While some patients with OHS present with acute on chronic exacerbation of respiratory failure with acute respiratory acidosis, other patients remain clinically stable at the time of diagnosis. Majority patients have classic symptoms including loud snoring, nocturnal choking episodes with witnessed apneas, excessive daytime sleepiness, and morning headaches. Patients often exhibit dyspnea and may have signs of cor pulmonale. Classical physical examination findings include an enlarged neck circumference, crowded oropharynx, a prominent pulmonic component of the second heart sound on cardiac auscultation, and lower extremity edema.

Clinical suspicion should be high in patients with BMI > 30 kg/m2 with unexplained dyspnea on exertion and hypersomnolence [3]. The diagnostic approach's aim is to demonstrate daytime hypoventilation. The most definitive diagnostic test for alveolar hypoventilation is an arterial blood gas analysis. Unfortunately, an ABG is not readily done in an outpatient setting. However, most patients with OHS most common initial presentation is in a hospital setting after presenting with an acute exacerbation where an ABG along with a basic metabolic panel can be done. Their initial laboratory values will show elevated serum bicarbonate level which is typically seen as a result of metabolic compensation of respiratory acidosis which points toward the chronic nature of hypercapnia. This is why a serum bicarbonate level can sometimes serve as a sensitive test to screen for chronic hypercapnia but ultimately an arterial blood gas should show evidence of hypoventilation in complete wakefulness. Polymnography is not required for diagnosis but helps distinguish between patients with coexistent OSA from those with actual sleep hypoventilation. Sleep hypoventilation is defined as a 10 mmHG increase in PaCO2 above that of wakefulness that is not secondary to obstructive apneas or hypopnea. The percent of total sleep time with SpO2 spent below 90% can be a useful polysomnographic variable for evaluation of OHS patients. OHS is a diagnosis of exclusion that requires to be distinguished from disorders that are also associated with hypoventilation. Pulmonary function testing can exclude other causes of hypercapnia such as COPD. In OHS, PFT typically shows a mild to moderate restrictive defect. The expiratory reserve volume is significantly reduced along with mild reductions in maximum expiratory and inspiratory pressures secondary to a combination of altered respiratory mechanics and weak respiratory muscles. Imagings may identify anatomical obstructions such as severe chest-wall disorders. A complete blood count should be obtained to rule out secondary erythrocytosis. Thyroid function tests are to be obtained as well to exclude severe hypothyroidism. 

OHS is associated with significantly high rate of morbidity and mortality. Although treatment modalities target different aspects of the underlying pathophysiology, the goal is normalization of arterial carbon dioxide, reduction of oxyhemoglobin desaturation and improvement in symptoms. Several therapeutic options have been tried including positive airway pressure therapy, weight reduction surgery and pharmacotherapy.[12][13]

Positive Airway Pressure Therapy

Noninvasive positive airway pressure therapy is typically the first-line treatment for OHS. Noninvasive airway pressure therapy significantly reduces the nocturnal built up of PaCO2 and improves sleepiness during the daytime. The available treatment options includes Continuous positive airway pressure (CPAP), bi-level PAP, and other noninvasive ventilation (NIV) modalities. Although there is no defined guidelines for using particular treatment therapy, the current recommendation is to use CPAP if concomitant sleep-related breathing disorders are present. NIMV can be beneficial in patients having hypercapnia in the absence of significant apnea or hypopnea. The German society of pneumology recommends the use of NIMV in the absence of OSA, in the presence of OSA with significant comorbidities and with a CO2 level above 55 mm Hg for over 5 minutes or saturation of under 80% for over 10 minutes. The Canadian thoracic society recommends CPAP use in patients with a minor degree of nocturnal desaturation and no nocturnal rise of PaCO2. Bi-level PAP is the treatment of choice in OHS patients with significant nocturnal desaturation or the nocturnal rise of PaCO2. A recent study compared the 3 standard treatments for OHS including NIV, CPAP, and lifestyle modification. This study showed that both NIV and CPAP significantly improved polysomnographic parameters, although NIV was superior in improving respiratory parameters as compared to other treatment modalities. In a total of 351 patients compared to baseline, at 2 months, the 3 treatments showed a reduction in PaCO2 of 5.5, 3.7, and 3.2 with NIV, CPAP, and lifestyle modification respectively.

Surgery

Tracheostomy 

Tracheostomy relieves the airway obstruction during sleep, thus improving the alveolar ventilation and waking PaCO2. However, some patients still may not return to eucapnic state post tracheostomy, as it does not affect CO2 production and impaired muscle strength.

Weight reduction 

Numerous studies have shown improvement in OHS symptoms with weight reduction. Weight loss significantly reduces CO2 production and improve sleep apnea severity and alveolar ventilation. It also improves pulmonary artery hypertension and left ventricular dysfunction which can greatly reduce the cardiovascular compromise in OHS patients. Ideally, lifestyle modification therapy should be tried initially for weight loss. Surgical options should be considered for refractory cases.Pharmacotherapy

Medroxyprogesterone and acetazolamide can potentially reverse the hypercapnia associated with OHS; however, routine use is not recommended given the narrow safety margin and long-term side effects.

Leptin replacement therapy has been shown to relieve nocturnal hypoventilation and airway obstruction during sleep secondary to increased respiratory drive to both upper airway and diaphragm in experimental mice studies, but human use is not recommended.

Limitation to Ventilation

• Chest wall diseases
• Neuromuscular diseases
• Obstructive lung disease

Central Control Defects

• Congenital Central Hypoventilation (Ondine’s curse)
• PHOX2B mutation on chromosome 4p12
• Brainstem lesions
• Carotid body disease
• Metabolic alkalosis

Combined Defects

• Cronic obstructive pulmonary disease (COPD)
• Hypothyroidism
• Sleep apnea

Obesity hypoventilation is associated with reduced quality of life and prolonged admission rates and time in intensive care unit. In patients with other medical conditions, such as diabetes, asthma , the mortality rates are significantly high with 23% over 18 months and 46% over 50 months. Early use of CPAP can reduce the associated mortality by 10%. 

• Obesity is associated with multiple medical complications. Obesity hypoventilation syndrome is one of the major respiratory consequence associated with obesity.
• Presence of hypoventilation during wakefulness with PaCO2 greater than 45 mm Hg in the presence of obesity (BMI greater than 30 kg/m2) confirms the diagnosis, given that hypoventilation is not due to lung parenchymal or airway disease, pulmonary vascular pathology or chest wall disorder.
• Serum bicarbonate levels, therefore, can be used as a sensitive test to screen for chronic hypercapnia.
• The percent of total sleep time with SpO2 spent below 90% can be a useful polysomnographic variable for evaluation of OHS patients
• Noninvasive positive airway pressure therapy is the first line treatment for OHS which significantly reduces the nocturnal built up of PaCO2 and improves sleepiness during the daytime.

Obesity is best managed by an interprofessional team including dietitians, nurses, therapists, and pharmacists. Obesity has significant morbidity and mortality if it is left untreated. The key is to educate the patient on the harms of obesity. Patients need to be told to change their lifestyle, become physically active, maintain a healthy weight, and exercise regularly. All current therapies for obesity hypoventilation syndrome are palliative until the patient loses weight.

For patients who do not lose weight, the prognosis is poor with a shortened life expectancy.[14][15] (Level V)