Obesity hypoventilation syndrome (OHS) is a condition in which severely overweight people fail to breathe rapidly or deeply enough, resulting in low

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

levels and high blood

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

(CO₂) levels. The syndrome is often associated with

obstructive sleep apnea Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial airway obstruction, obstruction of the respiratory tract#Upper respiratory tract, upper airway lea ...

(OSA), which causes periods of absent or reduced breathing in sleep, resulting in many partial awakenings during the night and sleepiness during the day. The disease puts strain on the heart, which may lead to

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

and leg swelling. Obesity hypoventilation syndrome is defined as the combination of

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

and an increased blood carbon dioxide level during the day that is not attributable to another cause of excessively slow or shallow breathing. The most effective treatment is

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

, but this may require

bariatric surgery Bariatric surgery (also known as metabolic surgery or weight loss surgery) is a surgical procedure used to manage obesity and obesity-related conditions. Long term weight loss with bariatric surgery may be achieved through alteration of gut ho ...

to achieve. Weight loss of 25 to 30% is usually required to resolve the disorder. The other first-line treatment is non-invasive positive airway pressure (PAP), usually in the form of continuous positive airway pressure (CPAP) at night. The disease was known initially in the 1950s, as "Pickwickian syndrome" in reference to a Dickensian character.

Signs and symptoms

Most people with obesity hypoventilation syndrome have concurrent

, a condition characterized by snoring, brief episodes of

apnea Apnea (also spelled apnoea in British English) 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 ...

(cessation of breathing) during the night, interrupted sleep and excessive daytime sleepiness. In OHS, sleepiness may be worsened by elevated blood levels of

, which causes drowsiness ("CO₂ narcosis"). Other symptoms present in both conditions are depression, and

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

(high blood pressure) which is difficult to control with medication. The high carbon dioxide can also cause

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

s, which tend to be worsening in the morning. 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''. 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 Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

(swelling), and in the abdominal cavity in the form of ascites; decreased exercise tolerance and exertional

chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...

may occur. On

physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...

, characteristic findings are the presence of a raised

jugular venous pressure The jugular venous pressure (JVP, sometimes referred to as ''jugular venous pulse'') is the indirectly observed pressure over the venous system via visualization of the internal jugular vein. It can be useful in the differentiation of different f ...

, a palpable parasternal heave, a heart murmur due to blood leaking through the tricuspid valve,

hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...

(an enlarged liver), ascites and leg edema. Cor pulmonale occurs in about a third of all people with OHS.

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 Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

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. 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 + H₂O + excess H₂O --> H₂CO₃ q, this causes acidosis (increased acidity of the blood). Under normal circumstances,

central chemoreceptors A central chemoreceptor is a chemoreceptor sensitive to the pH of its environment. Central chemoreceptors are located on the ventrolateral medulla oblongata, medullary surface in vicinity of the exit of CN IX and CN X in the central nervous syste ...

in the

brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...

detect the acidity, and respond by increasing the

respiratory rate The respiratory rate is the rate at which breathing occurs; it is set and controlled by the respiratory center of the brain. A person's respiratory rate is usually measured in breaths per minute. Measurement The respiratory rate in humans is mea ...

; in OHS, this "ventilatory response" is blunted. The blunted ventilatory response is attributed to several factors. Obese people tend to have raised levels of the hormone

leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...

, which is secreted by adipose tissue and under normal circumstances increases ventilation. In OHS, this effect is reduced. Furthermore, episodes of nighttime acidosis (e.g. due to sleep apnea) lead to compensation by the kidneys with retention of the

alkali In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The a ...

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...

. 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. 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 A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...

(

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

), which in turn puts strain on the

right ventricle A ventricle is one of two large chambers located toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium (heart), atrium, an adjace ...

, 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 Hydrostatics is the branch of fluid mechanics that studies fluids at hydrostatic equilibrium and "the pressure in a fluid or exerted by a fluid on an immersed body". The word "hydrostatics" is sometimes used to refer specifically to water and o ...

leads to accumulation of fluid in the skin (edema), and in more severe cases the liver and the abdominal cavity. The chronically low oxygen levels in the blood also lead to increased release of

erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...

and the activation of erythropoeisis, the production of

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

s. This results in

polycythemia Polycythemia (also known as polycythaemia) is a laboratory finding in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythr ...

, abnormally increased numbers of circulating red blood cells and an elevated hematocrit.

