Context Inhaled nitric oxide has been shown to improve oxygenation in acute
Objective To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric
oxide in patients with acute lung injury.
Design and Setting Multicenter, randomized, placebo-controlled study, with blinding of
patients, caregivers, data collectors, assessors of outcomes, and data analysts
(triple blind), conducted in the intensive care units of 46 hospitals in the
United States. Patients were enrolled between March 1996 and September 1999.
Patients Patients (n = 385) with moderately severe acute lung injury, a modification
of the American-European Consensus Conference definition of acute respiratory
distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of
≤250, were enrolled if the onset was within 72 hours of randomization,
sepsis was not the cause of the lung injury, and the patient had no significant
nonpulmonary organ system dysfunction at randomization.
Interventions Patients were randomly assigned to placebo (nitrogen gas) or inhaled
nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing,
Main Outcome Measures The primary end point was days alive and off assisted breathing. Secondary
outcomes included mortality, days alive and meeting oxygenation criteria for
extubation, and days patients were alive following a successful unassisted
Results An intent-to-treat analysis revealed that inhaled nitric oxide at 5
ppm did not increase the number of days patients were alive and off assisted
breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7]
days in the inhaled nitric oxide group; P = .97;
difference, –0.1 day [95% confidence interval, –2.0 to 1.9 days]).
This lack of effect on clinical outcomes was seen despite a statistically
significant increase in PaO2 that resolved by 48 hours. Mortality
was similar between groups (20% placebo vs 23% nitric oxide; P = .54). Days patients were alive following a successful 2-hour unassisted
ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8)
for nitric oxide patients (P = .54). Days alive and
meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric
oxide (P = .89).
Conclusion Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung
injury not due to sepsis and without evidence of nonpulmonary organ system
dysfunction results in short-term oxygenation improvements but has no substantial
impact on the duration of ventilatory support or mortality.