Obesity Hypoventilation Syndrome
Over the past few decades the incidence of obesity has doubled worldwide and current estimates classify more than 1.5 billion adults as overweight and at least 500 million of them as clinically obese, with body mass index (BMI) over 25 kg/m2and 30 kg/m2, respectively . Obesity prevalence rates are steadily rising in the majority of the modern Western societies, as well as in the developing world. Moreover, alarming trends of weight gain are reported for children and adolescents, undermining the present and future health status of the pediatric population . To highlight the related threat to public health, the World Health Organization has declared obesity a global epidemic, also stressing that it remains an under-recognized problem of the public health agenda [59, 60].
Because obesity has become both a national and global epidemic, it is imperative that physicians are able to recognize and treat obesity-associated diseases. Evidence suggests that obesity hypoventilation syndrome is under-recognized and undertreated. Obesity hypoventilation syndrome (OHS) (also known as Pickwickian syndrome from Charles Dickins character in the Pickwick Papers) is defined as the triad of obesity, daytime hypoventilation, and sleep-disordered breathing in the absence of an alternative neuromuscular, mechanical or metabolic explanation for hypoventilation.
During the last 3 decades the prevalence of extreme obesity has markedly increased in the United States and other countries. With such a global epidemic of obesity, the prevalence of OHS is bound to increase. Patients with OHS have a lower quality of life, with increased healthcare expenses, and are at higher risk of developing pulmonary hypertension and early mortality, compared to eucapnic patients with sleep-disordered breathing.
OHS often remains undiagnosed until late in the course of the disease. Early recognition is important, as these patients have significant morbidity and mortality. Effective treatment can lead to significant improvement in patient outcomes, underscoring the importance of early diagnosis .
What is obesity?
Obesity is described anatomically as an elevated level of fat storage in the form of hypertrophy (increased size) and/or hyperplasia (increased number) of fat cells, known as adipocytes. Given the complexities of body composition analysis, the body mass index (BMI) acts as a surrogate for the amount of bodily fat and facilitates patient comparison
and grouping for the purposes of research or discussion. Body mass index is defined as the body weight in kg divided by the square of the body height in meters (kg*m-2). Obesity has been defined as a BMI>30 kg*m-2, and morbid obesity has been referred to as a BMI>40 kg*m-2 or a BMI>35 kg*m-2 with an obesity-related comorbidity (Chart Below). Body mass index alone is not a good predictor of the distribution of excess body fat; central obesity with elevated visceral fat levels is associated with greater metabolic impact and complications than widespread subcutaneous fat. Body mass index may be misleading in patients with significant muscle bulk. It is also critical to understand that patients can have elevated body fat content despite a normal BMI, so-called ‘‘normal weight obesity’’, and this too can have an impact on organ function, with the risk of metabolic abnormalities and hypertension increasing as the percent of body fat (%BF) increases. Obesity impacts virtually all organ systems and is an independent risk factor for both morbidity and mortality .
The literature clearly highlights the complexity of severe obesity as a multisystem disease, and individuals caring for these patients must have a sound understanding of the changes in order to offer the highest quality care to these patients.
Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species.
Obesity is a multisystem chronic proinflammatory disorder associated with increased morbidity and mortality. Adipocytes are far more than storage vessels for lipids. They secrete a large number of physiologically active substances called adipokines that lead to inflammation, vascular and cardiac remodeling, airway inflammation, and altered microvascular flow patterns. They contribute to linked abnormalities, such as insulin
resistance and the metabolic syndrome, and they attract and activate inflammatory cells such as macrophages. These changes can lead ultimately to organ dysfunction,
especially cardiovascular and pulmonary issues .
The fat cell, or adipocyte, is central to the pathophysiological changes that terminate in obesity-associated comorbidity. Adipocytes have two main roles. The first role is lipid handling, where adipose tissue can be viewed as an adaptive response aimed at controlling the potential toxicity of free fatty acid (FFA) levels. The second role is an endocrine and paracrine function central to the adverse impact of obesity. These cells actively produce and secrete a large number of important biologically active hormones referred to as adipokines, which include substances with metabolic and growth regulation roles as well as cytokines
and collagens (see figure below). Pro-inflammatory substances are secreted mainly by visceral fat cells, whereas adiponectin and leptin are the key substances produced by subcutaneous adipocytes.7 These pro-inflammatory signals reach a point where they lead to macrophage and T-cell recruitment to the adipose tissue, further contributing to the inflammatory state. This adipocyte and inflammatory cell mix is the potent combination at the core of the metabolic disturbances in obesity .
