What is Pickwickian Syndrome?
Pickwickian syndrome, now formally termed Obesity Hypoventilation Syndrome (OHS), is defined by the triad of 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
Core Diagnostic Criteria
OHS requires all three components to be present simultaneously: 1
- Obesity: Body mass index exceeding 30 kg/m²
- Sleep-disordered breathing: Documented on polysomnography or sleep respiratory polygraphy
- Daytime hypercapnia: Awake resting arterial PaCO₂ greater than 45 mm Hg measured at sea level
- Exclusion requirement: Other causes of hypoventilation must be ruled out (neuromuscular disease, severe obstructive lung disease, chest wall deformities, etc.)
Clinical Presentation
Patients typically present with: 2, 3, 4
- Excessive daytime somnolence and chronic fatigue
- Dyspnea that worsens progressively
- Cyanosis and signs of hypoxemia
- Loud snoring with unrestful sleep
- Morning headaches from nocturnal CO₂ retention
- Peripheral edema and signs of right heart failure in advanced cases
The average patient is severely obese (often BMI >40 kg/m²), predominantly male, and middle-aged (average age ~50-60 years). 2, 3
Pathophysiologic Mechanisms
OHS develops through multiple interconnected mechanisms: 5
Mechanical respiratory dysfunction occurs as chest wall weight and abdominal fat mass restrict lung expansion and diaphragmatic excursion, particularly when supine, leading to low lung volumes and increased work of breathing. 5
Impaired central respiratory drive manifests as decreased ventilatory responsiveness to rising CO₂ levels, preventing appropriate compensatory hyperventilation despite progressive hypercapnia. 5
Sleep-disordered breathing coexists in approximately 90% of OHS patients, with nearly 70% having severe obstructive sleep apnea (apnea-hypopnea index >30 events/hour). 1, 5 Nocturnal hypoventilation occurs even between discrete apneic events.
Serious Clinical Consequences
OHS represents the most severe form of obesity-induced respiratory compromise and carries significant morbidity and mortality. 1 The condition leads to: 1, 5
- Pulmonary hypertension and cor pulmonale from chronic hypoxemia
- Polycythemia secondary to chronic hypoxia 2, 6
- Acute-on-chronic hypercapnic respiratory failure requiring hospitalization
- Increased mortality rates compared to eucapnic obese patients with sleep apnea
- Chronic heart failure and right ventricular dysfunction
Diagnostic Approach
When suspicion for OHS is not very high (<20%), use serum bicarbonate <27 mmol/L to exclude the diagnosis; however, measure arterial blood gases in patients strongly suspected of having OHS. 1
The diagnostic workup requires: 1, 3
- Arterial blood gas analysis showing PaCO₂ >45 mm Hg and typically PaO₂ <70 mm Hg
- Polysomnography to document sleep-disordered breathing patterns and determine if obstructive or non-obstructive hypoventilation predominates
- Serum bicarbonate often elevated (>27 mmol/L) as metabolic compensation for chronic respiratory acidosis
- Exclusion of alternative causes: Pulmonary function tests, chest imaging, and clinical evaluation to rule out COPD, neuromuscular disorders, and restrictive lung diseases
Prevalence and Epidemiology
The prevalence of OHS in the general population remains unknown, but it affects 8-20% of obese patients referred to sleep centers for evaluation of sleep-disordered breathing. 1, 4 The condition is likely increasing concurrent with the obesity epidemic, particularly as severe obesity (BMI >40 kg/m²) now affects approximately 7.6% of U.S. adults. 1
Critical Clinical Pitfall
OHS often remains undiagnosed until late in the disease course when patients present with acute respiratory failure. 4 Clinicians must maintain high suspicion in severely obese patients presenting with unexplained dyspnea, excessive somnolence, or signs of right heart failure, as early recognition and treatment significantly improve outcomes and reduce mortality. 1, 4