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Medroxyprogesterone acetate, a progestin, 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.
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 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 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.
People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that biphasic cuirass ventilation can effectively be used without the need for a tracheotomy. Other potential treatments for Ondine's curse include oxygen therapy and medicine for stimulating the respiratory system. Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia.
Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is diaphragm pacing.
One treatment for obstructive hypopnea is continuous positive airway pressure (CPAP). CPAP is a treatment in which the patient wears a mask over the nose and/or mouth. An air blower forces air through the upper airway. The air pressure is adjusted so that it is just enough to maintain the oxygen saturation levels in the blood. Another treatment is sometimes a custom fitted oral appliance. The American Academy of Sleep Medicine's protocol for obstructive sleep apnea (OSA) recommends oral appliances for those who prefer them to CPAP and have mild to moderate sleep apnea or those that do not respond to/cannot wear a CPAP. Severe cases of OSA may be treated with an oral appliance if the patient has had a trial run with a CPAP. Oral Appliances should be custom made by a dentist with training in dental sleep medicine. Mild obstructive hypopnea can often be treated by losing weight or by avoiding sleeping on one's back. Also quitting smoking, and avoiding alcohol, sedatives and hypnotics (soporifics) before sleep can be quite effective. Surgery is generally a last resort in hypopnea treatment, but is a site-specific option for the upper airway. Depending on the cause of obstruction, surgery may focus on the soft palate, the uvula, tonsils, adenoids or the tongue. There are also more complex surgeries that are performed with the adjustment of other bone structures - the mouth, nose and facial bones.
Treatment of the underlying cause is required. Endotracheal intubation and mechanical ventilation are required in cases of severe respiratory failure (PaO2 less than 50 mmHg). Respiratory stimulants such as doxapram are rarely used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote (naloxone or flumazenil, respectively) will be given.
There is tentative evidence that in those with respiratory failure identified before arrival in hospital, continuous positive airway pressure can be useful when started before conveying to hospital.
Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects.
If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants. However an opioid antagonist may also precipitate an opioid withdrawal syndrome in chronic users.
People with neuromuscular disorders or hypoventilation syndromes involving failed respiratory drive experience central hypoventilation. The most common treatment for this form is the use of non-invasive ventilation such as a BPAP machine.
In closed circuit SCUBA (rebreather) diving, exhaled carbon dioxide must be removed from the breathing system, usually by a scrubber containing a solid chemical compound with a high affinity for CO, such as soda lime. If not removed from the system, it may be re-inhaled, causing an increase in the inhaled concentration.
As a side effect of medicines or recreational drugs, hypoventilation may become potentially life-threatening. Many different central nervous system (CNS) depressant drugs such as ethanol, benzodiazepines, barbiturates, GHB, sedatives and opioids produce respiratory depression when taken in large or excessive doses, or mixed with other depressants. Strong opiates (such as fentanyl, heroin, or morphine), barbiturates, and certain benzodiazepines (short acting ones and alprazolam) are known for depressing respiration. In an overdose, an individual may cease breathing entirely (go into respiratory arrest) which is rapidly fatal without treatment. Opioids, in overdose or combined with other depressants, are notorious for such fatalities.
Let us consider some scenarios where there is a defect in ventilation and/ or perfusion of the lungs.
In condition such as pulmonary embolism, the pulmonary blood flow is affected, thus the ventilation of the lung is adequate, however there is a perfusion defect with defect in blood flow. Gas exchange thus becomes highly inefficient leading to hypoxemia as measured by arterial oxygenation. A ventilation perfusion scan or lung scintigraphy shows some areas of lungs being ventilated but not adequately perfused. This also leads to a high A-a gradient which is not responsive to oxygen
In conditions with right to left shunts, there is again a ventilation perfusion defect with high A-a gradient. However, the A-a gradient is responsive to oxygen therapy. In cases of right to left shunts more of deoxygenated blood mixes with oxygenated blood from the lungs and thus to a small extent the condition might neutralize the high A-a gradient with pure oxygen therapy.
