Skip to main content
Top
Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2018

Open Access 01-12-2018 | Original research

Traumatic brain injury is associated with increased syndecan-1 shedding in severely injured patients

Authors: Erika Gonzalez Rodriguez, Jessica C. Cardenas, Charles S. Cox, Ryan S. Kitagawa, Jakob Stensballe, John B. Holcomb, Pär I. Johansson, Charles E. Wade

Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Issue 1/2018

Login to get access

Abstract

Introduction

Head injury and exsanguination are the leading causes of death in trauma patients. Hemorrhagic shock triggers systemic endothelial glycocalyx breakdown, potentially leading to traumatic endotheliopathy (EoT). Levels of syndecan-1, a main glycocalyx component, have been used to assess the integrity of the glycocalyx. In TBI patients, it remains unclear whether syndecan-1 shedding occurs and its correlation with outcomes. We aimed to determine the frequency of EoT+, defined as a syndecan-1 level of 40 ng/ml or higher, after TBI in isolated and polytraumatic injury. We also investigated how the presence of EoT+ affected outcomes in TBI patients.

Methods

Severely injured trauma patients were enrolled. From blood samples collected upon patients’ arrival to the hospital, we measured syndecan-1 (main biomarker of EoT+), soluble thrombomodulin (sTM, endothelial activation) adrenaline and noradrenaline (sympathoadrenal activation), and assessed TBI patients’ coagulation capacity.

Results

Of the enrolled patients (n = 331), those with TBI and polytrauma (n = 68) had the highest rate of EoT+ compared to isolated TBI (n = 58) and Non-TBI patients (n = 205) (Polytrauma-TBI 55.9% vs. Isolated-TBI 20.0% vs. non-TBI polytrauma 40.0%; p = 0.001). TBI patients with EoT+ exhibited marked increases in sTM, adrenaline and noradrenaline levels, and physiological and coagulation derangements. In isolated TBI patients, increasing syndecan-1 levels (β for every 10 ng/ml increase: 0.14; 95% CI: 0.02, 0.26) and hypocoagulability were negatively associated with survival.

