Clinical trial NCT06670248: Evaluation of Endothelial Glycocalyx in the Surgical Resuscitation of Major Burn Patients
Official title: GlycoBURN Study: Determination of Endothelial Glycocalyx Status in the Surgical Resuscitation of Severe Burn Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Syndecan 1
Severe Burn
Endotheliopathy of Trauma
Endothelial Glycocalyx
Hemorrhagic Shock
Postoperative Complications
Keywords: Syndecan 1
Endotheliopathy
Glycocalyx
Proteoglycan
Severe burn
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
First posted: 2024-11-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the Burn Unit of Vall d'Hebron University Hospital with burned TBSA ≥ 20% who undergo debridement surgery (total area between the debrided and donor sites ≥ 20% of TBSA).

Brief summary: 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:

* Do severely burned patients present with EoT before undergoing burn debridement surgery?
* Does the surgical intervention worsen EoT, leading to increased postoperative syndecan 1 (sdc 1) levels compared to preoperative levels?

Participants will:

* Undergo debridement surgery where the total area of debrided and donor sites covers 20% or more of the Total Body Surface Area (TBSA).
* Have their sdc 1 levels measured before and after surgery.
* Have perioperative factors analyzed to assess their impact on endothelial damage and glycocalyx functionality.

This study aims to provide insight into how surgical resuscitation affects the endothelial glycocalyx in severely burned patients.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years old with burned TBSA greater than or equal to 20%.
* Patients who will undergo debridement of at least 20% of the burned TBSA (including the debrided area and the donor site).

Exclusion Criteria:

* Under 18 years old.
* Pregnant women.
* Patient refusal.
* Polytraumatized patients.
* Electrical or chemical burns.
* Patients with any of the following pre-burn conditions: complicated heart disease\*, renal disease on hemodialysis/hemofiltration or with Glomerular Filtration Rate (GFR) \< 30 ml/min/1.73m², and liver cirrhosis (Child A, B, and C).

(\* Definition of complicated heart disease: decompensated heart failure (NYHA class IV), Left Ventricular Ejection Fractio \< 40%, or severe valvular disease).

* Patients with a history of chronic inflammatory diseases (autoimmune disease).
* Patients on chronic treatment with corticosteroids or immunosuppressants.
* Patients requiring reintervention for debridement surgery who have already been included in the study during their first surgery.

Primary outcomes:
measure: Sdc-1 perioperative changes
timeFrame: From admission to our Burn Unit until 48 hours post-debridement surgery.
Secondary outcomes:
measure: Postoperative complications
timeFrame: A) Immediate complications: 24 hours postoperatively; B) Early complications: 7 days postoperatively; C) Late complications: 30 days postoperatively
measure: Fluid and transfusion requirements
timeFrame: During the surgical procedure and the first 48 hours postoperatively.
measure: Coagulation abnormalities (preoperative and postoperative)
timeFrame: Preoperative (from admission to surgery) and postoperative (up to 48 hours after surgery).
measure: Duration of Mechanical Ventilation
timeFrame: From the end of surgery until extubation, assessed over a period of up to 180 days.
measure: Length of Stay in the Intensive Care Unit (ICU)
timeFrame: From admission to the ICU, after de debridement surgery, until discharge from the ICU (assessed over a period of up to 180 days).
measure: Survival of severely burned patients after debridement surgery
timeFrame: From surgery until 180 days postoperatively.
Other outcomes:
measure: Inhalation injury
timeFrame: At admission
measure: Preoperative complications
timeFrame: 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.
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.