Obesity-related changes in respiratory function are, intuitively, related to the severity of the body mass increase and the location of the excess fat deposits. Clearly, upper body
(waist and above) fat will have a greater impact on diaphragmatic excursion, chest wall mechanics, and work of breathing. The major physiological changes are listed in table 2 below .
Excessive daytime sleepiness (EDS) is the primary concern for many patients presenting with sleep disorder and a significant public health problem. The International Classification of Sleep Disorders (ICSD-2) includes EDS as an essential feature for three diagnostic categories: narcolepsy, hypersomnia and behaviorally induced insufficient sleep syndrome. However, it is also associated with a wide range of diseases, including psychiatric and neurological disorders, pulmonary and cardiac conditions (listed in the Table below). Frequently, there may not be an identifiable cause and the only diagnosis possible is that of idiopathic hypersomnia. However, the most common causes may be found in a disturbance of sleep quality, sleep quantity or other contributors. Most frequently, insufficient sleep duration is responsible for this symptom. This review will give an overview of some of the most common causes of EDS encountered in clinical practice and identify important risk factors for sleepiness in the community.
When investigating potential causes of EDS, it is important to distinguish between fatigue and excessive sleepiness, or hypersomnia. Fatigue is, like hypersomnia, a common complaint in general practice; it is a poorly defined feeling of exhaustion or strain associated with many chronic diseases and psychiatric disorders. Importantly, severely fatigued patients will not necessarily be sleepy, suggesting that the underlying pathologies are distinct. However, in clinical practice it can be difficult to distinguish between the two and there are recognized cases where fatigue and sleepiness may not be clearly defined.
The clinical manifestations of hypoventilation syndromes usually are nonspecific, and in most cases, they are secondary to the underlying clinical diagnosis. Manifestations vary depending on the severity of hypoventilation, the rate of development of hypercapnia, and the degree of compensation for respiratory acidosis that may be present.All patients with OHS are obese (BMI >30 kg/m2) and most have coexisting obstructive sleep apnea (OSA). The most common symptoms and signs are due to the coexisting OSA , which include :
- excessive daytime sleepiness,
- loud snoring,
- choking during sleep,
- resuscitative snorting (i.e., a loud snort that follows an apnea as the patient partially awakens and reopens the upper airway),
- impaired concentration and memory,
- a small oropharynx, and a thick neck
Many patients as listed in the charts above have symptoms and signs of pulmonary hypertension with right-sided heart failure (e.g., elevated jugular venous pressure, hepatomegaly, and pedal edema) and, occasionally, a plethoric complexion (ruddy in complexion, congested or swollen with blood) from polycythemia [1,7]. Patients can also present with hypercapnic respiratory failure of unknown etiology. Generally speaking, patients with OHS tend to have more comorbidities than patients with eucapnic obesity, including systemic hypertension, heart failure, angina, and insulin resistance .
It can be difficult to distinguish individuals who have both OHS and OSA from individuals who have OSA alone. Dyspnea on exertion is a clue that OHS is present because patients with OSA alone generally do not develop dyspnea on exertion [1,4,7,9]. Severe obesity (BMI >50 kg/m2) is another clue that OHS may be present, since nearly 50 percent of such individuals have OHS .
Upon thoracic examination, patients with obstructive lung disease generally have
- Diffuse wheezing, hyperinflation (barrel chest),
- Diffusely decreased breath sounds,
- Hyperresonance upon percussion,
- Prolonged expiration,
- Coarse crackles beginning with inspiration may be heard,
- Wheezes frequently are heard upon forced and unforced expiration
- Cyanosis may be noted if accompanying hypoxia is present
- Clubbing may be present.
- A narrowly split and loud pulmonary component (P2) of the second heart sound,
- A large a-wave component in the jugular venous pulse,
- A left parasternal (right ventricular) heave,
- An S4 of right ventricular origin,
- A diastolic murmur indicative of pulmonic valve regurgitation may be auscultated
Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index (BMI) >30kg/m2) has awake alveolar hypoventilation (PaCO2 >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology [1-3].
Most patients with OHS present with chronic hypoventilation, although some may develop acute cardiopulmonary compromise. Cardiovascular comorbidities represent the main factor predicting mortality in patient with obesity-associated hypoventilation treated by NIV. In this population, NIV should be associated with a combination of treatment modalities to reduce cardiovascular risk . Prompt diagnosis and therapy are important to avoid the adverse effects of OHS, especially since untreated patients with OHS have a high mortality rate [4,5].
