Thrombin Worsens Extravascular Lung Water and Outcomes of Septic patients with Acute Respiratory Distress Syndrome

Abstract

Abstract Introduction: Endothelial cell (EC) activation may increase systemic vascular permeability caused an extravasation of water (EVLW) in sepsis with acute respiratory distress syndrome (ARDS). The correlation of thrombin and EVLW in sepsis and ARDS hasn’t addressed.Methods Septic patients with ARDS were prospectively enrolled during 2014 and 2016, and EVLW and serum thrombin on day 1 and 3 were measured and compared between those with survival and non-survival. Additionally, morphologic change of human umbilical vein endothelial cells (HUVECs) with serum from patients with high and low EVLW was conducted.Results Twenty-seven patients were enrolled and the baseline characters including age, gender, APACHE II, prior 24hrs fluid balance, BMI, and shock status were similar between survivors and non-survivors. But day 1 EVLW was higher in non-survivor (27.5 ± 8.4 vs. 22 ± 6.5 ml/kg, p = 0.049). EVLW of survivor was improved from day 1 to day 3 (22 ± 6.5 vs. 11 ± 3.8 ml/kg, p = 0.0001), but it did not improve in non-survivor (27.5 ± 8.4 vs. 28 ± 6.7 ml/kg, p = 0.89). Thrombin level of survivor significantly improved (1.03 ± 0.55 vs. 0.87 ± 0.25 U/ml, p = 0.04) but it did not improve in non-survivor (1.97 ± 0.75 vs. 2.2 ± 0.75 U/ml, p = 0.07) from day 1 to day 3. EVLW and thrombin revealed a positive correlation (r2 = 0.71, p < 0.0001). In vitro, the morphology and junction of HUVECs were changed when serum of patients with high EVLW was added, but those did not change when serum of patients with low EVLW was added.Conclusion The level of EVLW and thrombin correlated positively and may impact the survival of these patients. Thrombin inhibitor may act as a novel valuable approach for preventing endothelial hyper-permeability and provides the rational basis for the use of this kind of drug in patients with severe sepsis and ARDS.