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The purpose of this observational study is to examine whether Endotheliopathy of Trauma (EoT) is present in severely burned patients and how it is affected by burn debridement surgery.
The main questions it aims to answer are:
Participants will:
This study aims to provide insight into how surgical resuscitation affects the endothelial glycocalyx in severely burned patients.
The endothelial glycocalyx is a protective layer of glycoproteins, glycosaminoglycans, and proteoglycans that lines the luminal surface of blood vessels and plays a critical role in regulating vascular permeability and coagulation. The syndecan family, consisting of four members (syndecan 1-4), is the main proteoglycan. Of particular interest, sdc 1 is a marker of endothelial damage, with elevated levels (>40 ng/ml) being linked to EoT. This condition is characterized by increased transfusion requirements, prolonged hospital stays, and higher morbidity and mortality rates.
Early burn debridement (from the fifth day onward) has been associated with improved outcomes in severely burned patients. The purpose of this surgical intervention is to mitigate the inflammatory response triggered by the burned (and potentially infected) skin. However, this surgery presents significant challenges for anesthesiologists, as it typically involves massive blood loss and may exacerbate the shock that these patients frequently experience. To counteract hemorrhagic shock induced by the surgical trauma, fluid and blood product administration is critical. The state of the endothelial glycocalyx may influence the effectiveness of surgical resuscitation. When damaged, the glycocalyx heightens the risk of postoperative pulmonary edema, prolonged mechanical ventilation, abdominal or limb compartment syndrome, and deepened burns due to poor perfusion. These complications increase the likelihood of sepsis, multi-organ failure, and elevated mortality.
This study aims to evaluate whether EoT is present in severely burned patients before surgery and assess whether the surgical intervention exacerbates this condition. Investigators will conduct a two-year prospective observational cohort study at the Burn Unit of Vall d'Hebron University Hospital, from March 2024 to March 2026. The study will include patients undergoing burn debridement surgery involving 20% or more of their TBSA. Plasma sdc 1 levels will be measured preoperatively and postoperatively to assess glycocalyx disruption. Additionally, investigators will analyze perioperative factors to determine their relationship with endothelial damage.
The literature on severely burned patients and the endothelial glycocalyx is limited, with no studies to date specifically addressing its role in surgical resuscitation. Quantifying perioperative sdc 1 levels will help provide a clearer understanding of the status and function of the glycocalyx in these patients. This insight could contribute to strategies aimed at protecting the endothelial glycocalyx, potentially reducing postoperative complications related to fluid therapy and positively impacting the morbidity and mortality of severely burned patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Severe burn patients | Adult severely burned patients (TBSA â„ 20%) undergoing debridement surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Debridement Surgery | Procedure | Surgical debridement of burn wounds involving â„ 20% of the TBSA, including debrided and donor sites. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sdc-1 perioperative changes | Sdc-1 levels will be measured upon admission to our Burn Unit, 24 hours after admission, on the 5th day of admission if surgery has not yet been performed, immediately before debridement surgery, and during the first 48 hours postoperatively. | From admission to our Burn Unit until 48 hours post-debridement surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative complications |
(The following publication is used as a reference for the definition of complications: DOI: 10.1097/EJA.0000000000000118). |
| Measure | Description | Time Frame |
|---|---|---|
| Inhalation injury | Incidence of inhalation injury in severely burned patients | At admission |
| Preoperative complications | Incidence of pre-surgical complications including: pulmonary infection, urinary tract infection, renal dysfunction, skin infection, shock, pulmonary distress, ischemic heart disease, atrial fibrillation, thrombotic or hemorrhagic stroke. |
Inclusion Criteria:
Exclusion Criteria:
(* Definition of complicated heart disease: decompensated heart failure (NYHA class IV), Left Ventricular Ejection Fractio < 40%, or severe valvular disease).
