Because patients with OHS have persistent hypercapnia and hypoxia, frequent sleepiness, drowsiness, fatigue, and difficulty performing regular activities are common symptoms in these patients. Sleep disturbances, including loud snoring and morning headaches, are frequently described, and sleep apnea is present in the majority of cases [13]. Patients who develop complications such as pulmonary hypertension, or heart failure may present with dyspnea or edema of the extremities. All of these symptoms significantly impair the quality of life, and appropriate investigations should be made to establish the cause of such symptoms.

• Hypoxemia

  Thus, in obese patients treated with noninvasive positive pressure ventilation, a paradoxical worsening of hypoxemia may reveal the existence of a patent foramen ovale. [ncbi.nlm.nih.gov]

  Hypercapnia, [[Hypercapnia]]) Hypoxemia (see Hypoxemia, [[Hypoxemia]]) Obstructive Sleep Apnea (OSA) (see Obstructive Sleep Apnea, [[Obstructive Sleep Apnea]]) Epidemiology Approximately 90% of Patients with OHS Have Associated OSA, While 10% of Patients [mdnxs.com]

• Fatigue

  The pathogenesis involves mechanical, endocrine, and functional disturbances, while excessive fatigue and sleepiness are the most common symptoms. [symptoma.com]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 29, 2019 [patientslikeme.com]

  […] inspiratory muscle strength Severe obstructive sleep apnea (OSA; eg, apnea hypopnea index >60 events per hour) Symptoms and signs; patient suffering from OHS can have daytime hypersomnolence, loud snoring, choking during sleep, resuscitative snorting, fatigue [themetabolismclinic.com]

• Congestive Heart Failure

  Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]]) Right-Sided Congestive Heart Failure (Cor Pulmonale) Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]]): may occur with/without congestive heart failure Left-Sided [mdnxs.com]

  The most common comorbidities were arterial hypertension, diabetes mellitus, and congestive heart failure. [ncbi.nlm.nih.gov]

  heart failure, extreme somnolence, obstructive sleep apnea syndrome; O2 therapy may be fatal, as it removes the chemoreceptor drive needed for respiratory movement Cardiopulmonary obesity syndrome, sleep apnea/obesity hypoventilation syndrome A complication [medical-dictionary.thefreedictionary.com]

• Plethora

  Burwell 3 coined the term Pickwickian syndrome describing the constellation of morbid obesity, plethora, oedema and hypersomnolence. Hypercapnia, hypoxaemia and polycythemia were described on laboratory testing. [bjmp.org]

  The increasing trend of obesity and emergence of super obese individuals (body mass index [BMI] 50 kg/m 2 ) has led to a plethora of health consequences affecting major physiological and biochemical systems including the respiratory system (Finucane et [projmed.com]

  In the past 2 decades, there has been a plethora of data concerning diagnosis and management of SDB. [thoracicmedicine.org]

• Hypersomnia

  HYPERSOMNIA VS. FATIGUE When investigating potential causes of EDS, it is important to distinguish between fatigue and excessive sleepiness, or hypersomnia. [rjjaramillo.wordpress.com]

  Therapeutic effects of tracheostomy in two cases of hypersomnia with respiratory disturbance during sleep. Folia Psychiatr Neurol Jpn 1980;34:17-25. 103. Koziej M, Mankowski M, Radwan L, Maszczyk Z. [thoracicmedicine.org]

• Sleep Apnea

  A 50-year-old African woman was referred to our sleep center for severe obstructive sleep apnea syndrome and obesity hypoventilation syndrome. [ncbi.nlm.nih.gov]

  The spectrum of sleep disordered breathing ranges from habitual snoring, to upper airway resistance syndrome, to obstructive sleep apnea, and to obstructive apnea/hypoventilation syndrome. [emedicine.com]

  […] other sleep-breathing disorders in the vast majority of cases, most commonly with sleep apnea. [symptoma.com]

• Heart Disease

  In addition to the well-established risks of heart disease, stroke, diabetes, and some cancers, obesity is driving a new epidemic in sleep-disordered breathing in the form of obesity hypoventilation syndrome (OHS). [journals.lww.com]

  If accompanying diseases, such as heart failure or pulmonary hypertension are present, swelling of the extremities, dyspnea, and profound weakness is observed. [symptoma.com]

  Pagina 246 - Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 1 1 -year follow-up of the Paris Prospective Study. ‎ Pagina 165 - Livingstone MBE. [books.google.it]

  Apart from an increased risk of heart diseases and many other ailments like diabetes and erectile dysfunction, a condition that can happen because of obesity is Obesity Hypoventilation Syndrome also known as Pickwickian Syndrome. [vertihealth.com]

