What is obesity hypoventilation syndrome (OHS) and how is it treated in a patient with a history of obstructive sleep apnea (OSA) and obesity?

Obesity Hypoventilation Syndrome: Definition and Treatment

Obesity hypoventilation syndrome (OHS) is defined by the triad of obesity (BMI >30 kg/m²), awake daytime hypercapnia (PaCO₂ >45 mm Hg at sea level), and sleep-disordered breathing, after excluding other causes of hypoventilation, and should be treated with positive airway pressure therapy as first-line treatment, with CPAP preferred for patients with coexistent severe OSA. 1

What is Obesity Hypoventilation Syndrome?

OHS represents the most severe form of obesity-induced respiratory compromise, leading to chronic hypercapnic respiratory failure that persists even during wakefulness 2, 3. This condition affects approximately 8-20% of obese patients referred to sleep centers for evaluation of sleep-disordered breathing 1, 3.

Key Pathophysiologic Features

The syndrome develops from multiple failing compensatory mechanisms 3:

• Mechanical respiratory dysfunction from obesity-related chest wall restriction 4
• Impaired central respiratory drive that fails to compensate for increased work of breathing 4
• Sleep-related breathing disorders that perpetuate daytime hypercapnia 5

Critical Clinical Context

Approximately 90% of OHS patients have coexistent obstructive sleep apnea (OSA), with nearly 70% having severe OSA (AHI >30 events/h) 1, 2, 3. This overlap is crucial because it determines treatment selection.

Serious Consequences

OHS carries substantially worse prognosis than eucapnic obesity or OSA alone 2, 3:

• Increased mortality rates compared to obese patients without hypercapnia 2, 6
• Pulmonary hypertension develops in 30-88% of patients 2
• Chronic heart failure and cor pulmonale from chronic hypoxemia 2, 5
• Frequent hospitalizations for acute-on-chronic hypercapnic respiratory failure 1

How to Diagnose OHS

Screening Algorithm

For patients with low-to-moderate suspicion (<20% pretest probability):

• Measure serum bicarbonate first 1
• If bicarbonate <27 mmol/L, OHS is highly unlikely 1, 7
• If bicarbonate ≥27 mmol/L, proceed to arterial blood gas measurement 1

For patients with high suspicion (e.g., BMI >40 kg/m², very symptomatic):

• Measure arterial blood gases directly to confirm PaCO₂ >45 mm Hg 1, 7

Common pitfall: Do not rely on SpO₂ alone during wakefulness to decide when to measure PaCO₂, as it lacks sufficient sensitivity 7.

Confirmatory Testing

After documenting daytime hypercapnia, polysomnography or sleep respiratory polygraphy is required to 1, 7:

• Determine the pattern of sleep-disordered breathing (obstructive vs. nonobstructive)
• Quantify the severity of OSA (AHI)
• Guide treatment selection based on OSA severity

Treatment Algorithm

For Stable Ambulatory Patients

Step 1: Determine OSA Severity

The presence and severity of coexistent OSA determines initial PAP therapy choice 1:

If OHS with severe OSA (AHI >30 events/h):

• Start with CPAP as first-line treatment 1, 2, 3
• CPAP is preferred because it effectively treats both the obstructive events and often corrects the hypoventilation 5
• Perform CPAP titration in a sleep laboratory 1

If OHS without severe OSA (AHI <30 events/h or no OSA):

• Start with noninvasive ventilation (NIV/BiPAP) 1, 2
• This represents approximately 30% of OHS patients 5
• NIV provides both pressure support and backup rate to address hypoventilation 5

Step 2: Assess Treatment Response

After initiating PAP therapy 1:

• If adequate treatment response on CPAP (normalized gas exchange, improved symptoms), continue CPAP 1
• If inadequate treatment response on CPAP (persistent hypercapnia despite adherence), switch to NIV 1

For Hospitalized Patients with Acute-on-Chronic Respiratory Failure

Discharge patients on empiric NIV settings because of high risk of short-term (3-month) mortality without therapy 1. This recommendation applies even before formal sleep study confirmation, given the urgency of preventing early mortality 1.

Follow-up within 2-3 months with outpatient sleep study and PAP titration to optimize therapy and confirm diagnosis 1.

Weight Loss as Definitive Treatment

Pursue sustained weight loss of 25-30% of actual body weight to achieve resolution of OHS 1, 3. This level of weight loss is most likely achieved with bariatric surgery rather than lifestyle interventions alone 1.

Important caveat: Bariatric surgery should only be offered when estimated benefit outweighs perioperative risk, as these patients have significant surgical morbidity 1. However, when successful, it represents the only definitive cure for OHS 3.

Treatment Priorities

The treatment hierarchy should be 1:

1. Immediate: Initiate appropriate PAP therapy (CPAP or NIV based on OSA severity)
2. Concurrent: Manage cardiovascular and metabolic comorbidities 5
3. Long-term: Pursue sustained weight loss interventions, ideally bariatric surgery 1

Critical point: Do not delay PAP therapy while pursuing weight loss, as untreated OHS carries high mortality risk 2, 6. PAP therapy improves clinical symptoms, quality of life, gas exchange, and sleep-disordered breathing while weight loss efforts proceed 5.