Pickwickian syndrome
Encyclopedia
Obesity hypoventilation syndrome (also known as Pickwickian syndrome) is a condition in which severely overweight people fail to breathe rapidly enough or deeply enough
, resulting in low blood oxygen
levels and high blood carbon dioxide
(CO2) levels. Many people with this condition also frequently stop breathing altogether for short periods of time during sleep (obstructive sleep apnea
), resulting in many partial awakenings during the night, which leads to continual sleepiness during the day. The disease puts strain on the heart, which eventually may lead to the symptoms of heart failure, such as leg swelling
and various other related symptoms. The most effective treatment is weight loss, but it is often possible to relieve the symptoms by nocturnal ventilation with positive airway pressure (CPAP) or related methods.
Obesity hypoventilation syndrome is defined as the combination of obesity
(body mass index
above 30 kg/m2), hypoxia
(falling oxygen
levels in blood) during sleep, and hypercapnia
(increased blood carbon dioxide
levels) during the day, resulting from hypoventilation
(excessively slow or shallow breathing). The disease has been known since the 1950s, initially as "Pickwickian syndrome" in reference to a Dickensian
character but currently under a more descriptive name.
) 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.
, 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) that is difficult to control with medication
. The high carbon dioxide can also cause headache
s, which tend to be worse in the morning.
The low oxygen level leads to excessive strain on the right side of the heart, 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
(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. Cor pulmonale
occurs in about a third of all people with OHS.
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[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.
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. 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
.
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 constriction 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.
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 cell
s. This results in polycythemia
, abnormally increased numbers of circulating red blood cells and an elevated hematocrit
.
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), further investigations for OHS may be needed.
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. Blood tests are also recommended for the identification of hypothyroidism
and polycythemia
.
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.
, 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. Bariatric surgery is avoided if possible, given the high rate of complications, but may be considered if other treatment modalities are ineffective in improving oxygen levels and symptoms. 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 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.
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, addition of oxygen therapy
may be necessary. As a last resort, tracheostomy may 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.
, a form of the hormone progesterone
, has been shown to improve the ventilatory response, but this has been poorly studied and is associated with an increased risk of thrombosis
. Similarly, the drug acetazolamide
can reduce bicarbonate levels, and thereby augment to normal ventilatory response, but this has been researched insufficiently to recommend wide application.
, and people with the condition incur increased healthcare costs, largely due to hospital admissions including observation and treatment on intensive care unit
s. 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.
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.
exceeding 40 kg/m2) have elevated carbon dioxide
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 is 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.
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.
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. 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.
Hypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
, resulting in low blood oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
levels and high blood carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
(CO2) levels. Many people with this condition also frequently stop breathing altogether for short periods of time during sleep (obstructive sleep apnea
Obstructive sleep apnea
Obstructive sleep apnea or obstructive sleep apnea syndrome is the most common type of sleep apnea and is caused by obstruction of the upper airway. It is characterized by repetitive pauses in breathing during sleep, despite the effort to breathe, and is usually associated with a reduction in...
), resulting in many partial awakenings during the night, which leads to continual sleepiness during the day. The disease puts strain on the heart, which eventually may lead to the symptoms of heart failure, such as leg swelling
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
and various other related symptoms. The most effective treatment is weight loss, but it is often possible to relieve the symptoms by nocturnal ventilation with positive airway pressure (CPAP) or related methods.
Obesity hypoventilation syndrome is defined as the combination of obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
(body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
above 30 kg/m2), hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
(falling oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
levels in blood) during sleep, and hypercapnia
Hypercapnia
Hypercapnia or hypercapnea , also known as hypercarbia, is a condition where there is too much carbon dioxide in the blood...
(increased blood carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
levels) during the day, resulting from hypoventilation
Hypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
(excessively slow or shallow breathing). The disease has been known since the 1950s, initially as "Pickwickian syndrome" in reference to a Dickensian
Charles Dickens
Charles John Huffam Dickens was an English novelist, generally considered the greatest of the Victorian period. Dickens enjoyed a wider popularity and fame than had any previous author during his lifetime, and he remains popular, having been responsible for some of English literature's most iconic...
character but currently under a more descriptive name.
