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Treatment and prognosis of the obesity hypoventilation syndrome

Treatment and prognosis of the obesity hypoventilation syndrome
Author:
Thomas J Martin, MD
Section Editor:
M Safwan Badr, MD
Deputy Editor:
Geraldine Finlay, MD
Literature review current through: Dec 2022. | This topic last updated: Mar 31, 2022.

INTRODUCTION — Obesity hypoventilation syndrome (OHS; "pickwickian syndrome") exists when an individual with obesity (body mass index [BMI] >30 kg/m2) has awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg) which cannot be attributed to other conditions (eg, neuromuscular disease). Untreated OHS is a progressive disorder that is associated with significant morbidity such that prompt recognition and treatment is critical.

The treatment and prognosis of OHS are reviewed here. The clinical manifestations, diagnosis, complications, and pathogenesis of OHS are discussed separately. (See "Clinical manifestations and diagnosis of obesity hypoventilation syndrome" and "Epidemiology and pathogenesis of obesity hypoventilation syndrome".)

FIRST-LINE THERAPY — Noninvasive positive airway pressure (PAP) together with weight loss are the initial first-line therapies for patients with OHS [1]. A comprehensive and multidisciplinary approach utilizing experts in obesity, sleep, and pulmonary medicine is recommended.

Positive airway pressure — All patients with OHS have some form of sleep-disordered breathing, typically obstructive sleep apnea (OSA; 90 percent) or sleep-related hypoventilation (10 percent), warranting treatment with noninvasive PAP. PAP therapy should not be delayed while the patient tries to lose weight. Selection of the appropriate mode of PAP (eg, continuous PAP [CPAP], bilevel PAP [BPAP], volume cycled or hybrid modes of noninvasive ventilation) [2] and approach to initiating PAP therapy in patients with OHS are described in detail separately. (See "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome".)

Similar to patients with OSA who do not have OHS, patients with OHS have better outcomes when adherence to PAP is adequate [3]. (See "Assessing and managing nonadherence with continuous positive airway pressure (CPAP) for adults with obstructive sleep apnea".)

Obesity hypoventilation plus obstructive sleep apnea (continuous positive airway pressure) — CPAP is the typical mode chosen for treatment for OHS plus OSA, while BPAP, usually in the spontaneous–timed mode, is indicated in those who fail CPAP. (See "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome", section on 'Obesity hypoventilation and obstructive sleep apnea'.)

Obesity hypoventilation plus sleep-related hypoventilation (bilevel positive airway pressure) — Patients with OHS and sleep-related hypoventilation (absent of OSA) are, generally, initially managed with BPAP. (See "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome", section on 'Obesity hypoventilation and sleep-related hypoventilation'.)

Weight loss and lifestyle modifications — All patients with OHS should begin a weight loss program. Weight loss improves alveolar ventilation (sometimes normalizing the awake arterial carbon dioxide tension [PaCO2] and arterial oxygen tension [PaO2]), reduces the risk of cardiorespiratory complications (eg, pulmonary arterial hypertension and left ventricular function), improves nocturnal oxyhemoglobin saturation, decreases the frequency of respiratory events (ie, apneas, hypopneas) during sleep if the patient has coexisting OSA, and improves pulmonary function [4-11]. These benefits appear to occur regardless of whether the weight loss was due to lifestyle modification (ie, diet, exercise) or surgery. (See 'Additional treatments targeted at weight loss' below.)

Weight loss should be supervised and controlled. Rapid, unsupervised weight loss is discouraged because it is generally not sustained and may have serious side effects (eg, cholelithiasis). There are no reliable predictors of the exact amount of weight that must be lost to ameliorate nocturnal upper airway dysfunction and cardiorespiratory failure in OHS. Individuals with OHS are usually more than 50 percent above ideal body weight, and clinical experience suggests that weight loss of more than 100 pounds is often needed before clinically significant improvement is seen.

All patients with OHS should make lifestyle modifications to lose weight. Lifestyle modifications refer to various combinations of dietary change, exercise, and behavioral modification, which are described in detail separately. (See "Obesity in adults: Dietary therapy" and "Obesity in adults: Role of physical activity and exercise" and "Obesity in adults: Behavioral therapy".)