Patient with parenchymal lung diseases will have an increased A-a gradient with moderate response to oxygen therapy.
A patient with hypoventilation will have complete response to 100% oxygen therapy
The hypercapnic state is routinely used to calibrate blood-oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI), a modality that is sensitive to changes in blood oxygenation. However, this calibration crucially relies on the assumption that hypercapnia has no effect on neuronal function, which is a matter of debate.
Central hypoventilation syndrome (CHS) is a respiratory disorder that results in respiratory arrest during sleep. CHS can either be congenital (CCHS) or acquired (ACHS) later in life. It is fatal if untreated. It is also known as Ondine's curse.
ACHS can develop as a result of severe injury or trauma to the brain or brainstem. Congenital cases are very rare and involve a failure of autonomic control of breathing. In 2006, there were only about 200 known cases worldwide. As of 2008, only 1000 total cases were known. The diagnosis may be delayed because of variations in the severity of the manifestations or lack of awareness in the medical community, particularly in milder cases. However, as there have been cases where asymptomatic family members also were found to have CCHS, it may be that these figures only reflect those found to require mechanical ventilation. In all cases, episodes of apnea occur in sleep, but in a few patients, at the most severe end of the spectrum, apnea also occurs while awake.
Although rare, cases of long-term untreated CCHS have been reported and are termed late onset CCHS (LO-CCHS). Cases that go undiagnosed until later life and middle age, although the symptoms are usually obvious in retrospect. There have, however, even been cases of LO-CCHS where family members found to have it have been asymptomatic. Again, lack of awareness in the medical community may cause such a delay. CCHS susceptibility is not known to be affected by gender.
Currently there are no official tests or treatments for ROHHAD. Each child has the symptoms above at different ages, yet most symptoms are eventually present. Many children are misdiagnosed or are never diagnosed until alveolar hypoventilation occurs.
There are no medications currently approved for the treatment of obesity in children. The American Academy of Pediatrics recommends medications for obesity be discourage. Orlistat and sibutramine may be helpful in managing moderate obesity in adolescence. Metformin is minimally useful. A Cochrane review in 2016 concluded that medications might reduce BMI and bodyweight to a small extent in obese children and adolescents. This conclusion was based only on low quality evidence.
Treatment is typically achieved via diet and exercise, although metformin may be used to reduce insulin levels in some patients (typically where obesity is present). A referral to a dietician is beneficial. Another method used to lower excessively high insulin levels is cinnamon as was demonstrated when supplemented in clinical human trials.
A low carbohydrate diet is particularly effective in reducing hyperinsulinism.
A healthy diet that is low in simple sugars and processed carbohydrates, and high in fiber, and vegetable protein is often recommended. This includes replacing white bread with whole-grain bread, reducing intake of foods composed primarily of starch such as potatoes, and increasing intake of legumes and green vegetables, particularly soy.
Regular monitoring of weight, blood sugar, and insulin are advised, as hyperinsulinemia may develop into diabetes mellitus type 2.
It has been shown in many studies that physical exercise improves insulin sensitivity. The mechanism of exercise on improving insulin sensitivity is not well understood however it is thought that exercise causes the glucose receptor GLUT4 to translocate to the membrane. As more GLUT4 receptors are present on the membrane more glucose is taken up into cells decreasing blood glucose levels which then causes decreased insulin secretion and some alleviation of hyperinsulinemia. Another proposed mechanism of improved insulin sensitivity by exercise is through AMPK activity. The beneficial effect of exercise on hyperinsulinemia was shown in a study by Solomon et al. (2009), where they found that improving fitness through exercise significantly decreases blood insulin concentrations.
