Regardless of the underlying cause, the clinical presentation of patients with hypoventilation (which may be literally translated as lower breathing rate) is similar. Initial stages may be asymptomatic, but complaints such as dyspnea, fatigue and increased exertion effort may be reported. In obesity hypoventilation syndrome and nocturnal hypoventilation, disturbed sleep and hypersomnolence is frequently noted, whereas infections and COPD can present with expectorating cough and high fever. Central hypoventilation syndromes in newborns and infants present with severe cyanosis and apnea, often leading to cardiorespiratory arrest [5]. Respiratory acidosis may have either a severe acute or chronic asymptomatic course. Headaches, disturbed mental state, tremor, drowsiness and asterixis are clinical hallmarks of acute respiratory acidosis [1]. Additional signs include gait disturbances, papilledema, memory loss and even stupor [1].

• Hypoxemia

  Twenty-three patients did not have nocturnal hypoxemia and 18 were clinically asymptomatic. In 20 patients, PaCO 2 in daytime blood samples was normal. [ncbi.nlm.nih.gov]

  Sleep related hypoventilation/hypoxemia in condition Sleep related hypoxemia Sleep related hypoxemia, code first primary disease ICD-10-CM G47.36 is grouped within Diagnostic Related Group(s) (MS-DRG v 36.0): 011 Tracheostomy for face,mouth & neck diagnoses [icd10data.com]

  This is video 3 of the 5 main causes of hypoxemia: hypoventilation. Other videos in this series explain high altitude, pulmonary diffusion, shunting, and ventilation perfusion mismatch (VQ mismatch). [youtube.com]

  Arterial blood gas analysis (ABG), however, is a necessary diagnostic method which confirms hypercapnia and hypoxemia, while additional laboratory studies should be conducted in order to establish the underlying cause. [symptoma.com]

• Congestive Heart Failure

  Randomized controlled trial of nasal CPAP in 66 patients with congestive heart failure. [link.springer.com]

  Treatment and prognosis Compared to obese patients, patients with obesity hypoventilation syndrome are prone to more severe obesity, congestive heart failure, angina pectoris, cor pulmonale and secondary pulmonary arterial hypertension. [radiopaedia.org]

  Complications Chronic hypoventilation may be associated with congestive heart failure, cor pulmonale and angina. [patient.info]

  Haque WA, Boehmer J, Clemson BS, Leuenberger UA, Silber DH, et al. (1996) Hemodynamic effects of supplemental oxygen administrationin congestive heart failure. J Am Coll Cardiol 27: 353–7. pmid:8557905 View Article PubMed/NCBI Google Scholar 28. [journals.plos.org]

• Hypersomnia

  Artigo em Ro | MEDLINE | ID: mdl-17494270 Described in the specialty literature for over one century under the name of Pickwick syndrome, the obesity -- hypoventilation syndrome (OHS) includes the triad: obesity -- hypoventilation --hypersomnia. [pesquisa.bvsalud.org]

  NARCOLEPSY Narcolepsy is one of the major Sleep Disorders or Hypersomnia and is best described as an uncontrollable excessive sleeping tendency, particularly during what may be considered “normal” daylight hours. [americansleepassociation.org]

  HYPERSOMNIA VS. FATIGUE When investigating potential causes of EDS, it is important to distinguish between fatigue and excessive sleepiness, or hypersomnia. [rjjaramillo.wordpress.com]

• Hypothermia

  Causes : Inadequate reversal, overdose, hypothermia, pharmacological interactions, hypokalemia, respiratory acidosis, splinting from incisional pain or diaphragmatic dysfunction Treatment : pH less than 7.15, severely obtunded are indications for immediate [openanesthesia.org]

• Hypercapnic Respiratory Failure

  BACKGROUND: Non-invasive ventilation (NIV) is increasingly used in the treatment of patients with chronic hypercapnic respiratory failure (CRF). [ncbi.nlm.nih.gov]

  Managing the various problems associated with obesity is complex – hypoventilation and hypercapnic respiratory failure are a major problem. [nursingtimes.net]

  Some patients seem suddenly to experience life-threatening hypercapnic respiratory failure. [gbppa.org]

• Bradypnea

  Hypoventilation can be due to breathing that is too shallow (hypopnea) or too slow (bradypnea), or to diminished lung function. The opposite of hypoventilation is hyperventilation (overbreathing). [medicinenet.com]

