Beyond mean and maximum CO₂: introducing hypercapnic burden as a marker of sleep-related hypoventilation

In obesity hypoventilation syndrome (OHS), nocturnal hypoventilation can precede daytime respiratory failure. Therefore, the hypercapnic burden index was introduced to quantify sleep-related CO₂ retention.

Thirty-one patients who underwent polysomnography with transcutaneous capnography and met OHS criteria were retrospectively included in this single-center cross-sectional study. The area above the predetermined transcutaneous partial pressure of CO₂ thresholds of 45 mmHg (thresh45) and 50 mmHg (thresh50) from the extracted capnography graphs was computed and statistical associations between the calculated areas exceeding the CO₂ limits (OOL Area) and maximum nocturnal CO₂ (maxCO₂), mean nocturnal CO₂ (meanCO₂) and the percentage of predicted forced vital capacity (FVC%) were examined.

Very strong positive correlations were revealed between maxCO₂ and both thresh45 (Spearman's rho = 0.906, p < 0.000001) and thresh50 (Spearman's rho = 0.953, p < 0.000001), as well as between meanCO₂ and both thresh45 (Spearman's rho = 0.918, p < 0.000001) and thresh50 (Spearman's rho = 0.937, p < 0.000001), thereby validating hypercapnic burden against classic nocturnal hypercapnia metrics. Significant negative correlations of these metrics with FVC% (Spearman's rho = -0.49, p = 0.01 and Spearman's rho = -0.45, p = 0.02, respectively) also supported it as a marker of functional impairment. While not outperforming classic metrics in this regard, it captured clinically relevant variability, as several outliers displayed better alignment of FVC% with threshold-based indices than with meanCO₂.

This underscores the heterogeneity of nocturnal hypoventilation in OHS and the potential value of more nuanced markers in individual patients, as daytime hypercapnia might not be present yet, and maxCO₂ and meanCO₂ do not account for low or intermittent but cumulative CO₂ elevations. Identifying such outliers is clinically important, as these patients may be at heightened risk of progression or may respond differently to interventions such as non-invasive ventilation.