Obesity hypoventilation syndrome

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Obesity hypoventilation syndrome
Other namesPickwickian syndrome
Cpap-example.jpg
Obesity hypoventilation syndrome often improves with positive airway pressure treatment administered overnight by a machine such as this device
Specialty Respirology
Risk factors Obesity

Obesity hypoventilation syndrome (OHS) is a condition in which severely overweight people fail to breathe rapidly or deeply enough, resulting in low oxygen levels and high blood carbon dioxide (CO2) levels. The syndrome is often associated with obstructive sleep apnea (OSA), which causes periods of absent or reduced breathing in sleep, resulting in many partial awakenings during the night and sleepiness during the day. [1] The disease puts strain on the heart, which may lead to heart failure and leg swelling.

Contents

Obesity hypoventilation syndrome is defined as the combination of obesity and an increased blood carbon dioxide level during the day that is not attributable to another cause of excessively slow or shallow breathing. [2]

The most effective treatment is weight loss, but this may require bariatric surgery to achieve. [3] Weight loss of 25 to 30% is usually required to resolve the disorder. [3] The other first-line treatment is non-invasive positive airway pressure (PAP), usually in the form of continuous positive airway pressure (CPAP) at night. [4] [5] The disease was known initially in the 1950s, as "Pickwickian syndrome" in reference to a Dickensian character. [5]

Signs and symptoms

Most people with obesity hypoventilation syndrome have concurrent obstructive sleep apnea, a condition characterized by snoring, brief episodes of apnea (cessation of breathing) during the night, interrupted sleep and excessive daytime sleepiness. In OHS, sleepiness may be worsened by elevated blood levels of carbon dioxide, which causes drowsiness ("CO2 narcosis"). Other symptoms present in both conditions are depression, and hypertension (high blood pressure) which is difficult to control with medication. [4] The high carbon dioxide can also cause headaches, which tend to be worsening in the morning. [6]

The low oxygen level leads to physiologic constriction of the pulmonary arteries to correct ventilation-perfusion mismatching, which puts excessive strain on the right side of the heart. When this leads to right sided heart failure, it is known as cor pulmonale . [4] Symptoms of this disorder occur because the heart has difficulty pumping blood from the body through the lungs. Fluid may, therefore, accumulate in the skin of the legs in the form of edema (swelling), and in the abdominal cavity in the form of ascites; decreased exercise tolerance and exertional chest pain may occur. On physical examination, characteristic findings are the presence of a raised jugular venous pressure, a palpable parasternal heave, a heart murmur due to blood leaking through the tricuspid valve, hepatomegaly (an enlarged liver), ascites and leg edema. [7] Cor pulmonale occurs in about a third of all people with OHS. [5]

Mechanism

It is not fully understood why some obese people develop obesity hypoventilation syndrome while others do not. It is likely that it is the result of an interplay of various processes. Firstly, work of breathing is increased as adipose tissue restricts the normal movement of the chest muscles and makes the chest wall less compliant, the diaphragm moves less effectively, respiratory muscles are fatigued more easily, and airflow in and out of the lung is impaired by excessive tissue in the head and neck area. Hence, people with obesity need to expend more energy to breathe effectively. [8] [9] These factors together lead to sleep-disordered breathing and inadequate removal of carbon dioxide from the circulation and hence hypercapnia; given that carbon dioxide in aqueous solution combines with water to form an acid (CO2[g] + H2O[l] + excess H2O[l] --> H2CO3[aq]), this causes acidosis (increased acidity of the blood). Under normal circumstances, central chemoreceptors in the brain stem detect the acidity, and respond by increasing the respiratory rate; in OHS, this "ventilatory response" is blunted. [5] [10]

The blunted ventilatory response is attributed to several factors. Obese people tend to have raised levels of the hormone leptin, which is secreted by adipose tissue and under normal circumstances increases ventilation. In OHS, this effect is reduced. [5] [10] Furthermore, episodes of nighttime acidosis (e.g. due to sleep apnea) lead to compensation by the kidneys with retention of the alkali bicarbonate. This normalizes the acidity of the blood. However, bicarbonate stays around in the bloodstream for longer, and further episodes of hypercapnia lead to relatively mild acidosis and reduced ventilatory response in a vicious circle. [5] [10]