Diagnostic testing is necessary for the evaluation of suspected OHS. This section reviews the common diagnostic tests, including arterial blood gases, pulmonary function tests, polysomnography, chest radiographs, electrocardiography, and echocardiography. The role of these tests in the evaluation of suspected OHS is described in the next section.
Arterial blood gases — Arterial blood gas testing must be performed, since hypercapnia must be identified to diagnose OHS. The following abnormalities occur in patients with OHS:
- Hypercapnia (PaCO2 >45 mmHg) is always present during wakefulness. The PaCO2 can be reduced or normalized, however, by voluntary hyperventilation . It can also be reduced or normalized by involuntary hyperventilation caused by the arterial blood gas procedure.
- Hypoxemia (PaO2 <70 mmHg) is usually present. The calculated alveolar-arterial (A-a) oxygen gradient may be normal when there is no coexisting lung or heart disease [1,11-13]. An elevated hematocrit is common and may be a clue that the patient is hypoxemic [4,14].
Serum bicarbonate — A high serum bicarbonate level is a clue that the patient is chronically hypercapnic. This test is helpful if arterial blood gases cannot be obtained or are delayed [6,15].
Pulmonary function tests — The primary use of pulmonary function tests is to exclude obstructive lung disease. Most patients with OHS have pulmonary function tests that are characteristic of obesity. These include [7,14,16]
- A low forced vital capacity (FVC),
- FVC – Forced Vital Capacity – after the patient has taken in the deepest possible breath, this is the volume of air which can be forcibly and maximally exhaled out of the lungs until no more can be expired. FVC is usually expressed in units called liters. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
- A low forced expiratory volume in one second (FEV1),
- FEV1 – Forced Expiratory Volume in One Second – this is the volume of air which can be forcibly exhaled from the lungs in the first second of a forced expiratory maneuver. It is expressed as liters. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
- A normal FEV1/FVC ratio, and
- FEV1/FVC – FEV1 Percent (FEV1%) – This number is the ratio of FEV1 to FVC – it indicates what percentage of the total FVC was expelled from the lungs during the first second of forced exhalation – this number is called FEV1%, %FEV1 or FEV1/FVC ratio. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
- A low expiratory reserve volume (ERV)
- Expiratory reserve volume: the maximal volume of air that can be exhaled from the end-expiratory position
- Total lung capacity (TLC) may also be diminished in some patients
- Total lung capacity: the volume in the lungs at maximal inflation, the sum of VC and RV.
Polysomnography — Most patients with OHS have an abnormal number of apneas and hypopneas per hour of sleep (i.e., a high apnea hypopnea index [AHI]) due to coexisting OSA. The converse is not true; an elevated AHI does not predict the presence of coexisting OHS . In addition, patients with OHS usually have more profound oxyhemoglobin desaturation during sleep than patients with OSA alone [17-19].
AHI = Apnea-Hypopnea Index, IPAP = Inspiratory Positive Airway Pressure, EPAP = Expiratory Positive Airway Pressure , SaO2 = percentage of available hemoglobin that is saturated with oxygen
Chest radiograph — On a routine chest radiograph, both hemidiaphragms are usually elevated due to the obese abdomen and the heart is frequently enlarged due to right ventricular hypertrophy. Asymmetrical elevation of a hemidiaphragm suggests diaphragmatic paralysis, another condition that can cause hypoventilation. Hyperinflation and bullous disease suggest that the chronic hypercapnia may be due to pulmonary disease rather than OHS.
Cardiac studies — Patients with OHS often have an abnormal electrocardiogram (ECG), echocardiogram, and/or cardiac catheterization. The ECG and echocardiogram may show right atrial and right ventricular hypertrophy, while the cardiac catheterization frequently reveals pulmonary hypertension .
DIAGNOSTIC APPROACH — The diagnostic evaluation should be performed quickly because untreated OHS is associated with high mortality [4,5].
OHS is diagnosed when the following criteria are confirmed:
- Obesity (BMI be >30 kg/m2)
- Awake alveolar hypoventilation (PaCO2 >45 mmHg)
- An alternative cause of the hypoventilation cannot be identified
The absence of an alternative cause of hypoventilation is an important requirement for the diagnosis of OHS. In clinical practice, patients frequently have additional diseases that cause hypoventilation (e.g., COPD). If the other disease is mild and unlikely to cause hypercapnia, then it is reasonable to give the patient a diagnosis of OHS. If the other disease is more severe and probably contributing to hypercapnia, the situation becomes more complicated. In this setting, OHS cannot be diagnosed with certainty. However, if the patient has severe obesity, severe sleep apnea, and severe oxyhemoglobin desaturation during sleep, it is generally presumed that OHS may be contributing and treat the patient accordingly.