Diagnosis

Formal criteria for diagnosis of OHS are: *

Body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...

over 30 kg/m² (a measure of obesity, obtained by taking one's weight in kilograms and dividing it by one's height in meters squared) * Arterial carbon dioxide level over 45

mmHg A millimetre of mercury is a manometric unit of pressure, formerly defined as the extra pressure generated by a column of mercury one millimetre high. Currently, it is defined as exactly , or approximately 1 torr = atmosphere = &nb ...

or 6.0

kPa The pascal (symbol: Pa) is the unit of pressure in the International System of Units (SI). It is also used to quantify internal pressure, stress, Young's modulus, and ultimate tensile strength. The unit, named after Blaise Pascal, is an SI ...

as determined by arterial blood gas measurement * No alternative explanation for hypoventilation, such as use of

narcotic The term narcotic (, from ancient Greek ναρκῶ ''narkō'', "I make numb") originally referred medically to any psychoactive compound with numbing or paralyzing properties. In the United States, it has since become associated with opiates ...

s, severe obstructive or interstitial lung disease, severe chest wall disorders such as kyphoscoliosis, severe

hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...

(underactive thyroid), neuromuscular disease or congenital central hypoventilation syndrome 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 An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

, usually the

radial artery In human anatomy, the radial artery is the main artery of the lateral aspect of the forearm. Structure The radial artery arises from the bifurcation of the brachial artery in the antecubital fossa. It runs distally on the anterior part of the ...

. 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. To distinguish various subtypes,

polysomnography Polysomnography (PSG) is a multi-parameter type of sleep study and a diagnostic tool in sleep medicine. The test result is called a polysomnogram, also abbreviated PSG. The name is derived from Greek and Latin roots: the Greek πολύς ('' ...

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 Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignal, bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in ...

(electronic registration of electrical activity in the brain),

electrocardiography Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity through repeated cardiac cycles. It is an electrogram of the heart which is a graph of voltage versus time of t ...

(same for electrical activity in the heart), pulse oximetry (measurement of oxygen levels) and often other modalities. Blood tests are also recommended for the identification of

and

. To distinguish between OHS and various other lung diseases that can cause similar symptoms,

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...

of the lungs (such as a

chest X-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...

or CT/CAT scan), spirometry, electrocardiography and

echocardiography Echocardiography, also known as cardiac ultrasound, is the use of ultrasound to examine the heart. It is a type of medical imaging, using standard ultrasound or Doppler ultrasound. The visual image formed using this technique is called an ec ...

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.

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. Overall, 90% of all people with OHS fall into the first category, and 10% in the second.

Treatment

In people with stable OHS, the most important treatment is

—by diet, through

exercise Exercise or workout is physical activity that enhances or maintains fitness and overall health. It is performed for various reasons, including weight loss or maintenance, to aid growth and improve strength, develop muscles and the cardio ...

, 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. 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. 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 An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensive care medicine. An inten ...

with

intubation Intubation (sometimes entubation) is a medical procedure involving the insertion of a tube into the body. Most commonly, intubation refers to tracheal intubation, a procedure during which an endotracheal tube is inserted into the trachea to supp ...

and

mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...

is necessary. Otherwise, "bi-level" positive airway pressure (see the next section) is commonly used to stabilize the patient, followed by conventional treatment.

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. 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 Oxygen therapy, also referred to as supplemental oxygen, is the use of oxygen as medical treatment. Supplemental oxygen can also refer to the use of oxygen enriched air at altitude. Acute indications for therapy include hypoxemia (low blood o ...

may be necessary. As a last resort,

tracheostomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...

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.

Other treatments

People who fail first-line treatments or have very severe, life-threatening disease may sometimes be treated with

tracheotomy Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision on the front of the neck to open a direct airway to the trachea. The resulting stoma (hole) can serve independently as an airway ...

, which is a reversible procedure. Treatments without proven benefit, and concern for harm, include oxygen alone or respiratory stimulant medications.

Medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of ...

, a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

, and acetazolamide are both associated with an increased risk of

thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...

and are not recommended.

Prognosis

Obesity hypoventilation syndrome is associated with a reduced

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

, and people with the condition incur increased healthcare costs, largely due to hospital admissions including observation and treatment on

s. OHS often occurs together with several other disabling medical conditions, such as

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

(in 18–24%) and

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

(in 30–32%). Its main complication of heart failure affects 21–32% of patients. 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.

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. About a third of all people with morbid obesity (a

body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...

exceeding 40 kg/m²) have elevated

levels in the blood. 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 Black is a racial classification of people, usually a political and skin color-based category for specific populations with a mid- to dark brown complexion. Not all people considered "black" have dark skin and often additional phenotypical ...

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. 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 The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, where obesity is more common than in other countries.

History

The discovery of obesity hypoventilation syndrome is generally attributed to the authors of a 1956 report of a professional

poker Poker is a family of Card game#Comparing games, comparing card games in which Card player, players betting (poker), wager over which poker hand, hand is best according to that specific game's rules. It is played worldwide, with varying rules i ...

player who, after gaining weight, became somnolent and fatigued and prone to fall asleep during the day, as well as developing

of the legs suggesting

. 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. This report, however, was preceded by other descriptions of hypoventilation in obesity. In the 1960s, various further discoveries were made that led to the distinction between obstructive sleep apnea and sleep hypoventilation. 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).