Low oxygen levels lead to hypoxic pulmonary vasoconstriction, the tightening of small blood vessels in the lung to create an optimal distribution of blood through the lung. Persistently low oxygen levels causing chronic vasoconstriction leads to increased pressure on the pulmonary artery (pulmonary hypertension), which in turn puts strain on the right ventricle, the part of the heart that pumps blood to the lungs. The right ventricle undergoes remodeling, becomes distended and is less able to remove blood from the veins. When this is the case, raised hydrostatic pressure leads to accumulation of fluid in the skin (edema), and in more severe cases the liver and the abdominal cavity. [5]

The chronically low oxygen levels in the blood also lead to increased release of erythropoietin and the activation of erythropoeisis, the production of red blood cells. This results in polycythemia, abnormally increased numbers of circulating red blood cells and an elevated hematocrit. [5]

Diagnosis

Formal criteria for diagnosis of OHS are: [4] [5] [11]

If OHS is suspected, various tests are required for its confirmation. The most important initial test is the demonstration of elevated carbon dioxide in the blood. This requires an arterial blood gas determination, which involves taking a blood sample from an artery, usually the radial artery. Given that it would be complicated to perform this test on every patient with sleep-related breathing problems, some suggest that measuring bicarbonate levels in normal (venous) blood would be a reasonable screening test. If this is elevated (27 mmol/L or higher), blood gasses should be measured. [5]

To distinguish various subtypes, polysomnography is required. This usually requires brief admission to a hospital with a specialized sleep medicine department where a number of different measurements are conducted while the subject is asleep; this includes electroencephalography (electronic registration of electrical activity in the brain), electrocardiography (same for electrical activity in the heart), pulse oximetry (measurement of oxygen levels) and often other modalities. [4] Blood tests are also recommended for the identification of hypothyroidism and polycythemia. [4] [5]

To distinguish between OHS and various other lung diseases that can cause similar symptoms, medical imaging of the lungs (such as a chest X-ray or CT/CAT scan), spirometry, electrocardiography and echocardiography may be performed. Echo- and electrocardiography may also show strain on the right side of the heart caused by OHS, and spirometry may show a restrictive pattern related to obesity. [5]

Classification

Obesity hypoventilation syndrome is a form of sleep disordered breathing. Two subtypes are recognized, depending on the nature of disordered breathing detected on further investigations. The first is OHS in the context of obstructive sleep apnea; this is confirmed by the occurrence of 5 or more episodes of apnea, hypopnea or respiratory-related arousals per hour (high apnea-hypopnea index) during sleep. The second is OHS primarily due to "sleep hypoventilation syndrome"; this requires a rise of CO2 levels by 10 mmHg (1.3 kPa) after sleep compared to awake measurements and overnight drops in oxygen levels without simultaneous apnea or hypopnea. [4] [11] Overall, 90% of all people with OHS fall into the first category, and 10% in the second. [5]

Treatment

In people with stable OHS, the most important treatment is weight loss—by diet, through exercise, with medication, or sometimes weight loss surgery (bariatric surgery). This has been shown to improve the symptoms of OHS and resolution of the high carbon dioxide levels. Weight loss may take a long time and is not always successful. [4] If the symptoms are significant, nighttime positive airway pressure (PAP) treatment is tried; this involves the use of a machine to assist with breathing. PAP exists in various forms, and the ideal strategy is uncertain. Some medications have been tried to stimulate breathing or correct underlying abnormalities; their benefit is again uncertain. [5]

While many people with obesity hypoventilation syndrome are cared for on an outpatient basis, some deteriorate suddenly and when admitted to the hospital may show severe abnormalities such as markedly deranged blood acidity (pH<7.25) or depressed level of consciousness due to very high carbon dioxide levels. On occasions, admission to an intensive care unit with intubation and mechanical ventilation is necessary. Otherwise, "bi-level" positive airway pressure (see the next section) is commonly used to stabilize the patient, followed by conventional treatment. [12]

Positive airway pressure

Positive airway pressure, initially in the form of continuous positive airway pressure (CPAP), is a useful treatment for obesity hypoventilation syndrome, particularly when obstructive sleep apnea coexists. CPAP requires the use during sleep of a machine that delivers a continuous positive pressure to the airways and preventing the collapse of soft tissues in the throat during breathing; it is administered through a mask on either the mouth and nose together or if that is not tolerated on the nose only (nasal CPAP). This relieves the features of obstructive sleep apnea and is often sufficient to remove the resultant accumulation of carbon dioxide. The pressure is increased until the obstructive symptoms (snoring and periods of apnea) have disappeared. CPAP alone is effective in more than 50% of people with OHS. [5]

