiaphragms may be related to diaphragm weakness or paralysis or atelectasis.
    • Evidence of bony thoracic abnormalities such as kyphoscoliosis also may be present.
    • With complicating pulmonary hypertension, the hilar vascular shadows are prominent secondary to pulmonary artery enlargement, and the cardiac silhouette may become prominent secondary to right ventricular enlargement.
  • Chest computed tomography scanning
    • CT scan of the chest may be performed for the same reasons as the chest radiograph.
    • It is more sensitive for detecting disease and may reveal abnormalities not seen on the chest radiograph. CT scan is more sensitive in detecting emphysema, diaphragm abnormalities, and skeletal thoracic abnormalities.
  • Brain computed tomography scanning
    • Perform imaging of the brain if a central cause of hypoventilation is suspected.
    • Specific etiologies that may be diagnosed by brain CT scan include cerebrovascular accident, central nervous system tumor, and central nervous system trauma. Pay particular attention to the brainstem for lesions in the pons and medulla.
  • Magnetic resonance imaging of the brain
    • If a central cause of hypoventilation is suspected and the initial brain CT scan is negative or inconclusive, consider an MRI of the brain.
    • MRI may disclose abnormalities that are not seen on CT scan. Pay particular attention to the brainstem, as with the CT scan mentioned above.
  • Fluoroscopy: The fluoroscopic "sniff test" (in which paradoxical elevation of the paralyzed diaphragm is seen during inspiratory effort against a closed glottis) can confirm chest radiographic findings regarding unilateral diaphragmatic paralysis. This test is less useful in the diagnosis of bilateral diaphragmatic paralysis.
  • Echocardiography
    • Echocardiography is indicated to evaluate patients with hypoventilation syndromes for evidence of pulmonary hypertension and right ventricular enlargement. It also is useful to determine the presence of other potential complicating factors such as left ventricular dysfunction and valvular dysfunction.
    • On 2-dimensional echocardiography, patients with pulmonary artery hypertension have increased thickness of the right ventricle. As pulmonary hypertension becomes severe, a paradoxical bulging of the interventricular septum into the left ventricle occurs during systole. Later, the right ventricle dilates, becomes hypokinetic, and the septum develops diastolic flattening.
    • Doppler echocardiography is the most reliable method of estimating pulmonary artery pressure (PAP). Patients with pulmonary artery hypertension may have functional tricuspid valve regurgitation. The maximum tricuspid regurgitant (TR) jet velocity is recorded, and the PAP is calculated using a modified Bernoulli equation: PAP systolic = (4 X TR jet velocity squared) + RAP. RAP is right atrial pressure estimated from the size of the inferior vena cava (IVC) and respiratory variation in flow in the IVC.

Other Tests

  • Pulmonary function testing
    • These measurements are required for the diagnosis of obstructive lung disease and assessment of the severity of disease.
    • FEV1 is the most commonly used index of airflow obstruction. The ratio of FEV1 to forced vital capacity is reduced in airflow obstruction and is the diagnostic variable.
    • Lung volume measurements may document an increase in total lung capacity, functional residual capacity, and residual volume in obstructive pulmonary disease.
    • Measurement of maximal inspiratory and expiratory pressures may be useful in screening for respiratory muscle weakness.
  • Electrocardiography
    • An ECG may show signs of right heart strain, right ventricular hypertrophy, and right atrial enlargement.3
  • Electromyography and nerve conduction velocity
    • Electromyography (EMG) and nerve conduction velocity study are useful in diagnosing neuromuscular disorders such as myasthenia gravis, Guillain-Barré syndrome, and amyotrophic lateral sclerosis that may be the cause of ventilatory muscle weakness.
    • These studies may reveal a neuropathic or myopathic pattern, depending on the etiology.
  • Measurement of transdiaphragmatic pressure
    • This study is useful in documenting respiratory muscle weakness. This test is performed by placing an esophageal catheter with an esophageal balloon and a gastric balloon. The difference between the pressures measured at the 2 balloons is the transdiaphragmatic pressure.
    • Patients with diaphragmatic dysfunction and paralysis have a decrease in transdiaphragmatic pressures.
  • Polysomnography
    • Polysomnography should be performed in all patients with obesity hypoventilation syndrome (OHS) because the majority of patients also have OSA. Polysomnography involves monitoring of multiple physiologic variables to include respiratory effort, airflow, oxygen saturation, sleep stages, body position, limb movements, and ECG.
    • Sleep stages and arousals are monitored by electroencephalogram to determine brain wave activity, electrooculogram (EOG) to determine eye movement, and submental EMG to detect muscle tone. The EOG and EMG facilitate the determination of the REM sleep stage, which is associated with decreased muscle tone and increased frequency of obstructive apneas. Respiratory effort is recorded using devices to measure abdominal and chest wall movement. These devices include strain gauges, impedance devices, EMG bands, and an esophageal balloon with respiratory inductive plethysmography.
    • From the collected data, sleep stage distribution, arousals, apneas, and hypopneas can be quantitated. Central and obstructive apneas can be differentiated. The apnea index and apnea-plus-hypopnea index (AHI) can be calculated by dividing the total number of apneas or apneas plus hypopneas by the total sleep time. The AHI also is known as the respiratory disturbance index. An AHI is considered abnormal at 5 per hour, and an AHI of 5-15 represents mild OSA.
    • Also see the clinical guideline summary from the American Sleep Disorders Association, Practice parameters for the indications for polysomnography and related procedures: an update for 2005.10  
  • Arterial blood gas analysis
    • Alveolar hypoventilation can be documented by the presence of hypercapnia or an elevated PaCO2 (>45 mm Hg). The PaO2 should be evaluated because hypoxemia may be present and frequently is associated with alveolar hypoventilation.
    • HCO3 and pH should be evaluated to determine the presence of acute or chronic acidosis and the degree of compensation.

