Lung nitroxidative stress as a prognostic factor in ventilated septic patients

Introduction

During sepsis and mechanical ventilation, nitric oxide (•NO) is produced by lung cells. We study whether pulmonary •NO production is a prognostic factor in mechanically ventilated septic patients.

Materials and methods

We studied 50 patients with sepsis within the first 48 hours of sepsis. Operating room patients served as control a group (ORCG). Nitrite and nitrate (NO_x^-) and 3-nitrotyrosine (3NT) in plasma and bronchoalveolar lavage fluid (BALF) were analyzed by the Griess/vanadium chloride method and ELISA, respectively. Results were expressed as median and interquartile range. Receiver operator curves were constructed to compare the predictive value of NO_x^- values in BALF at admission with other variables. Kaplan–Meier analysis was used to compare survival between high and low BALF NO_x^- levels at admission. A P value less than 0.05 was considered significant.

Results

At study admission in the sepsis group, nonsurvivors had higher levels of BALF NO_x^- than survivors: 20 (17–33) μM, 27 versus 72 (46–91) μM, 23, P = 0.0001. At day 7, BALF 3NT was higher in nonsurvivor septic patients than in survivors: 1,666 (30–3,173) pmol/mg protein versus 291 (13–1,908) pmol/mg protein. BALF NO_x^- had the highest area under the receiver operator curve for mortality (0.812, P = 0.001) in relation to other variables. Septic patients with BALF NO_x^- above 36 μM had a relative risk for mortality of 4.23 and an OR of 15.84. The difference between the low bronchoalveolar •NO group (BALF [NO_x^-] < 36 μM at admission) versus the high bronchoalveolar •NO group (BALF [NO_x^-] ≥36 μM at admission) in ICU mortality was significant: 19% versus 78% (log rank 18.19, P = 0.00001).

Conclusion

During sepsis there is enhanced lung •NO production that is associated with ICU mortality.