Nitric oxide exacerbates systemic inflammation in adults with severe acute respiratory

Inhaled nitric oxide (iNO) is used as rescue therapy for severe acute respiratory distress syndrome (ARDS), but its dose-dependent effects on systemic inflammation and outcomes remain controversial. This study aimed to compare clinical outcomes between high- and low-dose iNO in adults with severe ARDS. In this single-center retrospective cohort study, 117 patients with severe ARDS (PaO₂/FiO₂ ≤100 mmHg) treated with iNO between January 2020 and July 2024 were categorized by the maximum iNO concentration received: high-dose (≥ 10 ppm, n = 59) and low-dose (< 10 ppm, n = 58). Baseline characteristics, inflammatory markers (white blood cells, interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α]), thromboelastography maximum amplitude (MA) value, Sequential Organ Failure Assessment (SOFA) score, vasopressor requirement, and 30-day survival were analyzed. Baseline characteristics were balanced between groups. Compared to the low-dose group, the high-dose group had significantly higher levels of inflammatory markers (WBC, IL-6, TNF-α; all P < 0.001), lower MA values (P < 0.001), higher SOFA scores (P = 0.031), greater norepinephrine requirements (P = 0.026), longer mechanical ventilation duration (P < 0.001), and fewer 30-day survival days (P < 0.001). Receiver operating characteristic curve analysis indicated good discriminatory power (AUC > 0.7) for these parameters in identifying high-dose exposure. Kaplan-Meier analysis showed significantly worse 30-day survival in the high-dose group (Log-rank P = 0.019). In this retrospective cohort, high-dose iNO (≥ 10 ppm) was associated with exacerbated systemic inflammation, impaired coagulation function, greater organ dysfunction, and increased 30-day mortality compared to low-dose iNO in severe ARDS. These findings suggest cautious use of higher iNO concentrations, emphasizing monitoring of inflammatory and coagulation responses.