The first line treatment is change of lifestyle (e.g., Dietary Guidelines for Americans and physical activity). However, if in three to six months of efforts at remedying risk factors prove insufficient, then drug treatment is frequently required. Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated, and to raise HDL levels if they are low. Use of drugs that decrease insulin resistance, e.g., metformin and thiazolidinediones, is controversial; this treatment is not approved by the U.S. Food and Drug Administration. Weight loss medications may result in weight loss. As obesity is often recognized as the culprit behind many of the additional symptoms, with weight loss and lifestyle changes in diet, physical activity, the need for other medications may diminish.
A 2003 study indicated cardiovascular exercise was therapeutic in approximately 31% of cases. The most probable benefit was to triglyceride levels, with 43% showing improvement; but fasting plasma glucose and insulin resistance of 91% of test subjects did not improve.
Many other studies have supported the value of physical activity and dietary modifications to treat metabolic syndrome. Some natural compounds, like ursolic acid, have been suggested as a treatment for obesity/metabolic syndrome based on the results of extensive research involving animal models; it is argued, however, that there is still a lack of data regarding the use of ursolic acid in humans, as phase-II/III trials of that drug have not been carried so far.
Restricting the overall dietary carbohydrate intake is more effective in reducing the most common symptoms of metabolic syndrome than the more commonly prescribed reduction in dietary fat intake.
The combination preparation simvastatin/sitagliptin (marketed as Juvisync) was introduced in 2011 and the use of this drug was to lower LDL levels and as well as increase insulin levels. This drug could have been used to treat metabolic syndrome but was removed from the market by Merck in 2013 due to business reasons.
High-dose statins, recommended to reduce cardiovascular risk, have been associated with higher progression to diabetes, particularly in patients with metabolic syndrome. The biological mechanisms are not entirely understood, however, the plausible explanation may lie in competitive inhibition of glucose transport via the solute carrier (SLC) family of transporters (specifically "SLCO1B1"), important in statin pharmacokinetics.
Some studies on mice suggest that a Time Restricted Diet (TRD) could be helpful in reversing obesity and possibly metabolic syndrome
Weight management has two steps: weight loss and weight maintenance. In the weight loss phase, energy intake from food must be less than the energy expended each day. Achieving weight loss in cats and dogs is challenging, and failure to lose weight is common.
Medical treatments have been developed to assist dogs in losing weight. Dirlotapide (brand name Slentrol) and mitratapide (brand name Yarvitan) were authorized for use in the EU by the European Medicines Agency for helping weight loss in dogs, by reducing appetite and food intake, but both of these drugs have been withdrawn from the market in the EU. The US Food and Drug Administration approved dirlotapide in 2007. Up to 20% of dogs treated with either dirlotapide or mitratapide experience vomiting and diarrhea; less commonly, anorexia may occur. When these drugs are stopped, the dog's appetite returns to previous levels. If other weight-loss strategies are not employed, the dog will again gain weight.
In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in "Pa"CO. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:
- Acute respiratory acidosis: HCO increases 1 mEq/L for each 10 mm Hg rise in "Pa"CO.
- Chronic respiratory acidosis: HCO rises 3.5 mEq/L for each 10 mm Hg rise in "Pa"CO.
The expected change in pH with respiratory acidosis can be estimated with the following equations:
- Acute respiratory acidosis: Change in pH = 0.008 X (40 − "Pa"CO)
- Chronic respiratory acidosis: Change in pH = 0.003 X (40 − "Pa"CO)
Respiratory acidosis does not have a great effect on electrolyte levels. Some small effects occur on calcium and potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.
Ventilation Perfusion mismatch or "V/Q defects" are defects in total lung ventilation perfusion ratio. It is a condition in which one or more areas of the lung receive oxygen but no blood flow, or they receive blood flow but no oxygen due to some diseases and disorders.
The V/Q ratio of a healthy lung is approximately equal to 0.8, as normal lungs are not perfectly matched., which means the rate of alveolar ventilation to the rate of pulmonary blood flow is roughly equal.