All individuals with suspected OHS should have their BMI measured and arterial blood gases (ABGs) performed. The purpose of the ABGs is to confirm alveolar hypoventilation. ABGs are most helpful when performed while the patient is breathing room air because the A-a oxygen gradient can be calculated. A normal A-a oxygen gradient excludes pulmonary parenchymal or airways disease. A normal A–a gradient for a young adult non-smoker breathing air, is between 5–10 mmHg.
Additional testing is necessary to exclude other diseases that can cause alveolar hypoventilation, such as [20-22]
- chronic obstructive pulmonary disease (COPD),
- restrictive disease (e.g., neuromuscular weakness (or neuromuscular weakness), interstitial lung disease, chest wall disease),
- hypothyroidism, and
- diaphragmatic paralysis
- primary CNS disorders
- primary central hypoventilation syndromes
- brain stem infarction and tumors
- metabolic abnormalities
This generally requires the following tests:
- Thyroid function tests (or Thyroid function tests) and serum electrolytes (including magnesium and phosphorus) to look for hypothyroidism and electrolyte-related neuromuscular weakness, respectively.
- Pulmonary function tests (or Pulmonary function tests), including (in patients with severe respiratory failure, these tests will need to be deferred until the patients are stabilized)
- lung volumes,
- diffusing capacity, and
- inspiratory and expiratory pressures, to look for evidence that COPD or a restrictive disease may be a prominent contributor to the alveolar hypoventilation.
- A chest radiograph to look for parenchymal lung disease, chest wall disease, asymmetrical elevation of a hemidiaphragm (ie, diaphragm paralysis), and cardiomegaly.
- Comprehensive Metabolic Chemistry Panel
Although polysomnography is not required for the diagnosis of OHS, it should be performed in all patients with OHS for several reasons. First, in-laboratory polysomnography is the gold-standard diagnostic test for OSA, which frequently coexists with OHS and should be both identified and treated. Second, positive airway pressure therapy, the preferred treatment for OHS, can be titrated during polysomnography. Finally, polysomnography can give the clinician an impression of disease severity by determining the severity and duration of oxyhemoglobin desaturation, as well as the presence of cardiac dysrhythmias. The role of level 3 portable monitoring rather than in-laboratory polysomnography in OHS is unclear.
The preceding discussion assumes that the patient with suspected OHS presented with chronic alveolar hypoventilation. However, presentation with acute or chronic hypercapnic respiratory failure is also common . When a patient presents with severe acute respiratory failure due to OHS, diagnostic polysomnography with positive airway pressure titration during the same night is optimal if the patient is stable enough to go to the sleep laboratory. However, the diagnostic evaluation may need to be postponed and therapy immediately initiated if the patient is not well enough to go to the sleep laboratory. Overnight oximetry is a reasonable surrogate diagnostic test in this situation. Significant oxyhemoglobin desaturation not corrected by oxygen administration after several hours of recording should prompt empiric positive airway pressure therapy.
SUMMARY AND RECOMMENDATIONS
- Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index (BMI) >30kg/m2) has awake alveolar hypoventilation (PaCO2 >45 mmHg), which cannot be attributed to other conditions, such as pulmonary parenchymal disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology.
- All patients with OHS are obese and most have coexisting obstructive sleep apnea (OSA). The most common symptoms and signs are due to the coexisting OSA, which include excessive daytime sleepiness, loud snoring, choking during sleep, resuscitative snoring, fatigue, hypersomnolence, impaired concentration and memory, a small oropharynx, and a thick neck. Some patients present with hypercapnic respiratory failure or uncertain etiology.
- Diagnostic testing is necessary for the evaluation of suspected OHS. Commonly performed diagnostic tests include arterial blood gases, pulmonary function tests, polysomnography, and chest radiographs.
- The diagnostic evaluation should be performed quickly because untreated OHS is associated with high mortality. All individuals with suspected OHS should have arterial blood gases (ABGs) performed. The purpose of the ABGs is to confirm alveolar hypoventilation. Additional testing is necessary to exclude other diseases that can cause alveolar hypoventilation, such as chronic obstructive pulmonary disease (COPD), restrictive disease (e.g., neuromuscular weakness, interstitial lung disease, chest wall disease), hypothyroidism, and diaphragmatic paralysis.