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 indexApnea-hypopnea index
The apnea-hypopnea index is an index of sleep apnea severity that combines apneas and hypopneas. The apneas must last for at least 10 seconds and are associated with a decrease in blood oxygenation...
) 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.
Signs and symptoms
Most people with obesity hypoventilation syndrome have concurrent obstructive sleep apneaSleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
, a condition characterized by snoring
Snoring
Snoring is the vibration of respiratory structures and the resulting sound, due to obstructed air movement during breathing while sleeping. In some cases the sound may be soft, but in other cases, it can be loud and unpleasant...
, brief episodes of apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
(cessation of breathing) during the night, interrupted sleep and excessive daytime sleepiness
Excessive daytime sleepiness
Excessive daytime sleepiness is characterized by persistent sleepiness, and often a general lack of energy, even after apparently adequate night time sleep...
. In OHS, sleepiness may be worsened by elevated blood levels of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
, which causes drowsiness ("CO2 narcosis"). Other symptoms present in both conditions are depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
(high blood pressure) that is difficult to control with medication
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...
. The high carbon dioxide can also cause headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, which tend to be worse in the morning.
The low oxygen level leads to excessive strain on the right side of the heart, known as cor pulmonale
Cor pulmonale
Cor pulmonale or pulmonary heart disease is enlargement of the right ventricle of the heart as a response to increased resistance or high blood pressure in the lungs ....
. 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
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(swelling), and in the abdominal cavity in the form of ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
; decreased exercise tolerance and exertional chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...
may occur. On physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
, characteristic findings are the presence of a raised jugular venous pressure
Jugular venous pressure
The jugular venous pressure is the indirectly observed pressure over the venous system...
, a palpable parasternal heave, a heart murmur
Heart murmur
Murmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
due to blood leaking through the tricuspid valve
Tricuspid insufficiency
Tricuspid insufficiency , a valvular heart disease also called tricuspid regurgitation , refers to the failure of the heart's tricuspid valve to close properly during systole. As a result, with each heart beat some blood passes from the right ventricle to the right atrium, the opposite of the...
, hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
(an enlarged liver), ascites and leg edema. Cor pulmonale
Cor pulmonale
Cor pulmonale or pulmonary heart disease is enlargement of the right ventricle of the heart as a response to increased resistance or high blood pressure in the lungs ....
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 tissueAdipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
restricts the normal movement of the chest muscles and makes the chest wall less compliant, the diaphragm
Thoracic diaphragm
In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration...
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[g] + H2O[l] + excess H2O[l] --> H2CO3[aq]), this causes acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
(increased acidity of the blood). Under normal circumstances, central chemoreceptors
Central chemoreceptors
Central chemoreceptors of the central nervous system, located on the ventrolateral medullary surface, are sensitive to the pH of their environment....
in the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
detect the acidity, and respond by increasing the respiratory rate
Respiratory rate
Respiratory rate is also known by respiration rate, pulmonary ventilation rate, ventilation rate, or breathing frequency is the number of breaths taken within a set amount of time, typically 60 seconds....
; 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
Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
, 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
Renal compensation
Renal compensation is a mechanism by which the kidneys can regulate the plasma pH. It is slower than respiratory compensation, but has a greater ability to restore normal values....
with retention of the alkali
Alkali
In chemistry, an alkali is a basic, ionic salt of an alkali metal or alkaline earth metal element. Some authors also define an alkali as a base that dissolves in water. A solution of a soluble base has a pH greater than 7. The adjective alkaline is commonly used in English as a synonym for base,...
bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
. 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
Virtuous circle and vicious circle
A virtuous circle and a vicious circle are economic terms. They refer to a complex of events that reinforces itself through a feedback loop. A virtuous circle has favorable results, while a vicious circle has detrimental results...
.
