Nitric oxide exacerbates systemic inflammation in adults with severe acute respiratory.

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.