Patients with acute lung injury but without other organ system failure or sepsis did not experience improved outcomes with inhaled nitric oxide, compared with placebo, according to the findings of a blinded study conducted at 46 hospitals in the United States.

"Inhaled nitric oxide induced a rapid improvement in the oxygenation of these patients, which was maintained for 24 hours," writes R. Phillip Dellinger, MD, Robert Wood Johnson Medical School-UMDNJ, Cooper University Hospital, Camden, New Jersey, and colleagues. However, inhaled nitric oxide "was not associated with any clinically relevant change in patient outcomes," the researchers add.

Between March 1996 and September 1999, 385 patients, mean age 50 years, with moderately severe acute lung injury defined as a ratio of 250 or less in partial arterial oxygen to fraction of inspired oxygen, underwent randomisation within 72 hours of onset of acute respiratory distress syndrome (ARDS) to either nitrogen gas as placebo or 5 ppm inhaled nitric oxide. Patients had no history of immunocompromise, persistent systemic hypotension, or evidence of nonpulmonary organ dysfunction. The 193 patients assigned to placebo and the 192 assigned to nitric oxide underwent treatment for up to 28 days, the discontinuation of assisted breathing, or death.

In the intent-to-treat analysis, patients treated with nitric oxide survived a mean of 10.7 days without assisted breathing, compared with 10.6 days for placebo patients. The patients who received nitric oxide survived for a mean of 11.4 days after successful a 2-hour unassisted ventilation trial, compared with 11.9 days for those who received placebo. Likewise, the mean days alive after reaching oxygenation criteria were 16.7 in the nitric oxide group and 17.0 in the placebo group.

By day 28, 66% of each group was alive and not receiving breathing assistance. Mortality occurred in 23% and 20% of the nitric oxide and placebo group, respectively.

Overall, 630 adverse events occurred in the nitric oxide group compared with 666 in the placebo group. Adverse events of the respiratory system occurred in 51% of the nitric oxide and in 51% of the placebo group.

"These data do not support the routine use of inhaled nitric oxide in the treatment of acute lung injury or ARDS," the authors conclude, adding "Inhaled nitric oxide may be considered as a salvage therapy in acute lung injury or ARDS patients who continue to have life-threatening hypoxemia despite optimization of conventional mechanical ventilator support."