• Hepatomegaly

  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 [en.wikipedia.org]

  […] hypersomnolence, 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 [rjjaramillo.wordpress.com]

  […] diastolic and systolic dysfunction. 101 A focused cardiopulmonary examination should be directed at discovering signs of congestive heart failure (rales, S3, jugular venous distension) and pulmonary hypertension (loud P2, right ventricular heave, congestive hepatomegaly [anesthesiology.pubs.asahq.org]

• Headache

  Sleep disturbances, including loud snoring and morning headaches, are frequently described, and sleep apnea is present in the majority of cases. [symptoma.com]

  Daytime sleepiness Morning headaches Memory or concentration problems Irritability and depression Fast, shallow breathing Shortness of breath during activity Treatment The most effective treatment is weight loss, but it is often possible to relieve the [lakelandhealth.org]

  The main symptoms of OHS are due to lack of sleep and include: Poor sleep quality Sleep apnea Daytime sleepiness Depression Headaches Tiredness Symptoms of low blood oxygen level (chronic hypoxia) can also occur. [nlm.nih.gov]

  OHS symptoms include: Dyspnoea 2, Excessive daytime sleepiness (EDS) 2, Morning headache 2, Depression. As many as 90% of patients with OHS also suffer from obstructive sleep apnoea (OSA). [resmed.com]

• Guillain-Barré Syndrome

  The specific causes can be summarized as follows: COPD Neuromuscular disorders [3] - Amyotrophic lateral sclerosis, muscular dystrophies (Duchenne and Becker dystrophies), diaphragm paralysis, Guillain-Barré syndrome, myasthenia gravis Chest wall deformities [emedicine.com]

• Memory Impairment

  The chronic suffering from Obesity hypoventilation syndrome causes the following symptoms: Snoring Apneas Disturbed sleep Early morning headache Reduced recital Lack of concentration Memory impairment Learning difficulty Worse the condition leads to pulmonary [syndromespedia.com]

Once the suspicion toward OHS is made, a full diagnostic workup should be initiated. Primarily, laboratory tests, including CBC, which will likely show erythrocytosis, while bicarbonate levels in the blood are always increased. Hypothyroidism should be excluded as a potential cause of hypoventilation, and thyroid hormone levels should be measured. Noninvasive pulse oximetry reveals decreased oxygen saturation, and arterial blood gasses should be measured, which will reveal increased PCO2 and decreased PO2.

Under such circumstances, spirometry, chest X-ray, and possibly CT scan should be performed to assess the respiratory system, and exclude other causes of hypoventilation and hypercapnia. Spirometry may reveal restrictive lung disease, and reduced inspiratory and expiratory pressures, as well as reduced expiratory reserve volume. Echocardiography and chest X-ray may reveal right heart enlargement.

Polysomnography should be performed in all patients with suspicion for sleep apnea and involves overnight evaluation of PCO2 concentrations during nighttime [14]. It is used as a definite diagnostic procedure in OHS.

Once all other potential causes of hypercapnia and respiratory failure have been excluded, and the presence of sleep-disordered breathing is confirmed in an obese individual, the diagnosis of Obesity hypoventilation syndrome can be confirmed, and appropriate therapeutic measures can be taken.

Treating OHS requires several steps, and involves multiple principles [15]:

• Weight reduction - Initial treatment should be aimed at reducing body weight, as it has been shown that weight loss can significantly relieve the workload of the lungs, thus reducing the severity of hypoxemia and increased ability of tissue perfusion with oxygen, while eliminating hypercapnia. In patients with severe obesity, and in those who develop refractory obesity despite adequate dietary management, bariatric surgery may be indicated. However, other treatment modalities should be initiated along with weight reduction, because sole weight loss cannot relieve the patient of the symptoms and the condition. Moreover, patients with severe comorbidities may not be eligible for surgery, which is why other treatment principles must be used.
• Oxygen therapy - Because hypoxemia is a common finding in these patients, particularly during sleep, supplementary oxygen may be indicated in some patients. Although oxygen is helpful in relieving the pulmonary workload, it cannot resolve persistent hypoventilation, which is why positive ventilation techniques are the primary treatment of choice.
• Positive airway pressure ventilation - Patients with severe respiratory failure and persistent hypercapnia are treated by positive pressure ventilation. Under such circumstances, the mechanical force of the lungs is reduced, the accompanying obstructive diseases and hypoventilation can be overcome, and improvement of the central respiratory centers can be supposedly achieved [16]. This technique can be used for both acute and chronic states and shows good results, which is why it is commonly indicated as the treatment of choice. Alternatively, this mode of ventilation can be slightly altered, since some patients cannot tolerate this mode of ventilation, or if frequent episodes of hypoventilation occur despite adequate treatment. In that case, the machine is set to independently create positive inspiratory and expiratory pressure (biphasic PAP, or bi-PAP)
• Tracheostomy is indicated in patients with severe airway obstruction, and in whom ventilation therapy is insufficient, and it shows good results in such patients [17].
• Medroxyprogesterone acetate and Acetazolamide are therapeutic drugs that have been reported as potentially useful in the management of OHS [18]. Medroxyprogesterone is a synthetic analogue of progesterone, and its role in OHS is presumably through breathing stimulation, while acetazolamide belongs to the group of carbonic anhydrase inhibitors, and stimulates bicarbonate loss through urine, thus eliminating excessive HCO3 from the blood.

