Nocturnal hypercapnia in obstructive sleep apnoea and obesity hypoventilation: from pathophysiology to measurement and treatment

Breathing disturbances during sleep are associated with intermittent hypoxaemia, arousal and sympathetic activation, which in turn lead to oxidative stress and cardiovascular and metabolic consequences. However, they are also characterised by fluctuations of carbon dioxide levels, switching between hypercapnia and hypocapnia, which contribute to acute and sustained physiological and cellular effects. Changes in arterial carbon dioxide tension ( P aCO 2 ) influence cerebral blood flow, respiratory control and renal function. The complex pathophysiology requires the integration of clinical entities and therapeutical options based on precise measurement of CO 2 . Continuous measurements during the night best reflect nocturnal changes in CO 2 levels. Alveolar, arterial, capillary and transcutaneous CO 2 measurements represent distinct characterisations of CO 2 fluctuations. Alveolar and arterial CO 2 levels are very similar and correlate closely to the end-tidal CO 2 ( P ETCO 2 ) in healthy subjects. However, the validity of P ET CO 2 is limited in diseases with inhomogeneous lung ventilation and, due to artefacts, during mechanical ventilation. Transcutaneous CO 2 measurement has proven to adequately represent P aCO 2 , although time delays in response and absolute figures can differ. Obesity hypoventilation syndrome (OHS) exemplifies a frequent clinical condition with multiple pathophysiological components impacting P CO 2 levels differently across 24 h. Treatment is often delayed due to limited awareness of mild hypercapnia occurring exclusively during night-time. Positive airway pressure (PAP) therapy remains the cornerstone of management. The choice between continuous positive airway pressure or noninvasive ventilation should be guided by the predominant OHS phenotype and the severity of daytime hypercapnia. Management of OHS should also focus on cardiometabolic comorbidities and include a multimodal approach to the underlying obesity.