MED-NERD

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

Clinical Presentation:

 

The triad of OHS includes: obesity, hypercapnia, and the absence of other causes of gas exchange abnormalities (hypoventilation).

Patients of OHS may present with hypercapnia and exacerbation of chronic hypoxemia leading to respiratory failure that require ventilator support (non-invasive or invasive positive pressure ventilation) and have to be managed in the intensive care unit (ICU).

 

Symptoms:

Typically, patients of OHS are obese, BMI >35 kg/m^2 is associated with high risk of daytime sleepiness and hyper-somnolence, snoring, dyspnoea, apnoea, nocturnal choking, difficulty breathing during exercise, wheezing, daytime fatigue, impaired concentration and memory, confusion, irritability, morning headaches, swelling in the feet, ankles, and legs, fever, flushed skin, increased sweating, nausea.

 

Physical examination:

An obese patient with short-wide neck, increased neck circumference, low-lying uvula, and crowded oropharynx. If associated with heart failure due to pulmonary hypertension, the patient presents with second heart sound with a prominent pulmonic component, elevated jugular venous pressure, hepatomegaly, and lower limb oedema. Patients may have signs of cor pulmonale.

 

Typically, the diagnosis occurs between 50-60 years old patients due to delay in the diagnosis. A study showed that about 8% of patients admitted to the ICU presented with acute on top of chronic hypercapnic respiratory failure and met the diagnostic criteria of OHS:

-BMI >40 kg·m−2

-PaCO2 >45 mmHg

-No evidence of intrinsic lung disease or musculoskeletal disease

-No history of smoking

About 75% of these patients were misdiagnosed and were considered  obstructive lung disease cases for which they received treatment despite the pulmonary function tests showing no evidence of obstruction.

Severely obese patients (BMI ≥40 kg·m−2) have severe Obstructive sleep apnea (OSA) (≥30 events·h-1).

 

Diagnosis:

 

The diagnosis of OHS is often delayed and patients present with acute stages of respiratory failure or cardiac decompensation. Early diagnosis is crucial due to high morbidity and mortality.

The diagnosis of OHS is made by exclusion of other causes of hypoventilation (e.g., chest wall disorders such as kyphoscoliosis causing mechanical respiratory limitation, COPD, severe interstitial lung disease, myasthenia gravis, untreated hypothyroidism, cerebrovascular disease and other neurological diseases, and Ondine’s syndrome which is a congenital disease).

 

Diagnostic criteria:

The diagnostic criteria for OHS (released in 2014)  according to the American Academy of Sleep Medicine (AASM):

-Obese patients with BMI> 30 kg·m−2

-Hypoventilation during wakefulness

-Elevated blood levels of carbon dioxide > 45mm Hg

-Absence of other disorders and no history of medications

 

Suspected patients can be initially managed by: evaluation of serum levels of venous bicarbonate, and pulse oximetry.

 

Pulse oximetry:

A common finding is borderline oximetry. Pulse oximetry finding with the oxygen nadir and percent time spent below O2 saturation (SpO2) < 93% may be considered hypoventilation but does not confirm the diagnosis of OHS. Sustained hypoxemia without apneas in nocturnal oximetry suggest hypoventilation.

 

Serum levels of venous bicarbonate:

Serum levels of venous bicarbonate level ≥ 27 mEq/L can be used in screening. It has 92% sensitivity and 50% specificity values. It has a 97% negative predictive value for excluding a diagnosis of OHS. Elevation of serum bicarbonate level may occur in other cases including: dehydration, vomiting, and some medications.

 

Arterial blood gases (ABGs) analysis:

ABG is more accurate and definitive test for hypoventilation showing the partial pressure of arterial CO2 (PaCO2) > 45 mmHg and PaO<70 mmHg.

