What is Pickwickian syndrome, also known as obesity hypoventilation syndrome (OHS), in patients with a body mass index (BMI) of 40 or higher and a history of sleep disorders, such as obstructive sleep apnea (OSA)?

What is Pickwickian Syndrome?

Pickwickian syndrome, now formally termed Obesity Hypoventilation Syndrome (OHS), is defined by three essential components: obesity (BMI > 30 kg/m²), sleep-disordered breathing, and awake daytime hypercapnia (PaCO₂ > 45 mm Hg at sea level), after excluding other causes of hypoventilation. 1, 2

Core Diagnostic Criteria

The American Thoracic Society requires all three of the following to establish the diagnosis: 1, 2

• Obesity: BMI exceeding 30 kg/m² (though most patients have BMI > 40 kg/m²) 1
• Daytime hypercapnia: Arterial PaCO₂ greater than 45 mm Hg measured during wakefulness at sea level 1, 2
• Sleep-disordered breathing: Documented on polysomnography or sleep respiratory polygraphy 1
• Exclusion of other causes: No alternative neuromuscular, mechanical, or metabolic explanation for the hypoventilation 1, 3

Clinical Significance and Severity

OHS represents the most severe form of obesity-induced respiratory compromise and carries substantially worse prognosis than obstructive sleep apnea alone. 2, 4 The syndrome leads to serious complications including: 1, 2

• Significantly increased mortality rates compared to eucapnic obese patients 2, 4
• Pulmonary hypertension (develops in 30-88% of patients) 4
• Chronic heart failure and cor pulmonale from chronic hypoxemia and hypercapnia 4, 5
• Acute-on-chronic hypercapnic respiratory failure requiring hospitalization 1, 5

Epidemiology

The prevalence of OHS is 8-20% among obese patients referred to sleep centers for evaluation of sleep-disordered breathing, with an estimated 0.15-0.4% prevalence in the general adult population. 2 Given that 7.6% of U.S. adults have BMI > 40 kg/m², the absolute number of affected patients is substantial and increasing. 1

Pathophysiologic Mechanisms

OHS develops from multiple failing compensatory mechanisms that distinguish it from simple obesity or OSA: 2, 5

Mechanical Respiratory Dysfunction

• Physical weight on the chest wall increases work of breathing and oxygen cost 5
• Abdominal fat restricts diaphragmatic excursion, particularly when supine 5
• Low lung volumes and decreased respiratory system compliance develop 5
• Increased small airway resistance occurs from poor lung base expansion 5

Impaired Central Respiratory Drive

• Decreased ventilatory responsiveness to CO₂ prevents appropriate compensatory hyperventilation despite rising PaCO₂ 5
• Shallow and inefficient breathing patterns develop as the respiratory center adapts maladaptively to chronic hypercapnia 5

Sleep-Related Breathing Disorders

• Approximately 90% of OHS patients have coexistent obstructive sleep apnea (AHI > 5 events/h), with nearly 70% having severe OSA (AHI > 30 events/h) 1, 2, 4
• Nocturnal alveolar hypoventilation occurs even during periods without discrete apneas or hypopneas 5
• Inadequate respiratory muscle strength fails to meet increased ventilatory demand during sleep 5

Diagnostic Approach

For obese patients with known or suspected sleep-disordered breathing, measure arterial blood gases directly if there is high suspicion for OHS. 1, 4 The American Thoracic Society recommends: 1

• Use serum bicarbonate < 27 mmol/L to exclude OHS when suspicion is not very high (< 20%) 1
• Measure arterial blood gases in patients strongly suspected of having OHS to document PaCO₂ > 45 mm Hg 1, 2
• Perform polysomnography or sleep respiratory polygraphy to determine the pattern of sleep-disordered breathing and tailor treatment 1

Treatment Recommendations

Positive Airway Pressure Therapy

The American Thoracic Society recommends CPAP as first-line treatment for stable ambulatory patients with OHS who have coexistent severe OSA (AHI > 30 events/h). 1, 2, 4 For patients without severe OSA, noninvasive ventilation (BiPAP) is recommended. 4

Hospitalized Patients

Patients hospitalized with respiratory failure and suspected OHS should be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory, ideally within 2-3 months. 1

Weight Loss

Sustained weight loss of 25-30% of body weight can achieve resolution of OHS, representing definitive treatment when achievable. 1, 2 This magnitude of weight loss is most likely obtained with bariatric surgery. 1, 2

Critical Clinical Pitfalls

The syndrome often remains undiagnosed until late in the disease course, leading to preventable morbidity and mortality. 6, 7, 3 Maintaining a high index of suspicion in obese patients with sleep-disordered breathing is essential for early recognition and treatment. 6 The presence of daytime hypercapnia distinguishes OHS from simple OSA and mandates more aggressive management. 4