Objective:

To evaluate the safety and kinetics of methemoglobin and nitrogen dioxide during intermittent inhaled nitric oxide at 300 ppm in healthy volunteers, providing insights for future clinical studies on its antimicrobial potential.

Approach:

Key Findings:

• 148 treatments were administered without major adverse effects.
• Peak methemoglobin averaged 5.5 ± 1.2% at rest and 9.0 ± 1.1% during exercise; 6 transient asymptomatic elevations above 10% occurred in 3 of 10 subjects, exclusively during exercise.

Interpretation:

The study did not assess antimicrobial efficacy.

Limitations:

• Small sample size and inclusion of healthy volunteers limit generalizability.
• Study was not designed to assess antimicrobial efficacy.
• Exercise may not accurately represent the complex pathophysiology of pneumonia or ARDS.

Conclusion:

Further studies are needed to define safe exposure thresholds, optimal dosing, and monitoring approaches.

Sources:

• Bruno et al. Study
• Berra et al. Review
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