Traumatic Endotheliopathy: A Prospective Observational Study of 424 Severely Injured Patients

Abstract

Objective: Investigate and confirm the association between sympathoadrenal activation, endotheliopathy and poor outcome in trauma patients.

Background: The association between sympathoadrenal activation, endotheliopathy, and poor outcome in trauma has only been demonstrated in smaller patient cohorts and animal models but needs confirmation in a large independent patient cohort.

Methods: Prospective observational study of 424 trauma patients admitted to a level 1 Trauma Center. Admission plasma levels of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial damage (syndecan-1, thrombomodulin, and sE-selectin) were measured and demography, injury type and severity, physiology, treatment, and mortality up till 28 days were recorded.

Results: Patients had a median ISS of 17 with 72% suffering from blunt injury. Adrenaline and noradrenaline correlated with syndecan-1 (r = 0.38, P < 0.001 and r = 0.23, P < 0.001, respectively) but adrenaline was the only independent predictor of syndecan-1 by multiple linear regression adjusted for age, injury severity score, Glascow Coma Scale, systolic blood pressure, base excess, platelet count, hemoglobin, prehospital plasma, and prehospital fluids (100 pg/mL higher adrenaline predicted 2.75 ng/mL higher syndecan-1, P < 0.001). By Cox analyses adjusted for age, sex, injury severity score, Glascow Coma Scale, base excess, platelet count and hemoglobin, adrenaline, and syndecan-1 were the only independent predictors of both <24-hours, 7-day and 28-day mortality (all P < 0.05). Furthermore, noradrenaline was an independent predictor of <24-hours mortality and thrombomodulin was an independent predictor of 7-day and 28-day mortality (all P < 0.05).

Conclusions: We confirmed that sympathoadrenal activation was strongly and independently associated with endothelial glycocalyx and cell damage (ie, endotheliopathy) and furthermore that sympathoadrenal activation and endotheliopathy were independent predictors of mortality in trauma patients.

FIGURE 1

3-D plots displaying associations between plasma adrenaline, injury severity, base excess, transfusions, mortality, and plasma levels of endothelial glycocalyx damage in 424 trauma patients admitted to a Level I Trauma Centre in the United States. Injury severity score (ISS) were categorized into four groups (ISS <9, ISS 9–15, ISS 16–25, and ISS >25) and plasma adrenaline were categorized into quartiles (Q1 28 pg/mL (IQR 16–28), Q2 93 pg/mL (IQR 77–124), Q3 263 pg/mL (IQR 217–316), and Q4 884 pg/mL (IQR 659–1901). Transfusions refers to inhospital transfusions (yes, no). The 3-D plots display: (A) ISS, adrenaline quartile, and syndecan-1 (ng/mL); (B) Base excess, adrenaline quartile, and syndecan-1 (ng/mL); (C) Transfusions, adrenaline quartile, and syndecan-1 (ng/mL); and (D) 28-day mortality, adrenaline quartiles, and syndecan-1 (ng/mL).