Individuals with OHS may have more difficulty maintaining long term weight loss than persons with uncomplicated obesity because of exercise limitations related to their chronic respiratory failure. Thus, while lifestyle modifications are necessary in patients with OHS, they are seldom sufficient [12] to achieve and maintain a degree of weight loss that satisfactorily improves alveolar ventilation and sleep-related breathing disorders [13]. Thus, patients should be educated in weight loss interventions that produce significant and sustained weight loss of 25 to 30 percent of body weight (eg, bariatric surgery) [1]. (See 'Additional treatments targeted at weight loss' below.)

Compared with positive airway pressure therapy, lifestyle modification alone is less effective at improving symptoms, polysomnographic parameters, hypercapnia, and some pulmonary function measurements [14].

SECOND-LINE THERAPY — Second-line therapies are reserved for patients with OHS who fail or do not tolerate first-line therapies (ie, noninvasive positive airway pressure [PAP] and weight loss measures). Bariatric surgery is also an option for those who wish to discontinue or reduce the need for PAP therapy. In general, these therapies are only considered after aggressive attempts have been made to optimize PAP therapy as they are suboptimal and associated with increased risk of adverse effects. Choosing among them depends upon factors that include the severity of OHS, degree of obesity, likelihood of efficacy or adverse effects, and patient preferences.

Treatments targeted at obesity hypoventilation and sleep-disordered breathing

Tracheostomy — Since the introduction of noninvasive PAP therapy, tracheostomy for treatment of OHS is now rarely necessary. Tracheostomy itself (without ventilation through the device) may be effective in patients with OHS and coexisting 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 [15]. However, not all patients return to eucapnia following tracheostomy because upper airway obstruction is just one factor responsible for alveolar hypoventilation in this population; other factors (eg, decreased respiratory compliance and ventilatory muscle strength) are unaltered by tracheostomy. In keeping with this hypothesis is our experience and available data, which suggest that, despite tracheostomy placement, most patients still require nocturnal ventilation through the device for residual OSA [16].

Tracheostomy alone cannot be used to treat OHS with sleep-related hypoventilation (absent of OSA) unless the tracheostomy is also used for nocturnal ventilation.

In addition to the typical risks and complications of the procedure [17-20], tracheostomy in the individual with obesity is technically more difficult because debulking of excess adipose tissue may be required in order to securely insert a standard tracheostomy tube [21,22]. In addition, it may be associated with a higher risk of tube displacement [17,20]. (See "Tracheostomy: Rationale, indications, and contraindications".)

The role of tracheostomy and other surgical procedures (eg, maxillomandibular advancement) sometimes used in the treatment of OSA have not been rigorously tested in patients with OHS and are discussed separately. (See "Surgical treatment of obstructive sleep apnea in adults", section on 'Global upper airway procedures'.)

Additional treatments targeted at weight loss — For patients in whom lifestyle modifications are insufficient (see 'Weight loss and lifestyle modifications' above) and/or for patients who either want to discontinue or do not tolerate noninvasive PAP, referral to a bariatric expert is appropriate. Weight loss medications are potentially harmful and often insufficient, so we believe that they should only be used on a case-by-case basis after a careful evaluation of the potential benefits and risks to the individual patient.

Bariatric surgery — For patients with class 2 or 3 obesity who have OHS, considerable attention has been directed toward bariatric surgery, since lifestyle modifications alone are generally insufficient and pharmacological therapy is of uncertain efficacy and safety [23]. Although no study has specifically enrolled patients with OHS, improvements in gas exchange, OSA, and indices of pulmonary hypertension have been reported in individuals with obesity undergoing bariatric surgery [4,6-8,10,11,24]. However, patients with OHS may be excluded from surgery due to the presence of comorbid conditions (eg, pulmonary hypertension or obesity itself). Additionally, the response to bariatric surgery (degree of weight loss, improvement in OSA, improvement in physiologic parameters) is dependent on both individual patient variables and surgical technique. Thus, complete resolution of OHS and freedom from PAP therapy is not uniform. The indications, contraindications, techniques, and complications of bariatric surgery and the preoperative evaluation of OSA prior to bariatric surgery, including recommendations on consultation with a sleep expert and/or repeat polysomnography, are reviewed in detail separately. (See "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Bariatric procedures for the management of severe obesity: Descriptions" and "Surgical risk and the preoperative evaluation and management of adults with obstructive sleep apnea".)