More on Hypoventilation Syndromes

Overview: Hypoventilation Syndromes
Differential Diagnoses & Workup: Hypoventilation Syndromes
Treatment & Medication: Hypoventilation Syndromes
Follow-up: Hypoventilation Syndromes
References
[ CLOSE WINDOW ]

References

  1. Lesser DJ, Ward SL, Kun SS, Keens TG. Congenital hypoventilation syndromes. Semin Respir Crit Care Med. Jun 2009;30(3):339-47. [Medline].

  2. Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central sleep apnea: Pathophysiology and treatment. Chest. Feb 2007;131(2):595-607. [Medline].

  3. Mokhlesi B, Tulaimat A. Recent advances in obesity hypoventilation syndrome. Chest. Oct 2007;132(4):1322-36. [Medline].

  4. Piper AJ, Grunstein RR. Current perspectives on the obesity hypoventilation syndrome. Curr Opin Pulm Med. Nov 2007;13(6):490-6. [Medline].

  5. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. Jun 2007;11(2):117-24. [Medline].

  6. Powers MA. The obesity hypoventilation syndrome. Respir Care. Dec 2008;53(12):1723-30. [Medline].

  7. Miller A, Granada M. In-hospital mortality in the Pickwickian syndrome. Am J Med. Feb 1974;56(2):144-50. [Medline].

  8. Weitzenblum E, Kessler R, Canuet M, Chaouat A. [Obesity-hypoventilation syndrome]. Rev Mal Respir. Apr 2008;25(4):391-403. [Medline].

  9. Paschoal IA, Villalba Wde O, Pereira MC. Chronic respiratory failure in patients with neuromuscular diseases: diagnosis and treatment. J Bras Pneumol. Feb 2007;33(1):81-92. [Medline].

  10. [Guideline] Kushida CA, Littner MR, Morgenthaler T, et al. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep. Apr 1 2005;28(4):499-521. [Medline].

  11. Ozsancak A, D'Ambrosio C, Hill NS. Nocturnal noninvasive ventilation. Chest. May 2008;133(5):1275-86. [Medline].

  12. Banerjee D, Yee BJ, Piper AJ, Zwillich CW, Grunstein RR. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest. Jun 2007;131(6):1678-84. [Medline].

  13. [Guideline] Kushida CA, Littner MR, Hirshkowitz M, et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep. Mar 1 2006;29(3):375-80. [Medline].

  14. [Guideline] Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. National Guidelines Clearinghouse. 2008.

  15. Lyons HA, Huang CT. Therapeutic use of progesterone in alveolar hypoventilation associated with obesity. Am J Med. Jun 1968;44(6):881-8. [Medline].

  16. Morrison DA, Goldman AL. Oral progesterone treatment in chronic obstructive lung disease: failure of voluntary hyperventilation to predict response. Thorax. Aug 1986;41(8):616-9. [Medline].

  17. Johnson W, DeMaria E. Surgical treatment of obesity. Curr Treat Options Gastroenterol. Apr 2006;9(2):167-74. [Medline].

  18. Taira T, Takeda N, Itoh K, Oikawa A, Hori T. Phrenic nerve stimulation for diaphragm pacing with a spinal cord stimulator: technical note. Surg Neurol. Feb 2003;59(2):128-32; discussion 132. [Medline].

  19. Chen ML, Tablizo MA, Kun S, Keens TG. Diaphragm pacers as a treatment for congenital central hypoventilation syndrome. Expert Rev Med Devices. Sep 2005;2(5):577-85. [Medline].

  20. Chakrabarti B, Angus RM. Ventilatory failure on acute take. Clin Med. Nov-Dec 2005;5(6):630-4. [Medline].

  21. Chen ML, Turkel SB, Jacobson JR, Keens TG. Alcohol use in congenital central hypoventilation syndrome. Pediatr Pulmonol. Mar 2006;41(3):283-5. [Medline].