The ventilation perfusion ratio can be measured by measuring the A-a gradient i.e. the alveolar-arterial gradient.
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 blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type I or Type II, based on whether there is a high carbon dioxide level. The definition of respiratory failure in clinical trials usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing.
The normal partial pressure reference values are: oxygen PaO more than , and carbon dioxide PaCO lesser than .
An appropriate weight training and weight loss program can help to improve the patient's condition.
There is no known cure available for the Wilson-Turner Syndrome. Instead, treatment options are available to fight individual symptoms. For obesity, a nutritional diet manipulation is combined with an exercise regimen that has a greater energy expenditure than intake. For hypogonadism, testosterone replacement is done. Finally, for gynecomastia, weight loss using similar methods for obesity is prescribed. However, if the individual finds his increased breast tissue psychologically distressing and/or is too severe, reduction mammaplasty is done. Currently, researchers are investigating therapy using antiestrogens and aromatase inhibitors to treat persistent pubertal gynecomastia.
During pregnancy, doctors recommend light exercise. Doctors state that exercise can help the comfort of the mother and the well-being of the unborn child. Some benefits include, but are not limited to: reduced back pain, decrease in constipation, less likely to gain excess weight, decreased chance of gestational diabetes, easier labor, quicker recovery, and better physical and emotional health of the baby.
If negative signs and symptoms occur after exercising, pregnant females should stop immediately. Some signs include: dizziness, faintness, headache, shortness of breath, uterine contractions, vaginal bleeding, fluid leaking, or heart palpitations.
Obesity in children is treated with dietary changes and physical activity. Dieting and missing meals should; however, be discourage. The benefit of tracking BMI and providing counselling around weight is minimal.
The main treatment for obesity consists of dieting and physical exercise. Diet programs may produce weight loss over the short term, but maintaining this weight loss is frequently difficult and often requires making exercise and a lower food energy diet a permanent part of a person's lifestyle.
In the short-term low carbohydrate diets appear better than low fat diets for weight loss. In the long term; however, all types of low-carbohydrate and low-fat diets appear equally beneficial. A 2014 review found that the heart disease and diabetes risks associated with different diets appear to be similar. Promotion of the Mediterranean diets among the obese may lower the risk of heart disease. Decreased intake of sweet drinks is also related to weight-loss. Success rates of long-term weight loss maintenance with lifestyle changes are low, ranging from 2–20%. Dietary and lifestyle changes are effective in limiting excessive weight gain in pregnancy and improve outcomes for both the mother and the child. Intensive behavioral counseling is recommended in those who are both obese and have other risk factors for heart disease.
Five medications have evidence for long-term use orlistat, lorcaserin, liraglutide, phentermine–topiramate, and naltrexone–bupropion. They result in weight loss after one year ranged from 3.0 to 6.7 kg over placebo. Orlistat, liraglutide, and naltrexone–bupropion are available in both the United States and Europe, whereas lorcaserin and phentermine–topiramate are available only in the United States. European regulatory authorities rejected the latter two drugs in part because of associations of heart valve problems with lorcaserin and more general heart and blood vessel problems with phentermine–topiramate. Orlistat use is associated with high rates of gastrointestinal side effects and concerns have been raised about negative effects on the kidneys. There is no information on how these drugs affect longer-term complications of obesity such as cardiovascular disease or death.
The most effective treatment for obesity is bariatric surgery. The types of procedures include laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, vertical-sleeve gastrectomy, and biliopancreatic diversion. Surgery for severe obesity is associated with long-term weight loss, improvement in obesity related conditions, and decreased overall mortality. One study found a weight loss of between 14% and 25% (depending on the type of procedure performed) at 10 years, and a 29% reduction in all cause mortality when compared to standard weight loss measures. Complications occur in about 17% of cases and reoperation is needed in 7% of cases. Due to its cost and risks, researchers are searching for other effective yet less invasive treatments including devices that occupy space in the stomach.