Compensatory metabolic and central respiratory drive mechanisms in ALS

Introduction: Airway pressure in the first 100 ms of an occluded inspiration (P0.1) evaluates respiratory center activity. Its increase compensates for respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). We aimed to evaluate if an exhaustion over disease progression emerges. Methods: Consecutive ALS patients with P0.1 at baseline (T0) above 90th percentile for the whole population were included. There were two patient categories within this population: G1 patients had respiratory function tests (RFT) at T0 and 6 months later (T1); G2 patients were immediately adapted to noninvasive ventilation at T0. Functional ALS rating scale (ALSFRS) and its subscores, RFT including maximal inspiratory pressure (MIP), P0.1 percentage (%P0.1), P0.1/MIP, blood gas analyses, phrenic nerve motor amplitude and nocturnal pulsed oximetry (NPO) were compared at T0 between groups (Mann-Whitney U test) and longitudinal progression in G1 was assessed (Wilcoxon test). p < 0.05 was taken as significant. Results: Forty-nine patients were studied: 13 men, mean disease duration 17.1 ± 19.5 months, 21 with spinal-onset; 27 bulbar-onset; one with respiratory presentation. In G1, there was a progressive deterioration in all variables but P0.1/MIP did not significantly change (p = 0.394). PCO₂ (p = 0.045) and bicarbonate ion (HCO₃^-p = 0.054) increased. In G2, the ALSFRS (p = 0.049) scores were lower, PCO₂ (p = 0.057) and HCO₃^- (p = 0.016) higher, and reduced arterial oxygen saturation (SpO₂<90%) at NPO (p = 0.007). Discussion: Patients with high central respiratory drive responses did not develop a short-term "exhaustion phenomenon". Both metabolic and central respiratory mechanisms interact to compensate for respiratory muscle weakness. The role of spasticity and the respiratory-metabolic-renal buffering system deserves further studies.