Original scientific article
Elevated Syndecan-1 after Trauma and Risk of Sepsis: A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial

Presented at the regional and national American College of Surgeons Committee on Trauma Resident Paper Competitions in Fort Worth, TX, November 2017, and San Antonio, TX, March 2018.
https://doi.org/10.1016/j.jamcollsurg.2018.09.003Get rights and content

Background

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.

Study Design

We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p < 0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.

Results

We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL [IQR 67 to 336 ng/dL] in those who did (p < 0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.

Conclusions

Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

Section snippets

Methods

We performed a retrospective cohort study using patients enrolled in the PROPPR trial to determine if there is a relationship between patients with elevated serum Synd-1 ≥ 40 ng/mL at 4 hours after admission and subsequent development of sepsis during hospitalization. The PROPPR patients were severely injured adult trauma patients who received pre-hospital blood or any blood product within 1 hour of hospital arrival and who were predicted to require additional massive transfusions. They were

Results

The PROPPR trial enrolled 680 patients, 152 of whom died within 72 hours of admission, and an additional 16 did not have Synd-1 data available. Of the 512 patients who were included in the final analysis, 402 (79%) patients had elevated Synd-1 levels, and 180 (35%) patients developed sepsis. Of the 402 patients with elevated Synd-1, 165 (41%) developed sepsis, while of the 110 patients with lower Synd-1 levels, 15 (14%) developed sepsis (Fig. 2).

Patients with elevated Synd-1 were significantly

Discussion

This secondary analysis of a randomized trial evaluated severely injured adult trauma patients with and without elevated serum Synd-1 levels 4 hours after hospital admission, who went on to develop sepsis. After adjusting for ISS and transfusion requirements, elevated Synd-1 status was independently associated with the development of sepsis during hospitalization. This is the first study to report the finding that elevated Synd-1 after trauma is positively associated with subsequent development

Conclusions

Elevated Synd-1 plasma levels in severely injured adult trauma patients are associated with subsequent sepsis. Interventions that modulate serum Synd-1 as a surrogate marker for treatment response warrant further investigation because they may improve outcomes in hemorrhagic and septic shock populations

Author Contributions

Study conception and design: Wei, Gonzalez Rodriguez, Wade

Acquisition of data: Wei, Gonzalez Rodriguez

Analysis and interpretation of data: Wei, Gonzalez Rodriguez, Holcomb, Kao, Wade

Drafting of manuscript: Wei, Gonzalez Rodriguez, Kao, Wade

Critical revision: Wei, Gonzalez Rodriguez, Chang, Holcomb, Kao, Wade

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    • Cited by (0)

    Drs Wei and Gonzalez Rodriguez contributed equally to this work.

    Members of the PROPPR Study Group are listed in the Appendix.

    Disclosure Information: Nothing to disclose.

    Disclosures outside the scope of this work: Dr Wade is supported by grants from Grifols and Masimo and has stock options with Deciseo Health.

    Support: Dr Wei is supported by a T32 fellowship (grant no 5T32GM008792) from NIGMS.

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    © 2018 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.