What is Pickwickian syndrome, also known as Obesity Hypoventilation Syndrome (OHS)?

What is Pickwickian Syndrome (Obesity Hypoventilation Syndrome)?

Pickwickian syndrome, formally known as Obesity Hypoventilation Syndrome (OHS), is a severe obesity-related respiratory disorder 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

Clinical Definition and Diagnostic Criteria

OHS represents the most severe form of obesity-induced respiratory compromise, characterized by chronic hypercapnic respiratory failure that persists during wakefulness. 1, 2 The diagnosis requires:

• Obesity: BMI > 30 kg/m² (though most patients have severe obesity with BMI > 40 kg/m²) 1, 3
• Daytime hypercapnia: Arterial PaCO₂ > 45 mm Hg measured while awake 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 hypoventilation 1, 4

Epidemiology and Prevalence

The prevalence of OHS is estimated at 8-20% among obese patients referred to sleep centers for evaluation of sleep-disordered breathing. 1 In the general adult population, prevalence ranges from 0.15-0.4%. 5, 6 With the global obesity epidemic, particularly the 7.6% of U.S. adults with BMI > 40 kg/m², OHS prevalence is expected to increase substantially. 1

Pathophysiology

OHS develops from multiple failing compensatory mechanisms that distinguish it from simple obesity or obstructive sleep apnea alone. 2 The key pathophysiologic components include:

Mechanical Respiratory Dysfunction

• Increased work of breathing from physical weight on the chest wall and thoracic cage 7
• Reduced lung volumes and decreased respiratory system compliance as abdominal fat restricts diaphragmatic excursion 7
• Increased small airway resistance due to poor lung base expansion 7
• Worsening respiratory capacity when supine as abdominal pressure elevates the diaphragm 7

Impaired Central Respiratory Drive

• Decreased ventilatory responsiveness to CO₂, preventing appropriate compensatory hyperventilation despite rising PaCO₂ 7, 8
• Maladaptive central respiratory center adaptation to chronic hypercapnia 7

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, 7
• Nocturnal alveolar hypoventilation occurs even during periods without discrete apneas or hypopneas 7
• Inadequate respiratory muscle strength fails to meet increased ventilatory demands during sleep 7

Clinical Consequences and Prognosis

OHS carries substantially worse prognosis than eucapnic obesity or OSA alone, with significantly increased mortality rates. 2, 7 Major complications include:

• Pulmonary hypertension: Develops in 30-88% of OHS patients versus lower rates in OSA alone 2
• Chronic heart failure and cor pulmonale: Result from chronic hypoxemia and hypercapnia 1, 2, 7
• Acute-on-chronic hypercapnic respiratory failure: Requiring frequent hospitalizations 1, 7
• Reduced quality of life: From combined cardiopulmonary dysfunction and impaired exercise tolerance 7, 4

Diagnostic Approach

Screening Strategy

For obese patients with known or suspected sleep-disordered breathing, the American Thoracic Society recommends a risk-stratified approach: 1

• Low to moderate suspicion (< 20% pretest probability): Use serum bicarbonate < 27 mmol/L to exclude OHS 1, 3
• High suspicion: Measure arterial blood gases directly to document PaCO₂ > 45 mm Hg 1, 3

Confirmatory Testing

• Arterial blood gas analysis: Required to document awake hypercapnia (PaCO₂ > 45 mm Hg) 1, 3
• Polysomnography or sleep respiratory polygraphy: Necessary to determine the pattern of sleep-disordered breathing (obstructive versus nonobstructive) and tailor treatment 1

Common pitfall: Avoid relying on SpO₂ during wakefulness alone to decide when to measure PaCO₂, as this can miss the diagnosis. 3

Treatment Recommendations

Positive Airway Pressure Therapy

The American Thoracic Society provides clear treatment algorithms based on OSA severity: 1

• OHS with severe OSA (AHI > 30 events/h): CPAP is first-line treatment 1, 2
• OHS without severe OSA: Noninvasive ventilation (BiPAP) is preferred 2, 5
• Hospitalized patients with respiratory failure: Discharge with noninvasive ventilation until outpatient diagnostic procedures and PAP titration can be completed (ideally within 2-3 months) 1

Weight Loss Interventions

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

Key Clinical Distinctions

OHS is a distinct disease entity from simple obesity or obstructive sleep apnea alone. 6 Unlike OSA patients who maintain normal daytime ventilation, OHS patients have multiple failing compensatory mechanisms resulting in chronic daytime hypercapnia. 2, 8 This fundamental difference explains the substantially higher morbidity and mortality in OHS compared to eucapnic obese patients with sleep-disordered breathing. 2, 7