Conclusions

This study provides evidence of syndecan-1 shedding after TBI supporting the notion that breakdown of the glycocalyx contributes to the physiological derangements after TBI.
Literature
1.
go back to reference Oyeniyi BT, Fox EE, Scerbo M, Tomasek JS, Wade CE, Holcomb JB. Trends in 1029 trauma deaths at a level 1 trauma center: impact of a bleeding control bundle of care. Injury. 2017;48(1):5–12.CrossRef Oyeniyi BT, Fox EE, Scerbo M, Tomasek JS, Wade CE, Holcomb JB. Trends in 1029 trauma deaths at a level 1 trauma center: impact of a bleeding control bundle of care. Injury. 2017;48(1):5–12.CrossRef
2.
go back to reference Fox EE, Holcomb JB, Wade CE, Bulger EM, Tilley BC, Group PS. Earlier endpoints are required for hemorrhagic shock trials among severely injured patients. Shock. 2017;47(5):567–73.CrossRef Fox EE, Holcomb JB, Wade CE, Bulger EM, Tilley BC, Group PS. Earlier endpoints are required for hemorrhagic shock trials among severely injured patients. Shock. 2017;47(5):567–73.CrossRef
3.
go back to reference Wang KW, Chen HJ, Lu K, Liliang PC, Liang CL, Tsai YD, et al. Simvastatin attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. Ann Clin Lab Sci. 2014;44(2):145–50.PubMed Wang KW, Chen HJ, Lu K, Liliang PC, Liang CL, Tsai YD, et al. Simvastatin attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. Ann Clin Lab Sci. 2014;44(2):145–50.PubMed
4.
go back to reference Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013;148(2):127–36.CrossRef Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013;148(2):127–36.CrossRef
5.
go back to reference Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471–82.CrossRef Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471–82.CrossRef
6.
go back to reference Chignalia AZ, Yetimakman F, Christiaans SC, Unal S, Bayrakci B, Wagener BM, et al. The glycocalyx and trauma: a review. Shock. 2016;45(4):338–48.CrossRef Chignalia AZ, Yetimakman F, Christiaans SC, Unal S, Bayrakci B, Wagener BM, et al. The glycocalyx and trauma: a review. Shock. 2016;45(4):338–48.CrossRef
7.
go back to reference Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014;69(7):777–84.CrossRef Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014;69(7):777–84.CrossRef
8.
go back to reference Johansson PI, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann Surg. 2017;265(3):597–603.CrossRef Johansson PI, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann Surg. 2017;265(3):597–603.CrossRef
9.
go back to reference Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective. Hematology Am Soc Hematol Educ Program. 2013;2013:656–9.CrossRef Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective. Hematology Am Soc Hematol Educ Program. 2013;2013:656–9.CrossRef
10.
go back to reference Johansson P, Stensballe J, Ostrowski S. Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism. Crit Care. 2017;21(1):25.CrossRef Johansson P, Stensballe J, Ostrowski S. Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism. Crit Care. 2017;21(1):25.CrossRef
11.
go back to reference Rahbar E, Baer LA, Cotton BA, Holcomb JB, Wade CE. Plasma colloid osmotic pressure is an early indicator of injury and hemorrhagic shock. Shock. 2014;41(3):181–7.CrossRef Rahbar E, Baer LA, Cotton BA, Holcomb JB, Wade CE. Plasma colloid osmotic pressure is an early indicator of injury and hemorrhagic shock. Shock. 2014;41(3):181–7.CrossRef
12.
go back to reference Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, et al. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015;13:117.CrossRef Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, et al. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015;13:117.CrossRef
13.
go back to reference Torres Filho I, Torres LN, Sondeen JL, Polykratis IA, Dubick MA. In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy. Microvasc Res. 2013;85:128–33.CrossRef Torres Filho I, Torres LN, Sondeen JL, Polykratis IA, Dubick MA. In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy. Microvasc Res. 2013;85:128–33.CrossRef
14.
go back to reference Torres Filho IP, Torres LN, Salgado C, Dubick MA. Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids. Am J Physiol Heart Circ Physiol. 2016;310(11):H1468–78.CrossRef Torres Filho IP, Torres LN, Salgado C, Dubick MA. Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids. Am J Physiol Heart Circ Physiol. 2016;310(11):H1468–78.CrossRef
15.
go back to reference Gonzalez Rodriguez E, Cardenas JC, Lopez E, Cotton BA, Tomasek JS, Ostrowski SR, et al. Early identification of the patient with endotheliopathy of trauma by arrival serum albumin. Shock. 2018;50(1):31-37.CrossRef Gonzalez Rodriguez E, Cardenas JC, Lopez E, Cotton BA, Tomasek JS, Ostrowski SR, et al. Early identification of the patient with endotheliopathy of trauma by arrival serum albumin. Shock. 2018;50(1):31-37.CrossRef
16.
go back to reference Ban K, Peng Z, Pati S, Witkov RB, Park PW, Kozar RA. Plasma-mediated gut protection after hemorrhagic shock is lessened in syndecan-1−/− mice. Shock. 2015;44(5):452–7.CrossRef Ban K, Peng Z, Pati S, Witkov RB, Park PW, Kozar RA. Plasma-mediated gut protection after hemorrhagic shock is lessened in syndecan-1−/− mice. Shock. 2015;44(5):452–7.CrossRef
17.
go back to reference Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011;6(8):e23530.CrossRef Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011;6(8):e23530.CrossRef
18.
go back to reference Kozar RA, Pati S. Syndecan-1 restitution by plasma after hemorrhagic shock. J Trauma Acute Care Surg. 2015;78(6 Suppl 1):S83–6.CrossRef Kozar RA, Pati S. Syndecan-1 restitution by plasma after hemorrhagic shock. J Trauma Acute Care Surg. 2015;78(6 Suppl 1):S83–6.CrossRef
19.
go back to reference Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011;112(6):1289–95.CrossRef Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011;112(6):1289–95.CrossRef
20.
go back to reference Peng Z, Pati S, Potter D, Brown R, Holcomb JB, Grill R, et al. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013;40(3):195–202.CrossRef Peng Z, Pati S, Potter D, Brown R, Holcomb JB, Grill R, et al. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013;40(3):195–202.CrossRef
21.
go back to reference Sillesen M, Rasmussen LS, Jin G, Jepsen CH, Imam A, Hwabejire JO, et al. Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model. J Trauma Acute Care Surg. 2014;76(1):12–9 discussion 9-20.CrossRef Sillesen M, Rasmussen LS, Jin G, Jepsen CH, Imam A, Hwabejire JO, et al. Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model. J Trauma Acute Care Surg. 2014;76(1):12–9 discussion 9-20.CrossRef