Treatment is important because untreated OHS can progress to acute, life-threatening cardiopulmonary compromise. In addition, untreated OHS is associated with a high mortality rate, a reduced quality of life, and numerous morbidities, including pulmonary hypertension, right heart failure, angina, and insulin resistance [4,5,8,23].
The therapeutic goals for patients with OHS include:
- normalization of the arterial carbon dioxide tension (PaCO2) during wakefulness and sleep (ie, PaCO2 <45 mmHg);
- prevention of oxyhemoglobin desaturation during
- sleep and wakefulness,
- pulmonary hypertension, and
- cor pulmonale;
- relief of hypersomnia and altered mentation.
Therapeutic interventions for OHS therapy include four main components: PAP (positive airway pressure) therapy, supplemental oxygen, weight reduction surgery, and pharmacologic respiratory stimulants . Therefore, all patients with OHS are managed with nocturnal positive airway pressure and lifestyle modifications directed at losing weight. Bariatric surgery may be considered for patients who fail to lose sufficient weight with lifestyle modifications and either hope to eventually discontinue nocturnal noninvasive positive airway pressure or do not tolerate nocturnal noninvasive positive airway pressure. Routine treatment of comorbid conditions and the prevention of complications are also necessary in all patients with OHS.
POSITIVE AIRWAY PRESSURE — Nocturnal noninvasive positive airway pressure is first-line treatment for OHS, regardless of whether or not the patient has a coexisting sleep-related breathing disorder. It is indicated for all patients with OHS and should NOT be delayed while the patient tries to lose weight. Patients with OHS alone are generally managed with bilevel positive airway pressure (BPAP). In contrast, patients with OHS and coexisting obstructive sleep apnea (OSA) are usually managed initially with continuous positive airway pressure (CPAP) and then changed to BPAP if the CPAP is insufficient.
Negative pressure ventilation is not a useful alternative because there are numerous practical problems and its efficacy has not been established in patients with OHS. The rationale for considering negative pressure ventilation is that it may mitigate or prevent chronic respiratory failure by decreasing the work of breathing and ventilatory muscle fatigue. However, its practical limitations include the following:
- fitting the various negative pressure ventilation systems (e.g., shells, poncho wraps, and tank ventilators) is difficult due to the obesity,
- even if a negative pressure ventilation system is found that fits the patient, the level of ventilatory support is limited by reduced chest wall and abdominal compliance, and
- patients with OHS are predisposed to obstructive sleep apnea and negative pressure ventilation during sleep may promote upper airway occlusion.
Medication – Pharmacologic therapy for obesity is not universally accepted because of concerns about efficacy and safety, the observation that weight loss slows with ongoing treatment, and the observation that most patients regain their weight when the medications are discontinued. Regarding efficacy, many of the weight loss medications initially achieve weight loss of 5 to 10 kg over 3 to 12 months before the weight loss plateaus [24,25], but this is typically not enough to normalize the awake PaCO2. Regarding safety, pharmacologic therapy has the potential to cause drug-induced pulmonary hypertension . This is a particular concern in patients with OHS whose respiratory abnormalities already place them at increased risk for this complication.
Bariatric surgery – Considerable attention has been directed towards surgical methods of weight loss (ie, bariatric surgery), since lifestyle modifications alone are generally insufficient and pharmacological therapy is of uncertain efficacy and safety . Bariatric surgery leads to a restriction of caloric intake alone or in combination with malabsorption of nutrients, thereby causing weight loss. Bariatric techniques include Roux-en-Y gastric bypass, adjustable gastric banding, sleeve gastrectomy, biliopancreatic diversion, duodenal switch, intragastric balloon, vertical banded gastroplasty endoluminal vertical gastroplasty, jejunoileal bypass, and liposuction. Perioperative mortality related to bariatric surgery is dependent on comorbidities and the procedure performed, but is reported to be less than 2 percent of patients who undergo bariatric surgery [28,29]. Reassessment of OHS following bariatric surgery is performed after significant weight loss has occurred, usually within one to two years after the surgery. It consists of an arterial blood gas to reassess the awake PaCO2 and PaO2 in all patients, as well as in-laboratory polysomnography in patients who had coexisting OSA to assess for resolution or improvement of the OSA. A 2005 evidence-based analysis of the effectiveness and cost-effectiveness of bariatric surgery used as a method of last resort concluded that the evidence to support the use of such programs was suboptimal. However, a 2009 systematic review and economic evaluation found bariatric surgery appears to be a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions
TREATMENT OF COMORBID CONDITIONS
Comorbid conditions that impair ventilation or reduce the ventilatory response to hypoxemia or hypercapnia are likely to contribute to the impairment caused by obesity. As a result, the clinician should make an effort to identify and treat such comorbid conditions. Examples include chronic obstructive pulmonary disease (COPD) and hypothyroidism.
