US EPA

3244024 

Journal Article 

Low-dose inhaled nitric oxide in patients with acute lung injury - A randomized controlled trial 

Taylor, RW; Zimmerman, JL; Dellinger, RP; Straube, RC; Criner, GJ; Davis, K; Kelly, KM; Smith, TC; Small, RJ; Inhaled Nitric Oxide ARDS Study Gr 

2004 

Yes 

JAMA: Journal of the American Medical Association
ISSN: 0098-7484
EISSN: 1538-3598 

291 

13 

1603-1609 

WOS:000220649000025 

Context Inhaled nitric oxide has been shown to improve
oxygenation in acute lung injury. 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 FiO(2) of less than or equal to250, 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, or death. 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 ventilation test. 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.