  See also hypopnea and bradypnea. hy·po·ven·ti·la·tion ( hī'pō-ven'ti-lā'shŭn ), Reduced alveolar ventilation relative to metabolic carbon dioxide production, so that alveolar carbon dioxide pressure increases above normal. [medical-dictionary.thefreedictionary.com]

  Recurrent respiratory events in the postanesthesia care unit, including apnea for ≥10 s, bradypnea of less than 8 breaths/min, pain-sedation mismatch, or desaturations to less than 90%, can be used to identify patients at high risk of postoperative respiratory [anesthesiology.pubs.asahq.org]

• Abnormal Breathing

  Changes in neuromodulators resulting from the effects of hypoxia may further exacerbate the problem by depressing arousal from sleep in the face of abnormal breathing. [ 1 ] Differentiation has been made between people who have sleep apnoea hypoventilation [patient.info]

  Last but not least, the sustained hypoxia characteristic of sleep breathing in OHS may further contribute to the perpetuation and progression of abnormal breathing through impairment of the arousal response, further adding to the inability of these subjects [respiratory-research.biomedcentral.com]

• Hyperpnea

  In the first cycle, the interevent hyperpnea is sufficient to excrete the carbon dioxide accumulated during hypopnea. In the second cycle, much more carbon dioxide is accumulated during apnea than is excreted after the event. [anesthesiology.pubs.asahq.org]

• Hypertension

  In addition, they are more exposed than obese control subjects to comorbidities, including hypertension, heart failure, pulmonary hypertension, asthma and diabetes mellitus, resulting in higher medical resource utilisation and shorter life expectancy [erj.ersjournals.com]

  Pulmonary hypertension (PH) with kyphoscoliosis-related alveolar hypoventilation is uncommon, so little is known about the effectiveness of treatments for this condition. [ncbi.nlm.nih.gov]

  Pulmonary hypertension Patients with central alveolar hypoventilation, COPD, and OHS may show evidence of pulmonary hypertension from examination findings. [emedicine.medscape.com]

  Treatment and prognosis Compared to obese patients, patients with obesity hypoventilation syndrome are prone to more severe obesity, congestive heart failure, angina pectoris, cor pulmonale and secondary pulmonary arterial hypertension. [radiopaedia.org]

• Hypotension

  ‘Hypotension or hypoventilation that would have precluded transfer was no more common in older patients than in younger patients.’ ‘The airway is reduced and the person will experience hypoventilation (inadequate breathing).’ [en.oxforddictionaries.com]

• Abnormal Behavior

  The first symptom was rapid-onset obesity in 10 of 13 (77%) cases, behavioral abnormalities in two (15%) cases and alveolar hypoventilation in two (8%) cases. [nature.com]

• Headache

  The headache was relieved with oxygen. The physician, while travelling to Sucre (2500 m), for a Medical meeting located at 2500 m, was examined at 3600 m. for the intense headache,. [altitudeclinic.com]

  Headaches, disturbed mental state, tremor, drowsiness and asterixis are clinical hallmarks of acute respiratory acidosis. Additional signs include gait disturbances, papilledema, memory loss and even stupor. [symptoma.com]

  Symptoms include: Bluish coloration of the skin caused by lack of oxygen Daytime drowsiness Fatigue Morning headaches Swelling of the ankles Waking up from sleep unrested Waking up many times at night People with this disease are very sensitive to even [account.allinahealth.org]

  Some symptoms of hypoventilation include stomach problems, headaches, heart problems, faintness, and poor sleep. Issues with sleep commonly occur due to frequent awakenings or sleeping throughout the day. [study.com]

• Seizure

  To investigate specific features and responses to immunotherapy of atypical anti-NMDAR antibody positivity patients, the authors reviewed and evaluated previous case reports/series including patients without seizure, involuntary movement, hypoventilation [ncbi.nlm.nih.gov]

  […] hypoventilation can be an associated cause for other health conditions, such as: stroke impotence hypertension memory loss psychiatric problems cognitive dysfunction coronary heart disease And extreme case of hypercapnia can cause acidosis, myoclonus, seizures [healthblurbs.com]

  Some affected individuals will not be identified until after receiving sedation, anesthesia, or anti-seizure medications. [clinicaladvisor.com]

