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Background <p>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.</p> Methods <p>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, <i>n</i> = 59) and low-dose (&lt; 10 ppm, <i>n</i> = 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.</p> Results <p>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 <i>P</i> &lt; 0.001), lower MA values (<i>P</i> &lt; 0.001), higher SOFA scores (<i>P</i> = 0.031), greater norepinephrine requirements (<i>P</i> = 0.026), longer mechanical ventilation duration (<i>P</i> &lt; 0.001), and fewer 30-day survival days (<i>P</i> &lt; 0.001). Receiver operating characteristic curve analysis indicated good discriminatory power (AUC &gt; 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 <i>P</i> = 0.019).</p> Conclusions <p>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.</p>

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Nitric oxide exacerbates systemic inflammation in adults with severe acute respiratory

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月6日

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  • Yong Bai,
  • Minglang Liao,
  • Ruiling Shang,
  • Lehong Zhou,
  • Haili Hu

摘要

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.