Continuous On-Demand Diaphragm Neurostimulation to Prevent Diaphragm Inactivity During Mechanical Ventilation: A Phase 1 Clinical Trial (STIMULUS)

Rationale: Diaphragm inactivity during invasive mechanical ventilation may predispose the lung and diaphragm to injury and is associated with adverse clinical outcomes. Objectives: Assess the feasibility of continuous on-demand diaphragm neurostimulation-assisted mechanical ventilation to maintain diaphragm activity in the absence of respiratory drive for at least 24 hours of mechanical ventilation. Methods: In a single-center phase 1 clinical trial, patients receiving invasive mechanical ventilation for acute hypoxemic respiratory failure or after thoracic surgery underwent transvenous diaphragm neurostimulation delivered in synchrony with mechanical ventilation. Diaphragm neurostimulation was delivered when breaths were initiated by the ventilator and not by the patient until a successful spontaneous breathing trial was performed or for up to 7 days. The coprimary outcomes were safety and feasibility of maintaining diaphragm activity over the first 24 hours of intervention. Measurements and Main Results: Twenty participants were enrolled and 19 underwent study procedures. Diaphragm neurostimulation was successfully initiated in all 19 patients (100%), and on-target diaphragm activity was maintained for ⩾50% of hours of passive mechanical ventilation over the initial 24-hour period in 18/19 (95%) patients. Diaphragm neurostimulation was well tolerated; one pneumothorax unrelated to the device occurred after subclavian catheter placement before surgery. Over the 7-day study period, diaphragm activity was maintained during a median of 100% (interquartile range, 95-100%) hours with absent respiratory drive. Conclusions: Continuous on-demand diaphragm neurostimulation-assisted mechanical ventilation is feasible and can prevent diaphragm inactivity during mechanical ventilation. Clinical Trial registered with www.clinicaltrials.gov (NCT05465083).