Just a lot of hot air

Nitric oxide not shown to improve mortality in acute lung injury

By Henry Peters

One of the simplest compounds in nature, nitric oxide has enjoyed over a decade of acclaim in the world of medicine. It turned heads in the science world when it was nominated Molecule of the Year by Science in 1992. It's been shown to help the immune system fight disease and to improve oxygenation in acute lung injury. But appearances can be deceiving. Apparently, the compound brings no clinical benefit, according to a study published in the April 7 issue of the Journal of the American Medical Association.

In a clinical trial to measure the health effects of the gas, researchers found no improvement in the duration of ventilatory support nor in overall mortality in all test subjects. "These data do not support the routine use of inhaled nitric oxide in the treatment of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)," noted Dr R Phillip Dellinger and colleagues from Cooper University Hospital in Camden, New Jersey.

The findings are based on a study of 385 patients with lung injury and without sepsis or nonpulmonary organ dysfunction. The patients were randomized to receive inhaled nitric oxide at 5ppm or placebo for 28 days, or until death or discontinuation of ventilatory support.

Patients who received nitric oxide were alive and off assisted breathing for an average of 10.7 days, no different from the 10.6 days seen in the placebo group. There were also no differences between the groups in the number of days patients were alive after a successful two-hour unassisted ventilation trial. Mortality in the nitric oxide group was 23%, slightly higher than the 20% in the placebo group.

Oxygenation improved during the first day in patients receiving inhaled nitric oxide, but this effect didn't last. In a related editorial, Dr Neill Adhikari, from Sunnybrook and Women's College Health Science Centre, and Dr John Granton, from the University of Toronto, observed that most patients with ALI and ARDS don't generally die of refractory hypoxemia but rather due to multiple-organ system failure.

Despite many trials of different therapies, the only interventions shown to reduce mortality have been lung-protective strategies of mechanical ventilation that decreased tidal volume � the amount of air that's inhaled and exhaled in one breath. Although this technique actually reduces oxygenation, it's also been shown to reduce mortality by 22%.

Drs Adhikari and Granton agreed with the study's authors that nitric oxide has no place in the routine management of patients with ALI. However, they suggested that for severe ARDS cases with refractory hypoxemia or pulmonary hypertension, "short-term physiological improvements may be crucial for patient survival. In these limited situations, nitric oxide may have a role as 'salvage' therapy."

At present the only application of nitric oxide shown to be clinically effective is in the treatment of respiratory failure in newborns.