Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury.
BACKGROUND
Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI).


OBJECTIVE
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.
McClintock
Dana E
DE
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, USA. dana.mcclintock@ucsf.edu
Ware
Lorraine B
LB
Eisner
Mark D
MD
Wickersham
Nancy
N
Thompson
B Taylor
BT
Matthay
Michael A
MA
D000328:Adult; D000368:Aged; D015415:Biomarkers; D003404:Creatinine / Q000652:urine; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000652:urine*; D017063:Outcome Assessment, Health Care; D018384:Oxidative Stress; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000175:diagnosis* / Q000401:mortality* / Q000652:urine; D012720:Severity of Illness Index
D015415:Biomarkers; D009569:Nitric Oxide; D003404:Creatinine