Excessive or insufficient respiratory drive and inspiratory effort during mechanical ventilation may worsen outcomes through patient self-inflicted lung injury or diaphragm disuse. We evaluated whether bedside measures of respiratory drive and effort during the first 48 hours of ventilation were associated with outcomes in critically ill adults with acute respiratory failure.

In this single-center, prospective, observational study, adults aged 18–75 years with acute respiratory failure requiring invasive mechanical ventilation and a PaO ₂ /FiO ₂ ratio > 150 mmHg were enrolled within 24 hours of ICU admission. Airway occlusion pressure at 100 ms (P _0.1 ) and occlusion pressure (P _occ ) were measured at baseline and at 12, 24, 36, and 48 hours. Calculated respiratory muscle pressure (P _mus ) and calculated transpulmonary driving pressure (ΔP _L ) were calculated from P _occ. Median values over the first 48 hours represented exposure. The primary outcome was 28-day ventilator-free days (VFDs). Secondary outcomes included 28-day mortality, oxygenation changes, and correlations with Richmond Agitation-Sedation Scale scores. Multivariable Poisson and Cox regression analyses were performed.

A total of 206 patients were included. Patients within prespecified preferred ranges (P _0.1 1.5–3.5 cmH2O, calculated P _mus 5–10 cmH2O, and calculated ΔP _L ≤20 cmH2O) had more 28-day VFDs than those with low or high values. In multivariable Poisson regression, low and high P _0.1 , low calculated P _mus , and high calculated ΔP _L were independently associated with fewer VFDs. In multivariable Cox regression adjusted for age, immunocompromised status, peak airway pressure, and APACHE II score, calculated ΔP _L > 20 cmH2O was independently associated with increased 28-day mortality (hazard ratio 6.57, 95% confidence interval 2.29-18.86; P   <  0.001). Both low and high P _0.1 were also independently associated with mortality (hazard ratios 3.75 and 4.81, respectively). Oxygenation improved in patients with preferred effort levels, whereas ΔP _L > 20 cmH2O was associated with new-onset hypoxemia. Richmond Agitation-Sedation Scale scores correlated most strongly with calculated P _mus (r = 0.76), followed by P0.1 (r = 0.50) and ΔPL (r = 0.43).

Early respiratory drive and inspiratory effort within preferred physiological ranges were associated with more VFDs and lower mortality. Calculated ΔP _L showed the strongest association with adverse outcomes, supporting bedside monitoring of drive and effort during assisted ventilation.

NCT06433076. Registered 29 May 2024, retrospectively registered.