MED-NERD

Treatment, Complications, and Prognosis of obesity hypoventilation syndrome (OHS)/Pickwickian syndrome

 

Management and Treatment:

Treatment of OHS includes targeting weight loss, lifestyle modifications, managing sleep-disordered breathing, surgical methods, and drug therapy.

 

Positive Airway Pressure (PAP):

The first line of treatment is Positive Airway Pressure (PAP) including continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BPAP).  Through constant pressure (over 15 cm H2O) throughout respiration, CPAP helps in maintaining the patency of upper airway leading to reducing the obstructive events. About 90% of  OHS patients are associated with Obstructive Sleep Apnea (OSA) therefore, CPAP is the modality of choice while BPAP is the first choice in OHS with sleep-related hypoventilation and few obstructive events during sleep.

Hypercapnia without improvement despite the adherence to CPAP and intolerance to CPAP require the use of BPAP. Titration of inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) are used for initiation of BPAP. The main factor affecting ventilation and CO2 elimination is the delta or the pressure difference between IPAP and EPAP. In case of decreased lung compliance due to atelectasis and poor chest wall compliance due to require high positive pressure. Monitoring Arterial Blood Gases (ABGs) is required. The modality of ventilation depends on the severity of respiratory failure. Conscious patients with intact cough and gag reflex may respond to non-invasive positive pressure ventilation.

Patients not improving rapidly, unprotected airway, and intolerance to BPAP may require early intubation.

The average hours of daily use over the previous 30 days is used to assess adherence to PAP therapy. This is difficult and considered the most challenging aspect of managing OHS due to patient non-compliance, financial constraints, lack of education, and difficulty with the device and the masks. Patients should be informed that various types of masks can be used in treatment of OHS and should be educated about the disease.

A meta-analysis of 25 studies showed the advantages of using PAP in the management of OHS such as improving the symptoms and mortality of OHS, improving  daytime sleepiness, gas exchange, and improving the quality of sleep and life.

 

Oxygen supplementation:

Oxygen supplementation may be required and Arterial Blood Gases (ABGs) should be assessed regularly. Oxygen supplementation is required to correct hypoxemia that occur in 50% of OHS patients despite the use of PAP however, using PAP correctly may correct hypoxemia. Regular assessment is necessary to avoid the toxicity and long-term cost of oxygen supplementation therapy. Prolonged oxygen therapy may cause adverse effects. A recent study has shown that using 100% oxygen therapy may worsen CO2 retention and hypercapnia decreased minute ventilation (by 1.4 L/min) and (CO2 increased by 5.0 mmHg) in obesity-associated hypoventilation stable patients.

 

Lifestyle modifications:

Lifestyle modifications especially weight loss, should be encouraged in all OHS patients. The target weight loss is 25-30% of actual body weight.  Following a weight loss program improves ventilation and nocturnal oxy-hemoglobin saturation, improves pulmonary function, reduces the frequency of respiratory apneas hypopneas and the incidence of some complications including pulmonary hypertension.

When diet and lifestyle modifications fail with intolerance to PAP therapy or worsening of symptoms, surgeries such as bariatric surgery are recommended to achieve weight loss. However, bariatric surgery is associated with complications and high mortality rate which may become higher for OHS patients.

 

Tracheostomy:

Tracheostomy is needed in patients with intolerance or non-adherence to PAP therapy, or in patients with complications such as cor pulmonale. Tracheostomy does not alter the respiratory drive of pulmonary mechanism therefore, PAP therapy is still required. Tracheostomy may be limited in use due to the difficulty of the procedure and the surgical risks in obese patients.

 

Pharmacotherapy (Drug therapy):

The use of drugs including respiratory stimulants (e.g., acetazolamide, medroxyprogesterone, and theophylline) in treatment of OHS is controversial. Pharmacologic agents may be used when PAP therapy and weight loss fail to improve hypoventilation.