Patients should continue their noninvasive PAP therapy pre- and postoperatively. Inability to tolerate PAP therapy prior to bariatric surgery may necessitate a temporary tracheostomy either prior to or at the time of bariatric surgery [25]. Even with optimal titration of nocturnal noninvasive PAP preoperatively, patients with sleep-disordered breathing may be at further risk for hypoventilation postoperatively due to the effects of surgery, general anesthesia, or medications, such that empiric adjustments to PAP settings may be needed for a short period. Postoperative management of patients with obesity and OSA is discussed separately. (See "Bariatric surgery: Postoperative and long-term management of the uncomplicated patient" and "Postoperative management of adults with obstructive sleep apnea".)

Medication — Pharmacologic therapy for weight loss should only be administered in patients with OHS who fail diet and exercise measures. However, many of the approved weight loss medications may initially only achieve weight loss of 5 to 10 kg over 3 to 12 months before the weight loss plateaus, which is typically not enough to improve or eliminate awake hypoventilation. In addition, most patients regain their weight if the medications are discontinued. Indications, efficacy, and adverse effects of weight loss pharmacotherapy are discussed separately. (See "Obesity in adults: Drug therapy".)

THERAPIES OF LIMITED VALUE OR ASSOCIATED WITH HARM

Oxygen alone — Oxygen should not be administered as the sole therapy for OHS. This is because oxygen may increase hypercapnia, as demonstrated in two studies of stable newly diagnosed untreated patients with OHS [26,27]. In addition, although supplemental oxygen will treat sleep-related hypoxemia, it does not address the pathophysiologic contributors to awake alveolar hypoventilation, including altered chemoresponsiveness, nocturnal upper airway occlusion, and impaired respiratory mechanics.

In situations in which a patient with OHS requires supplemental oxygen (eg, for comorbid chronic obstructive pulmonary disease, severe nocturnal desaturations unresponsive to noninvasive positive airway pressure therapy [PAP]), it should be used concurrently with optimally titrated PAP therapy. Monitoring the need for oxygen is important since hypercapnia may improve and diurnal oxygen requirements may decrease with adherence to PAP therapy [28].

If supplemental oxygen is necessary and the patient cannot tolerate PAP, the patient should be carefully monitored (clinically and/or with polysomnography) to detect potential adverse effects of worsening hypercapnia on hemodynamics and symptoms. (See "Mechanisms, causes, and effects of hypercapnia", section on 'Oxygen-induced hypercapnia' and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure", section on 'Administration of oxygen'.)

Respiratory stimulants — Respiratory stimulants (ie, progestins and acetazolamide) are adjunctive therapies that are a last resort for patients who continue to have serious alveolar hypoventilation despite PAP therapy and weight loss. If prescribed, it should be done on a trial basis only in conjunction with optimally titrated PAP.

Progestins (eg, medroxyprogesterone) alone have been shown to improve but not to eliminate awake hypercapnia and hypoxemia in patients with OHS [29,30], while acetazolamide has been shown to improve alveolar ventilation in patients with OHS [15,31,32]. However these agents 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 [33-37] or the altered respiratory mechanics [38]. Leaving these contributors untreated typically results in undertreatment of OHS. In addition, progestins and acetazolamide have potentially serious side effects (eg, electrolyte disturbance, venous thromboembolism) [39,40]. The respiratory stimulant theophylline has not been studied in patients with OHS. (See "Management of obstructive sleep apnea in adults".)

SUPPORTIVE THERAPIES

Avoidance of alcohol and sedatives — Patients with OHS should be advised to avoid alcohol, benzodiazepines, opiates, muscle relaxants, and barbiturates. Failure to abstain from these agents may mitigate the benefit of positive pressure therapy. If any of these agents is considered imperative in the treatment of an individual with OHS, clinical monitoring is warranted to evaluate the impact of the medication on symptoms and arterial gas exchange. Polysomnography may be a useful adjunct to help assess nocturnal ventilation and adequacy of therapy. (See "Management of obstructive sleep apnea in adults", section on 'Alcohol avoidance'.)

