Obesity hypoventilation syndrome

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Keywords and Synonyms: Pickwickian syndrome, OHS

Overview
The obesity hypoventilation syndrome consists of the combination of obesity (body mass index above 30 kg/m2), falling oxygen levels in blood (hypoxia) during sleep and increasing carbon dioxide levels (hypercapnia); this is the result of hypoventilation (excessively slow or shallow breathing) during sleep. Obstructive sleep apnea is often but not necessarily present.

It may cause dyspnea (difficulty breathing), poor sleep with daytime tiredness, leg swelling and various other symptoms. The main treatments are weight loss and nocturnal ventilation (with CPAP or related methods). The exact pathophysiologic mechanism remains unknown.

Historical Perspective
The Pickwickian syndrome, also known as obesity hypoventilation syndrome, is the combination of severe obesity, suffering from obstructive sleep apnea causing hypoxia and hypercapnia resulting in marked daytime somnolence and chronic respiratory acidosis. Although it is an eponym, it is not named after the doctor who first described it (as commonly happens), but after a literary character by Charles Dickens.

In The Posthumous Papers of the Pickwick Club, originally published in 1837 by Charles Dickens, there was an extremely obese boy named Joe who could not help falling asleep during the day.

A most violent and startling knocking was heard at the door; it was not an ordinary double knock, but a constant and uninterrupted succession of the loudest single raps, as if the knocker were endowed with the perpetual motion, or the person outside had forgotten to leave off. ..

The object that presented itself to the eyes of the astonished clerk, was a boy - a wonderfully fat boy - habited as a serving lad, standing upright on the mat, with his eyes closed as if in sleep. He had never seen such a fat boy with titties, in or out of a travelling caravan; and this, coupled with the calmness and repose of his appearance, so very different from what was reasonably to have been expected in the inflicter of such knock, smote him with wonder.

"What's the matter" inquired the clerk.

The extraordinary boy replied not a word; but he nodded once, and seemed, to the clerk's imagination, to snore feebly.

"Where do you come from?" inquired the clerk.

The boy made no sign. He breathed heavily, but in all other respects was motionless.

The clerk repeated the question thrice, and receiving no answer, prepared to shut the door, when the boy suddenly opened his eyes, winked several times, sneezed once, and raised his hand as if to repeat the knocking. Finding the door open, he stared about him with astonishment, and at length fixed his eyes on Mr. Lowten's face.

"What the devil do you knock in that way for?" inquired the clerk, angrily.

"Which way?" said the boy, in a slow and sleepy voice.

"Why, like forty hackney-coachmen," replied the clerk.

"Because master said, I wasn't to leave off knocking till they opened the door, for fear I should go to sleep," said the boy.

The name Pickwickian came up after 119 years, when in 1956 Dr. C.S. Burwell and colleagues published a medical case report titled "Extreme Obesity Associated With Alveolar Hypoventilation a Pickwickian Syndrome." After quoting Dickens's description of the fat boy the authors went on to describe their patient, a 51-year-old business executive who stood 5 feet 5 inches and weighed over 260 pounds (118 kg):

"(He) entered the hospital because of obesity, fatigue and somnolence...The patient was accustomed to eating well but did not gain weight progressively until about one year before admission...As the patient gained weight his symptoms appeared and became worse..he had often fallen asleep while carrying on his daily routine...on several occasions he suffered brief episodes of syncope (fainting) Persistent edema of the ankles developed... Finally an experience which indicated the severity of his disability led him to seek hospital care. The patient was accustomed to playing poker once a week and on this crucial occasion he was dealt a hand of three aces and two kings. According to Hoyle this hand is called a 'full house.' Because he had dropped off to sleep he failed to take advantage of this opportunity. &#91;Italics original&#93;. A few days later he entered...hospital."

Pathophysiology
Despite many studies, it is still unclear why some obese people develop hypoventilation and others do not. Impairment of lung expansion by adipose tissue means that one need to breathe faster and deeper to still absorb sufficient amounts of oxygen and remove adequate amounts of carbon dioxide. It appears that the respiratory center (an area in the brain stem that regulates breathing) becomes relatively insensitive to normal stimuli, leading to a decreased response to low oxygen levels. While this may be the result of obstructive sleep apnea, it does not explain why some people with OHS have no features of obstruction. Recent studies postulate that there is a vicious cycle in which low oxygen levels make the respiratory center progressively more insensitive to hypoxia, impairing normal compensatory mechanisms normally in place to prevent hypercapnia. It appears that insensitivity to the hormone leptin, which is elevated in obesity, plays a role in this process, but there is no conclusive evidence that this is the case.

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. The dysfunction of the right ventricle improves with treatment.

Epidemiology and Demographics
The exact prevalence of OHS is unknown. In patients with a BMI over 35 who were admitted to hospital, 31% had elevated carbon dioxide levels. It is not known whether men or women are at greater risk. The presence of OHS is associated with an increased risk of death compared to those with obesity but no OHS (24% vs 9% over an 18 month period).

Symptoms

 * Blurred vision secondary to papilledema
 * Cor pulmonale or right heart strain due to pulmonary hypertension with symptoms of edema (swelling) of the legs, decreased exercise tolerance, ascites (accumulation of fluid in the abdominal cavity) and exertional chest pain.
 * Depression
 * Headaches occuring in the morning.
 * 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").

Vitals
Hypertension that is difficult to control with medication

Eye

 * Papilledema (swelling of the optic disc) in response to the raised carbon dioxide levels.

Diagnostic Criteria
If OHS is suspected, various tests are required for its confirmation. Arterial blood gas levels are determined to measure oxygen and carbon dioxide levels; this requires a blood sample from an artery, usually the radial artery. 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. To distinguish between OHS and various other lung diseases that can cause similar symptoms, computed tomography (CT/CAT scan) and spirometry may be performed.

Formal criteria for diagnosis of OHS are:
 * Body mass index over 30 kg/m2 (a measure of obesity, obtained by taking ones weight in kilograms and dividing it by ones height in meters squared)
 * Arterial carbon dioxide level over 45 mmHg or 6.0 kPa as determined by arterial blood gas measurement
 * No alternative explanation for hypoventilation, such as use of narcotics

Two subtypes are recognized. 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. In many patients, both phenomena are present.

Treatment
Reduction in weight, either through a regimen of diet and exercise, medication or sometimes through bariatric surgery, 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.

Overnight mask ventilation with positive airway pressure may lead to an improvement in most symptoms of OHS. The type of mask ventilation depends on the underlying problem. If the main abnormality on investigations is obstructive sleep apnea, CPAP (continuous PAP) may be sufficient; this involves sleeping with a face mask connected to a machine that delivers a continuously high atmospheric pressure; this stops tissues in the mouth and throat area from collapsing and obstructing air flow. If sleep hypoventilation is the predominant problem, CPAP may be insufficient, and increased pressure ("pressure support") needs to be delivered during inspiration to allow more airflow into the alveoli (the sacs of the lung where gas transport takes place). This is referred to as BIPAP ("bi-level" PAP). In patients whose symptoms are highly disabling but are unable to tolerate CPAP or BIPAP, ventilation through a tracheostomy (opening in the windpipe) is sometimes required.

Despite some initial positive reports about improvement of OHS with medroxyprogesterone, this is not recommended in practice.