Different techniques can be used to measure carbon dioxide level such as daytime arterial blood gases, venous blood gases, arterialised capillary blood gases, transcutaneous carbon dioxide and end-tidal carbon dioxide monitoring. Elevated carbon dioxide levels (≥45 mmHg) during wakefulness can indicate hypoventilation. Measuring carbon dioxide levels continuously during sleep by end-tidal or transcutaneous monitoring is the most reliable method for diagnosis of sleep hypoventilation. Hypoventilation and carbon dioxide levels are worsened during sleep particularly in the rapid eye movement (REM) stage of sleep.

 

Polysomnogram:

Gold standard for diagnosis of OHS is polysomnography with continuous nocturnal CO2 monitoring.

 

Complete blood count (CBC):

Chronic hypoventilation and hypoxia may lead to polycythaemia. Exclude secondary causes of erythrocytosis.

 

Exclusion of other causes:

-For exclusion of other respiratory causes of hypoventilation: pulmonary function testing, chest X-ray or computed tomography (CT), assessment of respiratory muscle strength (MIP and MEP)

-For exclusion of thyroid causes: thyroid function testing to exclude hypothyroidism.

-For exclusion of cardiac causes: electrocardiography (ECG) and echocardiogram showing right heart enlargement and failure secondary to pulmonary hypertension occurring in late stages of OHS.

-Exclusion of drug administration: alcohol, opiates, sedatives, and hypnotics.

Differential Diagnosis:

 

1- Obstructive lung diseases:

Hypercapnic and obese patients with chronic obstructive pulmonary disease (COPD) commonly have breathing disorders during sleep. Arterial blood gases (ABGs) and a complete pulmonary function test are required to confirm the diagnosis.

 

2- Restrictive lung diseases:

May be associated with hypoxemia without hypercapnia. Patients with extrapulmonary chest wall restriction such as pectus deformity, scoliosis, and kyphosis commonly present with acute hypercapnic respiratory failure. Severe bowel distension and ascites can affect respiratory mechanism by applying a significant force on the diaphragm. Poor ventilatory reserve without significant respiratory failure are common in extrapulmonary chest wall restriction.

 

3- Central sleep apnea (CSA):

Characterized by intermittent reduced central drive to breathe. It is associated with hyperventilation, normocapnia or slightly hypocapnica on blood gas testing.

 

4- Myxedema:

Characterized by low levels of circulating free thyroid hormones, respiratory insufficiency and even hypercapnic failure, bradycardia, hypothermia, sluggish tendon reflexes, neurological deficits, hemodynamically unstable, and coma in severe cases.

 

5- Neuromuscular disease:

Amyotrophic lateral sclerosis (ALS) can lead to hypercapnic respiratory failure. Typical findings in ALS patients include muscle weakness, hyperactive deep tendon reflexes, and fasciculation.

In case of spinal cord injuries (SCI), patients are not usually obese, have history of acute injury or trauma, may present with chronic hypercapnia during sleep and wakefulness and sleep-disordered breathing.

 

6- Muscular dystrophies:

Muscular dystrophies associated with hypercapnic respiratory failure include Duchenne or Becker disease. It is characterized by muscle weakness, cardiomyopathies, delayed growth, elevated creatinine kinase (CK), with variable and benign course.

 

7- Autoimmune disorders:

Guillain-Barre syndrome is characterized by rapid onset of  ascending, symmetric paralysis with areflexia over 2-4 weeks.

Patients with dysautonomia commonly present with cardiac arrhythmias and are hemodynamically unstable

 

In case of Myasthenia gravis, the hallmark is muscle fatigue, limb weakness, dysarthria, diplopia, ptosis, and weak cough.

 

8- Poliomyelitis:

Patients of poliomyelitis and post-polio syndrome present with new weakness and fatigability or acute flaccid paralysis. Its incidence has declined due to vaccination.

 

Other disorders:

-Acute infection

-Vascular disorder

-Erythrocytosis

-Diaphragmatic weakness or phrenic nerve injury

-Medications (sedatives or illicit drugs)

See:

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

-Etiology and Epidemiology 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. 

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.

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