Sleep-Related Hypoventilation

Sleep-related hypoventilation is inadequate ventilation during sleep.

It is shown by an arterial or surrogate carbon dioxide level of more than 6.7 kPa (50 mmHg), or a rise of 1.3 kPa (10 mmHg) or more from the awake supine value to more than 6.7 kPa. Oxygen desaturation to 88% or less for at least 5 minutes that is not explained by obstructive apnoea or hypopnoea also qualifies.

• Causes:
  • Obesity hypoventilation syndrome (body mass index of 30 kg/m2 or more with awake PaCO2 of more than 6.0 kPa): present in about 10 to 20% of obese patients with obstructive sleep apnoea and about 0.4 to 0.6% of the general adult population.
  • Chronic obstructive pulmonary disease with severe obstruction (FEV1 less than 30 to 40% predicted).
  • Neuromuscular disease (motor neurone disease, Duchenne muscular dystrophy, myasthenia, post-polio, diaphragm paralysis), chest wall disease (kyphoscoliosis, thoracoplasty).
  • Drugs and substances: opioids, benzodiazepines, alcohol, barbiturates.
  • Central causes (brainstem lesions, congenital central hypoventilation, hypothyroidism).
• Mechanism: loss of wakefulness drive and reduced respiratory muscle tone in sleep (particularly rapid eye movement sleep) reduce tidal volume; in obesity, leptin resistance, increased load and upper airway collapse blunt the ventilatory response.

Morning headache, daytime sleepiness, fatigue, unrefreshing sleep, poor concentration, breathlessness, nocturnal restlessness, vivid dreams, frequent awakenings, nocturia, and loss of libido.

• Signs: obesity, plethora, cyanosis, peripheral oedema, raised jugular venous pressure and loud second heart sound (cor pulmonale), flapping tremor, papilloedema in severe hypercapnia, weak cough and paradoxical breathing in neuromuscular disease.
• Orthopnoea with abdominal paradox in diaphragm weakness.
• Differential diagnosis: obstructive sleep apnoea, central sleep apnoea, hypothyroidism, depression, heart failure, nocturnal asthma, chronic obstructive pulmonary disease, drug effect, narcolepsy.
• Complications: chronic hypercapnic respiratory failure, pulmonary hypertension, right heart failure, secondary polycythaemia (haemoglobin more than 180 g/L in men), cardiac arrhythmia, cognitive impairment, acute-on-chronic respiratory failure with sedation or oxygen, and early mortality (about 20 to 25% at 18 months without treatment in obesity hypoventilation).

Awake arterial or capillary blood gas: PaCO2 more than 6.0 kPa (45 mmHg) with a raised bicarbonate (27 mmol/L or more) is the screening finding; check pH and base excess.

• Overnight polysomnography or respiratory polygraphy with transcutaneous or end-tidal carbon dioxide monitoring (carbon dioxide rise of 1.3 kPa or more, or more than 6.7 kPa for 10 minutes or more); overnight oximetry showing sustained desaturation (below 88% for 5 minutes or more).
• Serum bicarbonate of 27 mmol/L or more has about 85% sensitivity for obesity hypoventilation (use as a screen); full blood count (haemoglobin), thyroid function, creatine kinase, glucose.
• Lung function: spirometry (restriction or obstruction), fall in forced vital capacity of more than 20% from sitting to supine (diaphragm weakness), maximal inspiratory pressure (less than minus 60 cmH2O is weak), sniff nasal pressure (less than 40 cmH2O is weak).
• Chest imaging, echocardiogram (pulmonary hypertension), ECG, and, where appropriate, MRI brain or brainstem, sleep testing for apnoea.
• Neurology referral and creatine kinase for suspected neuromuscular disease; review drugs.

Stop or reduce drugs that depress breathing (opioids, benzodiazepines, alcohol, sedating antihistamines, gabapentinoids); treat hypothyroidism with levothyroxine 50 micrograms daily, rising to 100 to 150 micrograms.

