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Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury
A Randomized Controlled Trial
Robert W. Taylor, MD;
Janice L. Zimmerman, MD;
R. Phillip Dellinger, MD;
Richard C. Straube, MD;
Gerard J. Criner, MD;
Kenneth Davis, Jr, MD;
Kathleen M. Kelly, MD;
Thomas C. Smith, MD;
Robert J. Small, RN; for the Inhaled Nitric Oxide in ARDS Study Group
JAMA. 2004;291:1603-1609.
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 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, 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.
Author Affiliations: Critical Care Medicine, St Louis University/St John's Mercy Medical Center, St Louis, Mo (Dr Taylor); Department of Medicine, Baylor College of Medicine and Ben Taub General Hospital, Houston, Tex (Dr Zimmerman); Critical Care Medicine, Robert Wood Johnson Medical School–UMDNJ, Cooper University Hospital, Camden, NJ (Dr Dellinger); INO Therapeutics Inc, Clinton, NJ (Dr Straube and Mr Small); Pulmonary and Critical Care Medicine, Temple Lung Center, Temple University Hospital, Philadelphia, Pa (Dr Criner); Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio (Dr Davis); Department of Clinical Research, Ortho Biotech, Bridgewater, NJ (Dr Kelly); and Department of Pulmonary Medicine, Albany Medical College, Albany, NY (Dr Smith).
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