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Patients admitted to the Burn Unit of Vall d'Hebron University Hospital with burned TBSA â„ 20% who undergo debridement surgery (total area between the debrided and donor sites â„ 20% of TBSA).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Laura Pons Pellicé, MD | Contact | +34 626498575 | laura.pons@vallhebron.cat | |
| Luis Abarca Vilchez, MD, PhD | Contact | +34 661968807 | luis.abarca@vallhebron.cat |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitari Vall d'Hebron | Recruiting | Barcelona | Spain | 08035 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34089618 | Background | Keyloun JW, Le TD, Brummel-Ziedins KE, Mclawhorn MM, Bravo MC, Orfeo T, Johnson LS, Moffatt LT, Pusateri AE, Shupp JW; SYSCOT Study Group. Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study. J Burn Care Res. 2022 Mar 23;43(2):432-439. doi: 10.1093/jbcr/irab102. | |
| 33394974 |
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De-identified individual participant data that will be shared include:
The IPD and supporting information will be available starting 6 months after the final study results are published and will remain available for 5 years.
Qualified researchers affiliated with academic, medical, or scientific institutions will be able to access the IPD and supporting information. They will be able to access de-identified individual participant data, including demographic information, clinical data, and outcome measures. Researchers can request access to the data by submitting a data-sharing proposal to Vall d'Hebron University Hospital and signing a data use agreement. Requests will be evaluated on a case-by-case basis.
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All blood samples will be properly labeled with each patient's identification and sent to the central laboratory of our hospital, where they will be centrifuged and stored at -80ÂșC. Sample processing will be conducted once all patients have been recruited. The analysis of syndecan-1 will be performed using an enzyme-linked immunosorbent assay (ELISA). Each blood draw will consist of 10 ml. No DNA analysis will be conducted at any point; only syndecan-1 levels will be measured
| Sdc-1 Level Measurement | Diagnostic Test | Measurement of plasma sdc-1 levels in different situations to assess endothelial glycocalyx damage using an enzyme-linked immunosorbent assay (ELISA): Preoperatively:
Postoperatively:
|
|
| A) Immediate complications: 24 hours postoperatively; B) Early complications: 7 days postoperatively; C) Late complications: 30 days postoperatively |
| Fluid and transfusion requirements | Volume of fluids and blood products transfused during surgery and in the postoperative period. | During the surgical procedure and the first 48 hours postoperatively. |
| Coagulation abnormalities (preoperative and postoperative) | Analysis of the coagulation abnormalities (guided by classic coagulation tests and thromboelastometry parameters) resulting from burn debridement surgery | Preoperative (from admission to surgery) and postoperative (up to 48 hours after surgery). |
| Duration of Mechanical Ventilation | Number of days on mechanical ventilation after debridement surgery | From the end of surgery until extubation, assessed over a period of up to 180 days. |
| Length of Stay in the Intensive Care Unit (ICU) | Number of days of ICU stay | From admission to the ICU, after de debridement surgery, until discharge from the ICU (assessed over a period of up to 180 days). |
| Survival of severely burned patients after debridement surgery | Survival from surgery until 180 days postoperatively. | From surgery until 180 days postoperatively. |
| From admission to the Burn Unit until the day of the first debridement surgery, assessed over a period of up to 30 days following admission. |