• Non-invasive ventilation (the first treatment in most patients):
  • Obesity hypoventilation with no or mild obstructive apnoea: bilevel pressure support, starting inspiratory pressure of 10 to 12 cmH2O and expiratory pressure of 4 to 6 cmH2O.
  • Titrate by 1 to 2 cmH2O every few minutes to reach inspiratory pressure of 16 to 24 cmH2O and expiratory pressure of 6 to 10 cmH2O, with a backup rate of 12 to 14 breaths per minute.
  • Aim to normalise PaCO2 or a fall of at least 0.5 to 1 kPa, and SpO2 of 90% or more.
  • Average volume assured pressure support gives a target tidal volume of 8 mL/kg ideal body weight.
  • Obesity hypoventilation with severe obstructive sleep apnoea (apnoea-hypopnoea index of 30 or more): continuous positive airway pressure 8 to 15 cmH2O first; change to bilevel if PaCO2 fails to improve at 2 to 3 months or hypoxaemia persists.
  • Add supplemental oxygen (1 to 4 L/min) only after adequate ventilation, aiming for SpO2 of 90 to 94%.
  • Neuromuscular disease: start non-invasive ventilation when symptoms (orthopnoea, morning headache) occur with a forced vital capacity of less than 50% predicted, sniff nasal pressure of less than 40 cmH2O, or nocturnal hypercapnia; use mechanical insufflation-exsufflation for cough.
  • Chronic obstructive pulmonary disease: high intensity ventilation (inspiratory pressure of 20 to 30 cmH2O) for patients with persistent hypercapnia (PaCO2 above 7.0 kPa) after an acute episode, 2 to 4 weeks after discharge.
  • Chest wall disease: bilevel ventilation and avoidance of oxygen alone.
• Weight loss in obesity: a target loss of 10 to 20% of body weight with a supervised diet, semaglutide 0.25 mg weekly rising to 2.4 mg weekly or tirzepatide 2.5 mg weekly rising to 5 to 15 mg weekly.
• Bariatric surgery for body mass index of 35 kg/m2 or more (reduces PaCO2 and often removes the need for ventilation). Perioperative bilevel ventilation.
• Respiratory stimulants: acetazolamide 250 mg twice daily may lower bicarbonate and carbon dioxide (evidence limited); medroxyprogesterone 20 mg three times daily has limited and inconsistent evidence and raises thrombosis risk; no stimulant is first line.
• Treat cor pulmonale: furosemide 20 to 80 mg daily with potassium monitoring; venesection when haematocrit is more than 55% with symptoms.
• Acute-on-chronic respiratory failure: controlled oxygen to SpO2 88 to 92%, acute non-invasive ventilation (inspiratory pressure of 10 to 20 cmH2O, expiratory pressure of 4 to 5 cmH2O), and intensive care for failure.
• Tracheostomy ventilation for non-invasive ventilation failure in neuromuscular disease or intractable disease.
• Special groups:
• Children: neuromuscular or syndromic causes; weight-based pressure settings in specialist centres.
• Pregnancy: weight gain and supine position worsen disease. Use bilevel ventilation and lateral position, avoid carbon dioxide above 6.0 kPa, and liaise with obstetrics.
• Elderly: low doses of sedatives and cautious oxygen.
• Renal impairment: acetazolamide dose halved if creatinine clearance less than 50 mL/min and avoided below 10 mL/min.
• Anaesthesia: preoperative non-invasive ventilation, regional technique, recovery in monitored bed, avoid long-acting opioids.
• Red flags: drowsiness or confusion, PaCO2 of more than 8 kPa, pH of less than 7.35, right heart failure, rapid decline in vital capacity, inability to tolerate the mask, bulbar failure.
• Follow-up: review at 4 to 6 weeks with device download (use for 4 hours or more per night, leak, residual events).
• Morning blood gas or capillary gas at 3 months, then every 6 to 12 months. Overnight oximetry or carbon dioxide monitoring each year. Repeat echocardiogram at 6 to 12 months.