In some occasions, the oxygen levels are persistently too low (oxygen saturations below 90%). In that case, the hypoventilation itself may be improved by switching from CPAP treatment to an alternate device that delivers "bi-level" positive pressure: higher pressure during inspiration (breathing in) and a lower pressure during expiration (breathing out). If this too is ineffective in increasing oxygen levels, the addition of oxygen therapy may be necessary. As a last resort, tracheostomy may be necessary; this involves making a surgical opening in the trachea to bypass obesity-related airway obstruction in the neck. This may be combined with mechanical ventilation with an assisted breathing device through the opening. [5]

Other treatments

People who fail first-line treatments or have very severe, life-threatening disease may sometimes be treated with tracheotomy, which is a reversible procedure. [13] Treatments without proven benefit, and concern for harm, include oxygen alone or respiratory stimulant medications. Medroxyprogesterone acetate, a progestin, and acetazolamide are both associated with an increased risk of thrombosis and are not recommended. [4] [5]

Prognosis

Obesity hypoventilation syndrome is associated with a reduced quality of life, and people with the condition incur increased healthcare costs, largely due to hospital admissions including observation and treatment on intensive care units. OHS often occurs together with several other disabling medical conditions, such as asthma (in 18–24%) and type 2 diabetes (in 30–32%). Its main complication of heart failure affects 21–32% of patients. [5]

Those with abnormalities severe enough to warrant treatment have an increased risk of death reported to be 23% over 18 months and 46% over 50 months. This risk is reduced to less than 10% in those receiving treatment with PAP. Treatment also reduces the need for hospital admissions and reduces healthcare costs. [5]

Epidemiology

The exact prevalence of obesity hypoventilation syndrome is unknown, and it is thought that many people with symptoms of OHS have not been diagnosed. [4] About a third of all people with morbid obesity (a body mass index exceeding 40 kg/m2) have elevated carbon dioxide levels in the blood. [5]

When examining groups of people with obstructive sleep apnea, researchers have found that 10–20% of them meet the criteria for OHS as well. The risk of OHS is much higher in those with more severe obesity, i.e. a body mass index (BMI) of 40 kg/m2 or higher. It is twice as common in men compared to women. The average age at diagnosis is 52. American Black people are more likely to be obese than American whites, and are therefore more likely to develop OHS, but obese Asians are more likely than people of other ethnicities to have OHS at a lower BMI as a result of physical characteristics. [5]

It is anticipated that rates of OHS will rise as the prevalence of obesity rises. This may also explain why OHS is more commonly reported in the United States, where obesity is more common than in other countries. [5]

History

The discovery of obesity hypoventilation syndrome is generally attributed to the authors of a 1956 report of a professional poker player who, after gaining weight, became somnolent and fatigued and prone to fall asleep during the day, as well as developing edema of the legs suggesting heart failure. The authors coined the condition "Pickwickian syndrome" after the character Joe from Dickens' The Posthumous Papers of the Pickwick Club (1837), who was markedly obese and tended to fall asleep uncontrollably during the day. [14] This report, however, was preceded by other descriptions of hypoventilation in obesity. [5] [15] In the 1960s, various further discoveries were made that led to the distinction between obstructive sleep apnea and sleep hypoventilation. [16]

The term "Pickwickian syndrome" has fallen out of favor because it does not distinguish obesity hypoventilation syndrome and sleep apnea as separate disorders (which may coexist). [16] [17]

Related Research Articles

<span class="mw-page-title-main">Sleep apnea</span> Disorder involving pauses in breathing during sleep

Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times a night. In the most common form, this follows loud snoring. A choking or snorting sound may occur as breathing resumes. Because the disorder disrupts normal sleep, those affected may experience sleepiness or feel tired during the day. In children, it may cause hyperactivity or problems in school.

<span class="mw-page-title-main">Respiratory failure</span> Inadequate gas exchange by the respiratory system

Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes increased respiratory rate, abnormal blood gases, and evidence of increased work of breathing. Respiratory failure causes an altered mental status due to ischemia in the brain.