Treatment of comorbid conditions — Routine treatment of comorbid conditions and the prevention of complications are also necessary in all patients with OHS. 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 comorbid conditions, including:

Chronic obstructive pulmonary disease (COPD) – Treatment of coexisting COPD includes the cessation of smoking and the prescription of inhaled bronchodilators and, possibly, inhaled corticosteroids. Supplemental oxygen benefits patients with hypoxemic COPD but should not be administered in OHS without coprescribing positive airway pressure (PAP) since it can worsen alveolar hypoventilation. The diagnosis and management of COPD are reviewed separately. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Stable COPD: Initial pharmacologic management" and "Long-term supplemental oxygen therapy".)

Hypothyroidism – Hypothyroidism may contribute to the chronic ventilatory failure of OHS by decreasing chemoresponsiveness, causing obstructive sleep apnea (due to macroglossia and/or upper airway dilator muscle dysfunction), or causing either a myopathy or neuropathy that affects the respiratory muscles [41-44]. These consequences of hypothyroidism may be improved with thyroid hormone replacement. In cases of subclinical hypothyroidism, which is characterized by mild elevation of serum thyroid stimulating hormone (<10 mU/L) and a normal free T4 level, we prefer to monitor these patients (eg, every six months) for the development of overt hypothyroidism using clinical examination and thyroid function tests. (See "Treatment of primary hypothyroidism in adults".)

FOLLOW-UP — The therapeutic goals for patients with OHS include [45]:

Normalization of the arterial carbon dioxide tension (PaCO2) during wakefulness and sleep (ie, PaCO2 <45 mmHg).

Elimination of oxyhemoglobin desaturation during wakefulness and sleep; to avoid worsening hypercapnia, it is recommended that the provision of supplemental oxygen during positive airway pressure (PAP) therapy be the minimum amount required to maintain an oxyhemoglobin saturation of ≥90 percent.

Relief of the symptoms of OHS (typically daytime hypersomnolence).

Prevention of complications, including erythrocytosis, pulmonary hypertension, and right heart failure.

Treatment of underlying obstructive sleep apnea (OSA; ie, elimination of obstructive and hypopnea events) or sleep-related hypoventilation (ie, nonobstructive events).

Improvement of sleep architecture and quality, reducing nocturnal work of breathing, and providing respiratory muscle rest.

While there are no standard recommendations for the follow-up of patients undergoing treatment for OHS, follow-up should include clinical evaluation of the response to noninvasive PAP and/or weight loss (eg, every six months). Notably, duration of therapy, and therefore follow-up, are typically indeterminate and often lifelong since the degree of support may change over time depending upon factors including weight loss/gain, medications, or the development or treatment of contributing comorbidities.

Follow-up after noninvasive PAP – The follow-up of those treated with noninvasive PAP is focused on ensuring adequate settings and compliance with therapy as well as the evaluation of symptoms, repeating arterial blood gases (ABG), and, in select circumstances, repeating polysomnography, the details of which are discussed separately. (See "Titration of positive airway pressure therapy for adults with obstructive sleep apnea" and "Mode selection for titration of positive airway pressure in adults with obstructive sleep apnea", section on 'Follow-up after initial titration' and "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome", section on 'Assessing treatment response' and "Mode selection for titration of positive airway pressure in adults with obstructive sleep apnea".)

Follow-up after weight loss – It is unusual that weight loss, even if significant, eliminates the need for nocturnal ventilation. Thus, long term PAP is still typically needed, but most patients have reduced PAP settings or can switch to continuous PAP (CPAP) if originally receiving bilevel PAP (BPAP). Reassessment of OHS is performed after significant weight loss has occurred (eg, usually within one to two years after bariatric surgery). An ABG should be performed to examine the awake partial arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2), as well as in-laboratory polysomnography to assess for accurate PAP and supplemental oxygen settings so that adjustments can be made if necessary. Early, rapid weight loss (typically 45 to 70 percent of excess body weight) during the first postoperative year after bariatric surgery is often associated with improvement of OHS [46]. However, this has not been universal and some patients have residual OSA despite amelioration of symptoms [4,6,13,47-52]. Thus, discontinuation of noninvasive PAP therapy after weight loss should not be performed unless polysomnography demonstrates that residual OSA or hypoventilation warranting therapy is absent.