22.
go back to reference Di Battista AP, Rhind SG, Hutchison MG, Hassan S, Shiu MY, Inaba K, et al. Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury. J Neuroinflammation. 2016;13:40.CrossRef Di Battista AP, Rhind SG, Hutchison MG, Hassan S, Shiu MY, Inaba K, et al. Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury. J Neuroinflammation. 2016;13:40.CrossRef
23.
go back to reference Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal activation is associated with acute traumatic coagulopathy and endotheliopathy in isolated brain injury. Shock. 2016;46(3 Suppl 1):96–103.CrossRef Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal activation is associated with acute traumatic coagulopathy and endotheliopathy in isolated brain injury. Shock. 2016;46(3 Suppl 1):96–103.CrossRef
24.
go back to reference Gonzalez Rodriguez E, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, et al. Syndecan-1: a quantitative marker for the endotheliopathy of trauma. J Am Coll Surg. 2017;225:419.CrossRef Gonzalez Rodriguez E, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, et al. Syndecan-1: a quantitative marker for the endotheliopathy of trauma. J Am Coll Surg. 2017;225:419.CrossRef
25.
go back to reference Ostrowski SR, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: a prospective observational study of 404 severely injured patients. J Trauma Acute Care Surg. 2017;82(2):293–301.CrossRef Ostrowski SR, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: a prospective observational study of 404 severely injured patients. J Trauma Acute Care Surg. 2017;82(2):293–301.CrossRef
26.
go back to reference Cotton BA, Faz G, Hatch QM, Radwan ZA, Podbielski J, Wade C, et al. Rapid thrombelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma. 2011;71(2):407–14 discussion 14-7.CrossRef Cotton BA, Faz G, Hatch QM, Radwan ZA, Podbielski J, Wade C, et al. Rapid thrombelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma. 2011;71(2):407–14 discussion 14-7.CrossRef
27.
go back to reference Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254(2):194–200.CrossRef Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254(2):194–200.CrossRef
28.
go back to reference Genet GF, Johansson PI, Meyer MA, Solbeck S, Sorensen AM, Larsen CF, et al. Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury. J Neurotrauma. 2013;30(4):301–6.CrossRef Genet GF, Johansson PI, Meyer MA, Solbeck S, Sorensen AM, Larsen CF, et al. Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury. J Neurotrauma. 2013;30(4):301–6.CrossRef
29.
go back to reference Halaweish I, Bambakidis T, Nikolian VC, Georgoff P, Bruhn P, Piascik P, et al. Early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock. J Trauma Acute Care Surg. 2016;81(6):1080–7.CrossRef Halaweish I, Bambakidis T, Nikolian VC, Georgoff P, Bruhn P, Piascik P, et al. Early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock. J Trauma Acute Care Surg. 2016;81(6):1080–7.CrossRef
30.
go back to reference Halaweish I, Bambakidis T, He W, Linzel D, Chang Z, Srinivasan A, et al. Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. J Am Coll Surg. 2015;220(5):809–19.CrossRef Halaweish I, Bambakidis T, He W, Linzel D, Chang Z, Srinivasan A, et al. Early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery. J Am Coll Surg. 2015;220(5):809–19.CrossRef
31.
go back to reference Wu F, Peng Z, Park PW, Kozar RA. Loss of syndecan-1 abrogates the pulmonary protective phenotype induced by plasma after hemorrhagic shock. Shock. 2017;48:340.CrossRef Wu F, Peng Z, Park PW, Kozar RA. Loss of syndecan-1 abrogates the pulmonary protective phenotype induced by plasma after hemorrhagic shock. Shock. 2017;48:340.CrossRef
32.
go back to reference Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: factor concentrate versus fresh frozen plasma. J Trauma Acute Care Surg. 2016;80(4):576–84 discussion 84-5.CrossRef Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: factor concentrate versus fresh frozen plasma. J Trauma Acute Care Surg. 2016;80(4):576–84 discussion 84-5.CrossRef
33.
go back to reference Brettner F, von Dossow V, Chappell D. The endothelial glycocalyx and perioperative lung injury. Curr Opin Anaesthesiol. 2017;30(1):36–41.PubMed Brettner F, von Dossow V, Chappell D. The endothelial glycocalyx and perioperative lung injury. Curr Opin Anaesthesiol. 2017;30(1):36–41.PubMed
34.
go back to reference McCredie VA, Alali AS, Xiong W, Rubenfeld GD, Cuthbertson BH, Scales DC, et al. Timing of withdrawal of life-sustaining therapies in severe traumatic brain injury: impact on overall mortality. J Trauma Acute Care Surg. 2016;80(3):484–91.CrossRef McCredie VA, Alali AS, Xiong W, Rubenfeld GD, Cuthbertson BH, Scales DC, et al. Timing of withdrawal of life-sustaining therapies in severe traumatic brain injury: impact on overall mortality. J Trauma Acute Care Surg. 2016;80(3):484–91.CrossRef
35.
go back to reference Turgeon AF, Lauzier F, Simard J-F, Scales DC, Burns KEA, Moore L, et al. Withdrawing life-sustaining therapy for patients with severe traumatic brain injury. CMAJ. 2011;183(14):1570–1.CrossRef Turgeon AF, Lauzier F, Simard J-F, Scales DC, Burns KEA, Moore L, et al. Withdrawing life-sustaining therapy for patients with severe traumatic brain injury. CMAJ. 2011;183(14):1570–1.CrossRef
36.
go back to reference Gonzalez Rodriguez E, Cardenas JC, Cox CS, Kitagawa RS, Stensballe J, Holcomb JB, et al. Traumatic brain injury is associated with increased syndecan-1 shedding in severely injured patients dataset. V1 ed. Mendeley 2018. Gonzalez Rodriguez E, Cardenas JC, Cox CS, Kitagawa RS, Stensballe J, Holcomb JB, et al. Traumatic brain injury is associated with increased syndecan-1 shedding in severely injured patients dataset. V1 ed. Mendeley 2018.
Metadata
Title
Traumatic brain injury is associated with increased syndecan-1 shedding in severely injured patients
Authors
Erika Gonzalez Rodriguez
Jessica C. Cardenas
Charles S. Cox
Ryan S. Kitagawa
Jakob Stensballe
John B. Holcomb
Pär I. Johansson
Charles E. Wade
Publication date
01-12-2018
Publisher
BioMed Central
DOI
https://doi.org/10.1186/s13049-018-0565-3

Other articles of this Issue 1/2018

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2018 Go to the issue