When total respiratory compliance is considered in obese patients, the effects of obesity on the chest wall must be separated from the effects attributable to decreased lung compliance, as seen in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This distinction has major implications for the application of mechanical ventilation
in obese patients.
COPD – COPD may exacerbate the symptoms and signs of OHS because both diseases impair alveolar ventilation and increase the work of breathing. It is reasonable to perform spirometry in patients with OHS, in order to detect coexisting COPD. Treatment of the COPD is indicated for all patients who are found to have coexisting COPD. This includes the cessation of smoking, bronchodilators, and, possibly, inhaled corticosteroids.
Bronchodilators — Medications that help open the airways, called bronchodilators, are a mainstay of treatment for chronic obstructive pulmonary disease. Bronchodilators help to keep airways open and possibly decrease secretions.
Bronchodilators are most commonly given in an inhaled form using a metered dose inhaler (MDI), dry powder inhaler (DPI), or nebulizer. It is important to use the inhaler properly to deliver the correct dose of medication to the lungs. If you do not use the inhaler correctly, little or no medicine reaches the lungs.
There are several types of bronchodilators that can be used alone or in combination.
- Short-acting beta agonists – Short-acting beta agonists, sometimes called rescue inhalers, can quickly relieve shortness of breath and can be used when needed. Examples of short-acting beta agonists include albuterol, levalbuterol, and pirbuterol.
- Short-acting anticholinergics – Short-acting anticholinergic medication (ipratropium, Atrovent) improves lung function and symptoms. If symptoms are mild and infrequent, short-acting anticholinergic medication may be recommended only when you need it. Or, if symptoms are more severe or more frequent, it may be recommended on a regular basis.
- Short-acting combination inhaler – A combination inhaler that contains albuterol and ipratropium (Combivent) is also available. Combination inhalers may be used just when needed or regularly, depending on the frequency and severity of your symptoms.
Long-acting treatments are often recommended for people who must use medication on a regular basis to control COPD symptoms.
- Long-acting beta agonists – Long-acting beta agonists may be recommended if your symptoms are not adequately controlled with other treatments. Examples of long-acting beta agonists include salmeterol, formoterol, and arformoterol.
- Long-acting anticholinergics – The long-acting anticholinergic medication, tiotropium (Spiriva), which is taken once daily, improves lung function while decreasing shortness of breath and flares of COPD symptoms. Aclidinium (Tudorza), a long-acting anticholinergic that is taken twice daily, also improves lung function. This type of medication may be recommended if your symptoms are not adequately controlled with other treatments, such as the short-acting bronchodilators.
- Theophylline – Theophylline in slow release form (e.g., Theo-Dur, Slo-bid) is a long-acting bronchodilator that is taken in pill form. Theophylline is not commonly used, but may be beneficial to some people with more severe, but stable chronic obstructive pulmonary disease. The dose of theophylline must be monitored carefully by blood tests because of its potentially toxic effects.
Glucocorticoids — Glucocorticoids (also called steroids, although they are very different from muscle building steroids) are a class of medication that has anti-inflammatory properties. Glucocorticoids can be taken with an inhaler, as a pill, or as an injection. Inhaled glucocorticoids may be recommended if your symptoms are not completely controlled with bronchodilators and/or if you have frequent flares of chronic obstructive pulmonary disease.
Glucocorticoids taken in pill form are sometimes used for short term treatment (e.g., for flares of COPD), but are not generally used long-term because of the risk of side effects.
Combination treatments — Combinations of short and long-acting bronchodilators, anticholinergics, and/or glucocorticoids are often used in people whose symptoms are not completely controlled with one medication.
Supplemental Oxygen – Supplemental oxygen therapy is a widely accepted therapy for hypoxemic patients with COPD alone; it has been shown to improve survival and it is not associated with worsening hypercapnia [30-32]. In contrast, supplemental oxygen therapy may worsen hypercapnia in coexisting OHS and COPD. In situations in which a patient with OHS and COPD requires supplemental oxygen, it should be used along with noninvasive positive airway pressure therapy because there is evidence that hypercapnia may not worsen if the supplemental oxygen is used with noninvasive positive airway pressure. If the patient cannot tolerate noninvasive positive airway pressure therapy, the patient should be carefully monitored to ensure that worsening of nocturnal asphyxia does not have adverse effects on hemodynamics, symptoms, or alveolar ventilation.