PROGNOSIS — Morbidity and mortality in untreated patients with OHS is high [53,54]. OHS tends to be progressive if left untreated, with many patients developing cardiovascular complications including pulmonary hypertension and right heart failure.

The main cause of death is generally from cardiovascular disease [54,55]. The impact of therapy, particularly noninvasive positive airway pressure, on cardiovascular complications and mortality is uncertain and appears limited based upon extrapolated data from patients with obstructive sleep apnea (OSA). Even when sleep-disordered breathing is treated with positive airway pressure therapy, mortality in those with severe OHS remains substantially worse than individuals with OSA alone [55]. (See "Obstructive sleep apnea and cardiovascular disease in adults".)

Hospitalization rates are higher in OHS compared with eucapnic individuals with obesity [56], and once hospitalized, patients with OHS are more likely to need intensive care unit management, be intubated, and require long-term care at discharge [57].

Individuals with OHS have considerably worse health status and access more health care resources compared to the general population, with differences apparent up to eight years before a diagnosis is made [58].

The presence of significant awake hypoxemia at diagnosis and during PAP therapy has been associated with a poor prognosis [59,60].

SUMMARY AND RECOMMENDATIONS

Obesity hypoventilation syndrome (OHS; "pickwickian syndrome") exists when an individual with obesity (body mass index [BMI] >30 kg/m2) has awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg), which cannot be attributed to other conditions (eg, neuromuscular disease). (See 'Introduction' above and "Clinical manifestations and diagnosis of obesity hypoventilation syndrome".)

For patients with OHS, we recommend a comprehensive and multidisciplinary approach targeted at the immediate initiation of noninvasive positive airway pressure (PAP) together with lifestyle modifications for weight loss. (See 'Positive airway pressure' above and "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome".)

For patients with OHS who fail or do not tolerate first-line therapies in whom aggressive attempts have been made to optimize PAP therapy, options include tracheostomy for the treatment of sleep-disordered breathing and bariatric surgery or rarely medication for weight loss. In general, these therapies are suboptimal and associated with increased risk of adverse effects. Choosing among them depends upon factors including severity of OHS, degree of obesity, medical comorbidities, likelihood of efficacy or adverse effects, and patient preferences. (See 'Weight loss and lifestyle modifications' above and 'Second-line therapy' above.)

For patients with OHS in whom supplemental oxygen is indicated (eg, for significant sleep-related oxyhemoglobin desaturation or for hypoxemic respiratory failure), we suggest that it be administered in conjunction with noninvasive PAP, based upon the rationale that supplemental oxygen alone may worsen hypercapnia. Oxygen should not be administered as a sole therapy for OHS. Respiratory stimulants (ie, progestins and acetazolamide) are adjunctive therapies that are a last resort for patients who continue to have serious alveolar hypoventilation despite PAP therapy and weight loss. However, such agents are typically minimally effective and are associated with adverse effects. (See 'Therapies of limited value or associated with harm' above.)

Patients with OHS should be advised to abstain from alcohol and sedatives (eg, benzodiazepines, opiates, muscle relaxants, and barbiturates), which can contribute to hypoventilation and mitigate the benefits of PAP therapy. In addition, the clinician should identify and treat comorbid conditions that may contribute to hypoventilation (eg, chronic obstructive pulmonary disease and hypothyroidism) or can complicate OHS (eg, pulmonary hypertension). (See 'Supportive therapies' above.)

Patients with OHS should be followed clinically for their response to noninvasive PAP and/or weight loss (eg, every six months). Notably, duration of therapy, and therefore follow-up, are typically indeterminate and often lifelong since the degree of support may change over time depending upon factors including weight loss/gain, medications, or the development or treatment of contributing comorbidities. (See 'Follow-up' above and "Noninvasive positive airway pressure therapy for the obesity hypoventilation syndrome", section on 'Assessing treatment response'.)

Morbidity and mortality in untreated patients with OHS is high, with most deaths due to cardiovascular complications including pulmonary hypertension and right heart failure. The impact of therapy on cardiovascular complications and mortality is uncertain. (See 'Prognosis' above.)

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Topic 7713 Version 33.0

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