 

-Acetazolamide:

Theoretically, acetazolamide blocks CO2 conversion to bicarbonate therefore lowers the pH in the brain and increases central ventilatory drive.

 

-Medroxyprogesterone:

Medroxyprogesterone may stimulate respiration in hypothalamus but increases the risks of hypercoagulability and venous thromboembolism, increases uterine bleeding in females, and decreasing libido with erectile dysfunction in males.

 

-Theophylline:

Theophylline is a direct respiratory stimulant and bronchodilator. Other respiratory stimulants include buspirone and mirtazapine.

 

-Leptin (metreleptin):

Enough studies about the effects of leptin in OHS patients are not available  yet. The Subcutaneous injection of recombinant human leptin (metreleptin) has been approved by the US Food and Drug Administration in patients congenital or acquired generalized lipodystrophy to treat metabolic complications of leptin deficiency.

 

Complications:

Complications of OHS are multiple especially if not treated correctly including pulmonary hypertension, and volume overload, and biventricular heart failure increasing mortality rates compared to non-hypercapnic patients with sleep-disordered breathing only. Pulmonary Hypertension occurs in about 50% in OHS cases compared to OSA patients (15%). In general, obesity leads to other diseases such as  dyslipidemia, systemic arterial hypertension, diabetes, hypothyroidism, osteoarthritis, and liver dysfunction. A study involving 246 OHS patients, 122 patients out of the participants had elevated systolic pulmonary artery pressures (40 mmHg or more).

OHS in associated with lower quality of life, continued daytime sleepiness, with high healthcare costs and expenses. Early diagnosis and management of OHS decreases the risks of complications and mortality rates.

Prognosis:

OHS is characterized by progressive course and is associated with high risk of cardiovascular complications (Pulmonary hypertension and right heart failure) therefore, high morbidity and mortality rates. Due to misdiagnosis of OHS even in patients with morbid obesity, hospitalizations with hypercapnic respiratory failure is frequent.

Comorbidities such as heart failure, coronary artery disease, and cor pulmonale are more likely in OHS patients than in OSA or overlap syndrome. About 12-32% of 3-year mortality rate despite treatment with ventilator therapy is associated with OHS. The use of health care resources is high in OHS patients with increased frequency of invasive mechanical ventilation or Intensive Care Unit (ICU) admission.

According to studies, OHS associated with other medical conditions show high mortality rates within 18 months (23%), and within 50 months (46%). Early treatment of OHS with PAP therapy may lead to 10% reduction in mortality rates.

See:

-Introduction on Obesity hypoventilation syndrome (OHS)/ Pickwickian Syndrome

-Etiology and Epidemiology of Obesity hypoventilation syndrome (OHS)/Pickwickian Syndrome

-Clinical Presentation and Diagnosis of Obesity Hypoventilation Syndrome (OHS)/Pickwickian syndrome

References:

(1)Ghimire P, Sankari A, Kaul P. Pickwickian Syndrome. [Updated 2022 Nov 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542216/ 

(2)Masa JF, Pépin JL, Borel JC, Mokhlesi B, Murphy PB, Sánchez-Quiroga MÁ. Obesity hypoventilation syndrome. Eur Respir Rev. 2019 Mar 14;28(151):180097.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491327/ 

(3)Shah, N.M., Shrimanker, S. and Kaltsakas, G. (2021) Defining obesity hypoventilation syndrome, Breathe (Sheffield, England). U.S. National Library of Medicine. Available at:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753617/ 

(4)Athayde RAB, Oliveira Filho JRB, Lorenzi Filho G, Genta PR. Obesity hypoventilation syndrome: a current review. J Bras Pneumol. 2018 Nov-Dec;44(6):510-518.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459748/ 

(5) Jay  Summer (2022) Pickwickian syndrome: Symptoms, causes, and treatments, Sleep Foundation. Available at:

https://www.sleepfoundation.org/sleep-apnea/pickwickian-syndrome