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

PROPPR Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)587-595
Number of pages9
JournalJournal of the American College of Surgeons
Volume227
Issue number6
DOIs
StatePublished - Dec 1 2018

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Syndecan-1
Sepsis
Blood Platelets
Wounds and Injuries
Logistic Models
Glycocalyx
Injury Severity Score
Biomarkers

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

@article{9e391980e0814b15b303e076e09451e8,
title = "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",
abstract = "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.",
author = "{PROPPR Study Group} and Shuyan Wei and {Gonzalez Rodriguez}, Erika and Ronald Chang and Holcomb, {John B.} and Kao, {Lillian S.} and Wade, {Charles E.} and Holcomb, {John B.} and Wade, {Charles E.} and {del Junco}, {Deborah J.} and Fox, {Erin E.} and Nena Matijevic and Jeanette Podbielski and Beeler, {Angela M.} and Tilley, {Barbara C.} and Sarah Baraniuk and Hongjian Zhu and Joshua Nixon and Roann Seay and Appana, {Savitri N.} and Hui Yang and Gonzalez, {Michael O.} and Lisa Baer and {Willa Wang}, {Yao Wei} and Hula, {Brittany S.} and Elena Espino and An Nguyen and Nicholas Pawelczyk and Arora-Nutall, {Kisha D.} and Rishika Sharma and Cardenas, {Jessica C.} and Elaheh Rahbar and Tyrone Burnett and David Clark and {van Belle}, Gerald and Susanne May and Brian Leroux and David Hoyt and Judy Powell and Kellie Sheehan and Alan Hubbard and Arkin, {Adam P.} and Hess, {John R.} and Jeanne Callum and Cotton, {Bryan A.} and Laura Vincent and Timothy Welch and Tiffany Poole and Pivalizza, {Evan G.} and Gumbert, {Sam D.} and Martin Croce",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.jamcollsurg.2018.09.003",
language = "English (US)",
volume = "227",
pages = "587--595",
journal = "Journal of the American College of Surgeons",
issn = "1072-7515",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Elevated Syndecan-1 after Trauma and Risk of Sepsis

T2 - A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial

AU - PROPPR Study Group

AU - Wei, Shuyan

AU - Gonzalez Rodriguez, Erika

AU - Chang, Ronald

AU - Holcomb, John B.

AU - Kao, Lillian S.

AU - Wade, Charles E.

AU - Holcomb, John B.

AU - Wade, Charles E.

AU - del Junco, Deborah J.

AU - Fox, Erin E.

AU - Matijevic, Nena

AU - Podbielski, Jeanette

AU - Beeler, Angela M.

AU - Tilley, Barbara C.

AU - Baraniuk, Sarah

AU - Zhu, Hongjian

AU - Nixon, Joshua

AU - Seay, Roann

AU - Appana, Savitri N.

AU - Yang, Hui

AU - Gonzalez, Michael O.

AU - Baer, Lisa

AU - Willa Wang, Yao Wei

AU - Hula, Brittany S.

AU - Espino, Elena

AU - Nguyen, An

AU - Pawelczyk, Nicholas

AU - Arora-Nutall, Kisha D.

AU - Sharma, Rishika

AU - Cardenas, Jessica C.

AU - Rahbar, Elaheh

AU - Burnett, Tyrone

AU - Clark, David

AU - van Belle, Gerald

AU - May, Susanne

AU - Leroux, Brian

AU - Hoyt, David

AU - Powell, Judy

AU - Sheehan, Kellie

AU - Hubbard, Alan

AU - Arkin, Adam P.

AU - Hess, John R.

AU - Callum, Jeanne

AU - Cotton, Bryan A.

AU - Vincent, Laura

AU - Welch, Timothy

AU - Poole, Tiffany

AU - Pivalizza, Evan G.

AU - Gumbert, Sam D.

AU - Croce, Martin

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85054425709&partnerID=8YFLogxK

U2 - 10.1016/j.jamcollsurg.2018.09.003

DO - 10.1016/j.jamcollsurg.2018.09.003

M3 - Article

VL - 227

SP - 587

EP - 595

JO - Journal of the American College of Surgeons

JF - Journal of the American College of Surgeons

SN - 1072-7515

IS - 6

ER -