| Keyloun JW, Le TD, Pusateri AE, Ball RL, Carney BC, Orfeo T, Brummel-Ziedins KE, Bravo MC, McLawhorn MM, Moffatt LT, Shupp JW; and the SYSCOT study group. Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients. Shock. 2021 Aug 1;56(2):237-244. doi: 10.1097/SHK.0000000000001709. |
| 25058504 | Background | Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Pelosi P, Leva B, Rhodes A, Hoeft A, Walder B, Chew MS, Pearse RM; European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM); European Society of Anaesthesiology; European Society of Intensive Care Medicine. Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures. Eur J Anaesthesiol. 2015 Feb;32(2):88-105. doi: 10.1097/EJA.0000000000000118. |
| 30174566 | Background | Luker JN, Vigiola Cruz M, Carney BC, Day A, Moffatt LT, Johnson LS, Shupp JW. Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity. Ann Burns Fire Disasters. 2018 Mar 31;31(1):17-22. |
| 29023362 | Background | Osuka A, Kusuki H, Yoneda K, Matsuura H, Matsumoto H, Ogura H, Ueyama M. Glycocalyx Shedding is Enhanced by Age and Correlates with Increased Fluid Requirement in Patients with Major Burns. Shock. 2018 Jul;50(1):60-65. doi: 10.1097/SHK.0000000000001028. |
| 31866179 | Background | Welling H, Henriksen HH, Gonzalez-Rodriguez ER, Stensballe J, Huzar TF, Johansson PI, Wade CE. Endothelial glycocalyx shedding in patients with burns. Burns. 2020 Mar;46(2):386-393. doi: 10.1016/j.burns.2019.05.009. Epub 2019 Dec 20. |
| 28579548 | Background | Rodriguez EG, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, Stensballe J, Cotton BA, Holcomb JB, Johansson PI, Wade CE. Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. J Am Coll Surg. 2017 Sep;225(3):419-427. doi: 10.1016/j.jamcollsurg.2017.05.012. Epub 2017 Jun 1. |
| 28179016 | Background | Johansson PI, Stensballe J, Ostrowski SR. Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism. Crit Care. 2017 Feb 9;21(1):25. doi: 10.1186/s13054-017-1605-5. |
| 32839038 | Background | Tapking C, Hernekamp JF, Horter J, Kneser U, Haug V, Vogelpohl J, Schulte M, Kremer T, Hundeshagen G. Influence of burn severity on endothelial glycocalyx shedding following thermal trauma: A prospective observational study. Burns. 2021 May;47(3):621-627. doi: 10.1016/j.burns.2020.07.021. Epub 2020 Aug 5. |
| 34259440 | Background | Abdullah S, Karim M, Legendre M, Rodriguez L, Friedman J, Cotton-Betteridge A, Drury R, Packer J, Guidry C, Duchesne J, Taghavi S, Jackson-Weaver O. Hemorrhagic Shock and Resuscitation Causes Glycocalyx Shedding and Endothelial Oxidative Stress Preferentially in the Lung and Intestinal Vasculature. Shock. 2021 Nov 1;56(5):803-812. doi: 10.1097/SHK.0000000000001764. |
| 36923287 | Background | Bunch CM, Chang E, Moore EE, Moore HB, Kwaan HC, Miller JB, Al-Fadhl MD, Thomas AV, Zackariya N, Patel SS, Zackariya S, Haidar S, Patel B, McCurdy MT, Thomas SG, Zimmer D, Fulkerson D, Kim PY, Walsh MR, Hake D, Kedar A, Aboukhaled M, Walsh MM. SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock. Front Physiol. 2023 Feb 27;14:1094845. doi: 10.3389/fphys.2023.1094845. eCollection 2023. |
| 36804690 | Background | Basas VA, Schutzman LM, Brown IE. Implications of the Regulation of Endothelial Glycocalyx Breakdown and Reconstitution in Severe Burn Injury. J Surg Res. 2023 Jun;286:110-117. doi: 10.1016/j.jss.2022.12.033. Epub 2023 Feb 17. |
| 30502286 | Background | Vigiola Cruz M, Carney BC, Luker JN, Monger KW, Vazquez JS, Moffatt LT, Johnson LS, Shupp JW. Plasma Ameliorates Endothelial Dysfunction in Burn Injury. J Surg Res. 2019 Jan;233:459-466. doi: 10.1016/j.jss.2018.08.027. Epub 2018 Sep 22. |
| ID | Term |
|---|---|
| D002056 | Burns |
| D012771 | Shock, Hemorrhagic |
| D011183 | Postoperative Complications |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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