• Irritability

  Signs and Symptoms People with obesity hypoventilation syndrome -- OHS -- typically complain of daytime sleepiness, morning headaches, problems with concentration or memory, mood swings, irritability and depression. [livehealthy.chron.com]

  […] generally defined as a PaCO 2 greater than 45, although hypoventilation is usually only clinically significant when PaCO 2 is greater than 60 or pH is Signs/Symptoms : Somnolence, airway obstruction, slow respiratory rate, tachycardia, HTN or cardiac irritability [openanesthesia.org]

  OHS complications related to a lack of sleep may include: Depression, agitation, irritability Increased risk of accidents or mistakes at work Problems with intimacy and sex OHS can also cause heart problems, such as: High blood pressure ( hypertension [medlineplus.gov]

  Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more. [nytimes.com]

A detailed approach to the patient must be conducted in order to determine the underlying cause of hypoventilation. A meticulous physical examination coupled with a properly obtained patient history should provide an initial insight into the pathology, but various laboratory and imaging studies are necessary to solidify the diagnosis. Firstly, arterial blood gasses (ABGs) should be evaluated in all patients in whom dyspnea and impaired breathing rates are observed, together with a complete blood count (CBC), serum electrolytes (particularly bicarbonate), and renal function tests including creatinine and blood urea nitrogen [1]. Serum levels of thyroid hormones can be useful in excluding hypothyroidism as a potential cause. Imaging studies, such as plain radiography or chest CT are useful methods to assess the lungs and can detect elevation of hemidiaphragms or diaphragmal flattening and hyperinflation (considered as a hallmark of COPD). Spirometry is a vital diagnostic procedure in patients with suspected hypoventilation and can determine the functional capacity of the respiratory system. If the cause is not found after these tests, neuromuscular evaluation through electromyography (EMG) and measurement of transdiaphragmal pressure should be done. Polysomnography should be considered in patients who report sleep disturbances.

• Hypercapnia

  Finally, 13/29 patients with NH had isolated nocturnal hypercapnia without nocturnal hypoxia, clinical NH symptoms, or daytime hypercapnia. [ncbi.nlm.nih.gov]

  […] do in fact develop chronic diurnal hypercapnia. [bjmp.org]

  Nocturnal hypercapnia has been defined as a mean overnight P CO 2 >50 mmHg. [err.ersjournals.com]

Correction of the underlying disorder that caused hypoventilation is the single most important therapeutic strategy. However, ensuring adequate ventilation and correction of PaCO2 and PaO2 are also vital, which is most commonly performed by instating various forms of assisted ventilation. Supplemental oxygen should be instated in all patients, whereas noninvasive positive pressure ventilation has shown to be an optimal method [8]. The necessity for more invasive methods such as endotracheal intubation or even tracheostomy may be warranted in severe cases [3]. Administration of bronchodilators and correction of electrolytes, mainly potassium, bicarbonate and chloride is important as well. NaHCO3 should, in theory, markedly increase blood pH in the setting of respiratory acidosis, but it is contraindicated in this group of patients because bicarbonate can be converted to CO2 and cross the blood brain barrier [1], thus causing marked disbalance between blood and brain pH and putting the patients at great risk for seizures. Drug-induced hypoventilation is effectively treated by flumazenil (in the case of benzodiazepine overdose) or naloxone (used in patients with opioid overdose).

It is difficult to predict the outcome of patients who develop hypoventilation and most important factors include the underlying etiology, severity of other accompanying symptoms and responsiveness to therapy. Additionally, the time of diagnosis is equally important, as milder gas-exchange disturbances can be more effectively treated. Moreover, the development of pulmonary hypertension and cor pulmonale in advanced stages of diseases can't be reversed in many patients. One of the most important complications of hypoventilation, however, is respiratory acidosis, in which profound hypercapnia, hypoxia and acidosis can lead to rapid deterioration of the patient's general condition [1].

Under physiological conditions, factors that determine adequate ventilation and gas exchange include the functionality of the respiratory muscles (the diaphragm, abdominal and the intercostals) and proper regulation by higher structures [3]. Numerous conditions can impair the activity of the chest wall, gas exchange or cause defective central nervous system breathing regulation and provoke hypoventilation [1] [2] [7] [8]:

• Neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) Guillain-Barré syndrome, myasthenia gravis, poliomyelitis and various muscular dystrophies, including Duchenne muscular dystrophy and Becker muscular dystrophy.
• Lung diseases - COPD, emphysema, chronic bronchitis and asthma.
• Chest wall deformities - scoliosis (with or without kyphosis) and fibrothorax.
• Obesity hypoventilation syndrome, in which a triad of obesity, sleep-disordered breathing and daytime hypoventilation causes significant breathing impairment [9].
• Various conditions that fall under the group central hypoventilation syndromes (examples include Arnold Chiari malformation, Prader-Willi syndrome and achondroplasia), which most commonly appear in infancy and early childhood.
• Other notable causes include hypothyroidism, drug-induced (opioids, benzodiazepines) and cystic fibrosis.

