Effects of inhaled nitric oxide on ventilation/perfusion mismatch assessed by electrical impedance tomography in intubated patients with moderate-to-severe ARDS: a prospective physiological study

Inhaled nitric oxide (iNO) improves oxygenation in acute respiratory distress syndrome (ARDS), but its precise physiological effects on ventilation-perfusion (V/Q) matching and inflammation over 24 h remain to be fully elucidated. To determine the effect of iNO on V/Q matching, gas exchange, and systemic inflammatory response in mechanically ventilated patients with moderate-to-severe ARDS. We conducted a prospective, single-center, randomized controlled trial in 40 mechanically ventilated patients with moderate-to-severe ARDS (PaO 2 /FiO 2 ≤ 200 mmHg). Patients were randomized 1:1 to receive either iNO at a clinician-determined dose plus standard mechanical ventilation (iNO group) or standard mechanical ventilation alone (Control group). The primary endpoint was the change in V/Q matching parameters, assessed by electrical impedance tomography (EIT), at 24 hours. Forty patients were randomized (20 per group). At 24 h, the iNO group showed a significantly greater improvement in V/Q matching compared to the control group. The magnitude of reduction in both EIT-measured dead space (between-group difference, P < 0.001) and shunt (between-group difference, P < 0.001 was significantly larger in the iNO group. This physiological improvement was reflected in gas exchange: the median PaO 2 /FiO 2 ratio in the iNO group increased from 114.0 to 240.0 ( P < 0.001), an improvement significantly greater than that in the control group ( P < 0.001). Similarly, the physiological shunt (Q s /Q t ) decreased more substantially in the iNO group ( P < 0.001). iNO treatment also resulted in a greater reduction in pulmonary artery pressure ( P < 0.001). No significant between-group differences were observed in inflammatory biomarkers or safety parameters. In patients with moderate-to-severe ARDS, 24-hour administration of inhaled nitric oxide significantly improves oxygenation by enhancing ventilation-perfusion matching. This effect is driven by a marked reduction in both EIT-measured shunt and dead space. This study provides a direct mechanistic rationale for iNO’s physiological effects and supports the potential of using EIT to guide a more personalized therapeutic approach. Clinicaltrials.gov; Unique identifier: ChiCTR2500113100; Retrospectively registered; Registration date: 25 November 2025.