Hypothyroidism – Hypothyroidism may contribute to the chronic ventilatory failure of OHS by decreasing chemo-responsiveness, causing OSA (due to macroglossia and/or upper airway dilator muscle dysfunction), or causing either a myopathy or neuropathy that affects the respiratory muscles [33-36]. These consequences of hypothyroidism may be improved with thyroid hormone replacement. Screening for hypothyroidism by measuring the serum thyroid stimulating hormone (TSH) concentration is warranted in all individuals presenting with OHS, since the clinical presentation of the hypothyroidism may be quite similar to that of euthyroid patients with OHS.
In cases of subclinical hypothyroidism, which are characterized by mild elevation of the serum TSH (<10 mU/L) and a normal free T4 level, there are no data to strongly support either treating OHS patients with supplemental thyroid hormone or observing them. Given the potential contribution of superimposed hypothyroidism to the respiratory failure present in OHS and also the potential for a substantial portion of individuals with subclinical hypothyroidism to eventually progress to overt hypothyroidism over a number of years, the decision to observe patients with OHS who have laboratory evidence of subclinical hypothyroidism mandates periodic laboratory and clinical monitoring for the development of overt hypothyroidism.
Patients with OHS should be advised to abstain from alcohol. In addition, benzodiazepines, opiates, and barbiturates should be avoided if possible. While most of the dangers of these agents have been described as worsening sleep-related breathing abnormalities in patients with coexisting OHS and OSA, however this evidence is relevant to all patients with OHS, since most patients with OHS also have OSA and there are theoretical risks of adversely affecting ventilatory chemoresponsiveness and upper airway function in OHS.
In addition to the sedatives described above, supplemental oxygen must be approached cautiously in patients with OHS because it may increase hypercapnia . In situations in which a patient with OHS requires supplemental oxygen, it should be used along with noninvasive positive airway pressure therapy because there is evidence that hypercapnia may not worsen if the supplemental oxygen is used with noninvasive positive airway pressure. If supplemental oxygen is necessary and the patient cannot tolerate noninvasive positive airway pressure therapy, the patient should be carefully monitored to ensure that worsening of nocturnal asphyxia does not have adverse effects on hemodynamics, symptoms, or alveolar ventilation.
OBESITY AND ACUTE RESPIRATORY DISTRESS SYNDROME
(ARDS) – When total respiratory compliance is considered in obese patients, the effects of obesity on the chest wall must be separated from the effects attributable to decreased lung
compliance, as seen in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This distinction has major implications for the application of mechanical ventilation
in obese patients.
In all these commonly encountered clinical scenarios obesity magnifies patient risk, by predisposing to the underlying condition, contributing to the associated pathophysiological
derangements and complicating management from a technical and logistical point of view. Regrettably, the problem of morbid obesity is flourishing and an increasing proportion of patients in the ICU suffer from its pervasive effects, adding to its status as the one of the greatest challenges to the health of communities in the developed world.
Few drugs known for their respiratory stimulant effects, like progesterone, acetazolmide, almitrine and aminophylline, have been tried in patients with sleep apnea syndromes; however, the two most widely quoted drugs when dealing with OHS patients are medroxyprogesterone and acetazolmide .
Respiratory stimulants (i.e., progestins and acetazolamide) are a therapy of last resort for patients with who continue to have serious alveolar hypoventilation despite positive airway pressure therapy. Progestins have been shown to improve awake hypercapnia and hypoxemia in patients with OHS [38,39], while acetazolamide has been shown to improve alveolar ventilation in patients with OHS [40-42]. Medroxyprogesterone acetate stimulates respiration at the hypothalamic level. Acetazolamide is a carbonic anhydrase inhibitor that increases minute ventilation by inducing metabolic acidosis through increased excretion of bicarbonate by the kidneys. Acetazolamide has been shown to improve AHI, increase PaO2, and reduce PaCO2 in patients with OSA .