The exact prevalence and incidence rates of hypoventilation are unknown, as they appear in a myriad of conditions in variable and often unpredictable rates. Hypoventilation can be seen in patients of all ages and gender, but some conditions can be restricted to certain age groups. Central hypoventilation syndromes are almost exclusively seen in neonates or infants, some of them being present as early as birth and incidence rates of 1 in 200,000 live births indicate their rare occurrence in clinical practice [5]. Obesity hypoventilation syndrome (OHS), on the other hand, is most commonly seen in obese adults and is shown to be present in up to 0.1-0.3% of the adult population [9]. In fact, approximately 10-20% of obese individuals with obstructive sleep apnea suffer from OHS [9]. COPD and lung-related diseases have shown high prevalence rates of hypoventilation, whereas all patients who are diagnosed with neuromuscular diseases will eventually develop respiratory muscle weakness and hypoventilation.

Several mechanisms of hypoventilation have been described. Firstly, neuromuscular diseases, which are mainly characterized by progressive muscle weakness, cause hypoventilation through progressive weakening of the respiratory muscles that leads to reduced capacity for gas exchange [7]. On the other hand, COPD and other intrinsic lung diseases create much harsher conditions for normal air conduction through the bronchial tree as a result of increased amount of dead space and because the expiratory breathing effort is much higher in these patients [6]. Mechanical compression, either due to obesity or chest wall deformities [10], creates a profound load on the thorax and the respiratory muscles to carry out their function, resulting in fatigue and reduced functional capacity. Central nervous system regulation of breathing has also shown to be a target for many diseases that belong to the group of central hypoventilation syndromes, which may be either congenital or acquired [5] [11]. In congenital forms, various gene mutations have been identified, but the exact pathophysiological mechanism remains unknown. Presumably, these diseases cause defects in sensory and integration signaling, as well as functional impairment of the brain stem, the main site of breathing regulation [5]. Regardless of the causative mechanism, inability of the respiratory muscles to perform adequate inhalation and exhalation reduces PaO2 and increases the concentration of PaCO2, leading to hypoxemia and hypercapnia, respectively.

Prevention of hypoventilation can be achieved primarily through identifying the underlying cause before its clinical progression leads to severe respiratory deficits. Early recognition of symptoms and a thorough laboratory workup can significantly aid in reducing the burden of hypercapnia and hypoxemia, which are well-established as factors that severely impair the quality of life and the ability of the patient to perform daily activities. Screening of patients with sleep disorders could be advocated, as it is not uncommon for these patients to develop hypoventilation.

Hypoventilation is a clinical entity characterized by reduced alveolar ventilation with accompanying disturbances in partial pressures of O2 and CO2 (PaO2 and PaCO2, respectively) [1]. The main pathophysiological mechanisms include chest wall abnormalities and reduced capacity for thoracic expansion, weakness of respiratory muscles, mechanical alterations in airflow and bronchial resistance, but also dysregulation of breathing rates by the regulatory centers in the brain [2] [3]. As a result, elevations of PaCO2 and a decrease in PaO2 are observed, which can be detrimental if not managed adequately on time. Neuromuscular diseases, hypothyroidism, chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS) and numerous disorders of the central nervous system (known as central hypoventilation syndromes, some of them being Arnold Chiari malformation and achondroplasia) are listed as potential causes [5] [4] [5]. Hypoventilation can also be a physiological occurrence, for ex. during sleep, when several regulatory changes lead to very small variations in PaCO2 and PaO2, but nocturnal hypoventilation can occur and present as a significant challenge for diagnosis [3]. One of the most important complications is respiratory acidosis, in which acute manifestations of headache, confusion, drowsiness, tremor and asterixis appear after extensive hypercapnia and hypoxia [1]. Other accompanying symptoms may be present, depending on the underlying cause and the initial diagnosis of hypoventilation can be made on clinical criteria. Arterial blood gas analysis (ABG), however, is a necessary diagnostic method which confirms hypercapnia and hypoxemia, while additional laboratory studies should be conducted in order to establish the underlying cause. Thyroid hormone levels and serum electrolytes should be evaluated, whereas spirometry, imaging studies such as plain radiography or computed tomography (CT) of the chest, and polysomnography, if necessary, are valuable tests that can point to the disease that triggered hypoventilation. In most cases, treatment principles rest on managing the disease that caused this respiratory disturbance [6]. Some form of ventilation therapy, however, is almost always necessary, ranging from oxygen supplementation and noninvasive positive pressure ventilation to endotracheal intubation or even tracheostomy. Because rapid deterioration of the patient's condition can occur, an early diagnosis is imperative in achieving good patient outcomes.

