Pilot study of frozen platelet extracellular vesicles as a therapeutic agent in hemorrhagic shock in rats.

BACKGROUND: Hemorrhage accounts for the most preventable deaths after trauma. Resuscitation is guided by studies that demonstrate improved outcomes in patients receiving whole blood or balanced administration of blood products. Platelets present a logistical challenge due to short shelf life and need for refrigeration. Platelet-derived extracellular vesicles (PEVs) are a possible platelet alternative. Platelet-derived extracellular vesicles are secreted from platelets, have hemostatic effects and mitigate inflammation and vascular injury, similar to platelets. This pilot study aimed to elucidate the therapeutic effects of PEVs in a rat model of uncontrolled hemorrhage. METHODS: Male rats were anesthetized and femoral vessels cannulated. Vital signs (MAP, HR, and RR) were monitored. Electrolytes, lactate and ABG were obtained at baseline, 1-hour and 3-hours post injury. Laparotomy was performed, 50% of the middle hepatic lobe excised and the abdomen packed with gauze. Rats received 2 mL PEVs or lactated Ringers (LR) over 6 minutes immediately after injury. Peritoneal blood loss was quantified using preweighed gauze at 5 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes. Laparotomy was closed 1-hour postinjury. Animals were monitored for 3 hours postinjury then euthanized. Generalized Linear Mixed Effects models were performed to assess effects of treatment and time on lactate and MAP. RESULTS: Twenty-one rats were included (11 LR, 10 PEV). Overall blood loss was between 6 mL and 10 mL and not significantly different between groups. There was a 36% mortality rate in the LR group and 0% mortality in the PEV group ( p = 0.03). The LR group had significantly higher lactates at 1 hour ( p = 0.025). At 15 minutes, 45 minutes, 60 minutes, and 180 minutes, the MAP of the PEV group was significantly higher than the LR group. CONCLUSION: Early studies are encouraging regarding the potential use of PEVs in uncontrolled hemorrhagic shock based on improved survival and hemodynamics.

Mortality in hypotensive combat casualties who require emergent laparotomy in the forward deployed environment.

INTRODUCTION: Mortality rates among hypotensive civilian patients requiring emergent laparotomy exceed 40%. Damage control (DCR) principles were incorporated into the military's Clinical Practice Guidelines (CPG) in 2008. We examined combat casualties requiring emergent laparotomy to characterize how mortality rates compare to hypotensive civilian trauma patients. METHODS: The DoD Trauma Registry (2004-2020) was queried for adults who underwent combat laparotomy. Patients who were hypotensive were compared to normotensive patients. Mortality was the outcome of interest. Mortality rates before (2004-2007) and after (2009-2020) DCR CPG implementation were analyzed. RESULTS: 1051 patients were studied. Overall mortality was 6.5% for normotensive casualties and 28.7% for hypotensive casualties. Mortality decreased in normotensive patients but remained unchanged in hypotensive patients following the implementation of the DCR CPG. CONCLUSION: Hypotensive combat casualties undergoing emergent laparotomy demonstrated a mortality rate of 29.5%. Despite many advances, mortality rates remain high in hypotensive patients requiring emergent laparotomy.

When is it safe to start venous thromboembolism prophylaxis after blunt solid organ injury? A prospective American Association for the Surgery of Trauma multi-institutional trial.

