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 h 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 h 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 h. Calculated respiratory muscle pressure (P _mus ) and calculated transpulmonary driving pressure (ΔP _L ) were calculated from P _occ. Median values over the first 48 h 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 cmH ₂ O, calculated P _mus 5–10 cmH ₂ 2O, and calculated ΔP _L ≤20 cmH ₂ O) 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 cmH ₂ O 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 cmH ₂ O 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.