Apnea, BrE: apnoea, is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are, there may or may not be a flow of gas between the lungs and the environment. If there is sufficient flow, gas exchange within the lungs and cellular respiration would not be severely affected. Voluntarily doing this is called holding one's breath. Apnea may first be diagnosed in childhood, and it is recommended to consult an ENT specialist, allergist or sleep physician to discuss symptoms when noticed; malformation and/or malfunctioning of the upper airways may be observed by an orthodontist.

<span class="mw-page-title-main">Positive airway pressure</span> Mechanical ventilation in which airway pressure is always above atmospheric pressure

Positive airway pressure (PAP) is a mode of respiratory ventilation used in the treatment of sleep apnea. PAP ventilation is also commonly used for those who are critically ill in hospital with respiratory failure, in newborn infants (neonates), and for the prevention and treatment of atelectasis in patients with difficulty taking deep breaths. In these patients, PAP ventilation can prevent the need for tracheal intubation, or allow earlier extubation. Sometimes patients with neuromuscular diseases use this variety of ventilation as well. CPAP is an acronym for "continuous positive airway pressure", which was developed by Dr. George Gregory and colleagues in the neonatal intensive care unit at the University of California, San Francisco. A variation of the PAP system was developed by Professor Colin Sullivan at Royal Prince Alfred Hospital in Sydney, Australia, in 1981.

<span class="mw-page-title-main">Hypercapnia</span> Abnormally high tissue carbon dioxide levels

Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation".

<span class="mw-page-title-main">Generalized hypoxia</span> Medical condition of oxygen deprivation

Generalized hypoxia is a medical condition in which the tissues of the body are deprived of the necessary levels of oxygen due to an insufficient supply of oxygen, which may be due to the composition or pressure of the breathing gas, decreased lung ventilation, or respiratory disease, any of which may cause a lower than normal oxygen content in the arterial blood, and consequently a reduced supply of oxygen to all tissues perfused by the arterial blood. This usage is in contradistinction to localized hypoxia, in which only an associated group of tissues, usually with a common blood supply, are affected, usually due to an insufficient or reduced blood supply to those tissues. Generalized hypoxia is also used as a synonym for hypoxic hypoxia This is not to be confused with hypoxemia, which refers to low levels of oxygen in the blood, although the two conditions often occur simultaneously, since a decrease in blood oxygen typically corresponds to a decrease in oxygen in the surrounding tissue. However, hypoxia may be present without hypoxemia, and vice versa, as in the case of infarction. Several other classes of medical hypoxia exist.

Upper airway resistance syndrome (UARS) is a sleep disorder characterized by the narrowing of the airway that can cause disruptions to sleep. The symptoms include unrefreshing sleep, fatigue, sleepiness, chronic insomnia, and difficulty concentrating. UARS can be diagnosed by polysomnograms capable of detecting Respiratory Effort-related Arousals. It can be treated with lifestyle changes, orthodontics, surgery, or CPAP therapy. UARS is considered a variant of sleep apnea, although some scientists and doctors believe it to be a distinct disorder.

<span class="mw-page-title-main">Mandibular advancement splint</span>

A mandibi splint or mandibi advancement splint is a prescription custom-made medical device worn in the mouth used to treat sleep-related breathing disorders including: obstructive sleep apnea (OSA), snoring, and TMJ disorders. These devices are also known as mandibular advancement devices, sleep apnea oral appliances, oral airway dilators, and sleep apnea mouth guards.

<span class="mw-page-title-main">Non-invasive ventilation</span> Breathing support administered through a face mask

Non-invasive ventilation (NIV) is the use of breathing support administered through a face mask, nasal mask, or a helmet. Air, usually with added oxygen, is given through the mask under positive pressure; generally the amount of pressure is alternated depending on whether someone is breathing in or out. It is termed "non-invasive" because it is delivered with a mask that is tightly fitted to the face or around the head, but without a need for tracheal intubation. While there are similarities with regard to the interface, NIV is not the same as continuous positive airway pressure (CPAP), which applies a single level of positive airway pressure throughout the whole respiratory cycle; CPAP does not deliver ventilation but is occasionally used in conditions also treated with NIV.

