Higher Nitric Oxide in Urine Means Better Outcome in Acute Lung Injury

February 1, 2007

SAN FRANCISCO -- Higher urinary nitric oxide levels correlated with better outcomes, including lower mortality, in a comparison of two ventilation approaches in acute lung injury.

SAN FRANCISCO, Feb. 1 -- A high level of nitric oxide (NO) in urine bodes well for patients with acute lung injury, investigators reported.

Although higher levels of NO in pulmonary edema fluid and bronchoalveolar lavage have been associated with worse outcomes in acute lung injury, higher urinary NO levels correlated with better outcomes in a comparison of two ventilation approaches, found Dana E. McClintock, M.D., of the University of California San Francisco, and colleagues.

"Contrary to our original hypothesis, higher urine NO, corrected or uncorrected for urine creatinine, was strongly associated with better clinical outcomes, including improved survival, more ventilator-free days, and more organ failure-free days, in patients with acute lung injury," the investigators wrote in the Feb. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

They speculated that higher levels of endogenous NO in urine may be a marker for less severe lung injury and better preservation of pulmonary and systemic endothelium.

Alternatively, NO might be protective in patients with acute lung injury, by scavenging oxygen free radicals and causing vasodilation of microscopic circulation to allow for better tissue perfusion, the authors suggested.

The study was part of the National Heart, Lung, and Blood Institute's Acute Respiratory Distress Syndrome (ARDS) network trial that is comparing ventilation with low tidal volumes (6ml/kg Vt) with higher volumes (12 ml/kg Vt) in acute lung injury.

The authors examined whether higher levels of NO in urine were associated with worse clinical outcomes, and whether ventilation with lower tidal volumes reduced urine NO, as a result of less stretch injury to the lungs.

They used chemiluminescence to measure NO in the urine of 566 patients who were enrolled in the trial, and recorded the data with and without correction for urine creatinine levels.

They found in multivariate analysis that for every log10 increase in urine NO, the risk of death decreased by more than half on both day 0 (odds ratio, corrected for creatinine, 0.39. 95% confidence interval, 0.27-0.57, P

The results were similar when they looked at NO alone, uncorrected for creatinine (day 0 odds ratio, 0.27, 95% CI, 0.18-0.42, P