Daytime CO₂ normalization with home ventilation in neuromuscular disease: No improvement in central respiratory drive

Chronic hypoventilation is common in individuals with neuromuscular disease (NMD). Nocturnal noninvasive home mechanical ventilation (NIHMV) reduces daytime PaCO₂, but the underlying mechanism remains unclear.

To evaluate the impact of NIHMV on central respiratory drive in individuals with NMD whose daytime PaCO₂ decreases following ventilation.

A prospective, longitudinal observational study was conducted in adults with NMD and chronic hypoventilation receiving usual clinical care. Central respiratory drive was assessed using CO₂ rebreathing and compared with healthy controls. Airway occlusion pressure (P_0.1) was related to P_ETCO₂ during rebreathing to calculate the P_0.1/P_ETCO₂ slope. Recruitment reflected real-world clinical practice, and data were analyzed post hoc.

P_0.1/P_ETCO₂ slopes were obtained in all 20 individuals at the six-month post-NIHMV evaluation; eight individuals subsequently completed a third CO₂ rebreathing assessment at 24 months. Baseline PaCO₂ (55.1 ± 8.2 mmHg) normalized post-NIHMV (p < 0.001), whereas the P_0.1/P_ETCO₂ slope remained unchanged (p = 0.338). The median slope in the NMD group was 0.011 (0.004-0.030), compared with 0.187 (0.150-0.244) in controls (p < 0.001). Breath-holding time was prolonged in 17 individuals and remained stable throughout the follow-up.

Consistent with previous studies, NIHMV can normalize daytime PaCO₂ in individuals with NMD. In those who achieved PaCO₂ normalization, no improvement in central respiratory drive was observed. The unchanged P_0.1/P_ETCO₂ slope indicates that daytime PaCO₂ normalization is unlikely to be mediated by enhanced central chemosensitivity. Further studies are needed to clarify the physiological mechanisms responsible for hypercapnia correction with NIHMV.