Diaphragm neurostimulation mitigates the adverse cardiopulmonary effects of positive pressure ventilation

BACKGROUND: Positive pressure ventilation has multiple adverse cardiopulmonary effects leading to impaired lung mechanics and hemodynamic performance. Controlled levels of diaphragm activity may mitigate these. The objectives of the study were to assess the effect of varying levels of diaphragm neurostimulation on respiratory mechanics and hemodynamics during positive pressure ventilation and to establish whether these effects depend on the level of applied positive end-expiratory pressure (PEEP). METHODS: Patients enrolled in a clinical trial of diaphragm neurostimulation underwent a nested randomized cross-over study assessing the effect of passive ventilation alone or in combination with three levels of diaphragm neurostimulation, performed at two levels of PEEP. Respiratory mechanics, distribution of ventilation, and hemodynamics were assessed. RESULTS: Sixteen patients were included. Diaphragm neurostimulation increased ventilation to the dorsal lung regions in a dose-dependent fashion (median 63% vs. 43% of tidal volume, p < 0.001) whereas increasing PEEP had a much more limited effect (median 43% vs. 43%, p = 0.05). Diaphragm neurostimulation increased end-expiratory lung volume by 617 mL and decreased respiratory system elastance from 1.4 to 1.2 cm H2O/(mL/kg), but only at higher PEEP (p = 0.025 and 0.021 for interaction, respectively). Neurostimulation significantly increased cardiac index (2.4 vs. 2.7 L/min/m2, p = 0.031) without increasing pulmonary artery transmural pressure (p = 0.26). In the absence of neurostimulation, increasing PEEP tended to decrease cardiac index (2.4 vs. 2.1 L/min/m2, p = 0.28). CONCLUSIONS: Diaphragm neurostimulation can mitigate the adverse cardiopulmonary effects of positive pressure ventilation. When combined with higher PEEP, diaphragm neurostimulation enhances dorsal lung recruitment without impairing hemodynamics. TRIAL REGISTRATION: The STIMULUS trial (NCT05465083) was prospectively registered at clinicaltrials.gov (July 2022).