A.M. Soo Ping Chow1,4,5, T. Orfeo2, M. Gissell2, M.C. Bravo2, E.E. Ziedins1, T.D. Le1, S.K. Matthew1, A.E. Pusateri3, B.C. Carney1,5,6, M.M. McLawhorn1, S. Tejiram1,4,5,7, T.E. Travis1,4,5,7, L.T. Moffatt1,5,6, J.W. Shupp1,4,5,6,7 1MedStar Health Research Institute, Firefighters’ Burn And Surgical Research Laboratory, Washington, DC, USA 2University Of Vermont College Of Medicine / Fletcher Allen Health Care, Department Of Biochemistry, Burlington, VT, USA 3San Antonio Military Medical Center, Naval Medical Research Unit San Antonio, Fort Sam Houston, TX, USA 4Washington Hospital Center, The Burn Center, Washington, DC, USA 5Georgetown University Medical Center, Department Of Surgery, Washington, DC, USA 6Georgetown University Medical Center, Department Of Biochemistry And Molecular & Cellular Biology, Washington, DC, USA 7Georgetown University Medical Center, Department Of Plastic And Reconstructive Surgery, Washington, DC, USA
Introduction:
Severe Burn injuries are associated with dysregulation of inflammation, coagulation, and endothelial functions. Previous studies have shown that the degree of shedding endothelial glycocalyx layer (EGL) components, such as syndecan-1 (SDC-1) and soluble thrombomodulin (sTM), can be used as surrogate markers for the extent of endotheliopathy. Increased plasma levels of these components are associated with mortality and morbidity in burn and trauma patients. Prior research has also demonstrated that measuring endothelial cells’ capacity for synthesis and release of enzymes, like tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and adhesion molecules, such as soluble P-selectin (sP-selectin), can provide additional insights into the degree of endothelial dysfunction. Colloids, such as fresh frozen plasma (FFP), can be used as adjuncts during resuscitation. There are hypotheses that FFP may mitigate endotheliopathy by restoring the glycocalyx, which are in contrast to literature that suggests FFP could pose a risk for exacerbated host inflammatory response or thromboinflammation. The degree to which FFP administration alters endothelial function in burn patients is unknown. In this study, we investigate the changes in plasma concentrations of the aforementioned biomarkers of endothelial damage before and after administration of FFP during burn shock resuscitation.
Methods:
Burn patients with ≥20% total body surface area (TBSA) burns resuscitated with FFP were included in this prospective study. Population demographics and burn injury characteristics were recorded. Blood samples were collected immediately prior to and immediately after administration of the first unit of FFP. Concentrations of SDC-1, sTM, tPA, PAI-1, and sP-selectin were quantified using ELISA and compared using a paired t-test prior to and after administration of FFP.
Results:
Twenty-five patients were included in the analysis. The patients were predominantly male (80%) with a mean (± SD) age of 49.2 years (±17.5) and sustained TBSA of 39.2% (±18.5). The overall mortality was 28.0%. SDC-1, sTM, tPA, PAI-1, and sP-selectin plasma levels did not change after administration of FFP (all p>0.05). When stratified by mortality status, SDC-1, sTM and PAI-1 levels did not differ before or after administration of FFP while tPA and sP-selectin levels were higher in patients who died compared to those who lived (247.1±95.6 vs 85.4±16.5 pM, p=0.041 and 99.9±9.1 vs 65.7±7.9 ng/ml, p=0.046) with the difference unaffected by FFP administration (p>0.05).
Conclusion:
The endothelium helps regulate inflammation, cellular migration, and coagulation. Administration of FFP did not worsen the endotheliopathy seen in burn shock. Additional studies should evaluate whether plasma may mitigate endothelial dysfunction by analyzing biomarkers across a longer time interval after administration of FFP.