Low oxygen levels lead to hypoxic pulmonary vasoconstriction
Hypoxic Pulmonary Vasoconstriction
Hypoxic pulmonary vasoconstriction is a paradoxical, physiological phenomenon in which pulmonary arteries constrict in the presence of hypoxia without hypercapnia , redirecting blood flow to alveoli with a higher oxygen content.The process might at first seem illogical, as low oxygen levels should...
, 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 constriction leads to increased pressure on the pulmonary artery
Pulmonary artery
The pulmonary arteries carry deoxygenated blood from the heart to the lungs. They are the only arteries that carry deoxygenated blood....
(pulmonary hypertension
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
), which in turn puts strain on the right ventricle
Right ventricle
The right ventricle is one of four chambers in the human heart. It receives deoxygenated blood from the right atrium via the tricuspid valve, and pumps it into the pulmonary artery via the pulmonary valve and pulmonary trunk....
, the part of the heart that pumps blood to the lungs. The right ventricle undergoes remodeling
Ventricular remodeling
Ventricular remodeling refers to the changes in size, shape, and function of the heart after injury to the ventricles. The injury is typically due to acute myocardial infarction , but may be from a number of causes that result in increased pressure or volume overload on the heart...
, 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.
The chronically low oxygen levels in the blood also lead to increased release of erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
and the activation of erythropoeisis, the production of red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s. This results in polycythemia
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...
, abnormally increased numbers of circulating red blood cells and an elevated hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
.
Diagnosis
Formal criteria for diagnosis of OHS are:- Body mass indexBody mass indexThe body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
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 mmHgTorrThe torr is a non-SI unit of pressure with the ratio of 760 to 1 standard atmosphere, chosen to be roughly equal to the fluid pressure exerted by a millimetre of mercury, i.e., a pressure of 1 torr is approximately equal to 1 mmHg...
or 6.0 kPaPascal (unit)The pascal is the SI derived unit of pressure, internal pressure, stress, Young's modulus and tensile strength, named after the French mathematician, physicist, inventor, writer, and philosopher Blaise Pascal. It is a measure of force per unit area, defined as one newton per square metre...
as determined by arterial blood gasArterial blood gasAn arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
measurement - No alternative explanation for hypoventilation, such as use of narcoticNarcoticThe term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
s, severe obstructiveObstructive lung diseaseObstructive lung disease is a category of respiratory disease characterized by airway obstruction. It is generally characterized by inflamed and easily collapsible airways, obstruction to airflow, and frequent office visits and hospitalizations. Types of obstructive lung disease include; Asthma,...
or interstitial lung disease, severe chest wall disorders such as kyphoscoliosisKyphoscoliosisKyphoscoliosis describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. Kyphoscoliosis is a musculoskeletal disorder causing chronic underventilation of the lungs and may be one of the major causes of pulmonary hypertension...
, severe hypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(underactive thyroid), neuromuscular diseaseNeuromuscular diseaseNeuromuscular disease is a very broad term that encompasses many diseases and ailments that either directly, via intrinsic muscle pathology, or indirectly, via nerve pathology, impair the functioning of the muscles....
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
Arterial blood gas
An arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
determination, which involves taking a blood sample from an artery
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
, usually the radial artery
Radial artery
In human anatomy, the radial artery is the main blood vessel, with oxygenated blood, of the lateral aspect of the forearm.-Course:The radial artery arises from the bifurcation of the brachial artery in the cubital fossa. It runs distally on the anterior part of the forearm...
. 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), further investigations for OHS may be needed.
To distinguish various subtypes, polysomnography
Polysomnography
Polysomnography , also known as a sleep study, is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. The test result is called a polysomnogram, also abbreviated PSG...
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
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
(electronic registration of electrical activity in the brain), electrocardiography (same for electrical activity in the heart), pulse oximetry
Pulse oximeter
A pulse oximeter is a medical device that indirectly monitors the oxygen saturation of a patient's blood and changes in blood volume in the skin, producing a photoplethysmograph. It is often attached to a medical monitor so staff can see a patient's oxygenation at all times...
(measurement of oxygen levels) and often other modalities. Blood tests are also recommended for the identification of hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
and polycythemia
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...
.