Despite these benefits, neither is considered an appropriate primary therapy for OHS because they do not affect all of the pathogenic contributors to OHS, in particular the recurrent upper airway collapse that occurs during sleep in patients who have coexisting obstructive sleep apnea (OSA) [43-46] or the altered respiratory mechanics . Leaving these contributors untreated may have adverse long-term consequences. In addition, progestins and acetazolamide have potentially serious side effects [48,49]. The respiratory stimulant, theophylline, has not been studied in patients with OHS.
Tracheostomy has no role in patients with OHS alone, but it may be effective in patients with coexisting OHS and obstructive sleep apnea (OSA) because it relieves upper airway obstruction during sleep with subsequent improvement in alveolar ventilation and the arterial carbon dioxide tension (PaCO2) during wakefulness . Not all patients return to eucapnia following tracheostomy because upper airway obstruction is just one of several factors responsible for chronic hypoventilation in patients with coexisting OHS and OSA; other factors include decreased compliance of the respiratory system and decreased ventilatory muscle strength, which are unaltered by tracheostomy.
Tracheostomy is rarely necessary since the same goals can be achieved without surgery using noninvasive positive airway pressure therapy. This is fortunate since tracheostomy is associated with many problems, including the following: The surgery is more difficult in obese individuals, debulking excess subcutaneous tissue may be required, obesity may limit the use of tracheostomy buttons during wakefulness to facilitate speech, recurrent episodes of purulent bronchitis may occur, and psychosocial problems after the procedure have been reported in a majority of patients, including disability, adjustment disorders, and marital discord .
SUMMARY AND RECOMMENDATIONS
- Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index [BMI] >30kg/m2) has awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, untreated hypothyroidism, or pleural pathology.
- Treatment is indicated because untreated OHS can progress to acute, life-threatening cardiopulmonary compromise. Untreated OHS is also associated with a high mortality rate, a reduced quality of life, and numerous morbidities.
- For all patients with OHS, it is recommended immediate initiation of noninvasive positive airway pressure therapy, rather than delaying the initiation of noninvasive positive airway pressure therapy until the outcome of the attempted weight loss is known (Grade 1B).
- All patients with OHS should undergo lifestyle modifications (ie, dietary changes, exercise, behavioral modifications) in an effort to lose weight. For those patients in whom weight loss due to lifestyle modifications is insufficient to correct the OHS, it is suggested NOT treating with weight loss medication (Grade 2B). For the same patients, referral to a bariatric surgeon is reasonable if they either hope to eventually discontinue or are not tolerating nocturnal noninvasive positive airway pressure.
- Comorbid conditions that impair ventilation or reduce the ventilatory response to hypoxemia or hypercapnia are likely to contribute to the impairment caused by obesity. As a result, the clinician should make an effort to identify and treat such comorbid conditions. Examples include chronic obstructive pulmonary disease (COPD) and hypothyroidism.
- Patients with OHS should be advised to abstain from alcohol. In addition, benzodiazepines, opiates, and barbiturates should be avoided in patients with OHS if possible. Supplemental oxygen must be approached cautiously in patients with OHS because it may increase hypercapnia.
- Pharmacological therapy with respiratory stimulants does not treat all of the pathogenic components of OHS and has potential side effects; therefore, it is regarded as a therapy of last resort for patients with who continue to have serious hypoventilation despite positive airway pressure therapy.
- Tracheostomy has no role in patients with OHS alone. It may be effective in patients with coexisting OHS and obstructive sleep apnea (OSA) because it relieves upper airway obstruction during sleep; however, not all patients return to eucapnia following tracheostomy because upper airway obstruction is just one of several factors responsible for chronic hypoventilation. In addition, tracheostomy has attendant surgical risks.
In the study, Long-Term Outcome of Noninvasive Positive Pressure Ventilation for Obesity Hypoventilation Syndrome, the Kaplan-Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and 77.3%, respectively. Using the Swedish Home Mechanical Ventilation Register, Laub and Midgren found a similar 5-year survival (≈ 75%) in Pickwick patients. The 5-year survival rate was higher (88%) in the study from Janssens et al, but that study included patients with lower baseline Paco2 than the original studies patients, (mean value of 49 ± 10 mm Hg and 42% of patients with baseline Paco2 < 45 mm Hg) .
Furthermore, these results correlate with the study Mortality and Prognostic Factors in Patients with Obesity-Hypoventilation Syndrome Undergoing Noninvasive Ventilation. In that study the authors found all-cause mortality was 12.7%, with 1-, 2- and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO2 <50 mmHg, C-reactive protein >= 5.1 mg L-1, leucocytes >= 7.8 · 103 micro l-1, or pH >= 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO2, pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO2 by >=23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival .
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