In addition to treatment of OHS via one or more of the strategies mentioned above, proper management of accompanying comorbidities, such as cardiovascular disease including heart failure, should be conducted, since significant morbidity and mortality is associated with other accompanying illnesses.

The prognosis depends on the severity of the disease at the time of diagnosis, the severity of obesity, presence of comorbidities, and adequate response to therapy. It is estimated that the majority of patients are undiagnosed until their 50s and 60s, which significantly impedes therapeutic principles to be effective [11]. However, the outcome is good for patients who are treated with aggressive ventilatory therapy, but respiratory failure, the presence of concomitant heart disease and pulmonary hypertension are the significant predictors for poor outcomes despite adequate treatment [12].

It is not completely understood why this syndrome occurs and which factors determine its onset among the obese. It is assumed that the respiratory system is burdened by the increased body weight, which necessitates an increased workload [3]. Eventually, chronically increased effort leads to respiratory complications and the inability of the lungs to perform gas exchange and supply the tissues with enough oxygen, with persistent hypercapnia and hypoventilation. Other factors, such as leptin resistance, and chronic elevation of inflammatory cytokines have been implicated in the development of this disease. Predisposing respiratory conditions, such as chronic obstructive pulmonary disease (COPD), or interstitial lung disease, have also been determined to have a potential role in these patients.

The actual number of obese individuals with OHS is not known, and the majority of epidemiological data is focused on obstructive sleep apnea [4]. Results have been obtained in certain studies and indicate that the prevalence of OHS is between 10 and 38% in different groups [5], while other studies have reported that among hospitalized patients with a BMI > 35 kg/m2, more than 30% have OHS. Based on these data, it is estimated that the overall prevalence of OHS in the United States and other parts of the world is about 0.3% [6]. It is determined that the greater the severity of obesity, the more increased the risk is of developing OHS.

Obesity hyperventilation syndrome is thought to involve multiple factors in its pathogenesis model. In addition to the increased effort of the lungs that is induced by mechanical obstruction of increased body weight, several other processes are thought to be involved:

• Obstructive sleep apnea (OSA) - Obesity hyperventilation syndrome is accompanied by other sleep-breathing disorders in the vast majority of cases, most commonly with sleep apnea. It is further noted that treatment of sleep apnea resulted in amelioration of daily hypercapnia, and cessation of symptoms, which led to the assumption that these disorders are important contributors to this disease [7].
• Leptin resistance - Leptin is secreted by adipocytes, and its primary function is appetite suppression, but it has been established that is also has a role in stimulating ventilation. In obese patients, leptin resistance is commonly observed, and it is thought that this resistance contributes to the development of hypoventilation in this population [8].
• Chronic inflammation and hypothalamic suppression - Activation of proinflammatory cytokines, including IL-1, IL-6, IL-18, TNF-alpha, CRP, and many other has been observed in obese individuals, which is thought to contribute to suppression of the hypothalamic regions involved in sleeping regulation and breathing, resulting in altered breathing rates during sleep [9].
• Altered neuromodulation, as a result of hypoxia, and altered regulation of sleep in the setting of prolonged hypoxia has been investigated as a possible factor in this disorder [10].

Since this disease exclusively occurs in obese individuals, proper management of body weight through appropriate diet and exercise is vital in reducing the chances of developing this syndrome. It is increasingly evident that more individuals are becoming obese throughout the world, but good dietary habits and regular physical activity are essential to reducing the burden of this disease, but also many other that appear in obese individuals.