  22. Adnet F, Plaisance P, Borron SW, Levy A, Payen D. Prolonged severe hypercapnia complicating near fatal asthma in a 35-year-old woman. Intensive Care Med. Dec 1998;24(12):1335-8. [Medline].

  23. American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. Aug 1 1999;22(5):667-89. [Medline].

  24. BaHammam A, Syed S, Al-Mughairy A. Sleep-related breathing disorders in obese patients presenting with acute respiratory failure. Respir Med. Jun 2005;99(6):718-25. [Medline].

  25. Caruana-Montaldo B, Gleeson K, Zwillich CW. The control of breathing in clinical practice. Chest. Jan 2000;117(1):205-25. [Medline].

  26. Culebras A. Sleep disorders and neuromuscular disease. Semin Neurol. Mar 2005;25(1):33-8. [Medline].

  27. De Troyer A, Borenstein S, Cordier R. Analysis of lung volume restriction in patients with respiratory muscle weakness. Thorax. Aug 1980;35(8):603-10. [Medline].

  28. Hoo GW, Hakimian N, Santiago SM. Hypercapnic respiratory failure in COPD patients: response to therapy. Chest. Jan 2000;117(1):169-77. [Medline].

  29. Kassirer JP, Madias NE. Respiratory acid-base disorders. Hosp Pract. Dec 1980;15(12):57-9, 65-71. [Medline].

  30. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. Aug 2001;120(2):369-76. [Medline].

  31. Krachman S, Criner GJ. Hypoventilation syndromes. Clin Chest Med. Mar 1998;19(1):139-55. [Medline].

  32. Langevin B, Petitjean T, Philit F, Robert D. Nocturnal hypoventilation in chronic respiratory failure (CRF) due to neuromuscular disease. Sleep. Jun 15 2000;23 Suppl 4:S204-8. [Medline].

  33. Masa JF, Celli BR, Riesco JA, et al. The obesity hypoventilation syndrome can be treated with noninvasive mechanical ventilation. Chest. Apr 2001;119(4):1102-7. [Medline].

  34. Nixon GM, Brouillette RT. Sleep and breathing in Prader-Willi syndrome. Pediatr Pulmonol. Sep 2002;34(3):209-17. [Medline].

  35. O'Donoghue FJ, Catcheside PG, Ellis EE, et al. Sleep hypoventilation in hypercapnic chronic obstructive pulmonary disease: prevalence and associated factors. Eur Respir J. Jun 2003;21(6):977-84. [Medline].

  36. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med. Sep 2005;118(9):948-56. [Medline].

  37. Perez de Llano LA, Golpe R, Ortiz Piquer M, Veres Racamonde A, Vázquez Caruncho M, Caballero Muinelos O. Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. Aug 2005;128(2):587-94. [Medline].

  38. Perrin C, D'Ambrosio C, White A, Hill NS. Sleep in restrictive and neuromuscular respiratory disorders. Semin Respir Crit Care Med. Feb 2005;26(1):117-30. [Medline].

  39. Plant PK, Owen JL, Elliott MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration. Thorax. Jul 2000;55(7):550-4. [Medline].

  40. Poulain M, Doucet M, Major GC, Drapeau V, Series F, Boulet LP. The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. CMAJ. Apr 25 2006;174(9):1293-9. [Medline].

  41. Schlichtig R, Grogono AW, Severinghaus JW. Current status of acid-base quantitation in physiology and medicine. Anesth Clin North Am. 1998;16 (1):211-33.

  42. Tuggey JM, Elliott MW. Titration of non-invasive positive pressure ventilation in chronic respiratory failure. Respir Med. Jul 2006;100(7):1262-9. [Medline].

  43. Ward S, Chatwin M, Heather S, Simonds AK. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Thorax. Dec 2005;60(12):1019-24. [Medline].

  44. Weitzenblum E, Chaouat A. Sleep and chronic obstructive pulmonary disease. Sleep Med Rev. Aug 2004;8(4):281-94. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hypoventilation syndrome, primary alveolar hypoventilation, alveolar ventilation, VA, obesity hypoventilation syndrome, OHS, chronic obstructive pulmonary disease with hypercapnia, hypercapnia, chronic obstructive pulmonary disease, COPD, chronic lung disease, hypoxemia, hypoxia, respiratory system, respiratory failure, obstructive sleep apnea, sleep apnea, OSA, chest wall deformities, respiratory insufficiency, myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barre syndrome, Guillain-Barré syndrome, muscular dystrophy, kyphoscoliosis, dyspnea, central respiratory drive depression, pickwickian syndrome

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Jazeela Fayyaz, DO, Senior Fellow, Department of Pulmonology, Lenox Hill Hospital
Jazeela Fayyaz, DO is a member of the following medical societies: American College of Physicians and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Medical Editor

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H, Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine
Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine
Disclosure: Keck School of Medicine, USC None None

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.