To distinguish between OHS and various other lung diseases that can cause similar symptoms, medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
of the lungs (such as a chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
or CT/CAT scan
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
), spirometry
Spirometry
Spirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...
, electrocardiography and echocardiography
Echocardiography
An echocardiogram, often referred to in the medical community as a cardiac ECHO or simply an ECHO, is a sonogram of the heart . Also known as a cardiac ultrasound, it uses standard ultrasound techniques to image two-dimensional slices of the heart...
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
Restrictive lung disease
Restrictive lung diseases are a category of extrapulmonary, pleural, or parenchymal respiratory diseases that restrict lung expansion, resulting in a decreased lung volume, an increased work of breathing, and inadequate ventilation and/or oxygenation...
pattern related to obesity.
Treatment
In people with stable OHS, the most important treatment is weight loss—by diet, through exercisePhysical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...
, with medication, or sometimes weight loss surgery
Bariatric surgery
Bariatric surgery includes a variety of procedures performed on people who are obese. Weight loss is achieved by reducing the size of the stomach with an implanted medical device or through removal of a portion of the stomach or by resecting and re-routing the small intestines...
(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. Bariatric surgery is avoided if possible, given the high rate of complications, but may be considered if other treatment modalities are ineffective in improving oxygen levels and symptoms. 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 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
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
with intubation
Intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...
and mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
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 co-exists. CPAP requires the nighttime use 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
Oxygen-haemoglobin dissociation curve
The oxygen–haemoglobin dissociation curve plots the proportion of haemoglobin in its saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis. The oxyhaemoglobin dissociation curve is an important tool for understanding how our blood carries and releases...
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, addition of oxygen therapy
Oxygen therapy
Oxygen therapy is the administration of oxygen as a medical intervention, which can be for a variety of purposes in both chronic and acute patient care...
may be necessary. As a last resort, tracheostomy may 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
MedroxyprogesteroneMedroxyprogesterone
Medroxyprogesterone is a pregnane that acts as a progestin. An acylated derivative, medroxyprogesterone 17-acetate is clinically used as a drug. Compared to MPA, MP is approximately 100 fold less potent as a progestin...
, a form of the hormone progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
, has been shown to improve the ventilatory response, but this has been poorly studied and is associated with an increased risk of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
. Similarly, the drug acetazolamide
Acetazolamide
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...
can reduce bicarbonate levels, and thereby augment to normal ventilatory response, but this has been researched insufficiently to recommend wide application.
Prognosis
Obesity hypoventilation syndrome is associated with a reduced quality of lifeQuality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
, and people with the condition incur increased healthcare costs, largely due to hospital admissions including observation and treatment on intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
s. OHS often occurs together with several other disabling medical conditions, such as asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
(in 18–24%) and type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
(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 indexBody mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
exceeding 40 kg/m2) have elevated carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
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 is 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 people
The term black people is used in systems of racial classification for humans of a dark skinned phenotype, relative to other racial groups.Different societies apply different criteria regarding who is classified as "black", and often social variables such as class, socio-economic status also plays a...
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
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, 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 pokerPoker
Poker is a family of card games that share betting rules and usually hand rankings. Poker games differ in how the cards are dealt, how hands may be formed, whether the high or low hand wins the pot in a showdown , limits on bet sizes, and how many rounds of betting are allowed.In most modern poker...
player who, after gaining weight, became somnolent and fatigued and prone to fall asleep during the day, as well as developing edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of the legs suggesting heart failure. The authors coined the condition "Pickwickian syndrome" after the character Joe from Dickens'
Charles Dickens
Charles John Huffam Dickens was an English novelist, generally considered the greatest of the Victorian period. Dickens enjoyed a wider popularity and fame than had any previous author during his lifetime, and he remains popular, having been responsible for some of English literature's most iconic...
The Posthumous Papers of the Pickwick Club
The Pickwick Papers
The Posthumous Papers of the Pickwick Club is the first novel by Charles Dickens. After the publication, the widow of the illustrator Robert Seymour claimed that the idea for the novel was originally her husband's; however, in his preface to the 1867 edition, Dickens strenuously denied any...
(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.