Circulating endothelin-1 and tumor necrosis factor-α: early predictors of mortality in patients with septic shock

Abstract

Objectives: To determine the predictive value of early determination of tumor necrosis factor (TNF)-α, TNF-α 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock.¶Design: Prospective study.¶Setting: Intensive care unit of a university hospital.¶Patients: Twenty-one patients with septic shock.¶Interventions: None.¶Measurements and Results: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-α were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-α and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100 % at 6 h, odds ratio 3.0, 95 % CI (1.2–7.6)].¶Conclusions: Increased levels of TNF-α were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-α and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.