Obesity hypoventilation syndrome (OHS) is a distinct clinical entity and is one of the many complications that may develop in obese patients. It is defined as the presence of hypercapnia during daytime (PaCO2 > 45 mmHg) and hypoventilation that has no other known causes in exclusively obese individuals (BMI > 30kg/m2) [1]. It is classified in the group of sleep disturbance disorders (SDBs), and it commonly occurs together with obstructive sleep apnea (OSA). The exact cause of this syndrome is unknown, but presumably involves several factors, including increased respiratory effort as a result of mechanical obstruction due to obesity; resistance to leptin (a hormone secreted by the adipose tissue to suppress appetite), which commonly develops in obese individuals, and contributes to hypoventilation, since leptin is additionally involved in maintaining normal respiration; and chronic elevation of inflammatory cytokines, including various members of the interleukin family and C-reactive protein (CRP), which presumably lead to chronic hypothalamic suppression and insulin resistance, all implicated in sleep-disordered breathing. Sleep apnea is diagnosed in the vast majority of patients with OHS. This disorder can carry a good prognosis if diagnosed and treated early, since the majority of symptoms, as well as disturbances in CO2/O2 content, are shown to be reversible. However, significant mortality rates are observed without appropriate therapy, because numerous complications may arise, including chronic states of hypoxemia, pulmonary hypertension and heart failure. Preexisting comorbidities play a role in patient outcomes as well. This syndrome is most commonly diagnosed in middle-aged males, and symptoms include frequent sleepiness, fatigue, poor daily performance, and in some cases, neurocognitive deficits. Snoring, morning headaches, and poor sleeping are commonly observed, as hypoventilation occurs during sleep as well and interferes with almost all sleep stages, more commonly with REM sleep [2]. If accompanying diseases, such as heart failure or pulmonary hypertension are present, swelling of the extremities, dyspnea, and profound weakness is observed. The diagnosis is made by a full blood workup, including complete blood count (CBC), blood levels of bicarbonate, and arterial blood gas analysis to confirm hypercapnia. The extensive diagnostic panel should be conducted in these patients, to exclude other causes of hypoventilation and hypercapnia, including thyroid hormone levels and neuromuscular diseases, and a definite diagnosis is made by polysomnography. Before initiating treatment, other accompanying illnesses should be assessed, including pulmonary hypertension, heart failure, and other metabolic and endocrine complication that may arise in obesity. Treatment depends on the severity of disease, and may include supplementary oxygen, tracheostomy, and assisted ventilation techniques that aid in restoring normal blood gas levels and reduce the burden on the respiratory system. Proper management of accompanying comorbidities can be challenging, and treatment of OHS may depend on the presence of various diseases. However, their management is vital in ensuring a good outcome in such patients, in addition to treating OHS.

Obesity hypoventilation syndrome (OHS) is a condition seen in obese individuals in which the lungs are not able to perform their normal function, resulting in accumulation of bicarbonate and lower levels of oxygen in the blood. This disease occurs because individuals cannot maintain proper breathing rate, which leads to decreased expiration of carbon dioxide while reducing the inspiration of oxygen. It is not completely understood why this syndrome occurs, and why some obese individuals develop it, and some not, but it is implied that the burden of the respiratory system is increased as a result of the mechanical pressure of increased weight and fat content. Additional factors have been implicated in the development of this disease, but perhaps the most notable finding is that the majority of patients have concomitant obstructive sleep apnea.

Patients who have this condition experience frequent fatigue, as they are not able to sleep properly, as well as daytime sleepiness or drowsiness, and frequent morning headaches. Individuals are significantly limited in performing their daily activities, and some patients may develop progressive heart disease and respiratory failure, in which case difficulty breathing and swelling of the extremities may be observed. Because most of the symptoms can be reversed and almost completely managed with therapy, prompt identification and treatment are essential in maintaining the quality of life. It is important to note that several comorbidities may arise in the setting of obesity, such as diabetes mellitus, cardiovascular disease, and many other, and they may play a significant role in the outcome of patients with OHS.

The diagnosis of this syndrome is achieved by performing several laboratory tests. Measurement of oxygen and carbon dioxide concentrations in the blood are performed, and assessment of the heart and lungs is performed as well. To confirm the diagnosis, studies that evaluate blood gas concentrations and activity of the chest wall during sleep will be performed.

Treatment comprises several principles. Weight loss is essential in reducing the burden of the respiratory system, while assisted ventilation by introducing air under pressure into the lungs is the method of choice, but also aiding in the forceful expiration of carbon dioxide, thus promoting normal gas exchange. Other treatment principles include supplementary oxygen, medications, and in severe cases, surgery and tracheostomy.

The prognosis is good for patients in whom this diagnosis is made early, and in whom proper therapy is initiated and maintained. Various factors may play a role in the outcome of patients, such as the presence of comorbidities and the severity of the disease at the time of diagnosis, which is why an early diagnosis is vital in reducing the mortality rates.

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