Elevated Plasma Soluble Thrombomodulin Is Associated with Increased Risk for ARDS in Sepsis
Year: 2021
Type: conference-abstract
Abstract: Rationale: Acute respiratory distress syndrome (ARDS) is a severe complication of sepsis characterized by alveolar capillary barrier dysfunction and is associated with high mortality.Thrombomodulin (TM) is a transmembrane endothelial glycoprotein with anti-coagulant and anti-inflammatory properties that is released into plasma as soluble TM (sTM) in sepsis.Plasma sTM can serve as a marker of endothelial damage, and has been demonstrated to be predictive of ARDS mortality.It is unknown, however, if sTM is associated with ARDS risk in sepsis.Our objective was to determine the association of sTM measured at intensive care unit (ICU) admission and ARDS in sepsis.Methods: We conducted a prospective cohort study of 496 patients presenting to a single-center medical ICU with sepsis, defined by the Sepsis-3 definition.Plasma sTM was measured in plasma collected at ICU admission using a commercially available ELISA assay.Patients were followed for 6 days for development of ARDS according to Berlin Criteria as determined by independent review of two trained investigators, with adjudication as necessary.Median sTM levels were compared between patients who did and did not develop ARDS using the Wilcoxon rank sum test.The independent association of plasma sTM and ARDS was then determined via multivariable logistic regression adjusting for potential confounders selected from the Lung Injury Prediction Score.Lastly, we determined the area under the receiver operating curve (AUC) to assess the ability of sTM to discriminate patients who subsequently developed ARDS.Results: Of 496 patients, 208 (42%) developed ARDS, and 201 (41%) had a pulmonary source.Plasma sTM concentrations were higher in patients who developed ARDS than those who did not [median (IQR); 8.86 (6.04, 13.26) versus 7.30 (5.20, 11.45) ng/mL; p=0.004].Plasma sTM was also higher in patients with a non-pulmonary source compared to those with a pulmonary source [8.96 (5.69, 13.28) versus 6.96 (5.22, 9.92); p<0.001].The odds of developing ARDS increased by 2.20 [(95% CI 1.46, 3.30); p<0.001] for every log increase in sTM after adjustment for age, race, sex, source of sepsis, shock, active malignancy, alcohol use, and diabetes.The addition of sTM to clinical variables alone increased the AUC from 0.67 to 0.72 (p=0.02).Conclusions: Plasma sTM concentrations measured at ICU admission with sepsis are strongly associated with subsequent ARDS risk, supporting the importance of endothelial dysfunction and coagulation in sepsis-associated ARDS.Future research aimed at understanding the role of sTM in ARDS development may identify new targets for therapeutics.
Institution: University of Pennsylvania
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4231592522