Possible Prognostic Value of Leukotriene B4 in Acute Respiratory Distress Syndrome

OBJECTIVE: To study the major eicosanoids implicated in the pathophysiology of acute respiratory distress syndrome (ARDS) in order to estimate their relative prognostic values. METHODS: We conducted a prospective study in a consecutive series of patients with ARDS admitted to a university hospital intensive care unit. We measured the plasma concentrations of 3 inflammatory mediators (thromboxane B2, 6-keto prostaglandin F1, and leukotriene B4) in peripheral arterial and mixed venous plasma samples. RESULTS: We studied 16 patients with ARDS, who had a mean SD baseline ratio of PaO2 to fraction of inspired oxygen (PaO2 /FIO2 )o f 147 37 mm Hg and a mean SD baseline lung injury score of 2.9 0.37. The plasma concentrations of thromboxane B2, 6-keto prostaglandin F1, and leukotriene B4 were greater than the general-population reference levels in both arterial and mixed venous plasma, but only leukotriene B4 was higher in arterial plasma than in mixed venous plasma (401 297 pg/mL vs 316 206 pg/mL, p 0.04). When we correlated the eicosanoid concentrations with specific indicators of clinical severity, we found correlations only between the baseline PaO2 /FIO2 and the arterial thromboxane B2 level (r 0.57, p 0.02), the arterial leukotriene B4 level (r 0.59, p 0.01), and the transpulmonary gradient of leukotriene B4 level (r 0.59, p 0.01). We also found a correlation between the transpulmonary gradient of leukotriene B4 and the lung injury score (r 0.51, p 0.04). The thromboxane B2 concentration in arterial plasma and the leukotriene B4 concentration in both arterial and mixed venous plasma were the only baseline plasma eicosanoid concentrations that predicted significant differences in outcome. When looking at the transpulmonary gradient of the eicosanoids studied, we found that only the gradient of leukotriene B4 showed significant differences of clinical interest. Among survivors we observed practically no gradient (4.9%), whereas among nonsurvivors we found a substantial positive gradient of 41.6% for the elevated arterial (postpulmonary) values, compared with the pulmonary-artery (pre-pulmonary) values, and this difference was statistically significant (p 0.02). CONCLUSIONS: The pro-inflammatory eicosanoid leukotriene B4 showed the best correlation with lung-injury severity and outcome in patients with ARDS. Key words: acute respiratory distress syndrome, ARDS, leukotriene B4, thromboxane B2, prostacyclin, prognostic value, outcome. [Respir Care 2007;52(12):1695–1700. © 2007 Daedalus Enterprises]