Tolerability, Safety and Effectiveness of Sigh Introduction During Non-Invasive Mechanical Ventilation Cycles in Patients With Amyotrophic Lateral Sclerosis

Background: Respiratory failure is the main cause of death in Amyotrophic lateral sclerosis (ALS), in which the physiological sigh reflex is impaired due to inspiratory muscle weakness. Aim of this study is to assess the tolerability, safety, and effectiveness of adding a sigh cycle to non-invasive mechanical ventilation (NIMV) settings in ALS patients. Methods: In this randomized, blind-controlled proof-of concept study, 44 consecutive ALS patients with indication for NIMV were randomized to: Group I: NIMV with Sigh cycles; Group II: NIMV without Sigh. The primary outcome was the reduction in the Oxygen Desaturation Index (ODI); secondary outcomes included: Overnight Oximetry (OvOx), Arterial blood gas (ABG), and Visual Analog Scale (VAS; 0–10) scores to assess sleep quality, symptom intensity, mask interface, and NIMV tolerance. Assessments were conducted at baseline, after NIMV adaptation (T1) and at 1-month follow-up (T2). Results: The Sigh cycle was safe and well tolerated. No significant group differences were observed at T1 or T2 in the primary outcome ODI (median ΔODI: Group A:–4.2; Group B:–4.6: p = 0.54), as well as in the OvOx parameters and pO2 and pCO2 ABG values. At T2, secondary analysis showed a significant difference in HCO₃− in favor of the Sigh arm (ΔHCO3−: −1.60 vs. 1.35 mmol/L, p = 0.042). Exploratory Cox-regression models suggested a potential independent effect of SIGH on survival. Conclusions: Sigh is safe, well tolerated in ALS patients. Although this study did not reach the primary outcome, we also cannot rule out that sigh doesn't benefit the patient.