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 F_1α, 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 P_aO2 to fraction of inspired oxygen (P_aO2/F_IO2) of 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 F_1α, 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 P_aO2/F_IO2 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 (post-pulmonary) 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.