<span class="mw-page-title-main">Obstructive sleep apnea</span> Sleeping and breathing disorder

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episodes are termed "apneas" with complete or near-complete cessation of breathing, or "hypopneas" when the reduction in breathing is partial. In either case, a fall in blood oxygen saturation, a disruption in sleep, or both, may result. A high frequency of apneas or hypopneas during sleep may interfere with the quality of sleep, which – in combination with disturbances in blood oxygenation – is thought to contribute to negative consequences to health and quality of life. The terms obstructive sleep apnea syndrome (OSAS) or obstructive sleep apnea–hypopnea syndrome (OSAHS) may be used to refer to OSA when it is associated with symptoms during the daytime.

<span class="mw-page-title-main">Hypoxemia</span> Abnormally low level of oxygen in the blood

Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body.

Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea, while other researchers have discovered hypopnea to have a "similar if not indistinguishable impact" on the negative outcomes of sleep breathing disorders. In sleep clinics, obstructive sleep apnea syndrome or obstructive sleep apnea–hypopnea syndrome is normally diagnosed based on the frequent presence of apneas and/or hypopneas rather than differentiating between the two phenomena. Hypopnea is typically defined by a decreased amount of air movement into the lungs and can cause oxygen levels in the blood to drop. It commonly is due to partial obstruction of the upper airway.

Apnea of prematurity is a disorder in infants who are preterm that is defined as cessation of breathing by that lasts for more than 20 seconds and/or is accompanied by hypoxia or bradycardia. Apnea of prematurity is often linked to earlier prematurity. Apnea is traditionally classified as either obstructive, central, or mixed. Obstructive apnea may occur when the infant's neck is hyperflexed or conversely, hyperextended. It may also occur due to low pharyngeal muscle tone or to inflammation of the soft tissues, which can block the flow of air though the pharynx and vocal cords. Central apnea occurs when there is a lack of respiratory effort. This may result from central nervous system immaturity, or from the effects of medications or illness. Many episodes of apnea of prematurity may start as either obstructive or central, but then involve elements of both, becoming mixed in nature.

<span class="mw-page-title-main">Continuous positive airway pressure</span> Form of ventilator which applies mild air pressure continuously to keep airways open

Continuous positive airway pressure (CPAP) is a form of positive airway pressure (PAP) ventilation in which a constant level of pressure greater than atmospheric pressure is continuously applied to the upper respiratory tract of a person. The application of positive pressure may be intended to prevent upper airway collapse, as occurs in obstructive sleep apnea, or to reduce the work of breathing in conditions such as acute decompensated heart failure. CPAP therapy is highly effective for managing obstructive sleep apnea. Compliance and acceptance of use of CPAP therapy can be a limiting factor, with 8% of people stopping use after the first night and 50% within the first year.

Paroxysmal nocturnal dyspnea or paroxysmal nocturnal dyspnoea (PND) is an attack of severe shortness of breath and coughing that generally occurs at night. It usually awakens the person from sleep, and may be quite frightening. PND, as well as simple orthopnea, may be relieved by sitting upright at the side of the bed with legs dangling, as symptoms typically occur when the person is recumbent, or lying down.

<span class="mw-page-title-main">ROHHAD</span> Medical condition

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition whose etiology is currently unknown. ROHHAD mainly affects the endocrine system and autonomic nervous system, but patients can exhibit a variety of signs. Patients present with both alveolar hypoventilation along with hypothalamic dysfunction, which distinguishes ROHHAD from congenital central hypoventilation syndrome (CCHS). ROHHAD is a rare disease, with only 100 reported cases worldwide thus far.

<span class="mw-page-title-main">Breathing</span> Process of moving air in and out of the lungs

Breathing is the process of moving air into and from the lungs to facilitate gas exchange with the internal environment, mostly to flush out carbon dioxide and bring in oxygen.

Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation. CSA is usually due to an instability in the body's feedback mechanisms that control respiration. Central sleep apnea can also be an indicator of Arnold–Chiari malformation.

A sleep-related breathing disorder is a sleep disorder in which abnormalities in breathing occur during sleep that may or may not be present while awake. According to the International Classification of Sleep Disorders, sleep-related breathing disorders are classified as follows:

Sleep surgery is a surgery performed to treat sleep disordered breathing. Sleep disordered breathing is a spectrum of disorders that includes snoring, upper airway resistance syndrome, and obstructive sleep apnea. These surgeries are performed by surgeons trained in otolaryngology, oral maxillofacial surgery, and craniofacial surgery.

References

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  2. ↑ American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
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