Published ahead of print on November 2, 2006, doi:10.1164/rccm.200607-947OC Am. J. Respir. Crit. Care Med., Volume 175, Number 3, February 2007, 256-262 A more recent version of this article appeared on February 1, 2007
Submitted on July 13, 2006 Higher Urine Nitric Oxide is Associated with Improved Outcomes in Patients with Acute Lung InjuryDana E McClintock1*,1 Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA, 2 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA, 3 Division of Occupational and Environmental Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA, 4 Pulmonary and Critical Care Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA * To whom correspondence should be addressed. E-mail: dana.mcclintock{at}ucsf.edu.
Rationale: Nitrogen oxide species are markers for oxidative stress that may be pathogenic in acute lung injury. Objectives: We tested two hypotheses in patients with acute lung injury: 1) higher levels of urine nitric oxide would be associated with worse clinical outcomes and 2) ventilation with lower tidal volumes would reduce urine nitric oxide as a result of less stretch injury. Methods: Urine nitric oxide levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg tidal volume ventilation. The data were expressed both corrected and uncorrected for urine creatinine. Results: Higher baseline levels of urine nitric oxide to creatinine were associated with lower mortality (odds ratio 0.43 per log (10) increase in the ratio), more ventilator free days (mean increase 1.9 days) and more organ failure free days (mean increase 2.3 days) on multivariate analysis (p<0.05 for all analyses). Similar results were obtained using urine nitric oxide alone. Furthermore, nitric oxide to creatinine levels were higher on day 3 in the 6 ml/kg than the 12 ml/kg tidal volume group (p=0.04). Conclusions: Contrary to our hypothesis, higher urine nitric oxide was associated with improved outcomes in acute lung injury both at baseline and after treatment with the 6 ml/kg tidal volume strategy. Higher endogenous nitric oxide may reflect less severe lung injury, better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with acute lung injury. Key words: ARDS, nitrogen oxide species, pulmonary endothelium, lower tidal volume
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