Evaluation of Endothelial Glycocalyx in the Surgical Resuscitation of Major Burn Patients

Recruiting

• Conditions: Syndecan 1; Severe Burn; Endotheliopathy of Trauma; Endothelial Glycocalyx; Hemorrhagic Shock; Postoperative Complications

• Registration Number: NCT06670248
• Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

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.

Study Timeline

• Study Start: 2024-03-05
• Status Verified: 2024-10
• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-30
• Last Update Submitted: 2024-10-30
• Study First Posted: 2024-11-01
• Last Update Posted: 2024-11-01
• Primary Completion: 2026-03
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Sdc-1 perioperative changes	From admission to our Burn Unit until 48 hours post-debridement surgery.	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.

Secondary Outcome Measures

Name	Time	Method
Postoperative complications	A) Immediate complications: 24 hours postoperatively; B) Early complications: 7 days postoperatively; C) Late complications: 30 days postoperatively	1. Cardiovascular complications (yes/no): new-onset atrial fibrillation or other arrhythmias, presence of non-fatal cardiopulmonary arrest, acute myocardial infarction, acute pulmonary edema, and myocardial injury after non-cardiac surgery (MINS).; 2. Pulmonary complications (yes/no): pneumonia, whether associated with mechanical ventilation or not, pleural effusion, acute respiratory distress syndrome (ARDS), pneumothorax, bronchospasm, and the need for tracheostomy.; 3. Renal failure (yes/no): need for dialysis or hemofiltration (yes/no).; 4. Abdominal compartment syndrome (yes/no).; 5. Thrombotic complications (yes/no): lower limb thrombosis, pulmonary embolism, and cerebrovascular accident.; (The following publication is used as a reference for the definition of complications: DOI: 10.1097/EJA.0000000000000118).
Fluid and transfusion requirements	During the surgical procedure and the first 48 hours postoperatively.	Volume of fluids and blood products transfused during surgery and in the postoperative period.
Coagulation abnormalities (preoperative and postoperative)	Preoperative (from admission to surgery) and postoperative (up to 48 hours after surgery).	Analysis of the coagulation abnormalities (guided by classic coagulation tests and thromboelastometry parameters) resulting from burn debridement surgery
Duration of Mechanical Ventilation	From the end of surgery until extubation, assessed over a period of up to 180 days.	Number of days on mechanical ventilation after debridement surgery
Length of Stay in the Intensive Care Unit (ICU)	From admission to the ICU, after de debridement surgery, until discharge from the ICU (assessed over a period of up to 180 days).	Number of days of ICU stay
Survival of severely burned patients after debridement surgery	From surgery until 180 days postoperatively.	Survival from surgery until 180 days postoperatively.

Trial Locations

Locations (1)

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain