BACKGROUND Severe burn injuries are known to initiate a profound systemic inflammatory response (SIRS) that may lead to burn shock and other SIRS-related complications. Damage-associated molecular patterns (DAMPs) are important early signaling molecules that initiate SIRS after burn injury. Previous work in a rodent model has shown that application of a topical immune modulator (p38MAPK inhibitor) applied directly to the burn wound decreases cytokine expression, reduces pulmonary inflammation and edema. Our group has demonstrated that tranexamic acid (TXA)-in addition to its use as an antifibrinolytic-has cell protective in vitro effects. We hypothesized that administration of TXA after burn injury would attenuate DAMP release and reduce lung inflammation. METHODS C57/BL6 male mice underwent a 40% Total Body Surface Area (TBSA) scald burn. Sham animals underwent the same procedure in room temperature water. One treatment group received the topical application of p38MAPK inhibitor after burn injury. The other treatment group received an intraperitoneal administration of TXA after burn injury. Animals were sacrificed at 5 hours. Plasma was collected by cardiac puncture. MtDNA levels in plasma were determined by quantitative Polymerase Chain Reaction (qPCR). Syndecan-1 levels in plasma were measured by ELISA. Lungs were harvested, fixed, and paraffin-embedded. Sections of lungs were stained for antigen to detect macrophages. RESULTS Topical p38MAPK inhibitor and TXA significantly attenuated mtDNA release. Both TXA and the topical p38MAPK inhibitor reduced lung inflammation as represented by decreased macrophage infiltration. Syndecan-1 levels showed no difference between burn and treatment groups. CONCLUSION Both p38 MAPK inhibitor and TXA demonstrated the ability to attenuate burn-induced DAMP release and lung inflammation. Beyond its role as an antifibrinolytic, TXA may have significant anti-inflammatory effects pertinent to burn resuscitation. Further study is required; however, TXA may be a useful adjunct in burn resuscitation.

Tranexamic acid suppresses the release of mitochondrial DAMPs and reduces lung inflammation in a murine burn model.

Burn shock and acute fluid resuscitation continue to spark intense interest and debate among burn clinicians. Following a major burn injury, fluid resuscitation of burn shock is life-saving, but paradoxically can also be a source of increased morbidity and mortality because of the unintended consequence of systemic edema formation. Considerable research over the past two decades has been devoted to understanding the mechanisms of edema formation, and to develop strategies to curb resuscitation fluids and limit edema development. Recognition of burn endotheliopathy - injury to the endothelium's glycocalyx layer- is one of the most important recent developments in our understanding of burn shock pathophysiology. Newer monitoring approaches and resuscitation endpoints, along with alternative resuscitation strategies to crystalloids alone, such as administration of albumin, or plasma, or high dose ascorbic acid, have had mixed results in limiting fluid creep. Clear demonstration of improvements in outcomes with all of these approaches remains elusive. This comprehensive review article on burn shock and acute resuscitation accompanies the American Burn Association's State of the Science meeting held in New Orleans, LA on November 2-3, 2021 and the Proceedings of that conference published in this journal.

Burn Shock and Resuscitation: Review and State of the Science.

The problem of fluid creep has generated renewed interest in the use of colloids during acute burn resuscitation. Currently, human albumin solution is usually chosen as the resuscitation colloid. However, human plasma was a fundamental component of numerous burn resuscitation formulas historically, but it largely fell out of favor due to concerns surrounding transmission of infectious viruses. Nevertheless, plasma is an effective volume expander which has been demonstrated to reduce overall volume requirements during burn resuscitation. Furthermore, plasma may have beneficial effects on the endothelium by diminishing the microvascular leak that follows a major burn injury. Fresh frozen plasma (FFP) is now much safer from a disease transmission standpoint, and newer forms of solvent-detergent-treated plasma and lyophilized plasma offer potentially even greater safety and efficacy. The use of FFP and newer forms of plasma, which have not been extensively studied, should be investigated as potential adjuncts to acute burn resuscitation.

A Review on the Use of Plasma During Acute Burn Resuscitation

Anticoagulant therapy poses a significant risk for patients undergoing emergency neurosurgery procedures, necessitating reversal with prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). Data on PCC efficacy lack consistency in this setting. This systematic review and metaanalysis aimed to evaluate efficacy and safety of PCC for anticoagulation reversal in the context of urgent neurosurgery. Articles from PubMed, Embase, and Cochrane databases were screened according to the PRISMA checklist. Adult patients receiving anticoagulation reversal with PCC for emergency neurosurgical procedures were included. When available, patients who received FFP were included as a comparison group. Pooled estimates of observational studies were calculated for efficacy and safety outcomes via random-effects modeling. Initial search returned 4505 articles, of which 15 studies met the inclusion criteria. Anticoagulants used included warfarin (83%), rivaroxaban (6.8%), phenprocoumon (6.1%), apixaban (2.2%), and dabigatran (1.5%). The mean International Normalized Ratio (INR) prePCC administration ranged from 2.3 to 11.7, while postPCC administration from 1.1 to 1.4. All-cause mortality at 30 days was 27% (95%CI 21, 34%; I2 = 44.6%; p-heterogeneity = 0.03) and incidence of thromboembolic events was 6.00% among patients treated with PCC (95%CI 4.00, 10.0%; I2 = 0%; p-heterogeneity = 0.83). Results comparing PCC and FFP demonstrated no statistically significant differences in INR reversal, mortality, or incidence of thromboembolic events. This metaanalysis demonstrated adequate safety and efficacy for PCC in the reversal of anticoagulation for urgent neurosurgical procedures. There was no significant difference between PCC and FFP, though further trials would be useful in demonstrating the safety and efficacy of PCC in this setting.

Safety and efficacy of prothrombin complex concentrate (PCC) for anticoagulation reversal in patients undergoing urgent neurosurgical procedures: a systematic review and metaanalysis.

Severely burned patients suffer significant hematologic pathologies. Anemia develops from burn excisions and the anemia of critical illness. Fluid shifts, resuscitation, and factor consumption can cause significant coagulopathy. Transfusion of red blood cells to treat anemia, plasma to treat coagulopathy, and other blood products are critical to burn management. Critical illness, injury, immobilization, and other factors create a hypercoagulable state requiring venothromboembolic prophylaxis. Hematopoietic changes reduce red blood cell generation as well as affecting downstream immunologic function. Facile management of these hematologic pathologies is essential to the medical and surgical management of burn patients.

Hematology, Hemostasis, Thromboprophylaxis, and Transfusion Medicine in Burn Patients

TRALI following fresh frozen plasma resuscitation from burn shock

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TRALI following fresh frozen plasma resuscitation from burn shock