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Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury

Cardiovascular Research Institute and Division of Occupational and Environmental Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee; and Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Dana McClintock, M.D., Cardiovascular Research Institute, 505 Parnassus Avenue, San Francisco, CA 94143-0130. E-mail: dana.mcclintock{at}ucsf.edu

Rationale: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI).

Objectives: We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury.

Methods: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr).

Results: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure–free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04).

Conclusions: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

Key Words: acute respiratory distress syndrome • nitrogen oxide species • pulmonary endothelium • tidal volume • pulmonary edema

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Higher levels of nitrogen oxide species in lavage and pulmonary edema fluid correlated with worse outcomes in human and animal studies of acute lung injury. What This Study Adds to the Field In a large-scale, multicenter trial of patients with the acute respiratory distress syndrome, higher urine nitric oxide levels correlated with better outcomes. This may reflect better preservation of the endothelium or a protective effect of nitric oxide.

 

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