Table 1.

Randomized Controlled Trials on Inhaled Nitric Oxide Administration in Classical Acute Respiratory Distress Syndrome

Study name/NCT	Sample size	Treatment group/study population	Control group	NO dose, ppm	Endpoint	Main results
NCT00240487	52 children	iNO for the first 4 hours, then no iNO for 4 hours	No iNO for the first 4 hours, then iNO for 4 hours	10	Changes in PaO2/FiO2 ratio	ns
Bronicki et al.51	53 children	iNO until death, ventilator free, or 28 days	Nitrogen	5	VFD at 28 days	14.2 ± 8.1 vs. 9.1 ± 9.5 days (iNO vs. placebo, p = 0.05)
Day et al.17	24 children	iNO until PEEP decreased to 6 days cmH2O and FiO2 0.5	Conventional care for 1 day, then iNO	10	OI and PVR/SVR	OI and PVR/SVR acutely improved in the first hour of treatment
Dellinger et al.52	177 adults	iNO for 28 days or until extubation	Nitrogen	1.25, 5, 20, 40 or 80	Duration of mechanical ventilation	ns
Dobyns et al.53	108 children	iNO for 3 days	Air	10	Proportion of pts meeting treatment failure criteria (OI ≥40 × 3 hours or ≥25 × 6 hours)	ns
Gerlach et al.55	40 adults	iNO, daily dose–response analysis	Conventional care	10	Dose–response analysis	Peak response at 10 ppm
Ibrahim and El-Mohamdy54	32 children	iNO at 5 ppm for 18 hours, then 1 ppm for 2 hours + prone position or supine position	Conventional care	1–5	Changes in PaO2/FiO2 ratio, OI	Better oxygenation parameters in the prone position iNO group
Lundin et al.56	180 adults	iNO for 10 min/day, up to 30 days	Conventional care	2–40 ppm	Reversal of ALI	ns
Mehta et al.57	14 adults	iNO titrated to best PaO2/FiO2 ratio until PaO2/FiO2 >200 mmHg on FiO2 <0.5	Conventional care	5–20	Changes in mean PAP, PaO2/FiO2	Reduction of mean PAP at 5–10 ppm and better PaO2/FiO2 at 5–10 ppm
Michael et al.58	40 adults	iNO at increasing doses every 6 hours for 1 day, then clinically adjusted.	Conventional care	5–20	Improvement in oxygenation within 3 days	Better PaO2/FiO2 at 1, 12, 24 hours in the iNO group vs. control group
Park et al.59	23 adults	iNO or iNO+lung recruitment	Conventional care+lung recruitment	5	Oxygenation and hemodynamic parameters	ns
Payen et al.60	203 adults	iNO	Nitrogen	10	Survival and off mechanical ventilation at 28 days	/
Schwebel et al.61	19 adults	iNO for 17 hours, then at the clinician's discretion	Nitrogen	10	Oxygenation and hemodynamic parameters	/
Taylor et al.16	385 adults	iNO for up to 28 days	Nitrogen	5	Days alive and off mechanical ventilation at 28 days	ns
Troncy et al.139	30 adults	iNO titration	Conventional care	2.5–40	Gas exchange	Better gas exchange in iNO group vs. control group in the first day of treatment

ALI, acute lung injury; iNO, inhaled nitric oxide; ns, not statistically significant; OI, oxygenation index; PaCO₂, partial pressure of arterial carbon dioxide; PaO₂/FiO₂, ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen; PAP, pulmonary arterial pressure; PEEP, positive end expiratory pressure; ppm, part per million; PVR, pulmonary vascular resistances; RCT, randomized controlled trial; SVR, systemic vascular resistances; VFD, ventilator-free days.