BACKGROUND: The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis (VTEp) after blunt solid organ injury remains controversial, as VTE mitigation must be balanced against bleeding promulgation. Evidence from primarily small, retrospective, single-center work suggests that VTEp ≤48 hours is safe and effective. This study was undertaken to validate this clinical practice. METHODS: Blunt trauma patients presenting to 19 participating trauma centers in North America were screened over a 1-year study period beginning between August 1 and October 1, 2021. Inclusions were age older than 15 years; ≥1 liver, spleen, or kidney injury; and initial nonoperative management. Exclusions were transfers, emergency department death, pregnancy, and concomitant bleeding disorder/anticoagulation/antiplatelet medication. A priori power calculation stipulated the need for 1,158 patients. Time of VTEp initiation defined study groups: Early (≤48 hours of admission) versus Late (>48 hours). Bivariate and multivariable analyses compared outcomes. RESULTS: In total, 1,173 patients satisfied the study criteria with 571 liver (49%), 557 spleen (47%), and 277 kidney injuries (24%). The median patient age was 34 years (interquartile range, 25-49 years), and 67% (n = 780) were male. The median Injury Severity Score was 22 (interquartile range, 14-29) with Abbreviated Injury Scale Abdomen score of 3 (interquartile range, 2-3), and the median American Association for the Surgery of Trauma grade of solid organ injury was 2 (interquartile range, 2-3). Early VTEp patients (n = 838 [74%]) had significantly lower rates of VTE (n = 28 [3%] vs. n = 21 [7%], p = 0.008), comparable rates of nonoperative management failure (n = 21 [3%] vs. n = 12 [4%], p = 0.228), and lower rates of post-VTEp blood transfusion (n = 145 [17%] vs. n = 71 [23%], p = 0.024) when compared with Late VTEp patients (n = 301 [26%]). Late VTEp was independently associated with VTE (odd ratio, 2.251; p = 0.046). CONCLUSION: Early initiation of VTEp was associated with significantly reduced rates of VTE with no increase in bleeding complications. Venous thromboembolism chemoprophylaxis initiation ≤48 hours is therefore safe and effective and should be the standard of care for patients with blunt solid organ injury. LEVEL OF EVIDENCE: Therapeutic and Care Management; Level III.

Dietary Intake and Systemic Inflammation: Can We Use Food as Medicine?

PURPOSE OF REVIEW: This review summarizes the current literature regarding the association between diet and systemic inflammation. RECENT FINDINGS: Data in humans suggests that consumption of plant-based nutrients is associated with a reduction in systemic inflammation, while consumption of red meat and excessive dairy has the opposite effect and may increase risk of acute flares in those that suffer from certain chronic diseases like inflammatory bowel disease or psoriasis and certain cancers. There is a known association between diet and systemic inflammation; thus, we recommend that clinicians discuss plant-based, whole food diets with patients, particularly those that suffer from chronic inflammatory diseases as an adjunct treatment for these conditions. Future research should evaluate whether adherence to these types of diets is sustainable in the long term and how these changes affect important quality of life concerns.

FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock.

BACKGROUND: Moderate injury can lead to a coagulopathy. Fresh frozen plasma (FFP) corrects coagulopathy by means of a balanced array of clotting factors. We sought to compare the late effects of FFP and a prothrombin complex concentrate (PCC) on the coagulopathy of trauma using a porcine model of pulmonary contusion (PC) and hemorrhagic shock (HS) designed to evaluate the organ protective effects of these treatments. METHODS: Female Yorkshire swine (40-50 kg) were randomized to receive PC + HS or control (instrumented and uninjured). A blunt PC was created using a captive bolt gun. To induce HS, a liver crush injury was performed. Eighty minutes after injury, swine were treated with 25 U·kg-1 PCC, 1 U FFP, or 50 mL lactated Ringer's vehicle in a blinded manner. Arterial blood samples were drawn every 6 hours. Swine were euthanized 48 hours postinjury. Data were analyzed by Pearson χ2, analysis of variance and Kruskal-Wallis tests with Tukey's or Mann-Whitney U tests for post hoc analysis. RESULTS: Twenty-seven swine received PC + HS, 3 groups of 9 per group received PCC, FFP, or vehicle. Nine were noninjured controls. When compared with control, PC + HS swine had significantly shortened R time at 6 hours, 36 hours, and 42 hours, decreased LY30 at 12 hours, shortened K time at 30 hours and reduced α angle at 42 hours. PC + HS swine showed significant differences between treatment groups in K and α angle at 3 hours, LY30 at 12 hours and 18 hours, and MA at 12 hours, 18 hours, and 30 hours. Post hoc analysis was significant for higher α angle in PCC versus vehicle at 3 hours, higher MA in vehicle versus PCC at 12 hours and 18 hours, and higher LY30 in PCC versus vehicle at 18 hours (p < 0.012) with no significant differences between FFP and vehicle. CONCLUSION: Severe injury with HS induced a coagulopathy in swine. While FFP maintained normal coagulation following injury, PCC induced more rapid initial clot propagation in injured animals.