Hypoventilation is a clinical manifestation of numerous conditions that interfere with functions of the respiratory system. In clinical terms, hypoventilation (in literal terms, decreased rate of breathing) demarcates reduced gas-exchange in the lungs that leads to accumulation of carbon dioxide in the body, as well as lack of oxygen. Numerous conditions can cause hypoventilation:

• Lung diseases such as bronchial asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD), but also conditions that cause chest wall deformities (scoliosis and kyphosis).
• Illnesses that target the neuromuscular system such as myasthenia gravis, Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and poliomyelitis
• Infections, hypothyroidism, obesity hypoventilation syndrome (OHS), drug-induced, and a group of illnesses known as central hypoventilation syndromes may all cause hypoventilation.

These conditions trigger hypoventilation by either causing weakness of the respiratory muscles, providing a much tougher task of expelling by increasing the resistance of the bronchial tree, or mechanical compression of the chest wall by obesity and other structural deformities. The end-result is inability of the lungs to perform exchange of oxygen and carbon dioxide, leading to the appearance of symptoms such as fatigue and shortness of breath, while many patients report an increased breathing effort. Numerous complications can develop, depending on the severity of disease, one of the most important being respiratory acidosis, in which severe headache, altered mental state and drowsiness may develop as a result of markedly reduced pH and oxygen in blood. To make the diagnosis, it is necessary to obtain levels of arterial blood gasses and serum electrolytes and perform a test that investigates the functional capacity of the lungs known as spirometry. Additionally, imaging techniques such as chest X-ray or computed tomography (CT scan) of the chest may be useful in confirming the underlying cause of hypoventilation. In terms of treatment, identification of the cause is, in fact, the most important step, while symptomatic management through supplemental oxygen and correction of electrolytes is mandatory. In virtually all patients, some form of ventilatory support is necessary, ranging from noninvasive oxygen therapy to intubation and assisted or total artificial ventilation. The prognosis of patients who develop hypoventilation significantly depends on the severity of symptoms at the time of diagnosis and the underlying disease, but prompt recognition can surely improve long-term outcomes.

1. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.

2. Chebbo A, Tfaili A, Jones SF. Hypoventilation syndromes. Med Clin North Am. 2011;95(6):1189-202

3. Piper AJ. Nocturnal hypoventilation - identifying & treating syndromes. Indian J Med Res. 2010;131:350-365.
4. Fukusumi M, Iidaka T, Mouri A, Hamamoto Y, Kamimura M. Respiratory failure associated with hypoventilation in a patient with severe hypothyroidism. Respirol Case Rep. 2014;2(2):79-80.
5. Cielo C, Marcus CL. Central Hypoventilation Syndromes. Sleep Med Clin. 2014;9(1):105-118.
6. Brown LK. Hypoventilation syndromes. Clin Chest Med. 2010;31(2):249-70
7. Paschoal IA, Villalba Wde O, Pereira MC. Chronic respiratory failure in patients with neuromuscular diseases: diagnosis and treatment. J Bras Pneumol. 2007;33(1): 81-92.
8. Muzumdar H, Arens R. Central Alveolar Hypoventilation Syndromes. Sleep Med Clin. 2008;3(4):601-615.
9. Chau EH, Lam D, Wong J, Mokhlesi B, Chung F. Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology. 2012;117(1):188-205.
10. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. 2001; 120: 369-376.
11. Kc P, Martin RJ. Role of Central Neurotransmission and Chemoreception on Airway Control. Respir Physiol Neurobiol. 2010;173(3):213-222.